Oral Abstract Session: Basic Science 1 2 3 4

Oral Abstract Session: Basic Science 1

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DETECTION OF ACUTE MYOCARDIAL INFARCTION USING A REAL-TIME CARDIAC ELECTRICAL BIOMARKER

MP4OX IMPROVES OXYGEN CONSUMPTION AND SURVIVAL IN A RAT MODEL OF EXTREME HEMODILUTION

David Schreck, Summit Medical Group

Mark Young, Jeff Lohman, Ashok Malavalli, Kim Vandegriff, Howard Levy, Sangart, Inc.

Introduction: The cardiac electric field is known to be dipolar such that 3 lead-vectors should describe the field. Eigenvalue modeling (EVA) of the 12-lead electrocardiogram (ECG) can quantify dipolar vs. multipolar forces yielding a cardiac “electrical” biomarker (CEB) for detection of acute myocardial infarction (AMI). Hypothesis: The objective was to test a CEB model that quantifies the multipolar activity of the derived 12-lead ECG to detect AMI. Methods: This is a blinded, case-controlled study in which voltage-time ECG data arrays were analyzed from 102 patients with AMI and 248 patients with non-AMI. ECGs with missing leads, wandering baseline, and excessive noise were excluded. Simplex optimization was used to derive the 12-lead ECG from just 3 basis leadvectors (I, II, V2) stored in the cardiac monitor. The CEB was computed from the derived ECG by EVA to detect AMI and then compared to both an ECG interpretive algorithm (ECGI), and to ST voltage changes (ST) consistent with AMI, tested against the interpretations of the blinded physician reference standard. Sensitivities, specificities, and negative and positive predictive values were calculated. The 95% confidence intervals were computed for analysis of statistical significance. The measured vs. derived ECGs morphologies were compared using the Pearson correlation. Results: The CEB had a sensitivity of 88.0%, specificity of 91.3%, negative predictive value (NPV) of 95.0% and positive predictive value (PPV) of 80.2%. The ECGI had a sensitivity of 54.3%, specificity 77.4%, NPV 80.9%, PPV 49.0%. The ST had a sensitivity of 59.5%, specificity 68.6%, NPV 80.7%, PPV 43.5%. The CEB showed superiority to the ECGI and ST at p ⬍ 0.0001. The derived 12-lead ECG morphologies showed high correlation with the measured 12-lead ECG. Conclusions: The multipolar forces of the cardiac electrical field can be quantified from the derived 12-lead ECG to compute a CEB that reliably detects the presence of AMI. This cardiac “electrical” biomarker is readily computed directly from the patient cardiac monitor and displayed in real-time. This will allow an immediate, cost-effective, and efficient means of detecting AMI in patients who are being monitored in acute care settings.

Introduction: Cell-free hemoglobin solutions employed as blood replacement fluids have failed to improve oxygen consumption (VO2) due to inappropriate oxygen release characteristics and vasoconstriction, properties that limit oxygen delivery. MP4OX (pegylated human Hb) is an oxygen therapeutic agent formulated at low Hb concentration (4.3 g/dL), with high oxygen affinity (P50 ⫽ 5 mmHg) and high colloid osmotic pressure (COP ⫽ 70 mmHg). Hypothesis: The present study was conducted to demonstrate that MP4OX maintains VO2 in a model of extreme hemodilution despite its high oxygen affinity. Methods: Studies were conducted in a rat model of continuous exchange transfusion (ET) and extreme anemia. Conscious male SD rats (290 - 327 g) received ET (0.5 ml/min ⫻ 100 min) with one of the following solutions 1) Hextend; 2) PEGalbumin; 3) MP4OX. PEG-albumin served as a pegylated non-O2 carrying protein with matched COP. Whole body VO2 was measured from O2 content in inlet and outlet air of known flow rate with the rat in a sealed chamber. Results: Baseline VO2 was similar in all groups (20-25 ml/kg/min). Hemodilution was similar in all groups as reflected by the trajectory of hematocrit decline with time, falling to ⬍5% after 70 min of ET. Hemodilution with either Hextend or PEGalbumin resulted in a rapid decline of VO2 (⬍4 mL/kg/min) at Hb below 4.2 g/dL, and mortality was 100% in both groups by 80 minutes, with terminal arterial lactate ⬎21 mmol/L. Hemodilution with MP4OX improved survival (87%), VO2 (11 ⫾ 4 ml/min/kg), and arterial lactate (8 ⫾ 2 mmol/L) at 160 minutes (1 hour after completion of ET).In follow up studies, rats that were initially hemodiluted with PEG-albumin for 40 minutes to a total Hb of 4.0 g/dL, followed by ‘rescue’ exchange transfusion with MP4OX, exhibited intermediate survival times, VO2, and lactate concentrations. Conclusions: These data demonstrate that MP4OX improves oxygen consumption compared to non-oxygen carrying plasma expanders and limits oxygen debt during extreme hemodilution. The data support the concept that MP4OX, a high-affinity hemoglobin molecule, imparts significant benefit as an oxygen therapeutic agent.

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A POLYMORPHISM WITHIN THE GLUTATHIONE BIOSYNTHESIS PATHWAY IS ASSOCIATED WITH INCREASED OXIDANT STRESS IN INFANTS AFTER UNDERGOING CARDIOPULMONARY BYPASS

CHANGES IN SUBSTRATE UTILIZATION IN RAT HEARTS FOLLOWING HEMORRHAGE AND RESUSCITATION WITH KETONE SOLUTION

Truc Le, Eloa Adams, Stanford University, Gary Cunningham, Children’s National Medical Center, Frederick Barr, Cincinnati Children’s Hospital Medical Center, Marshall Summar, Children’s National Medical Center, David Cornfield, Stanford University Introduction: Glutamate cysteine ligase (GCL) is the rate-limiting enzyme for de novo glutathione synthesis. Polymorphisms within the genes encoding GCL can lead to decreased glutathione synthesis and increased host susceptibility to oxidant injury. Hypothesis: We hypothesize that an insertion/deletion polymorphism, located within the gene that encodes the catalytic subunit of the GCL enzyme, predisposes infants undergoing cardiopulmonary bypass (CPB) to oxidant injury. Methods: Infants undergoing CPB were genotyped using the Taqman Allelic Discrimination assay. Urine isoprostane concentrations, an indicator of oxidant stress, were measured using gas chromatography-mass spectroscopy and compared between genotypes. To determine whether oxidants can directly affect pulmonary artery smooth muscle cells (PA SMC) tone, cytosolic calcium ([Ca2⫹]i), the major determinant of SMC tone, was measured in PA SMC from a 2.5 month old infant treated with H2O2. Results: Infants homozygous for the deletion allele (Del/Del genotype) had significantly higher median urine isoprostane levels (10.6 ng/mg creatinine) as compared to infants heterozygous (3.0 ng/mg creatinine) or homozygous (4.7 ng/mg creatinine) for the insertion allele (p ⬍ 0.05). Addition of H2O2 to PA SMC caused a significant increase in human PA SMC [Ca2⫹]i. Conclusions: Infants with the Del/Del genotype have increased urine isoprostane concentrations after undergoing CPB, suggesting an increased susceptibility to oxidant injury. Moreover, oxidant stress directly increases human infant PA SMC [Ca2⫹]i in vitro. Taken together, these findings suggest that patients with the Del/Del genotype may be uniquely vulnerable to oxidant injury and, therefore, at increased risk for pulmonary hypertension after CPB.

Crit Care Med 2010 Vol. 38, No. 12 (Suppl.)

Peter Perakis, William Beaumont Hospital, Royal Oak, MI, Philip Fong, Robert Hammond, Graham Long, C. Wong, Charles Shanley, William Beaumont Hospital Introduction: To determine if ketone bodies are an effective metabolic substrate for the support of cardiac metabolism after resuscitation from severe hemorrhage shock. Hypothesis: A resuscitative fluid containing ketone bodies improves cardiac function in hemorrhagic shock. Methods: 48 hours prior to the hemorrhagic shock exposure, two groups (n ⫽ 7/group) of male Sprague Dawley rats were maintained on a high protein diet. Then the animals were anesthetized and cardiac metabolism was assessed by Positron Emission Tomography after injection of 18-Fluorodeoxyglucose. (18-FDG; volume ⬍0.5 ml) in the tail vein. Scans were obtained at 60 and 120 minutes post-injection. The following day, the rats were again anesthetized and the femoral artery and vein were cannulated for measurement of hemodynamics, and sampling for blood gases, pH, base deficit, HCO3, glucose, Hgb, and oxygen saturation. After baseline measurements, arterial exsanguination was performed so that arterial pressure fell to 30-35 mmHg, and the shed volume was recorded. Data were recorded every 30’ after induction of shock for 180’. Following 55’ of hypotension, the animals were resuscitated over the course of 5’ with normal saline or a Ketone Ringer solution, with twice the volume of the blood shed. Then the PET scan was repeated to assess uptake of 18-FDG after 60 and 120 minutes post-injection. At 120’, surviving animals were euthanized and kidney and intestinal tissue samples were collected for subsequent histological analyses. Results: Hemodynamics and acid-base responses, including blood pressure, heart rate, base excess and pH were improved following resuscitation with ketone ringers solution. Intestinal ischemia/reperfusion injury was less in the group resuscitated with ketone ringers. Initial qualitative image analysis indicates that uptake of 18-FDG was greater in the animals resuscitated with ketone ringer’s solution as opposed to normal saline. Conclusions: In a model of severe hemorrhagic shock, cardiac function is improved sooner with rats resuscitated with ketone bodies as evidenced by improved hemodynamics, acid-base balance, and glucose uptake as seen in MicroPET imaging.

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ISOFLURANE INDUCES SPHINGOSINE KINASE-1 AND PROTECTS AGAINST HUMAN ENDOTHELIAL CELL APOPTOSIS

L-GLUTAMINE’S PROTECTIVE MECHANISM VIA THE INTEGRIN/SRC PATHWAY IS DEPENDENT ON CELL SWELLING, O-GLYCOSYLATION, HSF-1, AND HSP EXPRESSION

Adnan Bakar, Sang Won Park, Minjae Kim, Mihwa Kim, H. Thomas Lee, College of Physicians and Surgeons of Columbia University Introduction: Endothelial cell dysfunction is a major problem in critical care medicine and during the perioperative period as it plays a major role in many human diseases including ischemia and reperfusion injury, coronary artery disease, diabetes mellitus and systemic inflammatory response syndrome. Volatile anesthetics are frequently used during the perioperative period and have been shown to have diverse non-anesthetic effects, such as protection of the heart and kidney from ischemia and reperfusion injury. Hypothesis: We aimed to determine whether isoflurane, the most commonly used volatile anesthetic in the USA, protects against endothelial apoptosis and necrosis and the mechanisms involved in this protection. Methods: Cultured immortalized human umbilical vein endothelial cells (EA.hy926) were treated with 2.5% isoflurane or carrier gas (95% room air ⫹ 5% CO2) for up to 16 hours, and then subjected to apoptosis with tumor necrosis factor-␣ (20ng/ml for 48 hours) or to necrosis with hydrogen peroxide (2mM for 24 hours). DNA laddering and TUNEL staining were used to determine apoptosis; percent LDH release determined necrosis. We also determined how isoflurane modulates the activity of the pro-survival enzyme sphingosine kinase-1 (SK1), measured the SK1 phosphorylation product sphingosine1-phosphate (S1P), and the phosphorylation of extracellular signal-regulated kinase (ERK MAPK), an anti-apoptotic enzyme. Results: Isoflurane pretreatment significantly decreased EA.hy926 apoptosis without reducing necrosis. Mechanistically, isoflurane increased SK1 mRNA (1.97 ⫹ 0.08 fold over control, N ⫽ 3, P ⬍ 0.001) and protein expression (1.95 ⫹ 0.4 fold, N ⫽ 3, P ⬍ 0.05), increased sphingosine kinase activity (1.27 ⫹ 0.07 fold, N ⫽ 4, P ⬍ 0.01), and increased S1P synthesis (1.27 ⫹ 0.04 fold, N ⫽ 6, P ⬍ 0.001) in EA.hy926 cells. Isoflurane also increased phosphorylation of ERK MAPK (1.77 ⫹ 0.18 fold, N ⫽ 3, p ⬍ 0.001). Conclusions: Taken together, we demonstrate that isoflurane, in addition to its anesthetic properties, protects against endothelial apoptosis most likely via SK1 and ERK MAPK activation. Our findings have clinical implications for protection of endothelial cells during the perioperative period and in patients requiring critical care.

Stefanie Niederlechner, Jonathan Levi, Christine Hamiel Baird, Alyssa Kallweit, Paul Wischmeyer, University of Colorado Introduction: Glutamine (GLN) is known to increase the activation of transcription factors, such as heat shock factor 1 (HSF-1), via the O-glycosylation (OGlcNAc) pathway to induce the protective heat shock protein (HSP) response, and it is known that the integrin pathway can induce cellular protection. Hypothesis: We investigated whether the integrin/Src pathway is involved in GLN’s cell protective mechanism and whether this protective effect may be related to GLN-mediated cell swelling. Methods: Intestinal Epithelial Cells (IEC-6) treated for 15 min with increasing doses of GLN up to 20 mM, with or without the integrin inhibitor GRGDSP (50 ␮M), inactive control peptide GRGESP (50 ␮M) or Src-kinase inhibitor PP-2 (75 ␮M). Cell survival via MTS assay 24h post-heat-shock (HS) (44°Cx50min). O-glycosylated protein levels, HSF-1, Heme Oxygenase 1 (HSP32) and HSP70 levels determined via Western blot, and cell area size and cytoskeleton stabilization via fluorescence microscopy after non-lethal HS (43°Cx50min). Results: GRGDSP completely attenuated GLNmediated increases in cell area size (p ⬍ 0.001 vs. HS GLN; n ⫽ 3) and destabilized the F-actin cytoskeleton. GLN increased cell survival in a dose dependent manner (p ⬍ 0.001 vs. HS CT; n ⫽ 4). GRGDSP and PP2 attenuated GLN’s protection by 70%-100% (p ⬍ 0.001 vs. respective GLN groups; n ⫽ 4). GRGDSP attenuated GLN-mediated increases in HSF-1 expression by 79% (p ⬍ 0.05 vs. HS 10 mM GLN: n ⫽ 3). O-GlcNAc modified proteins increased 100% post-HS after 10 mM GLN (p ⬍ 0.001 vs. HS C; n ⫽ 5). GRGDSP attenuated 10 mM GLN’s effect on O-GlcNAc protein modification by 84% (p ⬍ 0.05 vs. HS 10 mM GLN; n ⫽ 5). GRGDSP and PP2 attenuated GLNmediated increases in HSP70 and HSP32 (2-3 fold) by 70%-100% after HS (p ⬍ 0.05 vs. HS CT; n ⫽ 4). GRGESP control peptide had no effect on any of the GLN-mediated cellular protection pathways. Conclusions: The integrin/Src pathway appears to be an essential component of GLN’s molecular mechanism of cellular protection. (Supported: R01 GM078312)

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AGE DEPENDENT DIFFERENTIAL EXPRESSION OF ADENO ASSOCIATED VIRUS SEROTYPE 9 ENCODED GREEN FLUORESCENT PROTEIN IN RATS

GLUTAMINE’S MECHANISM OF CELLULAR PROTECTION AND HEAT SHOCK PROTEIN 25, 32 AND 70 ENHANCEMENT IS DEPENDENT ON THE HEXOSAMINE BIOSYNTHETIC PATHWAY IN HEAT STRESSED INTESTINAL EPITHELIAL CELLS

Jeejabai Radhakrishnan, Iyad Ayoub, Madhav Upadhyaya, Jameson Azul, Rosalind Franklin University of Medicine and Science, Erik Kohlbrenner, Roger Hajjar, Mount Sinai School of Medicine, Raul Gazmuri, Rosalind Franklin University of Medicine and Science Introduction: Adeno associated viral (AAV) vectors are attractive gene delivery vectors because of their low immunogenicity and serotype dependent tissue specific tropism. Recently, the AAV serotype 9 (AAV9) was reported to preferentially transduce the myocardium. We investigated whether AAV9 mediated viral transduction is influenced by age. Hypothesis: We hypothesized that age plays a role in viral transduction and subsequent gene expression with better transduction potential in young subjects. Methods: Experiments were conducted in rats using an AAV9 encoding green fluorescent protein (AAV9-GFP). Transduction efficiency and tissue distribution was assessed after systemic injection of 1011 viral genome copies via the right jugular vein in two young (6-7 weeks old) and in two retired breeder (⬎6 months old) male Sprague Dawley rats. GFP expression was analyzed at 30 days after viral injection by assessing levels of GFP mRNA in left ventricular tissue by real-time PCR and levels of GFP in various tissues by ELISA. In addition, left ventricular tissue GFP distribution was assessed by direct and immuno-stained GFP fluorescence. Results: left ventricular tissue GFP mRNA levels (fold expression normalized to GAPDH) were comparable in young rats (17 ⫾ 0.5) and retired breeders (21 ⫾ 9) after 30 days of viral injection. However, the levels of left ventricular tissue GFP (pg/mg protein) were significantly higher in young rats compared with retired breeders (33 ⫾ 1 vs 6 ⫾ 5, p ⬍ 0.02) despite comparable levels in other organs such as liver (3 ⫾ 1 vs 2 ⫾ 0.5), skeletal muscle (1 ⫾ 1 vs 0.3 ⫾ 0.3), lung (0.7 ⫾ 0.5 vs 0.7 ⫾ 0.2), brain (0.3 ⫾ 0.2 vs 0.2 ⫾ 0.2), and kidney (0.1 ⫾ 0.1 vs 0.3 ⫾ 0). Conclusions: AAV9 preferentially transduces the myocardium. However, lower protein levels despite comparable mRNA levels in old rats shows age-dependent differential gene expression. This could reflect differences in post-transcriptional mechanisms (mRNA stability or splicing) or the translation per se and could be important in determining the success of cardio specific gene therapy using AAV9 viruses to ameliorate cardiac disease.

Alyssa Kallweit, University of Colorado Denver, Christine Hamiel Baird, University of Colorado Health Science Ctr., Stefanie Niederlechner, University of Colorado, Lauren Zager, Alexandra Sufit, University of Colorado Denver, Paul Wischmeyer, University of Colorado At Denver School of Medicine Introduction: Glutamine (GLN) increases heat shock protein 25 (HSP25), 32 (HSP32), and 70 (HSP70) in heat stressed intestinal epithelial cells (IEC-18). The hexosamine biosynthetic pathway (HBP) has been implicated as the pathway by which GLN enhances HSP70 in fibroblast cells, but no such literature exists in a more clinically relevant model of intestinal epithelial cells. Furthermore, the HBP’s involvement on HSP25 and HSP32 is also unknown. Hypothesis: The hexosamine biosynthetic pathway is an essential component for GLN mediated cellular protection and enhancement of heat shock protein 25, 32, and 70 expression in intestinal epithelial cells. Methods: Small interfering RNA (siRNA) knockdown of a key HBP enzyme, O-linked N-acetylglucosamine transferase (OGT), was used in IEC-18 cells to determine the importance of the HBP on GLN-mediated HSP25, HSP32, and HSP70 enhancement and cell survival. Cells were then treated with 0mM GLN (CT) or 8mM GLN (GLN), heat stressed (HS), and allowed to recover for 3 hours. HSP levels were evaluated in whole cell lysates via western blotting. Cell survival was determined using MTS assays normalized to non-HS controls for each group. Results: Western Blot analyses showed an increase in HSP25, 32, and 70 expression in GLN-treated cells (p ⬍ 0.05 vs. HS CT). OGT silencing attenuated GLN’s enhancement of all three HSPs (p ⬍ 0.03 vs. HS GLN). OGT levels were knocked down by 88% in the silenced group vs. non-silenced controls (p ⬍ 0.02). MTS Assays showed GLN increased cell viability by 63% in cells subjected to lethal HS (p ⬍ 0.01 vs. HS CT). OGT silencing decreased GLN’s protection by 59% (p ⬍ 0.001 vs. HS GLN) N ⫽ 3. Nonspecific control oligos did not change HSP expression or cell viability. Conclusions: GLN enhances HSP25, HSP32, and HSP70 expression via the HBP. GLN-mediated cellular protection is dependent on the hexosamine biosynthetic pathway in intestinal epithelial cells.


Oral Abstract Session: Epidemiology-Data 9

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RELATIONSHIP BETWEEN NEIGHBORHOOD POVERTY RATE AND MORTALITY IN THE CRITICALLY ILL

THE ‘WEEKEND EFFECT’ FOR HYPERTENSIVE EMERGENCIES: A NATIONWIDE STUDY

Sam Zager, Harvard Medical School, Mallika Mendu, Domingo Chang, Brigham and Women’s Hospital, Heidi Bazick, Fiona Gibbons, Massachusetts General Hospital, Kenneth Christopher, Brigham and Women’s Hospital

Sandeep Markan, Gagan Kumar, Medical College of Wisconsin, Abhishekh Deshmuk, University of Arkansas, Ankit Sakhuja, Jayshil Patel, Thomas Kaleekal, Medical College of Wisconsin, Rumi Ahmed Khan, Orlando Regional Medical Center, Amit Taneja, Rahul Nanchal, Medical College of Wisconsin

Introduction: Poverty is associated with increased risk of chronic disease but its contribution to critical care outcome is not well-defined. Hypothesis: We hypothesized that the neighborhood poverty rate is associated with all cause mortality following initiation of critical care. Methods: We performed a multicenter observational study of 40, 575 patients, age ⱖ 18 years, who received critical care between 1997 and 2007. The patients were treated in 209 medical and surgical ICU beds in two hospitals in Boston, Massachusetts. Data sources included Census and hospital administrative data. Census tracts were used as the geographic units of analysis. Neighborhood poverty rate is defined as the percentage of each neighborhood’s residents with incomes below the federal poverty line. The exposure of interest was neighborhood poverty rate categorized a priori as ⬍5%, 5-10%, 10-20%, 20-40% and ⬎40%. Logistic regression examined death by days 30, 90 and 365 post-ICU admission and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Adjustment included age, gender, race, admission year, medical vs surgical, DeyoCharlson Index, sepsis, CABG, MI, hematocrit, WBC, creatinine, and BUN. Sensitivity analysis was performed for 1-year post-discharge mortality among patients discharged to home. Sensitivity analysis was also performed for mortality among patients with distance from hospital ⬍50 miles. Results: Following multivariable adjustment, neighborhood poverty rate was not associated with all cause 30-day mortality: 5-10% OR 1.06 (95%CI 0.98-1.14;P ⫽ 0.1), 10-20% OR 0.96 (95%CI 0.88-1.06; P ⫽ 0.5), 20-40% OR 1.08 (95%CI 0.95-1.22; P ⫽ 0.2), ⬎ 40% OR 1.12 (95%CI 0.84-1.49; P ⫽ 0.5); referent in each is ⬍5%. Similar non-significant associations were noted at 90-day 365-day mortality postICU admission and in-hospital mortality. Among patients discharged to home or patients whom resided ⬍ 50 miles to the hospital of care, neighborhood poverty rate was not associated with 1-year-post-discharge mortality in either case. Conclusions: Our study suggests that there is no relationship between the neighborhood poverty rate derived from patient address and mortality following critical care.

Introduction: Hypertension is common medical condition affection more than 65 million Americans. Poor blood pressure control may lead to dangerously high blood pressures defined as hypertensive urgency and/or emergency based on end organ involvement. Literature has previously described poor outcomes for patients admitted over the weekend for a variety of acute medical conditions. Hypothesis: Patients admitted with hypertensive emergencies on weekends have worse outcomes than those admitted on weekdays. Methods: Nationwide Inpatient Sample database from 2000 to 2008 was used to identify patients discharged with the primary diagnosis of hypertensive emergency using ICD-9-CM codes 401.0, 402.00, 402.01, 403.00, 403.01, 404.00, 404.01, 404.02, 404.03, 405.01, 405.09. Weekend admissions were defined as all admissions between midnight on Friday through midnight on Sunday. Our primary outcome of interest was in-hospital mortality. Secondary outcomes included rates of acute myocardial infarction, acute aortic dissection, stroke and hypertensive encephalopathy. Chi square test and t tests were used to compare variables for unadjusted analysis. Multivariate logistic regression was used to obtain odds ratios. The model was adjusted for age, demographics, hospital characteristics and Elixhauser co-morbidity index. Results: Of the 1, 214, 169 estimated discharges with hypertensive emergency, 21.8% were admitted on a weekend. On unadjusted data analysis, patients admitted on a weekend had significantly higher mortality (3.1% vs. 2.5%; p ⬍ 0.001) than those admitted on a weekday. This effect persisted after multivariate logistic regression. The odds of mortality on weekends were 1.17 (95%CI 1.08-1.26) times higher when compared to weekdays. Similarly rates of acute myocardial infarction, acute aortic dissection, stroke and hypertensive encephalopathy were significantly higher on weekends. Conclusions: We conclude that there is a significant weekend effect for admissions with hypertensive emergencies. Weekend admissions for this disease have significantly higher rates of mortality and other complications. Investigations into the cause of this phenomenon are warranted.

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AGREEMENT BETWEEN COMMONLY APPLIED MORTALITY PREDICTION MODELS FOR MEDICAL INTENSIVE CARE PATIENTS IN A LARGE ACADEMIC MEDICAL CENTER SETTING

VTE PROPHYLAXIS IN CRITICAL CARE PATIENTS: DATA FROM VTE START (VENOUS THROMBOEMBOLISM STUDY TO ASSESS THE RATE OF THROMBOPROPHYLAXIS)

Eric Hixson, The Quality Institute - Cleveland Clinic Health System, Jorge Guzman, Cleveland Clinic Introduction: APACHE IV and MPM-0 III were validated with 2-5 % and 12% hospital transfer patients respectively. Prior research has suggested that hospital transfers may bias standardized mortality ratios (SMR). Our medical intensive care unit (MICU) has a high volume of admissions and up to 50% come from outside hospitals. Hypothesis: Commonly used mortality prediction models lack agreement in their predictive accuracy in a high acuity, high hospital transfer patient population. Methods: Consecutive admissions to a single MICU from January 1, 2008 to March 31, 2010. Hospital transfer (HT) status was determined by patient origin and transportation mode prior to arriving to this hospital. APACHE IV and MPM 0 III were calculated and compared using proprietary third party software. Data was collected manually using a standardized protocol. Only patients that qualified for both models are compared. Correlation coefficients (rho) and Receiver Operating Characteristic (ROC) analysis were performed to test agreement and predictive accuracy. Results: The population consisted of 2, 061 admissions with a mean APACHE IV score ⫽ 73.9; HT ⫽ 55.8%; and observed mortality ⫽ 29.2%. Correlation between the two models was low (rho ⫽ 0.382). MPM-0 III underpredicted mortality for both non-HT and HT subgroups. Predictive accuracy was also better for the APACHE IV model in both subgroups: (non-HT: APACHE IV ROC ⫽ 0.813 vs. MPM-0 III ROC ⫽ 0.641 p ⫽ ⬍ 0.001; HT: APACHE IV ROC ⫽ 0.798 vs. MPM-0 III ROC ⫽ 0.679 p ⫽ ⬍ 0.001). Conclusions: The APACHE IV model outperforms MPM-0 III in the high acuity, high hospital transfer setting though opportunities may exist to improve its predictive accuracy. A high proportion of HT can affect ICU benchmarking measures and caution is warranted when interpreting outcome data from such units.


Paul Dobesh, University of Nebraska Medical Center College of Pharmacy, Alpesh Amin, University of California- Irvine, Donald Klepser, University of Nebraska Medical Center College of Pharmacy Introduction: The risk of venous thromboembolism (VTE) can vary widely in critical care patients, but most patients have several risk factors. The American College of Chest Physicians (ACCP) guidelines suggest that most critical care patients will require VTE prophylaxis. While the ACCP provides recommendations on the appropriate type, dose, and duration of VTE prophylaxis, the frequency of hospital compliance with these guidelines in critical care patients is unknown. Hypothesis: To determine the rates of appropriate VTE prophylaxis in critical care patients in terms of type, dose, and duration. Methods: Discharge and billing records for patients admitted to any of 16 acute-care hospitals from January 2005 to December 2006 were obtained. Patients ⱖ 18 years who had an inpatient stay ⱖ 2 days, and no apparent contraindications to VTE prophylaxis were grouped into the categories of critical care, surgery, and medically ill. The recommended type (mechanical or pharmacologic), dose, and duration of VTE prophylaxis were identified based on the ACCP 7th guidelines and compared to the regimen actually received, if any. These data represent an analysis of the critical care patients in VTE START. Critical care patients had to have mention of a critical care unit stay during their hospitalization. Results: There were 22, 801 (33.4%) critical care patient in VTE START. More than half of critical care patients had multiple risk factors, with the most common risk factors being surgery (47.5%), heart/respiratory failure (45.3%), acute medical illness (36%), and a central venous catheter (11.9%). While some type of VTE prophylaxis was documented in 73.5% of critical care patients, only 12.5% had appropriate type, dose, and duration of prophylaxis. The most common reason for inappropriate prophylaxis was incorrect type selected (34.2%). Inappropriate dosing of prophylaxis was seen in 12.8% of patients, 3.8% had inappropriate duration, and 10.2% had both inappropriate dosing and duration. Conclusions: This analysis represents the largest evaluation of VTE prophylaxis in critical care patients. While most critical care patients receive some type of VTE prophylaxis, it is often not appropriate in terms of type, dose, and duration.

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RISK FACTORS ASSOCIATED WITH THE DEVELOPMENT OF PRESSURE ULCERS IN THE CRITICAL CARE SETTING

AMERICAN COLLEGE OF SURGEONS NATIONAL SURGICAL QUALITY IMPROVEMENT PROGRAM UNDERESTIMATES THE RISK ASSOCIATED WITH MILD AND MODERATE POSTOPERATIVE AKI

Margaret Fortino-Mullen, University of Pennsylvania Health System, Janet Spinks, Philips VISICU, Kathryn Brown, The Christ Hospital, Erkan Hassan, VISICU Introduction: The development of pressure ulcers in the critical care setting is a common problem that significantly contributes to length of stay and health care costs. In 2008, the Centers for Medicaid and Medicare no longer provides reimbursement for hospital acquired pressure ulcers as they are considered ‘reasonably preventable through the application of evidence based guidelines‘. There is however, concern among practitioners that pressure ulcers develop despite meticulous guideline implementation and that patient comorbidities may contribute significantly to incidence. Hypothesis: Risk factors of age, gender, length of stay, Braden score, mechanical ventilation and vasopressors significantly contributes to the development of pressure ulcers. Methods: A prospective cohort study was conducted in 2 ICU’s: a 24 bed surgical/trauma unit within an urban academic medical center and a 20 bed medical ICU of a large tertiary care facility. 789 patients admitted to the ICU’s from November 2009 until May 2010 were evaluated in the final analysis. Patients admitted with pressure ulcers were excluded from the study; only patients with hospital acquired pressure ulcers were included in the analysis. Results: The mean patient age was 61 (SD 14) years, 58% were male (N ⫽ 461) and the incidence of pressure ulcers was 27.5% (N ⫽ 217) during the observation period. Logistic regression analysis demonstrates a statistically significant relationship between the development of pressure ulcers and the use of vasopressors (OR ⫽ 0.583 [95% CI: 0.355 - 0.957], p ⬍ .05) and mechanical ventilation (OR ⫽ 0.594 [95% CI: 0.398 - 0.887, p. ⬍ .05. ICU length of stay also contributed significantly to the development of pressure ulcers (OR ⫽ 1.138 [95% CI: 1.102 - 1.175], p ⬍ .0001). There was not a statistically significant correlation between the Braden score and pressure ulcer development. Conclusions: While pressure ulcers remain an important indicator of quality, skin breakdown may be unaviodable in patients who present with respiratory and hemodynamic medical problems that impede optimal oxygenation to tissues. Use of guidelines may not sufficiently reduce the risk of pressure ulcers in patient with multiple comorbidities.

15 INCORPORATING THE EVIDENCE USING CPOE AND DASHBOARDS: IMPLEMENTATION OF SCCM ADULT RED BLOOD CELL TRANSFUSION CLINICAL GUIDELINES Eric Luehr, Vinita Bahl, Rob Davenport, Timothy Laing, Andrew Rosenberg, Pauline Park, University of Michigan, Lena Napolitano, University of Michigan School of Medicine Introduction: A majority of red blood cell (RBC) transfusions (tx) given to critically ill patients are for hemodynamically stable anemia. Institutional guidelines were created based on the SCCM RBC tx guideline and implemented in all adult ICUs. We sought to examine guideline compliance in these ICUs. Hypothesis: Implementation of a SCCM-based RBC tx guideline will result in decreased blood use in the ICU. Methods: The surgical ICU (SICU) had implemented RBC tx guideline 4 years prior, with 40% reduction in RBC use. A multidisciplinary blood LEAN team was established to review RBC use in all adult ICUs (n ⫽ 6) which confirmed variability in tx triggers amongst the ICUs. RBC utilization current state value stream maps were created. An evidence-based institutional RBC tx guideline was created [tx trigger hemoglobin (Hb) ⬍7 g/dL] and educational efforts initiated and reinforced through electronic order entry (CPOE) alerts linked to actual patient Hb. If Hb ⬎7, the practitioner could override the alert by provision of a reason for tx. Monthly trends in RBC tx by pre-tx Hb and RBC units used were provided as feedback to ICUs using electronic real-time dashboards. ICU Appropriate RBC use by pre-tx Hb was compared pre/post guideline implementation (7/2008-7/2010) by t-test for independent groups. Results: Analysis of current state documented that in SICU, 76% of patients (n ⫽ 832) had RBC tx with Hb ⬍8 compared to only 26% (310) in CVC-ICU where no guideline was in place. After guideline implementation, 4 ICUs demonstrated a statistically significant reduction in mean pre-tx Hb: Neuro-ICU (8.47-7.65, p ⬍ 0.0001), CVC-ICU (8.35-7.92, p ⫽ 0.0004), CCMU (7.89-7.69, p ⫽ 0.029), TB-ICU (7.59-7.21, p ⫽ 0.003); 2 ICUs demonstrated no change: SICU (7.48-7.45) and CCU (8.32-8.24). The most common reason for ordering a tx outside of the guidelines was “Attending physician deems necessary.” Institutional RBC transfusion significantly decreased from 3000 units 1/2009 to 2200 units in 2/2010. Conclusions: Implementation of the SCCM evidence-based RBC tx guideline using CPOE with alerts and real-time electronic dashboards for provider feedback led to a significant reduction in ICU blood utilization.

Meghan Brennan, Shahab Bozorgmehri, Charles Hobson, Darwin Ang, Philip Efron, A. Joseph Layon, Azra Bihorac, University of Florida Introduction: Postoperative AKI is associated with increased short and longterm morbidity and mortality. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) defines AKI as postoperative changes in serum creatinine (sCr) ⬎2 mg/dl compared to baseline sCr (BsCr). This definition may underestimate the occurrence of AKI in patients with small postoperative changes in sCr. Hypothesis: Small postoperative changes in sCr (⬍2 mg/dl) are predictive of in-hospital morbidity and mortality. Methods: Retrospective, single center study of 37, 321 adult surgical patients with estimated glomerular filtration rate (eGFR) ⬎ 65ml/min/m2 admitted to Shands Hospital from 2000-2008 for ⱖ2 days. AKI was defined using AKIN classification as postoperative change in sCr ⱖ0.3 mg/dl. Patients were also classified using NSQIP-AKI definition (postoperative change in sCr ⬎2 mg/dl compared to BsCr). ROC curves were generated by group and area under the curve (AUC) determined predictive ability of maximum change in sCr from baseline on inhospital mortality and morbidity. The level of change from BsCr that best predicts outcome was determined by maximizing sensitivity and specificity along the ROC curve. Results: NSQIP-AKI definition identified 2% of all patients as having AKI compared to 27% identified by AKIN definition. 93% of patients with AKI defined by AKIN were not classified as having AKI using NSQIP definition. Maximum change in sCr from baseline was predictive of in-hospital mortality (AUC range 0.86-0.81) and sepsis (AUC range 0.84-0.76). ROC results for both outcomes indicate that change of 0.2 - 0.3 mg/dl from BsCr is predictive of mortality and sepsis (sensitivity range 0.65-0.75, specificity range 0.76-0.85). The change of 2 mg/dl used for NSQIP-AKI cut-off had very low sensitivity for both mortality and sepsis (0.2). Conclusions: Conclusion: Postoperative sCr change as low as 0.2-0.3 mg/dl is predictive of hospital mortality and sepsis. Current ACS NSQIP severely underestimates the risk associated with mild and moderate postoperative AKI.

16 MISSING DATA IN LARGE ICU DATABASES Andre´ Fialho, Federico Cismondi, Massachusetts Institute of Technology, Susana Vieira, Joaõ Sousa, Technical University of Lisbon, Instituto Superior Tećnico, Shane Reti, Division of Clinical Informatics, Roy Welsch, Massachusetts Institute of Technology, Michael Howell, Silverman Institute For Health Care Quality and Safety, Stan Finkelstein, Massachusetts Institute of Technology Introduction: Missing data are a pervasive difficult problem, and little is known about their impact on large ICU datasets; failure to adequately deal with missingness can profoundly bias studies’ results. Hypothesis: We hypothesize that automated methods can correctly classify the mechanism of missingness in large ICU datasets. Methods: We used the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) II database, to explore two approaches to classify missing data as Observed At Random (OAR) or Observed Not At Random (ONAR). In the first approach, we used a traditional statistical method described by Allison (2001). In a second novel approach, we used methods drawn from Artificial Intelligence (AI) to classify missingness by generating rule sets that combine other variables’ values in a continuous non-linear fashion. We used blinded simulated ICU datasets with known patterns of missingness to evaluate algorithm performance. Results: MIMIC II database includes 26, 655 patients and 159, 972, 807 data points with varying sampling frequencies. After time-ordering these data points, approximately 40% of the information was found to be missing. Against simulated ICU datasets, statistical modeling correctly classified missing data as OAR or ONAR 69 ⫾ 2 % of the time with sensitivity 0.74 ⫾ 0.13 and specificity 0.68 ⫾ 0.10, and from the assessment of the inter-rater reliability, we found a kappa of 0.49. AI methods correctly classified missing data 80.6 ⫾ 1.86 % of the time, with sensitivity 0.80 ⫾ 0.08, specificity 0.62 ⫾ 0.06, and a kappa of 0.62. Conclusions: Critical care databases are a rich source of information, but researchers must be cautious to avoid bias. Classifying the pattern of missingness is a critical step that enables the application of appropriate correction methods to improve reliability. We present two approaches for automated classification of missing data, and show that AI methods are likely to produce better results than traditional approaches. Future work will seek to expand and refine AI techniques in the management of missing data in large ICU datasets. 1-Allison, P.D. (2001) Missing Data. Sage University Paper Series on Quantitive Applications in the Social Sciences, 07-136. Thousand Oaks, CA


Oral Abstract Session: Epidemiology-Pediatrics 17

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AN INTENSIVIST-DIRECTED MULTIDISCIPLINARY PEDIATRIC CARDIAC CRITICAL CARE TEAM MODEL IS ASSOCIATED WITH IMPROVED OUTCOMES FOLLOWING PEDIATRIC CARDIAC SURGERY

DYSAUTONOMIA AFTER PEDIATRIC BRAIN INJURY IN A REHABILITATION SETTING

Erin Mayo, Jennifer Helman, Rajashekhar Siddappa, Lee Tosi, Alexandre Rotta, Riley Hospital for Children Introduction: Previous studies suggest an association between intensive care unit organizational models and outcomes in critically ill adults. However, little is known about whether the structure of a team caring for children and young adults following surgery for congenital heart defects affects outcomes. Hypothesis: We hypothesized that an intensivist-directed cooperative dedicated multi-disciplinary Pediatric Cardiac Critical Care (PCCC) team model would be associated with improved outcomes following cardiac surgery. Methods: On January 1, 2009, care at our institution transitioned from a surgeon-led team with physician extenders and on-demand multispecialty support to an intensivist-directed cooperative dedicated multidisciplinary PCCC team model. We retrospectively reviewed data from patients who required critical care following cardiac surgery from 2006 to 2008 (previous care model) and for 2009 (new care model). Continuous data were analyzed via t-test or the Mann-Whitney Rank Sum test. Categorical data were analyzed via risk ratios (RR) with corresponding 95% confidence intervals (CI). Values are means ⫾ SD, unless otherwise noted. Results: Despite a higher severity of illness (3.28 ⫾ 0.8 vs. 2.83 ⫾ 0.98, p ⬍ 0.001) the new care model was associated with decreased hospital mortality (0.94% vs 4.29%, RR 0.81, 95%CI 0.77-0.92, p ⫽ 0.004), shorter duration of mechanical ventilation (5 [2-10] vs. 6 [2-14] days [medians and 25-75th%ile], p ⫽ 0.023) and a trend in reduced ICU length of stay (6.6 ⫾ 12 days vs 8.92 ⫾ 18 days, p ⫽ 0.12) compared to the previous care model, respectively. Conclusions: Our data suggest that an intensivist-directed cooperative dedicated multi-disciplinary PCCC team model is associated with decreased mortality and decreased duration of mechanical ventilation in children and young adults who require critical care following cardiac surgery.

Katherine Kirk, University of Pittsburgh School of Medicine, Michael Shoykhet, Washington University School of Medicine, Jong Jeong, University of Pittsburgh Graduate School of Public Health, Maryanne Henderson, The Children’s Institute, Michael Bell, Ericka Fink, Children’s Hospital of Pittsburgh Introduction: Dysautonomia is a clinical diagnosis consisting of paroxysmal fever, hypertension, tachycardia, tachypnea, diaphoresis, and/or dystonia. It occurs in 9-33% of adults after brain injury and is associated with poor outcome, while little information is available in children. Hypothesis: We sought to determine the prevalence of dysautonomia in children with brain injury and to characterize clinical features, treatments utilized, and effects on outcome. Methods: We developed a database of children (1 wk – 18 y) with traumatic brain injury (TBI), cardiac arrest, stroke, central nervous system infection, or brain neoplasm admitted to an inpatient rehabilitation facility between 2002-2009. Diagnosis of dysautonomia, type of brain injury, daily clinical signs consistent with dysautonomia diagnosis, length of stay, readmissions, treatments, disposition, and WeeFIM testing were extracted from the medical record. Data were analyzed for differences between groups with and without dysautonomia using t-test, Fisher exact, and ROC curves. Results: Dysautonomia occurred in 13% of children with brain injury (n ⫽ 249, 62% male, 11.8 y ⫾ 5.6). Prevalence varied by injury type (TBI ⫽ 9%, cardiac arrest ⫽ 31%, p ⬍ 0.05). Fever, hypertension, tachycardia, tachypnea, diaphoresis, and dystonia were more frequent among dysautonomic children (all p ⬍ 0.05) and the combination of hypertension, diaphoresis, and dystonia had the highest accuracy in predicting dysautonomia (AUC ⫽ 0.92). Dysautonomic children received more benzodiazepines, antihypertensives, clonidine, and baclofen, had longer rehabilitation stays and more hospital readmissions (all p ⬍ 0.05). Children with dysautonomia also had lower admission and discharge WeeFIM scores and exhibited less improvement on the score’s motor component (all p ⬍ 0.05). Conclusions: Dysautonomia is common in children recovering from brain injury and is associated with prolonged and less effective rehabilitation. The combination of hypertension, diaphoresis, and dystonia was most closely associated with dysautonomia and may serve as a screening tool for prospective studies. More effective, standardized approaches to diagnosis and treatment of dysautonomia are needed to maximize patient outcomes.

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EXTREMES OF WEIGHT CENTILE ARE ASSOCIATED WITH INCREASED RISK OF MORTALITY IN PEDIATRIC INTENSIVE CARE PATIENTS

ORGAN DYSFUNCTION AND PLASMA EXCHANGE (PEX) IN CHILDREN WITH THROMBOCYTOPENIA-ASSOCIATED MULTIPLE ORGAN FAILURE (TAMOF): THE PROSPECTIVE CHILDREN’S TAMOF NETWORK STUDY

Andrew Numa, Gary Williams, John Awad, Hari Ravindranathan, John McAweeney, Sydney Children’s Hospital Introduction: Although numerous studies have linked extremes of weight with poor outcome in adult intensive care patients, the effect of weight on intensive care outcome has not previously been reported in the pediatric population. Hypothesis: The aim of this study was to investigate the relationship between admission weight centile and risk-adjusted mortality in pediatric intensive care patients. Methods: Data was collected on 6337 consecutively admitted patients over an 8.5 year period in a 15 bed paediatric intensive care unit located in a tertiary referral children’s hospital. Weight centile was entered into a multivariate logistic regression model that included all other Pediatric Index of Mortality (PIM-2) variables in order to determine whether weight centile was an independent risk factor for mortality. Results: Weight centile was associated with mortality in univariate analysis, with the lowest mortality being associated with weights on the 75th centile and increasing symmetrically around this nadir. Mortality for patients with the lowest weight centiles was more than double that of patients with weights on the 75th centile. A transformed weight centile variable (absolute value of weight centile-75) was entered into a multivariate logistic regression model that included all other PIM-2 variables. In multivariate analysis, the weight centile variable was independently associated with mortality (odds ratio 1.02 p ⬍ 0.001). Patients with low and high weight centiles were also over-represented numerically; 21.5% of patients had weights ⱕ3rd centile and 5.7% had weights ⱖ97th centile compared to the expected 3% in each group if the population were distributed normally (p ⬍ 0.001). Conclusions: Weight centile is an independent risk factor for mortality in the ICU, with mortality increasing for patients at either end of the weight spectrum. These observations suggest that the accuracy of mortality prediction algorithms may be improved by inclusion of weight centile in the models. A prospective multicentre study should be undertaken to confirm our findings.


James Fortenberry, Children’s Healthcare of Atlanta at Egleston, Trung Nguyen, Texas Children’s Hospital, Richard Toney, Children’s Healthcare of Atlanta, Andrea Knezevic, Rollins School of Public Health, Kristine Rogers, Children’s Healthcare of Atlanta, Children’s TAMOF Network Study Group -, Children’s Introduction: TAMOF is a thrombotic microangiopathy with ADAMTS-13 deficiency and increased vWF multimers described in septic children (Nguyen et al., Crit Care Med 2009). Use of PEx improved organ dysfunction survival in this small trial. We developed a multicenter pediatric study network to prospectively evaluate course, treatment and outcome of TAMOF in a larger study population. Hypothesis: Children with TAMOF demonstrate decreased ADAMTS-13 and increased vWf antigen levels. PEx is associated with improvement of organ dysfunction in TAMOF patients compared to those receiving standard therapy alone. Methods: Prospective nonrandomized observational trial with 10 US PICUs enrolling children 0-21 years (⬎5 kg) meeting TAMOF criteria: platelet count ⬍100K and organ failure index ⬎2. Demographics, PRISM/PELOD scores, and outcomes were collected via a web-based network registry. PEx use was at center attending discretion, but based on a standard centrifugation approach with 1.5x total plasma volume with FFP on day 1 and single volume daily exchanges ⫻ 5 days standard. Blood was obtained at intervals for biochemical evaluation. Results: 76 children with TAMOF (median age 8.6 yrs; range 1 mo-18 yr) were enrolled. Median platelet count was 54.5 ⫻ 103/mm3. Mean ADAMTS-13 levels were decreased: 53.8 ⫹ 27.8 (0-105); mean vWF antigen was 158 ⫹ 86%. 63 patients received PEx and 13 non-PEx. 30 patients required ECMO (45.9% of PEx, 15.4% of non-PEx). PELOD scores were significantly higher in PEx patients at baseline (p ⫽ 0.03) and were significantly decreased at 7 days with PEx (21.8a`12.2) compared to non-PEx (14.1a`9.9) (p ⬍ .003). PRISM scores were similar at baseline but showed greater decrease at 7 days with PEx (19a`13.7) vs. non-PEx (15.9a`14.2) (p ⫽ 0.03). Mean ADAMTS-13 increase at day 7 with PEx was 25.8 vs. 1.7 with non-PEx (p 0.1). 28 day mortality was 33.3% (21.2% in non-ECMO) in PEx patients and 46.1% (45.5% in non-ECMO) in non-PEx pts (p ⫽ 0.5; 0.139) Conclusions: In this septic TAMOF cohort, ADAMTS-13 levels were decreased, and PEx was associated with greater improvement in organ dysfunction compared to standard therapy alone. These results can inform a randomized trial to determine the contribution of PEx to TAMOF outcome.

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MYELIN BASIC PROTEIN LEVEL INCREASES IN THE CEREBROSPINAL FLUID OF CHILDREN AND INFANTS FOLLOWING TRAUMATIC BRAIN INJURY: THE EFFECT OF THERAPEUTIC HYPOTHERMIA.

ICU USE AND MORTALITY ARE HIGHER AMONG CHILDREN WITH ACUTE CNS DISORDERS THAN CHILDREN WITH OTHER ACUTE DISORDERS

Erik Su, Childrens Hospital of Pittsburgh, Patrick Kochanek, University of Pittsburgh Medical Center, Michael Bell, Children’s Hospital of Pittsburgh, David Adelson, Phoenix Children’s Hospital, Hulya Bayir, Children’s Hospital of Pittsburgh, Keri Janesko-Feldman, Safar Center for Resuscitation Research, Rachel Berger, Children’s Hospital of Pittsburgh Introduction: Axonal injury is a key feature of severe traumatic brain injury (TBI) and includes primary axotomy, secondary axotomy (from calcium accumulation and cytoskeletal compaction), and Wallerian degeneration. Several studies have reported increased CSF levels of myelin basic protein (MBP), a constituent of the intact neuronal sheath, after neurologic insults including TBI. However, studies of the serial assessment of CSF MBP levels in pediatric TBI or the effects of therapeutic hypothermia (TH) on MBP levels are lacking. Hypothesis: CSF MBP levels would be increased vs control after severe TBI, exhibit a specific temporal profile, and would be attenuated by TH. We also explored the relationship between gender, outcome (GOS) and MBP level. Methods: We examined serial CSF MBP levels daily for up to 8 days after severe TBI in children enrolled in RCTs assessing the safety and efficacy of TH. We compared these levels to those in CSF from control subjects who were evaluated for, and were subsequently found to not have a CNS infection. TBI subjects received standard clinical care including continuous CSF drainage via ventriculostomy. MBP levels were assessed using a commercial ELISA (IPOC Inc.; Toronto, ON Canada). MBP levels were compared using Wilcoxon Rank-Sum Test. Results: 27 Pediatric TBI cases (14 TH, 13 normothermia (NT), 113 total samples) and 57 controls were enrolled. MBP levels from samples collected 5 or more days postinjury averaged the highest among all time points (93.39 ⫾ 9.40 ng/ml mean ⫾ SEM, ), demonstrating significantly greater levels than postinjury day 1 sample levels (46.01 ⫾ 3.05 ng/ml, p ⫽ 0.026) and controls (0.11 ⫾ 0.01 ng/ml, p ⬍ 0.001). TH did not affect MBP levels. There was no relationship between gender, GOS, and MBP level. Conclusions: This is the first study demonstrating that CSF MBP increases over time in children with severe TBI. Peak levels were dramatically (⬃1000fold) increased vs control. CSF MBP levels were not attenuated by TH vs NT. Our data suggest that injury to myelinated axons represents a major potential target for therapy development in severe pediatric TBI. Support T32HD040686

Jacqueline Moreau, University of Pittsburgh Critical Care Medicine, CRISMA Laboratory, Ericka Fink, University of Pittsburgh Critical Care Medicine, Safar Center, Mary Hartman, Washington University in St. Louis, Derek Angus, University of Pittsburgh Critical Care Medicine, CRISMA Laboratory, Michael Bell, University of Pittsburgh Critical Care Medicine, Safar Center, Walter LindeZwirble, Z D Associates, Robert Watson, University of Pittsburgh Critical Care Medicine, CRISMA Laboratory Introduction: Children with acute disorders of the CNS, including traumatic and non-traumatic injuries, are at risk of substantial morbidity and mortality. However, no study has determined the volume and outcomes of hospitalization for these disorders in the US. Hypothesis: Compared with children hospitalized for other conditions, those with acute CNS disorders receive more critical care and have higher mortality. Methods: We studied all 806, 083 non-federal hospitalizations of children 29 days to 19 years old in 2005 in 10 states (AZ, FL, IA, MA, MD, NC, NJ, NY, TX, & WA), comprising 34% of the US pediatric population. Using ICD-9 codes, we identified 85, 360 admissions with acute CNS disorders and classified them as traumatic (brain [TBI] or spinal cord) and/or non-traumatic. We calculated age- and sex-adjusted population-based incidences using data from the US Census and CDC and generated national estimates of hospitalizations. Results: Nearly a quarter of a million children (247, 970) were hospitalized with an acute CNS disorder in the US in 2005 (2.98/1000 children). Non-traumatic disorders accounted for 79.7% (197, 520 nationally), and the most common specific disorders were seizures (60.1%) and mild TBI (19.2%). Children with acute CNS disorders had nearly 3 times greater ICU use than other hospitalized children (29.5% vs. 11.3%, p ⬍ .001) and made up almost a quarter (23.6%) of patients receiving ICU care. Although only 10.6% of hospital admissions were for acute CNS disorders, they were associated with nearly half (41.7%) of deaths (3, 960 deaths nationally). Among ICU patients, children with CNS disorders had higher in-hospital mortality (4.6 vs.1.7%, p ⬍ .001) and made up 46.1% of deaths. Conclusions: Although they account for a minority of hospital admissions, children with acute CNS disorders more frequently receive critical care and have higher in-hospital mortality than do children hospitalized for other reasons. A focus on this population has the potential to greatly benefit the outcomes of critically ill children.

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INCIDENCE, RISK FACTORS, AND OUTCOMES OF ACUTE KIDNEY INJURY AFTER PEDIATRIC CARDIAC SURGERY – A PROSPECTIVE MULTICENTER STUDY

FACTORS ASSOCIATED WITH RESPIRATORY FAILURE AND MORTALITY AMONG CHILDREN HOSPITALIZED WITH SEASONAL INFLUENZA AND PANDEMIC 2009 H1N1

Simon Li, Maria Fareri Children’s Hospital, Catherine Krawczeski, Cincinnati Children’s Hospital Medical Center, Michael Zappitelli, Montreal Children’s Hospital, Prasad Devarajan, Cincinnati Children’s Hospital, Heather ThiessenPhilbrook, University of Western Ontario, Steven Coca, Richard Kim, Chirag Parikh, Yale University School of Medicine

Carl Eriksson, Adrienne Randolph, Children’s Hospital Boston

Introduction: Acute kidney injury (AKI) occurs frequently after pediatric cardiac surgery. The incidence and risk factors for AKI are unclear because prior studies used varying definitions of AKI and were limited by their single center, retrospective design often over many years.Hypothesis: To determine the incidence, severity and risk-factors of AKI in children undergoing cardiac surgery for congenital heart defects. Methods: We conducted a prospective observational multicenter cohort study in three pediatric intensive care units at academic centers and enrolled 311 children between the ages of 1 month and 18 years undergoing pediatric cardiac surgery from July 2007 to December 2009. The primary outcome, AKI, was defined as a ⱖ50% increase in serum creatinine from the pre-operative value in the first 7 days after surgery. We a priori defined and collected information on 28 candidate risk factors for AKI. Secondary outcomes were length of mechanical ventilation, length of ICU and hospital stays, acute dialysis, and in-hospital mortality. Results: The cohort had an average age of 3.8 years with 45% females and was mostly white (82%). One third had prior cardiothoracic surgery, 91% of the surgeries were elective, and almost all patients required cardiopulmonary bypass (CPB). AKI occurred in 42% (130 patients) within 3 days after surgery. Children ⱖ 2 years old and less than 13 years old had 72% lower likelihood of AKI (adjusted OR: 0.28, 95% CI: 0.16, 0.48), and patients 13 years and older had 70% lower likelihood of AKI (adjusted OR: 0.30, 95% CI: 0.10, 0.88) compared to patients less than 2 years old. CPB time was linearly and independently associated with AKI. Development of AKI was independently associated with prolonged ventilation and with increased length of hospital stay. Conclusions: AKI is common after pediatric cardiac surgery and impacts in-patient outcomes. CPB time and age were independently associated with AKI risk.

Introduction: Annual influenza epidemics cause significant morbidity and mortality in children. In severe influenza pandemics, high rates of respiratory failure and death occur in patients without risk factors. Hypothesis: Hospitalization with 2009 pandemic influenza A(H1N1) virus (2009 H1N1) resulted in increased rates of respiratory failure and death than would be expected in children hospitalized with seasonal influenza. Methods: Using data from 43 U.S. pediatric hospitals in the Pediatric Health Information System (PHIS) database, we identified children hospitalized with influenza from July 2006 through December 2009. We created and validated multivariate logistic regression models to identify risk factors for acute respiratory failure and mortality among seasonal influenza admissions. We applied the models to children admitted with 2009 H1N1, comparing observed to expected rates (standardized complication ratio (SCR) for respiratory failure and standardized mortality ratio (SMR)). Results: We included 20, 215 discharges. Factors associated with respiratory failure in the seasonal influenza cohort were age ⬍1 year, high-risk (HR) health conditions (OR 6.5, 95% CI, 5.5-7.6), medium-risk (MR) health conditions (OR 2.3, 95% CI, 1.9-2.9), and a co-diagnosis of Staphylococcus aureus pneumonia (OR 21.5, 95% CI, 13.7-33.7). Factors associated with mortality were adolescent age, HR conditions (OR 9.2, 95% CI, 5.6-15.2), MR conditions (OR 1.6, 95% CI, 1.0-2.5), and S. aureus pneumonia (OR 18.5, 95% CI, 10.4-32.9). The same factors were predictive of respiratory failure and mortality in 2009 H1N1 cases, but we found lower than expected rates of respiratory failure (SCR 0.73, 95% CI, 0.67-0.79) and mortality (SMR 0.74, 95% CI, 0.57-0.94) using coefficients from the seasonal influenza model. Conclusions: Although there was a higher rate of pediatric influenza-related hospitalization during the 2009 H1N1 pandemic, this was associated with decreased rates of respiratory failure and mortality than would be predicted with seasonal influenza. Co-diagnosis of S. aureus pneumonia was associated with a significant increase in the odds of respiratory failure and death in children hospitalized with seasonal and 2009 H1N1 influenza.


Oral Abstract Session: Infectious Disease-Sepsis 25

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ICU-ACQUIRED CLOSTRIDIUM DIFFICILE IS AN INDEPENDENT PREDICTOR OF IN-HOSPITAL MORTALITY

TALACTOFERRIN ALFA REDUCES 3 AND 6 MONTH ALLCAUSE MORTALITY IN PATIENTS WITH SEVERE SEPSIS

Frank Vandy, Andrea Kussman, Nick Osborne, Paul Reckard, Christy Zalewski, Craig Meldrum, Pauline Park, Lena Napolitano, Krishnan Raghavendran, University of Michigan School of Medicine

Mitchell Levy, Brown University, Kalapatha Guntupalli, Baylor Collage, R. Dellinger, Cooper University Hospital, Nathan Dean, Children’s National Medical Center, Peter Morris, Wake Forest University School of Medicine, Venkata Bandi, Ben Taub General Hospital, B Margolis, West Suburban Medical Center, Emanuel Rivers, Henry Ford Hospital, Robert Lodato, University of Texas Health Science Center, J Schaumberg, Agennix Inc

Introduction: The natural history of Clostridium difficile (CD) infection is changing as epidemic strains are associated with greater virulence and drug resistance. The effect of ICU acquired CD on in-hospital mortality is unclear. Hypothesis: Acquisition of CD, while admitted to the ICU, is associated with higher in-hospital mortality. Methods: Retrospective data collection was performed on all admissions to a 20 bed tertiary care academic hospital surgical ICU from January 2004 to July 2010. Per hospital policy, CD was diagnosed by an immunoassay detecting toxins A and B. During the latter half of the study period, diagnosis included antigen testing and PCR. Patients with a first time diagnosis of CD were compared to those who did not acquire CD during the study period. Primary outcome was in-hospital mortality. Amongst survivors and non-survivors with CD, a two-tailed Student’s t-test and Fisher’s exact test compared continuous and categorical variables respectively. Logistic regression was performed to determine the odds ratio of in-hospital CD associated death. Results: During the study period 148 patients were positive for CD compared to 7096 patients without CD. The unadjusted in-hospital mortality rate was 23.13% for those patients with CD and 8.07% for those without. CD was an independent predictor of in hospital mortality (odds ratio, 1.79; 95% CI, 1.21-2.88; p ⫽ .015). Non-survivors had higher day 1 APACHE III scores (66.91 vs. 80.1; p ⫽ .007) and were in septic shock (56% vs. 22%; p ⬍ .001) and renal failure (47% vs. 20%; p ⫽ .005) on the day CD was diagnosed. There was no significant difference between CD survivors and non-survivors with respect to age, gender, history of hypertension, diabetes, or coronary artery disease, active malignancy, immunosuppressive therapy, antibiotic choice following diagnosis, white blood cell count or albumin at the time of diagnosis. CD was associated with an increased ICU length of stay compared to those without CD (24.2 days vs. 4.3 days; p ⬍ .001). Conclusions: Acquiring CD infection during an ICU admission is independently associated with increased in-hospital mortality. The role of CD as a causative factor or rather a marker of severe illness remains uncertain.

Introduction: Severe sepsis affects approximately 750, 000 people in the USA annually, is increasing in incidence, and causes an estimated ICU mortality of 30%. Talactoferrin is an oral biologic therapy with immunomodulatory and antibacterial properties. Hypothesis: Talactoferrin will reduce 3 and 6 month mortality in patients with severe sepsis. Methods: In this multicenter, randomized, placebo-controlled double blind study, patients with severe sepsis (N ⫽ 190) were randomized to receive talactoferrin 1.5 g or placebo every eight hours for up to 28 days. The primary endpoint was 28 day all cause mortality. Secondary endpoints for the study included 3 & 6 month all cause mortality. Eligible patients had onset of severe sepsis within 24 hours prior to randomization. During the conduct of the trial errors occurred in the course of drug labeling that affected randomization and consequently altered drug assignment for some patients. The primary endpoint were therefore analyzed using logistic regression in a modified intent-to-treat (MITT) population using “as treated” instead of “as randomized” for group assignment. Patients were assigned to the treatment group according to the study drug they received during the first week on study. We previously reported that talactoferrin decreased 28-day all-cause mortality compared to placebo and was very well tolerated. Results: The baseline characteristics were similar in both groups. By modified intent-to-treat analysis, 3 month all cause mortality was reduced (17.9 versus 29.7%, P ⫽ 0.09), and 6 month all cause mortality was reduced (21.1 versus 35.6%, P ⫽ 0.04.) The incidence of grade 3 to 5 adverse events was similar in both groups. Conclusions: The effect of talactoferrin on reduction in 28-day all-cause mortality was sustained to 6 months. The reduction in mortality was seen in patients with and without cardiovascular dysfunction although there appeared to be a greater, significant effect in patients without cardiovascular dysfunction. Talactoferrin appears to be very well tolerated and further study of this compound is warranted in patients with severe sepsis. Study was funded in part by a grant from the National Institutes of Health

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HOSPITAL BATH BASINS ARE FREQUENTLY CONTAMINATED WITH MULTI-DRUG RESISTANT ORGANISMS (MDRO) WHICH ARE COMMON ICU PATHOGENS

STATIN USE NOT PROTECTIVE FOR SEPSIS-INDUCED ACUTE KIDNEY INJURY

Dror Marchaim, Sanjeet Panda, Wayne State University, Alexis Taylor, Wane State University, Teena Chopra, Kayoko Hayakawa, Diixa Patel, Jason Pogue, Paul Lephart, Sorabh Dhar, Keith Kaye, Wayne State University Introduction: Hospital-acquire infections (HAIs) are the 5th leading cause of death in US hospitals. Twenty-five percent of HAIs occur in intensive care units (ICUs). Patient-to-patient transmission of pathogens is common and ultimately leads to infection and increased morbidity, mortality and costs. Many HAIs are no longer being reimbursed by Medicare, which further increases attributable costs. The environment plays an important role of spread of HAIs in the hospital and many objects can serve as unrecognized reservoirs for pathogens. The aim of the study was to investigate the role of bath basins as potential reservoir of MDROs in nosocomial settings. Hypothesis: Bath basins in hospitals are contaminated with nosocomial MDROs. Methods: A prospective multicenter trial, involving 53 hospitals from 20 different states in the US and from Canada was conducted between 03/2008 – 07/2010. Local Infection Preventionists randomly cultured basins, using a uniform standardized method. At the time of culture, the basins were not visibly contaminated and were considered to be “clean”. All microbiological processing was conducted by an external central laboratory, blinded to the origin of samples. All bacteriologic processing was conducted according to Clinical and Laboratory Standards Institute criteria. Samples were additionally processed, by using selective media, to diagnose the presence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Gram-negative bacilli. Results: Overall, 576 basins from 53 hospitals were sampled during the study period, and 63.34% of the samples were contaminated. There were 199 (34.55%) basins from 52 (98.11%) hospitals that were colonized with VRE, 251 (43.58%) basins from 47 (88.70%) hospitals that were colonized with Gram-negative bacilli; and 24 (4.17%) basins from 19 (35.85%) hospitals that were colonized with MRSA. Conclusions: Basins in hospitals are frequently contaminated with serious nosocomial MDRO pathogens. In today’s era, where there is a growing need for hospitals to reduce HAI rates, diagnosing hidden reservoirs of hospital pathogens and MDROs can facilitate interventions that improve patients’ safety and decrease infection rates.


Raghavan Murugan, The CRISMA Center, Dept of CCM, University of Pittsburgh School of Medicine, Lisa Weissfeld, University of Pittsburgh Graduate School of Public Health, Sachin Yende, Kai Singbartl, Derek Angus, John Kellum, The CRISMA Center, Dept of CCM, University of Pittsburgh School of Medicine Introduction: Sepsis is a leading cause of acute kidney injury (AKI) and animal studies suggest that pleiotropic effects of statins attenuate the risk of AKI. Hypothesis: We tested the hypothesis that prior statin use compared to no statin use is associated with a lower risk for developing AKI in the setting of communityacquired pneumonia (CAP). Methods: Genetic and Inflammatory Markers of Sepsis was a prospective, multicenter, cohort study of patients hospitalized with CAP. Demographics, pneumonia severity and statin use within 7 days of presentation were ascertained prospectively at admission. Risk of AKI was ascertained using the Risk, Injury, Failure, Loss, End stage kidney criteria. The association between statin use and the risk of AKI was modeled using generalized estimating equations after controlling for propensity for statin use including healthy user effect. Results: Of the 1836 patients with CAP, 413 (22.5%) were statin users. Statin users were older (72.4 vs 66.8 years, P ⬍ 0.001), had higher prevalence of cardiac disease (54.1% vs 21.9%, P ⬍ 0.001), had higher pneumonia severity index (93.4 vs 86.2, P ⬍ 0.001), but similar prevalence of chronic kidney disease (2.1% vs 1.6%, P ⫽ 0.50). Nevertheless, statin users compared to non-users were healthier as they were more likely to have health insurance (99.4% vs 94.4%, P ⬍ 0.001); be admitted from home (92.7% vs 87.7%, P ⬍ 0.001), and had independent mobility (67.5% vs 61.2%, P ⬍ 0.001). Exposure to statins was associated with a higher risk of AKI during CAP hospitalization (42.6% vs 32%, P ⬍ 0.001). When adjusted for differences in age, severity of pneumonia, and admission from nursing home, statin use was associated with increased odds of AKI (odds ratio [OR] ⫽ 1.38, 95% CI, 1.05 -1.80, P ⫽ 0.04). This higher risk was attenuated following adjustment for propensity for statin use (OR ⫽ 1.32, 95% CI, 0.99 – 1.75, P ⫽ 0.084). Conclusions: In a large cohort of patients hospitalized with CAP, we were unable to confirm the protective effect of prior statin use on the risk of AKI following pneumonia. The higher risk of AKI observed among statin users may be due to indication bias. Our results do not support the use of statins for prevention of sepsis-induced AKI in humans.

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EFFECT OF CHRONIC KIDNEY DISEASE ON OUTCOMES OF SEVERE SEPSIS

DYNAMIC CHANGE OF PROCALCITONIN, RATHER THAN CONCENTRATION ITSELF, IS PREDICTIVE OF SURVIVAL IN SEPTIC SHOCK PATIENTS

Gagan Kumar, Puneet Sood, Nilay Kumar, Sandeep Markan, Medical College of Wisconsin, Amit Taneja, Jayshil Patel, The Medical College of Wisconsin, Ankit Sakhuja, Medical College of Wisconsin, Rumi Ahmed Khan, Orlando Regional Medical Center, Rahul Nanchal, Medical College of Wisconsin Introduction: Severe sepsis is the most common causes of mortality in noncoronary intensive care units. Acute kidney injury (AKI) in these patients has shown to be an independent risk factor for poor outcomes. Though a few studies have documented that increased prevalence and mortality from severe sepsis in the end stage renal disease population, the same remains largely unknown for patients with chronic kidney disease (CKD). We sought to examine the outcomes of severe sepsis in patients with CKD. Hypothesis: CKD is an independent predictor of worse outcomes in patients with severe sepsis. Methods: Using the Nationwide Inpatient Sample Database (NIS) 2007, patients aged 18 or more who had discharge diagnosis of severe sepsis were identified through ICD-9 code 995.92. The secondary diagnoses of CKD was identified by ICD-9-CM codes 585.1 to 585.5 and 585.9. Outcome variables included all cause in-hospital mortality, development of acute kidney injury, frequency of new dialysis and length of stay. Chi square test and t tests were used to compare the variables for unadjusted analysis. Multivariate logistic regression was used to obtain odds ratios. The model was adjusted for demographics, organ dysfunction in severe sepsis and related co-morbidities. ␣ was set at 0.05. Results: In the 2007 NIS database, there were an estimated 338, 456 discharges with severe sepsis. The unadjusted mortality in CKD patients was 31.9% when compared to 37% in patients with normal kidney function. The multivariate analysis showed that the in hospital mortality from severe sepsis was significantly higher in CKD patients (OR 1.31; 95%CI 1.17-1.46). CKD patients had higher rates of ARF than those with normal kidney function (79% vs. 51.7%). The frequency of new dialysis was significantly higher in CKD patients when compared to normal kidney function (10.3% vs. 6.6%). Conclusions: This observational study shows that in-hospital mortality of severe sepsis is higher in CKD patients when compared to the general population. There is higher frequency of AKI and higher use of new dialysis in these patients. Prospective studies are needed to investigate the reasons for our findings.

Jun Guan, Zhaofen Lin, Hong Lue, Shanghai Changzheng Hospital Introduction: The prognostic value of procalcitonin (PCT) for survival is controversial, mainly due to the much overlap of PCT values in severe sepsis patients. Recent studies shown that dynamic change of PCT concentration is more valuable in distinguishing survivors and nonsurvivors in severe septic patients. PCT concentration greater than 10ng/mL represents severe sepsis condition compatible for septic shock. Hypothesis: Dynamic change of PCT concentration, rather than PCT concentration itself, is predictive of hospital survival when greater than 10ng/mL. Methods: Thirty seven septic shock patients with PCT concentration greater than 10ng/mL were enrolled in this prospective cohort study. Patients were divided into survivors(N ⫽ 25) and non-survivors(N ⫽ 12) based on 28-day hospital outcome. Second PCT measurements were taken 5 days after enrollment and initial measurements. Sequential organ failure assessment (SOFA) score were recorded simultaneously. PCT measurements were blind to the physicians in charge. Dynamic change of PCT and SOFA score were defined as the difference between the second and initial measurement. Mann-Whitney U test and Spearman’s correlation were used for analysis when appropriate. Results: There were no significant difference between survivors and nonsurvivors in age, sex, initial measurement of PCT and SOFA. All survivors had a decrease of PCT concentration, median decrease was 9.73ng/mL. All nonsurvivors had an increase of PCT concentration, median increase was 5.95ng/mL. Significant decrease of PCT concentration (⬎25%) was observed in all the 25 survivors while none of the 12 nonsurvivors had a significant decrease of PCT concentration after 5 days’ management, p ⬍ 0.001. PCT concentration of initial measurement, second measurements, and dynamics were all significantly correlated with their counterparts of SOFA score, p ⫽ 0.026, ⬍0.001 and ⬍0.001, respectively. Conclusions: Significant decrease of PCT concentration, rather than PCT concentration itself, is a perfect indicator of survival in septic shock patients when PCT concentration is greater than 10ng/mL. PCT concentration is highly correlated with SOFA score in septic shock patients even when PCT concentration is above 10ng/mL.

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DETERMINANTS OF TRANS-ENDOTHELIAL MIGRATION OF TRYPANOSOMA CRUZI

ELDERLY PATIENTS WITH INFECTIONS IN THE ICU. RESULTS OF THE EPIC II STUDY

Bria Coates, Conrad Epting, Children’s Memorial Hospital, David Engman, Northwestern University

George Dimopoulos, Attikon University Hospital, Athens, Greece, Despoina Koulenti, Attikon University Hospital, Athens, Greece, Yasser Sakr, Friedrich-Schiller University, Jena, Germany, Antonio Anzueto, The University of Texas Health Science Center At San Antonio, USA, Apostolos Armaganidis, Attikon University Hospital, Athens, Greece, Claude Martin, Nord University Hospital, Marseille, France, Jean-Louis Vincent, Erasme University Hospital, Brussels, Belgium

Introduction: Chagas heart disease (CHD), an inflammatory cardiomyopathy following infection with the parasite Trypanosoma cruzi, is the leading cause of heart failure in Latin America. T. cruzi, an obligate intracellular pathogen, parasitizes the heart, initiating both parasite-specific and autoimmune-mediated inflammation. Although the parasite disseminates intravascularly, the mechanisms by which it exits the bloodstream to target the heart and other organs has never been defined. Understanding the interaction between T. cruzi and the endothelium, a key step in parasite dissemination, could inform therapy to limit the sequelae of infection. Hypothesis: We hypothesized that T. cruzi transmigrates across the endothelial monolayer through monolayer disruption, as distinguished from the regulated diapedesis of leukocytes or direct transit through the endothelial cells. We further hypothesize thatT. cruzi cysteine proteases activate bradykinin receptor (BR) agonists to facilitate this transendothelial migration (TEM). Methods: Human umbilical vein cells were grown to confluence atop a collagen matrix in a 96 well plate or atop 3 um transwell inserts. Agonists and inhibitors of the cysteine protease/bradykinin pathway were added to the endothelial monolayer prior to infection with trypomastigotes. After two hours, the number of transmigrated cells were counted. Monolayer disruption was detected by leakage of FITC-dextran and/or a decrease in electrical resistance across the endothelial monolayer. Results: Our data support that T. cruzi is indeed capable of TEM, with 15 ⫹/⫺ 4% of parasites undergoing TEM instead of infection. Further, a decrease in electrical resistance and an increase in dextran permeability suggest that monolayer disruption is operative. As predicted, inhibition of cysteine proteases or antagonism of BR diminish TEM by up to 40%. Conclusions: T. cruzi clearly has the ability to migrate across an intact endothelial monolayer. This process is likely accomplished through monolayer disruption, and liberation of bradykinin by parasite cysteine proteases increases TEM.

Introduction: Data regarding elderly patients (pts) with infection in the ICU are limited despite the fact that they represent a considerable number. Hypothesis: Patterns of infection and outcomes of the ICU elderly pts with infection have differences compared to those of younger pts. Methods: We included all pts with infection (inf.) enrolled in the Extended Prevalence of Infection in Intensive Care (EPICII) Study; a 1-day prevalence international multicenter observational study performed on May 8, 2007. The elderly [ⱖ76 years old (yo)] pts with infection (inf) were compared with pts 18-40yo and 41-75yo. Results: A total of 7087 of the 13796 adult pts enrolled in the EPICII Study was considered infected: 1553 (21.9%) were ⱖ76yo, 1001 (14.1%) 18-40yo and 4533 (64%) 41-75yo. Observed differences in the type, reason and source of ICU admission were statistically significant only between elderly pts and 18-40yo (p ⬍ 0.05). Elderly pts with infection had more co-morbidities (com) than the 18-40yo (ⱖ1 com: 67vs28%; ⱖ2: 30vs10%, p ⬍ 0.05). The incidence of heart failure (19vs2%), COPD (30vs2%), DM (12vs4%), chr. renal failure (16vs4%) and cancer (17vs7%) was significantly higher in the elderly pts compared to the 18-40yo (p ⬍ 0.05 for all pairwise comparisons). SAPSII score, ICU-and hospital mortality were greater in the elderly pts than in both 18-40yo and 41-75yo (SAPSII: 43vs25vs36; ICU mortality: 31vs16vs 26%; hospital mortality: 43vs21vs33%, p ⬍ 0.05 between groups). The elderly pts had more abdominal inf than the 18-40yo (21vs16%, p ⬍ 0.05), less blood stream inf. than the 41-75yo (12vs17%, p ⬍ 0.05), and less CNS inf. than both 18-40 and 41-75yo pts (1vs3vs7%, p ⬍ 0.05). Microbiological diagnosis was established less frequently in the elderly pts compared to both 18-40yo and 41-75yo pts (64vs71vs72%, p ⬍ 0.05). Gram-negative microorganisms were isolated more frequently in the elderly than in both 18-40yo and 41-75yo pts (68vs59vs62%, p ⬍ 0.05), while viruses (1vs4vs2%, p ⬍ 0.05) and parasites (0.1vs2vs1%, p ⬍ 0.05) were less frequent. Conclusions: Elderly ICU pts with infection are more likely to have more co-morbid conditions, abdominal infections, gram-negative bacteria, and increased ICU and hospital mortality than younger pts.


Oral Abstract Session: Potpourri 33

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ASSOCIATION OF LOW SERUM 25-HYDROXYVITAMIN D LEVELS AND MORTALITY IN THE CRITICALLY ILL

IMPACT OF VITAMIN D DEFICIENCY ON OUTCOME IN CRITICALLY ILL PATIENTS

Andrea Braun, Domingo Chang, Karthik Mahadevappa, Brigham and Women’s Hospital, Fiona Gibbons, Massachusetts General Hospital, Edward Giovannucci, Yan Liu, Harvard School of Public Health, Kenneth Christopher, Brigham and Women’s Hospital

David Higgins, Kelly Queensland, University of Colorado School of Medicine, Alexandra Sufit, University of Colorado Denver, Daren Heyland, Kingston General Hospital, Paul Wischmeyer, University of Colorado At Denver School of Medicine

Introduction: The association between vitamin D deficiency and ICU survival is unknown. Hypothesis: Deficiency in 25-hydroxy vitamin D (25(OH)D) prior to hospital admission is associated with all cause mortality in the critically ill. Methods: Multicenter observational study of patients who received medical or surgical critical care in Boston, Massachusetts. The study cohort was 2, 399 patients, age ⱖ18 years, in whom 25(OH)D was measured less than 1 year prior to hospitalization between 1998 and 2009. Pre-admission 25(OH)D was categorized as deficiency (25(OH)D ⱕ15ng/mL), insufficiency (25(OH)D ⫽ 16-29ng/mL) or sufficiency (25(OH)D ⱖ30ng/mL). Logistic regression examined death by days 30, 90 and 365 post-ICU admission, in hospital mortality and blood culture positivity. Adjusted odds ratios were estimated by multivariable logistic regression models. Results: Pre-admission 25(OH)D deficiency is predictive for short term and long term mortality. 30 days following ICU admission, patients with 25(OH)D deficiency have an OR for mortality of 1.69 (95% CI, 1.28-2.23;P ⬍ .0001) relative to patients with 25(OH)D sufficiency. 25(OH)D deficiency remains a significant predictor of mortality at 30 days following ICU admission following multivariable adjustment (adjusted OR 1.69; 95% CI, 1.26-2.26;P ⬍ .0001). 30 days following ICU admission, patients with 25(OH)D insufficiency have an OR of 1.32 (95% CI, 1.02-1.72; P ⫽ 0.036) and an adjusted OR of 1.36 (95% CI, 1.03-1.79;P ⫽ 0.029) relative to patients with 25(OH)D sufficiency. Results were similar at 90 and 365 days following ICU admission and for in hospital mortality. In a subgroup analysis of patients who had blood cultures drawn (n ⫽ 1, 160), 25(OH)D deficiency was associated with increased risk of blood culture positivity. Patients with 25(OH)D insufficiency have an OR for blood culture positivity of 1.64 (95% CI, 1.05-2.55;P ⫽ 0.03) relative to patients with 25(OH)D sufficiency which remains significant following multivariable adjustment: OR 1.58 (95% CI, 1.01-2.49;P ⫽ 0.048). Conclusions: Deficiency of 25(OH)D prior to hospital admission is a significant predictor of short and long term all cause patient mortality and blood culture positivity in a critically ill patient population.

Introduction: Although vitamin D deficiency has been associated with a myriad of disease conditions, the importance of this deficiency in critically ill patients is still unclear. Hypothesis: We conducted a prospective multi-center study of 195 patients admitted to the ICU to evaluate vitamin D status and its effect on primary (mortality, infection status and length of stay) and secondary (APACHE II and SOFA score, sepsis, pneumonia, CRP and serum creatinine) outcomes. Methods: Utilizing samples from the Waveform Abnormalities of the aPTT in Critically Ill Hospitalized Patients (WaTTCH) study we obtained serum vitamin D levels via a radioimmunoassay kit (DiaSorin). Levels of vitamin D were split into 3 categories: normal ⬎60 nmol/L; insufficient ⬎30 and ⬍60 nmol/L; and deficient ⬍ 30 nmol/L. Cox proportional hazard or logistic/linear regression models were used for statistical analysis with adjustment for age, sex and BMI. Results: Of the 195 patients, 26% were vitamin D deficient 56% were insufficient and 18% were sufficient. Mean levels decreased from 47.0 ( ⫹/⫺ 1.7) nmol/L on admission to 44.4 ( ⫹/⫺ 2.0) nmol/L on 3 days post admission. Vitamin D status did not correlate with all cause mortality (hazard rate ratio (HR) 1.004; 95% CI 0.99-1.01). However, patients with normal levels of vitamin D had a shorter length of stay compared to deficient patients (HR 2.096, 95% CI 1.26-3.45). Vitamin D deficient patients had a higher incidence of infection but this was not significant (Odds ratio 2.18; 95% CI 0.68-7.0). However patients with pneumonia did have significantly lower levels of vitamin D compared to those who did not (p ⬍ .01). Lower vitamin D levels were also associated with increased SOFA scores and elevated serum Cr levels (p ⬍ .05). Conclusions: In conclusion, this is the largest prospective cohort trial to date showing vitamin D deficiency is a common condition in the ICU and the first data showing a significant correlation of vitamin D deficiency with longer length of ICU stay, increased risk of pneumonia, and elevated organ failure scores. This may be due the vital role of vitamin D in regulating immune surveillance and function.

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SEEK AND YOU WILL FIND: IMPROVING DETECTION OF DELIRIUM IN THE INTENSIVE CARE UNIT

MICROTUBULE-ASSOCIATED PROTEIN-2: A NEW SENSITIVE AND SPECIFIC MARKER FOR TRAUMATIC BRAIN INJURY

Sanjeet Grewal, Dennis Hanseman, Betty Tsuei, University of Cincinnati

Stefania Mondello, Banyan Biomarkers, inc and University of Florida, Ross Bullock, University of Miami, Gretchen Brophy, Virginia Commonwealth University, Andras Buki, University of Pecs, Jacskon Streeter, Banyan Biomarker, Inc., Kara Schmid, Frank Tortella, Walter Reed Army Institute of Research, Ronald Hayes, Kevin Wang, Banyan Biomarkers, inc

Introduction: Testing for delirium in the intensive care unit (ICU) often occurs only once daily and may underreport the true prevalence of this disorder. “Sundowning”, or nighttime delirium, is believed to be common during hospitalization, but there is little evidence of this phenomenon. This study investigates delirium in a surgical intensive care unit (SICU) of a tertiary referral center where testing is performed up to six times daily. Hypothesis: Increased frequency of delirium assessment throughout the day will improve delirium detection and quantify the prevalence of nighttime delirium, or “sundowning”. Methods: All SICU admissions during 2009 that were entered into Critical Outcomes, an ICU specific database, were reviewed. Patients with ICU stay of ⬍ 2 days or Glasgow Coma Score ⱕ14 were excluded. The SICU protocol for delirium assessment utilized the Confusion Assessment Method for the ICU (CAM-ICU) every four hours while the patient was awake. A delirious patient was defined as having at least one delirious day. A delirious day was defined as a 24 hour period beginning at 7 AM which included at least one positive CAM-ICU assessment. CAM-ICU evaluations were further characterized as daytime (7AM-7PM) or nighttime (7PM-7AM). Results: Three hundred and thirty four admissions (310 patients with 24 readmissions) and 11, 097 CAM-ICU assessments were analyzed. Using only the commonly employed single morning assessment, delirium was detected in 117(34.0%) patients; in contrast, using assessments performed every four hours, delirium was detected in 138(41.3%) patients. With more frequent testing, delirium was detected 55% more often than single morning assessment (387 days per 1000 ICU days vs. 249 days per 1000 ICU days). CAM-ICU testing was positive in 521 of 1533 (34%) daytime intervals and 524 of 1474 (36%) of nighttime intervals (p ⫽ 0.37). Conclusions: Multiple CAM-ICU assessments on a daily basis increased the detection of delirium both in the number of patients diagnosed and in the overall number of delirious days. There was no difference in daytime vs. nighttime detection of delirium, dispelling the myth of ‘sundowning‘. Better detection of delirium may promote earlier treatment and improve outcomes.


Introduction: Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neurons. Hypothesis: We hypothesize that MAP-2 is a potentially reliable and specific biomarker for traumatic brain injury (TBI) in humans. Therefore, we examined CSF levels of MAP-2 in adults with severe TBI and compared them to controls; and the relationships between MAP-2 levels and injury severity, outcome and survival in patients with severe traumatic brain injury. Methods: This multicenter prospective case control study enrolled 95 patients with severe TBI (Glasgow Coma Score [GCS] ⱕ8), who underwent ventriculostomy. Patients requiring CSF drainage for other medical reasons served as controls. CSF samples were taken from each TBI patient at admission and every 6 hours thereafter for a maximum of 7 days and measured by ELISAs for MAP-2. Results: Levels of MAP-2 in CSF were significantly increased in TBI patients at all time points after injury, compared to control subjects. ROC curve analyses showed high sensitivity and specificity (within the first 6h post injury, AUC ⫽ 0.95; cut off ⫽ 0.86 mg/ml, sensitivity 94% specificity 89%). MAP-2 levels in CSF within the first 24hrs correlated significantly with CT findings as assessed by Marshall Classification (p ⫽ 0.01).There was also significant correlation between MAP-2 CSF levels and number of episodes of increased intracranial pressure in the first 24h (⬎20 mmHg) (rs ⫽ 0.36, p ⫽ 0.04). The total levels of MAP-2 in CSF were predictive of mortality at 6 weeks (adjusted odds ratios 1.034 [95% CI 1.014-1.053]). The mortality rate was 52.6% among patients with MAP-2 levels ⬎5 ng/mL, compared with 35.7% among those with levels ⬍5 ng/mL. Two different time courses were identified: in survivors, MAP-levels tended to normalize over the monitoring period (192 hours); in nonsurvivors MAP-2 showed higher initial levels and tended to increase with time or remain abnormally elevated. Conclusions: MAP-2 is a novel, sensitive and specific marker for severe TBI. MAP-2 may be a promising marker for assessing the extent of primary injury and the prediction of outcome after severe head injury.

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RIVASTIGMINE DOES NOT DECREASE DURATION OF DELIRIUM AND MAY INCREASE MORTALITY IN CRITICALLY ILL PATIENTS: A MULTICENTRE, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED ADD-ON TRIAL

ERYTHROPOIETIN AMELIORATES MITOCHONDRIAL INJURY DURING RESUSCITATION FROM VF EVIDENCED BY LESS POST-RESUSCITATION MYOCARDIAL DYSFUNCTION AND LOWER PLASMA CYTOCHROME C LEVELS

Maarten Van Eijk, Kit Roes, University Medical Center Utrecht, Marina Honing, Alkmaar Medical Center, Michael Kuiper, Leeuwarden Medical Center, Attila Karakus, Diakonessenhuis Utrecht, Mathieu Van Der Jagt, Onze Lieve Vrouwe general Hospital, Peter Spronk, Gelre Ziekenhuizen, Loc. Lukas, Jozef Kesecioglu, Arjen Slooter, University Medical Center Utrecht

Jeejabai Radhakrishnan, Madhav Upadhyaya, Iyad Ayoub, Raul Gazmuri, Rosalind Franklin University of Medicine and Science

Introduction: Delirium is frequently encountered in critically ill patients and is associated with adverse outcome. Impaired cholinergic neurotransmission seems to play an important role in the development of delirium. The cholinesterase inhibitor rivastigmine is increasingly prescribed ‘off-label’ to delirious patients who do not respond to antipsychotics. Hypothesis: We aimed to study whether rivastigmine shortens the duration of delirium in critically ill patients. Methods: In this multicentre, double-blind trial, Intensive Care Unit (ICU) patients with delirium were randomized to rivastigmine or placebo, as add-on medication to standard pharmacotherapy with haloperidol. The primary outcome was the duration of hospital delirium. Results: After inclusion of 104 patients with delirium, the Data Safety Monitoring Board recommended halting the trial because 12 of the 54 patients who received rivastigmine had died compared to 4 of the 50 patients who received placebo (p ⫽ 0.07, corrected for multiple interim analyses). The duration of hospital delirium in the rivastigmine group (median 5 days, range: 1 to 64) tended to be longer than in the placebo arm (median 3 days, range: 1 to 28 days), which almost reached statistical significance (Mann-Whitney test, p ⫽ 0.06). Patients in the rivastigmine group had, on average, a higher severity of delirium (p ⬍ 0.005). Conclusions: This is the first double-blind, randomized, placebo controlled trial on a cholinesterase inhibitor to treat delirium in ICU patients. Continuous follow-up ensured correct data collection and the safety of the participants. With post-hoc analyses no explanation for the higher mortality rate was found in the rivastigmine group. The trial was halted because of safety concerns and lack of evidence for any beneficial effects on the primary outcome. Our trial indicated that in ICU patients, rivastigmine did not decrease duration of delirium. Moreover, an increased mortality associated with the use of rivastigmine could not be ruled out.

Introduction: We have previously reported that resuscitation from VF is associated with release of cytochrome c from mitochondria to cytosol and further to the bloodstream attaining levels that are inversely proportional to survival, suggesting that mitochondrial injury is associated with hemodynamic deterioration. In another study we demonstrated that erythropoietin (EPO) administered at the start of CPR ameliorates post-resuscitation myocardial dysfunction. Hypothesis: We hypothesized that EPO could mediate functional myocardial benefits in part by ameliorating mitochondrial injury resulting in reductions in plasma cytochrome c levels and improved post-resuscitation myocardial function. Methods: VF was electrically induced in 10 Sprague-Dawley male rats and left untreated for 8 minutes before attempting resuscitation by 8 minutes of CPR and electrical shocks. Rats received a right atrial bolus of EPO (5000 U/kg, n ⫽ 5) or saline vehicle (n ⫽ 5) immediately before chest compression. Rats were monitored for 120 minutes post-resuscitation. Plasma cytochrome c was measured by HPLC. Results: Administration of EPO markedly improved post-resuscitation myocardial function, which was associated with significant reductions in plasma cytochrome c levels (ng/ml) at 60 minutes (463 ⫾ 68 vs 656 ⫾ 124, p ⫽ 0.016) and 120 minutes (356 ⫾ 149 vs 588 ⫾ 70, p ⫽ 0.014) post-resuscitation. Plasma cytochrome c level was inversely correlated with mean aortic pressure (r ⫽ -0.697; p ⫽ 0.02) and cardiac work index (r ⫽ -0.693; p ⫽ 0.02) and showed borderline statistical correlation with cardiac index (r ⫽ -0.621; p ⫽ 0.05) and stroke volume index (r ⫽ -0.631; p ⫽ 0.05) at 120 minutes post-resuscitation. Conclusions: We conclude that EPO ameliorates post-resuscitation myocardial dysfunction in part by reducing mitochondrial injury reflected by reductions in plasma cytochrome c. The inverse correlation between plasma cytochrome c and post-resuscitation myocardial function suggests that mitochondrial injury could represent a key pathogenic feature and plasma cytochrome c could be used to predict the severity of such injury.

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IMPACT OF USING A VALIDATED DELIRIUM SCREENING TOOL, WITH OR WITHOUT A PHARMACIST AND NURSELED DELIRIUM EDUCATION PROGRAM, ON THE ABILITY OF NURSES TO RECOGNIZE DELIRIUM IN A SURGICALTRAUMA ICU

ATTITUDES AND PERCEPTIONS OF ANESTHESIOLOGY AND SURGICAL RESIDENTS TOWARDS CRITICAL CARE MEDICINE TRAINING

Andrew Lin, Brittany Russell, Carolinas Medical Center, John Devlin, Northeastern University School of Pharmacy, H. Norton, Carolinas Medical Center, Susan Evans, Carolinas Healthcare System, Gail Gesin, Carolinas Medical Center

Introduction: Despite a projected shortage of intensivists, few surgery and anesthesia residents choose to train in critical care medicine (CCM). Loan burden, fellowship difficulty, and limited employment options are often cited as deterrents. Hypothesis: Surgery and anesthesia residents have interest in CCM but differing attitudes and priorities ultimately impact career decisions. Methods: An electronic survey was distributed by email to all ACGME anesthesia and general surgery residency directors. Responses were collected between March 22, 2010 and May 17, 2010. Results: 596 residents [340 anesthesia (57%); 256 surgery (43%)] completed the survey. Although surgery residents (SR) were older than anesthesia residents (AR); there were no differences in marital status, gender, or estimated debt. 47.5% of SR and 29.7% of AR indicated interest in CCM training. On a 6-point Likert scale, AR rated continuity of care (5.1 ⫹/⫺ 1.0), multidisciplinary care (5.0 ⫹/⫺ 0.92), and evidence-based practice (4.5 ⫹/⫺ 0.89) as attractive features of CCM, while SR prioritized complexity of patients (5.1 ⫹/⫺ 0.84), evidence-based practice (4.7 ⫹/⫺ 0.77), and intellectual challenge (4.6 ⫹/⫺ 0.88). For AR, only a desire for complex patients (OR 1.72, 95% CI 1.13-2.63, p ⫽ .01) and perceived level of prestige (OR 1.46, 95% CI 1.022.09, p ⫽ .04) were significant predictors of interest in CCM fellowship, while for SR, only the perceived intensity of work (OR 2.03, 95% CI 1.25-3.29, p ⫽ .004) and level of stress (OR 0.44, 95% CI 0.26-0.75, p ⫽ .003) were predictive. AR rated a lighter call schedule and move to a closed ICU model as most likely to increase resident interest in CCM training while SR preferred more opportunities to learn advanced procedures, improved interaction with nursing and respiratory therapy, and increased income potential. SR were less likely than AR to consider quantity of work hours, intensity, and level of stress as negative factors in choosing CCM (p ⬍ .0001). Conclusions: A significant portion of AR and SR have interest in CCM, however, differences in motivation and attitudes exist that could complicate shared training environments, impact teamwork while in training, and adversely affect future practice satisfaction.

Introduction: Although ICU guidelines advocate that bedside nurses should screen for delirium using a validated tool, it remains unclear whether this practice improves the ability of STICU nurses to recognize delirium, whether the type and intensity of education accompanying implementation of a delirium screening effort influence their recognition of it, and whether ICU pharmacists can play a role in the delivery of this education. Hypothesis: Use of a validated delirium screening tool accompanied by a multifaceted delirium education program will improve the ability of STICU nurses to recognize delirium and their knowledge surrounding it compared to using one or neither of these strategies. Methods: Both the ability of 19 experienced STICU nurses to recognize delirium in a patient they were caring for compared to the independent evaluation of the same patient by a validated judge (VJ) [a trained ICU nurse who always used the Intensive Care Delirium Screening Checklist (ICDSC)] and the knowledge of each nurse surrounding delirium and use of the ICDSC (through administration of 10 randomly selected multiple choice questions from a bank of 30 validated questions) were evaluated in 3 distinct phases: Phase 1: Neither use of a delirium screening tool nor delirium-related education. Phase 2: Use of the ICDSC with education consisting solely of distribution of the 2001 ICDSC validation study. Phase 3: Use of the ICDSC combined with a multifaceted education program (a didactic lecture by an ICU pharmacist, web-based module, and bedside training by the VJ). Results: Agreement between the STICU nurses and VJ for the presence of delirium improved over each phase: Kappa (␬) ⫽ 0.403 (phase 1); ␬ ⫽ 0.624 (phase 2); ␬ ⫽ 0.735 (phase 3). Nursing knowledge [mean (SD) out of 10] was similar between phase 1 (6.1 ⫾ 1.4) and phase 2 (6.5 ⫾ 1.4; p ⫽ 0.08) but greater in phase 3 (8.2 ⫾ 1.4; p ⫽ 0.001). Conclusions: While use of a validated delirium screening tool that is not accompanied by intensive education will improve the ability of STICU nurses to recognize delirium, implementation of a multifaceted, pharmacist and nurse-led education program will further improve their ability to recognize delirium and their knowledge surrounding it.

Jeremy Huff, Theresa Hartsell, Todd Dorman, Pamela Lipsett, Samuel Galvagno, Johns Hopkins Medical Institutions, Baltimore, MD


Oral Abstract Session: Pulmonary 41

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REFINING THE LUNG INJURY PREDICTION MODEL FOR EMERGENCY DEPARTMENT PATIENTS AT RISK FOR ACUTE LUNG INJURY

THE IMPACT OF OBESITY AND SLEEP DISORDERED BREATHING ON POSTOPERATIVE PULMONARY COMPLICATIONS

Peter Hou, Aya Mitani, Brigham and Women’s Hospital, Marie Elie-Turenne, Univerity of Medicine and Dentistry, New Jersey, Jason Cohen, Brigham and Women’s Hospital, Vicki Norton, Angela Meyer, Temple University School of Medicine, Gyorgy Frendl, Brigham and Women’s Hospital, Ognjen Gajic, Mayo Graduate School of Medicine(Rochester), Nina Gentile, Temple University School of Medicine

Jonathan Bloom, Santosh Agarwal, Mary Erslon, Douglas Hansell, Covidien

Introduction: Early identification of patients at high risk of developing acute lung injury (ALI) is critical for potential preventative strategies. We aimed to derive and validate an acute lung injury prediction score (LIPS) in a multicenter sample of patients admitted from the emergency department (ED). Hypothesis: A refined LIPS model with better calibration can be attained for ED patients. Methods: From March through August 2009, 22 centers performed an observational cohort study and enrolled 5584 patients, of which 4361 were admitted from the ED. Predisposing conditions (shock, aspiration, sepsis, pancreatitis, pneumonia, sepsis, emergency surgery, high risk surgery, high risk trauma) and risk modifiers (alcohol abuse, obesity, chemotherapy, diabetes, tachypnea, oxygen saturation less than 95%, fractional inspired oxygen greater than 0.35, hypoalbunemia, acidosis) associated with ALI development were identified. LIPS points were derived from logistic regression analysis on a random set of 2000 ED patients; the model was validated in the remaining 2361 patients. Discrimination of the model was assessed with area under receiver operating characteristic curve (AUC) and testing for fit. Results: The overall incidence of ALI in the ED subgroup was 7.0% (303/4361) and varied with underlying acute condition. LIPS discriminated ED patients who developed ALI from those who did not with an AUC of 0.80 (95%CI 0.76 to 0.83). At a cut off of 5.5 for the LIPS score that ranged from 0 to 15, positive and negative likelihood ratios (95%CI) for ALI development were 3.14 (2.77 to 3.57) and 0.40 (0.32 to 0.50), with a sensitivity of 0.69 (0.61 to 0.76), specificity of 0.78 (0.76 to 0.80), positive predictive value of 0.20 (0.17 to 0.24), and negative predictive value of 0.97 (0.96 to 0.98). The Hosmer and Lemeshow Goodness-of-Fit Test resulted in a p-value of 0.65. Conclusions: The refined LIPS model fits well and identified ED patients at high risk for ALI development early in the course of their presentation. This model may facilitate enrollment of ED patients into future ALI prevention trials.

Introduction: Obese patients are believed to be at increased risk of pulmonary complication in the course of standard postoperative opioid regimens. The impact of obesity and sleep disordered breathing (SDB), a common concurrent condition, has been examined in a number of small studies however there is no current estimate of their relative significance on pulmonary complication. Hypothesis: History of obesity and SDB are independent risk factors for postoperative pulmonary complications (PPC) in patients receiving parenteral opioids and are associated with increased morbidity, mortality, and resource use. Methods: We selected all adult surgical discharges less than 65 years old with parenteral opioid administration during their stay, using the Premier PerspectiveTM Database 2009. Obesity, SDB, and PPC were identified using secondary ICD-9-CM codes. A 1:2 match was performed between those with PPC (cases) and those without (controls) based on propensity scores accounting for age, gender, race, Charlson Comorbidity Index (CCI) and provider institution. We used multivariate logistic regression to estimate the adjusted odds for development of PPC during the hospital stay. Obesity and SDB were identified as a priori predictors of PPC. Results: Of the 764, 805 discharges that met the inclusion criteria, 7.17% had at least one PPC. Post-matching, 164, 820 discharges were included in the study (54, 940 cases and 109, 880 controls), with a mean age and CCI of 50.1 and 1.97, respectively. PPC cases were associated with increased mortality (6.5% vs 0.61%, p ⬍ 0.0001), length of stay (14.4d vs 5.4d, p ⬍ 0.0001), and total cost ($44, 223 vs $16, 930, p ⬍ 0.0001). Obesity (OR: 1.15, 95% CI: 1.11-1.19), SDB (1.34, 1.27-1.40), and obesity & SDB (1.86, 1.77-1.94) were significant independent risk factors for PPC. Conclusions: Obesity and SDB are independently associated with increased PPC rate in surgical patients receiving parenteral opioids, which results in significantly increased mortality, length of stay, and cost. Risk is increased nearly twofold when both conditions are present. Better strategies for prevention of, monitoring for, and management of PPC in this population could lead to greatly improved outcomes and substantial savings.

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DOES WEEKEND EFFECT EXIST FOR ACUTE PULMONARY EMBOLISM?

URINARY HEAVY METALS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): RESULTS FROM NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (19992006)

Gagan Kumar, Amit Taneja, Puneet Sood, Jayshil Patel, Thomas Kaleekal, Sandeep Markan, Medical College of Wisconsin, Rumi Ahmed Khan, Orlando Regional Medical Center, Rahul Nanchal, Medical College of Wisconsin Introduction: Previous studies have implicated worse outcomes for weekend admissions of emergent medical conditions like acute myocardial infarction, subarachnoid hemorrhage and stroke. Limited data exists in terms of outcomes of patients admitted over the weekend for acute pulmonary embolism (PE). Hypothesis: We hypothesized that patients admitted over the weekend with PE suffered worse outcomes in terms of mortality as compared to weekdays. Methods: Retrospective analysis using the Nationwide Inpatient Sample database from year 2003 to 2007 was performed. All discharges with primary diagnosis of PE were identified using International Classification of Diseases, ninth edition codes of 415.11x or 415.19. Weekend admissions were defined as all admissions between midnight on Friday through midnight on Sunday. Primary outcome measured was all cause in-hospital mortality. Placement of inferior vena cava (IVC) filters was additionally examined. Multivariate logistic regression was used to estimate the odds ratios. The model was adjusted for patient demographics, hospital characteristics and disease severity using Pulmonary Embolism Severity Index (PESI) score. Results: Of the 684, 031 estimated discharges with primary PE, 148, 888 patients (21.8%) were admitted on a weekend. Patients admitted on a weekend had significantly increased all cause in hospital mortality (4.5% vs. 3.8%; p ⬍ 0.001); which persisted after adjustment for various factors as described above (Odds ratio 1.22; 95% confidence interval 1.13-1.31). There were no significant differences in the severity of PE between the weekday and weekend.Total number of IVC filters placed were not different between weekends and weekdays, but time to placement of IVC filters was significantly higher in those admitted on weekends (0.19 days longer; 95%CI 0.05-0.33). Conclusions: 1. All cause adjusted in hospital mortality for PE is significantly higher for weekend admissions2. Time to placement of IVC filters is significantly higher on weekends3. Prospective studies are required investigate outcomes


Haala Rokadia, Shikhar Agarwal, Cleveland Clinic Introduction: Chronic heavy metal exposure is thought to play a role in pathogenesis of chronic obstructive pulmonary disease (COPD). Hypothesis: We aim to study the association between COPD and long-term heavy metal exposure assessed using urine metal concentration. Methods: Cross-sectional data from National Health and Nutritional Examination Survey 1999-2006 were used. COPD was determined using standardized questionnaire including history of emphysema or active chronic bronchitis. Survey statistics traditionally used to analyze complex semi-random survey designs were employed to analyze these data. Data obtained from the website were pooled using standard methods, and subsequently, 8 year combined weights were calculated. Urine metal levels were measured by atomic absorption spectrometry. We studied the association of COPD with 14 heavy metals (barium, beryllium, cobalt, cadmium, cesium, lead, platinum, thallium, tungsten, mercury, antimony, molybdenum, uranium and arsenic). We used the log transformed urinary metal concentration expressed as micrograms per mg of urinary creatinine in logistic regression equations. Results: We studied the association of prevalent COPD with urine metal concentration in a sample of 249 COPD and 5634 non-COPD participants. This translated to a prevalence estimate of 4.2% (95% CI: 3.5 – 5.0 %) amongst non-institutionalized US population. Statistically significant associations between COPD and 3 heavy metals were observed: cadmium [adjusted OR: 8.1 (95% CI: 3.9 – 16.9)]; lead [adjusted OR: 2.3 (95% CI: 1.2 – 4.3)]; cobalt [adjusted OR: 2.5 (95% CI: 1.5 – 4.2)]. The association of COPD with other heavy metals was not statistically significant after adjusted logistic regression analysis. Conclusions: Significant association between urine cadmium, lead and cobalt with COPD was observed. The persistence of association even after adjustment for glomerular filtration rate and C reactive protein suggests that mechanisms other than impaired renal function and inflammation are involved in pathogenesis of COPD. Human exposure to heavy metals from several discrete sources (air pollution, cigarette smoke, food and water) in our environment may have important implications on pulmonary morbidity.

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MATRIX METALLOPROTEINASE-9 ACTIVITY IN RSV-INDUCED RESPIRATORY FAILURE

MECHANICAL EFFECTS OF A DISPOSABLE ANESTHETIC CIRCLE CIRCUIT ON VENTILATION OF A TEST LUNG

Michele Kong, Patrick Maeng, Yao Li, Jeong Hong, JP Clancy, University of Alabama at Birmingham

Bradley Fuhrman, Women & Children’s Hospital of Buffalo, Mark Dowhy, Children’s Hospital of Buffalo

Introduction: Dysregulation of matrix metalloproteinase-9 (MMP-9) has been implicated in both acute and chronic lung diseases in infants, and may play a role in RSV-induced respiratory failure. Hypothesis: RSV is a specific stimulus of MMP-9 release from human airway epithelial cells, and MMP-9 may serve as a target to interrupt viral replication. MMP-9 is elevated in tracheal aspirates of infants with RSV-induced respiratory failure relative to controls and correlates with clinical indicators of disease severity and outcome measures. Methods: Human bronchial epithelial cells (16HBE cells) were infected with RSV A2 strain, and cell lysate and media were analyzed for MMP-9 expression using real time RT-PCR, Western blotting and ELISA assays. For human samples, tracheal aspirates were collected prospectively from 40 infants with RSV-induced respiratory failure and 30 non-RSV respiratory failure controls at 48 hours of intubation. MMP-9 activities were measured by ELISA, and correlated with clinical indicators of disease severity and outcome measures. Results: In vitro studies demonstrated up-regulation of MMP-9 transcription and protein release in RSV infected 16HBE cells compared to controls (cells infected with replicating adenovirus, heat killed and UV irradiated RSV). Increasing MMP-9 expression was seen with duration of RSV infection, with apical ⬎ basolateral release. Cells transfected with siRNA directed against MMP-9, and treated with small molecule inhibitors of MMP-9 prior to and during RSV infection resulted in lower RSV titers. In patient samples, MMP-9 activity was significantly elevated in infants with RSV-induced respiratory failure compared to controls. Infants with lower number of ventilator free days (VFDs) had higher active MMP-9 levels at 48 hours of disease onset. Conclusions: Our studies demonstrated RSV as a potent stimulus of MMP-9 expression in human airway cell monolayers, and suggest a potential role for MMP-9 in RSV replication. Dysregulated MMP-9 activity was seen in infants with RSV-induced respiratory failure, with higher levels observed in those with lower VFDs. Together, these results identify MMP-9 as a potential therapeutic target and early biomarker for RSV disease.

Introduction: Current technology for delivery of inhaled anesthetics in the ICU requires use of an anesthesia machine. This is cumbersome, costly, requires substitution of an anesthesia ventilator for a standard ICU ventilator, and requires vigilance against circle circuit collapse from air leak or suctioning. Hypothesis: We hypothesized that a disposable anesthesia re-breathing circuit could be interposed between patient and ventilator with little effect on mechanics of breathing, and that air leak compensation could be automated. Methods: We have designed a disposable anesthesia circle circuit that can deliver volatile anesthetics at analgesic or anesthetic doses (set by a standard vaporizer) to intubated ICU patients. Any standard ICU ventilator can be used to inflate an encased spherical anesthesia bag, displacing re-breathing air around it to the patient. Continuous inflow of 1.5 L/min provides fresh gas and anesthetic to the patient. The anesthesia bag is tethered so that inflation creates a slight pressure difference between ventilator and patient, which is used to signal need for supplemental fresh gas flow to compensate for air leak. A Starling resistor is used to allow entrainment scavenging of exhaust, to seal the exhaust during inspiration and to match patient PEEP to ventilator PEEP. Soda lime is used to scrub CO2.A Servo I ventilator (Maquet) was used in volume mode to deliver tidal volumes (TV) of 100-600 ml/breath at 5-25 cm H2O PEEP to the re-breather. A volumetric test lung (TL, Bio-Tek Instruments) was ventilated by the re-breather, and was used to simulate patient ventilation. Test lung tidal volume (TV) and PEEP were recorded. Results: There was excellent agreement between ventilator and TL tidal volumes: TV TL ⫽ 0.93 ⫻ TV Vent ⫹ 10, r ⫽ 0.99 There was also excellent agreement between test lung and ventilator PEEP: PEEP TL ⫽ 1.01 ⫻ PEEP Vent - 0.2, r ⫽ .99Leaks were well compensated. Conclusions: A disposable re-breathing circuit can be interposed between a standard ICU ventilator and patient without significant distortion of delivered TV and PEEP. Leak compensation can be automated. .Supported by NIH SBIR 1R44NR011252-01A1.

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THE PROTECTIVE EFFECTS OF LOW-DOSE HYDROCORTISONE ON EARLY ACUTE LUNG INJURY RESULTING FROM SEPSIS IN RAT MODEL

ROLE OF HEAVY METALS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): RESULTS FROM NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES 1999 –2006)

Da-Wei Wu, Miao-Miao Peng, Yu-Xia Wu, Chen Chen, Deprtment of Intensive Care Medicine, Qilu Hospital, Shandong University, Jinan, China Introduction: Our aim was to investigate the protective effects of low-dose hydrocortisone on early acute lung injury resulting from sepsis in rat model. Hypothesis: The protective effects of low-dose hydrocortisone on early acute lung injury resulting from sepsis is by up-regulating the expression of GR-␣ in the lung, and then restraining the inflammatory responses and excessive activation of the proteinase in the downstream. Methods: The fifty healthy wister male rats were randomly assigned to three groups: a sham group(control group, n ⫽ 10), a model group(ALI group, n ⫽ 20) and the low-dose hydrocortisone group (HC group, n ⫽ 20), using cecum ligation and puncture(CLP) method to prepare the sepsis with acute lung injury model. 24 hours after the operation the rats were killed to collect the lung and plasma specimen. The expression of GR-␣ NF-␬B and MMP-9 in the lung tissue were detected by immunohistochemistry method. The expression of IL-1␤ and IL-6 in the plasma were detected by ELLSA, and the pathological changes of the lung tissue were detected by the HE staining. Results: (1) NF-␬B and MMP-9 were higher expressed in ALI group and HC group, but GR-␣ was diminished expressed in the two groups, compared with the control group(P ⬍ 0.01); NF-␬B and MMP-9 were higher expressed and GR-␣ was diminished expressed in HC group compared with the ALI group(P ⬍ 0.01). (2)IL-1␤ IL-6 in the plasma were higher expressed in ALI group and HC group, compared with the control group (P ⬍ 0.01);both IL-1␤ and IL-6 were diminished expressed in the HC group compared with the ALI group(IL-1␤, P ⬍ 0.01; IL-6, P ⬎ 0.05). (3)The pathological changes of the lung were more serious in ALI group than in HC group. (4)The expression of GR-␣ was inversely correlated with NF-␬B MMP-9 and IL-1␤(P ⬍ 0.01);the levels of NF-␬B in the lung were positively correlated with MMP-9 and IL-1␤(P ⬍ 0.01);the expression of MMP-9 was positively correlated with IL-1␤ in the plasma(P ⬍ 0.01). Conclusions: The protective effects of low-dose hydrocortisone on early acute lung injury resulting from sepsis is by up-regulating the expression of GR-␣ in the lung, and then restraining the inflammatory responses and excessive activation of the proteinase in the downstream.

Haala Rokadia, Shikhar Agarwal, Cleveland Clinic Introduction: Cigarette smoke consists of a variety of substances implicated in the pathogenesis of COPD. Hypothesis: We aim to assess role of lead and cadmium exposure as partial mediators in the association between smoking and COPD. Methods: Cross sectional data from NHANES 1999-2006 were pooled using standard methods. The composite outcome of COPD was determined using standardized questionnaire for history of emphysema and active chronic bronchitis. Active smoking was defined as self reported current smoking or measured serum cotinine ⬎ 10 ng/mL. Serum lead and cadmium levels were measured by atomic absorption spectrometry. Survey statistics used to analyze complex semi-random survey designs were employed to analyze these data. Results: After adjustment of demographic and comorbid conditions, odds ratios (OR) (95%CI) for COPD comparing quartiles 2 to 4 of serum lead levels with the lowest quartile were found to be 1.23 (0.92 – 1.65), 1.56 (1.16 – 2.08) and 1.81 (1.32 – 2.48) (p trend ⬍ 0.001). The corresponding ORs (95% CI) for cadmium were 1.18 (0.77 – 1.80), 1.33 (0.90 – 1.96) and 2.98 (2.02 – 4.39) (p for trend ⬍ 0.001). Logarithm transformed lead and/or cadmium levels were introduced into the logistic regression model to study the effect of the heavy metal on the OR between smoking and COPD. OR for former smokers and active smokers in comparison to never smokers was 1.59 (1.16 – 2.18) and 2.95 (2.09 – 4.17), respectively. Adjustment for lead did not significantly affect the OR but adjustment for cadmium significantly reduced the respective ORs to 1.40 (1.02 – 1.91) (p ⬍ 0.001) and 1.65 (1.21 – 2.26) (p ⬍ 0.001). Stratifying the population by cotinine levels, similar reduction in OR was observed after adjustment for serum cadmium level among categories with serum cotinine ⬎10 ng/mL (active smoking range). Adjustment for lead alone did not significantly affect the association between smoking and COPD. Conclusions: High levels of lead (⬎1.1 microgram/dL) and cadmium (⬎0.6 microgram/L) were found to be associated with COPD. Risk of COPD was significantly higher despite levels of lead and cadmium being much lower than the current safety standard. Cadmium may partially mediate the relationship between smoking and COPD.


Oral Abstract Session: Therapeutics 49

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EFFECT OF N-ACETYLCYSTEINE(NAC) ON ACUTE LUNG INJURY AND ACUTE KIDNEY INJURY IN HEMORRHAGIC SHOCK

TO BOLUS OR NOT TO BOLUS: A COMPARISON OF TWO INSULIN NOMOGRAMS

Jin Hee Lee, Kyuseok Kim, Tae Yun Kim, You Hwan Jo, Yu Jin Kim, Jae Hyuk Lee, Kwang Pil Rim, Seoul National University Bundang Hospital, Woon Yong Kwon, Department of Emergency Medicine, Seoul National University Hospital, Gil Joon Suh, Seoul National University Hospital, Joong Eui Rhee, Seoul National University Bundang Hospital

Krista Wahby, Harper University Hospital, Patricia Clark, Huron Valley Siani Hospital, Bryan Dotson, Harper University Hospital, Lowell Schmeltz, Huron Valley -Sinai Hospital, Steven D. Tennenberg, Harper University Hospital

Introduction: Acute lung injury (ALI) and acute kidney injury(AKI) develop in various clinical situations and are associated with high morbidity and mortality. The basic mechanisms of organ injury have focused on ischemia, inflammation and oxidant-mediated damage. N-acetylcysteine (NAC) has antioxidant and anti-inflammatory properties. So, NAC is expected to attenuate organ injury after global ischemia/reperfusion related to resuscitation from hemorrhagic shock (HS). However, results in various experimental and human studies were controversial. Hypothesis: NAC would reduce ALI and AKI. Methods: A Sprague-Dawley rat model of hemorrhagic shock was used. Rats (n ⫽ 10 per group) were randomized into 2 groups with NAC (diluted with D5W) or control group (D5W alone). Intravenous NAC was given continuously from 15min after induction of hemorrhagic shock to the end of observation period. Pressure controlled hemorrhagic shock model was performed with mean arterial pressure to 40 ⫾ 2mmHg for 90min, and then, animals were resuscitated by transfusion with the shed blood for 15min followed by 2h observation period, We measured serum IL-6, 10, and nitric oxide (NO). Malondialdehyde (MDA) and histopathological findings in lung and kidney were also evaluated. Results: Mean arterial pressure (MAP) did not differ between the control and the NAC group at baseline, during shock state, reperfusion and observation period (p ⬎ 0.05). Withdrawn blood amount was comparable between both groups(7.9 ⫾ 1.7mL vs 8.1 ⫾ 1.3mL, NAC vs control, p ⫽ 0.74). Serum NO, IL-6 and IL-10 were significantly lower in the NAC group (NO was 6.5 ⫾ 2.1 nmol/l vs 19.3 ⫾ 2.3 nmol/l, IL-6 was 227.1 ⫾ 96.5 pg/ml vs 530.3 ⫾ 308.5 pg/ml, IL-10 was 35.1 ⫾ 15.2 pg/ml vs 62.8 ⫾ 30.8 pg/ml, p ⬍ 0.05; NAC vs control, respectively). Lung MDA was significantly lower in the NAC group (214.8 ⫾ 93.3 nmol/g) than the control group(361.6 ⫾ 111.7 nmol/g)(p ⬍ 0.05), and kidney MDA was also lower in the NAC group(64.7 ⫾ 27.5 nmol/g vs117.9 ⫾ 37.6 nmol/g, p ⬍ 0.05). ALI and AKI scores were significantly lower in NAC group(6.6 vs 8.9, 1.2 vs 2.2, p ⬍ 0.05 ; NAC vs control, respectively). Conclusions: Our data demonstrated that NAC attenuated inflammatory response and acute lung and kidney injury after hemorrhagic shock in rats

Introduction: Glycemic control with continuous insulin infusions has become a standard of care in critically ill patients with hyperglycemia. However, controversy exists as to whether insulin boluses should be incorporated into glycemic control insulin nomograms. While the use of insulin boluses prior to rate increases may be pharmacokinetically justified, its implementation is difficult and its clinical value is less well tested. Hypothesis: We hypothesized that intravenous insulin boluses prior to rate increases would allow for improved blood glucose (BG) control, decreased glycemic variability (GV) and less frequent rate adjustments. Methods: During the study period, we prospectively collected data on all patients (pts) in the ICUs of two hospitals who received insulin infusions for hyperglycemia. The insulin nomograms between the hospitals only differed by whether insulin boluses were used prior to rate increases. Mean and standard deviation (an index of GV) of all BG for each pt were assessed. Incidence of hypoglycemia (BG ⬍ 60 mg/dl) was determined. Student’s t-test and Chi Square analysis were used to compare results between the two groups. Results: The BOLUS group (B) consisted of 42 pts with 4257 BG determinations. The NON-BOLUS group (NB) consisted of 72 pts with 2595 BG determinations. Both groups consisted of medical and surgical ICU pts. Data are mean ⫾ SD. BG was 148 ⫾ 48 and 152 ⫾ 48 mg/dl in the B and NB groups respectively. The overall percentage of BG levels within the target range of 100-150 mg/dl was B ⫽ 50% and NB ⫽ 54%. GV was 47.1 ⫾ 25 and 45 ⫾ 27 mg/dl in the B and NB groups. More BG levels and rate adjustments were necessary in the B vs the NB group (17 ⫾ 4 vs 11 ⫾ 4 and 6 ⫾ 2 vs 4 ⫾ 3, respectively (p ⬍ 0.01). The rate of hypoglycemia (⬍60 mg/dl) was higher in the B group (23.8% vs 2.8%, p ⬍ 0.001). Conclusions: Both nomograms achieved equal and acceptable glycemic control in terms of mean BG, percent BG in target range and GV. The BOLUS group had a higher incidence of hypoglycemia and required more rate adjustments per day. Incorporation of insulin bolus doses to an insulin infusion protocol does not appear to improve endpoints of glycemic control and may increase the risk for hypoglycemia.

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ANTIRETROVIRAL THERAPY ADMINISTRATION IN HIVINFECTED ICU PATIENTS REDUCES ALL CAUSE ICU MORTALITY

VASOPRESSIN IS DETECTABLE IN CONTINUOUS VENO-VENOUS HEMODIALYSIS EFFLUENT OF PATIENTS WITH VASODILATORY SHOCK TREATED WITH EXOGENOUS VASOPRESSIN

Sarah Bozorgnia, Cooper University Hospital, Quinn Czosnowski, Jomy George, Philadelphia College of Pharmacy, Christa Schorr, Barry Milcarek, Constantine Tsigrelis, Cooper University Hospital , John Baxter, Robert Wood Johnson Medical School, R. Dellinger, Cooper University Hospital Introduction: Since the introduction of antiretroviral therapy (ART), the life expectancy of patients infected with HIV has increased. However, the role of ART in critically ill patients with HIV infection has remained controversial. The purpose of this study was to evaluate the impact of ART on mortality in the ICU. Hypothesis: Antiretroviral administration in the ICU reduces all cause ICU mortality Methods: All HIV-infected patients admitted to the medical/surgical ICU at Cooper University Hospital between 10/02 and 10/09 and who were included in the hospital’s Project IMPACT database were reviewed. ART was defined as three active antiretroviral agents from at least 2 different classes. Patients were categorized into four groups for comparison: group 1 ⫽ patients on ART prior to admission (PTA) and continued in the ICU; group 2 ⫽ patients on ART PTA and discontinued in the ICU; group 3 ⫽ patients not on ART PTA and started in the ICU; and group 4 ⫽ patients not on ART PTA and not started in the ICU. The primary outcome variable was all cause ICU mortality. Univariate significance tests were used to compare admission and hospital characteristics. Cox Proportional Hazards regression was utilized to assess the impact of admission and hospital characteristics on all cause ICU mortality. Results: There were 141 HIV-infected ICU patients included in the analysis: group 1 (n ⫽ 39); group 2 (n ⫽ 21); group 3 (n ⫽ 13); group 4 (n ⫽ 68). The mean age of patients was 44 years and 58.9% were male. Patients were predominantly medical patients (89.4%) and African American (57.4%). The mean CD4 for the patients in this study was 103 cells/mm3 and 43% of patients were admitted with an AIDSdefining opportunistic infection. Patients who received ART while in the ICU received a PI based regimen 73.1% of the time. Multivariate logistical regression analysis revealed patients in groups 1 and 3 had a significantly reduced risk of mortality compared to patients who did not receive ART (p ⬍ 0.01, OR 0.15, 95% CI 0.06-0.38 and p ⫽ 0.05, OR 0.27, 95% CI 0.08-0.98). Conclusions: Administration of ART to critically ill patients with HIV infection was associated with a reduction in all cause ICU mortality in our population.


Seth Bauer, Daniel Culver, Simon Lam, William Fissell, Susamma Abraham, Herbert Wiedemann, Anita Reddy, Cleveland Clinic Introduction: Patients with septic shock receiving vasopressin with renal failure may require continuous veno-venous hemodialysis (CVVHD). Since vasopressin is not protein bound and has a relatively low molecular weight, it may be removed by CVVHD. Hypothesis: We hypothesized that vasopressin is detectable in CVVHD effluent. In addition, we hypothesized there were factors affecting vasopressin levels in CVVHD effluent. Methods: This prospective observational study included adult patients with vasodilatory shock receiving stable dose continuous intravenous vasopressin along with concomitant uninterrupted CVVHD for at least 4 hours. Vasopressin levels in CVVHD effluent fluid were assessed via radioimmunoassay. Factors such as CVVHD parameters, fluid status, blood pressure, administration of corticosteroids, and catecholamine requirements were also recorded. Analysis was performed with Pearson correlation, and multivariate linear regression was utilized to assess for independent factors associated with vasopressin levels in CVVHD effluent. Results: CVVHD effluent of 27 patients was assessed for vasopressin levels. Most patients were in the medical ICU (85%), and were receiving norepinephrine (85%) and corticosteroids (85%) in addition to vasopressin. The mean ⫾ SD exogenous vasopressin dose was 0.037 ⫾ 0.032 units/min, while CVVHD effluent flow rates were 23.1 ⫾ 4.4 mL/kg/hr. Vasopressin was detectable in all samples (median [IQR], 88.8 pg/mL [36.4-113.7 pg/mL]). CVVHD effluent vasopressin levels strongly correlated with exogenous vasopressin dose (r ⫽ 0.92, p ⬍ 0.001). After adjustment for CVVHD effluent flow rate and administration of corticosteroids with multivariate linear regression, only exogenous vasopressin dose was independently associated with CVVHD effluent vasopressin level (p ⬍ 0.001). Conclusions: Vasopressin is detectable in CVVHD effluent, suggesting it is removed by CVVHD. Exogenous vasopressin infusion dose is independently associated with CVVHD effluent vasopressin level. CVVHD removal of vasopressin may lead to decreased serum vasopressin levels that are not accounted for through a fixed-dose infusion of exogenous vasopressin.

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IMPACT OF A MANDATORY SCREENING PROTOCOL FOR PROPOFOL INFUSION SYNDROME IN HIGH RISK TRAUMA PATIENTS

A REDUCTION IN FASTING PLASMA GHRELIN CONCENTRATION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN THE CRITICALLY ILL

Thomas Schroeppel, University of Tennessee Health Science Center, Lesley Clement, Regional Medical Center at Memphis, Peter Fischer, University of Tennessee - Memphis College of Medicine, Louis Magnotti, University of Tennessee Health Science Center, Marilyn Lee, Regional Medical Center at Memphis, Martin Croce, University of Tennessee Health Science Center, Timothy Fabian, Univ. of Tennessee Medical Group

Adam Deane, Antony Zaknic, Matthew Summers, Marianne Chapman, Royal Adelaide Hospital, Michael Horowitz, University of Adelaide

Introduction: Propofol is an ideal drug for sedation in the ICU. Its short half-life and rapid onsetallow easier patient assessment and liberation from mechanical ventilation, especially in trauma patients. PropofolInfusion Syndrome (PIS) is an adverse reaction to propofol marked byarrhythmia, rhabdomyolysis, lactic acidosis, and if unrecognized leads todeath. Hypothesis: As little evidence for PIS exists in trauma patients, we sought determine the incidence, establish a screening protocol, and determine its effectiveness. Methods: All trauma patients who received propofol from 1/1/05 to 12/31/08 were reviewed. Patients who died within 24 hours, received ⬍100 ml or only received propofol in the operating room were excluded. Demographic data, medications, ISS, GCS, ICP, infusion time and dose, rates of infusion, sodium (Na), Na dose, and adverse events were compared. Patients were diagnosed with PIS if two of the following criteria were met in the absence of another explanation: 1) cardiac arrythmia/collapse, 2) metabolic acidosis, and 3) rhabdomyolysis. The screening protocol required propofol cessation if serum lactate and/or CPK worsened. Logistic regression was used to identify risk factors for PIS. Results: 767 patients received continuous propofol infusions. All 8 of the PIS patients suffered traumatic brain injury (TBI). Prior to implementation of the screening protocol (1/06), the rate of PIS was 2.90%/yr. After screening, the rate of PIS dropped to 0.3%/yr (p ⫽ 0.02). All 8 of the PIS patients suffered a traumatic brain injury (TBI). Total propofol dose was significantly higher in those that developed PIS (median 10, 570 vs 32, 245mg, p ⫽ 0.0005). Na levels and Na dose were also significantly higher in those that developed PIS (160 vs 147mmol/L, p ⬍ 0.0001) and (2, 495 vs 822 meq, p ⫽ 0.0016). After adjusting for Na dose received, logistic regression identified hypernatremia (Na ⬎ 155) as being associated with PIS (OR ⫽ 36.89, p ⫽ 0.0009). Conclusions: PIS is a real entity in trauma patients with a high mortality (63%). Hypernatremic TBI patients receiving large amounts of propofol appear to be at the highest risk. The screening protocol decreased the incidence of PIS by 90%.

Introduction: Abnormally delayed gastric emptying occurs frequently in the critically ill and represents a major cause of morbidity. In health gastric emptying is modulated by hormones secreted from the gut – ghrelin may accelerate gastric emptying, while glucagon-like peptide-1 (GLP-1) and amylin may slow it. Ghrelin agonists accelerate gastric emptying in other patient groups. Hypothesis: Fasting ghrelin concentrations will be reduced in critically ill patients with delayed gastric emptying. Fasting GLP-1 and amylin concentrations will be increased in critically ill patients with delayed gastric emptying. Methods: Written, informed consent was obtained from next of kin. Fasting arterial blood was obtained in 23 mechanically ventilated patients (age 53 (20, 85) yrs; 18M; weight 70 (45, 110) kg; APACHE II score 21 (11, 38)) for measurement of plasma ghrelin, GLP-1 and amylin concentrations. A test ‘meal’ of 100 ml of nutrient liquid 1 kcal/ml - mixed with 100 ␮l 13C-octanoic acid - was administered intragastrically over 5 min. Breath samples were collected at intervals (t ⫽ 0-330 min) and analysed for 13CO2 to calculate the gastric emptying coefficient (GEC), a global index of the gastric emptying -the higher the number indicating more rapid emptying. A GEC ⬍2.64 defined delayed gastric emptying. Data are median (range) and comparisons were performed using Mann-Whitney U tests. Results: Nine (40%) patients had delayed gastric emptying. Fasting plasma ghrelin was lower in patients with delayed, when compared to those with normal, gastric emptying (delayed: 8.3 (7.4, 12.7) pg/mL vs. normal: 11.2 (6.9, 37.9) pg/mL; P ⫽ 0.05), but there was no difference in GLP-1 (delayed: 1.6 (0.2, 7.3) vs. normal: 1.4 (0.7, 5.4); P ⫽ 0.83) or amylin concentrations (delayed: 152 (27, 1282) pg/mL vs. normal: 131(29, 449) pg/mL; P ⫽ 0.83). Conclusions: A reduction in fasting plasma ghrelin concentrations is associated with delayed gastric emptying in the critically ill. Exogenous ghrelin is a potential novel prokinetic agent that warrants further study in this group.

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INTERACTION OF CORTICOSTEROIDS WITH DOPAMINE OR NOREPINEPHRINE IN SHOCK STATES

COMPARISON OF PROTHROMBIN COMPLEX CONCENTRATE (PCC) AND LOW-DOSE RECOMBINANT FACTOR VIIA (RFVIIA) FOR WARFARIN ANTICOAGULATION REVERSAL

Daniel De Backer, Erasme University Hospital, Patrick Biston, Chu Charleroi, Jacques Devriendt, Brugmann University Hospital, Christian Madl, Medical University of Vienna, Didier Chochrad, Hospital Ixelles, Cesar Aldecoa, Rio hortega University Hospital, Jean-Louis Vincent, Erasme University Hospital Introduction: We recently demonstrated that, compared to norepinephrine, dopamine was associated with a non significant increase in 28 day mortality (odds ratio 1.17 [0.97-1.42])(De Backer et al NEJM 362:779-789;2010). On the other hand, steroid use can be associated with more rapid shock reversal and perhaps with an improved outcome, especially in the most severe forms of septic shock. We evaluated whether steroids may interfere with outcome in patients treated with adrenergic agents. Hypothesis: We hypothesized that steroid use may interfere with outcome in patients treated either with dopamine or norepinephrine. Methods: We evaluated steroid (prednisolone or hydrocortisone) use within 24h of randomization to dopamine or norepinephrine in a prospective, randomized study (NCT00314704) evaluating the effects of these agents for the treatment of shock. Steroid use was not randomized and left at discretion of attending physicians. The detail of the protocol are described in detail elsewhere (De Backer et al NEJM 362:779-789;2010). Of the 1679 patients, data on steroid use was available in 1664 patients (853 in dopamine group and 811 in norepinephrine group). Chi-square was used to compare 28-day mortality in patients according to steroid therapy. Results: Steroids were used in 885 (53.2%) patients (including hydrocortisone in 670) and was well balanced between dopamine and norepinephrine groups. Globally, 28-day mortality tended to be higher in patients receiving steroids (52.4 vs 48.8%, OR 1.16 [0.95-1.40], p ⫽ 0.15). In patients receiving steroids, 28-day mortality was significantly higher in patients randomized to dopamine compared to norepinephrine (55.8 vs 48.8%, OR 1.33 [1.01-1.74], p ⬍ 0.05) while it was similar in patients not receiving steroids (48.9 vs 48.8%, OR 1.01 [0.76-1.32], p ⫽ 0.99). Conclusions: The combination of steroid and dopamine is associated with an increased 28-day mortality in patients with shock. The exact mechanism remains to be elucidated.

Scott Chapman, University of Minnesota/North Memorial Medical Center, Eric Irwin, North Memorial Medical Center, Nichole Kulinski, University of Minnesota, Katherine Hutson, North Memorial Medical Center Introduction: PCC and rFVIIa are recommended for warfarin reversal in serious or life threatening bleeding. No published data compare the safety and efficacy of PCC and rFVIIa for warfarin reversal. Hypothesis: PCC and rFVIIa are equally effective and safe for warfarin reversal. Methods: Patients (pts) who received PCC or rFVIIa for warfarin reversal were identified, charts reviewed for demographics, indication for warfarin reversal, initial and follow-up INR, vitamin K, units of FFP, and dose(s) of PCC or rFVIIa. Efficacy was defined as achievement of and time to INR ⱕ 1.5, change in INR, second dose of PCC or rFVIIa, and operative or postoperative bleeding. Thromboembolic events were evaluated for safety. Mortality and LOS were compared. Data are presented as mean (SD). Results: Sixty two pts (41 PCC and 21 rFVIIa) are analyzed. PCC pts were older (71.8 vs. 64.9 years, p ⫽ 0.03). 46.3% of PCC and 71.4% of rFVIIa pts (p ⫽ 0.06) required surgery. There was more neurosurgical intervention in the rFVIIa pts (62.5% with ICH and 60% with trauma induced extra-axial blood collections) vs. 0 PCC pts. Initial INR was 3.7 for PCC and 3.2 for rFVIIa (p ⫽ ns). The initial dose was 1765(651) units for PCC and 1029 (72) mcg for rFVIIa. Repeat INR was 1.9 (0.7) at 5:54 (4:50) hours for PCC and 1.3 (0.3) at 4:50 (2:41) hours for rFVIIa (p ⬍ 0.0002). INR was ⱕ 1.5 in 36.6% and 86% of PCC and rFVIIa pts (p ⬍ 0.0001). The percent change in INR was 41.8% vs. 50.3% (p ⫽ 0.079). 10 (24%) PCC and 0 rFVIIa pts required a second dose to achieve an INR ⱕ1.5 (p ⫽ 0.012). No excessive operative bleeding was noted for any pt. DVTs were noted in two pts in each group, one in each group in a vein where a central line was present, and one lower extremity DVT in each group, one with anticardiolipin antibody syndrome and one with protein S deficiency. LOS was longer in the rFVIIa pts. Mortality trended towards favoring more rapid warfarin reversal with rFVIIa (34.1% PCC vs. 19.0% rFVIIa, p ⫽ 0.25) even though more pts required surgery. Conclusions: Low dose rFVIIa more effectively corrects warfarin anticoagulation than PCC at a similar cost. A trend toward fewer deaths in rFVIIa may correlate to more rapid reversal of warfarin anticoagulation with rFVIIa.


Oral Abstract Session: Pediatrics 57

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POST-INTUBATION CHEST X-RAY DURING PEDIATRIC/NEONATAL CRITICAL CARE TRANSPORT: IS IT WORTH THE WAIT?

“BOOSTER” TRAINING: LOW-DOSE, HIGH-FREQUENCY CARDIOPULMONARY RESUSCITATION (CPR) TRAINING IMPROVES SKILL RETENTION OF HOSPITAL-BASED PEDIATRIC PROVIDERS

Lynne Garrett, Akron Children’s Hospital, John Giuliano, Yale-New Haven Children’S Hospital, Hamilton Schwartz, Cincinnati Children’s Hospital, Michael Bigham, Akron Children’s Hospital Introduction: The Institute of Medicine has identified 6 features of high-quality healthcare, one of which is efficiency. In pedic/neo specialty critical care transport (P/N SCCT) some believe that a post-intubation chest xray (PI CXR) at the referral hospital is unnecessary and adds to transport inefficiency. Published neo/pedi data from the OR and ICUs have found high rates of ETT malpositioning (15-34%) using published ETT depth/size criteria (PALS, NRP, Braselow) and report the insensitivity of clinical exam in confirming correct ETT positioning. The purpose of this study is to explore the value of PI CXR in the P/N SCCT setting. Hypothesis: We hypothesize that PI CXR in neo/pedi intubated by a P/N SCCT team is unnecessary and can be eliminated to improve efficiency. Methods: This IRB-approved, non-intervention study included all intubations performed by the P/N SCCT team during over 18 months. A data tool was completed by the transport nurse after each trip where intubation was required. Data were tabulated and analyzed using Microsoft Excel and SPSS v17.0. Results: 77 patients (34 neo/43 pedi) were enrolled. The neo averaged 2.1 ⫾ 1.0kg with mean gestational age of 31.9 ⫾ 5.1wks. Pedi averaged 9.8 ⫾ 11.7kg and 1.8 ⫾ 3.9yrs. PI CXR was obtained in 66 of patients (85.3% neo, 86% pedi) and PI CXR showed malpositioned ETT in 48.5% of patients. The trend of ETT malpositioning by PI CXR was more common in neo vs pedi (55% vs 37%, p ⫽ 0.10). Neo ETT malpositions were more commonly deep whereas shallow ETT placement errors were more common in pedi. Neo ETT were moved 0.7 ⫾ 0.5cm vs 0.9 ⫾ 0.5 cm in pedi. Initial ETT depth was incorrectly calculated according to PALS (3x ETT inner diameter)/NRP in 50% neo and 58% pedi. PI CXR verified acceptable ETT positioning despite incorrectly calculated ETT depth in 41% neos and 56% pedi. PI CXR with subsequent ETT repositioning in appropriately calculated ETT occurred in both groups (neo 35% and pedi 72%, p ⫽ 0.03). Conclusions: PI CXR remains informative for infants/children intubated by the P/N SCCT team. The trend showed ETT malpositioning was more common in neos. There are opportunities for improvement in correctly calculating appropriate ETT depth though this should not obviate the need for PI CXR.

Robert Sutton, Dana Niles, Peter Meaney, Richard Aplenc, Children’s Hospital of Philadelphia, Benjamin French, The University of Pennsylvania School of Medicine, Benjamin Abella, University of Pennsylvania Health System, Robert Berg, Mark Helfaer, Vinay Nadkarni, Children’s Hospital of Philadelphia Introduction: As the quality of cardiopulmonary resuscitation (CPR) is related to survival, the educational programs for teaching pediatric CPR skills are a prime target for interventions to improve pediatric cardiac arrest survival. Hypothesis: We hypothesized that a low-dose, high-frequency bedside retraining program (Booster Training) would be effective to improve CPR skill retention. Methods: CPR recording/feedback defibrillators were used to evaluate CPR quality during simulated arrest. Basic life support (BLS) providers were randomized to one of four arms: 1) Instructor Only Training; 2) Automated Defibrillator Feedback Only; 3) Instructor Training Combined with Automated Feedback; and Control (No Structured Training). Each session (Time 0, 1 m, 3 m, and 6 m) consisted of a pre-training evaluation (60s), a Booster Training (120s), and a post-training evaluation (60s). Excellent CPR was defined as: chest compression (CC) depth ⱖ1/3 Anterior-Posterior chest depth, rate ⱖ90 and ⱕ120 CC/min, ⱕ 20% of CCs with incomplete release (⬎2500 grams), and no flow fraction ⱕ 0.30. Results: Eighty-nine providers were randomized; 74 (83%) completed all sessions. In a multivariable model, subjects were more likely to retain their excellent CPR skills after each subsequent session compared to the first: after 2 previous trainings, subjects were 2.3 times more likely to retain their skills (CI95: 1.1 – 4.5, p ⫽ 0.02) and after 3 previous trainings, subjects were 2.9 times more likely to retain their skills (CI95 1.4 – 6.2, p ⫽ 0.006). Subjects receiving Automated Defibrillator Feedback Only were less likely to retain skills compared to instructor groups (OR 0.42, CI95 0.18 – 0.98, p ⫽ 0.045). Without training (control group) there was no increased likelihood of subjects performing excellent CPR during the next session (OR 1.1 CI95: 0.9 – 1.4, p ⫽ 0.25). Conclusions: Bedside booster CPR training is effective to improve CPR skill retention. Our data suggest that a CPR instructor improves retention compared to automated feedback training alone. Future studies should investigate bedside training to improve CPR quality during actual pediatric arrests. Funding: Laerdal Foundation and the University of Pennsylvania SOM

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PRIFLE SCORE IDENTIFIES ACUTE KIDNEY INJURY AND PREDICTS MORTALITY IN CRITICALLY ILL CHILDREN: A PROSPECTIVE STUDY

CEREBROSPINAL FLUID (CSF) HSP72 LEVELS ARE A POTENTIAL BIOMARKER FOR BACTERIAL MENINGITIS IN CRITICALLY ILL CHILDREN

Yadira Soler, University of Puerto Rico, Mariely Nieves-Plaza, University of Puerto Rico- Medical Sciences Campus , Monica Prieto, Weill Cornell Medical College, Ricardo Garcia De Jesus, University Pediatric Hospital, Marta Sua´rezRivera, University of Puerto Rico School of Medicine

Stephen Standage, Patrick Lahni, Cincinnati Children’s Hospital Medical Center, William Ma, Indiana University School of Medicine, Steven Kernie, UT Southwestern Medical Center, Hector Wong, Derek Wheeler, Cincinnati Children’s Hospital Medical Center

Introduction: Acute Kidney Injury (AKI) has been associated with high rates of morbidity and mortality in critically ill children. To establish a uniform definition for AKI, the Acute Dialysis Quality Initiative created the Risk, Injury, Failure, Loss and End-Stage Kidney (RIFLE) classification in adults. A pediatric version, pRIFLE, was published to identify AKI earlier and more accurately in children. Hypothesis: pRIFLE score will predict morbidity and mortality of critically ill pediatric patients with AKI in a level 1 pediatric intensive care unit (PICU). Methods: A prospective cohort of 188 admissions to the PICU were studied. Inclusion criteria were: admission to PICU ⬎24 hr, ages 0.1-21 years, and no end-stage renal disease or renal transplant. Demographic, laboratory, and clinical data were collected for the first 14 days of admission, and pRIFLE scores were calculated using estimated creatinine clearance (CpRIFLE) and urine output (UpRIFLE). Bivariate analysis was done using Mann-Whitney and chi-square tests for continuous and categorical variables, respectively. Binary logistic regression was used to evaluate the association between pRIFLE score and mortality. Statistical significance was p ⬍ 0.05. Results: The incidence of AKI was 22.3%, of which 88% presented within 72hr of admission to PICU. Patients with AKI were younger, weighed less, and were more likely to be on inotropic support and diuretics (p ⬍ 0.05). A marginal difference was observed in hospital length of stay (hLOS) between AKI and no-AKI patients (p ⫽ 0.05). No difference in gender, use of nephrotoxins, or mechanical ventilation was observed (p ⬎ 0.05). In bivariate analysis, AKI defined by pRIFLE predicted mortality (OR 4.06, 95% CI: 1.42-11.59). UpRIFLE only identified 14.3% of all AKI vs. 85.7% identified by CpRIFLE (p ⬍ 0.001). Conclusions: In this cohort of critically ill pediatric patients, AKI identified by pRIFLE predicted mortality. CpRIFLE identified more cases of AKI than UpRIFLE, and thus might be a more useful diagnostic tool in this population. Also, pRIFLE score suggests increased morbidity as observed in longer hLOS, increased need of inotropics and diuretics. Further evaluation of these associations is ongoing.

Introduction: Several studies have shown that extracellular Hsp72 levels are elevated in critically ill patients with a diverse range of conditions. Extracellular Hsp72 has been detected in virtually every body compartment studied to date, including serum, urine, amniotic fluid, bronchoalveolar lavage fluid, and CSF and thus may be an important biomarker for critical illness. Hypothesis: We hypothesized that CSF levels of extracellular Hsp72 are increased in critically ill children with bacterial meningitis. Methods: Following IRB approval, we enrolled a convenience sample of 31 children who received lumbar puncture for suspected meningitis. Bacterial meningitis was defined as a positive CSF or blood culture with CSF WBC count ⬎10 cells/m3. CSF was analyzed for extracellular Hsp72, IL-6, IL-8, LPS binding protein (LBP), and TNF-␣ using commercially available ELISA. Data were expressed as median (IQR) due to the non-parametric nature of the data. We analyzed differences between groups using Mann-Whitney test. We also calculated receiver operating characteristic (ROC) curves for each biomarker. A p-value ⬍0.05 was significant. Results: There were no significant differences in children with bacterial meningitis (n ⫽ 14) compared to controls (n ⫽ 17) with respect to age or gender. Extracellular Hsp72 levels were significantly increased in the bacterial meningitis group (12.95 ng/mL, IQR 13.47) compared to controls (2.24 ng/mL, IQR 2.19) (p ⫽ 0.0002). All other measured cytokines were significantly increased in the meningitis group as well. ROC AUC were statistically significant for Hsp72 (0.90, 95% CI 0.77-1.00), IL-6 (0.98, 95% CI 0.82-0.99), LBP (0.98, 95% CI 0.87-1.0), TNF-␣ (0.90, 95% CI 0.71-0.99), and WBC (0.805, 95% CI 0.62-0.92). The ROC AUC for IL-8 (0.33, 95% CI 0.16-0.52) was not significant. ROC analysis showed that a CSF Hsp72 cut-off ⬎ 8.1 ng/mL has 79% sensitivity and 94% specificity for bacterial meningitis. Conclusions: CSF levels of Hsp72 are significantly increased in children with bacterial meningitis versus controls. CSF Hsp72 may be an important biomarker for bacterial meningitis in children, with comparable sensitivity and specificity to CSF WBC count. Supported by NIH K08 GM077432


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IMPLEMENTATION OF EARLY GOAL-DIRECTED THERAPY FOR CHILDREN WITH SUSPECTED SEPSIS: MINIMIZING UNNECESSARY VARIATION AND MAXIMIZING BENEFIT

GENETIC VARIATION IN DIMETHYLARGININE DIMETHYLAMINOHYDROLASE AFFECTS HEMODYNAMIC SHOCK IN PEDIATRIC SEPSIS

Eric Williams, Jeanine Graf, Andrea Cruz, Andrew Perry, Binita Patel, Baylor College of Medicine

Scott Weiss, Lawrence Jennings, Margaret Yu, Shannon Haymond, Mark Wainwright, Children’s Memorial Hospital, Northwestern Feinberg School of Medicine

Introduction: Evidence-based guidelines exist for early goal-directed therapy of pediatric patients with sepsis. Institutional barriers to achieve early goal-directed therapy across the hospital continuum were identified. Hypothesis: A multidisciplinary approach between the Emergency Department (ED) and Pediatric Intensive Care Unit(PICU) to develop a shock protocol can optimize delivery of early goal-directed therapy, minimize variation, and improve outcome. Methods: A protocol was developed from current evidence-based guidelines collaboratively between the ED and PICU. A computer triage system alerted on abnormal vital signs at intake. Children at high risk for sepsis, or those appearing toxic, were placed in a designated resuscitation room. The protocol included recruiting additional nursing, respiratory, and pharmacy personnel to bedside, and standardizing lab studies, antibiotics, and the rapidity of fluid administration. Frequent vital signs and interventions were documented on a graphical flow sheet to facilitate patient hand-offs. Children receiving 60mL/kg or more were admitted to the PICU. Patients with suspected sepsis seen in the ED during 6 months of 2010 were included prospectively. The shock protocol group was compared to a similar retrospective cohort from 2009. Non-gaussian times to interventions were compared using Mann Whitney U test between pre- and post-protocol patients. Data are presented as medians. Percent mortality was compared using chi-squared analysis. Results: The shock protocol was initiated at triage in 158 patients and 79 were admitted to PICU. The retrospective cohort included 105 patients admitted to PICU. Triage to first bolus decreased by 73%(81 to 22 min*). Triage to third bolus decreased by 70%(208 to 63 min*). Triage to first antibiotic decreased by 72%(143 to 40 min*). Mortality for PICU admission with sepsis decreased from 8.6 to 3.8% and mortality for PICU admission with sepsis and on inotropes decreased from 16.7 to 10%. *p ⬍ .001. Conclusions: The protocol resulted in earlier recognition of suspected sepsis, with substantial reductions in times to guideline interventions and a decrement in treatment variation. Mortality effects do not yet reach statistical significance.

Introduction: The role of the endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA), in vascular dysfunction in sepsis is not well understood. Plasma ADMA, which we have shown to be decreased in pediatric sepsis, is metabolized by dimethylarginine dimethlyaminohydrolase (DDAH). Hypothesis: Polymorphisms in the DDAH II gene are associated with plasma ADMA concentration and cardiovascular dysfunction in pediatric sepsis. Methods: We performed a prospective study of pediatric patients with septic shock and age-matched febrile/non-septic and healthy controls. Presentation with vasoconstricted (“cold”) or vasodilated (“warm”) shock and outcomes were compared. Plasma ADMA was measured using tandem mass spectrometry. A 572 bp region of the DDAH II gene was sequenced using PCR to detect the -871 6g/7g insertion/deletion and -449 G/C polymorphisms. Genotype frequencies and type of shock were compared using ␹2 or Fisher’s exact test. Plasma ADMA and inotrope score (IS)/duration were compared using Mann-Whitney U. Results: Of 83 children enrolled, DDAH II genotype was available in 90%—29 sepsis, 21 febrile, and 25 healthy controls. Gender (p ⫽ 0.14) and ethnicity (p ⫽ 0.08) were similar across groups. The -871 7g insertion allele was more common in sepsis (17%) compared with febrile (5%) and healthy (9%) controls, though this did not reach significance (p ⫽ 0.32). Genotype frequencies also did not vary between groups for -449 G/C (p ⫽ 0.36). ADMA did not differ between -871 6g/7g genotypes. However, ADMA (median, IQR) was lower in septic patients with a G allele at position -449 (0.37, 0.30-0.41 ␮mol/L) compared with C/C homozygotes (0.55, 0.49-0.64 ␮mol/L, p ⫽ 0.01). Neither polymorphism was associated with maximum IS on day of admission or vasoactive infusion duration (all p ⬎ 0.05). However, 47% (10/19) of patients with a -449 G allele presented with cold (vs warm) shock compared with zero (0/9) -449 C/C homozygous patients (p ⫽ 0.01). Conclusions: A genetic association with decreased plasma ADMA was also associated with presentation with vasoconstricted or “cold” shock. This suggests that genotypic differences in NO metabolism may contribute to phenotypic variations in sepsis pathophysiology.

64 SEASONAL AND 2009 H1N1 INFLUENZA IN CRITICALLY ILL CHILDREN IN CINCINNATI, OHIO Carrie Morgan, Michael Hobson, Cincinnati Children’s Hospital Medical Center, Brandy Seger, CCHMC, Derek Wheeler, Cincinnati Children’s Hospital Medical Center Introduction: The emergence of a novel swine-origin strain of influenza A, 2009 H1N1 in humans was first noted in the spring of 2009. Pandemic H1N1 has been responsible for over 18, 000 deaths worldwide and attack rates have been highest in younger age groups. Reports so far regarding H1N1 and disease severity have been conflicting. We sought to compare our local experience with pandemic H1N1 influenza to seasonal influenza from the previous 3 flu seasons. Hypothesis: We hypothesized that pandemic H1N1 would have higher disease severity and mortality than seasonal influenza. Methods: We reviewed, with IRB approval, all critically ill patients admitted to our PICU with pandemic H1N1 or seasonal influenza during the 3 previous flu seasons. We collected demographic data, clinical presentation, length of mechanical ventilation, need for additional modalities of treatment (HFOV, inhaled NO, ECLS), management, and outcome (PICU LOS, hospital LOS, mortality). Continuous data were compared between groups using Student’s t test for parametric variables and Mann-Whitney-U test for non-parametric variables. Categorical data were compared between groups using Fisher’s exact or Chi-square testing. A p value ⱕ0.05 was considered significant. Results: We admitted 40 critically ill children with pandemic H1N1. We compared these children with 28 critically ill children admitted to our PICU with seasonal influenza during the previous three flu seasons. Children with seasonal influenza had higher PRISM-III scores upon admission compared to children with pandemic H1N1 (10.7 vs 6.9, p ⬍ 0.001). Similarly, children with seasonal influenza were more likely to require mechanical ventilatory support (83% vs 48%, p ⫽ 0.003). Mortality was higher in the seasonal influenza group (17% vs 0%, p ⫽ 0.006). There were no significant differences between the two groups in PICU or hospital LOS. Co-morbid conditions, especially chronic respiratory diseases such as asthma, tended to be more common in the children with pandemic H1N1. Conclusions: In contrast to other studies, we found a significantly lower mortality rate in children requiring PICU care with pandemic H1N1 compared to seasonal influenza, likely due to the higher severity of illness in the latter group.


Poster: Research Citation Finalists 70 GLUTAMINE TREATMENT INCREASES HEME OXYGENASE 1 AND NUCLEAR FACTOR (ERYTHROID-DERIVED 2)-LIKE 2 AND PROTECTS INTESTINAL EPITHELIAL CELLS FROM HEAT AND OXIDANT STRESS Christine Hamiel, Alyssa Kallweit, Alexandra Sufit, Lauren Zager, Paul Wischmeyer, University of Colorado Denver Introduction: Glutamine (GLN) can protect against critical illness and injury via heat shock protein (HSP) expression. GLN treatment in heat stress (HS) injury is known to increase intracellular levels of multiple HSPs, however GLN treatment in oxidant stress is incompletely understood. The effects of GLN treatment on HSP32 (heme oxygenase 1 (HO1)) and nuclear factor (erythroid-derived 2)-like 2 (NRF2), levels and cellular localization in intestinal epithelial cells (IEC) are currently unknown. Hypothesis: GLN treatment will increase HO1and NRF2 levels and nuclear translocation in both HS and oxidant injury. Methods: Cells were treated for 15 min with either 0mM (CT) or 10mM GLN, and then subjected to either lethal injury (HS-44° for 50 min or 2mM H2O2 for 30 min) or non-lethal injury (HS-43° for 45 min or 800uM H2O2 for 30 min). Cell survival was evaluated via MTS assay in HS and oxidant injured cells ⫹/⫺ GLN. Injured groups were normalized to their non-injured controls. HO-1 and NRF2 expression levels and cellular localization were determined by western blot (N ⫽ 3). Results: GLN treatment protected cells from lethal HS (p ⬍ 0.01 vs. HS CT) and lethal oxidant injury (p ⬍ 0.001 vs. H2O2 only). GLN treatment increased HO1 expression in CT, HS and oxidant injured cells (p ⬍ 0.05 vs. CT groups). Cells treated with GLN also showed an increase in nuclear HO-1 content in all treatment groups (p ⬍ 0.05). Total NRF2 protein levels increased more than 3 fold with GLN treatment in CT cells (p ⫽ 0.003 vs. CT cells). H2O2 injury increased nuclear NRF2 however HS decreased levels (p ⬍ 0.05 vs. CT cells). Treatment with GLN showed a trend of increasing nuclear NRF2 in both injuries. Conclusions: GLN treatment can protect gut epithelial cells from both heat and oxidant injury. GLN increases total NRF2 levels in non-stressed cells. HO1 levels and nuclear translocation are enhanced with GLN treatment. These are the first data showing GLN can enhance nuclear translocation of HO1 and upregulate it’s transcription factor, NRF2, in intestinal cells. HO1 and NRF2 may play an integral role in GLN mediated cellular protection.

71 TRYPANOSOMA CRUZI TISSUE TROPISM Gary Fang, Children’s Memorial Hospital, David Engman, Northwestern University, Conrad Epting, Children’s Memorial Hospital Introduction: Trypanosoma cruzi is an intracellular parasite that causes Chagas heart disease, the leading cause of infectious cardiomyopathy worldwide and an emerging disorder in the US. After infecting the host, the parasite can invade the heart, causing an inflammatory cardiomyopathy characterized by arrhythmias and heart failure. Although the clinical manifestations of Chagas disease are relatively tissue restricted, tissue tropism has never been established. Outcomes clearly relate to the immune response and MHC phenotype. Previous studies in vitro demonstrated that most cells ultimately become infected, yet the differential kinetics between cell types have not characterized, nor has the relationship between initial tissue infection and clinical outcomes been established. Hypothesis: We hypothesize that T. cruzi is intrinsically cardiotropic and will demonstrate a predilection for cardiomyocytes over other cell types in a time dependent manner. We propose to establish tissue tropism among murine primary cells ex vivo. Methods: To study ex vivo tropism, primary cultures of adult murine cardiomyocytes, skeletal myoblasts, fibroblasts, and H9C2 cells (cell line controls for infectivity) were infected with T. cruzi (Brazil strain) for two hours. The cells were paraformaldehyde fixed and stained with wheat germ agglutinin to outline cell membranes and DAPI to label cell and parasite nuclei. Infection scores(#associated parasites/#host cells) were calculated for each cell type. Results: Cardiac myocytes demonstrated a significantly higher infection score (17.35 ⫹ 7.86) than skeletal myoblasts (5.85 ⫹ 0.85), fibroblasts (5.36 ⫹ 1.30), or H9C2controls (2.51 ⫹ 1.17), p ⬍ 0.05. Conclusions: Our preliminary data strongly suggest that T. cruzi preferentially interacts with cardiomyocytes in primary monoculture. Simultaneous mixed cultures will be examined to demonstrate selective infection, and the results of in vivo infection will be quantified by serial examination of tissue burden by qPCR. Demonstration of intrinsic tropism or preferential kinetics will permit study of the surface interacting domains to better understand and interrupt disease pathogenesis.

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GHRELIN ATTENUATES BRAIN INJURY AFTER TRAUMATIC BRAIN INJURY AND UNCONTROLLED HEMORRHAGIC SHOCK IN RATS

SEPSIS AGGRAVATES PROTEIN DEGRADATION, BUT DOES NOT ENHANCE THE MECHANICAL VENTILATION-INDUCED DECREASE IN PROTEIN SYNTHESIS IN PIG DIAPHRAGM

Lei Qi, Weifeng Dong, Jeffrey Nicastro, Gene Coppa, Ping Wang, Rongqian Wu, North Shore University Hospital and Long Island Jewish Medical Center Introduction: Traumatic brain injury (TBI) and hemorrhagic shock often occur concomitantly. Hemorrhagic shock exacerbates secondary brain damage. TBI, on the other hand, impairs shock compensation. Gastrointestinal dysfunction occurs frequently in patients with TBI. However, whether alterations in the gastrointestinal system are involved in neuronal damage and recovery after TBI is largely neglected. Ghrelin is a ’gut-brain’ hormone with multiple functions including anti-apoptosis and anti-inflammation. The purpose of this study was to determine whether ghrelin reduces brain injury in a rat model of TBI and uncontrolled hemorrhage (UH). Hypothesis: Ghrelin attenuates brain injury after TBI and uncontrolled hemorrhagic shock. Methods: Brain injury was induced by dropping a 450g weight from 1.5m onto a steel helmet attached to the skull of male adult rats. Immediately after TBI, a midline laparotomy was performed and both lumbar veins were severed at the junction with the vena cava. The abdomen was kept open but covered with a saline wet gauze for 20min, and it was closed in layers thereafter. At 45min after TBI-UH, ghrelin (4, 8 or 16nmol/rat) or 1ml saline (Vehicle) were injected iv. At 1.5 and 4h after TBI-UH, beam balance test, forelimb placing test and hindlimb placing test were used to assess sensorimotor and reflex function. At 4h after TBI-UH, brain samples were collected. Cleave PARP1 levels in the cortex, an indicator of apoptosis, were measured by Western Blot. Brain levels of TNF␣ and IL-6 were measured by ELISA. Results: Animals showed severe disturbances of sensorimotor and reflex function after TBI-UH. Although all three doses of ghrelin improved sensorimotor and reflex function, 16nmol/rat ghrelin provided the best protection. Similarly, ghrelin treatment reduced cortical apoptosis in a dose-dependent manner. Moreover, significantly increased brain levels of TNF␣ and IL-6 were markedly decreased by all three doses of ghrelin treatment. Conclusions: Ghrelin improves sensorimotor and reflex function, reduces cortical apoptosis and downregulates brain inflammation after TBI-UH. Ghrelin can be further developed as an effective resuscitation approach for the trauma victims with brain injury and severe blood loss.


Neeraj Srivastava, Maria Gazzaneo, Agus Suryawan, Samer El-Kadi, Roberto Torrazza, Marta Fiorotto, Hanh Nguyen, Rosemarie Almonaci, Teresa Davis, Baylor College of Medicine, Renan Orellana, Texas Children’s Hospital Introduction: Mechanical ventilation (MV) impairs diaphragmatic function, diminishing the ability to wean from ventilatory support. Sepsis leads to increased skeletal muscle protein catabolism and loss of muscle mass. The combined effect of MV and sepsis on diaphragm protein metabolism is not known. Hypothesis: To determine whether MV and sepsis lead to protein catabolism in the diaphragm of neonatal pigs. Methods: Neonatal pigs (n ⫽ 8-10/group) were sedated and subjected to MV for 9 hours (MV group) in the presence of LPS (MVLPS group), as well as dextrose and amino acids. Fractional protein synthesis rates and translation and degradation signals were determined in diaphragm muscle. Results: Plasma insulin levels were higher with MV and further increased in the presence of LPS. Compared to controls, fractional protein synthesis rates in the diaphragm decreased by 13% in the presence of MV but increased by 12% in the MVLPS group. MV increased AMPK phosphorylation which was enhanced by addition of LPS. Despite increased phosphorylation of PKB in response to higher levels of insulin, phosphorylation of mTOR did not change among the MV and MVLPS groups, due to lack of TSC 2 phosphorylation in response to PKB activation. eIF4G-eIF4E association and 4G phosphorylation decreased in both MV and MVLPS groups. NFkB phosphorylation and the abundance of muscle RINGfinger protein-1 (MURF-1) and muscle Atrophy F-box (MAFbx)/atrogin-1 increased in the presence of MV, and MURF-1 further increased in the presence of LPS. Diaphragmatic intact and cleaved ␣-actin fractions increased with MV, suggesting myofibrillar breakdown, and this effect further increased with addition of LPS. Conclusions: These findings suggest MV leads to decreased protein synthesis, inactivation of translation initiation, and enhanced proteolysis in the diaphragm, which appear mediated by AMPK and NFkB activation. However, the addition of LPS-induced sepsis aggravates protein degradation, but does not enhance the MV-induced decrease in protein synthesis.

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FADD SIRNA REDUCES AUTOPHAGY AND APOPTOSIS IN SEPTIC MICE

EPIGENETIC MACHINERY REGULATING GENE EXPRESSION IS ALTERED BY AN INFLAMMATORY STIMULUS

Naoyuki Matsuda, Hiroki Teramae, Nagoya University Graduate School of Medicine

Waseem Ostwani, C.S. Mott Children’s Hospital at UM, Timothy Cornell, CS Mott Children’s Hospital at UM, Thomas Shanley, C.S. Mott Children’s Hospital at University of Michigan

Introduction: Severe sepsis is a serious disorder with organ dysfunction via systemic activation of inflammatory receptors and death receptors. Fas-associated death domain protein (FADD) is an essential regulator in the infectious signaling pathways, which activates death receptor signaling in many cell types. Hypothesis: The aim of this study was to investigate how gene silencing of FADD by intravenous injection of the siRNA improves cell death in septic mice. Methods: In BALB/C male mice (8-12 week-old), sepsis was induced by cecal ligation and puncture (CLP), and lungs and the aorta were harvested 24 h after the onset of sepsis. At 10 h after CLP, siRNAs targeting FADD and the mismatched siRNA were delivered by intravenous injection of the liposome complexes. Accumulation of Cy3-labeled siRNA were confirmed by immunostaining. Western blot analysis and RT-PCR analysis were performed to determine the changes in expression of FADD and the other molecules, which are associated with autophagy and apoptosis. Transmission electron microscope (TEM) and TUNEL stain were adopted for detection of autophagy and apoptosis. The densitometric comparisons were made using one-wayanalysis of variance followed by Tukey’s multiple comparison test. The data were presented as mean ⫾ SEM (n ⫽ 4). Differences were considered significant when P values were ⬍ 0.05. Results: Septic mice showed a significant increase in FADD and a significant appearance of autophagy and apoptosis in lungs and aortas, compared with control (24 hours after sham operation). Injected Cy3-labbeled siRNA-lipo-complexes were strongly observed in type 2 alveolar cells and vascular endothelial cells. FADD siRNA, but not mismatched siRNA, caused a dose-dependent suppression of sepsis-induced activation of FADD, ATG5, ATG8, LC-3 and caspase-3 in lungs and aortas. TEM revealed that FADD siRNA improved cell survival in type 2 alveolar cells and vascular endothelial cells. 50 ␮g of FADD siRNA greatly improved the mortality of septic mice (n ⫽ 15). Conclusions: We suggest that sepsis-induced autophagy and apoptosis could be augmented by FADD activation. Gene silence of FADD strongly improved mortality in septic mice. FADD siRNA could be a future medication in severe sepsis.

Introduction: Previous studies in pediatric sepsis have identified significant repression of gene expression in non-survivors of septic shock. Recent data show epigenetic changes in the methylation state of histone proteins influence transcriptional activation of gene expression in a sepsis model. Dimethylation of lysine 27 of histone 3 (H3K27me2) is associated with repression of gene expression (“gene off” signature). The regulation of this signature under conditions of inflammation has not been examined. Hypothesis: We hypothesize that an inflammatory stimulus would alter the expression of the components regulating dimethylation of H3K27 to induce a “gene off” signature. Methods: THP-1 cells (human monocyte line) were used to model the circulating monocyte. Cells were differentiated before stimulation with LPS for 0 (control), 1, 2, 4, 6 and 8 hours. Real-time polymerase chain reaction (RT-PCR) analysis was carried out on cDNAs obtained from mRNA collected from LPS stimulated cells at similar time points for expression of EED (component of dimethyltransferase) and JMJD3 (H3K27 demethylase). Protein lysates were subjected to Western blotting (WB) with antibodies against the following epitopes: H3K27me2, EED, and JMJD3. Results: Following LPS stimulation, RT-PCR showed increased expression of EED by 1.7-fold at 4 hrs and 3.1-fold at 6 hrs as compared to unstimulated cells. JMJD3, also increased expression by 3- fold at 4 hrs and 10.8-fold at 6 hrs. The subsequent affect on H3K27me2 as determined by WB showed an early increased signal at 2 hrs which diminished at 4 and 6 hrs before increasing expression late (at 8 hrs). EED demonstrated expression patterns predicted by mRNA analyses of an early increase at 1 and 2 hrs followed by decreased expression at 6 hrs. Conclusions: The pattern of the “gene off” H3K27me2 signature is dynamically affected by LPS stimulation and would predict late repression of gene expression. This signature appears to be related to dynamic changes in expression of key components of the epigenetic machinery that regulates histone protein methylation and suggests epigenetics plays a key role in regulating gene expression in sepsis.

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ASSOCIATION OF LACTATE, MIXED VENOUS OXYGEN SATURATION (SVO2), AND TRANSCUTANEOUS OXYGEN (PTCO2) TO MORTALITY IN SURGICAL PATIENTS

HIGH GLUCOSE VARIABILITY INCREASES MORTALITY IN PATIENTS WITH SPONTANEOUS SUBARACHNOID HEMORRHAGE

Brian Nishiguchi, Damian DeFrancesch, Sho Furuta, Michael Hayashi, David Inouye, Kevin Pei, University of Hawaii , Fedor Lurie, Straub Foundation, Danny Takanishi, University of Hawaii , Mihae Yu, University of Hawaii School of Medicine, Department of Surgery, The Queen’s Medical Center

Jeffrey Barletta, Midwestern University, College of Pharmacy - Glendale, Bryan Figueroa, Robert DeShane, Great Lakes Neurosurgical Associates, PC, Steven Blau, Karen McAllen, Spectrum Health

Introduction: The initial resuscitation of surgical intensive care unit (SICU) patients has traditionally been guided by parameters such as blood pressure, heart rate, urine output, SvO2, and lactic acid (LA) but lacks measurement of tissue perfusion. The skin is the first tissue bed to vasoconstrict and the last to re-perfuse with resuscitation. Transcutaneous pressure of oxygen (PtcO2) correlates with PaO2 (and therefore FiO2) during normal perfusion. In shock states, PtcO2 changes with cardiac output but fails to increase in response to FiO2 of 1.0 due to vasoconstriction of the skin. The PtcO2 response to FiO2 of 1.0 called the oxygen challenge test (OCT) is a marker of tissue perfusion and a rise of ⱖ 25 mm Hg in PtcO2 (the dividing value between survivors and non-survivors) has been used as an endpoint of resuscitation (1). Hypothesis: Achieving the OCT goal at 24 hours of resuscitation is a better predictor of mortality than normalization of Lactate and SvO2. Methods: SICU patients requiring pulmonary artery catheter for acute resuscitation of septic shock, severe sepsis, cardiogenic shock and ARDS were analyzed. The goals of resuscitation were adequate oxygen delivery to achieve normal vital signs, SvO2 ⱖ70%, normal LA, and OCT ⱖ 24 at 24 hours of resuscitation (T24). Logistic regression analysis for mortality using LA on admission and at T24 of resuscitation, SvO2, age, APACHE II, gender, and achieving SvO2 and OCT goals at T24 was performed. Results: Demographics of the patients (n ⫽ 50) were: age of 63 ⫾ 16 yrs, 32 males and 18 females, 34 septic shock/severe sepsis, 9 cardiogenic shock, and 14 ARDS. The mean APACHE II Score was 24 ⫾ 3 with a mortality of 13/50 (26%). The only statistically significant predictor of mortality was reaching the OCT goal at T24 (p ⫽ 0.003) with a relative risk of 9.0 (95% CI, 2.8 to 31.6). Conclusions: The strongest predictors of survival in our surgical patients were achieving adequate skin perfusion within 24 hours of using the OCT. Using the OCT as one of the goals of resuscitation may be a good marker of tissue perfusion and is associated with survival. Case Reports: (1) Yu M et al, Shock.27:615-622. 2007.

Introduction: High glucose variability is a significant marker for poor outcome in critically ill patients but its influence has not been thoroughly evaluated in patients with intracranial pathology. Hypothesis: High glucose variability will lead to increased cerebral infarction and higher hospital mortality in patients with spontaneous subarachnoid hemorrhage (SAH). Methods: Consecutive adult patients with spontaneous SAH were retrospectively identified. Patients were excluded if their ICU length of stay was ⬍24 hours or if there were ⬍5 glucose assessments. All glucose values obtained from a point-of-care device were collected for the first 7 days of ICU admission. Glucose variability was calculated as the average change in glucose overtime for each patient and reported as mg/dL/hr. Cerebral infarction was evaluated on CT scan. Classification and regression tree (CART) analysis was used to determine high vs. low glucose variability and adjust for severity of SAH and other confounding variables. Cerebral infarction and mortality were compared between low and high glucose variability groups. Results: There were 64 patients with a mean age of 54 ⫾ 11 years and glucose of 127 ⫾ 15 mg/dL. The percentage of patients with a Hunt/Hess grading of 4 and 5 was 31% and 8%. CART analysis revealed Hunt/Hess score and high glucose variability as factors influencing cerebral infarction and mortality. Average glucose was not a factor. For patients having a Hunt/Hess score of 4 or 5, the incidence of cerebral infarction was 73% (11/15) when glucose variability was ⬎8 mg/dl/hr vs. 30% (3/10) when it was ⱕ8 mg/dl/hr (p ⫽ .049). When Hunt/Hess score was 4 or 5, mortality was 50% (7/14) when glucose variability was ⬎10 mg/dl/hr vs. 9% (1/11) when it was ⱕ 10 mg/dl/hr (p ⫽ .042). When Hunt/Hess score was ⱕ3, cerebral infarction was 18% (7/39) and mortality was 5% (2/39). Glucose variability did not influence either outcome in this subgroup. Conclusions: Glucose variability is a significant predictor of cerebral infarction and mortality in patients with severe spontaneous SAH defined as a Hunt/Hess score of 4 or 5. Whether this is a causal relationship or a marker of a more complex pathophysiologic process will require further study.


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GLUCOSE ABSORPTION FOLLOWING INTRA-GASTRIC AND SMALL INTESTINAL ADMINISTRATION IN CRITICAL ILLNESS

WHAT IS THE USEFULNESS OF 4T TEST, AND ENZYME LINKED IMMUNOSORBENT ASSAY IN DECISION MAKING IN POST CARDIAC SURGICAL ICU PATIENTS SUSPECTED OF HEPARIN INDUCED THROMBOCYTOPENIA?

Antony Zaknic, Matthew Summers, Royal Adelaide Hospital, Anna DiBartolomeo, Adelaide University, Marianne Chapman, Royal Adelaide Hospital, Robert Fraser, Repatriation General Hospital, Michael Horowitz, University of Adelaide, Adam Deane, Royal Adelaide Hospital Introduction: Recent studies comparing duodenal with intragastric feeding in the critically ill have failed to show clinically significant outcomes. Hitherto, malabsorption of nutrient in the critically ill was thought to be primarily due to delayed gastric emptying. However, glucose absorption has been shown to be markedly reduced in this group despite normal gastric emptying. Small intestinal absorption of nutrient has not been formally quantified in this group. Hypothesis: Glucose absorption in critically ill patients, following gastric and small intestinal administration, will be impared. Methods: 63 critically ill patients (CIP) (age: 49 ⫾ 18, APACHE II: 20 ⫾ 7) and 39 healthy volunteers (HV) (age: 39 ⫾ 21) were administered a ‘meal’ of 100mL of Ensure® (liquid nutrient 1.06kcal/ml), labelled with 3g of 3-O-Methylglucose (3-OMG) to evaluate glucose absorption. Subjects were fed via nasogastric (n ⫽ 33; CIP ⫽ 24; HV ⫽ 9) or small intestinal (n ⫽ 69; CIP ⫽ 39; HV ⫽ 30) catheters. Plasma 3-OMG concentrations were measured at intervals for 240min and AUC calculated. Data are mean ⫾ SEM and compared using non-paired Student’s t tests. Results: Glucose absorption was markedly reduced in the patients following both the intragastric (AUC0-240: CIP: 49 ⫾ 7 vs. HV: 83 ⫾ 3mmol/l.min; P ⫽ 0.007) and small intestinal meal (AUC0-240: CIP: 56 ⫾ 4 vs. HV: 72 ⫾ 4mmol/l.min; P ⫽ 0.008). There was no difference in glucose absorption when comparing gastric to small intestinal administration in the critically ill or healthy subjects (P ⫽ 0.38 and P ⫽ 0.16, respectively). Conclusions: Glucose absorption is substantially impaired in the critically ill even when delivered directly into the small intestine. This suggests mechanisms in the small intestine contribute to nutrient malabsorption. This may, in part, explain why small intestinal feeding has failed to show any outcome benefits.

Rizwan Manji, Hilary Grocott, University of Manitoba, Chee-Loong Saw, Peter Nickerson, Canadian Blood Services, Alan Menkis, Eric Jacobsohn, University of Manitoba Introduction: Thrombocytopenia (tcp), timing of platelet drop, thrombosis, and other causes for tcp (the 4 T test) can be done quickly, freely and is used in non-cardiac surgery patients to determine the probability of heparin induced thrombocytopenia (HIT). ELISA for HIT is readily available, is highly sensitive but less specific giving a high rate of false positives and is not free. The highly specific serotonin release assay (SRA) is currently the “gold standard” to confirm HIT, but is difficult to do, is costly and not readily available. Hypothesis: To correlate the 4T test to SRA and to correlate the ELISA to SRA in post cardiac surgical ICU (PCSICU) patients suspected of HIT to aid decision making in weighing the benefits (preventing thrombosis) vs. risks (bleeding and tamponade) of starting a non-heparin anticoagulant. Methods: We retrospectively analyzed PCSICU patients who had been investigated for HIT with both an ELISA and SRA. For the 4T test, the postoperative day 1 platelet count was the baseline count from which tcp and timing were determined; and thrombosis was documented deep venous thrombosis, pulmonary emboli or arterial occlusion (excluding stroke). A receiver operator characteristic (ROC) curve was created and the sensitivities/specificities were determined for the 4T test vs. SRA as well as the ELISA vs. SRA. Results: There were 47 patients who had both ELISA and SRA. The area under the curve for the ROC for 4T test vs. SRA was poor at 0.56 (p ⫽ 0.56). The sensitivity of having a positive SRA with a 4T score greater than 3 (intermediate risk of HIT) was less than 65%, with a specificity of less than 45%. The area under the curve for the ROC for ELISA vs. SRA was excellent at 0.97 (p ⬍ 0.001). An ELISA OD ⬎ 1.58 was associated with a sensitivity of 100% and a specificity of 94% when compared to the SRA suggesting this was a useful cut off point to use clinically in PCSICU patients. Conclusions: Our results suggest the 4T test may not be a useful clinical tool in PCSICU patients. An ELISA OD ⬎ 1.58 has a high likelihood of having a positive SRA, and therapeutic non-heparin anticoagulation should be started in this group of patients.

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MEASURING AND IMPROVING DISINFECTION IN CRITICAL CARE TRANSPORT VEHICLES

A PROSPECTIVE RANDOMIZED STUDY COMPARING METOPROLOL TO PLACEBO IN THE MANAGEMENT OF SEVERE TRAUMATIC BRAIN INJURY

Carol Sulis, Boston Medical Center, Ronald Estanislao, Michael Frakes, Boston MedFlight, Phillip Carling, Boston Medical Center, Suzanne Wedel, Boston Med Flight Introduction: Environmental contamination of medical equipment and high touch surfaces is believed to play a role in pathogen transmission in hospitals. There are hospital systems to assess completeness of cleaning. In critical care transport (CCT) vehicles, teams are expected to disinfect potentially contaminated surfaces after each transport and are taught that disinfection is a key component of the infection control program and the safety culture. Cleaning has not been assessed in CCT vehicles in the same manner as in hospitals. Hypothesis: A novel method to evaluate cleaning of CCT vehicles will provide objective data and improve performance. Methods: An investigator evaluated ten targets common to all transport vehicles using a previously validated fluorescent marking dye method. Cleaning was considered ‘complete‘ if the fluorescent mark was totally removed from the target 24 hours after marking. Targets included wall and portable suction, defibrillator (buttons, touch screen), ventilator (on/off switch, reset buttons), and monitor (BP and EKG recorders, touch screen). After baseline data collection, a review of updated disinfection practices was completed in in response to the appearance of pandemic Influenza. Follow-up data were collected 2, 8, and 14 months after that review. Results: 2310 standardized targets (10 objects) were assessed for outcomes comparisons. Overall, cleaning improved from 12% to 75% of all items evaluated, p ⬍ 0.00005) and improved in each vehicle type (rotor wing 12% to 79% of all items cleaned; fixed wing 2% to 75%, ground 18% to 68%; p ⬍ 0.00005 for all). There was not a consistent pattern by vehicle type. By the end of the study, several targets were cleaned ⬎ 90% of the time (the monitor screen and controls and the ventilator controls) regardless of vehicle type. Conclusions: This is the first use of an objective method to assess cleaning of CCT vehicles. After identifying an opportunity for improvement, re-education and objective feedback improved performance by more than 6-fold. Potential causes of incomplete cleaning include shared responsibility for disinfection (no single crew member assigned), ineffective technique, or competing priorities related to patient management.


Hassan Abu Khaber, Akram Fayed, Ahmed Khattab, University of Alexandria Introduction: Traumatic Brain Injury (TBI) is a major cause of death and neurologic disability after blunt trauma. A catecholeamine surge occurs after TBI and elevated plasma and urine catecholeamine levels correlate well with admission Glasgow Coma Score (GCS), neurologic recovery as measured by GCS or Glasgow Outcome score (GOS) after one month, survival, legnth of ICU stay and ventilator days. Hypothesis: To investigate the effect of metoprolol on patients with severe TBI within 24 hours of admission and to compare it with placebo regarding the effect on mortality, hospital stay, ICU stay, duration of MV and GOS at one month. To figure out the relation between early heart rate (HR) reduction to a target range of (60-70 b/min) and the above mentioned parameters. Methods: 60 patients with isolated blunt severe TBI were randomized into two groups. The first group was subjected to placebo effect, while the second group received metoprolol tartarate as an initial 25 mg enterally. The does was increased every 6 hours with a 25 mg increments till a target HR (60-70 b/min) was reached or a maximum of 400 mg/day. Results: Metoprolol use leads to a statistically significant reduction in mortality, hospital stay, ICU stay and a significant improvement of GOS. There was a trend in metoprolol patients to require less MV days than placebo group but did not reach a statistical significance. Mortality benefit of metoprolol was demonstrated in those above 40 years. Metoprolol patients who achieved target HR early had a better outcome than those who achieved it later. Logistic regression analysis has identified 5 independent predictors of mortality namely, the ICU stay, metoprolol, GCS (mortality protectors) while the duration of MV and age were positively affecting it (increased mortality). Conclusions: Metoprolol has a beneficial effect in severe TBI regarding reduction of mortality, improvement of GOS, reduction of the legnth of ICU and hospital stay. It has a mortality benefit when initiated early and when a target HR of 60-70 is achieved early. This benefit is significant in patients older than 40 years.

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ASPIRATION: RISK-FACTORS AND OUTCOMES IN THE LUNG INJURY PREVENTION STUDY 1 COHORT

NOVEL ADHESIVE GLOVE DEVICE (AGD) USE IN CONJUNCTION WITH AN IMPEDANCE THRESHOLD DEVICE (ITD) DURING ACD-CPR IN A PIGLET MODEL OF CARDIAC ARREST

Augustine Lee, Mayo Clinic, Ousama Dabbagh, University of Missouri, Raquel Bartz, Duke University, Adebola Adesanya, University of Texas, Daryl Kor, Ognjen Gajic, Emir Festic, Mayo Clinic Introduction: Although aspiration is a potentially modifiable risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), little is known regarding the risk factors for aspiration itself. Hypothesis: Clinical risk factors for aspiration can be identified at the time of hospital admission, allowing for potential ALI/ARDS prevention strategies. Methods: The US Critical Illness and Injury Trials Group identified a large cohort of patients admitted to acute-care hospitals in order to develop and validate the Lung Injury Prediction Score (LIPS). We had prospectively identified clinician-documented aspiration upon admission in this cohort. To determine aspiration risk factors and clinical outcomes, data on predefined clinical, laboratory, and physiologic variables were collected. Adjusted odds ratios [95% confidence intervals] were determined by multivariate logistic regression. Results: Of the 5584 patients, aspiration was identified in 212. Aspiration was positively associated with male gender (66% vs 56%, p ⫽ 0.007), but not with age (cohort mean 56 ⫾ 19). Those who aspirated had a higher APACHE II (13.7 vs 9.6, p ⬍ 0.0001), and a lower GCS (11 vs 14, p ⬍ 0.0001). In a logistic regression model incorporating all clinically important variables thought to contribute to aspiration, independent risk factors that increased the risk of aspiration included: admission from a nursing home (OR 2.99), alcohol use (OR 2.69), prior chest radiation (OR 4.74), Asian race (OR 6.45), the use of oral hypoglycemics (OR 3.49), and a lower GCS (OR 1.26). Eventually, 17% of the aspirators developed ALI/ARDS compared to 6% nonaspirators (adjusted OR 1.96 [1.27, 2.94]), with aspiration preferentially increasing the risk for ARDS over ALI. Aspiration also increased the risk of death (OR 1.91 [1.20, 2.96]), even after adjusting for severity of illness (APACHE II). Conclusions: Aspiration was associated with an increased risk of ALI/ARDS and death. Risk factors for aspiration included prior chest radiation, Asian race, use of oral hypoglycemics, admission from a nursing home, alcohol use, and a reduced GCS.

Andre Shih, Sharda Udassi, Gerry Kaliki-Venkata, Mark Blaiweise, S Malhotra, Carsten Bandt, A Zaritsky, Ikran Haque, Jai Udassi, University of Florida Introduction: Active compression-decompression CPR (ACD-CPR) with an impedance threshold device (ITD), improved venous return and coronary perfusion. We developed an adhesive glove device (AGD) to perform ACD-CPRin a piglet model of cardiac arrest. Hypothesis: We hypothesizedthat AGD-ACDCPR generates more negative intra-thoracic pressure as compared S-CPR; ITD with AGD-ACD-CPR will augment this effect. Methods: Prospective randomized animal study. Thirty-six anesthetized & ventilated (⬃two months old, 12 kg) piglets were randomized (n ⫽ 12) after 4 minutes of untreated VF to receiveeither S-CPR, AGD-ACD-CPR or AGD-ACD-CPR with ITD for 2 minutes by rescuers blinded to data recordings. AGD consisted of a velcro patch sewn into a leather glove with the counter patch adhered to the pig’s chest wall. Millar pressure catheters were introduced in to the pleural cavity and right atrium (RA) for pressure measurement. Data (mean ⫾ SD) was analyzed using two-way ANOVA; p ⱕ0.05 was significant. Results: RA pressure (mmHg) during decompression (diastolic) phase of CPR was 8.3 ⫾ 3.43 in S-CPR group, compared to AGDACD-CPR -0.8 ⫾ 8.05 (p ⫽ 0.006), and compared to AGD-ACD-CPR with ITD-3.9 ⫾ 6.23 (p ⫽ 0.01). Comparison of RA pressure between AGD-ACDCPR and AGD-ACD-CPR with ITD resulted in p ⫽ 0.03. No difference in peak (systolic) RA pressure between the groups. Pleural pressure (PP mmHg) during decompression was -0.3 ⫾ 4.2 in S-CPR, compared to AGD-ACD-CPR -13.4 ⫾ 6.7 (p ⫽ 0.01), compared to AGD-ACD-CPR with ITD -11.9 ⫾ 6.5 (p ⫽ 0.01). PP comparison of AGD-ACD-CPR and AGD-ACD-CPR with ITD p ⫽ 0.37. Conclusions: AGD resulted significantbetter chest decompression during ACDCPR and ITD had synergistic effect in apiglet model of cardiac arrest.

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CAN WE PREDICT THE NEED FOR MASSIVE TRANSFUSION AFTER HEMOSTATIC THERAPY IN TRAUMA PATIENTS WITH HEMORRHAGIC SHOCK?

“PLAN TO HAVE NO UNPLANNED”: A QUALITY IMPROVEMENT INITIATIVE

Nobuyuki Saito, Kunihiro Mashiko, Hisashi Matumoto, Chiba Hokusou Hospital, Nippon Medical School Introduction: The massive transfusion (MT) often required for trauma patients with hemorrhagic shock (HS) is associated with high mortality and morbidity. If we can predict the need for MT on ICU admission after hemostatic therapy, we can prepare for transfusion and decide re-hemostasis therapy as quickly as possible. Hypothesis: This study aimed to determine a predictor of massive transfusion in trauma patients with HS after hemostatic therapy. Methods: A singleinstitution prospective observational study was conducted from July 2007 to June 2010. Of 1713 adult trauma patients admitted during the study period, 110 developed HS requiring blood transfusion and mechanical ventilation. We divided the patients into the MT group (requiring ⬎ 10 U packed red blood cell transfusion after ICU admission) and the non-MT group and compared their clinical and laboratory data. Univariate analysis using the chi-square test and Mann-Whitney U test were used for comparing the two groups and multivariate analysis by the stepwise method was used to identify prognostic factors. Results: Victims of blunt trauma accounted for 91.8%. Emergency surgery was performed for 80% of the patients. Median age of the patients was 51.5 [37-70] years, median injury severity score (ISS) was 30 [22-41], and mortality rate was 10.9%. Eighty-four patients were assigned to the MT group and 26 to the non-MT group. Mortality, ISS, and rate of re-hemostasis treatment in the MT group were higher than in the non-MT group (p ⫽ 0.03, 0.01, and 0.01, respectively) The independent predictors for MT were pedestrian injury (odds ratio (OR) 4.3 [p ⫽ 0.04; 95%CI: 1.0-18.5]), implementation of damage control surgery (OR 5.8 [p ⬍ 0.001; 95%CI: 3-25.6]), transfusion from emergency department (OR 5.1 [p ⫽ 0.05; 95%CI: 0.9-28.0]), ionized calcium concentration ⫽ 0.01; 95%CI: 3-23.1]), prothrombin time international normalized ratio ⬎ 1.5 (OR5.6 [p ⫽ 0.01, 95%CI: 1.4-22.3]), and hemoglobin concentration ⬍ 0.01, 95%CI: 2.130.5]). Conclusions: The need for MT can be predicted, which will enable rapid treatment for latent hemorrhagic shock in trauma patients.

Sandeep Tripathi, Denise Nunez, The Children’s Hospital At Montefiore, Henry Ushay, Children’s Hospital At Montefiore Introduction: Endotracheal tubes are widely used for securing airways in intensive care units. These tubes are removed as soon as a patient is clinically stable. In contrast to a planned extubation, an unplanned extubation (UE) is an important and potentially lethal complication of tracheal intubation. In recent years, investigations, mostly in adult populations, have explored the incidence, factors, and consequences associated with UE .Little information is available regarding the incidence of, and patient conditions related to, UE and subsequent re-intubation in infants and children. Hypothesis: Specific factors that can be identified and potentially controlled play a role in UE in children. Methods: A prospective observational study conducted over a 1 year period in our Pediatric Intensive Care Unit (PICU). Data was collected on all extubations, planned and unplanned. After 6 months, specific quality improvement measures were designed and implemented based on analysis of the collected data. A second 6 months of observation is being carried out. Results: From 01/01/10 to 08/31/10, data was collected on 28 unplanned and 172 planned extubations with a UE rate of 3.1/100 intubation days. 7/28 (25%) of UE did not require reintubation. 8/28 (28.5 %) of UE were accidental, occurring during nursing procedures. Preliminary analysis suggests that UE is more frequent in children ⬍1 year (71.4% v 48.8%), who are noted to be agitated (57.1% v 24.4%) and have more secretions (50.0% v 7.0%). UE occurred more frequently between 4 pm and 8 am (42.9% vs 13.4%). The rate of UE was not related to nurse:pt ratio, duration of intubation, diagnosis or use of restraints. Adverse events occurred in 4/28 (25%) of the UE patients (desaturation ⬍70%, cardiac arrest). Changes in practice based on our observations were implemented in July 2010 and include use of a continuous sedation score (SBS), closer monitoring of patients during nursing interventions and daily extubation readiness evaluations. The impact of these interventions is being monitored. Conclusions: It is possible to predict which patients are at risk for UE. Patient care policy can be modified to target high-risk patients and circumstances.


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ACUTE KIDNEY INJURY FOLLOWING CARDIAC SURGERY: APPLYING A NEW DEFINITION OF KIDNEY INJURY TO QUALITY IMPROVEMENT INITIATIVES

HOW’S THE WEATHER? RELATIONSHIP BETWEEN TEMPERATURE AND TRAUMA ADMISSIONS AT A LEVEL I TRAUMA CENTER

Judith Kristeller, Wilkes University, Wilkes-Barre, PA, Russell Stahl, Community Medical Center, Scranton, PA, John Guzek, Wright Center for Primary Care

Vanessa Ho, Christopher Towe, Weill Cornell Medical College, Jeffrey Chan, Jamaica Hospital Medical Center, Philip Barie, Weill Cornell Medical College

Introduction: Acute kidney injury (AKI) after cardiac surgery is associated with worse outcomes including increased mortality. The incidence of AKI following cardiac surgery varies in part due to the lack of a uniform definition. Recently, the AKI Network (AKIN) has developed a standard definition which is summarized as an increased creatinine (Cr) by at least 0.3 mg/dL or at least 1.5 times baseline. As part of our cardiac surgery continuous quality improvement (QI) program, we sought to determine the incidence of AKI using the AKIN criteria to (1) establish a baseline (2) assess the incidence over time and (3) determine which QI strategies correlate with a reduced incidence of AKI. Hypothesis: Our incidence of AKI has declined over time and correlates with other QI indicators such as blood transfusions. Methods: This retrospective case control study compared patient outcomes from 2004-2005 (GroupA) to 2008-2010 (GroupB). Patients were excluded if they developed cardiogenic shock, required emergent surgery, or were revascularized without cardiopulmonary bypass (CPB). Categorical and continuous variables were analyzed using the chi square and students T-test respectively. Multivariate logistic regression was used to determine which characteristics correlated with AKI. Results: There were 586 patients in GroupA and 584 patients in GroupB. The groups were similar when comparing several predictors of AKI including age, sex, incidence of DM, and ejection fraction. GroupB had a higher risk of AKI (p ⬍ 0.05) based on other predictors including HTN (84% vs 76%), CHF (26% vs 12%), baseline hemoglobin (12.8 vs 13.1), and use of intraaortic balloon pump (10% vs 2%). Conversely, baseline Cr (1.02 vs 1.11) and CPB time (99 vs 108min) predicted a higher risk of AKI in GroupA (p ⬍ 0.05). Group B had a significantly reduced (p ⬍ 0.01) incidence of AKI (30% vs 62%), intraop RBC use (0.5 vs 1.1 unit), and use of any blood product (47% vs 71%). Several characteristics predicted AKI including the aggregate measure of transfusion of blood products (OR 1.40, 95% CI 1.04-1.89). Conclusions: The incidence of AKI is currently 30% and has declined over time at our institution. Any correlation to our blood conservation strategies requires further study.

Introduction: It is commonly believed that the rate of trauma admissions is affected by weather, particularly temperature (increased admissions). Hypothesis: We hypothesized that there are significant relationships between temperature and trauma admission rates. Methods: Trauma admission data (moderate-tosevere injuries as reported to the NY State Department of Public Health) from a Level I Trauma Center in Jamaica, Queens, NY were linked with archived hourly weather service data for JFK International Airport (4.8 mi distant) from the National Oceanic and Atmospheric Administration for the period January 2000December 2009. Admission rate was calculated as the total number of trauma admissions at a given temperature, divided by the total number of hours recorded at that temperature. Trauma admission rate was analyzed by linear and polynomial regression as a function of temperature; day of week and year were added to the model as control variables. Results: There were 9, 490 admissions over 87, 144 hours, at an average of 0.109 admissions per hour. 7, 157 (75.4%) were blunt and 1, 967 (20.7%) were penetrating; the remainder were burns, ingestions, or unknown. Correlation coefficient between trauma rate and temperature (firstorder polynomial) was 0.84. By regression analysis, each increase in temperature of 10 degrees Fahrenheit was associated with an increase of 0.0126 admissions per hour (95% Confidence Interval (CI) 0.0125 to 0.0128), model R2 ⫽ 0.752. Conclusions: Trauma admission rate is significantly associated with higher temperature. This observation may be important for planning of care provision, professional staffing, and resource allocation in trauma/surgical intensive care units and emergency departments.

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COMPARISON OF APACHE III AND IV, SAPS 3 AND MPM0 III AT A TERTIARY REFERRAL CENTER

EVALUATING THE OCCURRENCE OF QT PROLONGATION RESULTING FROM DRUG-DRUG INTERACTIONS

Mark Keegan, Ognjen Gajic, Bekele Afessa, Mayo Clinic

Michael Armahizer, UPMC Presbyterian-Shadyside, Amy Seybert, University of Pittsburgh Medical Center, Pamela Smithburger, Sandra Kane-Gill, University of Pittsburgh School of Pharmacy

Introduction: Severity of illness prognostic scoring systems may be used in the intensive care unit (ICU) for benchmarking, quality improvement and external audit. It is essential that such models perform well. Within the past five years each of the major adult prognostic systems (APACHE, SAPS, MPM) has been updated. There have been few comparisons between the new versions. Hypothesis: We hypothesized that there would be differences in the performances of APACHE IV, APACHE III, SAPS 3 and MPM0 III. Methods: A retrospective cohort study was performed. Demographic, physiologic and outcome data for 2596 patients admitted to one of three ICUs (medical, surgical, mixed) at our tertiary referral center in 2006 were collected. The performance of each of the four models was assessed using the area under the receiver operating characteristic curve (AUC) for discrimination and the Hosmer-Lemeshow statistic (HLS) for calibration. Discrimination was considered excellent, very good, good, moderate and poor with AUC values of 0.9-0.99, 0.8-0.89, 0.7-0.79, 0.6-0.69, ⬍ 0.6, respectively. Calibration was considered poor with HLS p-value ⬍ 0.05. Comparison of model performance was as described by Hanley.(1) Results: Of the 2596 patients studied, 283 (10.9%) did not survive to hospital discharge. The AUCs (95% confidence interval, CI) of the models for prediction of hospital mortality were 0.861 (0.847-0.874), 0.868 (0.854-0.880), 0.801 (0.785-0.816), and 0.721 (0.704-0.738) for APACHE IV, APACHE III, SAPS 3 and MPM0 III, respectively. The discriminatory performances of APACHE IV and APACHE III were similar (p ⫽ 0.621) and classed as “very good”. SAPS 3 also had very good discrimination, but was inferior to APACHE (p ⬍ 0.001). MPM0 III had “good” discrimination and was inferior to the other models (p ⬍ 0.001 for each comparison). The HLS for the models were 31.0, 33.7, 36.6, 21.8, respectively. Each of the HLS generated p values ⬍0.05. Conclusions: In our cohort of patients APACHE III and IV had similar discriminatory capability, both better than SAPS 3 and MPM0 III. The calibration of the models studied was poor. Support was provided by the institutional Critical Care Committee. Reference: 1.Hanley JA, McNeil BJ. Radiology 1983;148:839-843.


Introduction: Over 50 medications cause QT prolongation, which can deteriorate into torsade de pointes. Information is lacking on the frequency of QT prolongation due to drug-drug interactions (DDIs) accounting for temporal sequence in intensive care units (ICUs). This evaluation is of particular interest to clinicians in cardiac ICUs, since there is at heightened risk for adverse outcomes. Hypothesis: The primary objective was to determine the frequency of QT prolongation from potentially interacting drugs in the coronary ICU and cardiothoracic ICU. Methods: After obtaining IRB approval, a retrospective evaluation was performed using the institution’s electronic data repository. Inclusion criteria were admission to the cardiac ICUs between January 2009 and July 2009, age ⱖ 18 years, and electrocardiographic (EKG) evidence of a QTc ⱖ 500 ms. Medications known to prolong the QT interval were identified using the Arizona CERT database. Patients receiving 2 concomitant medications known to prolong the QT interval were considered to experience a pharmacodynamic DDI. Medications known to be CYP450 enzyme inhibitors of QT prolonging medications were considered to cause pharmacokinetic DDIs. Interactions were evaluated for temporal relationship to the QT prolongation. Results: 187 (54.5 % male) patients, with a mean age of 62 years, experienced QT prolongation out of a total of 501 patients (37%) admitted during the study period. 154 and 163 patients had a potential pharmacodynamic and pharmacokinetic interaction, respectively, receiving an average of 2.9 QT prolonging medications during their admission. Of these patients, 43% (66/154) had 133 pharmacodynamic interactions confirmed by temporal sequence, and 47% (77/163) of patients experienced 179 potential pharmacokinetic interactions temporally related to QT prolongation. Most common medications related to these DDIs were amiodarone, ondansetron, tacrolimus, diphenhydramine, voriconazole, risperidone and haloperidol. Conclusions: DDIs may be a significant cause of QT prolongation in cardiac ICUs. These data can be used to educate clinicians on safe medication use. Computerized clinical decision support could be applied to aid in the detection of these events.

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28-DAY MORTALITY IN HIGH-RISK WITH SEVERE SEPSIS RECEIVING ERITORAN WITH OR WITHOUT DROTRECOGIN ALFA: ANALYSIS OF DATA FROM A PHASE II TRIAL

EARLY METABOLIC CRISIS IS COMMON AFTER TRAUMATIC BRAIN INJURY

Gary Kinasewitz, Oklahoma University Health Sciences Center, Mark Tidswell, Baystate Medical Center Introduction: We sought to determine if 28-day all-cause mortality in high-risk patients receiving eritoran, a toll-like receptor 4 antagonist, for severe sepsis was affected by the concomitant use of drotrecogin alfa (DA), a recombinant form of human activated protein C. Hypothesis: We expected that administration of concomitant drotrecogin would result in additional reduction in mortality. Methods: We examined data from a randomized, placebo-controlled phase II trial which evaluated the efficacy of eritoran tetrasodium 105 mg vs placebo (PBO) in patients with severe sepsis aged 18-85. Our analysis was based on patients who had APACHE-II scores of ⱖ25. We compared 28-day all-cause mortality and safety in eritoran tetrasodium 105 mg and PBO pts who did and did not receive concomitant DA. Results: Ninety-eight subjects had baseline APACHE II ⱖ25 and were included in the mITT population, 47 receiving eritoran tetrasodium 105 mg and 51 PBO. Of the 35 eritoran pts not receiving concomitant DA, 12 (34%) died; of the 40 PBO pts not receiving DA, 20 (50%) died. Of the 12 eritoran pts receiving DA, 5 (42%) died; of the 11 PBO pts receiving DA, 5 (45%) died. Mean baseline APACHE II scores were as follows: eritoran alone 28.3; PBO alone 29.5; eritoran ⫹ DA 28.5; PBO ⫹ DA 30.1. Overall, better survival was observed in subjects treated with eritoran tetrasodium 105 mg (30/47, 64%) compared with PBO (26/51, 51%). The incidence of SAEs was similar in the eritoran and PBO arms, and the differences in the incidence of thrombotic and bleeding complications among pts who did and did not receive DA were not statistically significant. The Breslow-Day test suggested that outcomes were similar regardless of whether or not DA was used (P-value ⫽ 0.6075). The relative risk of all-cause mortality for eritoran tetrasodium 105 mg vs PBO was 0.74 with 95% CI of 0.46 to 1.18 using Cochran-Mantel–Haenszel statistics stratified by concomitant DA use. Conclusions: In patients with high-risk severe sepsis, eritoran appeared to reduce 28-day mortality over that seen with PBO. The addition of DA did not appear to further reduce mortality, but this apparent lack of effect may be explained by the small sample size.

Nathan Stein, David McArthur, UCLA, Paul Vespa, UCLA Health Sciences Center Introduction: Traumatic Brain Injury (TBI) results in disrupted brain metabolism including metabolic crisis, as defined by low brain glucose and elevated lactate/pyruvate ratio (LPR). Hypothesis: We hypothesize that silent metabolic crisis occurs early after TBI despite routine successful resuscitation efforts. Methods: Cerebral microdialysis (0.3 uL/min) was performed in normal appearing white matter in 117 consecutive patients with severe TBI (GCS ⬍ 9) for the initial 7 days starting between 12 and 24 hours after injury. A standardized resuscitation protocol using normal saline 2-4 L over 2 hours was used, CVP ⬎ 6, and norepinephine to keep MAP ⬎ 80 mm Hg . Hourly values of brain glucose, lactate, and pyruvate were obtained. The incidence dring the initial 48 hours after inury of low brain glucose (⬍0.8 mmol/L), and elevated lactate/pyruvate ratio (LPR) ⬎ 40, as well as the combination of both, termed metabolic crisis, were determined for the group. Scores of successful resuscitation were determined for each subject. We determined the influence of elevated ICP ⬎ 20 mm Hg, low blood glucose (⬍110 mg/dl), and fever (⬎38C) on the incidence of metabolic crisis and whether correcting each of these improved metabolic crisis. Results: Low brain glucose occurred in 74.9% of patients within 48 hours, while elevated LPR occurred in 70% and the combination of low brain glucose and elevated LPR, termed metabolic crisis, occurred in 60% of patients. Successful resuscitation occurred in 93% of patients, but was not associated with the absence of metabolic crisis ( p ⬍ 0.21). Metabolic crisis was more common if one or more of the potential physiological triggers (ICP, low blood glucose, or fever) were present (p ⬍ 0.001). Metabolic crisis was corrected in 60% of patients by treatments to correct one or more of the physiological triggers over the next 96 hours. Therapeutic normothermia was associated lessening of metabolic crisis as compared with the presence of fever (p ⬍ 0.001). Conclusions: Metabolic crisis frequently occurs after TBI despite routine physiological resuscitation. Specific treatment of potential brain insults, including ICP, hypoglycemia and fever may lessen the duration and magnitude of metabolic crisis.

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VANCOMYCIN DOSING IN CRITICALLY ILL PATIENTS – USING POPULATION PHARMACOKINETICS TO DEVELOP PERSONALISED DOSING REGIMENS TO ACHIEVE TARGET CONCENTRATIONS BY CONTINUOUS INFUSION

ACTIVATED PROTEIN C IN SEPTIC SHOCK: A PROPENSITYMATCHED ANALYSIS

Jason A Roberts, University of Queensland, Fabio Silvio Taccone, Erasme University Hospital, Andrew Udy, Royal Brisbane and Women’s Hospital, JeanLouis Vincent, Fre´de´rique Jacobs, Erasme University Hospital, Jeffrey Lipman, University of Queensland

Introduction: The use of human recombinant activated protein C(rhAPC) for the treatment of severe sepsis remains controversial despite multiple reported trials. A large multicenter trial in patients with septic shock is currently underway. The efficacy of rhAPC remains a matter of dispute. Hypothesis: We hypothesize that patients with septic shock who were treated with rhAPC had an improved in-hospital mortality compared to patients with septic shock with similar acuity who did not receive rhAPC. Methods: This retrospective cohort study was completed at a large University-affiliated hospital. All patients with septic shock(1992 SCCM/ACCP Consensus Conference definition) admitted to a 50-bed ICU between July 2003 and February 2009 were included. Patients were treated according to sepsis management guidelines. Results: A total of 554 septic shock patients were included(108 received rhAPC and 446 did not). Treated and untreated groups were matched in patient characteristics, comorbidities, physiologic variables, and Acute Physiology And Chronic Health Evaluation II (APACHE II) scores. Mean APACHE II scores were 24.5 for the matched treated and 23.9 for the matched untreated group(p ⫽ 0.58). In a 1:1 propensity-matched analysis, receipt of rhAPC was associated with reduced in-hospital mortality(35% vs. 53%, OR ⫽ 0.49, 95% CI, 0.27-0.74, p ⫽ 0.0046), similar mean days on vasopressors(2 vs. 2, p ⫽ 0.95), similar mean days on mechanical ventilation(9 vs. 8.7, p ⫽ 0.81), and similar mean length of ICU stay in days(11.0 vs. 11.3, p ⫽ 0.8997). No patients in either group had intracranial bleeding; differences in major transfusions(six or more units of red blood cells within 2 consecutive days or four or more units on any single day, 4% vs 9%), minor transfusions(two or three units on a single day, 35% vs 42%), and gastrointestinal bleeding(3% vs 0%) were not statistically significant. Conclusions: Patients in our institution with septic shock who were treated with rhAPC had a reduced in-hospital mortality compared with patients with septic shock with similar acuity who were not treated with rhAPC. In addition, Time on mechanical ventilation, time on vasopressors, length of ICU stay and bleeding complications did not differ between the groups.

Introduction: Despite the development of novel antibiotics with Gram positive activity, vancomycin remains the treatment of choice in affected critically ill patients, although rapidly achieving concentrations associated with maximal efficacy provides a unresolved challenge for clinicians. Hypothesis: Higher than recommanded loading and daily dose of vancomycin, given by continuous infusion (CI), are necessary in septic patients to achieve adequate drug concentrations. Methods: This was a retrospective data collection of adult septic critically ill patients receiving vancomycin by CI. Patients receiving renal replacement therapy were excluded from the analysis. All patients received a loading dose (15mg/kg) followed by a continuous infusion with dose adjustment guided by vancomycin concentration data at three time-points (approximately 24-, 48- and 72-hours). Target vancomycin concentrations were considered between 20 and 30 mg/L. The concentration versus time data for vancomycin in plasma were analysed by a non-linear mixed effects modelling approach using NONMEM (v 6.1). Bootstrapping and Monte-Carlo simulations were performed using the final covariate model. Results: We included 206 patients over a 24-month period. The best population pharmacokinetic model consisted of a one-compartment linear model and additive residual unknown variability. Vancomycin volume of distribution (1.4 L/kg) was described by total body weight and clearance (4.2 L/hr) by 24-hour urinary creatinine clearance (CrCl). Simulation data showed that a 30mg/kg loading dose was necessary to rapidly achieve vancomycin concentrations of 20 mg/L. Moreover, daily vancomycin regimen was dependant on CrCl and a patient with a CrCl of 100 ml/min would have required at least 35mg/kg per day by continuous infusion to maintain target concentrations. Conclusions: Using a rational approach to successfully dosing vancomycin with total body weight and 24-hour urinary CrCl, higher than recommanded regimen of vancomycin would be necessary to achieve adequate drug concentrations in septic patients.Further research to confirm the clinical implications of rapid achievement and maintenance of target vancomycin concentrations is suggested.

Farid Sadaka, Jacklyn O’Brien, Matthew Migneron, Julie Stortz, Alexander Vanston, Robert Taylor, Saint John’s Mercy Medical Center


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PERFORMANCE IMPROVEMENT REDUCES PROLONGED VENTILATION IN CORONARY ARTERY BYPASS PATIENTS

THE EFFECT OF A MOBILITY PROTOCOL ON DIRECT HOSPITAL COSTS AND MORTALITY IN A COMMUNITY HOSPITAL ADULT ICU

Ken Hargett, Faisal Masud, Michael Bocci, Methodist Hospital, Margaret Berger, Jose Rodriguez, Kathy Knaack, Dana Samways, The Methodist Hospital Introduction: The Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database report is a benchmark program for large cardiovascular centers. A key indicator is the percentage of prolonged ventilation (defined as ⬎ 24 hours) for Coronary Artery Bypass (CAB). In 2009, our institution experienced an increase in prolonged ventilation to 20.7%. Hypothesis: A performance improvement plan composed of a Multidisciplinary Team will reduce prolonged ventilation to ⬍ 10%. Methods: The design was a pre and post intervention observational study. A team including CV Surgeons, Nursing, Intensivist, Respiratory Care, and Performance Improvement was formed. Problems identified included: 1) lack of awareness of the 24 hour window, 2) inconsistent application of weaning protocols, and 3) inconsistent coordination of sedation. A plan was developed to1) increase awareness of 24 hour window, 2) improve communications between caregivers through structured report and 3) increase interventions before 24 hours. Specific interventions established included education of the 24 hour window to all caregivers especially consulting physicians. A highly visible green card posted on the ventilator that indicated time zero (admission to unit) with specific time intervals of 6, 12, 18, 20 and 22 hours for performance of sedation reduction and spontaneous breathing trials. Daily rounds were established to address every patient approaching 18-20 hours of ventilation. A weekly meeting was established to review patients and discuss reasons for patients that exceeded 24 hours. Additional interventions including follow-up from leadership to physicians that had contributed to prolonged ventilation cases. Results: Within the first month a reduction to 16.1% of CAB prolonged ventilation was realized. For the following 6 months with 306 CABs, prolonged ventilation was reduced to ⬍ 8%. A by-product of the program was an increase to 53.9% of CAB patients extubated in ⬍ 6 hours exceeding the STS benchmark of 32%. Conclusions: A Multi-Professional approach utilizing increased awareness, visual aids, effective communication, coordination of sedation and spontaneous breathing trials, can reduce the percentage of prolonged ventilation in CAB patients.

John Olsen, Kirsten Skillings, Robert Dilley, Jason Wesenberg, Scott Davis, St. Cloud Hospital Introduction: Participation in a physical therapy program has been reported to improve ambulation and strength and reduce hospital and ICU LOS, but there is little data available on the financial outcomes of enhancing mobility for these patients. Hypothesis: Incorporation of a mobility protocol into a ventilator bundle in a community hospital ICU will reduce costs and improve patient outcomes. Methods: Using a multidisciplinary team a mobility protocol was developed and incorporated into our ventilator bundle. The protocol included education, assessment by a physical therapist of all ventilated patients after 24 hours of ventilatory support and aggressive and progressive physical therapy. Process and outcome data were collected concurrently and compared to a benchmark period. Excluded were those patients on ventilatory support ⬍24 hours and all cardiac surgical patients. Outcome measures were hospital and ICU direct costs and LOS, ventilator hours, and hospital mortality. Patients were monitored for adverse effects of physical therapy. Data was collected for the last 6 months of FY 2009, before the use of the mobility protocol (benchmark period), and for the last 9 months of FY 2010 (study period). No other major quality improvement initiatives were begun during these periods. Results: There were 145 pts in the benchmark period and 366 pts in the study period. Physical therapy assessment was performed in 17.9% vs 44.6%; mean hospital costs were $56, 187 vs $50, 271; mean ICU cost were $38, 062 vs $33, 560. Annualized, this a $2, 887, 008 decrease in hospital cost. Hospital and ICU LOS fell from 16.1 and 8.7 days to 14.5 and 7.0 days respectively; ventilation hours fell by 0.8%. Hospital mortality fell from 32.4% to 23.8%. No adverse effects of physical therapy were observed. Conclusions: In our community hospital ICU the incorporation of a mobility protocol into the ventilator bundle was safely accomplished and was associated with a substantial cost savings for the hospital (total annualized: $2, 887, 008), a reduction in hospital LOS, and a decrease in hospital mortality. With 336 pts in the study period there may be 31 more survivors than expected since starting the mobility protocol.

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CLINICAL FACTORS AFFECTING ANTIBIOTIC DURATION IN PATIENTS RECEIVING ANTIBIOTIC THERAPY AT THE TIME OF ICU DISCHARGE: THE CONTINUATION STUDY

GASTRIC ACID SUPPRESSION AND THE RISK OF HOSPITAL-ASSOCIATED PNEUMONIA IN CRITCIALLY-ILL PATIENTS

Kristen Hillebrand, Neil Ernst, Eric Mueller, UC Health-University Hospital; University of Cincinnati

Kelli Rumbaugh, Marcus Dortch, Vanderbilt University Medical Center

Introduction: Prolonged antibiotic duration (AD) is associated with antibiotic resistance. This study looked to identify factors associated with AD in ICU patients receiving antibiotic therapy at ICU discharge and determine if ICU service-defined AD is associated with shorter definitive antibiotic therapy. Hypothesis: Among patients receiving antibiotic therapy at ICU discharge, patients with ICU service-defined antibiotic discontinuation dates will have shorter AD compared to those without ICU service-defined discontinuation dates. Methods: This prospective cohort study included all adult med and surg ICU patients receiving antibiotic therapy for confirmed/suspected infection at ICU discharge to non-ICU services at an academic medical center (Dec/09-May/10). Patients were stratified at ICU discharge: 1) prescribed antibiotic discontinuation dates (pDD) and 2) no prescribed antibiotic discontinuation dates (nDD). Primary endpoint was total duration of the antibiotic therapy present at the time of ICU discharge. Multivariate logistic regression (MVLR) determined clinical factors associated with AD ⱕ7 days. Results: 150 patients (MICU n ⫽ 90; SICU n ⫽ 60) were included: 52 pDD and 98 nDD. There were no differences in patient demographics or ICU discharge SOFA. pDD patients more often had pneumonia (25 v 11%; p ⫽ 0.05), known pathogen (64 v 43%; p ⫽ 0.046), and antibiotic susceptibilities (55 v 33%; p ⫽ 0.041) at ICU discharge. Overall, AD tended to be shorter in pDD v nDD patients (9.5 ⫾ 4.4 v 12.3 ⫾ 11 days; p ⫽ 0.28). Thirty (58%) pDD patients had AD as prescribed (adherent) compared to 15 (68%) of the 22 nonadherent pDD patients receiving longer AD (8.8 ⫾ 5.0 v 11.3 ⫾ 2.9 days; p ⫽ 0.007). pDD patients less often received ⬎ 14 days (6 v 21%; p ⫽ 0.029) and tended to more often receive ⱕ7 days (48 v 36%; p ⫽ 0.23). There were no differences in C.diff, multidrug resistant pathogens, or readmission. On MVLR, controlling for SOFA and pathogen, bacteremia was associated with longer AD, whereas pneumonia and pDD were associated with shorter AD. Conclusions: Prescribed discontinuation dates at ICU discharge is associated with shorter duration of antibiotic therapy. ICU services should prospectively define AD to discourage prolonged antibiotic therapy.


Introduction: Hospital-associated pneumonia (HAP) is associated with patient mortality and morbidity. Gastric acid suppression has been identified a predictor for HAP. Both proton pump inhibitors (PPI) and histamine type-2 antagonists (H2A) are routinely used for stress ulcer prophylaxis (SUP) in critically-ill patients. Given greater acid suppression of PPIs compared to H2As, concern has been raised regarding PPI use for SUP. Hypothesis: ICU patients receiving a PPI for SUP have an increased incidence of HAP compared to patients who receive H2A therapy. Methods: Data was collected retrospectively from a surgical ICU repository. Eligible participants were ⱖ 18 yo, had an ICU stay ⱖ48h, and received PPI or H2A for SUP. Patients with a GI bleed or those receiving both a PPI and H2A during the ICU stay were excluded. Age, APACHE II score, ICU length of stay, and duration of mechanical ventilation were evaluated. A diagnosis of HAP was based on the National Nosocomial Infections Surveillance System/ National Healthcare Safety Network (NNIS/NHSN) criteria. A forward stepwise binary logistic regression model was used to identify risk factors for HAP. Results: The study included 1663 patients, of whom 107 had a diagnosis of HAP. Patients with HAP had a significantly increased duration of ICU length of stay (4 vs 14.2 days, p ⬍ 0.001), duration of mechanical ventilation (3 vs 13.7 days, p ⬍ 0.001), and mortality (6.9% vs 17.8%, p ⬍ 0.001). In univariate analysis, patients in the PPI group had a significantly higher incidence of HAP as compared to patients in the H2A group (PPI - 8.6% versus H2A - 5.6%, p ⫽ 0.03). However, in a binary logistic regression model, choice of PPI or H2A was not associated with HAP (OR 1.06, 95%CI 0.62-1.82). Duration of ICU mechanical ventilation was the only covariate found to be independently associated with HAP (OR 1.22, 95% CI 1.09-1.36). Conclusions: Although there was a significant difference in the incidence of HAP between the PPI group and the H2A group, neither PPI nor H2A use is an independent risk factor for HAP. The only independent predictor of HAP is duration of mechanical ventilation in the ICU.

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HEMOLYTIC AND THROMBOCYTOPATHIC CHARACTERISTICS OF ECMO SYSTEMS AT SIMULATED FLOW RATE FOR NEONATES

ABSORPTION AND TRANSIT OF NUTRIENT IN CRITICAL ILLNESS

Andrew Meyer, Children’s National Medical Center, Andrew Wiles, Children’s National Medical Center Research Center For Genetic Medicine, Oswaldo Rivera, Childrens National Medical Center, Edward Wong, Children’s National Medical Center, Robert Freishtat, Children’s National Medical Center Research Center For Genetic Medicine, K. Rais-Bahrami, Children’s National Medical Center, Heidi Dalton, Phoenix Childrens Hospital Introduction: Modern centrifugal pump/hollow-fiber oxygenator systems for extracorpeal membrane oxygenation (ECMO) have advantages such as less priming volume and the inability to cause tubing rupture as compared to the more commonly used roller-head/ silicone membrane systems. Adoption of these modern systems has been slow in neonates due to past evidence of severe hemolysis leading to renal failure and mortality. Different ECMO systems have also been linked to platelet dysfunction which may be associated with intracranial hemorrhage, a leading cause of infant morbidity. Little data exists comparing the modern systems vs. conventional systems for their hemolytic and platelet function at low flow rates consistent with neonatal ECMO. Hypothesis: At low flow rates, hemolysis and platelet dysfunction occur at the same minimal rate in centrifugal pump/ hollow-fiber oxygenator systems as compared to roller-head/silicone membrane systems. Methods: Comparative study using two pumps, the Jostra Rotaflow (Maquet, Wayne, NJ) and the standard roller-head (Jostra, Maquet, Wayne, NJ) and two oxygenators, Quadrox-D (Maquet, Wayne, NJ) and silicone membrane (Medtronic, Minneapolis, MN). Five test runs of four circuit combinations were examined for hemolysis and platelet function during 6 hrs of continuous use in a simulated in vitro ECMO circuit circulating whole swine blood at 300 ml/min. Hemolysis was assessed by spectrophometric measurement of plasma free hemoglobin (fPH). Platelet aggregation and activation were evaluated using monoclonal CD61 and CD62P antibody fluorescent profiles. Results: All of the ECMO systems created fPH at a similar rate compared to a static blood control. There was no difference in the mean Normalized Index of Hemolysis of the centrifugal/hollow-fiber oxygenator system as compared to the roller-head/silicone membrane systems (0.0044 g/100L vs. 0037 g/100L, p ⬎ 0.3). None of the ECMO systems had a significant increase in platelet aggregation or activation above baseline. Conclusions: In a low-flow environment, centrifugal/hollow-fiber oxygenator and roller-head/silicone membrane systems create a similar amount of hemolysis and platelet dysfunction. Further study to correlate to patient care is warranted.

Adam Deane, Antony Zaknic, Matthew Summers, Marianne Chapman, Royal Adelaide Hospital, Michael Horowitz, University of Adelaide, Robert Fraser, Repatriation General Hospital Introduction: The absorption of nutrient during postpyloric feeding has not been assessed in the critically ill. In health, the rate of small intestinal transit is a major determinant of nutrient absorption. Hypothesis: Glucose absorption and duodeno-caecal transit times (DCTT) will be reduced in critical illness when compared to health. Methods: A prospective observational study was performed in 28 mechanically ventilated critically ill patients (21M, age 46(56)yr, BMI 24(13) kg/m2, ICU admission day 5(13), APACHE II score 19(26))and 14 healthy subjects (9M, age 49(70)yr, BMI 25(14)kg/m2). After a 6hr fast a 100 ml ‘meal’ (Ensure 1kcal/ml), labelled with 20 MBq 99mTc-sulphur colloid and 3 grams of 3-O-methylglucose (3-OMG) – an index of glucose absorption - was infused into the distal duodenum over 6 min. Dynamic anterior scintigraphic images were recorded in 3 min frames for 240 min and the time of first appearance of activity in the caecum, the DCTT, was recorded by three blinded operators. Glucose absorption was measured as Area Under Curve (AUC 0-240 min). Data are median(range). Data were assessed using Mann Whitney U test or Fischer exact test, and associations using Spearman’s rank correlation coefficient. Results: Glucose absorption (3-OMG AUC) was reduced in patients (66.3(96) mmol/l.min) compared to healthy subjects (78(99) mmol/l.min) (P⬍0.05). DCTTs were not significantly different between patients (192(231) min) and healthy subjects (168(236) min) (P⫽0.99). Small intestinal transit times were not associated with glucose absorption in critical illness (␳ ⫽ 0.22; P ⫽ 0.28) or health (␳ ⫽ ⫺0.17; P ⫽ 0.60). Conclusions: Absorption of glucose is reduced in the critically ill, but the DCTT does not appear to be substantially affected. Accordingly, malabsorption in this group may be mediated by factors other than transit of chyme through the small intestine.


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THE ‘GREEN LIGHT‘ PROGRAM: IMPROVING PATIENT THROUGHPUT IN A RAPID TURNOVER SURGICAL INTENSIVE CARE UNIT

DIFFERENTIAL MORTALITY IMPLICATIONS OF NUCLEATED RED BLOOD CELLS IN AFRICAN AMERICANS

Samantha Young, Donna Prow, Robert Hody, Takiya Reavis, Theresa Hartsell, The Johns Hopkins Medical Institutions Introduction: Direct admission of patients to the Johns Hopkins Weinberg ICU, a high turnover surgical unit, is often adversely affected by a lack of immediately available ICU beds. Patients are delayed in the operating room (OR) or diverted to the post-anesthesia care unit (PACU), leading to OR inefficiency and consumption of PACU resources. Evaluation suggested that an inability to transfer clinically stable patients to the floor in the early morning resulted in turnover delays for morning and afternoon surgical admissions. Hypothesis: Targeted interventions to facilitate early transfer of patients from the ICU will result in decreased frequency of OR and PACU delay. Methods: A multidisciplinary lean six sigma workgroup was formed with representatives from ICU, OR, and PACU nursing, ICU and OR physicians, surgical coordinators, an administrative fellow, and a lean six sigma consultant. Analysis of systems factors led to the following interventions: (1) early identification of clinically stable ‘green light‘ patients for transfer; (2) a goal of transferring two patients to the floor by 10AM, the ‘2x10‘ goal; (3) collaboration with downstream wards to implement the same processes; (4) improved accuracy of real-time patient data available to the surgical shift coordinator; and (5) collection of data to document compliance and demonstrate changes in OR/PACU utilization. Incentives were offered to encourage compliance. This performance improvement project was implemented in December 2008 and continues to date. Results: Pre-intervention review showed that 3.5% of ICU-bound surgical cases were subject to OR or PACU delays resulting from bed availability. The average length of each PACU stay was 3.5 hrs, or a total of 8 PACU patient hrs per week. Post-intervention, the absolute number of morning patient transfers increased by 5%. The number of patients delayed in the OR or PACU dropped to 0.6%, an 83% decrease. This effect has been sustained over the 18 months of the project, independent of overall ICU utilization. Conclusions: Targeted interventions to improve early ICU transfer using the ‘green light‘ and ‘2x10‘ programs result in significant and sustainable improvement in ICU throughput.

Subhash Reddy, Jerry Stassinopoulos, Mathilda Horst, Manpreet Chadha, Jack Jordan, Ilan Rubinfeld, Henry Ford Hospital Introduction: The presence of nucleated red blood cells (NRBC) in blood has been identified as a poor prognostic indicator. We sought to understand the implications in our critically ill patients, specifically; the African American (AA) population has not been previously well represented in previous data. Hypothesis: We hypothesized that NRBC levels would be associated with increased risk of mortality and would be similar regardless of gender or race. Methods: This is retrospective study of hospital administrative data collected between 2005 to 2009 regarding NRBC positives in patients admitted at our institution. We selected all patients with a non-zero value for NRBC, at least one day in intensive care and excluded patients ⬍ 18 yrs. We obtained highest value during admission and time from first non-zero value to discharge or expiration. Odds ratio (OR) & Multi variate logistic regression were performed using SPSS (Chicago). Results: Over 10668 patients were noted to have non-zero NRBC, of which 4709 had some time in an intensive care unit during their stay. Of these 1311 (27.8%) expired and 3398 survived. The median number of days between first positive lab to expiration was 4.6 days (mean 10.2 day), while the median number of days between first positive lab and discharge (alive) was 9.6 (mean 14.5 days) and p ⬍ .001. Maximum measurement for each patient of NRBC demonstrated a median of 2 (mean 8.4). 290 patients had an NRBC reading above 20/100 wbc count (6.2%). Mortality in this group was 61.7% compared to 25.6% of those with value ⬍ 20 (OR 4.7, p ⬍ .001). In a multivariate logistic regression (LR) model including age, gender and race, NRBC ⬎ 20 proved to independently predict mortality, OR 5.0, p ⬍ .001. 64% (3007) of our study patients were AA. AA were relatively protected with decreased mortality 24.6% compared to their non-AA patients 33.5%, OR 0.65, p ⬍ .001. This too was an independently significant variable by LR as a protective variable with OR .648 and p ⬍ .001. Conclusions: In our mixed critical care perspective we noted a significant association with the presence of NRBCs, levels ⬎ 20 and increased risk of death. The potential survival benefit in African American needs further studies to clarify it.

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PERCEIVED BENEFIT OF A CONSULTATIVE TELEMEDICINE SERVICE IN A HIGHLY STAFFED INTENSIVE CARE UNIT

NON-TRAUMA EMERGENCY (NTE) SURGERY PATIENTS IN THE ICU: INCREASING IN NUMBER AND ACUITY

Mark Romig, Asad Latif, Peter Pronovost, Randeep Gill, Adam Sapirstein, John Hopkins University School of Medicine Introduction: Telemedicine use in the ICU is increasing in efforts to improve delivery of intensivist resources. Little is known about the attitudes and perceptions of bedside staff working in these systems. Hypothesis: The use of nocturnal ICU telemedicine service improves ICU culture, staff satisfaction, and perceptions of quality of care in a highly staffed university hospital. Methods: The study used a pre-post design with concurrent controls in an academic medical center with full time intensivist staffing. We surveyed ICU staff using a previously validated tool before deployment and following a two month program of ICU telemedicine. Surveys were concurrently administered in a control ICU and in the test ICU in which a telemedicine center provided consultative care between 19:00 – 07:00 daily. The responses of individuals to questions exploring perceptions of patient care, effectiveness of care, relations, communication, psychological working conditions, burnout, job satisfaction, intention to quit, and education were compared before implementation and after completion of the telemedicine program. Responses were measured using a five point Likert scale and results were analyzed using paired t testing. Results: Nurses in the intervention ICU (n ⫽ 27) showed statistically significant improvement in the relations and communication score (2.99 ⫾ 1.13 pre-intervention vs. 3.27 ⫾ 1.27 postintervention p ⬍ 0.01), the psychological working conditions and burnout score (3.10 ⫾ 1.10 pre vs. 3.23 ⫾ 1.11 post p ⬍ 0.02), and the education score (3.52 ⫾ 0.84 pre vs. 3.76 ⫾ 0.78 post p ⬍ 0.03) while nurses in the control ICU (n ⫽ 11) showed a significant decline in the patient care and perceived effectiveness score (3.94 ⫾ 0.80 pre vs. 3.48 ⫾ 0.86 post p ⬍ 0.01) and the education score (3.95 ⫾ 0.39 pre vs. 3.50 ⫾ 0.80 post p ⬍ 0.05). There were no significant changes in bedside intensivist attitudes. Conclusions: The introduction of ICU telemedicine services in a highly staffed academic ICU was associated with an improvement in nursing perceptions of working conditions and communications while these perceptions decreased in a control ICU. Telemedicine has the potential to improve ICU staff satisfaction in highly staffed ICUs.


Eric Luehr, Michael Todd, Barbra Miller, Gerard Doherty, Pauline Park, University of Michigan, Lena Napolitano, University of Michigan School of Medicine Introduction: We established a non-trauma emergency (NTE) general surgery service in 2005 to care for surgical patients requiring urgent or emergent surgical intervention. We previously examined our NTE admissions to the Surgical ICU (SICU) over a 1-year period (2005-2006) and documented that NTE patients had higher ICU mortality, but that study was limited by small sample size (n ⫽ 77). We then established a prospective NTE data registry and evaluated the critical care characteristics of the NTE cohort over a 4-year period (2006-2010) since our initial study. Hypothesis: NTE patients have higher ICU acuity and higher ICU mortality compared to non-NTE patients in a surgical ICU. Methods: All SICU admissions were examined over a 4-year period (2006-2010). A dedicated registrar prospectively identified all adult NTE surgery patients admitted to our tertiary care university hospital and prospectively collected all surgical and non-ICU data. Additional, prospective critical care data were collected by a single APACHE-ICU coordinator. Characteristics of NTE patients were compared to non-NTE patients using comparison of means and t-test. Results: A total of 4572 patients were admitted to the SICU, with 393 NTE patients comprising 8.6% of all SICU admissions. Over the study period, NTE admission to the ICU significantly increased, from 77 (6.1%) in 2005 to 116 (11.5%) by an average of 11.4% per year (9.5%, 9.8%, 14.9% increase over the last 3 years). NTE ICU patients comprised 11.5% of all NTE admissions, with 68% of all NTE patients requiring surgery. Mean APACHE III scores on ICU day 1 were significantly higher in NTE patients (59.21 ⫾ 1.12 SD) compared to non-NTE patients (51.1 ⫾ 2.75 SD, p ⫽ 0.0003). NTE patients had greater ICU length of stay (7.4 ⫾ 1.5 vs. 4.8 ⫾ 0.2, p ⫽ 0.0049) and higher readmission rate to the ICU (13.5% vs. 8.8%). NTE patients had a nearly two-fold increase in ICU mortality compared to non-NTE patients (mean 8.26% ⫾ 1.47 vs. 4.23% ⫾ 0.76, p ⫽ 0.0006). Conclusions: NTE surgery patients comprise an increasing cohort of patients in the SICU and have high acuity and high ICU mortality. Specific efforts targeted at improved outcomes in NTE patients in the SICU are warranted.

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DEVELOPMENT AND ASSESSMENT OF STRUCTURED HAND-OFF PROCESS IN A MULTI-DISCIPLINARY, MULTISPECIALTY PEDIATRIC INTENSIVE CARE UNIT

USE OF TELEMEDICINE TO PROVIDE ENHANCED COMMUNICATION BETWEEN AT-HOME ATTENDINGS AND BEDSIDE PERSONNEL IN A PEDIATRIC INTENSIVE CARE UNIT

Hemant Agarwal, Vanderbilt Children’s Hospital, Wenli Wang, Benjamin Saville, Brian Donahue, Vanderbilt University, Suanne Daves, The University of Chicago, David Bichell, Karla Christian, Vanderbilt Childrens Hospital, Zena Harris, Johns Hopkins University and School of Medicine Introduction: Every time a patient moves from one environment to another, there is loss of communication of essential information regarding care. Hypothesis: A structured hand-off process developed for the multidisciplinary, multispecialty clinical team working in a Pediatric Cardiac Intensive care Unit (PCICU) improves quality of hand-off and decreases loss of patient care information. Methods: A standardized structured hand-off communication process was developed for every patient transferred from the operating room (OR) to the PCICU following pediatric cardiac surgery. An anonymous survey was administered to the PCICU clinical team prior to introduction of the hand-off to study existent patient care communication between the OR team and the PCICU team. The structured hand-off process was studied for a period of one year (July 2009 to June 2010). A second survey was subsequently administered to the PCICU clinical team to re- assess patient care communication as well as quality of the structured hand-off process on a Likert scale (1-5) response. Patient care communication was compared between pre and post hand-off periods from the two survey responses. Results: Structured hand-off process was documented for 355 patients (95.4%) patients. The survey response rate for the pre and post hand-off surveys were 69% and 92% respectively. Wilcoxon Rank Sum test comparing pre and post hand-off surveys revealed significant difference (p ⬍ 0.001) for each of the 6 variables that included patient demographics, medical background, anesthesia administered, surgical procedure, post-surgical hemodynamics and post-operative laboratory results. The overall quality of the structured hand-off process based on physical environment, consistency, accuracy and knowledge of operative period was assessed to be excellent (mean response on the Likert scale 4.4 ⫾ 0.7). Conclusions: Structured hand-off process in a multi-disciplinary, multi-specialty pediatric intensive care unit improves the quality of hand-off with minimal loss of patient care information. The role of a structured hand-off process on outcomes of the patients needs to be further evaluated.

Phoebe Yager, Michael Whalen, Brian Cummings, Natan Noviski, Massachusetts General Hospital Introduction: In a pediatric intensive care unit (PICU), where fellows provide in-house coverage with an attending on home-call during nights and weekends, the lack of face-to-face interaction among the attending, medical staff, patient and family may compromise communication. Hypothesis: Teleconferencing provides the PICU attending at home a tool to assess the patient and communicate simultaneously with all members of the interdisciplinary care team and the patient’s family at the bedside. Methods: A mobile telemedicine cart in the PICU and a home-based unit for each PICU attending were used to enable a HIPPAsafe internet connection. The PICU cart included a video camera and accessories enabling close-up patient examination. The at-home attending controlled the camera in the PICU to examine the patient, view the bedside monitors and communicate with the team and parents in real time. Consent was obtained from the family at the time of PICU admission. Following each teleconference the attending completed a form to record the quality and duration of the connection, participants and comments about its utility. Data was collected retrospectively from these forms. Results: Twenty-four consecutive intake forms completed between May and August 2010 were analyzed. Connectivity was established in 92% of attempts. Audio and video quality was ‘excellent’ 98% of the time. Calls lasted 5-40 minutes (median 15 min). The fellow was present for 100% of the conferences, nurse 86%, resident 36%, respiratory therapy 9% and parents 63%. Attendings noted an impact on medical management in 59% of encounters, e.g two decisions to intubate, one to extubate and one to refrain from intubation. The attending reinforced the existing care plan in 27% of encounters. A parental update was provided in 68% of encounters. Conclusions: Telemedicine offered an additional tool to help attending physicians manage critically ill patients, communicate with bedside care teams, and provide reassurance to families.

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IMPROVING PRESCRIBING AND DOCUMENTATION OF IMMUNIZATION AND EDUCATION IN PATIENTS WHO UNDERGO EMERGENCY SPLENECTOMY

DECREASED RATES OF CODE TEAM ACTIVATION FOLLOWING THE INTRODUCTION OF RAPID RESPONSE TEAMS TO AN ACADEMIC MILITARY MEDICAL CENTER

Bonnie Falcione, University of PIttsburgh, Elisabeth George, University of Pittsburgh Medical Center, Richard Day, University of Pittsburgh, Susan Skledar, University of Pittsburgh Medical Center

Sean Reilly, US Army, Jeremy Pamplin, Louie Pineda, Rebecca Hebert, Deborah Marquez, BAMC, Kevin Chung, USAISR

Introduction: Patients undergoing emergency splenectomy (ES) are candidates for immunization to prevent overwhelming post-splenectomy sepsis. Due to multiple vaccines and the urgent care setting, the immunization process is errorprone. A quality improvement audit at our institution showed errors in vaccine prescribing (RX), dispensing, administration and documentation (DOC). Hypothesis: Implementation of a customized physician orderset and corresponding dispensing and DOC procedure will improve vaccine RX and required DOC in ES. Methods: After phased implementation of a customized physician orderset with corresponding dispensing and DOC procedure, an IRB-approved retrospective review of medical records for patients who had ES between January 1, 2008 and December 31, 2009 was conducted to evaluate RX and DOC of vaccine administration and patient education compared to 2007 historical baseline. Statistical analysis was performed with Chi-square and Fisher’s Exact tests. Results: We found 76, 110, and 108 patients had splenectomy in ’07, ’08 and ’09 with 56, 44 and 46 evaluable medical records for diagnosis confirmed ES, respectively. RX and DOC of vaccine administration for ⱖ1 required vaccines increased after implementing a pre-printed physician orderset in ’08(100% vs. 88.6%; p ⫽ 0.033 and 100% vs. 77.8%; p ⫽ 0.001, respectively), and a computerized physician orderset in ‘09(100% vs. 88.6%; p ⫽ 0.031 and 100% vs. 77.8%; pⱕ.001, respectively) while vaccines prescribed correctly also increased significantly in ’08 and ’09, compared to baseline. All required vaccine DOC elements: site, lot #, expiration date and manufacturer, increased in ’09(54.5% vs. 97.8%, p ⬍ .001; 31.6% vs. 77.8%, p ⬍ .001; 31.6% vs. 57.8%, p ⫽ 0.014; 7% vs. 26.7%, p ⫽ 0.013; respectively) after implementing dispensing and DOC procedure in ’08, versus baseline. Patient education DOC increased during the last six months of ’09 compared to baseline(17.1% vs. 46.4%; p ⫽ 0.008). Conclusions: These results suggest implementation of a customized physician orderset and corresponding dispensing and documentation procedure may reduce prescribing errors and omission of required documentation, including education, in patients who undergo emergency splenectomy. APHA Foundation

Introduction: In 2008, The Joint Commission (TJC) mandated that accredited hospitals develop methods for staff to request additional resources from “specially trained individuals” when a patient’s condition worsens. In 2010, TJC further required that accredited hospitals employ systems to identify early signs of patients in distress. The scientific literature, however, still has no definitive conclusion that rapid response systems (RRS) improve long term outcomes. Hypothesis: Introduction of an adult rapid response system to a teaching institution will decrease in-patient cardiac arrest rates outside of intensive care units. Methods: We analyzed the rate of true codes, false codes, and in-hospital mortality before and after the implementation of a RRS within a 250-bed teaching hospital. True codes were defined as code responses during which the code team provided emergency life saving interventions and/or ACLS. False codes were defined as false alarms (false triggers) or as code responses where the first responder needed resources not immediately available but during which the code team did not provide life saving interventions or ACLS. Differences were analyzed using analysis of variance (ANOVA). Results: Since implementation of a rapid response system, our institution has had a mean of 23 ⫹/⫺15 rapid response team (RRT) calls/1000 discharges in a 16 month period. Both true code and false code rates significantly decreased (12 ⫹/⫺ 6 vs 5 ⫹/⫺3, p ⬍ 0.0001 and 7 ⫹/⫺3 vs 2 ⫹/⫺1, p ⬍ 0.0001 per 1000 discharges respectively) when compared to the 16 month period prior to RRT implementation. There was no difference in mortality rates between the two time periods (13 ⫹/⫺4 vs 15 ⫹/⫺5, p ⫽ 0.40 deaths per 1000 discharges). Conclusions: RRT implementation in our institution has had a dramatic impact in decreasing both true and false code rates despite a very low activation rate. There was no impact on mortality.


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USE OF A LABORATORY-DRUG COMBINATION ALERT TO DETECT DRUG-INDUCED THROMBOCYTOPENIA IN CRITICALLY ILL PATIENTS

CAN GAINSHARING SIGNIFICANTLY IMPACT COST SAVINGS IN CRITICAL CARE UNITS?

Lisa Harinstein, Cleveland Clinic, Sandra Kane-Gill, Pamela Smithburger, Colleen Culley, Amy Seybert, University of Pittsburgh School of Pharmacy Introduction: Thrombocytopenia has a potentially significant negative impact on mortality, duration of mechanical ventilation, and bleeding risk in critically ill patients. Adverse drug reactions (ADRs) as a cause of thrombocytopenia in intensive care units (ICUs) remain difficult to accurately identify. Computerized clinical decision support systems (CDSS) have been previously evaluated to aid in the identification of drug-induced thrombocytopenia (DIT); however, results have shown low positive predictive values (PPV) ranging from zero to 0.33. Prior systems have focused trigger development on laboratory values, we propose using laboratory and drug combinations. Hypothesis: Using a commercial CDSS drug-thrombocytopenia alert containing 3 platelet triggers and 160 drugs associated with DIT, will result in a higher PPV compared to prior alerts. Methods: With Quality Improvement Committee approval, all adults admitted to the medical ICU and cardiac ICU during an 8-week period identified by the CDSS alert were included in the evaluation. The alert was generated when the patient met criteria for a low platelet count (PLC) and was treated with a potentially causal drug. PLC for each trigger was: Trigger 1 ⫽ PLC of ⬍ 100, 000 mm3; Trigger 2 ⫽ PLC decreased by ⱖ50% between the 2 most recent laboratory results; Trigger 3 ⫽ PLC decreased by ⱖ 25% between the 3rd most and previous result. A pharmacist evaluated the alert for the presence of an ADR using three published causality instruments. Agreement of 2 out of 3 instruments for possible or greater indicated the presence of an ADR. The PPV for the alert was calculated as the number of times the alert detected an ADR divided by the total number of alerts fired overall. Results: 64 patients met inclusion criteria (52 medical ICU and 12 cardiac ICU) generating a total of 350 alerts. Overall, there were 137 ADRs identified. Heparin, vancomycin, and famotidine were the 3 most common potential drug causes. PPVs ranged from 0.36 to 0.83, with Trigger 1 being the least predictive of an ADR and Trigger 3 having the highest PPV. Conclusions: A commercial CDSS drug-thrombocytopenia alert more accurately identifies DIT in an ICU setting and may improve patient safety.

P. Greg Plumb, I. Michael Leitman, Beth Israel Medical Center, Claudie Jimenez, St Lukes Roosevelt Hospital, Latha Sivaprasad, Beth Israel Medical Center, Ruth Levin, Continuum Health Partners, David Bernard, Beth Israel Medical Center Introduction: Gainsharing is a pay-for-performance program that provides incentives to attending physicians to reduce hospital costs while maintaining quality care. Since its inception in 2006, participation in Gainsharing has been offered to physicians and surgeons, but has excluded intensivists. Hypothesis: The present study examines the impact of Gainsharing on overall hospital costs and ICU costs for patients with critical illness during their admission. Methods: Retrospective analysis was performed on the most frequent hospital and ICU admissions by All Patient Refined - Diagnosis Related Group (APR-DRG (TM), 3M Health Information Systems, Salt Lake City, UT) at four levels of severity. A best practice norm (BPN) was calculated by taking the mean hospital cost of the top 25 percentile. Savings opportunity (SO) was defined by subtracting the BPN from the actual cost.The admissions of adult patients who were admitted to the coronary care unit, medical ICU and the surgical ICU from July 2006 through December 2009 were evaluated. Gainsharing payments to the discharging physicians required meeting specific quality standards. Results: 9034 patients were admitted to the ICU during the study period under this program. Among all APR-DRGs, total hospital costs decreased by $2.7 million (10%) for these admissions, mostly related to a shorter overall hospital stay. However average ICU costs actually rose during the same period by $0.9 million (32%). The DRG with the greatest ICU SO was “tracheostomy with long-term mechanical ventilation” ($1.7 million). This group averaged $67, 000 in ICU costs per patient but accounted for only 0.8% of the total number of admissions. There was also a savings opportunity for “septicemia” ($0.4 million, 2% of patients) and “small and large bowel surgery” ($0.4million, 1.5% of patients). Conclusions: This study concludes that gainsharing can decrease hospital costs but thus far has excluded intensivists. By including them, it is likely that total hospital costs may be further decreased by the reduction of ICU costs. Focusing on costly DRG’s, such as patients with respiratory failure, may yield greater savings than focusing on more frequent diagnoses in the ICU.

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MULTI-DISCIPLINARY QUALITY IMPROVEMENT PROJECTS CAN RESULT IN IMPROVEMENTS IN TRANSFER TIMES FROM THE EMERGENCY DEPARTMENT TO THE PEDIATRIC INTENSIVE CARE UNIT

DEVELOPMENT OF A HANDOFF CONTINUITY SCORE (HCS) TO IMPROVE PEDIATRIC ICU PHYSICIAN SCHEDULE DESIGN FOR ENHANCED HANDOFF EFFICIENCY AND CONTINUITY

Adam Silverman, Christopher Carroll, Kathy Morgan-Gorman, Joan Cahill, Michelle Koss, Nancy Sears-Russell, Karen Howard, Connecticut Children’s Medical Center

Hannah Smalley, Pinar Keskinocak, School of Industrial and Systems Engineering, Georgia Institute of Technology, Atul Vats, Emory University School of Medicine and Children’s Healthcare of Atlanta

Introduction: Once a decision is made to admit a child to a pediatric intensive care unit (PICU) from a pediatric emergency department (PED), it is crucial that this intrahospital transfer occur in a timely fashion.We identified reducing the time of transfer of these critically ill children as an important quality improvement goal.Because of unit staff skills, level of monitoring and specialized modalities of care provided in the PICU, there was consensus amongst the staff of both units that rapid transfer to the PICU had the potential to improve the quality of care. Hypothesis: We hypothesized that we could reduce the transfer time from the PED to the PICU by identifying the steps involved in the transfer process and implementing changes in these processes. Methods: Physicians and nurses met on multiple occasions to identify specific steps involved in the transfer process starting in October 2009.Intervention were begun in November 2009.Transfer times were defined as the period between the time of decision to admit the child to the PICU and the time of arrival in the PICU.Those steps that had the potential for creating delays were analyzed monthly in greater depth by multidisciplinary teams of nursing and physician leaders.Outliers were analyzed in order to identify systemic changes that could streamline process. Results: Comparing October 2009 to July 2010, average time of transfer decreased from 60 minutes (n ⫽ 22) to 47 minutes (n ⫽ 27) with a monthly range during that period of 30-61 minutes.Transfers that occurred in ⱕ 30 minutes increased from 20 to 38 % with a monthly range of 14 to 50%.On aggregate, transfer times decreased from 62 ⫾ 40 minutes (April-October 2009, n ⫽ 144) to 52 ⫾ 33 minutes (November 2009-July 2010, n ⫽ 222) (p ⫽ 0.02).Identifiable sources or delay were difficulty in starting IVs, delays in physician-to-physician sign out, delays in nurse-to-nurse sign out and medicine delivery from pharmacy. Conclusions: Multidisciplinary quality improvement projects can result in decreased times for transfer from the PED to the PICU.Having specific targets on the Balanced Scorecard of both units and having regular physician and nurse review of performance can help achieve significant improvements.

Introduction: Few studies investigate the benefits of familiarity or continuity during physician-to-physician handoff of inpatients. Factors such as how recently physicians (MDs) have worked with the patients and successive days caring for patients increase continuity, and thus, could lead to enhanced handoff efficiency. Evaluating the efficacy of MD scheduling to provide continuity is currently subjective. Hypothesis: A Handoff Continuity Score (HCS) can be used to analyze a pediatric intensive care unit (PICU) MD schedule for continuity and handoff efficiency. Methods: An MD group redesigned its PICU physician coverage schedule to enhance continuity. A survey of the MDs was used to numerically estimate continuity at each handoff based on prior days worked within a defined timeframe (N) for oncoming MDs in a 30 bed PICU (9 attendings/7 fellows). HCS was calculated as the summation of Fi*Xi, where i ⫽ 1, . . . , N. Fi(familiarity factor) represents a physician’s familiarity based on time since last shift. Xi is 1 if the physician worked i days ago or 0 otherwise. HCS ranges between 0 and 1 (1 ⫽ most familiar). For this analysis, N was defined as the current PICU length of stay (5 days). A mathematical model was used to construct schedules to optimize HCS while considering scheduling constraints (e.g., duty hours, MD preferences). To validate HCS, MD service/call schedules were evaluated for 6-month periods before/after the institution. MDs were asked to rate the impact of the schedule change on continuity and efficiency (5 point Likert scale: 1 ⫽ worse, 3 ⫽ no change, 5 ⫽ better). Results: HCS before and after redesign was 0.57 and 0.68 (19% increase, p ⬍ 0.05). Mean MD rating was 4.22 ⫹ 0.56 for continuity, and 4.00 ⫹ 0.65 for efficiency. Further schedule optimization improved the average HCS to 0.79 (39% increase). Conclusions: Increased HCS was associated with MD qualitative assessment of enhanced continuity and efficiency from a schedule redesign. Additional HCS modeling identified potential additional scheduling improvements. HCS provides an objective measurement of continuity with various scheduling models and facilitates resource optimization, particularly in the face of increased duty hour constraints.


Poster: Administration-2 112

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EXAMINATION OF EMERGENCY AIRWAY SERVICE PATTERNS IN A LARGE ACADEMIC MEDICAL CENTER

OPTIMIZING PATIENT FLOW OUT OF THE ICU: IMPACT OF “NO-BED DAYS” ON COST AND ICU UTILIZATION

M Adams, Massachusetts General Hospital, Ulrich Schmidt, Massachussets General Hospital, H. Stelfox, University of Calgary, Edward Bittner, Massachusetts General Hospital

Frank Vandy, Pauline Park, Vinita Bahl , Louisa Griffes, Lena Napolitano, University of Michigan School of Medicine

Introduction: A database of emergency airway consults was analyzed to determine the presence, if any, of temporal or spatial patterns in consult frequency. Hypothesis: Emergent airway management utilizes a high number of resources. As such, it is important to optimize staffing to provide the safest level of care. We hypothesize that there are temporal and spatial fluctuations in airway consult frequency which would lend to more efficient resource use. Methods: Retrospective analysis of a database detailing 1483 emergency airway consults performed between September 2007 and June 2010 at a large (900 bed) academic medical center. The database contains information including date, time, and consult location. Using Pearson’s chi-square test, these data were analyzed for variations in consult frequency throughout the day and year, as well as the hospital location. Dates were analyzed by examining month-to-month distributions. Time data were analyzed by splitting 24-hour days into six 4-hour tranches. Location data were analyzed for differences in consult demand from various care areas across weekdays vs. weekends. Results: There is a nonsignificant trend toward increased airway consults during the months of January - March (Pearson chi2(11) ⫽ 16.38, Pr ⫽ 0.127). The number of consults is not evenly distributed across four-hour tranches of a 24-hour day. Specifically, there are significantly fewer consults during the 8 PM - midnight and midnight - 4 AM shifts (Pearson chi2(5) ⫽ 20.94, Pr ⫽ 0.001). Lastly, there is no difference in the level of consult demand on weekdays vs. weekends across hospital locations (Pearson chi2(12) ⫽ 3.39, Pr ⫽ 0.992). Conclusions: These data contradict notions that emergency airway consults occur more frequently during the late night and early morning. This may have implications for decreasing staffing resources overnight. The data do not support a sense of more consults on weekend days or of a ‘July effect‘ of increased consults as new trainees arrive. Finally, the trend toward increased frequency during the winter months is likely secondary to a higher hospital census and higher incidence of respiratory disease. These data may be used to guide emergency airway resource allocation.

Introduction: Providing timely access to critical care with prompt ICU admission is an essential element of high quality critical care, i.e. “right care, right now”. Lack of ICU beds is, in part, related to the inability to transfer patients out of the ICU due to lack of general care or telemetry beds during high hospital occupancy. We sought to examine the effect of high hospital occupancy on discharge out of the ICU. Hypothesis: Inability to transfer patients out of the ICU secondary to high hospital occupancy results in increased hospital cost and poor ICU bed utilization. Methods: Prospective data (APACHE database) and hospital billing (TSI cost accounting system) from the surgical ICU (20 beds) were reviewed for 4 years (2006 –2009). A “No Bed Day” was defined as a 24-hour period in which an ICU patient could not be discharged from the ICU due to lack of general care or telemetry beds. Actual total variable direct cost (VDC) and VDC assuming patients would have been able to transfer out of the ICU to the appropriate general or telemetry ward were calculated. Results: Total annual ICU admissions were 1353, 1354, 1275 and 1294 with mean APACHE III score on ICU day 1 of 49.1 (range 0-152), 50.5 (range 4-188), 55.8 (range 5-214) and 56.8 (range 6-172). Mean age was 59.4, 58.2, 56.4, and 56.1 years with 40.9%, 37.5%, 34.7% and 42.3% of patients age ⬎ 65 years. Mean ICU length of stay was 4.8, 4.6, 4.9, and 4.6 days. A total of 307, 574, 726 and 714 no bed days were recorded for 2006-2009, increasing over this time period related to increasing periods of high hospital occupancy. Total VDC for CY 2009 was $1, 021, 534. Patients were ready for transfer to general care or telemetry in 73% and 27% of the days respectively. Assuming these patients could be discharged from the ICU, total VDC would have been $650, 696, reflecting a difference in total VDC of $370, 839. With a difference in daily VDC of $519.38/day, and a cumulative total of 2321 no bed days over this 4-year period, a total cost of $1, 205, 481 was incurred. Conclusions: Increasing “No Bed Days” in the surgical ICU over this 4-year period was associated with increased cost and reduced ICU admissions and interfacility transfers.

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DELAY IN TRANSFER FROM THE SURGICAL ICU: INCIDENCE, CAUSES AND FINANCIAL IMPACT

ARE LONG TERM ICU PATIENTS ASSOCIATED WITH DECREASED PROFITABILITY IN A FEE FOR SERVICE REIMBURSEMENT SYSTEM?

Daniel Johnson, Edward Bittner, Ulrich Schmidt, Richard Pino, Massachusetts General Hospital/Anesthesia, Critical Care & Pain Medicine/Harvard Medical School Introduction: Minimal literature exists regarding ICU patients who are medically ready to leave the ICU but experience a significant delay before transfer to the floor. This study analyzed the incidence, causes and costs of delayed transfer from a surgical ICU. Hypothesis: Delayed transfer from the surgical ICU is common, is multi-factorial in cause, and has a significant financial impact. Methods: An IRB-approved prospective observational study was conducted from 1/24/2010 to 7/31/2010 of all 731 patients transferred from a 20-bed SICU. Data were collected on patients deemed medically ready for transfer to the floor who remained in the SICU for at least one extra day. Reasons for delay were examined. Economic analysis was performed to evaluate the additional costs of delayed transfer from the SICU. This was based on the difference in cost of ICU care versus floor care. Results: Transfer to the floor was delayed in 22% (n ⫽ 160) of the 731 patients transferred from the SICU. Delays ranged from 1 to 6 days (mean 1.5 days). The estimated additional cost of delayed transfer during the 27-week study period was $791, 628 ($29, 319 per week). The most common reasons for delay in transfer were: lack of available surgical floor bed [71% (114/ 160)], lack of room appropriate for infectious contact precautions [18% (28/ 160)], change of primary service (Surgery to Medicine) [7% (11/160)], and lack of available patient attendant (“sitter” for mildly delirious patients) [3% (5/160)]. There was a positive association between the daily hospital census and the daily number of SICU beds occupied by patients delayed in transfer (Spearman’s rho ⫽ 0.27, p ⬍ 0.0001). Delayed patients were significantly more likely than nondelayed patients to be transferred during night shifts, between 19:00 to 06:59, [21% (33/160) versus 12% (67/571), chi square ⫽ 10.6, p ⬍ 0.005]. Conclusions: Delay in transfer from the SICU is common and costly. The most common reason for this delay was insufficient availability of surgical floor beds. Delay in transfer was associated with high hospital census, and delayed patients were more likely than non-delayed patients to be transferred during night shifts.

Fernando De Marco, Fatima Almeida, Mara Oliveira, Hospital Vivalle Introduction: Long term ICU stay has been associated with financial losses for private hospitals operating on capitation, flat fee or prospective payment systems. Hypothesis: The aim of this study is to evaluate the impact of ICU length of stay (LOS) on profitability for hospitals operating in a fee for service system with a cost-plus pricing strategy. Methods: The study was conducted in a 50-bed surgical private hospital in Brazil with no commercial relationship with public healthcare insurance. From January to June 2010 we prospectively followed consecutive patients admitted for intensive care therapy and registered all revenues, fixed and variable costs generated in ICU environment. We used a bottom-up approach (TASY Electronic Healthcare Record-Wheb Sistemas®, Brazil) to determine all relevant costs and we have considered taxes and physicians fees as variable costs. We calculated the total cost/revenue ratio(%) and related with LOS for each patient.We also calculated the mean revenue and cost (US dollars) per ICU day.We established the mean operating margin (total revenue minus total cost)per ICU day for the following groups of patients according to their LOS: 2 days, 4 days, 6 days and ⬎ 6 days. Results: We enrolled 184 patients.The mean LOS was 5.75 ⫾ 11.4 days.The mean APACHE II score was 13.2 ⫾ 8.5.The overall mortality rate was 9%.We have observed that for all range of ICU LOS (1 to 88 days) the total cost/revenue ratio was always inferior to 100% (range 42% to 74%) making the ICU a profit driver regardleess the LOS.The mean revenue and cost per ICU day were respectively $ 1, 936 and $ 1, 117. The operating margins per patient per day increased with long term stay: 2 days - $ 663, 4 days - $ 621, 6 days - $ 1, 100 and ⬎ 6 days - $ 1, 245. Conclusions: These preliminary data showed that private hospitals do not lose money with long term ICU patients in a fee for service reimbursement and cost-plus pricing strategy setting (brazilian private healthcare sector). If this is a misaligned incentive to providers to promote aggressive management of LOS in ICU, early adoption of end of life care best practices and to reduce costs with acute hospital care of critically ill patients requires further investigation.


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PROCESS IMPROVEMENT DATA COLLECTION IS AS SIMPLE AS ASKING DAILY QUESTIONS USING A CHECKLIST

ADMINISTRATIVE PROCESS OF ICU PROTOCOL DEVELOPMENT IN URBAN AND RURAL HOSPITALS IN MINNESOTA

Roderick Kuwamoto, STICU Brooke Army Medical Center, Jeremy Pamplin, John Linfoot, BAMC, Kurt Grathwohl, San Antonio Uniformed Services-Health Ed, Kevin Chung, USAISR

Soichiro Nagamatsu, Sarah Roark, Craig Weinert, University of Minnesota

Introduction: Data collection for process improvement in institutions without robust support or research staff is challenging. Governing bodies mandate reporting of specific aspects of quality care that are often difficult to access using the medical record and alternative methods of data collection or database support. Daily checklists have been demonstrated to improve adherence to evidence based practices and patient outcomes in the intensive care unit (ICU) and may be a robust source for this type of data. Hypothesis: Entering answers to daily checklist questions into a process improvement database is an efficient method to improve data collection and improve adherence to evidence based processes. Methods: This process improvement project was conducted in a 20-bed surgical ICU in a 450-bed academic military medical center. This unit utilizes a daily checklist for each patient to ensure they receive appropriate evidenced based therapies. The checklist is completed during multidisciplinary ICU rounds. The checklist is “web-based” and the answers are entered directly into the database during rounds for tracking and analysis. During this evaluation, a new requirement for daily chlorhexidine (CHG) oral care was added to our institution’s ventilator associated pneumonia bundle. This requirement was incorporated into our daily checklist and data on our compliance was immediately tracked. Results: Answers to a daily checklist can be easily entered into a process improvement database and. is immediately available for review. Introduction of a new requirement during our evaluation period allowed our tool to be tested in a real world scenario. Data on CHG oral care showed a 40% compliance on the first day of asking the question and increased to 81.25% compliance over the next 3 weeks without any additional education to the healthcare team. Our experience is that real time data collection is more palatable than third party data collection to the bedside clinician and is more likely to affect his practice pattern. Conclusions: Real-time process improvement data collection is feasible. Using a daily checklist is an efficient method to collect this data while concurrently improving patient care.

Introduction: Protocols translate research findings into patient care but little is known about the administrative process of ICU protocol development. Hypothesis: Hospital size and administrative structure influence protocol implementation. Methods: From 49 ICUs in Minnesota, we obtained patient-care protocols and order sets and conducted in-person interviews with nurse managers. Results: 45% of ICUs were urban, 55% rural. 80% had a dedicated RN administrator. All ICUs used some type of protocol or order set to standardize care. 94% had DVT prevention protocols; 92% ventilator management; 90% intensive insulin therapy, 80% sedation management. In larger ICUs, protocols are jointly developed by ICU physicians and administrator RNs with assistance from pharmacists and respiratory therapists. In rural ICUs, RN managers have greater solo responsibility for moving protocols through the design and implementation process. They are hindered by difficulty in obtaining original research papers and their medical directors are not ICU-trained. Nurses save time by searching for extant protocols on websites of accrediting agencies or QI organizations such as IHI. RNs obtain protocols from sister hospitals or at regional conferences. AACN was mentioned as a source more than SCCM, ATS or ACCP. Protocols progress through a committee-based approval process which slows implementation. From idea to active protocol takes 1 to 12 months; 6 months was a common response. Smaller, unaffiliated hospitals could implement protocols faster than hospitals that were part of a chain and their protocols were more influenced by local custom or patient population. Only 63% of ICUs had a post-implementation process for revising protocols. Conclusions: Although the foundation for evidence-based medicine is usually built by academic physicians, the actual process of translating evidence into patient-care documents is done by hospital-employed nurses, often with limited resources, especially in rural communities. Professional societies could improve patient care not only by publishing research papers and expertopinion guidelines but by developing free protocol templates that hospitals can modify for local use.

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USING A BUSINESS REVIEW AND SCORECARD TO MANAGE THE BUSINESS OF ICU INTEGRATION

EPINEPHRINE IN ANAPHYLAXIS: IN-PATIENT PROCESS FOR SAFE AND COST-EFFECTIVE USE

Stephen Davis, The Cleveland Clinic , David Priganc, Mary Jo Chrobak, Sheareen Shahamat, Katherine Hancock, Alexander Harrison, Cleveland Clinic

Michelle Allen, Marilyn Farinre, Susan Ohnmacht, Michelle McLaughlin, Sibley Memorial Hospital

Introduction: The Cleveland Clinic Health System (CCHS) is integrating all 30 of our ICUs. The business of ICU operations is extremely complex and is impacted by personnel, processes, technology, and a host of external pressures. These factors must be managed to ensure optimal performance of clinical care while meeting service, quality, financial and productivity commitments. Patient satisfaction and employee engagement are also priorities. Hypothesis: Tools exist to manage such performance metrics, but they have not been widely adopted in medicine. The use of the Business Review Process (BRP) is increasing at the Cleveland Clinic, but has not previously been used across our system hospitals. Methods: We developed a CCHS ICU scorecard through a collaborative group process. The scorecard tracks data for 42 performance-related metrics in six categories: Service, Employee Engagement and Teamwork, Quality, Risk Management, Productivity and Financial. Each ICU was tasked with reporting performance to the metrics applicable to their site and performance against the targets is discussed in a monthly business review meeting of multidisciplinary leadership from all 12 hospitals. Gaps between targeted and actual performance are analyzed, and a plan to close the gap are developed and implemented. Results: At the time of scorecard development, only 19% of the metrics had system-wide targets. Two major benefits of this tool are 1) It highlighted pockets of excellence and best practices, and 2) it allowed us to quickly recognize lack of consensus or clarity on the targets for many metrics. Conclusions: The monthly business review and balance scorecard meeting are very effective management tools for ICUs, particularly across our system. The process of setting up the Business Review had a positive effect on teamwork and collaboration and identified disparities in resources and performance across a diverse group of ICUs. These tools enable identification and response to trends in key metrics. They also enable leadership to identify metrics that are critical to operational success and to improve performance gaps. These tools are excellent for managing care delivery, productivity, quality, and patient safety data.

Introduction: Medication errors are frequently the instigator for quality improvement that leads to safer patient care, and institutional process change is often expensive and complicated. The purpose is to describe an inexpensive and multifaceted systems approach to address recovery from a medication error: epinephrine administered via the intravenous route to a patient with suspected anaphylaxis. Hypothesis: The use of an anaphylaxis kit would be safer than the alternative approach of keeping the medication and the supplies separated. Methods: Benchmarking data to assess utilization of manufacturer-prepackaged anaphylaxis kits was obtained via e-mails sent to over 240 individuals at various institutions around the United States and British Columbia. Process transformation was created via a work group consisting of pharmacy, nursing, medical staff, and education and training. Results: One hundred and twenty-one institutions constitute the institutional benchmarking. Less than 16 percent of responding institutions (19/121) stock manufacturer-prepackaged anaphylaxis kits; seven of those respondents specified that the product is not used in-house—instead they use the kits as outpatient prescriptions dispensed prior to emergency department (ED) discharge. Four institutions stated than a medication error was the reason the kit was used in their institution.Our institution’s work group created and disseminated process changes throughout the institution, not just in the ED where the medication error occurred. Every automated dispensing machine and code cart was stocked with two home-grown anaphylaxis kits. Each kit contains step-by-step instructions for how to calculate, prepare and administer the medication and every nurse is required to participate in anaphylaxis training during annual competency. Conclusions: The system improvement strategies utilized in response to a medication error are straight forward and inexpensive. In addition, implementation of these strategies has the potential benefit of avoiding a lifethreatening medication error.


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MODELING LENGTH OF STAY IN CARDIAC CRITICAL CARE USING THE LOGNORMAL DISTRIBUTION

IMPACT OF HOSPITAL-BASED PEDIATRIC TRANSPORT TEAM CLOSURE ON TRANSPORTS AND TRANSPORT REQUESTS TO A PEDIATRIC INTENSIVE CARE UNIT

David Strum, University of Pennsylvania, Luis Vargas, University of Pittsburgh Introduction: Cardiac critical care units provide care that can be resource-intensive and life saving. Demand for these services fluctuates within medical institutions leading to cycles of clinical and economic inefficiencies and insufficiencies. The distribution of length of stay (LOS) in a cardiac intensive care unit (ICU) patient is highly skewed. There are a number of patients who spend weeks or even months in the ICU receiving care. Cardiac operating room utilization is complicated by variability inherent in ICU LOS. Hypothesis: We hypothesized that a lognormal distribution would be superior to a normal distribution for modeling LOS in an ICU following cardiac surgeries. Methods: With institutional approval, we studied all admissions to a cardiac ICU following various cardiac surgeries undertaken at a large teaching hospital. We modeled LOS for cardiac surgeries categorized by an ICD-9 procedure code. We modeled and tested 2, 352 surgeries and 66 different ICD-9 codes performed by 23 different surgeons. We used Shapiro-Wilk (SW) tests to determine if data samples for each ICD-9 code were consistent with 3 model distributions: normal (N), 2 parameter lognormal (2PLN), and 3 parameter lognormal (3PLN). The 3PLN is a 2PLN model with an added 3rdparameter, the location parameter. We compared overall performance of the three models using Friedman tests. Results: We tested using SW tests 66 different ICD-9 codes (those with samplesizes (n ⬎ 9) sufficient to fit a model distribution. The data fitted better the 3PLN ⬎ 2PLN ⬎ N model (Friedman tests, P ⬍ 005). To illustrate these statistical models we plotted the actual(empirical) data (illustrated as a frequency histogram) with the fitted 3PLN, 2PLN and normal models. The cardiac ICU LOS illustrated is ICD-9 ⫽ 37.51, heart transplantation, n ⫽ 120 cardiac surgeries). Conclusions: Choosing an appropriate statistical model is an important first step in forecasting ICU LOS with known precision. Our results also help to legitimize the use of log transforms to normalize LOS prior to hypothesis testing using linear statistical models to investigate factors associated with capacity planning for cardiac ICUs.

Brian Cummings, Phoebe Yager, JoAnne Riley, Anita Carew, Natan Noviski, Massachusetts General Hospital Introduction: The impact of closing a hospital-based pediatric specialized transport team on pediatric intensive care unit (PICU) admissions has not been previously published. In 2003, our pediatric transport team was discontinued and an out-of-the hospital independent specialized transport team vendor was contracted to provide pediatric critical care transports. Hypothesis: Closure of a hospital-based pediatric transport team has a negative effect on requests for transports and on transport admissions to the PICU. Methods: Review of internal PICU transport database over 9 year period. Transport volume data by fiscal year were compared between pre-change (1999-2002), transition year (2003), and post-change (2004-2007) period. The number of lost PICU admissions was estimated based on the average transports pre- and post- closure and factoring in zero as well as observed growth and refusal rates after the change. Results: During the above period, there were no changes in number of referring hospitals, hospital transfer agreements or affiliations. Transports numbers went from an average of 160/year pre-change, to 109 during the transition year to an average of 145/year post-change. Requests to transport critically ill patients to the PICU increased from an average of 169/year pre-change to an average of 175/year post-change in association with increased community outreach efforts. However, our refusal rate for transport requests increased from 5% pre-change to 17% post-change. The transport vendor was unavailable for transport for 13% of requests. Assuming no growth in the number of transport requests, we estimate the loss of 187 patients for the PICU over the 5 years post-change period. Moreover, if we use the observed annual growth rate of 13% in transports requests, we estimate the loss of 364 patients during the same period. Conclusions: Closure of a hospital-based pediatric specialized transport team affected transport activity. This impact should be taken in consideration and strategies to mitigate it put in place, whenever a similar change is considered.

122 IMPACT OF A CHANGE IN CARE MODEL ON RESIDENT DUTY HOURS IN A PEDIATRIC INTENSIVE CARE UNIT Tara Lemoine, Jill Sweney, Rajendu Srivastava, University of Utah, Holly Webster, Tanya Stout, Primary Children’s Medical Center, William Poss, University of Utah School of Medicine Introduction: There are approximately 350 Pediatric Intensive Care Units (PICU) in the United States with a wide variety of staffing models that have significant clinical, economic, and educational implications. The utilization of advanced licensed independent practioners (LIP) such as nurse practitioners has evolved in part due to changing medical education requirements and resident duty hour restrictions. At our institution, a large multidisciplinary PICU, pediatric nurse practitioners have been an essential part of our care team for over 21 years. Recently, we have adapted a two team model to meet the demands of a growing patient load and continued resident work hour violations. Previously our care team consisted of a single attending physician, PICU fellow, resident physicians and a nurse practitioner with responsibility of all patients admitted to the PICU. A new model was introduced in November 2008 with a second team consisting of an additional attending and the nurse practitioner. These 2 independent teams now function to care for all PICU patients, allowing direct comparison of a change in staffing model in regard to patient outcomes as well as resident work hours. Hypothesis: The addition of a non-tradional care team into the PICU would reduce resident duty hour violations without impacting quality of care. Methods: Data was collected for a 12 month period prior to the initiation and for 12 months after the introduction of the LIP service. Outcome measures included, length of stay, diagnostic categories, Pediatric Risk of Mortality Scores (PRISM III), unplanned readmissions within 48 hours, and resident work hour violations. Simple descriptive statistics were used to compare data. Results: Admitting diagnosis, age distribution, PRISM III scores, length of stay, and unplanned readmissions were similar between the two teams. Prior to the initiation of the additional team, there were a total of 56 reported duty hour violations with only four violations reported after implementation. Conclusions: The addition of non-traditional care teams into the PICU can help meet the often competing demands of patient care and restricted resident duty hours.


Poster: Basic Science: Cardiovascular 123

124

THERAPEUTIC HYPOTHERMIA IMPROVES POST RESUSCITATION MYOCARDIAL FUNCTION IN A RAT MODEL OF MYOCARDIAL INFARCTION

VASODILATION AND MEASURES OF CELLULAR ENERGY FAILURE PRECEDE CARDIOVASCULAR COLLAPSE AFTER HEMORRHAGIC SHOCK

Jeonghyun Park, Sung Phil Chung, Weil Institute of Critical Care Medicine, Yinlun Weng, The Second Affiliated Hospital of Sun Yat-sen University, Xiaobo Wu, Weil institue of critical care medicine, Feng-Qing Song, Weil Institute of Critical Care Medicine, Shijie Sun, Max Weil, Wanchun Tang, Institute of Critical Care Medicine

Hernando Gomez, University of Pittsburgh, Jaume Mesquida, Hospital de Sabadell, Linda Hermus, Patricio Polanco, Sven Zenker, University of Pittsburgh, Rajaie Namas, Hurley Medical Center, Gilles Clermont, Yoram Vodovotz, Juan Puyana, Michael Pinsky, University of Pittsburgh

Introduction: Therapeutic hypothermia (TH) is a promising treatment for cardiac arrest and resuscitation. It improves neurological and hemodynamic outcomes and reduces mortality among survivors of out-of-hospital cardiac arrest. Animal and human studies have also shown that TH results in improved salvage of the myocardium, reduced infarct size, reduced left ventricular remodeling and better long-term left ventricular function in settings of regional myocardial ischemia. Hypothesis: In the present study, we investigated the effect of TH on myocardial function in a rat model of myocardial infarction (MI) during global ischemia of cardiac arrest and resuscitation. Methods: This study consisted of 2 groups; a) Acute MI-Normothermia, and b) Acute MI–Hypothermia (32e for 4 h). Thoracotomies were performed in 10 male Sprague-Dawley rats, weighing 450 to 550g. Acute MI was induced by ligation of the left anterior descending coronary artery (LAD). After 90 min, ventricular fibrillation was induced and subsequent cardiopulmonary resuscitation was performed prior to attempted defibrillation. Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured echocardiographically. Results: In acute myocarial infarcted rats, ejection fraction, cardiac output and myocardial performance index were significantly better in the TH group than those of the normothermic group during the first 4 h after resuscitation. Conclusions: This study suggested that TH attenuated post-resuscitation myocardial dysfunction in acute MI and would be a potential strategy in postresuscitation care.

Introduction: The mechanisms leading to cardiovascular collapse (CC) during hemorrhagic shock are unknown and current diagnostic techniques do not identify early CC. Hypothesis: We hypothesized that loss of vascular tone characterizes the processes leading to CC, and that clinical surrogates such as the vascular tone index (VTI), identify it. Methods: 14 anesthetized, thoracotomized Yorkshire-Durock pigs (wt 31.6 ⫾ 3.9 kg) were bled to 30 mmHg mean arterial pressure (MAP) and held there by repetitive bleeding until rendered unable to compensate or for 90 min, whichever came first. The animals were then resuscitated in equal parts to shed volume with HextendTM and observed for 2h. CC was defined as a MAP ⬍30 mmHg for 10 min or ⬍20 mmHg for 10s. Swine were classified as either CC or NoCC (did not decompensate). Hemodynamic/ metabolic variables were recorded at baseline (BL), 30, 60, and 90 min after bleeding (B30, B60, B90), and at resuscitation (R0), 30 and 60 min after resuscitation (R30, R60). VTI ⫽ arterial pulse pressure/stroke volume index. Lactate increase rate (LIR) ⫽ lactate difference/time elapsed between two timepoints. Data were analyzed using non-parametric methods (* ⫽ P ⬍ 0.05) and reported as mean ⫾ SD. Results: Average bleeding was 32 ⫾ 9% of a calculated total blood volume of 2134 ⫾ 262 ml. Peak epinephrine (Epi) and VTI werelowinNoCCafterbleedingascomparedtoCC,inwhichbothincreased(173⫾181 to939⫾474ng/ml,and0.97 ⫾0.22to2.57⫾1.42,*respectively),despitenodifference in bled volume (722 ⫾ 154 vs. 544 ⫾ 159 ml). VTI identified CC from NoCC swine before CC occurred, as well as survivors from non-survivors at R0 (1.55 ⫾ 0.51 vs. 1.1 ⫾ 0.09*). LIR was higher at B90-R0 for CC (BL-B30, 0.23 ⫾ 0.23; B30-B60, 0.19 ⫾ 0.11; B60-B90, 0.18 ⫾ 0.08 vs. B90-R0, 2.41 ⫾ 0.68 mmol/L/min, * all) and was coincident with a VTI decrease before CC occurred. LIR did not change in NoCC. Conclusions: In severe hemorrhagic shock, vasodilatation immediately prior to CC occurs simultaneously with an increment in LIR. This suggests that loss of vasomotor tone is an integral mechanism leading to CC and that it may be secondary to energetic failure. However, vasodilatation-induced lactate washout cannot be excluded.

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126

DIFFUSE MYOCARDIAL DAMAGE BY LEVOSIMENDAN USED FOR POSTCONDITIONING IN MYOCARDIAL ISCHEMIA REPERFUSION INJURY

COMPARISON OF DEFIBRILLATION EFFICACY DURING CARDIOPULMONARY RESUSCITATION IN RAT MODELS OF ACUTE AND CHRONIC MYOCARDIAL INFARCTION

Anna Roehl, University Hospital Aachen, Nikolaus Kuehn-Velten, Medical Laboratory of Bremen, Andreas Goetzenich, Rolf Rossaint, Marc Hein, University Hospital Aachen

Sen Ye, Shijie Sun, Yinlun Weng, Jeonghyun Park, Max Weil, Wanchun Tang, Weil Institute of Critical Care Medicine

Introduction: Postconditioning by levosimendan has been proven to be efficient for myocardial infarct-size reduction. Hypothesis: Levosimendan although widely used in therapy of acute heart failure may itself cause a– diffuse myocardial damage. Methods: 36 female German landrace pigs (30-35kg) were subjected to 90 minutes of right ventricular ischemia and 120 minutes of reperfusion under thiopental anesthesia in an open-chest model. All animals were randomized into three groups. Treatment was initiated 30 min after coronary artery occlusion. A bolus of milrinone (n ⫽ 12; 50 ␮g/kg) or levosimendan (n ⫽ 10; 24 ␮g/kg) was applied for 10 min, followed by a continuous infusion of the drugs at 0.5 and 0.2 ␮g/kg/min respectively. The effects of myocardial injury and inflammation were compared to a control group. Results: Effective serum drug concentrations of levosimendan and milrinone measured by HPLC were correlated to markers of inflammation in the non-ischemic myocardium (MPO, TNF-␣, IL-6) and to serum markers of myocardial injury (myoglobin, troponin I). Milrinone and levosimendan reduced the resulting infarct size with respect to the area at risk (41.7 ⫹/⫺10.2%, 45.7 ⫹/⫺8.1%) when compared to the control group (58.3 ⫹/⫺6.1%), whereas troponin I and myoglobin remained elevated. Myocardial TNF-␣ levels were elevated after levosimendan treatment and correlated with levosimendan serum concentrations.Milrinone lacks this effect. Conclusions: Despite its infarct size limiting effect, levosimendan increased serum markers of myocardial injury, which might be a consequence of diffuse injury within the non-ischemic myocardium as indicated by higher TNF-␣ concentration. Therefore, a dual action of levosimendan has to be postulated. As contractile dysfunction and LV dilatation coincide with the peak increase of TNF-␣ after myocardial infarction the benefit of mere infarct size reduction by levosimendan might be abolished.


Introduction: Earlier studies demonstrate that following myocardial infarction (MI), cardiac remodeling and fibrosis lead to a poor prognosis. However, the relationship between remodeling and the efficacy of defibrillation during cardiopulmonary resuscitation (CPR) remains unclear. In the present study, we investigated the success rate of defibrillation during CPR following acute (1 h) or chronic MI (4 weeks) in a rat model of cardiac arrest and CPR. Hypothesis: Ventricular fibrillation (VF) following acute MI is more easily terminated than following chronic MI. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 450-550 g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD) either one h or four weeks prior to inducing VF. VF was electrically induced and untreated for six min. CPR was performed for eight min prior to attempted defibrillation with a fixed energy of 2 J. The number of shocks required to achieve ROSC was recorded. Results: The number of shocks that were required for restoring spontaneous circulation (ROSC) was significantly lower in acute MI group when compared to the chronic MI group (1 ⫾ 0 vs. 5.2 ⫾ 4.6, p ⬍ 0.05). Conclusions: Cardiac arrest following acute MI requires fewer electrical shocks to achieve ROSC compared with chronic MI.

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ACUTE ADVERSE CARDIOPULMONARY AND METABOLIC EFFECTS OF EPINEPHRINE INJECTION

GUT BARRIER DYSFUNCTION AND ACTIVATION OF ENDOTOXIN SIGNALING PATHWAYS IN CHILDREN UNDERGOING SURGERY FOR CONGENITAL HEART DISEASE

David Hiller, University of Illinois College of Medicine, Vijay Krishnamoorthy, University of Illinois Hospital, Stephen Vogel, Richard Minshall, University of Illinois at Chicago, Rick Ripper, Univeristy of Illinois at Chicago, Guy Weinberg, University of Illinois College of Medicine Introduction: In current medical practice, epinephrine is the first line of pharmacologic therapy for acute cardiac arrest; the purpose of our study to is to assess the immediate pulmonary effects of a bolus dose of epinephrine. Hypothesis: We suspect that blocking epinephrine’s alpha effect may attenuate immediate pulmonary damage. Methods: Male Sprague-Dawley rats anesthetized with isoflurane were given a bolus epinephrine i.v. injection (25, 50 or 100mcg/kg). Arterial blood pressure and ECG were monitored continuously and arterial blood gases measured at baseline, 1 and 10 minutes after epinephrine injection. Results: Epinephrine injection (25, 50, and 100 mcg/kg) caused rapid, sustained decline of paO2 which at 25, and 50 mcg/kg was prevented by pretreatment with phentolamine. Arterial lactate and pH at 10 minutes were significantly lower than baseline following 50 mcg/kg or 100 mcg/kg epinephrine (p ⬍ 0.001 for both) but were no different than baseline when epinephrine was preceded by phentolamine. Rate pressure product at 10 minutes after 100mcg/kg epinephrine was lower than baseline (p ⬍ 0.001); this effect was also prevented by phentolamine pretreatment. Conclusions: Our data indicates that there is an immediate decrement in pulmonary function after bolus administration of epinephrine. These results were attenuated with pretreatment with phentolamine, a direct intravenous alpha-blocker. Our results suggest that the initial decline in paO2 is likely due to an increase in pulmonary edema, likely with an alpha-mediated component. This suggests that the alpha-agonistic properties of epinephrine may have a role in both pulmonary capillary permeability and an increased afterload, resulting in a pressure edema. This effect is prevented with pre-treatment with an alpha-blocker.

Nazima Pathan, Imperial College London, Margarita Burmester, Tanja Adamovic, Royal Brompton Hospital, Maurice Berk, Giovanni Montana, Michael Levin, Jane Mitchell, Imperial College London Introduction: Children requiring surgery for congenital heart disease are likely to have a number of risk factors that predispose them to gut mucosal injury and bacterial translocation pre- and post-operatively. This may exacerbate the inflammatory response and increase disease severity. Hypothesis: Perioperative intestinal injury and endotoxaemia in children undergoing congenital heart disease is associated with adverse outcome measures. Methods: We examined levels of the intestinal injury biomarker IFABP and endotoxin in children undergoing surgery for congenital heart disease and analysed gene expression using RNA obtained from serial pre- and post-operative blood samples. Results: Children with ductdependent cardiac lesions had increased IFABP levels pre-operatively compared to non-duct dependent lesions (Medians 279.4 and 89 respectively). Similarly endotoxin levels were greater pre and post-operatively for duct-dependent compared to non duct-dependent lesions. Median pre-operative EA was 0.41 in duct-dependent lesions compared to non duct-dependent lesions (0.14), whilst the peak post-operative EA was 0.62 in duct-dependent lesions compared to 0.27 in non duct-dependent lesions.Pre-operative endotoxaemia was predictive of the severity of post-operative inflammatory activation (the peak CRP) r2 ⫽ 0.513; p ⫽ 0.029 and acidosis (the peak Lactate) r ⫽ 0.44 ; p ⫽ 0.005, as well as being associated with subsequent length of stay on PICU (r ⫽ 0.33; p ⫽ 0.044). Post-operative endotoxaemia was correlated with duration of invasive ventilation R ⫽ 0.36 p ⫽ 0.027as well as length of PICU stay (r ⫽ 0.44, p ⫽ 0.005). Gene expression profiling of the changes in gene expression patterns showed significant differential expression over time of a number of genes of pathogen sensing pathways (including TLR5, TLR8, IRAK3, CCL5, STAT1 and MAPK14) and downstream activation of inflammation and cytokine activated genes (including C3AR1, IL-8, IL-1R2 and PF4V1). Conclusions: Children with congenital heart disease suffer from significant risk of inflammatory activation and organ dysfunction following surgery. Further studies in larger patient groups could indicate patient groups most likely to benefit from anti-endotoxin and immune modulating therapies.

129 THE USEFULNESS OF NON-INVASIVE METHB MONITORING AT HBOT DEPARTMENT (PULSE CO-OXIMETRY MASIMO RAINBOW SET RAD-57TM) Masakazu Nakashima, St. Mary’s Hospital, Yoshimitsu Tsutsumi, St.Mary’s Hospital, Takeshi Ifuku, St. Mary’s Hospital, Hideyuki Tachibana, St.Mary’s Hospital, Kazuhito Tamehiro, Kenji Taki, Hiroji Shima, St. Mary’s Hospital Introduction: To diagnose carbon monoxide poisoning (CMP), carboxyhemoglobin (COHb) is routinely measured by blood analysis.MetHb value was high even though COHb value was getting low in several cases. However, taking a blood sample may be harmful for the patients. Rad57 is measure S COHb(SpCO) and MetHb(SpMet) noninvasively and continuously. We compared SpMet and MetHb values in CMP patients before and after Hyperbaric Oxygen Therapy (HBOT). Methods: Ten patients with CMP undergoing HBOT participated. MetHb levels before and after HBOT were analyzed by CO-Oximetry (Radiometer ABL735) and recorded, simultaneously Rad57 continuously measured SpMet. A clip sensor was placed on middle or ring finger, and in 7 subjects the sensors were covered with black plastic bags to shield from ambient light. The values of SpMet were recorded simultaneously with blood samples. Data was analyzed using Peason’s correlation coefficient ® and bias, and precision were calculated. Results: Eighty-four blood samples from ten subjects with informed consent were collected. The average age of the subjects (7 males; 3 females) was 32.4 ⫾ 11.4. Causes of CMP included 4 cases of briquettes coal, 4 fires, and 2 auto exhausts. MetHb and SpMet ranged 0.4% - 1.4% and 0.2% - 1.5% respectively. Comparison the data between MetHb group and SpMet group in all subjects, r ⫽ 0.68 (N ⫽ 84). Conclusions: There was correlation between SpMet and MetHb levels in venous blood. Especcially between SpMet obtained with shield sensor showed higher accuracy. A conventional pulse oximeter measures with two wavelengths, whereas Rad57 is able to measure dyshaemoglobin such as COHb and MetHb when used concurrently Masimo Rainbow SET with more than seven wavelengths. Thus, ambient light may influence the accuracy of Rad57. Our data suggests that shielding a sensor may improve the accuracy of SpMet values. In conclusion, this new monitor, Rad57, may provide for rapid and easy diagnosis of CMP as well as a reliable monitor during treatment of CMP.


Poster: Basic Science: Cell Biology (NO and Signal Transduction, Signal Transduction) 130 NOVEL EXPRESSION OF VOLUME REGULATED ANION CHANNELS IN HUMAN AIRWAY SMOOTH MUSCLE CELLS Kenneth Remy, Columbia University/Morgan Stanley Children’s Hospital of New York, Sucie Chang, Peter Yim, Dingbang Xu, Charles Emala, Columbia University College of Physicians and Surgeons Introduction: Exercise induced bronchoconstriction (EIB) has been postulated to be caused by an increase in the osmolarity of secretions. Although the effect of osmolarity on airway epithelium cell function has been investigated, the functional effect of osmolarity of human airway smooth muscle (HASM) cells is largely unknown and may play a role in EIB. Several members of the volume regulated anion channel (VRAC) family are known to regulate anion flux following osmotic change in cell volume. Chloride flux is a known modulator of HASM tone. Most notably, two members of the family, CLC-1 and CLC-3 have been well described in human skeletal muscle cells which modulate anion flux following a change in cell volume. However, the expression of VRACs and their potential regulation of anion flux in response to cell volume in HASM cells is unknown. Hypothesis: CLC-1 and CLC-3 are expressed in HASM cells and changes on cell volume can be detected by using the halide-sensitive fluorescent dye, MQAE (N-9-ethoxycarbonylmethyl)-6-methoxyquinolinium bromide). Methods: Total RNA was extracted from native and cultured HASM and subjected to RT-PCR analysis for mRNA encoding CLC-1 and CLC-3 using total RNA from human skeletal muscle and human retina as positive controls. Cell volume changes were measured in cultured HASM cells using MQAE. Cultured cells were loaded with 10mM MQAE for 10 hours and following washing were exposed to a hypo-osmotic (250 mOSM) challenge. Results: At least two members of the VRAC family (CLC-1 and CLC-3) are expressed in human airway smooth muscle cells. Changes in cell volume are detectable using MQAE fluorescence following hypo-osmotic challenge in these cells (Change in RFU: 170 ⫹/⫺20 control vs 630 ⫹/⫺ 138 hypotonic, n ⫽ 5, p ⬍ 0.05). Conclusions: CLC-1 and CLC-3 mRNA are expressed in native and cultured HASM cells. These human airway smooth muscle cells are likely exposed to osmotic extremes in the interstitial space of the airway wall. Osmotic effects on cell volume inducing chloride flux are a potential important mechanism in the control of airway smooth muscle contractile tone. These responses to changes in osmolarity may offer future targets of investigation in the understanding and treating EIB.


Poster: Basic Science: GI/Nutrition 132 ENHANCING APOPTOTIC CELL CLEARANCE MITIGATES BACTERIAL TRANSLOCATION AND PROMOTES TISSUE REPAIR AFTER GUT ISCHEMIA-REPERFUSION INJURY IN MICE Rongqian Wu, Weifeng Dong, zhimin wang, Tianpen Cui, Ping Wang, North Shore University Hospital and Long Island Jewish Medical Center Introduction: A key aspect of gut ischemia/reperfusion (I/R) injury is the increased occurrence of apoptotic cell death in the gut. Insufficient clearance of apoptotic cells after I/R leads to the increased inflammation and impaired tissue repair. Our recent studies have shown that administration of milk fat globule EGF-factor 8 (MFG-E8), a crucial molecule for apoptotic cell clearance, reduces apoptosis and inflammation under various disease conditions. The purpose of this study was to determine whether MFG-E8 reduces bacterial translocation and promotes tissue repair after gut I/R. Hypothesis: Enhancing apoptotic cell clearance by MFG-E8 reduces bacterial translocation and promotes tissue repair after gut I/R. Methods: Gut ischemia was induced by superior mesenteric artery occlusion for 90 minin male adult mice. After removing the clip, recombinant murine MFG-E8 (rmMFG-E8) (0.4 ␮g/20g) or normal saline (Vehicle)was injected ip. At 4 h after reperfusion, apoptosis in the gut was measured by TUNEL staining. The mesenteric lymph node (MLN) complex was homogenized for bacterial culture. Neutrophil infiltration was assessed by examining myeloperoxidase (MPO) activity in the gut. VEGF levels in the gut, an indicator of tissue repair, were measured by Western blot. Results: TUNEL positive staining in the gut increased significantly in gut I/R vehicle treated mice. Treatment with rmMFG-E8 markedly suppressed the number of apoptotic cells in the gut. Bacterial translocation to the MLN was minimal in sham mice, but was extensive in gut I/R vehicle treated mice. rmMFG-E8 treatment significantly reduced bacterial translocation to the MLN. Similarly, gut I/R induced a significant increase in intestinal MPO activities in vehicle-treated mice. rmMFG-E8 treatment markedly reduced the increase in intestinal MPO activities after gut I/R. Intestinal levels of VEGF deceased significantly at 4 h after gut I/R. rmMFG-E8 treatment significantly increased intestinal VEGF levels. Conclusions: Enhancing apoptotic cell clearance by rmMFG-E8 mitigates bacterial translocation, inhibits neutrophil infiltration, and promotes tissue repair after gut I/R. Enhancing apoptotic cell clearance can be a novel concept in the treatment of gut I/R injury.


Poster: Basic Science: Hematology 133

134

THE EFFECT OF RFVIIA ON THROMBIN GENERATION OF MODERATELY DILUTED AND HYPOTHERMIC HUMAN BLOOD EX VIVO

HEMODILUTION EFFECTS COAGULATION OF HUMAN BLOOD EX VIVO

Michael Dubick, Daniel Darlington, Bijan Kheirabadi, Chriselda Fedyk, Michael Scherer, Igor Kremenevskiy, US Army Institute of Surgical Research, Angel Delgado, Kinetic Concepts, Anthony Pusateri, US Army Institute of Surgical Research Introduction: Coagulopathy occurs in hemorrhage/trauma and may be associated with hypothermia and hemodilution after resuscitation. Lactated Ringer’s (LR) and Hextend (Hex) are used by the US Army for pre-hospital resuscitation. However, their use can lead to significant hemodilution of coagulation factors and coagulopathy. Activated recombinant Factor VII (rFVIIa) has been used ‘off-label’ as a hemostatic agent for treating coagulopathy in trauma patients. Hypothesis: Does combined hemodilution and/hypothermia affect Thrombin Generation or the activity of rFVIIa on Thrombin Generation in blood? Methods: Blood from 9 consented normal healthy volunteers, was used undiluted, or diluted 40% with LR or Hex, centrifuged, and the platelet-poor plasma frozen for later analysis. Thrombin generation was triggered by adding Tissue Factor, phospholipids, CaCl2 and a fluorogenic thrombin substrate to 80␮L platelet poor plasma. The increase in fluorescence intensity was measured at 34°C or 37°C, in undiluted or 40% diluted samples, with and without rFVIIa (1.29mcg/ml, Novo Nordisk). The thrombin generation curve was generated with variables lagtime, ttPeak (time to peak), Peak, and ETP (endogenous thrombin potential). Results: In undiluted blood, thrombin generation was unaffected by incubation at 34°C. Furthermore, thrombin generation was unaffected by 40% hemodilution at 37°C. However, Peak and ETP were significantly elevated at 34°C in 40% hemodiluted plasma. The addition of rFVIIa to plasma significantly shortened the Lagtime, but had no effect on ttPeak, Peak or ETP in undiluted plasma at 37°C, but significantly elevated Peak and ETP in undiluted plasma at 34°C. Conclusions: Our study shows that thrombin generation was not affected by hypothermia (34 °C) in undiluted blood, or 40% hemodilution with LR or Hex at normal temperature (37°C). However, thrombin generation was enhanced by combined hypothermia (34°C) and 40% hemodilution. Recombinant FVIIa was more effective on Thrombin Generation (Peak) at 34°C than at 37°C. These data suggest that the hemostatic effects of rFVIIa in enhancing thrombin generation may persist in trauma patients even with significant hemodilution and hypothermia. Supported by the ARMY MRMC.


Daniel Darlington, Chriselda Fedyk, Michael Scherer, USA ISR, Angel Delgado, Kinetic Concepts, Bijan Kheirabadi, Anthony Pusateri, USA ISR, Charles Wade, University of Texas, Andrew Cap, Michael Dubick, USA ISR Introduction: Hemorrhage and trauma are associated with coagulopathy that can be caused by hemodilution of coagulation factors after resuscitation. Various “triggers” have been used by clinicians to decide when to begin transfusion of blood and blood products. Commonly used triggers and their values include, Hemoglobin (Hb) ⱕ 100, 000/mm3 and fibrinogen concentration ⬍ 100mg/dl. However, the values of these triggers are based more on expert opinion rather than on hard evidence when treating hemodilution after resuscitation. Hypothesis: The above trigger values are accurate in relation to various coagulation parameters measured during hemodilution. Methods: Blood specimens were collected from 9 normal healthy volunteers and hemodiluted from 0 to 90% with normal saline containing 20mM HEPES (pH7.4). Blood chemistry, platelet count, fibrinogen concentration, prothrombin time, (PT), activated partial thromboplastin time, (aPTT), and thromboelastography, (TEG) were measured. Results: Sequential dilution of whole blood led to a linear fall in plasma potassium, calcium, lactate, glucose, hemoglobin, platelet count, fibrinogen and FVII activity. However, sequential dilution had a more complex effect on PT, aPTT and TEG parameters. PT, aPTT, R, K, and ␣ angle showed little change until 60% hemodilution. MA began to change after 30% hemodilution. The greatest change in PT and aPTT occurred after Hb was diluted below 7g/dl, and at fibrinogen concentrations below 200mg/dl. The greatest change in TEG parameters occurred after Hb was diluted below 7g/dl, and at platelet counts below 80, 000/mm3. The correlations between fibrinogen concentration and TEG parameters were not as strong. Conclusions: Our study clearly shows a strong correlation between Hb, platelets and fibrinogen concentration verses coagulation parameters at different degrees of hemodilution. These data also agree, for the most part, with trigger values that are commonly used by clinicians to start or discontinue blood or blood product transfusion. This project was funded by ARMY MRMC.

Poster: Basic Science: Hepatic 135 XUEBIJING AND ULINASTATIN AMELIORATE PARAQUATINDUCED HISTOPATHOLOGICAL CHANGES IN RAT LIVER Ming-Li Sun, Xiao-Liang Liu, Hai-Feng Li, Ya-Xin Yu, Yuan Yuan, Yan Tan, First Affiliated Hospital of Jilin University , Gui-Lan Ye, Qiqihar Medical University Introduction: Paraquat (PQ) is continuing a major suicide agent indeveloping countries. PQ poisoning can cause failure of liver, lung, kidney, and heart in days and weeks. There are no specific antidotes or effectivetherapeutics currently available. Hypothesis: In this study, we evaluated theprotective effect of Xuebijing (XBJ, a newly developed injection concoctedfrom Chinese herbs), Ulinastatin (Uli), and a combination of the two againstPQ toxicity in liver and kidney in Wistar rats. Methods: Rats wereintoxicated with a sublethal dose of PQ (40mg/ kg, p.o.) to produce liver andkidney injury followed by treatment twice daily with saline, XBJ (10ml/kg, i.p.), Uli (20, 000 iu/kg, i.p.), or the combination (n ⫽ 20 in each group). Thehepatic and renal protective effect was assessed histopathologically withhematoxylin and eosin staining at post-treatment day 3, 7, 14, and 28. Results: PQ induced toxicity was evidenced by lobular and interlobularhepatocellular degeneration, vacuolation, and necrosis in the liver, whilemoderate proximal tubule epithelial cell swelling or vacuolar degenerationonly in the kidney at earlier time points. Comparing to PQ group, thehistopathological changes observed in the liver were remarkably alleviated inall three treatment groups, with the mildest changes seen in the combinationgroup. In addition, the duration for lesion to be seen was also shortened in allthe three treatment groups in comparison to saline control. The protectiveeffect was, however, not found in the kidney. Conclusions: It is concluded that PQ, exposed orally, results in more severe damage in the liver than inthe kidney, and XBJ and Uli, alone and in combination, protect liver fromPQ-induced damage. The effect of the combination is additive, suggesting apotential for the two agents, especially in combination, as clinical alternativesto the conventional management of Paraquat poisoning.


Poster: Basic Science: Immunology 136

137

BACTERIAL CLEARANCE AND SURVIVAL IS ENHANCED IN ADAM17 DEFICIENT MICE WITH PSEUDOMONAS AERUGINOSA PNEUMONIA

MITOCHONDRIAL LYSATES STIMULATE MACROPHAGE MIGRATION INHIBITION FACTOR RELEASE AND POTENTIATE THE ACTIVATION OF IN VITRO-CULTURED HUMAN MACROPHAGES

Patrick Arndt, Brian Strahan, University of Minnesota, Bryan Williams, Vanderbilt Pulmonary Division, Yue Wang, Bruce Walcheck, University of Minnesota Introduction: Recently we have shown that A Disintegrin and A Metalloproteinase 17 (ADAM17) regulates pulmonary neutrophil recruitment in lipopolysaccharide or lipoteichoic acid-induced acute lung inflammation. A role for ADAM17 in regulating the pulmonary inflammatory response during bacterial infection has not been previously examined. Methods: Conditional ADAM17 knock-out mice (ADAM17flox/ flox/Vav-Cre), which lack neutrophil expressed ADAM17, or ADAM17 flox/ ⫹ /Vav-Cre littermates controls, were used in all experiments. The genotype and phenotype of mice were confirmed by PCR and functional screening. Mice were inoculated intra-tracheally with Pseudomonas aeruginosa (strain PA103)(5 ⫻ 105 colony forming units) then sacrificed 6 or 24 hours after infection. Bronchoalveolar lavage (BAL) was performed and lungs and spleen were harvested. Cell counts on BAL fluid and lung neutrophil accumulation, as assessed by myeloperoxidase assay, were determined, and cytokine/chemokine levels in BAL fluid and lung homogenates were measured by ELISA. Bacterial colony counts on BAL fluid and lung and spleen homogenates were assessed from serial dilution cultures. Results: Deficiency of neutrophil expressed ADAM17 increased neutrophil recruitment to the alveolar space and lung 6 and 24 hours after infection compared to infected controls. Cell surface expression of L-selectin was increased on neutrophils isolated from BAL fluid from ADAM17 KO mice. Levels of TNF-a and interleukin-6 were reduced in both BAL fluid and lungs in ADAM17 KO mice. Interestingly, levels of the neutrophil chemoattractants CXCL1, CXCL2, and CXCL5 were decreased in ADAM17 KO mice even though neutrophil recruitment was accentuated. Bacterial counts in BAL fluid and lungs were decreased in ADAM17 KO mice with fewer KO mice having extrapulmonary spread of bacteria. Finally, survival of ADAM17 KO mice was improved 48 hours after infection. Conclusions: Our findings suggest that a deficiency of neutrophil expressed ADAM17 augments neutrophil recruitment tothe lung during infection with Pseudomonas aeruginosa, with this effect associated with improved bacterial clearance from the lung, a decrease in extrapulmonary bacterial spread, and improved survival.


Richard Shimonkevitz, HeathOne Swedish Medical Center, David Bar-Or, Swedish Medical Center, Denetta Sue Slone, HealthONE Swedish Medical Center, Charles Mains, St. Anthony General Hospital Trauma Service Introduction: It has been recently demonstrated that mitochondrial lysates stimulate the activation of human neutrophils and, in an animal model, result in organ injury. This response involves the interaction of the toll-like receptor Tlr-9 with CpG-rich DNA of mitochondria. Hypothesis: Do mitochondrial antigens activate macrophages to release cytokines that might influence or participate in immune responses following traumatic injury? Methods: Mononuclear cells were isolated on Ficoll-Hypaque from whole blood donated by healthy donors and monocytes were allowed to adhere to plastic monolayers overnight in medium supplemented with Macrophage-Colony Stimulating Factor. Non-adherent cells were then removed and the adherent cells cultured for an additional 4 days in medium plus M-CSF. Medium was then removed and macrophage cultures were stimulated overnight with a WISH cell mitochondrial lysate. Culture supernatants were assayed for cytokine content using specific enzyme immunoassays. Cells were analyzed for intracellular cytokine content and intracellular Tlr-9 expression by flow cytometry. Results: Stimulation with mitochondrial lysates resulted in an increased release of Macrophage Migration Inhibition Factor by 1.5 to 10-fold compared to unstimulated cultures, depending upon the particular donor. No release of IL-12 or CXCL10 cytokine was observed, but mitochondrial antigen-stimulated macrophages increased mean intracellular expression of these cytokines approximately 1.5 to 2-fold. Stimulated macrophages increased their granularity 1.4 to 3.7-fold by side scatter analysis and down-regulated mean intracellular Tlr-9 expression by 40% compared to unstimulated cultures. Conclusions: In vitro-cultured human macrophages were activated by mitochondrial antigens to secrete Macrophage Migration Inhibition Factor, a cytokine implicated in septic shock and manifestations of critical illness. Stimulated macrophages increased their intracellular content of IL-12 and CXCL10, two additional cytokines relevant to immune cell activation and recruitment.

Poster: Basic Science: Infection 139

140

EVALUATION OF PSEUDOMONAS AERUGINOSA AND STAPHYLOCOCCUS AUREUS GROWTH ON CHEMICALLY ETCHED ENDOTRACHEAL TUBES AND AGENTO® IN VITRO

DAPTOMYCIN COMPARED TO PENICILLIN AND CLINDAMYCIN AGAINST VIRULENT GROUP A STREPTOCOCCUS ASSOCIATED WITH NECROTIZING FASCIITIS

Keiko Tarquinio, Hasbro Children’s Hospital, Rhode Island Hospital, Nathan Rubien, Rhode Island Hospital, Thomas Webster, Brown University Introduction: Ventilator associated pneumonia (VAP) is a common nosocomial infection in the pediatric ICU, resulting in significant morbidity and mortality. Silver coated endotracheal tubes (ETTs) are attractive for VAP prevention; however, they have not been studied in a pediatric population due to limited availability of smaller ETT sizes. Nanotechnology is an innovative technique to overcome issues associated with coating such as toxicity or allergic reaction. After creating a nano-rough surface on ETTs, growth of planktonic and sessile Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) bacteria on conventional, nano-surface and silver-coated Agento® ETTs were compared using crystal violet staining. Hypothesis: Bacteria growth is different among ETT surfaces. Methods: A lipase 0.1% solution in potassium phosphate was used to soak commercially available ETTs with Rhizopus arrhizus (Nano-R) for 24 hours to change the nano-smooth surface to nano-rough. After cutting conventional, Nano-R and commercially available Agento® tubes into small pieces, they were sterilized and inoculated with either P. aeruginosa or S. aureus. All experiments were triplicated and repeated 3 times. Optical density was measured by spectrometer at 4, 12, 24 and 72 hours and compared using linear regression with post-hoc comparisons. Results: Both P. aeruginosa and S. aureus grew up to 72 hours on all tube types.For planktonic bacteria, Agento® suppressed S. aureus growth most effectively up to 24 hours and P. aeruginosa growth up to 12 hours, however no difference was observed at 72 hours. For sessile bacteria, an overall difference was observed among the 3 ETT types, with Agento® most effective on P. aeruginosa biofilm up to 12 hours, and Nano-R showing a trend to decreased S. aureus biofilm growth at 24 hours. Conclusions: Not only the species, but also the different metabolic stage of bacteria (planktonic vs. sessile) was affected by the ETT material and surface features. Agento® was more effective for planktonic S. aureus and sessile P. aeruginosa, and Nano-R showed a trend toward increased effect for sessile S. aureus biofilm at 24 hours.

Elizabeth Coyle, University of Houston, Kimberly Halton, University of Houston College of Pharmacy Introduction: Group A Streptococcus (GAS) is a virulent pathogen associated with severe skin infections. GAS produces a number of exotoxins that can lead to high morbidity and mortality with complicated infections such as necrotizing fasciitis, and prompt eradication is imperative. Penicillin is the gold standard in the treatment of GAS infections. Hypothesis: Daptomycin is a novel antibiotic with rapid bactericidal activity against pertinent gram positive pathogens. The purpose of this study was to compare the activity of daptomycin to that of penicillin and clindamycin against virulent GAS. Methods: An in-vitro pharmacodynamic model was utilized to emulate infection against a known exotoxin producing GAS isolate (T12). All experiments were performed over 24h in triplicate using cation-adjusted Mueller Hinton medium supplemented with 75 mg/L of calcium and a starting inoculum of ⬎ 1 ⫻ 106 CFU/mL. Simulated regimens were daptomycin 6mg/kg/24h, penicillin 4, 000, 000 units every 4h, and clindamycin 900 mg every 8h. Targeted peak concentrations/half lives for daptomycin, penicillin, and clindamycin were 98 mg/L/8h, 20 mg/L/1h, and 12 mg/L/3h, respectively. Bacterial quantification occurred over 24 hours. Results: MICs for daptomycin, penicillin and clindamycin against T12 were ⱕ 0.125 mg/L, ⱕ 0.125 mg/L and 0.125 mg/L, respectively. 99.9% kill (⬎3 log reduction in CFU/mL) was achieved with daptomycin at 1 hour, and penicillin at 6 hours. A ⬎ 2 log reduction in CFU/mL was observed with clindamycin at 24 hours. No regrowth was seen with any of the regimens. Conclusions: These data suggest that daptomycin is rapidly bactericidal and as effective as penicillin in the eradication of severe GAS organisms. Daptomycin may be a viable option in the treatment of necrotizing fasciitis. This study was funded by a grant from Cubist Pharmaceuticals.

141 NMDA MEDIATED INDUCTION AND SUPPRESSION OF TNF SECRETION OF RAW 264.7 MACROPHAGES STIMULATED BY COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (CA-MRSA) Rebekah Shappley, University of Tennessee Health Science Center, Elizabeth Meals, Keith English, Thomas Spentzas, University of Tennessee Introduction: CA-MRSA infections are common cause of pediatric sepsis. In previous work, ketamine suppressed TNF-␣ (TNF) secretion in an MRSA macrophage sepsis simulation model. In this series, we tested TNF induction in response to N-methyl-D-aspartate (NMDA), to either D-2-amino-5-phosphonovalerate (APV), a competitive inhibitor of the NMDA receptor, and to ketamine, another competitive inhibitor of the NMDA receptor. Hypothesis: In response to MW-2 MRSA, murine macrophage TNF secretion will be augmented by NMDA, and will be diminished by either APV or ketamine. The combination of APV and ketamine will not further decrease TNF levels. Methods: RAW 264.7 murine macrophages were stimulated for 18 hrs with 105 to 107 CFU/mL (retrospective confirmation) of MW2 type MRSA isolated from septic patients. Supernatants were collected and assayed for TNF concentration by ELISA. Results: Preliminary results indicate a differential response. Presence of NMDA stimulates TNF production (p ⬍ 0.05). Addition of the antagonist APV causes dose related TNF suppression (p ⬍ 0.05). Exposure to both APV and ketamine does not increase the suppression. TNF secretion was reduced by approximately 30-40% when macrophages were pre-incubated with either APV, ketamine, or APV ⫹ ketamine. The magnitude of inhibition by ketamine and high-dose APV was similar and there was no additive or synergistic effect observed with combinations of ketamine and APV. Addition of NMDA (30␮M) led to substantial increases in the amount of TNF secreted in response to the MW2 MRSA, and this augmented response was blocked by ketamine and high dose 3 mM of APV and partially blocked by APV at 300 ␮M. Conclusions: Our data indicate that NMDA modulation by agonists and antagonists plays a significant role in TNF secretion by macrophages exposed to a MRSA. These finding can have therapeutic impact on Staphylococcal sepsis.


Poster: Basic Science: Neurology 143 BLAST OVERPRESSURE INJURY IN RATS WITH BODY PROTECTION INCREASES PRO-INFLAMMATORY BRAIN CYTOKINE CONCENTRATIONS David Shellington, Childrens Hospital of Pittsburgh, Larry Jenkins, University of Pittsburgh School of Medicine, Richard Bauman, Walter Reed Army Institute of Research, Peter Swauger, Steven Parks, ORA, Inc., C. Edward Dixon, University of Pittsburgh School of Medicine, Hulya Bayir, Children’s Hospital of Pittsburgh, Edwin Jackson, University of Pittsburgh, Robert Garman, Consultants in Veterinary Pathology, Inc., Patrick Kochanek, Safar Center for Resuscitation Research

sham vs 5.12 ⫾ 1.54 pg/mg), a macrophage and T-cell chemoattractant(p ⬍ 0.05). MIP-1␣ was the only chemokine to remain elevated at 24h (p ⬍ 0.05). Antiinflammatory cytokines were not increased in brain after blast. Conclusions: In rats subjected to blast TBI with body protection, there is a marked proinflammatory cytokine response as early as 2h. A prolonged chemokine response suggests that acute inflammation is an important target, even without extracerebral blast exposure. Support: DARPA PREVENT

Introduction: Blast-induced traumatic brain injury (TBI) caused by improvised explosive devices has been described as the “signature injury” of members of the armed services Iraq and Afghanistan. Survival from otherwise lethal blast exposures may be in part related to protection of lungs/gut by body armor. We described the neuropathology of rats subjected to a head only helium/air shock tube injury characterized by a 35 PSI exposure with 4 ms positive-phase duration—a model associated with 25% mortality. Marked fiber tract degeneration in deep white matter (cerebellum/brainstem) was seen along with fiber track damage in hippocampus at 24 and 72h. Permanent axonal injury was seen in cerebellum at 2wks. We characterized the cytokine/ chemokine response in brain in this model. Hypothesis: Blast TBI is associated with an acute inflammatory response despite total body protection. Methods: Using an IACUC-approved protocol, isofluorane anesthetized rats were placed in a 21ft blast tube (5ft from the end) inside a Mach stem device to produce head only exposure (left side facing the blast). A leather head restraint prevented whiplash. Shams included anesthesia exposure. Ipsilateral cortex was extracted at 2 (n ⫽ 3/group) and 24h (n ⫽ 4/group)(or sham). Multiplex cytokine/chemokine analysis (pg/mg protein) was performed to assess IL-1␣, IL-1␤, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17, IL-18, TNF␣, IFN␥, MIP-1␣, GRO/KC, MCP-1, RANTES, G-CSF, GM-CSF, eotaxin, IP-10. Results: Brain cytokine levels of IL-1␣ (1.3 ⫾ 0.4 pg/mg vs 3.5 ⫾ 0.6 pg/mg), IL-6 (5.5 ⫾ 0.6 pg/mg vs 13.4 ⫾ 2.0 pg/mg), and IL-12p70 (8.3 ⫾ 1.9 pg/mg vs 16.9 ⫾ 2.2 pg/mg) were elevated vs control at 2h (all p ⬍ 0.05). The greatest change was seen for MIP-1␣ (undetectable in

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IMPACT OF HEMORRHAGIC SHOCK ON THE INFLAMMATORY RESPONSE TO EXPERIMENTAL TRAUMATIC BRAIN INJURY

RESUSCITATION OF EXPERIMENTAL TRAUMATIC BRAIN INJURY AND HEMORRHAGIC SHOCK IN MICE: ACUTE EFFECTS OF POLYNITROXYLATED PEGYLATED HEMOGLOBIN AND 100% OXYGEN

Steven Shein, David Shellington, Children’s Hospital of Pittsburgh of UPMC, Edwin Jackson, University of Pittsburgh, Hulya Bayir, Robert Clark, Children’s Hospital of Pittsburgh of UPMC, Larry Jenkins, Edward Dixon, University of Pittsburgh School of Medicine, Keri Janesko-Feldman, Vincent Vagni, Patrick Kochanek, Safar Center for Resuscitation Research Introduction: Secondary insults such as hemorrhagic shock (HS) after traumatic brain injury (TBI) worsen outcome. Little is known about the effect of HS on inflammation after TBI. We characterized a mouse model of TBI ⫹ HS where damage after TBI is exacerbated by HS. Multiplex can be used to study profiles of cytokines/ chemokines to gain insight into inflammatory signaling. Hypothesis: TBI ⫹ HS magnifies the serum and brain tissue inflammatory response vs TBI or HS alone. Methods: With IACUC approval, adult male C57BL6J mice were randomized to 5 groups (n ⫽ 4/group), 1) naı¨ve, 2) sham (surgery/anesthesia), 3) HS (35 min of HS; MAP ⫽ 27 mmHg), 4) TBI by controlled cortical impact (1 mm depth, 4 m/s to left parietal cortex) or 5) TBI ⫹ HS. Femoral catheters were placed and brain temperature monitored. After 35 min of HS, mice in HS or TBI ⫹ HS groups were resuscitated with LR (MAP ⫽ 70 mmHg, 90 min); shed blood was then reinfused. ABGs/ physiological parameters were monitored. Serum and brain samples (hippocampus, cortex, cerebellum) were obtained at 2 or 24h.Cytokines (IL-1␣, IL-1␤, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IFN, TNF␣), and chemokines (eotaxin, IP-10, KC, MCP-1, MIP-1␣ and RANTES) were assessed by Multiplex. Data (median [range])were analyzed by Kruskall-Wallis. Results: Serum IL-6 increased in HS, TBI, and TBI ⫹ HS, all p ⬍ 0.05 vs naı¨ve. However, serum chemokines MCP-1 and MIP-1␣ were increased at 2h only in HS and TBI alone (p ⬍ 0.05 vs naı¨ve). Serum IL-10 was only increased in TBI ⫹ HS (p ⬍ 0.05 vs naı¨ve). In brain only 3 of 14 cytokines, IL-1␣ and IL-6 were increased after injury (p ⬍ 0.05 vs naı¨ve), however, the chemokines eotaxin, IP-10, KC, MCP-1, MIP-1␣ were all increased at 24h (p ⬍ 0.05 vs naı¨ve) and increases were similar in TBI vs TBI ⫹ HS. Conclusions: Surprisingly, TBI ⫹ HS depresses aspects of systemic inflammation and triggers an antiinflammatory cytokine profile. In brain, TBI was required to elicit inflammation, that was dominated by chemokines at 24h. HS after TBI did not magnify the chemokine response. We suggest that in addition to testing traditional anti-inflammatory agents, immune-stimulatory therapies should be explored in TBI ⫹ HS. Support: DARPA PREVENT and US Army W81XWH-09-2-0187


Brian Blasiole, University of Pittsburgh, Hulya Bayir, Children’s Hospital of Pittsburgh, Vincent Vagni, Keri Janesko-Feldman, Safar Center for Resuscitation Research, Li Ma, Georgia Southern University, Carelton Hsia, SynZyme Technologies LLC, Patrick Kochanek, Safar Center for Resuscitation Research Introduction: Hemorrhagic shock (HS) worsens traumatic brain injury (TBI) outcomes, but optimal treatment is unclear. The novel covalently modified bovine hemoglobin (Hb) polynitroxylated pegylated Hb (PNPH) is a uniquely neuroprotective rather than neurotoxic Hb. The effects of PNPH on cerebrovascular hemodynamics and its interaction with oxygen (O2) in TBI resuscitation are undefined. Hypothesis: Resuscitation of TBI ⫹ HS in mice with PNPH vs lactated Ringer’s (LR) would improve mean arterial pressure (MAP), intracranial presure (ICP) and cerebral perfusion pressure (CPP). We also determined if 100% O2 vs room air (RA) influenced TBI resuscitation with PNPH or LR. Methods: With IACUC approval, adult male C57BL6 mice received controlled cortical impact (CCI; 4mm depth, 5m/s to L parietal cortex) ⫹ HS (MAP 25 ⫾ 2mmHg for 35min). After HS, a 90min period simulating prehospital (PH) resuscitation was begun (MAP ⬎ 70mmHg via IV PNPH or LR) in 4 groups: 1) PNPH ⫹ 100%O2 (n ⫽ 6), 2) PNPH ⫹ RA (n ⫽ 6), 3) LR ⫹ 100% O2 (n ⫽ 6), and 4) LR ⫹ RA (n ⫽ 8). After the PH phase, shed blood was reinfused simulating inhospital (IH) resuscitation. Brain temperature, MAP, ICP and CPP were monitored, and blood lactate serially obtained. ANOVA was performed at baseline (BL), end HS, end PH, and end IH. Results: Fluids required (mL/kg) during PH phase were greatly reduced in PNPH vs LR (26.00 ⫾ 0 for both PNPH groups vs 161 ⫾ 9.91 for LR ⫹ 100% or 187.25 ⫾ 6.39 for LR ⫹ RA, p ⬍ 0.05). After PH phase, MAP was higher in the PNPH ⫹ 100% and PNPH ⫹ RA vs either LR group (p ⬍ 0.05), ICP was less in PNPH ⫹ 100% vs LR ⫹ RA (11.46 ⫾ 1.52 vs 18.09 ⫾ 1.51mmHg, p ⬍ 0.05), and CPP higher in PNPH ⫹ 100% and PNPH ⫹ RA vs LR ⫹ 100% or LR ⫹ RA (66.94 ⫾ 1.73, 65.58 ⫾ 2.30, 47.78 ⫾ 2.47, 40.29 ⫾ 3.29mmHg, respectively, p ⬍ 0.05). Lactate did not differ after PH. MAP, ICP, or CPP did not differ in LR ⫹ 100% vs LR ⫹ RA, but, fluid requirements were less in LR ⫹ 100% (p ⬍ 0.05). Conclusions: PNPH is a small volume resuscitation fluid that confers marked benefit vs LR on MAP, ICP, and CPP after TBI ⫹ HS. PNPH ⫹ 100% O2 best limited ICP. PNPH did not impair lactate clearance. 100% O2 modestly reduced fluid required in LR resuscitation. PNPH merits further study as a promising agent in TBI resuscitation. Support: W81XWH06-1-0247/W81XWH09-2-0187

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EFFECT OF RESUSCITATION WITH DIFFERENT VENTILATORY OXYGEN LEVELS ON FUNCTIONAL OUTCOME AFTER PEDIATRIC ASPHYXIAL CARDIAC ARREST

CEREBROSPINAL FLUID 20-HYDROXYICOSATETRAENOIC ACID IS ASSOCIATED WITH DELAYED CEREBRAL ISCHEMIA AND POOR OUTCOMES AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

Sirine Baltagi, Childrens Hospital of Pittsburgh, Robert Clark, Children’s Hospital of Pittsburgh, Jing Ji, University of Pittsburgh, Alicia Au, Childrens Hospital of Pittsburgh, Mioara Manole, Children’s Hospital of Pittsburgh, Henry Alexander, University of Pittsburgh, Patrick Kochanek, University of Pittsburgh Medical Center, Hulya Bayir, Children’s Hospital of Pittsburgh Introduction: Current AHA guidelines recommend the use of 100% O2 during resuscitation and for an undefined period thereafter in pediatric cardiac arrest (CA). However, studies in adult canine ventricular fibrillation CA models suggest that use of 21% O2 during and after resuscitation improves neurological outcome. Unlike adults, asphyxia is the principal cause of CA in children. There currently exist no comparable studies in pediatric models of CA. We used an age appropriate rodent model of asphyxial CA (ACA) to simulate this condition. Hypothesis: We hypothesized that resuscitation with 21% O2 will produce a favorable effect on functional outcome after ACA in juvenile rats. Methods: Anesthetized post-natal day 16-18 rats were randomized to resuscitation and ventilation for 1 hour with 100% O2 (n ⫽ 10), 21% O2 (n ⫽ 10), or goal directed (GD) O2 to maintain ⬎ 90% systemic O2 saturation (pulse-oximetry) (n ⫽ 10) after 9 min of ACA. Two sham groups (100% O2, n ⫽ 6) and (21% O2, n ⫽ 5) were used as controls. Neurological function was assessed using established motor (beam-balance and inclined plane) and cognitive (spatial learning/memory in Morris water maze (MWM)) tasks on post-insult day 1-5 and 7-14, respectively. 2-way RM ANOVA was used to test statistical significance. Results: Time to maintain beam balance, traverse an elevated beam, and to locate a submerged platform in MWM was recorded. Motor performance was affected by ACA compared to sham but no difference was noted between the treatment groups. Two aspects of memory function were tested on MWM: spatial memory acquisition and probe trial. Although there was no significant difference in spatial memory acquisition, rats resuscitated with 100% O2 spent significantly more time in the target quadrant compared to rats resuscitated with 21% and GD O2 during probe trial (30% ⫾ 3 vs. 17% ⫾ 3 vs. 21% ⫾ 2 respectively, p ⬍ 0.05). Conclusions: Unlike adult VF cardiac arrest models, neurologic outcome is improved rather than impaired by the use of 100% O2 during and after resuscitation in experimental pediatric ACA and this effect was seen specifically for cognitive outcome. Whether this is a result of age- or mechanismrelated differences remains to be determined. Support: NS061817, HD045968

Elizabeth Crago, C Kuo, P Sherwood, University Of Pittsburgh School of Nursing, M Horowitz, University of PIttsburgh Medical Center, S Poloyac, University of Pittsburgh School of Pharmacy Introduction: Delayed cerebral ischemia (DCI), a mismatch between available cerebral blood flow (CBF) and the metabolic needs of brain tissue, affects outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Preclinical evidence has shown that 20-hydroxyicosatretaenoic acid (20-HETE) affects cerebral microvascular tone and CBF after SAH. The purpose of this study was to determine if 20-HETE cerebral spinal fluid (CSF) concentrations are associated with DCI and outcomes in patients after aSAH. Hypothesis: 20-HETE cerebral spinal fluid (CSF) concentrations will be associated with the incidence of DCI and neuropsychological (NP) dysfunction in patients after aSAH. Methods: CSF samples collected twice daily from 0-14 days after hemorrhage on 108 acute, adult aSAH patients were analyzed for the presence of 20-HETE using solid phase extraction, HPLC and MSQ single quadrupole mass spectrometry. DCI was defined as the presence of impaired CBF (angiographic vasospasm, elevated transcranial Dopplers, and/or abnormal CT/MR perfusion scans) accompanied by neurological decline (change in consciousness, new focal neurological deficit, pupil change, worsening Glasgow coma or National Institutes of Stroke Score). Outcomes covering 7 domains were completed at 3 months after hemorrhage by trained personnel. Fisher’s exact and Mann-Whitney U-tests were used to analyze the association between detectable and non-detectable levels of 20-HETE and clinical and socio-demographic data while multivariable regression models were created to evaluate the presence of 20-HETE and NP outcomes. Results: Detectible levels of 20-HETE, observed in 31% of patients, were associated with severity of hemorrhage (Hunt & Hess p ⫽ .04; Fisher p ⫽ .05). Although not associated with angiographic vasospasm (p ⫽ .34), the presence of 20-HETE was significantly associated with DCI (p ⫽ .01). Preliminary evidence suggests that the presence of 20-HETE was also associated with decreased performance in 5 NP domains. Conclusions: These results provide the first evidence that CSF 20-HETE concentrations are associated with DCI in humans and provide impetus for future studies to explore the clinical utility of inhibiting 20-HETE as a therapeutic intervention in patients with aSAH.

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ROSUVASTATIN CAN ATTENUATE CEREBRAL MICROCIRCULATION AND METABOLISM IMPAIRMENT DURING EXPERIMENTAL SEPSIS.

EFFICACY OF POLOXAMER P188 COMPARED TO P407 AND POLYETHYLENE GLYCOL AFTER TRAUMATIC BRAIN INJURY IN MICE

Fabio Silvio Taccone, Fuhong Su, Erasme University Hospital, Cathy De Deyne, ZOL St Jan, Laura Penaccini, Ali Abdelhadii, Charalampos Pierrakos, He Xinrong, Erasme University Hospital, Olivier Dewitte, Erasme Hospital, Jean-Louis Vincent, Daniel De Backer, Erasme University Hospital

Eyup Keles, Jimmy Zhang, Rajani Koppula, Joon Chung, Michael Whalen, Massachusetts General Hospital

Introduction: Alterations of cerebral microvascular blood flow may develop during sepsis1 and have negative effects on cerebral oxygenation and metabolism2. Statins have shown protective effects on endothelium and the injured brain. Hypothesis: We studied the impact of rosuvastatin on cerebral microcirculation, oxygen delivery and cerebral metabolism in a clinically relevant ovine model of septic shock. Methods: Sixtheen invasively monitored, mechanically ventilated female sheep were randomized to placebo (n ⫽ 8) or intravenous rosuvastatin 2 mg/kg (n ⫽ 8), given before the surgery. Peritonitis was induced by injection of 1.5g/kg feces into the abdominal cavity. Brain microcirculaion was evaluated using side dark-field videomicroscopy applied on the cerebral frontal cortex after bilateral craniectomy. At least 5 areas were recorded at each time point (baseline, 6, 12 and 18 hours). Cerebral functional capillary density (FCD) and proportion of small perfused vessels (PSPV) were calculated using standard formulas. Partial oxygen pressure in the brain (PbO2) was hourly measured by LICOX probes (Integra Lifesciences, France). Brain metabolism was estimated by lactate/pyruvate ratio (LPR) collected via microdialysis (CMA, Sweden). Sheep were observed for 18 hours. Results: The evolution of hemodynamics, respiratory parameters and lactate levels was similar in both groups. Cerebral microcirculation was similar at baseline and progressively deteriorated in both groups, but was better preserved in animals treated by rosuvastatin at 18 hours (FCD 2.7 ⫾ 1.1 vs. 1.6 ⫾ 0.4 n/mm, p ⬍ 0.05; PSPV from 91 ⫾ 5 to 84 ⫾ 8%, p ⬍ 0.01). PbO2 similarly decreased over the study period in both groups. LPR progressively increased and was higher in placebo group than in rosuvastatin group at 18 hours (38.7 ⫾ 20.3 vs. 21.5 ⫾ 7.8, p ⬍ 0.001). Conclusions: When administrated prior to induction of sepsis, rosuvastatin attenuated the impairment of cerebral microcirculation and concomitantly prevented the development of ischemic patterns in cerebral metabolism. Grant: Fondation Erasme, Bourse de Recherche; Integra Lifesciences Service SAS ; AstraZeneca1. Taccone FS et al. Crit Care 2010; 14:R140.2. Taccone FS et al. 39th SCCM Congress (Abstract A32)

Introduction: Poloxamer P188 is a FDA approved triblock copolymer (Polyethylene glycol [PEG]-polyethylene oxide-PEG] that inserts into and reseals damaged cell membranes. Polyethylene glycol (PEG) has been hypothesized to act in a similar fashion as P188 and has been proposed as a treatment for acute brain and spinal cord injury. Hypothesis: P188 is more effective at reducing secondary damage after controlled cortical impact (CCI) in mice and that its in vivo efficacy is related to its ability to reseal damaged cell membranes. Methods: We used a mouse CCI model (0.6mm depth, 6 m/s, 100 ms impact duration) and in vivo administration of fluorescent markers YOYO-1 and propidium iodide to label permeable cells damaged after CCI. YOYO-1 was given before and propidium iodide after administration of drugs (P188, 5 mM; PEG 8000, 5 mM; P407, 5 mM; PBS; each 500 ul IV at 60 min after injury). Resealed cells were identified by fluorescence microscopy as YOYO-1 ⫹ /PI-. Brain edema was assessed by wet to dry weights; blood brain barrier damage by Evans blue dye; motor function by wire grip test; resealed cell counts were done in randomly selected x400 fields in injured cortex and hippocampus. ANOVA followed by t-test was used to analyze all data except motor data (RM ANOVA, group ⫻ time). Results: In adult mice, P188 and PEG-8000 each resealed damaged cell membranes (p ⬍ 0.05 vs. PBS) whereas P407 did not. P188 but not PEG-8000 nor P407 reduced brain edema by almost 50% (p ⬍ 0.05) and significantly reduced BBB damage (p ⬍ 0.05) and brain tissue loss (p ⬍ 0.05) vs. PBS. Strikingly, in immature (3 week old) mice, P188 did not reseal injured cell membranes and had no effect on brain edema, BBB damage, postinjury motor function, and lesion size. Conclusions: P188 reseals injured cell membranes and reduces brain edema and other measures of secondary injury after CCI in mice in an age-dependent fashion. P188 is a promising agent to reduce brain edema and improve outcome in adults with traumatic brain injury characterized by focal contusion. The protective properties of P188 are not shared by PEG-8000 and poloxamer P407 in the mouse CCI model.


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INHIBITION OF AUTOPHAGY USING ATG7 SIRNA IMPROVES NEUROLOGICAL FUNCTION AND NEURONAL SURVIVAL AFTER ASPHYXIAL CARDIAC ARREST IN JUVENILE RATS

TREATMENT WITH DOCOSAHEXANOIC ACID AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY MODULATES THE INFLAMMATORY RESPONSE

Alicia Au, Childrens Hospital of Pittsburgh, Craig Smith, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Sirine Baltagi, Childrens Hospital of Pittsburgh, Yaming Chen, Safar Center for Resuscitation Research, Henry Alexander, University of Pittsburgh, Christina Hosler, Safar Center for Resuscitation Research, Mioara Manole, Hulya Bayir, Children’s Hospital of Pittsburgh, Patrick Kochanek, University of Pittsburgh Medical Center, Robert Clark, Children’s Hospital of Pittsburgh

Elizabeth Newell, Children’s Hospital of Pittsburgh of UPMC, C. Edward Dixon, University of Pittsburgh School of Medicine, Joseph Carcillo, Children’s Hospital of Pittsburgh of UPMC, Edwin Jackson, University of Pittsburgh, Hong Yan, University of Pittsburgh School of Medicine, Hulya Bayir, Robert Clark, Children’s Hospital of Pittsburgh of UPMC, Keri Janesko-Feldman, Patrick Kochanek, Safar Center for Resuscitation Research

Introduction: Autophagy, an intracellular pathway involved in the recycling of proteins and organelles, is upregulated in the brain after hypoxia-ischemia (HI). However, whether autophagy is beneficial or harmful after HI is controversial. We previously showed effective inhibition of autophagy in the cerebellum via intracisternal (i.c.) injection of small interfering RNA (siRNA) targeting Atg7, a protein essential for autophagy (Crit Care Med 2009;37:A16). Thus, Atg7 siRNA represents a specific tool to evaluate the role of autophagy after HI in brain in vivo. Hypothesis: Treatment with Atg7 siRNA will improve neurological outcome after asphyxial cardiac arrest (ACA) in postnatal day (PND) 17 rats. Methods: 800 pmol (25 uL) of Atg7 or control siRNA was injected i.c. into male and female PND 15 rats. At 2d rats underwent 9 min ACA (n ⫽ 9/sex/group) or sham surgery (n ⫽ 6/sex/group). Since we previously showed efficient Atg7 knockdown in cerebellum, beam balance and incline plane testing on d1-5 and selectively vulnerable Purkinje cell (PC) survival (sagittal sections at 0, 0.5, and 1mm from midline) were evaluated at d14. Results: After ACA, treatment with Atg7 siRNA improved performance on the beam balance vs control, but only in females (P ⫽ 0.02 logrank). No differences were seen in the inclined plane test. After ACA in females Atg7 siRNA increased PC survival vs control (569 ⫾ 37:476 ⫾ 37:376 ⫾ 32 vs 457 ⫾ 29:422 ⫾ 28:312 ⫾ 34 cells/section, mean ⫾ SE; P ⬍ 0.01 2-F ANOVA). After ACA in males there was no difference between treatment with Atg7 vs control (687 ⫾ 42:691 ⫾ 40:518 ⫾ 29 vs 654 ⫾ 75:595 ⫾ 65:432 ⫾ 69 cells/section; P ⫽ 0.13 2-F ANOVA). Greater numbers of PC were seen in male vs female rats in both ACA and sham groups, suggesting a sex-difference in PC number. Comparison of all rats undergoing ACA adjusting for baseline sex-differences revealed a favorable effect of Atg7 siRNA on PC survival vs control (P ⬍ 0.01 2-F ANOVA). Conclusions: Inhibition of autophagy after global ischemia leads to improved beam balance performance and increased survival of cerebellar PC in a sex-dependent manner. This is consistent with a detrimental role for increased autophagy after HI, warranting further testing of therapies targeting autophagy. R01HD045968/T32HD040686

Introduction: Neuroprotective therapies are needed in severe TBI to complement ICPdirected care. Microglia, the immunocompetent cells of the CNS, and systemic monocytes/macrophages are activated and accumulate in injured brain after TBI and may mediate neurotoxicity. Omega-3-polyunsaturated fatty acids such as docosahexanoic acid (DHA) are available in nutritional formulas and attenuate axonal injury after experimental TBI (Ward et al, J Neurotrauma 2010). DHA also has antiinflammatory properties (Endres et al, N Engl J Med, 1989) that may modulate microglial and monocyte/macrophage activation and accumulation after TBI, possibly reducing secondary damage. Hypothesis: Treatment with DHA after controlled cortical impact (CCI) in rats will decrease both the neuro- and systemic inflammatory response. Methods: In the first experiment, with IACUC approval, CCI was induced in isoflurane-anesthetized adult male Sprague Dawley rats. Rats were then randomized to treatment for 21d with DHA at either 1mg/kg, 16mg/kg, or vehicle (daily IP, n ⫽ 5/group). The microglial response (accumulation and activation state) in ipsilateral and contralateral hippocampus, corpus callosum, and thalamus was examined (Iba-1 immunohistochemistry). In a second experiment, blood samples were obtained in rats exposed to CCI and treated for 3, 7 or 21d with IP injections of DHA at 16mg/kg (n ⫽ 3/group). Ex vivo production of TNF␣ by monocytes/macrophages in LPS-stimulated whole blood was measured by ELISA. Results: In rats treated with DHA (16mg/kg) after CCI, there was a trend towards reduced microglia accumulation in corpus callosum. This was not seen in other regions. The activation state of microglia did not differ between groups. In contrast, ex vivo TNF␣ production in whole blood differed significantly vs naı¨ve depending on duration of DHA treatment. TNF␣ production was less only in the 21d treatment group vs naı¨ve (20.99 ⫾ 4.58 vs 57.50 ⫾ 8.12 pg/mL, p ⬍ 0.05). Conclusions: Our data suggests DHA attenuates the systemic inflammatory response after experimental TBI. Effects are dose dependent and require sustained treatment. The contribution of these antiinflammatory effects to neuropathological and functional outcome are being investigated. SUPPORT: NS30318

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ANATOMIC EVIDENCE OF INJURY TO THALAMOCORTICAL STRUCTURES IN A RODENT MODEL OF PEDIATRIC ASPHYXIAL CARDIAC ARREST

ROLE OF ECTO-5’-NUCLEOTIDASE IN REGULATING ADENOSINE IN BRAIN AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY

Mish Shoykhet, Childrens Hospital of Pittsburgh, Daniel Simons, University of Pittsburgh School of Medicine, Patrick Kochanek, University of Pittsburgh Medical Center, Robert Clark, Children’s Hospital of Pittsburgh

Steven Shein, Jieshen Wu, Children’s Hospital of Pittsburgh of UPMC, Edwin Jackson, University of Pittsburgh, Keri Janesko-Feldman, John Melick, Patrick Kochanek, Safar Center for Resuscitation Research

Introduction: Pediatric cardiac arrest (CA) results in significant mortality and morbidity, and targeted interventions have yet to be identified. Most studies of brain injury in CA have focused on neuronal death in CA1hippocampus, however, the thalamus is a key structure that has received limited exploration. Our previous neurophysiologic data indicated disruption of thalamocortical (TC) information transfer in a rodent model of pediatric asphyxial CA (ACA). The disruption was consistent with injury to the inhibitory thalamic Reticular Nucleus (nRT), which regulates information processing in the TC circuit. Here, we sought to define the anatomic substrate underlying thalamic injury after ACA. Hypothesis: ACA results in degeneration of nRT neurons. Methods: PND17-19 rats underwent a sham insult (n ⫽ 4) or a 9 min ACA (n ⫽ 12) followed by resuscitation. At 24 or 72h after ACA, the brains were extracted and stained for markers of cell degeneration. We employed 4 stains: a) immunohistochemistry (IHC) for glutamic acid decarboxylase (GAD) to identify nRT neurons; b) Fluoro-Jade B (FJB) to identify degenerating cells; c) cupric silver (CuAg) to identify degenerating neuronal elements, including soma, neurites and synaptic boutons; and d) IHC for Ionized Calcium Binding Adaptor molecule 1 (Iba1) to reveal microglial activation. Results: Neither GAD IHC nor FJB revealed detectable neuronal somal damage in nRT. Iba1 IHC did demonstrate microglial activation within nRT at 24h after ACA. FJB also revealed an injury pattern suggesting neurite damage in a thalamic ventroposteromedial nucleus (VPM), which serves as the major somatosensory TC relay nucleus and receives nRT axonal input. CuAg stain confirmed degeneration of neurites withinVPM at 72h after ACA. Conclusions: After ACA, injury to nRT and to the TC system occurs as evidenced by microglial activation within nRT and by degeneration of neuronal processes projecting to VPM. Direct damage to neuronal soma in nRT was not seen with either GAD or FJB stains. Future studies are needed to verify the source of the degenerating neurites. These anatomical and previous physiologic data suggest that TC circuitry represents a possible therapeutic target in pediatric ACA.

Introduction: Adenosine is an endogenous neuroprotectant with antiexcitotoxic, antiepileptic, antiinflammatory and cerebral blood flow promoting effects in brain. Adenosine A1 receptor knockout (KO) mice exhibit 50% acute mortality from status epilepticus after traumatic brain injury (TBI). Early after TBI brain interstitial levels of adenosine markedlyincrease. Adenosine is produced in part via ecto-5’-nucleotidase (CD73), which catalyzes the conversion of 5’-AMP to adenosine. Hypothesis: CD73 KO mice will have decreased adenosine levels, seizures, and neuronal death after TBI vs WT. Methods: TBI was produced by controlled cortical impact (CCI, 4 m/s, 1mm depth) in CD73 KO and WT littermate adult male mice. Four groups were studied: WT-CCI, KO-CCI, WTsham (anesthesia/craniotomy but no CCI), and KO-sham. In the first experiment, amicrodialysis probe was inserted in injured hippocampus to measure brain interstitial levels of adenosine and 5’-AMP in the initial 2h after CCI. In the second experiment, mice were observed for seizures after CCI and then allowed to recover for 1wk. Brain sections from injured hippocampus/thalamus were taken and stained for neuronal death (FluoroJade-C). Neurons were quantified with Image J. Data were analyzed by ANOVA or Mann-Whitney test. Results: Adenosine was increased after CCI in both KO and WT vs sham (P ⬍ 0.0001) and levels of post-CCI adenosine were ⬃2-fold lower in KO vs WT (14.2 ⫾ 2.0 vs 36.0 ⫾ 14.0). Levels of the adenosine precursor 5’-AMP were dramatically increased (⬎12-fold) in the KO vs WT after CCI (89.0 ⫾ 16.7 vs 6.2 ⫾ 1.8, p ⬍ 0.0001). However, seizures werenot noted in the KO after CCI and there were no differences in the amount of neuronal death in KO vs WT in hippocampus or thalamus after CCI. Conclusions: CD73 plays a role in producing adenosine after TBI. However, the decrease in adenosine in brain in the CD73 KO did not lead to seizures or increase neuronal death. Adenosine levels in brain after TBI in the CD73 KO were still increased 10-fold vs sham indicating alternative pathways for adenosine production, such as the newly discovered 2’, 3’ cAMP-adenosine pathway. 5’-AMP, which increased markedly after TBI in the KO, may also be neuroprotective. Support: NS070003 and NS30318


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POSSIBLE ROLE FOR HAPTOGLOBIN AND HEMOGLOBIN AGGREGATES IN PATHOMECHANISM OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

INTRACRANIAL HEMORRHAGE – A NEW LARGE ANIMAL MODEL OF BRAIN DEATH

Laura Watkins, Childrens Hospital of Pittsburgh, Sheila Alexander, Alexandr Kapralov, University of Pittsburgh, Dianxu Ren, Elizabeth Crago, Yvette Conley, University of Pittsburgh School of Nursing, Valerian Kagan, University of Pittsburgh, Hulya Bayir, Children’s Hospital of Pittsburgh Introduction: Delayed cerebral vasospasm (DCV) is the leading preventable cause of death and disability in aneurysmal (a)SAH. The main mechanism of DCV includes released free hemoglobin (Hb) but haptoglobin (Hp) seems to play a substantial role as well. In the presence of H2O2, Hb acts as a peroxidase yielding high molecular weight aggregates with Hp, not dissociable by the disulfide reducer dithiothreitol (DTT), suggesting the formation of non-Cys crosslinks (likely, di-Tyr). Uptake of these Hb-Hp aggregates (but not their complexes) by macrophages is accompanied by oxidative stress and cytotoxicity. Hypothesis: Hp-Hb aggregates in CSF are associated with higher severity of aSAH. Methods: Patients (n ⫽ 8/group) were grouped in increasing order of severity: group A: asymptomatic & negative angiography, group B: asymptomatic & positive angiography, group C: symptomatic & positive angiography, and matched for: Fisher grade, age, sex, race, Hunt-Hess score and admission GCS. We performed 7.5% Native polyacrylamide gel electrophoresis (PAGE) of CSF followed by WestPICO to evaluate for presence of peroxidase activity, followed by silver staining and Western Blot (WB) with antiHp antibodies (Ab). In addition, 10% SDS-DTT PAGE of CSF was performed followed by WB with antiHp and antiHb Ab. Results: On native PAGE, Hp complexes and aggregates were detectable. On SDS-DTT PAGE, we found dissociated Hp subunits as well as Hp aggregates in all samples. In 6 out of 8 series of matched patients, intensity of Hp aggregates correlated with increasing disease severity (group C ⬎ B ⬎ A). Staining for Hb in the aggregates did not correlate with the disease severity. There was also no correlation between the severity of the disease and peroxidase activity of Hb or of Hp-Hb complexes or aggregates. Conclusions: Hp-Hb aggregates are present in CSF of aSAH patients; accumulation of Hp aggregates correlates with severity of the disease. Thus indicating a possible novel pathway involved in the disease pathogenesis whose detailed mechanisms should be studied further. Support: NS061817, NR004339

Christine Hvas, Anne Barklin, Frederikke Rosendal, Jens Christian Sorensen, Michael Pedersen, Christian Fenger-Eriksen, Else Tonnesen, Aarhus University Hospital Introduction: Brain death impairs the function of organs in the potential donor and has a negative impact on organ retrieval. The underlying mechanisms are not clarified. In previous animal models brain death was induced by inserting a balloon sub- or epidurally, often with a sudden onset of brain death, and without intracranial bleeding. In this study we established a new model, where there is contact between blood and brain parenchyma. This creates a clinically relevant model mirroring patients suffering from brain death due to spontaneous intracranial hemorrhage. Hypothesis: This study was conducted to develop a new brain death model where brain death is induced by intracranial hemorrhage and validated by CT angiography (CTA). Methods: Eleven Danish land race pigs (24-38 kg) were anesthetized, orally intubated and their heads were fixated in a stereotaxic localizer box. A needle was stereotaxically inserted in the capsula interna at the level of the lateral ventricle. Intracranial pressure (ICP) was measured with Camino Intracranial Pressure Monitoring kit. Brain stem reflexes (pupil and cornea) were tested before and after induction of brain death. Autologous blood was infused through the needle and a silicone tube and different rates tested. At the speed of 40 ml/h coning was obtained at approximately 30 min. The infusion continued for another 60 min to maintain an ICP sufficient to ensure brain death. Fluid resuscitation was performed with Ringer acetate until MAP ⬎ 60 mmHg. CTA was performed 120-180 min after brain death. Atropine 3 mg was given and the heart rate observed for 60 seconds. Results: Tachycardia, hypertension and diabetes insipidus developed as a response to increased ICP and intracranial bleeding. A second phase was recognized by a significant reduction in blood pressure. Atropine had no effect on the heart rate. Brain stem reflexes disappeared and CTA confirmed brain death by the absence of contrast material in and above the circle of Willis. Conclusions: This is the first large animal model mimicking intracranial hemorrhage with subsequent brain death validated by CTA. This model is being further validated with the aim to examine the effects of brain death on coagulation and inflammation.


Poster: Basic Science: Pulmonary 157

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IMPROVED SURFACTANT EFFECT WITH PHOSPHATIDYLINOSITOL-3, 5-BISPHOSPHATE IN ACUTE NEONATAL INFLAMMATORY LUNG INJURY

BONE MARROW CELLS ATTENUATE ENDOTOXIN-INDUCED ACUTE LUNG INJURY

Stefanie Preu␤, Friede Omam, Julia Scheiermann, Sabrina Stadelmann, Sabine Adam-Klages, Philipp von Bismarck, Supandi Winoto-Morbach, Stefan Schu¨tze, Martin Krause, Universita¨tsklinikum Schleswig-Holstein, Campus Kiel Introduction: Phosphatidyl-inositol-3, 5-bisphosphate (PIP) is an intermediate product of surfactant metabolism and a potent inhibitor of acid sphingomyelinase (aSMase), the key enzyme for ceramide generation and pro-apoptotic downstream products such as the caspases. Ceramide itself integrates into the surfactant bilayer and increases the surfactant surface tension in neonatal and adult ALI. Hypothesis: We wished to evaluate the benefit of PIP admixed to exogenous surfactant in a triple-hit neonatal lung injury model of severe pulmonary inflammation by assessment of gas exchange, lung function, and hemodynamics over 72h of mechanical ventilation. Methods: After repeated airway lavage to induce hypoxemic respiratory failure (PaO2/FiO2 ⬍ 120 mm Hg), 32 piglets weighing ⬃2.5 kg were randomized into 4 groups receiving either an air bolus as a control (C-group), or surfactant alone (50 mg/kg Curosurf®, S-group), or surfactant with 2 mg PIP (S ⫹ PIP-group), or surfactant with 5 mg crystalline imipramine (S ⫹ Imi-group) as a reference group for aSMase inhibition. 24h and 48h later, injurious ventilation for 2h using zero-PEEP and doubled tidal volume (14 mL/kg), and tracheal deposition of 2.5 mg E. coli lipopolysaccharide, respectively, was followed by a second and third set of interventions. Results: At the end of the clinical study after 72h of mechanical ventilation, we observed significantly differing oxygenation index values (C: 13.3 ⫾ 2.3 (MAPx%O2/PaO2), S: 10.7 ⫾ 1.6, S ⫹ PIP: 5.6 ⫾ 0.4, S ⫹ Imi: 8.2 ⫾ 2.0; p ⬍ 0.05, one-way ANOVA) and ventilation efficiency index values (C: 0.09 ⫾ 0.01 (3800/(PeakPEEP)xfxPaCO2), S: 0.11 ⫾ 0.01, S ⫹ PIP: 0.20 ⫾ 0.01, S ⫹ Imi: 0.17 ⫾ 0.05; p ⬍ 0.05), respectively. Moreover, aSMase-inhibition increased specific compliance of the respiratory system, and reduced airway resistance and extra-vascular lung water index. Cell concentrations in BALF differed between the groups (C: 435 ⫾ 95 cells/␮L, S: 326 ⫾ 98, S ⫹ PIP: 149 ⫾ 46, S ⫹ Imi: 223 ⫾ 44, p ⬍ 0.05) affecting mainly CD14 ⫹ and CD18 ⫹ cells. Conclusions: The naturally occurring aSMase-inhibitor PIP significantly improves gas exchange and lung function in this neonatal inflammatory lung injury model and deserves further evaluation for its clinical use in respiratory failure.

Jin Won Huh, Yunyoung Park, Asan Medical Center, Chae-Man Lim, Asan Medicial Center, Younsuck Koh, ASAN Medical Center Univ. of Ulsan College of Medicine, Sang-Bum Hong, Asan Medical Center Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain a serious problem in health care because it carries a high mortality (up to 30-40%) and morbidity. Recent study reported that intrapulmonary via the trachea treatment with mesenchymal stem cells (MSCs) improved survival and reduced pulmonary edema formation in endotoxin-induced ALI in mice, although the exact mechanisms of benefit were not identified. Hypothesis: Our goal was to determine whether stem cell type makes a difference in the repair of acute lung injury (ALI). We tested the capacities of bone marrow cells (BMC) and mesenchymal stem cells (MSC) to repair endotoxin-induced acute lung injury. Methods: 7-week-old C57BL/6 male mice (Orient, South Korea) were used. ALI was then induced by the instillation of LPS from Escherichia coli 055:B5 intratracheally (i.t.). Then, 4h after the induction of injury, mice were given either MSC (7.5⫻105 cells in 30 ml medium) or whole bone marrow (BM) cell (1.5⫻106 cells in 30 ml medium) i.t. At the end of 48h, samples were collected from each mouse for assessment of lung injury, biochemical analysis, and histology. Results: ⫻The BMC (54.5 ⫾ 16.2⫻104/ml vs. 81.0 ⫾ 30.7⫻104/ml, p ⬍ 0.05) or MSC (42.1 ⫾ 12.9⫻104/ml vs. 81.0 ⫾ 30.7⫻104/ml, p ⬍ 0.05) treatment significantly decreased neutrophil count in bronchoalveolar lavage (BAL) fluid compared with LPS treatment. The BMC (0.38 ⫾ 0.09 mg/ml vs. 0.67 ⫾ 0.31 mg/ml, p ⬍ 0.05) treatment significantly decreased protein in BAL fluid compared with LPS treatment. TNF-␣ (175.1 ⫾ 174.9 pg/ml vs. 354.6 ⫾ 252.9 pg/ml, p ⬍ 0.05) level and IL-1␤(77.7 ⫾ 49.1 pg/ml vs. 158.9 ⫾ 11.9 pg/ml, p ⬍ 0.05) level in BMC treatment were significantly decreased compared with LPS treatment. IL-6 (281.7 ⫾ 168.8 pg/ml vs. 588.2 ⫾ 107.0 pg/ml, p ⬍ 0.05) level in MSC treatment were significantly decreased compared with LPS treatment. Conclusions: We found that BMC and MSC attenuate endotoxininduced ALI and the difference of stem cell lineage may induce a difference in the repair of acute lung injury

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GROUPVIB PHOSHOLIPASEA2 IS ASSOCIATED WITH ACUTE LUNG INJURY FOLLOWING TRAUMA AND HEMORRHAGIC SHOCK

ENDOTHELIN-1LEVELS AND MARKERS OF OXIDATIVE STRESS IN REGIONAL ATELECTASIS OF THE LUNG

Koji Morishita, Junichi Aiboshi, Saori Mikami, Yasuhiro Otomo, Tokyo Medical and Dental University, Tetsuyuki Kobayashi, Ochanomizu University Introduction: A variety of inflammatory mediators enter into the systemic circulation through the mesenteric lymph duct after hemorrhagic shock, thus leading to acute lung injury(ALI)/multiple organ dysfunction syndrome (MODS). Recent studies reported that post-hemorrhagic shock mesenteric lymph (PHSML) contains pro-inflammatory mediators which activates neutrophils/vascular endothelial cells. Our studies have demonstrated that the PHSML contains biologically active lipids, such as lyso-phosphatidylcholines and lyso-phosphatidylethanolamines with linolic acid and arachidonic acid. Hypothesis: We hypothesize that GroupVIB phosholipaseA2 (iPLA2␥) may be the enzyme involved in the production of these lipids. The purpose of our study is to determine the role of iPLA2␥ in acute lung injury following trauma and hemorrhagic shock (T/HS) using (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL), an iPLA2␥ specific inhibitor. Methods: Male SD rats were anesthetized and femoral artery and jugular vein were cannulated. A midline laparotomy (trauma) was performed. The blood was withdrawn via jugular vein from the T/HS group until the MAP was reduced to 40 mmHg and maintained for 30 minutes. The animals were resuscitated over 2 hours with shed blood and normal saline. Evans blue dye (EBD) was injected and then the lungs were harvested. The trauma and sham shock (T/SS) group underwent the same procedures without shock and resuscitation.The concentration of EBD was measured by the EBD method.Rats were randomly allocated into three groups: T/SS ⫹ dimethyl superoxide (DMSO), T/HS ⫹ DMSO, T/HS ⫹ BEL. BEL or DMSO was injected into the artery 30 minutes before T/HS or T/SS. The final concentration of BEL was calculated to be 10␮M. Results: Lung permeability of T/HS ⫹ BEL (0.024 ⫾ 0.0041␮g/g of tissue wt) was significantly decreased in comparison to that of T/HS ⫹ DMSO (0.044 ⫾ 0.01␮g/g of tissue wt; p ⬍ 0.01) . Fortheremore lung permeability of T/HS ⫹ BEL was not significantly different from that of T/SS ⫹ DMSO (0.019 ⫾ 0.014␮g/g of tissue wt; p ⫽ 0.899). Conclusions: BEL attenuates pulmonary permeability following T/HS.iPLA2␥ may be the key enzyme involved in the pathogenesis of ALI/MODS.


Manish Lavhale, Midwestern University, Chinedu Oranu, Suresh Havalad, Advocate Lutheran General Hospital, Seema Briyal, Midwestern University, Anil Gulati, Midwestern University, College of Pharmacy Introduction: Regional atelectasis of the lung is commonly seen in critically ill infants and children, and predisposes the collapsed area to hypoxic pulmonary vasoconstriction (HPV).The mechanisms responsible for HPV, however, are poorly understood. Hypothesis: We hypothesized that levels of endothelin (ET1), a major pulmonary vasoconstrictor, would be increased in atelectasis and that there would be evidence of increased oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH). Methods: Mechanically ventilated male Sprague Dawley rats served as either atelectatic subjects or controls. Atelectasis was induced by right thoracotomy and manual prevention of right lung expansion. Control animals underwent a right thoracotomy without causing lung collapse. Plasma ET-1 levels and blood gases were obtained at various time intervals. Following 3 hours of mechanical ventilation the animals were euthanized and their lungs harvested. Lungs were analyzed for levels of ET-1 and oxidative stress markers MDA, SOD and GSH. Results: There were no differences in pH, paCO2 and paO2 between the two groups. Plasma ET-1 levels in the atelectatic group(44.66 ⫹/⫺ 5.88 pg/mL) were similar (p0.3163) to control animals(53.24 ⫹/⫺5.20 pg/mL). Similarly ET-1 levels in the lungs of atelectatic animals(0.76 ⫹/⫺0.07 pg/ug) were similar (p ⫽ 0.146) to the lungs of control animals (0.62 ⫹/⫺0.06 pg/ug). Plasma MDA levels were increased (p ⬍ 0.01) in atelectatic group (48.2 ⫹/⫺8.7 nM/mL)compared to control group (15.8 ⫾ 1.1 nM/mL). MDA levels in lung tissue were also increased (p ⫽ 0.0012) in atelectatic group (171.8 ⫾ 11.4 nM/g wet tissue) compared to control group (118.3 ⫾ 3.6 nM/g wet tissue). SOD levels in lung tissue were decreased (p ⫽ 0.0068) in atelectatic group (5.4 ⫾ 0.4 U/mg protein) compared to control group(17.0 ⫾ 2.8 U/mg protein). There was no change in GSH levels. Conclusions: Hypoxic pulmonary vasoconstriction seen in atelectasis does not appear to be mediated by ET-1. However evidence of significant oxidative stress in atelectatic lungs would suggest that hypoxic pulmonary vasoconstriction is mediated by reactive oxygen species.

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THE ADDITIVELY PROTECTIVE EFFECT OF XUEBIJING AND ULINASTATIN ON PARAQUAT-INDUCED LUNG INJURY IN RATS

PREOPERATIVE ANGIOTENSIN I-CONVERTING ENZYME INHIBITOR/ANGIOTENSIN II RECEPTOR BLOCKER ADMINISTRATION IS ASSOCIATED WITH A REDUCED INCIDENCE OF EARLY POSTOPERATIVE ACUTE LUNG INJURY

Xiao-Liang Liu, Ming-Li Sun, Hai-Feng Li, Ya-Xin Yu, Yuan Yuan, Yan Tan, First Affiliated Hospital of Jilin University , Gui-Lan Ye, Qiqihar Medical University Introduction: Acute Paraquat (PQ) poisoning results in high mortality rate due to hypoxemia secondary to lung fibrosis. Hypothesis: The present study aimed to evaluate the protective effect of Xuebijing (XBJ), Ulinastatin (Uli), and the combination against PQ-induced lung toxicity in Wistar rats. Methods: Rats were divided into control, PQ, XBJ, Uli, and XBJ ⫹ Uli group (n ⫽ 30each). They received saline as control or PQ (40mg/kg p.o.) to induce lunginjury, then treatment with saline, saline, XBJ (10ml/kg, i.p.), Uli (20, 000iu/kg, i.p.), or the combination twice a day respectively. Five rats from eachgroup were used for pathological examination of lung injury with HE andMasson’s trichrome staining and semi-quantitative measurement oftransforming growth factor beta 1 (TGFb1) in immunohistochemistry at day1, 3, 7, 14, 21 and 28. Results: One dose of PQ intoxication resulted in alveolar septa thickening, small blood vessels dilation, pulmonary interstitial edema, alveolar structure disruption, and collagen deposition from day 1 to 7, then spotty hemorrhage, necrosis, at day 14. At day 21 to 28 inflammatory cells infiltration started to subside with appearance of alveolar septalthickening, alveolar fusion, and fibrosis. These changes were significantlyameliorated in all three treatment groups. The intensity of TGF-b1 signal forPQ group was two fold over control group but significantly reduced withtreatment (p ⬍ 0.01 for all treatment groups comparing to PQ group, ANOVA, Bonferroni) at the time points studied. Furthermore, the protective effect ofthe combination was additive. Conclusions: These data demonstrated histopathologically the protective effect of XBJ, Uli, and in combination against PQ-induced lung injury, recommending them to clinical managementof PQ toxicity. This protective effect might be mediated through inhibition of PQ-induced TGF-1b overexpression in rat lung.

Anas Alsara, Mayi Clinic, Guangxi Li, Vitaly Herasevich, Osama Alsara, Mayo Clinic, Ognjen Gajic, Mayo Graduate School of Medicine (Rochester), Daryl Kor, Mayo Clinic (CCM) Introduction: Acute lung injury (ALI) is a devastating postoperative complication with an estimated mortality exceeding 45% in certain surgical populations. The pathogenesis of ALI is believed largely mediated by activation of the inflammatory cascade. Angiotensin I-converting enzyme (ACE) plays an important role at multiple levels of this cascade. ACE inhibitors (ACE-I) and Angiotensin II receptor blockers (ARB) may suppress the inflammatory response and protect against ALI. Hypothesis: We aimed to evaluate the association between preoperative ACE-I and/or ARB administration and early postoperative ALI in patients undergoing elective high-risk surgery. Methods: We performed a retrospective cohort evaluation of the association between preoperative ACE-I/ARB therapy and early postoperative ALI. The study population included consecutive elective high-risk surgery patients undergoing general anesthesia of ⬎ 3 hours duration. Postoperative ALI was considered present if American-European Consensus Conference criteria for ALI were met within the first 5 postoperative days. Univariate analysis was performed to evaluate the association between preoperative ACE-I/ARB administration and postoperative ALI. To control for potential ACE-I/ARB indication bias and other confounding factors, we performed a multivariate logistic regression analysis of the association between ACE-I/ ARB administration and early postoperative ALI. Variables included in this multivariate model included preoperative ACE-I/ARB administration, age, sex, CHF, CAD, HTN, DM, COPD, ILD, and immunosuppressive therapy. Results: Out of 4366 surgical patients, 1675 were receiving preoperative ACE-I and/or ARB therapy. The frequency of early postoperative ALI among those who were receiving ACE-I/ARB therapy versus those who were not was 3.0% vs. 2.3% (OR ⫽ 0.78, 95% CI ⫽ 0.53 - 1.14; p ⫽ 0.19). After multivariate adjusting, the odds ratio for early postoperative ALI in those who were exposed to preoperative ACE-I/ARB therapy versus those who were not was 0.62 (95% CI ⫽ 0.41 - 0.94, p ⫽ 0.03). Conclusions: After adjusting for pertinent confounding variables, preoperative ACE-I/ARB therapy was associated with a reduced incidence of early postoperative ALI.

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SURFACTANT DYSFUNCTION CORRELATES WITH THE DEGREE OF PERMEABILITY INJURY IN A MOUSE MODEL OF LUNG CONTUSION

THE ACTIVITY OF TRANSGLUTAMINASE-2 IN LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY

David Machado, University of Michigan, Z Wang, University of Rochester, Bi Yu, University of Michigan, Robert Notter, University of Rochester, Krishnan Raghavendran, UMHS Introduction: Lung contusion (LC) is an independent risk factor for ALI/ARDS. Using a bilateral model of LC in rats, previous studies in our lab suggest that the degree of surfactant dysfunction correlate with inflammation. The current study was under taken to evaluate the nature and timing of surfactant dysfunction in mouse model of unilateral LC. Hypothesis: Surfactant dysfunction in LC correlates with the degree of permeability injury. Methods: Using a mouse model of non-lethal unilateral LC, mice were sacrificed at 5, 24, 48 and 72 hours following the insult (n ⫽ 6-9).At the time of harvest, individual mice were subjected to BAL and measurement of P-V compliance using a Flexivent. The BAL was centrifuged and cell fee BAL was analyzed for total phospholipid (phosphorus assay of Ames) and total protein (permeability injury) was determined by modified Lowry with the addition of 15% SDS to allow accurate quantification in the presence of lipid. The content of large aggregates as a percentage of total BAL phospholipid was determined by phosphate assay. Data expressed as mean ⫾ SEM; comparisons with ANOVA, p ⬍ 0.05*. Results: After initial LC injury, BAL composition changes as early as 5 hours. Compared to controls, injured animals have a decrease in the percentage of large aggregates in their BAL fluid (51.14 ⫾ 1.46 v. 27.17 ⫾ 2.02 at 5 h and 32.96 ⫾ 0.98 at 24 h). Corresponding increases in the concentration of phospholipids in the surfactant content (0.22 ⫾ 0.01 v 0.23 ⫾ 0.01 mg/ml at 5 h and 0.26 ⫾ 0.01 mg/ml at 24 h) as well as BAL protein from 152.9 ⫾ 5.63 mcg/ml peaking to 1111.16 ⫾ 121.81 mcg/ml at 24 h, were observed. These changes in surfactant composition correlate with decreases in lung compliance: Vmax (volume at pressure of 30 cm H20) is significantly decreased at 24 h (0.542 ⫾ 0.01v 0.443 ⫾ 0.1 ml). The surfactant composition and lung mechanics start to improve by 72 h. Conclusions: Surfactant dysfunction in unilateral model of ung contusion correlate with the degree of permeability injury.

Je Hyeong Kim, Korea University Ansan Hospital, Min Hyun Suk, CHA University, Dae Wui Yoon, Se Joong Kim, Korea University Ansan Hospital, Eun Joo Lee, Korea University Anam Hospital, Gyu Young Hur, Sung Yong Lee, Korea University Guro Hospital, Sang Yeub Lee, Korea University Anam Hospital, Chol Shin, Korea University Ansan Hospital Introduction: Transglutaminase-2 (TG-2), the most ubiquitous member of transglutaminase, has been reported to play an important role in the process of inflammation. However, the studies about the TG-2 in ALI are very sparse. Hypothesis: The TG-2 plays a pivotal role in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Methods: Specific pathogen-free, 5 weeks of age, male C57BL/6 mice were used. Through the midcervical incision and exposure of trachea, ALI was induced by an intratracheal instillation of LPS 0.5 mg/Kg/50 ␮L of saline. At 3, 6, 12, 24, 36, 48 and 72 hours after LPS administration, TG-2 activities were measured in the lung tissue homogenates (n ⫽ 6 at each time point) and compared those of the control mice (n ⫽ 6). TG-2 activity was measured using fluorescence based protein arrays. The TG-2 activity was expressed as relative fluorescence units (RFU). Results: The TG-2 activities in the control group (23577.75 ⫾ 869.54 RFU) and at each time points (3H: 27090.08 ⫾ 779.47 RFU, 6H: 24390.40 ⫾ 2568.76 RFU, 12H: 27756.40 ⫾ 1740.85 RFU, 24H: 31207.50 ⫾ 2512.60 RFU, 36H: 34255.10 ⫾ 1231.69 RFU, 48H: 33764.70 ⫾ 4001.56 RFU and 72H: 33264.10 ⫾ 4546.33 RFU) were signigicantly different (p ⫽ 0.000 by Kruskal-Wallis test). Compared with TG-2 activity of the control group, the TG-2 activities of 12H, 24H, 36H, 48H, and 78H were significantly higher than the control group (p ⬍ 0.05). The TG-2 activity was peaked at 36 hours after LPS administration. Conclusions: In LPS-induced ALI, TG-2 activity increases significantly from early to late phase, and peaks at 36 hours after the insult. These results strongly suggest the important roles of TG-2 in the pathogenesis of ALI.


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PRONE POSITIONING ATTENUATES LUNG INFLAMMATORY INJURY IN AN ACUTE LUNG INJURY MODEL IN RABBITS UNDER HIGH-FREQUENCY OSCILLATORY VENTILATION

EPINEPHRINE INDUCES PULMONARY EDEMA THROUGH AN INCREASE IN CARDIAC OUTPUT

Jose Fioretto, Botucatu Medical School - Sao Paulo State University - UNESP, Rafaelle Batistella, Sao Paulo State University- Botucatu Medical School.UNESP, Rossano Bonatto, Botucatu Medical School - Sao Paulo State University-UNESP, Brazil, Mario Carpi, Botucatu Medical School - Sao Paulo State University-UNESP, Cilmery Kurokawa, Marcos Moraes, Botucatu Medical School - Sao Paulo State University-UNESP, Brazil Introduction: Prone positioning associated with high-frequency oscillatory ventilation (HFOV) may increase lung protection. Hypothesis: The objective of this study was to compare prone and supine positioning for oxygenation (PaO2 and oxygenation index) and lung inflammatory injury (tumor necrosis factor-alpha in bronchoalveolar lavage) in an experimental model of acute lung injury (ALI) induced in rabbits under HFOV. Methods: Thirty rabbits were instrumented and randomly assigned to two groups: 1) ALI animals under HFOV ⫹ supine position (Supine Group; SG, n ⫽ 15); 2) ALI animals under HFOV ⫹ prone position (Prone Group; PG, n ⫽ 15). Lung injury was induced by tracheal saline infusion (30mL/kg, 38°C).Initially, HFOV was set at 16 cmH2O mean airway pressure (MAP). Every 30 minutes, MAP was reduced to 14, 12, and then 10cmH2O. After two hours, animals from both groups were placed in supine position for 30 minutes. Results: Lung injury decreased pulmonary compliance (SG before: 3.48 ⫾ 0.69 ⬎ SG after: 1.13 ⫾ 0.22mL/Kg/cmH2O; p ⬍ 0.05 – PG before: 3.64 ⫾ 1.06 ⬎ PG after: 1.21 ⫾ 0.28mL/Kg/cmH2O; p ⬍ 0.05) and oxygenation (PaO2 - SG before: 427.92 ⫾ 89.88 ⬎ SG after: 68.18 ⫾ 19.08 – PG before: 448.06 ⫾ 91.96 ⬎ PG after: 63.81 ⫾ 19.08; p ⬍ 0.05). After 150 minutes of HFOV, there was no statistically significant difference in PaO2 or oxygenation index between groups at each moment. However PG showed a significant reduction in TNF-alpha levels compared with SG (PG: 0.32 ⫾ 0.2 ⬍ SG: 0.96 ⫾ 0.9ng/mL; p ⬍ 0.05). Conclusions: Prone positioning associated with HFOVattenuates lung inflammation compared to supine position in ALI rabbits.


Vijay Krishnamoorthy, University of Illinois Hospital, Stephen Vogel, University of Illinois at Chicago, Guy Weinberg, University of Illinois College of Medicine, Richard Minshall, University of Illinois at Chicago, David Hiller, University of Illinois College of Medicine Introduction: Intravenous epinephrine injection has been the standard clinical maneuver employed to resuscitate patients in cardiac arrest; using an isolated, perfused lung preparation, we address the edemagenesis mechanism of high-dose epinephrine on the pulmonary system. Hypothesis: We predict that epinephrine may exert an indirect effect on the pulmonary system, through an increase in cardiac output; this may lead to clinically significant pulmonary edema. Methods: Murine lungs were isolated under anesthesia (2.5% isoflurane), ventilated at 120 breaths/min (PIP, 10 cm H2O), and perfused at various flow rates (RPMI medium). We continuously monitored lung wet weight, pulmonary arterial pressure (Ppa), and left atrial pressure (Ppv) during experiments. Brief (5 sec), simultaneous occlusions of the arterial inflow and venous outflow paths were implemented at 5-min intervals with the aid of electronic valves. Pulmonary capillary pressure (Ppc) was estimated by the measured double-occlusion pressure. Results: In 6 isolated, constantly perfused lung preparations (2 ml/min), epinephrine (100 ␮M) decreased lung wet weight. Epinephrine increased pulmonary arterial pressure from 10 to 16 cm H2O. Despite the increase in Ppa, epinephrine raised Ppc by only 2 cm H2O - this was insufficient to cause pulmonary edema. Calculations confirmed that epinephrine increased precapillary resistance in the pulmonary circulation, which thus limited the rise in Ppc. In 3 preparations, increasing the perfusion rate to simulate the beta effect of epinephrine (from 2 to 4 ml/min) doubled Ppc and thereby produced an increase in lung wet weight (pulmonary edema); subsequent addition of epinephrine produced a mild further increase in Ppc and lung wet weight. Conclusions: A higher cardiac output induced by epinephrine leads to increased pulmonary capillary pressures; this has the potential to cause clinically significant pulmonary edema.

Poster: Basic Science: Renal 167 FGF-2: A NOVEL URINARY BIOMARKER FOR ACUTE KIDNEY INJURY IN CHILDREN WITH CRITICAL ILLNESSES Kitman Wai, Angel Soler-Garcia, Sofia Perazzo, Patricio Ray, Children’s National Medical Center Introduction: Acute kidney injury (AKI) causes significant morbidity in pediatric intensive care units (ICU). New urinary biomarkers are needed to identify children with AKI in a timely manner. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a highly sensitive predictor of AKI in children with septic shock. Previous studies show that the urinary levels of Fibroblast Growth Factor-2 (FGF-2) and Epidermal growth factor (EGF) might be promising biomarkers to identify children undergoing acute kidney injury. Hypothesis: A biomarker profile corresponding to urinary levels of NGAL, FGF-2, and EGF will identify children undergoing AKI secondary to sepsis or shock, and be useful to follow their renal outcome. Methods: In a prospectively observational pilot study in a large urban children’s hospital, urine samples were collected from 27 children at risk of AKI admitted to PICU with sepsis, shock, or after cardiopulmonary bypass (ECMO). AKI was defined by the p-RIFLE criteria. The urinary levels of NGAL, FGF-2, and EGF were measured by ELISA. All values were expressed as a ratio of the urinary creatinine (UCr), and adjusted to the normal values for age. ROC analysis was performed to generate cut-off values for each biomarker and define their sensitivity and specificity. Differences between two or more groups were compared using the Student-Newman-Keul’s test, ANOVA, Chi-square for trend, or Fisher’s exact test. Results: Five out of 17 septic children and 6 out of 11 ECMO children developed AKI. A urinary cut-off value of NGAL above 150 ng/mg was highly sensitive (1.0) but not specific (0.25) to identify children with AKI. The urinary cut-off values for FGF-2 adjusted for age were less sensitive (0.91) but more specific (0.62) than NGAL. In contrast urinary EGF was less sensitive and specific when compared to NGAL or FGF-2 respectively. Conclusions: Our findings suggest that the urinary levels of NGAL in combination with FGF-2, an angiogenic growth factor released by injured endothelial and tubular epithelial cells, may provide a highly sensitive and more specific biomarker tool to identify critically ill children undergoing AKI secondary to sepsis and other forms of shock.


Poster: Basic Science: Sepsis-1 171

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RADICICOL INHIBITS IL-8 GENE EXPRESSION IN CULTURED RESPIRATORY EPITHELIAL CELLS

MINERALOCORTICOID THERAPY IMPROVES SHOCK, LUNG DYSFUNCTION, AND SURVIVAL IN A CANINE MODEL OF BACTERIAL PNEUMONIA

Derek Wheeler, Patrick Lahni, Cincinnati Children’s Hospital Medical Center, Basilia Zingarelli, Children’s Hospital Medical Center, Hector Wong, Cincinnati Children’s Hospital Medical Center Introduction: Radicicol, a macrocyclic antifungal antibiotic originally isolated from the fungus Monosporium bonorden has been shown to inhibit the transcription factors AP-1 and NF-␬B. NF-␬B plays an important role in the pathobiology of sepsis and acute lung injury. Several pro-inflammatory genes are regulated at the transcriptional level by NF-␬B, including the neutrophil chemokine, interleukin (IL)-8. Hypothesis: We hypothesized that radicicol inhibits IL-1␤mediated activation of IL-8 gene expression in cultured respiratory epithelial cells, primarily through inhibition of NF-␬B. Methods: Human lung epithelial (A549) cells were treated with IL-1␤ (1 ng/mL) following pre-treatment with radicicol at 0, 50, 100, 300, or 500 ng/mL for 1 h. IL-8 gene expression was directly measured via ELISA. IL-8 promoter activity was measured by transient transfection with an IL-8 promoter luciferase reporter plasmid. NF-␬B activation was measured by EMSA. Radicicol toxicity was assessed with MTT assay. Experiments were performed at least 3 times in duplicate and data were compared by ANOVA. A p-value ⬍ 0.05 was considered significant. Results: Radicicol was not toxic to the A549 cells at the range of doses used in these experiments (data not shown). IL-1␤ treatment significantly increased IL-8 levels, by ELISA, compared to control (5687 pg/mL vs 219 pg/mL, p ⬍ 0.05). Radicicol treatment produced a dose-dependent reduction in IL-8 levels (Rad50 1178 pg/mL, Rad100 1235 pg/mL, Rad300 504 pg/mL, Rad500 481 pg/mL, p ⬍ 0.05). Similarly, radicicol inhibited IL-1␤-induced IL-8 promoter activity in a dosedependent manner (7.4 fold induction by IL-1␤ decreased to 1.5 fold induction with Rad500, p ⬍ 0.05). IL-1␤ significantly increased NF-␬B activation, by EMSA. In contrast, radicicol produced a dose-dependent and significant reduction in NF-␬B activation. Conclusions: Radicicol inhibits IL-1␤-mediated activation of IL-8 gene expression in cultured respiratory epithelial cells, primarily through inhibition of NF-␬B. Future studies will attempt to extend these findings to a murine model of acute lung injury. Supported by NIH K08 GM077432

Caitlin Hicks, Daniel Sweeney, Robert Danner, Peter Eichacker, Anthony Suffredini, Jing Feng, Junfeng Sun, National Institutes of Health, Ellen Behrend, Auburn University, Steven Solomon, Charles Natanson, National Institutes of Health Introduction: Corticosteroid therapies with both glucocorticoid and mineralocorticoid activity have consistently reversed vasopressor-dependent hypotension in clinical trials of septic shock. Mineralocorticoids have not been studied alone in septic patients or animals. Hypothesis: Septic shock can be ameliorated by treatment with a mineralocorticoid agonist alone. Methods: A selective mineralocorticoid agonist, desoxycorticosterone pivalate (DOCP; 2.2 mg/kg IM given 72 h prior to bacterial challenge to produce therapeutic concentrations by T0), was studied over 96 h in a canine model of Staphylococcus aureus pneumonia. Results: DOCP was associated with improved survival [control (n ⫽ 17) 12% vs. DOCP (n ⫽ 19) 58%; p ⫽ 0.0002], lower mean norepinephrine requirements (p ⫽ 0.01), A-aO2 gradients (p ⫽ 0.004), and plateau pressures (p ⫽ 0.004); and higher mean MAP (p ⫽ 0.004) and CVP (p ⫽ 0.02). DOCP also reduced sepsis-associated fever (p ⫽ 0.006), serum or plasma aldosterone concentrations (p ⫽ 0.02), ACTH (p ⫽ 0.04), serum creatinine (p ⫽ 0.05), lactate (p ⫽ 0.02), and IL-6 (p ⫽ 0.04) concentrations, and AST activity (p ⫽ 0.03) compared to controls. Similarly in controls and DOCP animals, infection caused significant increases in basal cortisol levels (p ⫽ 0.0001) and reversible loss of cortisol responsiveness to ACTH stimulation, that in survivors returned to baseline by 48 h. Conclusions: DOCP appeared to improve survival by maintaining intravascular volume and limiting non-cardiogenic pulmonary edema without altering adrenal glucocorticoid function. DOCP also reduced fever, stress hormone secretion, cytokine release, and markers of organ injury. Selective mineralocorticoid ligands may warrant further investigation in patients with septic shock.

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DECREASED MORTALITY FOLLOWING EPIDERMAL GROWTH FACTOR TREATMENT IS ASSOCIATED WITH ATTENUATED INTESTINAL INJURY IN PSEUDOMONAS AERUGINOSA PNEUMONIA

ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN KINASE MEDIATES SKELETAL MUSCLE PROTEIN CATABOLISM IN MECHANICALLY VENTILATED SEPTIC PIGS

Jessica Dominguez, Ludmila Khailova, University of Colorado Denver School of Medicine, Paul Vithayathil, Chris Lawrance, Washington University School of Medicine, Craig Coopersmith, Emory University School of Medicine Introduction: Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. Hypothesis: We hypothesized that EGF treatment would attenuate intestinal injury and improve mortality in a murine model of Pseudomonas aeruginosa pneumonia. Methods: Mice were intratracheally injected with 2-4x108 CFU P. aeruginosa or saline and treated with or without EGF (150 ␮g/kg/d i.p.). At 24 hr, intestine and lungs were evaluated for injury. For survival studies, EGF was given immediately postoperatively or 24 hr later and mice were followed for 7 days. To determine if EGF protection is gut-specific, transgenic mice that overexpress EGF exclusively in enterocytes and WT mice were subjected to pneumonia and followed for survival. Results: EGF treatment decreased mortality from 65% to 10% when initiated immediately after the onset of pneumonia (p ⬍ 0.001) and to 27% when initiated 24 hr after the onset of pneumonia (p ⬍ 0.05). The survival advantage conferred by EGF was not associated with improvements in pneumonia-induced pulmonary pathology, myeloperoxidase activity, lung apoptosis, or systemic cytokine levels. However, EGF caused significant restoration of intestinal integrity by reversing pneumonia-induced increases in gut epithelial apoptosis (9 ⫾ 1 vs. 16 ⫾ 1; p ⬍ 0.001) and decreases in intestinal proliferation (858 ⫾ 55 vs. 672 ⫾ 54; p ⬍ 0.05) and villus length (386 ⫾ 13 vs. 245 ⫾ 7 ␮m; p ⬍ 0.001). Mice that overexpress EGF exclusively in enterocytes had improved survival compared to WT mice following pneumonia (50% vs. 28%; p ⬍ 0.05) and were protected from pneumonia-induced gut injury. Conclusions: Systemic administration of EGF preserves intestinal integrity and improves survival in P. aeruginosa pneumonia. Further, EGF protection appears to be mediated in an intestine-specific fashion. Thus, EGF may be a novel therapeutic agent that could be used to target the deleterious extrapulmonary effects seen in pneumonia.


Neeraj Srivastava, Maria Gazzaneo, Agus Suryawan, Samer El-Kadi, Roberto Torrazza, Marta Fiorotto, Hanh Nguyen, Rosemarie Almonaci, Teresa Davis, Baylor College of Medicine, Renan Orellana, Texas Children’s Hospital Introduction: Mechanical ventilation (MV) of septic patients leads to loss of muscle mass and failure to thrive. AMP-activated protein kinase (AMPK) acts as a cellular energy sensor of AMP to ATP ratio and plays an important role in muscle protein metabolism. AMPK mediates translation initiation by modulating mammalian target of rapamycin (mTOR) and degradation by affecting muscle RING-finger protein-1 (MURF-1) and muscle Atrophy F-box (MAFbx)/ atrogin-1. Hypothesis: We hypothesize that MV and sepsis affect peripheral skeletal muscle protein synthesis and degradation through an AMPK dependent mechanism. Methods: Neonatal pigs (n ⫽ 8-10/group) were sedated and subjected to MV for 9 hours (MV group) in the presence of LPS (MVLPS group), as well as dextrose and amino acids. Fractional protein synthesis rates and translation and degradation signals were determined in longissimus dorsi muscle. Results: Plasma insulin levels were higher with MV and further increased in the presence of LPS. Compared to controls, fractional protein synthesis rate in muscle decreased by 22% with MV and by 32% in MVLPS group. MV alone increased AMPK phosphorylation, which was enhanced by addition of LPS. Despite increased phosphorylation of PKB in response to higher levels of insulin, TSC 2 phosphorylation decreased in MV and MVLPS groups while mTOR phosphorylation decreased in the presence of LPS only. MV decreased eIF4G●eIF4E association, which further decreased in the MVLPS group. MV increased MURF-1 and atrogin-1 abundance, and atrogin-1 further increased with addition of LPS. Muscle and plasma ␣-actin, a product of myofibrillar degradation, increased in response to MV, and augmented further in the presence of LPS. Conclusions: These findings show that mechanical ventilation and sepsis, alone and in combination, lead to AMPK activation in peripheral skeletal muscle, which is associated with decreased protein synthesis, inhibition of translation initiation, and enhanced proteolysis. Plasma ␣-actin levels can be used as a tool to assess muscle degradation in critical illness.

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EFFECT OF A GLP-1 RECEPTOR AGONIST ON NEUTROPHIL COUNT, TNF-ALPHA AND IL-1BETA CONCENTRATIONS IN A RAT MODEL OF SEPSIS

THE BLACK TEA POLYPHENOL THEAFLAVIN IMPROVES MORTALITY IN A MURINE MODEL OF ENDOTOXIN SHOCK

Ofer Yanay, Adam Bailey , Kalia Ulate, Kelly Kernan, Jerry Zimmerman , William Osborne, University of Washington

John Giuliano, Yale-New Haven Children’s Hospital, Patrick Lahni, Basilia Zingarelli, Hector Wong, Derek Wheeler, Cincinnati Children’s Hospital Medical Center

Introduction: GLP-1, a major incretin, is well characterized biochemically and widely used in treatment of type II diabetes. There is increasing evidence mostly from in vitro studies, indicating GLP-1 mediates a wide range of anti-inflammatory effects on the cardiovascular, pulmonary, renal and central nerve systems. Hypothesis: This study was designed to evaluate the effects of treatment with a GLP-1 Receptor agonist (GLP-1RA), exendin-4, on absolute neutrophil count (ANC) and pro-inflammatory cytokines (IL-1␤, TNF-␣) in a rat model of sepsis. We hypothesized it will improve neutrophil counts and attenuate the inflammatory response. Methods: 2 month old Whistar rats were used in all experiments. Sepsis was induced by intraperitoneal (IP) LPS injection (20 mg/Kg). Treatment group received IP exendin-4 (1micromole/Kg) 10 minutes later. Three control groups received IP injections of LPS/normal Saline (NS), NS/NS and NS/exendin-4. Blood samples were drawn before, 1, 3 and 6 hours following LPS injection. ANC was quantified using a coulter counter. IL-1␤ and TNF-␣ levels were measured using multiplex assay. Results: Rats injected with LPS developed neutropenia. IL-1␤ and TNF-␣ levels were elevated from baseline at 3 and 6 hours post LPS injection. Exendin-4 treatment prevented neutropenia (mean ANCs were 2.7, 0.9 and 0.6 compared to 3.1, 4.25, 4.7 [103] in LPS injected rats compared to LPS injection followed by exendin-4 treatment at 0, 3 and 6 hours respectively, p ⬍ 0.001 at 3 and 6h). Exendin-4 also reduced pro-inflammatory cytokine levels (mean TNF-␣ was 0, 317, 150 compared to 0, 19, 0; mean IL-1␤ was 7.7, 103, 119 compared to 7, 15.1, 17 in LPS injected rats compared to LPS injection followed by exendin-4 treatment at 0, 3, 6h respectively, p ⬍ 0.001 at 3 and 6 hours [all concentrations pg/mL]). Other control groups exhibited no significant changes in ANC, IL-1␤ and TNF-␣ levels from baseline. Conclusions: These data suggest that treatment with exendin-4 attenuated pro-inflammatory cytokine production and preserved neutrophil count in a rat model of peritoneal sepsis. Additional studies examining the potential clinical benefits of GLP-1RA in sepsis are warranted.

Introduction: The medicinal properties of tea are widely appreciated. We have previously shown that the green tea polyphenol EGCG inhibits pro-inflammatory gene expression in vitro and in vivo. Moreover, our group has shown that a similar tea polyphenol derived from black tea, theaflavin, inhibits pro-inflammatory gene expression in cultured respiratory epithelial cells, primarily through inhibition of the transcription factor, NF-␬B. Hypothesis: We hypothesized that theaflavin would improve mortality in a murine model of endotoxin shock. Methods: We used a murine model of endotoxin shock, in which a lethal dose of lipopolysaccharide (LPS), 60 mg/kg is administered via intraperitoneal injection to 4-6 week old C57Bl/6 mice. Three groups of mice (approximately 30 mice per group) were studied - LPS ⫹ DMSO vehicle, LPS ⫹ theaflavin, and theaflavin alone. Theaflavin stock solution was mixed in DMSO vehicle and administered at a dose of 10 mg/kg body wt via intraperitoneal injection, beginning at 1 hour following LPS and every 6 h thereafter. Survival was monitored for 5 days and analyzed with the log-rank test. A p-value ⬍ 0.05 was considered statistically significant. Results: LPS-treated mice developed signs and symptoms of systemic illness, with ruffled fur, decreased activity, and diarrhea. In contrast, these signs and symptoms did not develop in the mice treated with theaflavin. There were no deaths in the group of mice treated with theaflavin alone (16/16, 100% survival). As expected, LPS treatment significantly increased mortality, with only 26% (8/31) mice surviving at 5 days. Theaflavin treatment significantly decreased mortality following LPS administration, with 54% (21/39) mice surviving at 5 days (p ⬍ 0.05). Conclusions: The black tea polyphenol appears to have antiinflammatory effects in vivo and significantly improves survival in a murine model of endotoxin shock, even when administered after LPS. Future studies will hopefully provide additional mechanistic data and will extend these findings to a more clinically relevant model of septic shock. Supported by NIH K08 GM077432

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RECOMBINANT HUMAN MILK FAT GLOBULE EGF FACTOR 8 PRODUCES DOSE-DEPENDENT BENEFITS IN SEPSIS

EFFECTS OF HEMOADSORPTION ON INFLAMMATION IN E. COLI INDUCED FIBRIN PERITONITIS

Kavin Shah, Rongqian Wu, Asha Jacob, Ernesto Molmenti, Jeffrey Nicastro, Gene Coppa, Ping Wang, North Shore University Hospital and Long Island Jewish Medical Center

Rami Namas, University of Pittsburgh, Rajaie Namas, Hurley Medical Center, Derek Barclay, Qi Mi, University of Pittsburgh, Zhiyong Peng, University of Pittsburgh Medical Center, Morgan Dileo, Isabella Valenti, William Federspiel, University of Pittsburgh, John Kellum, University of Pittsburgh Medical Center, Yoram Vodovotz, University of Pittsburgh

Introduction: Sepsis remains a major healthcare burden. The morbidity and mortality from this condition requires us to find new strategies for treatment. Although various therapies have emerged to combat sepsis, the majority have failed. Animal milk fat globule EGF factor 8 (MFG-E8) is beneficial in multiple disease conditions. In this study, we plan to demonstrate a dose-dependent benefit with recombinant human MFG-E8 (rhMFG-E8) in a rat model of polymicrobial sepsis. Hypothesis: Human MFG-E8 reduces organ injury and inflammation in an animal model of polymicrobial sepsis, as well as improves survival in a dose-dependent manner. Methods: Male adult rats were subjected to cecal ligation and puncture (CLP) to induce polymicrobial sepsis. At 5h post-CLP, animals were infused with various doses of rhMFG-E8 (20 – 160 ␮g/kg) over 30 min in 1-ml normal saline. After 20h, animals were sacrificed, and blood was collected for evaluation of inflammatory cytokines as well as organ injury markers. A 10-day survival study was also performed in a separate group of animals. Results: At 20h after CLP, liver enzymes (AST, ALT), creatinine and lactate were all significantly increased as compared to Sham animals. Furthermore, pro-inflammatory cytokines IL-6, TNF-␣, and HMGB-1 were also significantly increased following CLP. Treatment with various doses of rhMFG-E8 produced significant reductions of up to 43% in AST, 49% in ALT, 45% in creatinine and 48% in lactate (P ⬍ 0.05). Furthermore, serum levels of IL-6, TNF-␣, and HMGB-1 demonstrated reductions of up to 44%, 50%, and 83% (P ⬍ 0.05), respectively, following treatment with rhMFG-E8. In a 10-day survival study, vehicle treated animals produced a 36% survival rate, whereas rhMFG-E8 significantly improved the survival rate up to 72% (P ⬍ 0.05). Conclusions: Administration with the human form of MFG-E8 significantly reduced organ injury and inflammation, as well as improving survival in an animal model of sepsis. Furthermore, we have demonstrated a dose-dependent effect with rhMFG-E8. These results show that human MFG-E8 can be developed as a potential therapy for patients with sepsis.

Introduction: Sepsis is projected to affect more than a million cases annually in 2020 in the US alone, with few therapeutic options. Hemoadsorption (HA) is an emerging approach to modulate sepsis-induced inflammation. We sought to define the effects of HA on inflammation in E. coli-induced fibrin peritonitis in rats. Hypothesis: We hypothesized that HA both reduces and reprograms inflammation. Methods: 14 Spraque-Dawley male rats (6-7 months; 430-480g) were subjected to a midline laparotomy followed by the introduction of fibrinencapsulated ATCC 25922 E. coli (1.5x108 – 2x108 CFU/clot). 24 h later, a femoral vein to ipsilateral internal jugular vein (IJV) extracorporeal circuit was established and HA bead column (MedaSorb Technologies, Princeton, NJ) was connected to a minipump. For Sham, all procedures were the same but without the HA column. Blood (IJV) samples were collected at 0, 1, 3, and 6 h of HA or Sham; peritoneal samples were collected at 0 and 6 h of HA or Sham. Collected samples were assayed for 14 cytokines (Luminex™). Data were analyzed using one way ANOVA followed by Tukey post hoc test (* ⫽ P ⬍ 0.05). Results: Baseline and 1h levels of cytokines in HA and Sham animals were the same (P ⫽ NS). At 3 and 6h, both TNF-␣ (P ⫽ 0.007 and 0.001, respectively) and IL-6 (P ⫽ 0.001 and 0.003, respectively) were lower in HA vs. Sham. Principal Component Analysis suggested that HA was influenced primarily by MCP-1, GRO/KC and IL-10, while Sham was influenced by MCP-1, IL-6 and TNF-␣. In vitro studies showed that HA columns adsorb IL-10 ⬎ TNF-␣, suggesting that compensatory responses account for the similar levels of IL-10 observed in HS and Sham, as well as for the driving role of IL-10 discerned from PCA. Conclusions: Our results suggest that HA may both reduce and reprogram inflammation in a rat model of bacterial sepsis.


Poster: Basic Science: Sepsis-2 180

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MODULATION OF CHEMOKINE GRADIENTS IMPROVES LEUKOCYTE TRAFFICKING IN DIFFERENT COMPARTMENTS DURING SEPSIS

MODULATION ON EXPRESSION AND FUNCTION OF CALCIUM AND POTASSIUM CHANNELS IN SEPTIC GUINEA PIG ATRIUM

Zhiyong Peng, Jeffery Bishop, Xiaoyan Wen, Gilles Clermont, John Kellum, University of Pittsburgh Medical Center

Noboru Hatakeyama, Toyama University Hospital, Yuta Aoki, University of Toyama, Hiroyuki Kinoshita, Wakayama Prefectural Medical College, Naoyuki Matsuda, Nagoya University, Mitsuaki Yamazaki, University of Toyama

Introduction: To modulate chemokines gradients between plasma and the nidus of infection using hemoadsorption (HA) and to determine whether changing chemokines gradients improves leukocyte function in animals with abdominal sepsis. Hypothesis: The chemokines gradients between the local and central compartments would determine the leukocyte trafficking among different compartments during sepsis. Methods: Sepsis was induced with cecal ligation and puncture (CLP). Forty rats were randomly assigned to either hemoadsorption (HA) or sham treatment 18h after CLP. HA consisted of a single 4 hr intervention using CytoSorbTM via a veno-venous circuit. Sham consisted of the same circuit but no HA. All animals were sacrificed 48h after treatment. Fluid from peritoneal lavage (PF) and bronchoalveolar lavage (BAL) as well as blood were collected for leukocyte counts, leukocyte function (chemotaxis, phagocytosis and oxidative burst), cytokines, chemokines, and bacterial culture. Tissues from the lung, liver, spleen and kidney were collected for myeloperoxidase (MPO) measurements. Results: HA decreased chemokines (CINC-1 and MCP-1) in the blood and BAL fluid. The ratios of PF to blood for both CINC-1 and MCP-1 were significantly higher after HA (1.99 vs 0.55 CINC-1; 2.85 vs 1.25 MCP-1, P ⬍ 0.05), and the ratios of BAL to blood in both CINC-1 and MCP-1 concentrations were lower (0.11 vs 0.39 CINC-1;0.05 vs 0.13 MCP-1, P ⬍ 0.05)) after HA compared to sham. HA significantly enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased polymorphonuclear leukocyte (PMN) recruitment into the lung (BAL fluid 1.3 x105 /ml HA vs 4.4 x105 /ml sham, P ⫽ 0.013). HA also significantly reduced MPO contents in the lung (0.98 vs 2.01 U/mg, P ⫽ 0.04). Conclusions: Modulation of chemokine gradients with HA enhanced leukocyte recruitment into peritoneal cavity and reduced PMN infiltration in the lung, which induced the improved bacterial clearance in the primary infection loci and the decreased secondary lung injury.

Introduction: Sepsis is a serious systemic disorder and tachyarrhythmia is often observed in the course of sepsis and sometimes resistant to drug therapy. We have previously reported that shortening of action potential duration, inhibition of L-type voltage dependent Ca2⫹ channel current (ICa), but not voltage dependent Na⫹ channel current, were observed in septic atrial myocyte. Hypothesis: Enhancement of repolarizing K⫹ current as well as the inhibition of ICa would be a reason for the shortening of action potential duration. So, we examined the expression of Ca2⫹ and K⫹ channels and monitored those channel currents in septic atrial myocyte. Furthermore, we examined the involvement of overexpressed NO for the modulation of channel function. Methods: Male Guinea Pigs were divided into four groups (control, LPS, LPS ⫹ L-NAME, L-NAME). LPS and L-NAME were injected intraperitoneally. After 10h of drug administration, hearts were removed. For the measurement of ionic channel currents, single atrial myocytes were prepared by enzymatic dispersion. In LPS and control groups, the expression level of Ca2⫹ and K⫹ channels, iNOS, and nitrotyrosine were examined by immunoblotting or immunostaining. Results: Whole cell voltage clamp experiments revealed the inhibition of ICa in septic state and it was reversed by the simultaneous administration of L-NAME. Delayed rectified K⫹ current (IK) was enhanced in septic state and this was also reversed by L-NAME treatment. Western blotting revealed that expression levels of Ca2⫹ channel decreased while that of K⫹ channel was enhanced in this condition. Also the LPS treatment enhanced the expression of iNOS and nitrotyrosine in the atrium. Conclusions: In septic state, inhibition of ICa and enhancement of IK were observed. And, expression of Ca2⫹ and K⫹ channels are altered in the atrium. Furthermore, overexpressed NO could have an effect on posttranslational modification. These changes may play a role for sepsis-induced tachyarrhythmia via shortening of action potential duration.

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ACTIVATED PROTEIN C INCREASES MICRORNA EXPRESSION FOLLOWING SEPSIS

COMBINED RHAPC AND CEFTAZIDIME PREVENTS AIRWAY OBSTRUCTION AND ARDS IN ACUTE LUNG INJURY AND SEPSIS

Cathy Moore, Iain McKillop, Toan Huynh, Carolinas Medical Center Introduction: Systemic sepsis remains a clinical challenge with mortality rates approaching 50%. Data from our group demonstrate activated protein C (aPC) improves endothelin-1 (ET-1)-mediated microcirculatory dysfunction in the liver during sepsis. MicroRNAs (miRNAs) represent critical mediators of mRNA translation. Recent studies report that hepatic ET-1 expression is regulated, at least in part, by miRNAs. Hypothesis: In the setting of systemic sepsis aPC selectively alters the expression of specific miRNAs implicated in regulating vasoactive peptides. Methods: Male Sprague-Dawley rats underwent sham or cecal ligation and puncture (CLP). Twenty-four later, animals were randomized and treated with aPC (1mg/kg) or vehicle (0.9% saline, w/v) via indwelling venous catheter twice daily for 4 days. Animals were subsequently sacrificed, hepatic tissue harvested, and total RNA isolated. RealTime PCR analysis was then performed to measure miR-199a-5p (ET-1-linked miRNA) and miR-122 (ubiquitous hepatic miRNA) expression. Results: No significant differences in hepatic miR-199a-5p or miR-122 expression were measured between untreated sham and CLP groups. Treatment with aPC significantly increased miR-199a-5p expression in CLP animals compared to both sham ⫹ aPC or CLP alone (8.3-fold and 8.5-fold increase; CLP ⫹ aPC vs sham ⫹ aPC and CLP alone respectively, n ⫽ 3, p ⬍ 0.05). Conversely, while miR-122 expression was elevated in sham and CLP animals, no significant differences were detected between sham ⫹ aPC and CLP ⫹ aPC. Conclusions: Previous data from our laboratory demonstrate ET receptor antagonism (bosentan) improves hepatic microcirculatory dysfunction in the setting of systemic sepsis. However, using bosentan in vivo is problematic due to an accompanying decline in MAP, an effect that offsets the benefits observed in preserving liver function. Data in this study identify selective changes in miR-199a-5p expression, an miRNA reported to inhibit ET-1 translation. Identifying novel targets of ET-1 expression are important in understanding both the mechanisms of action of aPC, as well as raising the possibility of developing future interventional therapies. Supported in part by Carolinas Healthcare Foundation Grant (TH).


Marc Maybauer, Dirk Maybauer, University of Texas Medical Branch, John Fraser, University of Queensland, Robert Cox, Hal Hawkins, David Herndon, University of Texas Medical Branch, Lillian Traber, Daniel Traber, University of Texas Medical Branch Hospitals Introduction: Recombinant human activated protein C (rhAPC) and ceftazidime (CEF) have shown to improve oxygenation as single treatment in ARDS resulting from septic shock. Hypothesis: We hypothesized that combined rhAPC and CEF will prevent ARDS in septic shock. Methods: Thirty sheep (35-40 kg) were operatively prepared for chronic study, and randomly allocated either to sham, control, CEF, rhAPC, or rhAPC/CEF groups (n ⫽ 6 each). After a tracheostomy, ALI and sepsis was produced in all groups, following an established protocol, sham group received the vehicle. Sheep were studied for 24h and ventilated with FiO2 1.0. CEF (3 g) was administered iv 1 and 13 h post injury. RhAPC was given as continuous infusion (24mcg/kg/h), starting 1h post injury. The animals were resuscitated with Ringer’s Lactate Solution. Post mortem, lung tissue was excised, HE-stained, and analyzed according to Cox’s airway obstruction scoring system. Statistical analysis: two-way ANOVA and Student-Newman-Keuls post hoc comparison. Data are expressed as mean ⫾ SEM. Significance P ⬍ 0.05. Results: Bronchi obstruction was 7 ⫾ 1% in sham animals, 60 ⫾ 1% in controls, 45 ⫾ 9% in CEF, 32 ⫾ 8% in rhAPC, and 30 ⫾ 8% in rhAPC/CEF animals. Obstruction in bronchioles was 3 ⫾ 1% in sham, 55 ⫾ 4% in control, 28 ⫾ 6% in CEF, 30 ⫾ 15% in rhAPC, and 15 ⫾ 5% in rhAPC/CEF animals. Bonchi and bronchiole scores were significantly increased in all injured groups, with significant reduction in airway obstruction of all treated groups compared to controls (p ⬍ 0.05), with a tendency of lowest obstruction in the combined group. PaO2/FiO2 ratio remained stable in sham (BL: 518 ⫾ 13 vs. 24h: 500 ⫾ 19) animals. The control group showed a significant decrease in PaO2/FiO2 ratio (BL: 497 ⫾ 21 vs. 24h: 76 ⫾ 5). The CEF group also showed a fall in PaO2/FiO2 ratio (BL : 524 ⫾ 11 vs. 24h: 165 ⫾ 47), as well as the rhAPC group (BL: 541 ⫾ 12 vs 24h: 118 ⫾ 17). Both goups showed a significant improvement of the PaO2/ FiO2 ratio compared to the control group. The PaO2/FiO2 ratio of the rhAPC/CEF group (BL: 525 ⫾ 10 vs. 24h: 280 ⫾ 20) was significantly higher than in all other injured groups. Conclusions: Administration of combined rhAPC/CEF after ALI associated with sepsis improved oxygenation more than either rhAPC or CEF alone.

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ABNORMAL NERVE CONDUCTION IN RAT SCIATIC NERVES INDUCED BY LIPOPOLYSACCHARIDE AND THE PROTECTIVE EFFECTS OF DANAPAROID

LACK OF BENEFIT FROM DEXAMETHASONE ADDED TO MINERALOCORTICOID THERAPY IN A CANINE MODEL OF BACTERIAL PNEUMONIA

Hirofumi Hino, Department of anesthesiology, St.Marianna University School of medicine, Arisa Miura, Wakako Kon, St.Marianna University School of Medicine

Caitlin Hicks, Daniel Sweeney, Robert Danner, Peter Eichacker, Anthony Suffredini, Jing Feng, Junfeng Sun, National Institutes of Health, Ellen Behrend, Auburn University, Steven Solomon, Charles Natanson, National Institutes of Health

Introduction: Peripheral nerve disorders represented by critical illness polyneuropathy are associated with sepsis but mechanisms involved remain unclear. Hypothesis: Potential mechanisms might include microcirculatory disorders. Danaparoid sodium (DS), an anticoagulant and anti-inflammatory agent, improves these phenomena. Here, we investigate whether lipopolysaccharide causes electrophysiological deterioration in rat peripheral nerves and the protective effect of DS on nerve conduction during administration of LPS. Methods: After 48hrs reagent administration, bronchotomy was performed and sciatic nerves exposed bilaterally for laser-Doppler measurement of individual nerve blood flow and nerve conduction studies (including nerve conduction velocity, latency and amplitude).30 Rats were randomly divided into 3 groups: a control group (Cgroup), a group administered with lipopolysaccharide (LPS;3mg/kg/day; L-group), and a group administered with both LPS and 400 units of DS (LDgroup). Results: Severe reductions were observed in L-group NBF (C-group: 25 ⫾ 3; L-group: 13 ⫾ 3 ml/100g/min; p ⬍ 0.001) which were not proportional to MAP and were observed to a lesser extent in the C-group. LPS did not affect latency and nerve conduction velocity but caused severe reduction in amplitude (C-group: 0.9 ⫾ 0.2; L-group 0.2 ⫾ 0.1mV; p ⬍ 0.001). Administration of DS improved not only the severe reductions in NBF induced by LPS (LD-group: 23 ⫾ 2 ml/100g/min; p ⬍ 0.001, vs. L-group), but also amplitude (LD-group: 0.5 ⫾ 0.1mV; p ⬍ 0.001, vs. L-group, C-group), though these remained significantly different from controls. Conclusions: The predicted nerve degeneration caused by severely reduced nerve blood flow might not play an important role in reduced amplitude because of the short term reach to degeneration in sepsis. DS has the potential to improve peripheral nerve function induced by sepsis. It is well known that DS, used in conjunction with antithrombin 3, inhibits not only the effect of coagulation factor Ten-A and thrombin during sepsis, but also stimulates Prostagrandin I2 which exhibits inhibitory effects upon NF-kB. Other actions of DS might be involved in the improvement of nerve function during sepsis.

Introduction: Pretreatment with desoxycorticosterone pivalate (DOCP), a selective long-acting mineralocorticoid agonist, improved shock, lung dysfunction, and survival in our canine staphylococcal model of staphylococcal pneumonia. Nonetheless, a substantial number of animals had depressed cortisol responses to ACTH stimulation consistent with relative adrenal insufficiency (RAI) and died despite receiving DOCP. Hypothesis: Dexamethasone (DEX), a selective glucocorticoid agonist, given therapeutically will further improve outcome when added to a background of mineralocorticoid therapy. Methods: Twenty-four (10-12 kg) purpose-bred beagles given intrapulmonary Staphylococcus aureus were randomized in a 1:2 allocation on alternating weeks to either study A: placebo (n ⫽ 3) vs. DEX (n ⫽ 6); or study B: DOCP (n ⫽ 5) vs. DOCP ⫹ DEX (n ⫽ 10). Results: DEX had significantly different effects on survival (p ⬍ 0.02), norepinephrine requirements (p ⫽ 0.03), plateau pressure (p ⫽ 0.04), SaO2 (p ⫽ 0.04), and LFTs (AST and ALT; p ⱕ 0.02) in the presence and absence of DOCP. DEX given in the presence of DOCP either had no effect on or decreased the benefit of DOCP alone, while DEX given alone was overall beneficial compared to no steroid treatment. Of note, the odds of having S. aureus-positive cultures in the blood and sputum in this and a previous study was significantly increased by DEX [OR ⫽ 1.75, 95% CI of (1.25, 2.44); p ⫽ 0.001], but not by DOCP [OR ⫽ 1.01, 95% CI of (0.63, 1.61); p ⫽ ns]. Conclusions: Even in doses that appear to provide benefit when given alone, DEX in combination with DOCP did not improve survival and worsened infection, acute shock, and lung injury compared to DOCP alone. A selective glucocorticoid agonist added to a background of prophylactic mineralocorticoid therapy to supplement adrenal function was not beneficial and potentially harmful in septic shock.

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ADRENAL FUNCTION IN A CANINE MODEL OF BACTERIAL PNEUMONIA-INDUCED SEPTIC SHOCK

ALTERATIONS OF EXPRESSION OF INFLAMMATORY MEDIATORS AND CASPASE 1 IN A MURINE MODEL OF COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS SEPSIS

Caitlin Hicks, Daniel Sweeney, Robert Danner, Peter Eichacker, Anthony Suffredini, Jing Feng, Junfeng Sun, National Institutes of Health, Ellen Behrend, Auburn University, Steven Solomon, Charles Natanson, National Institutes of Health Introduction: Despite elevated basal cortisol concentrations, a state of relative adrenal insufficiency due to adrenocortical exhaustion has been postulated in patients with persistent vasopressor-dependent septic shock. Hypothesis: Survivors compared to non-survivors will have different patterns of basal and ACTHstimulated cortisol levels during sepsis. Methods: Twenty-two (10-12 kg) purpose-bred beagles challenged with high-dose intrabronchial Staphylococcus aureus (1.5x10 9 cfu/kg) underwent ACTH stimulation testing prior to bacterial challenge and at 10, 24, 48, 72 and 96 h after infection. Results: At baseline (pre-sepsis) , the mean level of basal cortisol was 115 ⫾ 15 nmol/L and increased to 363 ⫾ 15 nmol/L in response to ACTH stimulation (5.0 ␮g/kg). Basal cortisol at 10 h (445 ⫾ 23 nmol/L; p ⬍ 0.0001) and 24 h (436 ⫾ 62 nmol/L; p ⫽ 0.0003) rose significantly from these baseline levels after the onset of infection, and no significant increase occurred in response to ACTH stimulation (delta cortisol) at those time points (p ⫽ ns comparing basal and ACTH-stimulated cortisol). In survivors, basal and delta cortisol concentrations returned to baseline values by 48 h, whereas in non-survivors basal cortisol levels remained elevated and delta cortisol levels remained depressed until death. Using a logistic regression to compare its association with survival status, basal total cortisol concentrations were superior for predicting survival compared to ACTH-stimulated and delta cortisol concentrations by area under the ROC curve analysis (0.84, 0.77, and 0.75, respectively). In addition, the association between basal cortisol and survival status improved over time from 10 to 24 to 48 h (AUC ⫽ 0.78, 0.84, and 0.86, respectively). Conclusions: Lethal bacterial challenges cause significant increases in adrenal output of cortisol over 24 h to the point of exhaustion, evidenced by a lack of cortisol response to ACTH stimulation at those time points. While this increase is reversible in survivors, non-survivors appear to have persistent increases in basal cortisol concentrations until death. Basal rather than delta or ACTHstimulated cortisol concentration appears to be a better predictor of survival.

Janet Hume, University of Texas Southwestern Medical Center, Deborah Carlson, UT Southwestern Med Ctr Introduction: Sepsis caused by community-acquired methicillin-resistant S. aureus (CA-MRSA) has become a significant cause of morbidity and mortality in both adult and pediatric intensive care units. While animal models of gramnegative bacterial sepsis have shown the key role of gram-negative bacterial products such as lipopolysaccharide in the pathophysiology of gram-negative sepsis, CA-MRSA sepsis pathophysiology has not been extensively studied in animal models. Hypothesis: We propose that study of inflammatory mediators and end organ effects in a model of CA-MRSA sepsis may uncover novel areas for therapeutics in CA-MRSA sepsis. Methods: We have developed a murine model of CA-MRSA sepsis that demonstrates clinically significant morbidity and mortality as well as expression of pro-inflammatory genes including IL-1␤, TNF-␣, and the IL-1␤ converting enzyme, caspase 1. Briefly, wild type BALB/c mice as well as caspase-1 knockout mice were intravenously injected with FPR3757, a sequenced strain belonging to the USA300 CA-MRSA type. Doses ranged from 1 ⫻ 106 to 1 ⫻ 109 CFU per mouse with a control group injected with PBS alone. Mice were sacrificed after 24 hours and hearts and blood harvested for RNA isolation and quantitative PCR analysis. Results: The higher doses (1 ⫻ 108 to 1 ⫻ 109) caused 50-100% mortality in pilot experiments in the caspase 1 knockout mice and clinical morbidity (ruffled fur, decreased activity) in wild type mice. Quantitative PCR analysis of heart tissue revealed upregulation of caspase 1 expression in wild type mice with a peak mean increase of 26 fold over the PBS control for the dose of 5 ⫻ 107CFU. IL-1␤ expression peaked at an inoculum of 1 ⫻ 108 CFU (42 fold increase over PBS control for wild type mice and 7.5 fold increase for caspase 1 KO mice). TNF-␣ expression peaked at 5 ⫻ 107 CFU (2.8 fold increase for wild type and 3.9 fold increase for caspase 1 KO). Conclusions: We conclude that this model of CA-MRSA sepsis in mice demonstrates relevant morbidity and mortality and upregulation of inflammatory markers consistent with a significant sepsis response at infectious inocula of 5 ⫻ 107 to 1 ⫻ 108 CFU per mouse, allowing further investigation of the pathophysiology of CA-MRSA sepsis.


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EFFECTS OF ENDOTOXIN ACTIVITY ON PLATELETS FUNCTION AND COAGULATION IN SEPTIC PATIENTS

CORTICOSTEROID THERAPY IS BENEFICIAL IN HIGHBUT NOT LOW-SEVERITY SEPTIC SHOCK IN A CANINE MODEL OF BACTERIAL PNEUMONIA

Michele Collareta, Giuseppe Mancino, Matteo Franchi, Francesco Forfori, Francesco Giunta, Antonio Abramo, Universita` di Pisa Introduction: Platelets and coagulation system are fully activated in sepsis. Hypothesis: We have presumed a correlation between endotoxin activity levels and the alterations of coagulation parameters in septic patients. Methods: We have studied 9 patients admitted to ICU with a severe sepsis/septic shock diagnosis. After written inform consent three peripheral blood samples were collected respectively from each patient, at the admission, on the 3rd and the 7th day of ICU stay. The EAA (Endotoxin Activity Assay) was performed on the sample. At the same time, platelets count, TEG test, PAI-1, vonWillebrand, factor VII, factor VIII, AT-III, fibrinogen, D-dimer measuring and arachidonic acid-induced platelets aggregation tromboelastographic test were performed with the aim of finding a significant correlation among these parameters - which were also related to overall mortality at the 28th day after the ICU admission. Non-parametric analysis has been used to process our data -Wilcoxon test and Mann-Whitney test for independent data and for paired data, respectively- and regression lines between EA and other data have been calculated. Results: Our data show a decrease of AT-III activity (mean 77, 13 – range 49-105 – n.v. 80-120) and of TEG C.I. (mean -3, 43 – range -8, 1-1, 8 – n.v. -3 – 3), and an increase of D-dimer levels (mean 2, 39 – range 0, 2-10, 13 – n.v.. 0, 22-0, 74), supporting the hypothesis of coagulation activation up to non-overt DIC. Patients affected by thrombocytopenia at the admission have a 50% death rate, while non-thrombocytopenic patients have a 20% death rate. TEG C.I. rises from 1st to 3rd day (p ⫽ 0, 016), more in survived patients than in non-survived patients (mean 4, 48 vs. 0, 95). In the whole sample, factor VII levels are correlated to EA (R ⫽ 0, 78). In the same patient, AT-III variations are highly and negatively correlated to EA variations (R ⫽ 0, 98). Conclusions: Hemostasis is activated up to non-overt DIC in septic patients. Greater alterations in hemostatic parameters are correlated to higher mortality rates. EA seems to directly affect coagulation abnormalities increasing factor VII levels and decreasing AT-III activity.

190 CARDIAC RESPONSE AND MOLECULAR MECHANISMS OF CARDIAC DYSFUNCTION AS RELATED TO AGE Deborah Carlson, UT Southwestern Med Ctr, Marita Thompson, Univ. of Texas Hypothesis: Purpose: To characterize and identify gene differences in cardiac response to septic challenge in different age groups. Methods: Experimental Design: Myocardial response following LPS was determined by fractional shortening (FS) and heart rate (HR) in weaned (3 week old), adolescent (9 week old) and adult (4 month old) rats. ECHO was done at 0, 2, 4, 8, 12, 24, and 36h post LPS. Hearts were collected and protein harvested at 4h. Cardiac protein was analyzed by protein kinase and apoptotic proteomic microarray. Results: Results: Heart rates of LPS challenged adolescent and adult rats elevated at 4h. In comparison, weaned rats demonstrated a heart rate drop of 18% at 2h, which then recovered and elevated at 8 and 24h. Weaned animals continued to differ in heart rate from other age groups, maintaining a normal heart rate. In difference to heart rate, the shortening fraction of all LPS challenged groups increased approximately 29% 2h post LPS. Weaned rats showed no significant change from controls, compared to adolescent and adult rats, which exhibited significant drops in fractional shortening (24% at 4h until recovery at 36h for a, and 18% for ad). Protein expression in the age groups was also examined. Sixty different proteins were screened, and 37 were altered in the weaned as compared to the older groups. One of the strongest regulated was Suppressor of Cytokine Signaling 4 (SOC4). Continuing work is examining the role of SOC4 in age related cardiac differences. Conclusions: Our results suggest there are differences in cardiac function and patterns of cardiac protein expression in different age groups of rats, suggesting there may be differing mechanisms for the physiologic differences in cardiac dysfunction seen in adults and children during a septic event.


Caitlin Hicks, Daniel Sweeney, Robert Danner, Peter Eichacker, Anthony Suffredini, Jing Feng, Junfeng Sun, National Institutes of Health, Ellen Behrend, Auburn University, Steven Solomon, Charles Natanson, National Institutes of Health Introduction: Corticosteroids have had inconsistent effects on survival in clinical trials of septic shock. Meta-analyses of these trials suggest that corticosteroids may only be beneficial when mortality is high, but have no effect or cause harm in less severely ill patient with low mortality. Hypothesis: Corticosteroid therapy is beneficial in high- but not low-severity septic shock in a canine model of bacterial pneumonia. Methods: Thirty-eight (10-12 kg) purpose-bred beagles given lowand high-dose intrapulmonary Staphylococcus aureus (1.05-1.2 x10 9 vs. 1.351.5 x10 9 cfu/kg, respectively) were randomized to receive stress-dose corticosteroid therapy vs. placebo (n ⫽ 6 vs. 6 for low- and n ⫽ 13 vs. 13 for high-dose bacteria) over 96 h. Results: The effect of corticosteroids on survival was significantly different for the high- vs. low-challenge bacteria groups (p ⫽ 0.065 for interaction): steroids improved survival in the high-challenge group compared to controls (p ⫽ 0.028), but had no significant effects in the low-challenge group (p ⫽ 0.86). Consistent with this, corticosteroids in the high- vs. low-challenge bacteria groups had significantly different effects on mean HR, A-aO2, RR, and pulmonary artery pressure (p ⱕ 0.05). Animals challenged with high inoculums of bacteria showed improvement in these parameters with corticosteroid treatment, but animals challenged with low bacterial loads showed no benefit from therapy. Conclusions: Consistent with clinical sepsis trials, corticosteroids only improved outcome in animals challenged with high-severity sepsis. Steroid therapy may have a role in improving survival in clinical sepsis, but treatment may have to be targeted to those patients who have a high risk of death.

Poster: Burns /Trauma -1 191

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ENOXAPARIN DOSE ADJUSTMENT IS ASSOCIATED WITH LOW INCIDENCE OF VENOUS THROMBOEMBOLIC EVENTS IN ACUTE BURN PATIENTS

PYRROLIDINE DITHIOCARBAMATE DECREASES MORTALITY, AND MODS FOLLOWING ISCHEMIA-REPERFUSION FROM HEMORRHAGE

Hsin Lin, Iris Faraklas, University of Utah Hospitals and Clinics, Amalia Cochran, University of Utah Department Of Surgery, Jeffrey Saffle, University of Utah

Molly Pallilonis, Carolinas Medical Center, Anna Montegudo, Carolinas Healthcare System, Iain McKillop, Susan Evans, Carolinas Medical Center

Introduction: In critically ill patients standard prophylactic dosing of enoxaparin has often resulted in subtherapeutic anti-Xa levels associated with a significant increase in the risk of venous thromboembolism (VTE). Hypothesis: In our burn center, a protocol for graduated enoxaparin dosing with concurrent monitoring to achieve peak anti-Xa level of 0.2-0.4 u/ml was implemented. This study was performed to assess the effectiveness of this regimen. Methods: From June 2009 to July 2010, patients with acute burn injuries who received VTE prophylaxis were given an initial dose of 30 mg subcutaneously twice daily. Doses were adjusted until therapeutic levels were obtained or until discharge. With IRB approval, a telephone interview with each patient was performed approximately thirty-days post discharge to determine if any VTE events had occurred. Results: Seventy-five patients were treated with this protocol during this period. Of these, 57 showed initial anti-Xa levels below 0.2u/ml for whom the enoxaparin dose was then increased. In 13 patients, the target anti-Xa level was never reached before discharged. Of 62 patients who had appropriate anti-Xa levels, one had a deep vein thrombosis during admission, one developed pulmonary embolism one month post discharge, two died of non-VTE causes and five were unable to be reached by telephone survey. No episodes of abnormal hemorrhage, thrombocytopenia or heparin allergy were documented. Median final enoxaparin dose required to achieve therapeutic anti-Xa level was 50mg every 12 hours (range 30 –70mg). Using linear regression, final enoxaparin dose correlated with TBSA and weight. Conclusions: The frequent occurrence of low anti-Xa levels observed in this study demonstrated that standard dosing of enoxaparin for VTE prophylaxis was often inadequate for patients with acute burns, and that enoxaparin dose adjustment was associated with a low incidence of VTE events. In patients with acute burn injury routine monitoring of anti-Xa levels is recommended.

Introduction: NFkB signaling is critical in mediating systemic responsiveness to septic shock. Hypothesis: We hypothesized that pretreatment with pyrrolidine dithiocarbamate (PDTC), an NFkB inhibitor, will decrease mortality associated with hemorrhagic shock by reducing multiple organ dysfunction syndrome (MODS). Methods: The right carotid artery and left jugular vein of male rats (250-300g) were cannulated. To induce hemorrhagic shock (HS group) arterial blood was withdrawn until MAP of 20-25mmHg was reached and maintained for 60mins. Resuscitation was initiated with i.v. shed blood/sterile saline (1:1) until original MAP was re-established. In parallel studies animals were injected with 100mg/kg PDTC dissolved in saline (i.p.) 12hrs pre-hemorrhage (PTDC-HS group). Measurements of base deficit, lactate, creatinine, AST, and lipase were made pre-hemorrhage, post- hemorrhage, and at time of death, or sacrifice (48hrs post-resuscitation). Results: In the HS group (n ⫽ 10) 70% mortality was observed ⬍48 hrs (mean time of death, those dying ⬍48 hrs ⫽ 154 ⫾ 18mins). Conversely, in PDTC-HS (n ⫽ 9), mortality ⬍48 hrs, was 30% (mean time of death, those dying ⬍48 hrs ⫽ 131 ⫾ 33mins). When compared to the HS-group, PDTC-HS had significantly lower base deficit (1.6 ⫾ 1.8 vs 14.9 ⫾ 2.1, p ⬍ 0.0005) and lactate (6.3 ⫾ 0.4 vs 11.7 ⫾ 1.1mg/dL, p ⬍ 0.001) post-hemorrhage. Similarly, creatinine, and lipase were significantly lower in PDTC-HS vs HS at time of death. Analysis of all animals surviving to 48hrs exhibited lower base deficit (-1.4 ⫾ 2.1 vs 22.8 ⫾ 4.8, p ⬍ 0.05), lactate (2.5 ⫾ 0.2 vs 15.2 ⫾ 2.4mg/dL p ⬍ 0.05) creatinine (0.9 ⫾ 0.3 vs 1.5 ⫾ 0.1mg/dl, p ⫽ 0.22), and lipase (7.7 ⫾ 0.15 vs 20.5 ⫾ 0.5mg/dL, p ⬍ 0.005) than those dying ⬍ 48 hours, respectively. Conclusions: In conclusion, pretreatment of animals with PDTC significantly inhibits mortality and MODS in a rat model of hemorrhagic shock.

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CLINICAL CHARACTERISTICS OF PATIENTS WITH CRITICAL ILLNESS RELATED CORTISOL INSUFFICIENCY FOLLOWING BURN INJURY

A TIER II TRAUMA TRIAGE SYSTEM WITHIN THE EMERGENCY DEPARTMENT IS EFFECTIVE IN IDENTIFYING INJURED GERIATRIC PATIENTS AT RISK FOR ICU ADMISSION

Kencee Graves, University of Utah, Iris Faraklas, Amalia Cochran, University of Utah Department of Surgery

Amanda McNicholas, Reading Hospital and Medical Center, Forrest Fernandez, Ari Malka, Luis Cardenas, The Reading Hospital and Medical Center, Jared Zavilla, Reading Hospital and Medical Center, Charles Schwab, The Hospital of the University of Pennsylvania

Introduction: The goal of this retrospective case-control analysis was to characterize the clinical courses, including risk factors, of patients who develop Critical Illness Related Cortisol Insufficiency (CIRCI) following acute burn injury. Methods: With IRB approval we reviewed all adult patients with acute burn injury who developed CIRCI (cases) during hospitalization at our regional burn center during the 5-year period 2003-2008. Each CIRCI patient was matched by age, sex, and TBSA to all available controls. CIRCI was diagnosed in any patient who exhibited a random cortisol level ⱕ18 mcg/dl or response to a 250 ␮g cosyntropin stimulation test of ⱕ9 mcg/dl. All patients with confirmed CIRCI were treated with glucocorticoid replacement. Results: CIRCI was diagnosed in 23 (22% female) of 1183 adult patients during the period reviewed (1.9%); 159 controls were matched to these patients. Mean age (51.3 vs. 51.6 years, p ⫽ 0.68) and total body surface area burn (33.2 vs. 31.8%, p ⫽ 0.07) were not different between cases and controls. When compared to controls, CIRCI patients demonstrated significantly greater length of stay (35.1 vs. 65.8 days, pⱕ0.001), ventilator days (20.5 vs. 33.2 days, pⱕ0.001) and mortality (2.5% vs. 17.4%, pⱕ0.001). Patients with more comorbidities as measured by Charlson Comorbidity Index were more likely to develop CIRCI (1.5 vs 2.5, p ⫽ 0.02). Inhalation injury demonstrated an odds ratio of 10.85 for the development of CIRCI (pⱕ0.001). Antibiotics and sedative/hypnotics analyzed by class failed to demonstrate any differences in CIRCI occurrence between cases and controls. Etomidate was analyzed individually and did not show an association with CIRCI. Multivariate conditional logistic regression analysis including Charlson Comorbidity Index and inhalation injury showed significant association of both dependent variables with CIRCI (pseudo-R2 ⫽ 0.32, pⱕ0.001). Conclusions: The mortality rates in this study were much lower than those previously published for acute burn patients with CIRCI, demonstrating that an aggressive approach to CIRCI detection and treatment in critically ill burn patients may be associated with improved mortality.

Introduction: Trauma triage is designed to optimize patient outcomes through effective utilization of available resources. Factors such as physiology, anatomy, mechanism, and co-morbid conditions are essential when evaluating injured patients. The triage of the geriatric patient population is particularly challenging due to their increased frequency of occult injury. Ineffective triage places them at risk for delays in diagnosis and treatment of life threatening injuries. In February 2009, our Emergency Department (ED) employed an additional category of trauma triage for vulnerable injured patient populations who do not meet traditional American College of Surgeons (ACS) criteria for trauma activation. Hypothesis: A T3 triage system is effective for identifying and evaluating low to moderate risk injured geriatric patients within the ED of our Level II trauma center. Methods: A retrospective chart review of 1446 patients who met the criteria for T3 activation from the period March 2010 to July 2010 was performed. In March 2009, a protocol was designed that triaged patients into a T3 system based on the following criteria: short interval loss of consciousness with return to GCS 14-15, mechanism, complaints of dypsnea, chest or abdominal pain following torso trauma, history of a traumatic mechanism receiving anticoagulation/antiplatelet therapy (Aspirin, Coumadin or Plavix), age ⬎ 65 years with a suspected long bone fracture, or trauma at greater then 22 weeks gestation. These patients are initially evaluated and managed by the ED. Results: Our review revealed that 1446 patients evaluated as T3, 28% (N ⫽ 410) (Trauma 41%, Medicine/other 43%, Ortho 16%) were admitted. T3 Geriatric patients (age ⬎ 60) represented the majority of admits (80%). Of note, only 3% (N ⫽ 5) of medicine admissions went directly to the Medical ICU where as 47% (N ⫽ 62) of trauma admissions were admitted directly to Trauma ICU. Examination of similar populations by age yielded much lower ICU admission rates. Conclusions: A Tier III triage system is effective in identifying patients at risk for occult injury, particularly geriatric patients with traumatic injuries requiring ICU admission who do not meet traditional ACS criteria for trauma bay evaluation.


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CALCIUM AND SHOCK HEART IN BURN PATIENTS: HYPOCALCEMIA IS ASSOCIATED WITH BURN SHOCK REQUIRING INOTROPIC SUPPORT.

EFFECTIVENESS OF CLINICAL GUIDELINES FOR DVT PROPHYLAXIS IN REDUCING THE INCIDENCE OF VENOUS THROMBOEMBOLISM IN CRITICALLY ILL CHILDREN AFTER TRAUMA

Kunihiko Maekawa, Keigo Sawamoto, Shuji Uemura, Katsutoshi Tanno, Kazuhisa Mori, Yasufumi Asai, Sapporo Medical University Introduction: Burn shock is characterized by immediate hypovolemia reversed by sufficient fluid resuscitation and delayed myocardial dysfunction termed as “shock heart”, which occasionally needs inotropes. Serum calcium is known to play a role in myocardial contraction, but the relationship of hypocalcemia with shock heart has not been well established. Hypothesis: Acute hypocalcemia is associated with burn shock requiring inotropic support. Methods: We performed a retrospective cohort study of burn patients admitted to a single tertiary care center over 7 years period. All consecutive patients with ⬎⫽ 10% total body surface area (TBSA) burn were included in the study. They were received fluid resuscitation with Ringer’s solution and colloid according to clinical guidelines and inotropic support (dopamine or dobutamine) decided by the attending intensivists. Data were abstracted including demographic, burn injury characteristics, inotrope use, lowest serum level of calcium and albumin within 72 hours after burn injury. Hypocalcemia was defined as ⬍⫽ 2 mmol/L. Logistic regression model was used to investigate the factors associated with inotrope use. Results: Of 64 eligible patients, 24 (38.1%) required inotropic support (inotrope group) and 39 (61.9%) did not require inotropic support (non-inotropegroup). Compared to non-inotrope group, inotrope group had significantly higher TBSA burn (35 [25-48] vs. 21 [14-36] %, p ⫽ 0.03), more often inhalation injury (16/24 [69.6%] vs. 14/40 [35.0%], p ⫽ 0.028), carbon monoxide poisoning (8/24 [34.8%] vs. 4/40 [10.0%], p ⫽ 0.048), hypocalcemia (19/24 [82.6%] vs. 15/40 [37.5%], p ⫽ 0.001) and lower albumin level (2.1[1.8-2.4] vs. 2.6 [2.32.9] mg/dL, p ⫽ 0.0003). Multivariable logistic regression analysis showed that hypocalcemia solely had a significant association with inotrope use (adjusted odds ratio 7.1, 95%CI 1.2-42.5, p ⫽ 0.032). Conclusions: Acute hypocalcemia was associated with burn shock requiring inotropic support. Further study is warranted to establish the efficacy of calcium administration.

Sheila Hanson, Children’s Hospital of Wisconsin and Medical College of Wisconsin, Rowena Punzalan, Children’s Hospital of Wisconsin and Medical College of Wisconsin, Marjorie Arca, Children’s Hospital of Wisconsin and Medical College of Wisconsin, Pippa Simpson, Children’s Research Institute , Melissa Christensen, Medical College of Wisconsin, Kristen Braun, Children’s Hospital of Wisconsin, Peter Havens, Children’s Hospital of Wisconsin and Medical College of Wisconsin Introduction: In a previous study, about 6% of critically ill children after trauma developed venous thromboembolism (VTE) at our level 1 pediatric trauma center. Clinical guidelines for thrombosis prophylaxis have been developed incorporating sequential compression devices (SCDs) with VTE screening and/or anticoagulation (AC) for patients at high risk for VTE. Hypothesis: Implementation of guidelines for thrombosis prophylaxis will reduce the incidence of VTE. Methods: VTE was prospectively identified for all children admitted to the ICU after trauma during 3 time periods: Pre-implementation of guidelines for thrombosis prophylaxis (Pre) (4/1/06-6/30/07), Roll out (7/1/07 -11/4/08), and post-guideline implementation (Post) (11/5/08-6/1/10). For patients classified by the guidelines as high risk for VTE, SCDs and AC were recommended. For those with high risk of bleeding, AC was deferred and screening ultrasound performed. Results: Thirteen of 546 subjects developed VTE. There was a decreased incidence in total VTE (p ⫽ .041) and clinical VTE (p ⫽ .001) after the guidelines. The 9 VTE Pre (5.2% incidence) and 2 VTE during Roll out (1.0% incidence) were clinically symptomatic. The 3 VTE Post (1.8% incidence) were detected by screening ultrasound only. There were age differences in the study periods (median 12y Pre, 10y Rollout, and 7y Post, p ⫽ .043); with no difference in initial Glascow Coma Score or pediatric severity of illness or trauma scores. The incidence of prophylactic AC was similar (⬇ 10%) in the 3 periods; as ⬎ 65% of patients classified as high risk for VTE had a perceived high bleeding risk and did not receive AC. No bleeding complications occurred with AC. There were no VTE after implementation of guidelines in the patients classified by the guidelines as low risk for VTE. Conclusions: The incidence of clinical VTE and total VTE decreased after implementation of clinical guidelines for thrombosis prophylaxis in critically ill children after trauma. This decrease in VTE was not associated with an increase in prophylactic AC, and may be due to other effects from guideline implementation such as VTE risk education and vigilance. The guidelines were predictive in identifying patients at low risk for VTE.

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PROLONGED ARTERIAL LACTATE ELEVATION PREDICTS A POOR NEUROLOGICAL OUTCOME IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

OUTCOME ANALYSIS FOLLOWING BURN INJURY IN DIABETIC PATIENTS AS COMPARED TO NON-DIABETIC PATIENTS: A 10-YEAR RETROSPECTIVE STUDY

Keigo Sawamoto, Kunihiko Maekawa, Kei Miyata, Shuji Uemura, Katsutoshi Tanno, Kazuhisa Mori, Yasufumi Asai, Sapporo Medical University

Sachin Patil, E. Hani Mansour, Michael Marano, Abraham Houng, Sandra Johansen, Ronald Chamberlain, Saint Barnabas Medical Center

Introduction: The mortality and neurological morbidity associated with severe traumatic brain injury (TBI) is exceptionally high. Early and simple estimation of prognosis for the patient with severe TBI is an important factor in making treatment decisions and communicating with family. Hypothesis: The prolonged arterial lactate (LAC) elevation within 48 hours after admission predicts poor neurological outcome in patients with severe TBI. Methods: This retrospective cohort study evaluated consecutive adult patients (ages 16-80 years) with severe TBI during a 6-year period (2005-2010). Patients with a GCS score ⫽ ⬍ 8 and ⬎ 8 but with significant abnormalities on CT scan (obliterated basal cisterns, contusions ⬎ 5 cm in diameter, and hematoma requiring evacuation), who later deteriorated, were eligible for inclusion. Exclusion criteria were cardiac arrest at the scene and death within 48 hours after admission. Data abstracted include age, sex, Glasgow Coma Scale (GCS) score and pupil reactivity, injury severity score (ISS), probability of survival (PS) calculated by TRISS methods, introduction of therapeutic hypothermia (TH), and LAC. LAC data were obtained on admission (T0) and 3 (T3), 6 (T6), 12 (T12), 24 (T24), and 48 hours (T48) after admission respectively. Univariate analysis and multivariate logistic regression analysis were used to evaluate the relationship between their ‘poor’ neurological outcome (Glasgow Outcome Scale [GOS]: severe disability, vegetative state or death) 6 months after admission and LAC variables. Results: Of 57 eligible patients, 24 (42.1%) were ‘good’ neurological outcome. In univariate analysis we found statistically differences in PS and LAC on T3, T6, T12, T24 and T48. In multivariate logistic regression analysis, LAC on T6, T12, T24 and T48 were statistically significant predictors of ‘poor’ outcome, and theirs adjusted odds ratio for LAC ⫹ 0.1 mmol/L were 1.05 (95% CI 1.01-1.10, p ⫽ .02) on T6, 1.08 (95% CI 1.01-1.15, p ⫽ .01) on T12, 1.11 (95% CI 1.02-1.20, p ⫽ .02) on T24 and 1.28 (95% CI 1.06-1.56, p ⫽ .01) on T48, respectively. Conclusions: Our findings suggested that LAC obtained from 6 to 48 hours after admission are associated with 6-month neurological outcome in patients with severe TBI.

Introduction: Diabetes is the fourth most common comorbidity among hospitalized patients and the seventh leading cause of death in the United States. Diabetes can affect vision and peripheral sensation which increases the chances of contracting burn injury, and alterations in vascular supply and immune dysregulation may affect the outcome of a burn. We analyzed the clinical outcome of ⬎ 2, 500 burn patients admitted between 1999 and 2009 based on diabetes status. Hypothesis: Burn patients with diabetes have poor outcome. Methods: 2543 adult patients admitted to the SBMC burn unit (1999-2009) were studied. Age, TBSA, burn etiology, hospital and burn intensive care unit (ICU) length of stay (LOS) and discharge status were abstracted. Patients were grouped as diabetic (group A) or non-diabetic (group B) and further categorized based on TBSA (⬍20%, 21-40%, 41-60%, 61-80% and 81-100%). Differences were analyzed using the student’s t-test and Chi-Square. Results: 259 diabetic patients and 2284 non-diabetic patients were treated between 1999 and 2009. The mean age of patients was 58.8 years (18.5- 98, group A) and 44.7 (18-98.3, group B), p ⬍ 0.001. The M: F ratio was 2:1. Group A patients had higher (p ⬍ 0.05) TBSA burn (16 ⫾ 20 vs. 13 ⫾ 16), burn ICU admission rate (N ⫽ 152, 58.7% vs. N ⫽ 1002, 43.9%), burn ICU LOS (12 ⫾ 20 vs. 6 ⫾ 14), total ventilator days (6 ⫾ 16 vs. 3 ⫾ 11), total LOS (22 ⫾ 23 vs. 15 ⫾ 18) and mortality (N ⫽ 53, 20.4% vs. N ⫽ 209, 9.1%). Although more diabetic patients required ICU admission across all TBSA burn (p ⬍ 0.001), ICU LOS and ventilator days was significant only for patients with ⬍ 20% and those with 21- 40% TBSA burns, p ⬍ 0.001. Mean LOS was significant only for diabetic patients with ⬍ 20% burns (9 ⫾ 15 vs. 3 ⫾ 9, p ⬍ 0.001). Increased mortality in group A was seen with ⬍ 20% TBSA (N ⫽ 30, 14.5% vs. N ⫽ 78, 3.9%, p ⬍ 0.001) and those with 21- 40% TBSA (N ⫽ 10, 32.3% vs. N ⫽ 44, 22.4%, p ⬍ 0.001). Conclusions: Diabetic patients have a worse outcome following even small burn injuries compared to non-diabetic patients. Diabetes as a comorbidity in a burn patient is associated with an increased requirement for ICU admission, ventilator support, total LOS, the need for post-discharge skilled nursing care and overall mortality.


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EVALUATING THE SAFETY OF IMMEDIATE APPLICATION OF NEGATIVE PRESSURE THERAPY AFTER DECOMPRESSION FROM ABDOMINAL COMPARTMENT SYNDROME

EFFECT OF EARLY NEGATIVE PRESSURE THERAPY (NPT) ON PRO-INFLAMMATORY CHARACTERISTICS OF PERITONEAL FLUID (PF) AND PLASMA IN ABDOMINAL COMPARTMENT SYNDROME (ACS)

Shinil Shah, Fernando Jimenez, Peter Walker, Hasen Xue, Karen Uray, University of Texas Medical School at Houston, Kenneth Norbury, Kinetic Concepts, Inc, Randolph Stewart, Glen Laine, Texas A&M University, Charles Cox, University of Texas Medical School at Houston Introduction: Recent laboratory data suggests that use of negative pressure therapy (NPT) after decompression from abdominal compartment syndrome (ACS) may be associated with worsened outcomes. Hypothesis: The purpose of this study was to determine whether NPT is safe when used in the immediate postdecompression period after ACS. Methods: Using a hemorrhagic shock/resuscitation and mesenteric venous hypertension model, ACS was physiologically induced in 12 female Yorkshire swine. At decompression, animals were allocated to the ABThera™ Open Abdomen NPT System (ABThera, Kinetic Concepts, Inc., San Antonio, TX) (n ⫽ 6) or Bogota bag (n ⫽ 6) as temporary abdominal closure and studied for a period of 48 hours or until death. Outcomes measured included mortality, recurrent intra-abdominal hypertension (IAH), physiological and blood-related parameters, and organ (liver, kidney, lung, and intestinal) edema and histology at time of death/sacrifice. Results: ACS developed in all animals. Early application of NPT did not increase the incidence of post-decompression recurrent IAH (2/6 in each group) or decrease survival time (40.5 ⫾ 4.8 hours versus 29.8 ⫾ 8.2 hours, ABThera versus Bogota). There were no deleterious effects of NPT on physiological and blood related outcome measurements (cardiac output, mean arterial pressure, central venous pressure, hemoglobin, hematocrit, pulmonary artery pressure, pulmonary capillary wedge pressure, peak inspiratory pressure, pH, pO2, pCO2, SaO2, P:F ratio, mesenteric venous pressure, IAH, Na ⫹ , K ⫹ , Cl-, body temperature, glucose, PT, INR, plasma protein, urine output, BUN, creatinine, anion gap, base excess, HCO3-, or lactate). There were no significant differences in wet to dry ratio/histology in lung, liver, kidney, and small intestine (ileum). Conclusions: This study demonstrates that early application of NPT appears safe and not associated with increased mortality or recurrent IAH. Sources of Funding: Kinetic Concepts, Inc; NIH Grants T32 GM 0879201 and RO1 HL 092916; Children’s Memorial Hermann Hospital Foundation; Texas Higher Education Coordination Board.

Shinil Shah, Fernando Jimenez, Peter Walker, Hasen Xue, University of Texas Medical School at Houston, Kenneth Norbury, Kinetic Concepts, Inc, Karen Uray, University of Texas Medical School At Houston, Randolph Stewart, Glen Laine, Texas A&M University, Charles Cox, University of Texas Medical School at Houston Introduction: We have previously demonstrated in an animal model of ACS that PF collected after development of ACS primes naive neutrophils and monocytes and that NPT utilized as temporary abdominal closure (TAC) after decompressive laparotomy may result in improved outcomes as compared to controls. Hypothesis: The purpose of this study was to determine whether the effect of early NPT (ABThera™, Kinetic Concepts, Inc., San Antonio, TX) as compared to Bogota bag closure on the ability of PF and plasma to prime neutrophils and/or monocytes may explain the mechanism of benefit of NPT after decompression from ACS. Methods: Using a validated hemorrhagic shock/resuscitation and mesenteric venous pressure elevation model, ACS was physiologically induced in 12 female Yorkshire swine. At decompression, animals were treated with NPT (n ⫽ 6) or Bogota bag (n ⫽ 5) as TAC. PF/plasma were collected at 0, 6 and 12 hrs after decompression and studied as a primer of neutrophils/monocytes via receptor dependent (n-formyl-met-leu-phe) and independent (phorbol 12-myristate 13-acetate) pathways. Integrin/selectin expression and superoxide production were used as endpoints. Results: The results indicated that survival was 2 times higher in the NPT group than the Bogota bag group. The amount of PF removed by NPT during the first 12 hrs was 1029 ⫾ 243 mL, whereas no appreciable amount of PF leaked from the Bogota bag group. However, the ability of PF or plasma to prime neutrophils and monocytes did not change in either treatment group in the 12 hrs immediately post decompression. Conclusions: The confirmation of persistent pro-inflammatory properties of PF (as measured by neutrophil/monocyte priming) after decompression establishes the need to understand if augmented removal of PF with NPT leads to decreased systemic inflammation at later timepoints. Whether this represents a mechanism for improved outcomes with NPT remains a subject of active investigation. This data provides a platform for well designed studies to determine if early NPT use improves outcomes in patients with open abdomens by decreasing systemic inflammation via a peritoneal fluid related mechanism. Funding: Kinetic Concepts, Inc; NIH T32 GM 0879201/RO1 HL 092916


Poster: Burns /Trauma-2 201

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UTILITY OF AN INITIAL D-DIMER ASSAY IN SCREENING FOR FRACTURES IN BLUNT TRAUMA PATIENTS

FACTORS ASSOCIATED WITH AMPUTATION OF OPEN FRACTURES

Kohei Kato, Yoshihiro Takeyama, Naofumi Bunya, Yoichi Katayama, Toshihiro Tawara, Hiroyuki Okamoto, Hakodate Municipal Hospital, Kunihiko Maekawa, Katsutoshi Tanno, Kazuhisa Mori, Yasufumi Asai, Sapporo Medical University

Brett Waibel, Brody School of Medicine, East Carolina University, Claudia Goettler, East Carolina University Brody School of Medicine, Lisa Schlitzkus, Brody School of Medicine, East Carolina University, Joel Rose, East Carolina University, Scott Sagraves, Brody School of Medicine E. Carolina Univ., Christopher Hasty, Pitt County Memorial Hospital, Michael Rotondo, East Carolina University Brody School of Medicine

Introduction: Laboratory testing plays a minor role in screening for fractures of blunt trauma patients. Its main value is in the assessment of co-morbidity. Following an incidental observation, we investigated the association between elevated D-dimer levels and fractures. Hypothesis: Elevated D-dimer levels are associated with fractures in blunt trauma patients. Methods: A retrospective cohort study was performed on blunt trauma patients referred to our emergency department (ED) over 2 years (2008-2010). Patients were eligible for inclusion if they were referred within 24 hours after injury. Patients with polytrauma, head injury, aortic injury/disease and thromboembolic tendency were excluded. A D-dimer assay was obtained on ED arrival. Receiver-operator characteristic (ROC) curve analysis was used to evaluate the cut-off value of D-dimer. Logistic regression model was used to investigate the association of elevated D-dimer levels with fractures. Results: Of 341 eligible patients, 210 (61.6%) had fractures (Fx group) and 131 (38.4%) did not have fractures (non-Fx group). Compared to non-Fx group, Fx group was significantly older (61 ⫹⫺23 vs. 49 ⫹⫺23 yr, p ⬍ 0.0001) and had higher D-dimer levels (23.3 ⫹⫺38.0 vs. 2.8 ⫹⫺4.7 ␮g/ml, p ⬍ 0.0001). ROC analysis showed an area under the curve was 0.81 (95% CI 0.77⫺0.86) and identified D-dimer level ⬎ ⫽ 4.5 ␮g/ml as an optimal cut-off value, with a sensitivity of 68.6%, specificity of 84.7% and positive predictive value of 87.8% for detecting fractures. Multivariable logistic regression analysis showed elevated D-dimer levels (⬎⫽4.5 ␮g/ml) was significantly associated with fractures (adjusted odds ratio 10.7, 95%CI 6.0-19.0, p ⬍ 0.0001). Conclusions: Our findings suggested that an initial D-dimer assay may be efficient in screening for fractures in blunt trauma patients. Further study in the prospective setting is warranted to establish the efficacy.

Introduction: Amputation after open fracture is used as either primary therapy or after failure of attempted salvage. Hypothesis: The purpose of this study was to evaluate those factors associated with amputation in open fractures. Methods: All open fractures were retrospectively reviewed over 6.3 years (3/00-7/07) evaluating for demographics, injury severity, location, mechanism, Gustilo fracture grade, and time from injury to initial washout. Forward stepwise multivariate logistic regression was performed to identify variables associated with amputation. Adjusted odds ratios and 95% confidence intervals (xx, xx-xx) are reported. Results: 1, 487 open fractures were identified. 334 of these fractures involved digits (minor sites), while the remaining 1, 153 were major site fractures. 40 minor and 40 major amputations were performed during the study period. When all open fractures were considered, digit injury (6.1, 3.3-11.4), age (1.21 per decade, 1.05-1.40), penetrating trauma (2.3, 1.3-4.1), and Gustilo grade (vs grades II and IIIa combined: IIIb-6.3, 3.2-12.4, IIIc-19.2, 9.3-39.6) were associated with amputation. Increasing revised trauma score (0.88 per point, 0.80-0.96) was associated with decreased odds of amputation. When only major amputation risk was evaluated, lower extremity injury (3.6, 1.1-11.2), increasing injury severity score (1.05 per point, 1.01-1.08), and Gustilo grade (vs grade II: IIIb-17.8, 4.0-79.8, IIIc-123, 27-560) were associated with amputation. In neither model was time to washout found to be significantly associated with amputation. Conclusions: Gustilo grade was found to be the primary associated factor with amputation risk. Grades associated with significant soft tissue injury (Grade IIIb) or ischemia (Grade IIIc) were more likely to require amputation than lesser soft tissue injury. Factors evaluating physiology or overall injury burden were also found to correlate with amputation risk. In neither model was timely washout of the injury associated with improved salvage rates. Hence, soft tissue injury and patient physiology should be the driving factors in amputation decision making.

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IS REPEAT HEAD CT NECESSARY IN MILD HEAD INJURY AND NORMAL NEUROLOGIC EXAM?

THE EFFECT OF PREINJURY ANTIPLATELET THERAPY ON MORBIDITY AND MORTALITY IN HEAD INJURED PATIENTS

Emily Dawson, Christopher Montgomery, Tracy Koogler, David Frim, University of Chicago Introduction: Traumatic brain injury (TBI) is common after head trauma. Head computed tomography (HCT) is the gold standard to evaluate for intracranial injury in patients with suspected TBI. Children with mild head injury (MHI) and normal HCT (nHCT) typically only require observation. However, patients with MHI, normal neurologic exam (NNE), and abnormal HCT (aHCT) frequently undergo repeated HCT to identify progression of injury prior to clinical deterioration. The benefit of repeated HCT in these patients has not been demonstrated. The potential adverse effects of HCT in children, including increased cost and exposure to ionizing radiation, are considerable. Hypothesis: Children admitted with MHI, aHCT and NNE have unnecessary repeat HCTs and longer length of stay (LOS) compared with patients with nHCT. Methods: From Jan – Dec 2009, we retrospectively reviewed the Trauma Registry Database for all patients admitted with MHI in a Level I Pediatric Trauma Center. We reviewed the medical records for patient demographics, Glascow Coma Score (GCS), loss of consciousness, LOS and number of HCTs. Patients 2m -18y with MHI and NNE (GCS 13-15) were included. Two groups, children with TBI with nHCT and TBI with aHCT, were evaluated for LOS and number of HCTs. Patients with 1st HCT ⬎ 12h from injury, those with 1st HCTs not read at our institution, and those with epidural hemorrhage or depressed skull fractures were excluded. Results: 135 patients were admitted with MHI and NNE. 102 (75.6%) had nHCT and 33 (24.4%) had aHCT. Baseline demographics were the same except for median age (nHCT 10y, aHCT 1.58y) (p ⬍ 0.001). No one in either group required medical/surgical intervention. The median LOS in children with nHCT was 17.4 h (7.4-42.4) and in children with aHCT was 24.1 h (11.9-40.7) (p ⬍ 0.001). The median number of HCT in children with nHCT was 1 (1-2) and in children with aHCT was 2 (1-4) (p ⬍ 0.001). In addition, patients with aHCT (p ⫽ 0.017) and ⬎ 1 HCT (p ⫽ 0.040) were more likely to stay ⬎ 23h. Conclusions: Children with MHI, NNE and aHCT were more likely to have longer LOS and repeated HCT compared with children with nHCT. These results suggest that repeated HCT is unnecessary in the absence of clinical deterioration.


Ariana Nesbit, University of Vermont, Beth Gibbons, Armin Kiankhooy, Joanna Gernsback, Wesley McMillian, Fletcher Allen Health Care Introduction: No study has delineated the effect of preinjury clopidogrel (CLO) in rural head trauma patients, who frequently suffer from a lack of resources and long transport times. Hypothesis: Preinjury CLO would not worsen outcomes in head trauma at our Level 1 trauma center. Methods: A 4-year retrospective cohort analysis of all adult TBI patients was completed. Patients were found in the Neurosurgical Consultation Database and via chart review. Patients on CLO in combination with warfarin were excluded. CLO patients were matched 1:2:2 with patients on aspirin (ASA) or no premorbid antiplatelet (NONE) therapy by year of admission, age, and gender. Results: 988 TBI admissions were reviewed, with preinjury CLO use in 26 (2.6%) patients. The most common MOI was fall from standing (34.9%). There were no differences in mean age (74 years), sex (63% male), admit GCS (14), APACHE II (10), and INR (1.1) between the three groups. Median hospital LOS was longer in patients on CLO (115 hours, range 13-1149) than patients on ASA (83.5 hours, range 3-788) or NONE (77.3 hrs, range 2-1512). NONE had a longer median ICU LOS (28 hours, range 0-1512) than CLO (21 hours, range 0-1149) or ASA(13 hours, range 0-356). Patients in all three groups were most frequently discharged home (54%). Conclusions: Premorbid CLO use was associated with a longer hospital but not ICU LOS in the rural head injured patient. However, these differences do not appear to be clinically significant.

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SEVERE VITAMIN D DEFICIENCY INCREASES THE INCIDENCE, LENGTH OF STAY, AND HOSPITAL COSTS IN SURGICAL INTENSIVE CARE UNIT PATIENTS WITH VENTILATED-ASSOCIATED PNEUMONIA

HIGHER CUMULATIVE ICU FLUID BALANCE IS ASSOCIATED WITH HIGHER COMPLICATION RATES IN CRITICALLY ILL INJURED PATIENTS

Leslie Matthews, Morehouse School of Medicine, Yusuf Ahmed, Emory University SOM, Diane Griggs, Kenneth Wilson, Omar Danner, Morehouse School of Medicine Introduction: Vitamin-D deficiency affects immune function in critically-ill patients. This study investigates the impact of vitamin-D deficiency in surgical intensive care unit (SICU) patients with ventilated-associated pneumonia (VAP). Hypothesis: We hypothesize that severe vitamin-D deficiency increases the incidence, length of stay (LOS), hospital costs, and mortality rate in SICU patients with VAP. Methods: We performed a prospective assessment of the vitamin-D status on 191 patients admitted to the SICU between August 2009 and August 2010. Vitamin-D levels were measured by high pressure liquid chromatography (HPLC) and tandem mass spectrometry (Quest Lab). Vitamin-D deficiency was defined as follows: severe ⱕ 13; moderate 14-26; mild 27-39; and normal ⱖ 40 ng/ml. Results: Of the 191 patients, 129 (67.5%) were male, and 62 (32.5%) were female, 118 (61.8%) were African-American and 73 (38.2%) were Caucasian. 62.3% were severe vitamin-D deficient; 29.3% moderate deficient, and 6.8% mild deficiency. The incidence of VAP in the severe group was 30.3% versus 16% in the non-severe (moderate and mild deficiency) group (p value, 0.040). Mean LOS in the SICU for the severely deficient group was 13.7 days versus 5.9 days. Average ICU cost was $68, 862.52 for the severe group with VAP versus $31, 743.56 (p value, 0.001). Mortality rate the severe vitamin D deficient group with VAP was 10.9% versus 5.6% (p value, 0.220), a trend towards higher mortality. Conclusions: Severe vitamin-D deficiency increases VAP-incidence, LOS and total hospital costs in SICU patients. Therefore, vitamin D deficiency should be corrected in critically-ill SICU patients expeditiously.

207 PNEUMONIA IS PROMOTED BY SYSTEMIC HYPERGLYCEMIA AFTER SEVERE BURN INJURY Robert Kraft, Ahmed Al-Mousawi, University of Texas Medical Branch, Marc Jeschke, Sunnybrook Health Sciences Center, Celeste Finnerty, David Herndon, University of Texas Medical Branch Introduction: Pneumonia represents a major complication following major burns augmenting adverse outcome. Previous clinical studies have indicated that systemic hyperglycemia promotes the incidence of infections in critically-ill patients. Hypothesis: As burn injury causes profound hyperglycemia and an airway/blood glucose threshold over 150 mg/dl exists, we hypothesized that systemic high glucose levels promote bacterial growth in the airways. Methods: Onehundred and six severely burned pediatric patients were enrolled in the study. Patients were divided into two groups: high (H) defined as daily average glucose levels ⬎ 150 mg/dl for ⬎ 25% of length of stay (LOS) (n ⫽ 47); and low (L) with daily average glucose levels ⬍ 150 mg/dl for ⬎ 75% of the LOS(n ⫽ 59). Respiratory parameters were recorded, and incidences of pneumonia, atelectasis, infection, sepsis, and ARDS were assessed. Blood glucose and insulin levels were measured. Statistical analysis was performed using student‘s t-test and chi-square test, with significance set at p ⬍ 0.05. Results: Patient groups were similar in demographics and injury characteristics. Pneumonia in patients on the ventilator (L: 21% H: 32%) and off the ventilator (L: 5% H: 15%), as well as ARDS were significantly higher in the H group (L: 3% H: 19%), (p ⬍ 0.05), while atelectasis rates were not different. Patients in the H group required significantly longer ventilation compared to the L patients (p ⬍ 0.05). Furthermore, incidence of infection and sepsis were significantly higher in the H group (p ⬍ 0.05). Conclusions: Our results indicate that systemic glucose levels over 150 mg/dl are associated with a higher incidence of pneumonia. This finding might be attributed to the presence of glucose on the lung tissue surface promoting bacterial growth.

Daniel Yeh, San Francisco General Hospital, Julin Tang, University of California San Francisco General Hospital Introduction: The purpose of this study was to review ICU fluid balances in critically ill injured patients at San Francisco General Hospital (SFGH), a Level I trauma center. Hypothesis: Our hypothesis was that higher cumulative ICU fluid balance is associated with higher complication rates. Methods: We performed a retrospective analysis of injured patients admitted to the ICU from March 1, 2007 to June 30, 2009. Exclusion criteria were admission to an outside hospital or hospital ward prior to transfer to SFGH ICU, ICU stay ⬍ 58 h, brain or spinal cord injury, renal failure requiring dialysis and burn mechanism. Data collected included demographic data, physiologic data, lab tests, medications, mortality, complications/infections, ventilator days, ICU days, and hospital length of stay (LOS). Results: Our patients had a steady daily fluid gain in the ICU despite rapid normalization of physiologic parameters (HR, MAP, base deficit, CVP). 14% had ⬍ 5 liters fluid gain while ⬎ 30% had ⬎ 20 liters fluid gain. Higher ICU fluid balance was correlated with higher ISS, longer ICU LOS, longer hospital LOS, and higher incidence of complications. There was no difference between patients who received diuretics (DIURETICS) and patients who did not receive diuretics (NO DIURETICS) in terms of age (42 vs. 37, p ⫽ 0.171), ISS (21 vs. 22, p ⫽ 0.54), ICU admission weight (92.2 vs. 88.8, p ⫽ 0.49), and male gender (85% vs. 86%). DIURETICS were more likely to have a blunt injury mechanism (59% vs. 40%), and were more likely to have co-morbid medical conditions (56% vs. 39%). Conclusions: Overresuscitation was common in our patients. Higher cumulative ICU fluid balance was correlated with higher ISS, longer ICU and hospital LOS, and higher incidence of complications. 32% of our patients required diuresis; patients who received diuretics were more likely to have co-morbid medical conditions, blunt injury, as well as longer ICU and hospital LOS. For patients who did not receive diuretics, there was no increase in urine output (“auto-diuresis”) and they continued to accumulate fluid throughout the ICU course. In fully resuscitated critically ill trauma patients, aggressive diuresis may be a potential strategy to prevent complications.

208 PREDICTORS OF HYPOTHERMIA IN TRAUMA PATIENTS Brett Waibel, Brody School of Medicine, East Carolina University, Mark Newell, Brody School of Medicine at ECU, Christopher Durham, East Carolina Univeristy, Megan Barrett, Lisa Schlitzkus, Brody School of Medicine, East Carolina University, Michael Rotondo, East Carolina University Brody School of Medicine Introduction: Hypothermia, an independent predictor of death in trauma patients, has been associated with a greater degree of illness and injury. Whether the patient’s physiology versus the resuscitation itself causes the temperature abnormality is argued. Hypothesis: This study was done to identify those variables associated with admission hypothermia. Methods: Using the NTRACS registry (7/02 – 6/07), adult patients were case matched by ethnicity, gender, and survivor status. Hypothermic patients (ⱕ 35 C) were compared to a non-hypothermic patient (⬎36 C) for demographics, admission characteristics, prehospital fluid/ transfusion therapies, and laboratory data for acidosis and coagulopathy. A conditional logistic regression using the method of fractional polynomials to optimize the scale variables power transformation was performed to identify variables associated with hypothermia. Adjusted odds ratios and 95% confidence intervals (xx, xx-xx) are reported. Results: Of the 10, 075 patients admitted during the study period, 332 (3.3%) had an admission temperature ⱕ 35 C. Hypothermia was associated with acidosis (0.999956 per unit change in cube of bicarbonate, 0.999920-0.999993), hypotension (0.999962 per unit change in square of systolic blood pressure, 0.999942-0.999983), blood transfusion (1.040 per unit change in square root of blood transfused (ml), 1.005-1.077), low Revised Trauma Score (2.185 for RTS ⱕ 7, 1.146-4.166), aeromedical transport (1.729, 1.209-2.474), and need for airway support (2.032, 1.110-3.719). Transfer from outlying hospital (0.626, 0.432-0.908) was protective for admission hypothermia. Prehospital intravenous fluid administration was not associated with hypothermia. Conclusions: Based upon these results, admission hypothermia is associated primarily with altered physiology. These variables are easily identified both in the prehospital setting and by transferring facilities. Using these criteria, more resource intensive or costly rewarming techniques can be reserved for this high risk population. Selection of these patients for aggressive rewarming methods could help to prevent admission hypothermia, with the potential for reducing mortality in these critically injured patients.


209

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PLATELET COUNTS IN TRAUMA PATIENTS ADMITTED TO THE INTENSIVE CARE UNIT THAT RECEIVE ENOXAPARIN (LOVENOX) FOR VENOUS THROMBO-EMBOLISM PROPHYLAXIS

ONE IF BY LAND AND TWO IF BY AIR: EVALUATION OF INTERNET MAPPING TECHNOLOGY AND THE DECISION TO TRANSPORT TRAUMA PATIENTS BY HELICOPTER EMERGENCY MEDICAL SERVICES (HEMS)

Mary Wardrop, Florida State University, Matthew Lube, Christopher DuCoin, Orlando Health

Scott Sherry, Oregon Health & Sciences University, Zeki Karahan, Oregon Health and Science University, Karen Dooley, Oregon Health & Science University, Apostolos Alexandridis, Oregon Health and Sciences University, Kyle Lamb, Oregon Health & Science University, Samantha Underwood, Oregon Health and Science University, Jennifer Watters, Oregon Health & Science University

Introduction: Traumatically injured patients frequently receive low molecular weight heparin (enoxaparin (Lovenox™) ) for prophylaxis against venous thrombo-embolism (VTE). A potential complication of enoxaparin use is the development of heparin induced thrombocytopenia (HIT). The purpose of this study is to determine the effect of enoxaparin on platelet counts and to determine the incidence of HIT in traumatically injured patients receiving enoxaparin for VTE prophylaxis. Hypothesis: Enoxaparin administration for VTE prophylaxis in traumatically injured patients has a low incidence of thrombocytopenia and HIT. Methods: All traumatically injured patients admitted to the Surgical Trauma Intensive Care Unit (ICU) were prospectively followed and platelet counts were recorded (10(3)/␮l ). Heparin antibody studies were ordered when a patients platelet count dropped by 50% or below 100. Data are reported as mean ⫾ standard deviation and statistical analysis was obtained using students t test. Results: From March to August 2010 260 trauma patients were admitted to the ICU. 89 patients were excluded: discharged/died within 5 days (n ⫽ 58); other potential causes of platelet alteration (unfractionated heparin, Plavix™, aspirin use and advanced cirrhosis (n ⫽ 6) ), initial platelet count ⬍ 100 (n ⫽ 5), insufficient number of platelet determinations (n ⫽ 20). 171 patients formed the study group. 120 patients received enoxaparin during their hospital stay and 51 did not. In patients receiving enoxaparin mean baseline platelet count prior to enoxaparin administration was 211 ⫾ 107. 57/120 experienced a mean drop in the platelet count of 54 ⫾ 53 or 22%. 10 patients dropped below 100 and heparin antibodies were negative in all cases. In the 51 patients not receiving enoxaparin mean baseline platelet count was 214 ⫾ 67. 50/51 actually experienced a larger mean drop in platelet count of 77 ⫾ 50 or 36% (p ⫽ 0.02) when compared to the patients receiving enoxaparin. Conclusions: Trauma patients receiving enoxaparin for VTE prophylaxis may experience a small drop in platelet count but more severe thrombocytopenia is uncommon and HIT is a rare event.


Introduction: In the past 10 years there have been a number of HEMS crashes that have resulted in the deaths of patients and air crews with the peak coming in 2008 when there were 9 fatal crashes causing 29 deaths. This has lead to increased scrutiny of the use of these resources and their application. Guidelines suggest that HEMS may only be beneficial if it reduces transport time to a trauma center by more than 10 minutes. With emerging computer software mapping technology, dispatch centers could provide EMS personnel additional information to make decisions for mode of transportation. Hypothesis: Estimations of time to trauma center from the scene using internet mapping technology are similar to that of time from notification to arrival at the trauma center for HEMS. Methods: A trauma registry at a level 1 trauma center was reviewed for all patients admitted via HEMS from a trauma scene from 2007 to 2009. There were 329 HEMS transportations and of those 210 had complete information available. HEMS notification time to arrival at hospital time was calculated in each case (NAT). Using www.google.com/maps, estimated time by ground (GT) was obtained for each transport using the scene location and the trauma center location. Injury severity score (ISS) and mortality were also recorded. Results: The GT and the NAT times were compared at straight distances of ⬍ 15 and ⱖ15 miles, ⬍ 20 and ⱖ20 miles, and ⬍ 25 and ⱖ25 miles. ISS and mortality were compared at those same distances. GT was significantly shorter than NAT in the ⬍15, ⬍ 20, and ⬍ 25 miles (p ⬍ 0.001), but not at ⱖ15, ⱖ20, and ⱖ25 miles. There were no differences in ISS and mortality at each distance. Conclusions: Utilization of internet mapping technology can aid in the correct application of HEMS. Use of ground EMS to transport trauma patients should be the first consideration especially within a 25 mile radius from a trauma center. Prospective studies and application of additional mapping technology needs to be investigated. Limitations of this study include variables such as reasons for HEMS activation (limited EMS units, advanced procedures, prolonged extrication, and traffic conditions). Further research should explore decision making in utilization in HEMS.

Poster: Cardiovascular – Diagnostics 211

212

NO ASSOCIATION BETWEEN ATELECTASIS AND FEVER IN POST-OPERATIVE PEDIATRIC PATIENTS

HYPERLACTATEMIA CORRELATES WITH HYPERGLYCEMIA BUT NOT NECESSARILY DECREASED PERFUSION IN POST-OPERATIVE PEDIATRIC CARDIAC PATIENTS

Jason Kane, Rush University Medical Center, Matthew Friedman, J. Bryan Mitchell, Deli Wang, Carl Backer, Northwestern University- Children’s Memorial Hospital Introduction: Post-operative fever is common after cardiac surgery. Atelectasis is a suggested cause of fever; however, this conjecture is not supported by physiologic mechanisms. To date, there have been no studies on whether a relationship exists between atelectasis and fever in children. The purpose of this study was to investigate whether an association exists between atelectasis and post-operative fever. Hypothesis: The hypothesis is that no association exists between atelectasis and post-operative fever in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: A retrospective review was performed on consecutive pediatric patients (ⱕ18 years) who underwent cardiac surgery on CPB at Children’s Memorial Hospital in 2009. An attending radiologist independently reviewed and scored radiographs for atelectasis, and was blinded to clinical data. The highest daily temperature (Tmax) was reviewed for 72 consecutive hours post-op. Fever was defined as Tmax ⱖ 38°C. The Cochrane-Mantel-Haenszel test and generalized linear models were used to evaluate association between fever and atelectasis. Results: 203 patients met inclusion criteria. 139 patients (68.5%) had fever at least once during post-op day 0-2. The incidence of atelectasis on post-operative day 0, 1, and 2 was 42%, 56%, and 71% respectively. There was no association between fever and atelectasis on any post-op day (p ⫽ 0.29). Cultures were performed on 81 patients, and infection (7 ETT, 1 urine) was found in 8 patients (3.9%). Duration of CPB was associated with presence of fever (p ⫽ 0.002), but not with the actual Tmax (p ⫽ 0.374). Cyanotic patients were less likely to have fever compared to acyanotic patients over the 3 postoperative days (36% vs 39%, 36% vs 52%, 14% vs 34%) (OR ⫽ 0.56, 95% CI 0.32, 0.99, p ⫽ 0.04). The frequency of atelectasis was similar between cyanotic and acyanotic patients (p ⫽ 0.922). Conclusions: Post-operative fever and atelectasis in children are common after cardiac surgery; however there is no association between fever and atelectasis. This finding contradicts pervasive medical dogma. In children undergoing cardiac surgery with CPB, fever in the postoperative period should not be attributed to atelectasis.

Kevin Maher, Children’s Healthcare of Atlanta Emory University, Catherine Preissig, Medical Center of Central Georgia, Shri Deshpandi, Nikhil Chanani, Janet Simsic, Emory University, Children’s Healthcare of Atlanta at Egleston, Mark Rigby, Emory University School of Medicine, Children’s Healthcare of Atlanta Introduction: Hyperlactatemia is common in post-operative cardiac patients, and can occur in the setting of poor tissue perfusion (Type A) or when evidence of poor perfusion is absent (Type B). Further, hyperglycemia occurs frequently in critical illness, is associated with poor outcome, and glycemic control decreases morbidity and mortality in some patients. The interplay between cellular stress, glucose dysregulation, and lactic acidosis has not been well-studied. We aimed to evaluate the relationship between lactate, blood glucose (BG), and markers of perfusion in pediatric cardiac ICU patients. Hypothesis: We hypothesized that hyperlactatemia and hyperglycemia may be associated in pediatric post-operative cardiac patients. Methods: We retrospectively evaluated 25 post-operative patients admitted to a dedicated pediatric cardiac ICU. Lactate, BG, markers of perfusion and oxygenation, and demographic data were analyzed. Results: Mean patient age was 3.9 years, (range 3d- 16 years). A total of 200 simultaneous lactate and BG levels were analyzed. Lactate levels ranged from 0.33 to 10.9mmol/dl; BG values ranged from 98-447mg/dL. There was a positive correlation between BG and lactate values, where increasing BG values were closely related to increased lactate levels (r ⫽ 0.76). Mean BG associated with normal lactate was 120mg/dL. This was significantly lower than the mean BG associated with elevated lactate values (⬎2.22 mmol/l), which was 208.8 mg/dL (p ⬍ 0.01). Markers of poor perfusion, including pH and bicarbonate levels, were not associated with either hyperglycemia or hyperlactatemia. pH values ranged from 7.30-7.61, while bicarbonate levels ranged from 19-30.4mmol/L. Conclusions: Hyperglycemia is associated with Type B lactic acidosis in the post-operative pediatric cardiac patient, and resolution of high BG appears to be associated with resolution of hyperlactatemia. Reasons for this relationship are not fully understood. Lack of proper glucose utilization may lead to increased lactate production or impaired lactate clearance in this population. Further studies are needed to ascertain the significance of this relationship, and determine whether patient outcomes correlate to resolution of elevated lactate and BG.

213 TAKOTSUBO CARDIOMYOPATHY IN CRITICAL CARE MEDICINE Yeun Tarl Fresner Jao, Ching-Chang Fang, Yi Chen, Ching-Lung Yu, Shih-Pu Wang, Tainan Municipal Hospital Introduction: There is limited data as to the occurrence and presentation of transient left ventricular apical ballooning (TLVAB) occurring in the ICU in terms of ECG findings and symptomatology, compared with patients with TLVAB not initially admitted to the ICU. Hypothesis: To determine if patients with TLVAB in the ICU presents differently in terms of clinical features and ECG. Methods: Thirty-three patients were diagnosed to have TLVAB in our hospital from February, 2002 to March, 2009. Findings compatible with acute myocardial infarction or acute coronary syndrome prompted emergent coronary angiography. Clinical, ECG and angiographic findings were analyzed. Results: Eighteen (55%) patients were female. Mean age was 73 ⫾ 12yrs. 17(52%) patients developed pulmonary edema and 18(55%) developed respiratory failure. 8(24%) patients died during admission. Initial TLVAB presentation was pulmonary edema and ECG changes in 17(52%) and 16(49%) patients respectively. ST-segment elevation and T wave inversion were noted in 18(55%) and 21(64%) patients respectively. 16(48%) patients comprised the ICU-group, while 17(52%) patients comprised the non-ICU group. More patients in the non-ICU group presented with chest pain (35 vs. 6%, p ⫽ 0.041), while patients in the ICU group had dyspnea and pulmonary edema (75 vs. 29%, p ⫽ 0.009). STsegment elevation was the most prominent ECG change in the non-ICU group (p ⫽ 0.009), while T wave inversion was more common in the ICU group. Conclusions: Pulmonary edema, instead of chest pain occurred more frequently as the initial presentation of TLVAB in the ICU. Deep T wave inversion and poor R wave progression, instead of ST-segment elevation were the most prominent ECG findings in the ICU group. Patients with these features need not undergo emergent cardiac catheterization, or receive anticoagulants and thrombolytic agents.


Poster: Cardiovascular – Monitoring-1 215

216

ACCURACY OF NON-INVASIVE HEMOGLOBIN MONITORING IN INTENSIVE CARE UNIT PATIENTS WITH VERY LOW HEMOGLOBIN

ACTIVE CIRCULATION VOLUME (ACV) AS AN INDICATOR OF VOLUMETRIC AFTERLOAD IN PEDIATRIC PATIENTS

Anna Juhl, Sajjad Naqvi, Oshuare Aregbeyen , Selma Demir, Englewood Hospital and Medical Center , Aryeh Shander, Englewood Hospital & Medical Center Introduction: The introduction of the non-invasive continuous hemoglobin monitor, Rainbow SET Pulse CO-Oximeter (Masimo Corporation, Irvine, CA) allows for immediate and continuous reporting of hemoglobin level. The device is FDAcleared for clinical use, but limited data exist on its performance in severely anemic patients. Hypothesis: Hemoglobin levels obtained from SpHb monitoring are comparable with measurements made using a reference method in patients with critically low hemoglobin levels. Methods: After IRB approval, consenting ICU patients with hemoglobin levels less than 8g/dl, wore Rainbow Resposable finger sensors connected to Masimo Radical-7 Pulse CO-Oximeters for the continuous noninvasive recording of hemoglobin (SpHb). Venous blood samples were obtained on a daily basis and analyzed by a COULTER analyzer LH 780 (Beckman Coulter, Inc, Miami, FL) to obtain the reference hemoglobin levels. Bias and precision of the SpHB values reported from the Radical-7 at the time of blood draw compared with the invasive reference values were calculated. Results: Nine ICU patients with a median length of stay of 3 days (range 1-12 days) were included in the study. Hemoglobin values ranged from 2.9-9.6 g/dL from Pulse CO-Oximetry and 4.3-8.6 g/dL from the reference device. Despite very low hemoglobin levels, no patient expired. A total of 19 paired samples were collected from the patients. The mean bias and precision of SpHb values compared with laboratory reference values were 0.70 g/dL and 1.05 g/dL, respectively. Evaluation of the Bland-Altman plot of the bias versus mean measurements of 19 comparative samples indicated that bias was distributed uniformly across the range of the measurements with no specific trend spotted. The limits of agreement between the two methods were calculated to be 2.76 and -1.36 g/dL. Conclusions: The Radical-7 Pulse CO-Oximeter provided clinically acceptable agreement with laboratory reference values in ICU patients with critically low hemoglobin. The ability to measure hemoglobin noninvasively and continuously has the potential to facilitate the timely detection of changes in hemoglobin and thus improve patient blood management decisions in patients with critically low hemoglobin.

Ivory Crittendon, William Dreyer, Jamie Decker, Jeffrey Kim, Texas Childrens Hospital Introduction: Currently there exists no simple method to routinely measure volumetric afterload at the bedside in PICU patients. The novel COstatus system (Transonic Systems Inc, NY) works off standard in situ arterial and central venous lines and uses isotonic saline as an indicator to routinely measure cardiac output (CO) and blood volumes including ACV, which is defined as the blood volume in which isotonic saline mixes within one minute after injection. CO measurements were previously validated [1]. Hypothesis: To evaluate the utility of ACV as an indicator of afterload by comparing it to systemic vascular resistance (SVR) in the pediatric population. Methods: Twenty three patients (9.4-78 kg, aged between 1-17 years) with a structurally normal heart undergoing hemodynamic assessment in the cardiac catheterization laboratory were studied. For COstatus measurements [1], an extracorporeal AV loop, with two ultrasound sensors clamped on, was connected between the existing femoral arterial line and central venous catheter. For the duration (5-8 minutes) of measurements, blood was circulated at 12ml/min through the loop from artery to vein using a small roller pump. 1ml/kg (upto 30 ml) body temperature isotonic saline was injected to obtain SVR and ACV measurements, and 2-3 injections were performed and averaged for comparison. Results: A total of 23 averaged pairs were used for comparison. ACV ranged from 28 -59 ml/kg (3.4 ⫾ 1.2) and the SVRI ranged from 833-2078 dy/s/cm5/m2 (1352 ⫾ 326). A negative correlation of r ⫽ ⫺ 0.62 was observed between ACVI and SVRI, suggesting that the higher the resistance, the lower the volumetric afterload and vice versa. A similar relationship was also observed in adults [2]. Conclusions: This is the first study in children showing that COstatus measured active circulation volume strongly correlates with systemic vascular resistance and hence could be used as an indicator of afterload in this population. Further clinical studies in patients with different clinical conditions such as shock and sepsis are required to establish the clinical utility of ACV. NIH SBIR Grant# R44HL061994. [1] Crittendon I et al, Crit Care Med, 37, 2009; [2] Galstyan G et al, Intensive Care Med, S76, 34(1), 2008

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A COMPARATIVE STUDY OF SYSTOLIC PRESSURE VARIATION AND BLOOD VOLUME MEASUREMENTS

CONTINUOUSLY MONITORED CENTRAL VENOUS OXYGEN SATURATION AFTER PEDIATRIC OPEN HEART SURGERY

Sho Furuta, Kevin Pei, Damian DeFrancesch, Brian Nishiguchi, David Inouye, Michael Hayashi, University of Hawaii , Fedor Lurie, Straub Foundation, Danny Takanishi, University of Hawaii , Mihae Yu, University of Hawaii School of Medicine and the Queen’s Medical Center Introduction: Assessing circulating blood volume (BV) clinically has been a challenge especially in patients with third spacing of fluids during shock states. Studies suggest that systolic pressure variation (SPV), the difference between maximal and minimal systolic pressure (SP) values during one mechanical breath, is correlated with cardiac fluid responsiveness defined as an increase in the stoke index or cardiac index ⬎ 10 to 15%. However, SPV is confounded by the patient’s cardiac function, mechanism of breathing, and ventilator settings and may not reflect circulating BV. Hypothesis: There is no relationship between BV and SPV. Methods: Critically ill surgical patients had simultaneous measurement of BV and SPV. All data acquired during irregular heart rate and spontaneous respirations were excluded. BV was measured using BVA (Daxor, NY, NY). After obtaining a baseline sample of 5 mL of blood and a simultaneous blood hematocrit, I-131 was injected and allowed to mix completely for 12 minutes. To correct for albumin transudation, serial blood measurements of 5 mL were collected at 12, 18, 24, 30, and 36 minutes post I-131-albumin injection and extrapolated to time zero to calculate the plasma volume (PV). Hematocrit ⫽ red blood cell volume (RBCV)/ (RBCV ⫹ PV). BV ⫽ RBCV ⫹ PV. The BV values were presented as % deviation from normal/ ideal BV for the individual. Hypovolemia was defined as ⬍ 0%, hypervolemia as ⬎ 8% of the normal/ ideal BV. SPV ⫽ SPmaximum - SPminimum during one respiratory cycle. SPV ⬎ 10% indicates cardiac fluid responsiveness. Results: The patients (n ⫽ 100) contributed 301 data points with the following demographics: age 62 ⫾ 16 years, Femal: Male 61: 39, APACHE II ⫽ 24 ⫾ 3.0. Diagnoses included: severe sepsis/ septic shock (n ⫽ 68), ARDS (n ⫽ 37), Cardiogenic shock (n ⫽ 21). Regression analysis showed no correlation between BV and SPV (r ⫽ 0.023, R2 ⫽ 0.0005, p ⫽ 0.687). BV demonstrated hypovolemic state in 52 of 240 instances (22%) when SPV was ⬍ 10%. BV demonstrated hypervolemic state in 27 of 37 instances (73%) when SPV was ⬎ 10%. Conclusions: Although SPV values of ⬎10% have been used to suggest cardiac fluid responsiveness, SPV does not have a relationship to circulating BV.


Richard Fernandez, Children’s Memorial Hospital, Jason Kane, Rush University Medical Center, Carl Backer, Denise Goodman, Children’s Memorial Hospital Introduction: Monitoring of continuous central venous oxygen saturation (SCVO2) is a useful indicator of adequate resuscitation and allows calculation of arterio-venous oxygen difference (DAVO2). The utility of continuous SCVO2 to predict impending clinical deterioration after surgery for congenital heart disease has not been well established. Hypothesis: We hypothesize that changes in SCVO2 and DAVO2 anticipate critical events in post-operative pediatric patients. Methods: A convenience sample of 23 patients ⬍ 12 months undergoing surgery for congenital heart disease on cardiopulmonary bypass had Pediasat® Oximetric Catheters (Edwards Lifesciences, Irvine, CA) placed in the OR. SCVO2 and DAVO2 were measured continuously and somatic near infrared spectroscopy (rSO2) was recorded every 5 minutes. Critical events were defined a priori as changes in the heart rate (HR) or mean arterial pressure (MAP) by ⬎ 20%, changes in pulse oximetry (SPO2) by ⬎ 10 percentage points, or elevation of lactate above the upper limit of normal. Serial SCVO2 , DAVO2, and rSO2 preceding the events were analyzed using the Friedman test, given the nonparametric nature of data. Results: SCVO2 variation preceded elevations in MAP (p ⫽ .054), and decreases in SPO2 (p ⫽ .068). DAVO2 variation preceded decreases in MAP (p ⫽ .05). No variations were seen in SCVO2 or DAVO2 for all events in aggregate. rSO2 showed significant changes prior to all events in aggregate (p ⫽ .002). Specifically, rSO2 variation was seen preceding elevations in MAP (p ⫽ .006), decrease in SPO2 (p ⫽ .023), and higher HR (p ⫽ .025). No changes in rSO2 were noted for elevations in lactate (p ⫽ .37). Conclusions: In this pilot study, continuously measured SCVO2 and DAVO2 preceded alterations in MAP, but not changes in heart rate or lactate in this group of patients undergoing surgery for congenital heart disease. SCVO2 variation displayed a trend towards significance prior to arterial desaturation. rSO2 revealed significant variation prior to elevations in MAP, arterial desaturation, and tachycardia. The clinical utility of continuously measured SCVO2 in this unselected population is unclear.

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NOVEL SYSTEM FOR MEASUREMENT OF CARDIAC OUTPUT (CO) AND BLOOD VOLUMES IN NEONATAL ICU PATIENTS

NORMALIZING BLOOD VOLUMES IN NEONATAL AND PEDIATRIC ICU PATIENTS

Bonnie Marr, Crouse Hospital Introduction: Measurement of CO and blood volumes is important for the management of critically ill but there exists no technique that can be routinely used to measure these parameters in NICU patients. Novel COstatus system (Transonic Systems Inc, Ithaca, NY), based on ultrasound dilution (UD) technology, works off in-situ catheters without any blood loss to measure CO and blood volumes: Central Blood Volume Index (CBVI) and Active Circulation Volume Index (ACVI). Uniqueness of this system lies in its extracorporeal nature which allows for its use with patients of any age and weight. Hypothesis: Purpose of this study was to test the feasibility of using COstatus with NICU patients. Methods: Four NICU patients were studied. A primed AV loop was connected between in-situ umbilical arterial and dual lumen umbilical venous catheters with two UD sensors placed on the loop to measure venous injection and arterial dilution curves. A roller pump was used to circulate blood at 8-10 ml/min through this AV loop from the artery to vein up to 5 minutes for measurements. 2-4 ml of body temperature isotonic saline (indicator) was injected into venous side. At the end, AV loop is flushed with heparinized saline returning blood to the patient. Results: Patient CO (l/min) CI(l/min/m2) CBVI (ml/kg) ACVI (ml/ kg)#1 - 0.9 kg 0.23 ⫾ 0.04 2.4 ⫾ 0.4 19 ⫾ 1.4 71 ⫾ 5#2 - 1.13 kg 0.13 ⫾ 0.01 1.28 ⫾ 0.1 12 ⫾ 0.6 55 ⫾ 3.6#3 - 2.33 kg 0.28 ⫾ 0.03 1.59 ⫾ 0.2 8 ⫾ 0.6 52 ⫾ 4.9 #4 - 3.4 kg 0.46 ⫾ 0.02 2.2 ⫾ 0.1 8 ⫾ 0.9 35 ⫾ 4(before infusion)#4 - 3.4kg 0.53 ⫾ 0.03 2.5 ⫾ 0.1 8 ⫾ 0.6 50 ⫾ 4(after infsusion) Conclusions: This pilot study in NICU patients showed that COstatus can be used to measure CO in babies as small as 0.9 kg and blood volumes, which could be used to quantitatively assess the effects of therapies. Further clinical studies in NICU patients with different conditions are required. NIH SBIR Grant # R44 HL061994

Naveen Thuramalla, Victor Kislukhin, Nikolai Krivitski, Transonic Systems Inc Introduction: The relation between body surface area (BSA) and body weight (BW) changes with patient’s weight in neonates and pediatrics. According to the NIH database the ratio of BSA to BW changes 3 times in the weight range of 1-12 kg and 1.5 times in the weight range of 12-80 kg. The question remains what normalization approach has the most clinical relevance. Criteria for evaluation: parameter that is least dependant on weight should be considered the best for normalization. Hypothesis: Purpose of this study was to investigate the effect of normalizing by BSA and by BW on two blood volume parameters measured by COstatus (Transonic Systems Inc, NY) in neonatal and pediatric patients. Methods: Total heart end diastolic volume (TEDV) and Central blood volume (CBV) represent the blood volume in the heart, lungs and large vessels. Transonic data archive from 96 neonatal and pediatric patients was used. Cases with intra-cardiac shunts and ductus arteriosus were excluded. Results: Correlation (r2) values between weight and blood volumes normalized by weight (wt) and BSA are shown below n Weight (kg) CBVI-wt CBVI-BSA TEDVI-wt TEDVI-BSA 438 0.9-12 0.06 0.21 0.004 0.16 803 0.9-102 0 0.24 0.05 0.16 n - Number of measurements Conclusions: This study showed that normalization of blood volumes by body weight is more suitable in neonates and children, in the weight range of 1-12 kg. Normalizing these volumes by body surface area show some correlation with weight and hence could lead to misinterpretation of the hemodynamic status of the patient. NIH SBIR Grant # R44 HL061994

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IATROGENIC QTC PROLONGATION: INCIDENCE AND RISK FACTORS IN THE ICU

TOTAL END DIASTOLIC VOLUME (TEDV) AND CENTRAL BLOOD VOLUME (CBV) AS NOVEL PRELOAD INDICATORS IN PEDIATRIC PATIENTS

Dustin Gladden, Melissa Vandenberg, Spectrum Health, Gregory Neagos, Michigan Medical, PC, Heather Bockheim, Spectrum-Health Introduction: Critically ill patients often have several risk factors for QTc prolongation (QTcP) at baseline. Iatrogenic factors encountered in the ICU, including medications and electrolyte imbalances, may further prolong the QTc. QTcP may lead to torsades de pointes (TdP); however, the incidence of QTcP is illdefined. The aim of this study is to determine the incidence of QTcP in the critically ill and to identify risk factors associated with QTcP. Hypothesis: We expect the incidence of QTcP in the ICU to be uncommon and to increase with ICU length of stay. Methods: A single-center, retrospective, cohort study including adult patients admitted to the medical and surgical ICU in June 2009 was performed. Patients who stayed ⬍ 24 hours in the ICU or had insufficient ECG data were excluded. All ECGs collected during the first three weeks of ICU stay were manually measured to find the longest QT interval on the II and V1 leads and were corrected for heart rate with the Bazett formula to obtain the QTc. Iatrogenic QTcP was defined as measured QTc ⬎ 450 ms for males, ⬎ 470 ms for females, or a ⬎ 60 ms increase from baseline for patients with baseline QTcP. Demographics, established risk factors, and potential iatrogenic factors associated with QTcP were collected. All medications having a possible risk of QTcP/TdP and factors altering drug concentration were recorded. Results: 111 patients were evaluated (57% MICU, 43% SICU). 31.5% had iatrogenic QTcP per definition, none resulting in TdP. 58% had at least 1 prolonged QTc in the ICU, although 28% had QTcP at baseline. Upon univariate analysis, patients with iatrogenic QTcP were more likely to have a longer length of stay (5 v. 3 days, p ⫽ 0.01). 68.5% were administered a QTc prolonging medication, most often ondansetron, levofloxacin, and amiodarone. Iatrogenic and medication associated factors including PK/PD drug interactions were not significantly different between groups. Conclusions: While iatrogenic QTcP was common in the ICU, QTc prolonging medications did not make a significant impact in its prevalence. Response to QTcP should be individualized by weighing risks and benefits of therapy until further data is available.

Ivory Crittendon, William Dreyer, Jamie Decker, Jeffrey Kim, Texas Childrens Hospital Introduction: Measurement of cardiac index (CI) and preload assessment are crucial in the management of critically ill children [1]. The COstatus system works off standard in situ arterial and central venous lines and uses isotonic saline as an indicator to routinely measure CI and blood volumes, including TEDV (blood volume in four heart chambers at the end of diastole) and CBV (blood volume in the heart, lungs and major vessels). CI measurements were previously validated [2]. Hypothesis: To compare conventional preload parameters such as central venous pressure (CVP), pulmonary artery pressure (PAP) and wedge pressure (PAWP) with TEDV and CBV. Methods: Twenty-two patients (9.4-78 kg; 1-17 years) with structurally normal hearts undergoing hemodynamic assessment in the cardiac catheterization laboratory were studied. For COstatus measurements, blood was circulated at 12ml/min through an AV loop that was connected between insitu catheters. 2-3 injections of 1ml/kg (upto 30ml) warm saline was injected into the AV loop [2]. Results: ‘r’ values Range CI TEDVI CBVICVP, mm Hg 3-15 0.03 0.12 0.27PAP, mm Hg 12-35 0.035 0.01 0.01PAWP, mm Hg 6-26 0.072 0.052 0.25TEDVI, ml/kg 5.6 –14.6 0.62 0.64CBVI, ml/kg 9.9-29 0.58 0.64 -CI, l/min/m2 1.4 – 4.7; Mean ⫾ SD ⫽ 3.1 ⫾ 0.58 Compared to conventional preload parameters, novel TEDV and CBV showed significantly improved correlation with cardiac index. This is in agreement with results from a similar study [3] in adults. Conclusions: This is the first study in children suggesting that TEDV and CBV could be used as preload indicators. Thus, the COstatus system offers a less invasive means to assess volume status in pediatric patients. Further studies assessing the dynamic changes in these blood volumes in children with different clinical conditions are required. NIH SBIR Grant# R44HL061994. [1] Lopez-Herce J et al, Ped Intl, 51, 2009; [2] Crittendon I et al, Crit Care Med, 37, 2009; [3] Godje O et al, Eur J Cardio-Thor Surg, 13, 1998


223 THE IMPACT OF TEE MONITORING IN CRITICAL CARE Harold Hastings, Scott Roth, ImaCor Inc Introduction: The purpose of this study was to determine the impact of a miniaturized TEE probe (the ImaCor ClariTEE™, approximately the size of a nasogastric tube) on hemodynamic management in critical care settings, including cardiac surgery and general ICU patients. The ImaCor Zura™ ultrasound imaging system was designed and FDA for episodic hemodynamic monitoring over up to 72 hours. Hypothesis: TEE monitoring has a significant impact on hemodynamic management in critical care. Methods: A retrospective case review of 101 patients in a variety of ICU settings, including a series of 33 patients post cardiac surgery. Results: TEE monitoring led to clinical management changes in 51 of these 101 patients (50%). Most changes involved fluid administration and adjustment of vasoactive and/or inotropic agents. TEE monitoring also guided surgical decision making, avoiding reoperations in three of the 33 patients in our post cardiac surgery series and identifying tamponade requiring rapid intervention in one patient. Conclusions: TEE monitoring had a significant impact upon hemodynamic management. Clinical management was influenced in 50% of patients; c.f. Hu¨ttemann’s[1] reported 36% (range 10% - 69%). TEE monitoring was also shown to improve hemodynamic management by detecting underlying causes for hemodynamic instability not detected by other monitoring modalities. Improved management has the potential to reduce hospital stay[2]. TEE monitoring was also shown to guide surgical intervention for hemodynamic instability post cardiac surgery, including both identifying tamponade requiring rapid intervention and avoiding reoperations Surgical re-exploration after cardiac surgery has been shown to increase morbidity, extend mechanical ventilation time, and prolong time spent in the ICU [3] and increase cost[4]. References: 1. Hu¨ttemann E. 2006. Minerva Anestesiol 2006; 72: 891-913. 2. Pölönen P et al. Anesth Analg 2000;90:1052-9. 3. Ranucci M et al. Ann Thorac Surg 2008;86: 1557-62. 4. Speir AM et al. Ann Thoracic Surg. 2009; 88: 40-46.


Poster: Cardiovascular – Monitoring-2 224

225

THE USE OF LESS INVASIVE HEMODYNAMIC MONITORING IN 3 SPECIALTY SURGICAL ICUS : A 6 YEAR EXPERIENCE AT A TERTIARY MEDICAL CENTER

HOW WELL DO NURSING FLOWSHEETS REPRESENT MEASURED HEMODYNAMICS?

Orlando Kirton, Robert Brautigam, Kevin Keating, John Mah, Marc Palter, Judith Pepe, Manish Tandon, Randy Edwards, Karyn Butler, Hartford Hospital Introduction: Less invasive hemodynamic monitoring (esophageal doppler monitor:EDM and arterial pulse contour analysis: Flotrac) is increasingly used as an alternative to right heart catheterization (RHC) in the critically ill and injured. Hypothesis: The decrease use of RHCs is not associated with increased mortality or vasopressor administration. Methods: 6 year review (FY 2004-FY 2009) of all patients admitted to either the neuro-intensive care/ trauma, cardiac surgery, or general surgery/transplant ICUs. Data points included the # of admissions, case mix index, LOS, mortality, insertion of monitoring devices (RHC, EDM, and flotrac probes), and vasopressor administration. Cross tables analyzed by Chisquare. Results: No change in admissions, mortality, case mix, LOS (ICU and hospital) in any unit over the 6 years. (p ⬎ .05) There was a progressive decrease in RHC insertions, (p ⬍ .02) associated with an increase in Flotrac or EDM placement( p ⬍ .001), Moreover, there was a progressive increase in the number of monitored patients who did not receive vasopressors, (p ⬍ .001) and a decrease in the amount of vasopressors administered in those patients who were monitored.(p ⬍ .001) Conclusions: The increased insertion of less invasive monitoring devices did not negatively impact mortality, was associated with decreased vasopressor administration., and more frequent monitoring without vasopressor administration.

Jonathan Hastie, Andrew Rosenberg, University of Michigan, Kevin Tremper, University of Michigan Medical Center, James Blum, University of Michigan Health System Introduction: Phyisologic monitor networks record ICU data at far higher fidelity than hourly recording in nursing flowsheets, but there are fundamental questions as to how well nursing flowsheet data reflect the measured data recorded on a physiologic monitor network. Hypothesis: We hypothesize that the hourly hemodynamic variables recorded on a nursing flowsheet reflect the average physiologic monitor values within 10% variance at least 80% of the time. Methods: We reviewed 1680 hours of continually collected hemodynamic data (heart rate (HR), arterial systolic blood pressure [SBP], arterial diastolic blood pressure [DBP], noninvasive [cuff] SBP, and cuff DBP) for all patients within a surgical ICU at a tertiary care center. Median filtering over appropriate epochs was used to compare corresponding hourly nursing flowsheet data. For continuously collected data (arterial-line pressure andHR), epochs were defined as five-minute intervals preceding the recorded value. For intermittently collected data (cuff blood pressure), the median value over one hour was used. We then determined whether each physiologic monitor epoch was within 10, 20, or 40% of the value recorded on the nursing flowsheet. Results: Measured cuff SBP was within 10, 20, and 40% variance of the documented cuff SBP 56.6, 84.3, or 96.4% of the time, whereas the measured cuff DBP was within 10, 20, and 40% variance 47.1, 82.4, or 97.6% of the time. Measured arterial SBP and DBP correspondence within a 10, 20, and 40% variance of the documented values was 64.6, 90.1, and 99.1%; and 67.2, 90.5, and 97.9%, respectively. Measured HR demonstrated the highest correspondence, being within a 10, 20, and 40% variance in 84.4, 97.3, or 99.6% of all instances. Conclusions: Nursing flowsheet hourly data does not correspond to the values recorded on physiologic monitor networks. Further research is required to determine which values better represent the actual state of the patient.

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CORRELATION OF MIDLINE VENOUS PRESSURES WITH CENTRAL VENOUS PRESSURES

CARDIAC OUTPUT MEASUREMENTS WITH AN UNCALIBRATED PULSE CONTOUR METHOD IN CRITICALLY ILL PATIENTS: COMPARISON WITH THERMODILUTION AND ECHOCARDIOGRAPHY

Kavan Ramachandran, Kishan Ramachandran, Robbert Crusio, Yizhak Kupfer, Taek Yoon, Sidney Tessler, Maimonides Medical Center Introduction: Midline catheters are extended peripheral venous catheters that end in the axillary vein. We prospectively measured venous pressures from midline catheters and correlated with the pressures measured from a central venous catheter. Hypothesis: To compare venous pressures as measured by midline catheters as compared to central venous catheters. Methods: Eighteen gauge midline catheters were placed through either the basilic or cephalic veins with the catheter tip ending in the axillary vein. Sixteen gauge central venous catheters were placed through the subclavian or internal jugular veins with the catheter tip ending in the distal superior vena cava. Tip positions were confirmed radiographically. Measurements of venous pressures were simultaneously recorded from both catheters. Results: Sixteen patients in the medical intensive care unit (MICU) between July 2009 and June 2010 had simultaneous midline and central venous catheters. Multiple simultaneous venous pressures were measured. Mean central venous pressures were 11.7 cm H2O (⫾5.3) compared to 12.4 cm H2O (⫾5.7) from the midline catheters. The correlation coefficient was 0.935; coefficient of determination r2 ⫽ 0.875 (P ⫽ 0.001). Conclusions: There is a high correlation between venous pressures derived from midline catheters and central venous catheters. Midline catheters can be used to measure venous pressures. The insertion of midline catheters is safer than a central venous catheter because it does not cause pneumothoraces or hemothoraces.

Sabino Scolletta, Department of Intensive Care, Erasme Hospital, Laurent Bodson, Katia Donadello, Alessandro Devigili, Erasme Hospital, Fabio Silvio Taccone, Erasme University Hospital, Antoine Herpain, Erasme Hospital, JeanLouis Vincent, Daniel De Backer, Erasme University Hospital Introduction: Non invasive cardiac output (CO) measurements is increasingly used. A new uncalibrated pulse contour method (MostCare, Vytech Health, Vygon, Ecouen, France) based on the principle of physics theory of perturbation has recently been developed. Hypothesis: We hypothesized that this uncalibrated method could adequately reflect CO determined by thermodilution (ThD) or echography (Echo). Methods: We enrolled 70 patients admitted to a 35-bed university hospital mixed Intensive Care Unit who required an Echo evaluation and who had invasive monitoring of blood pressure. All the patients had the CO simultaneously assessed by Echo (Toshiba Xario SSA-660A, Japan) (CO-E) and MostCare (CO-M). In a subgroup of 19 patients also monitored with a pulmonary artery catheter, we also assessed the CO by continuous ThD (Vigilance, Edward Lifescience Corporation, Irvine, CA, USA)(CO-TH) by Echo and by MostCare. Linear correlation and Bland-Altman analyses were used to compare the three methods. Results: In all the 70 patients CO-E and CO-M ranged from 1.9-11.3 and 2.2-11.4 L/min, respectively. Mean CO-E was 5.8 ⫾ 2.1 L/min and mean CO-M was 6.1 ⫾ 1.9 L/min. The relationship between CO-E and CO-M showed an r2 of 0.86 and the bias was -0.25 L/min (LoA -1.85 to 1.35), yielding a percentage error (PE) of 26%.In the subgroup of 19 patients, mean CO-TH was 6.6 ⫾ 2.6 L/min, mean CO-E was 6.0 ⫾ 1.9 L/min and mean CO-M was 6.2 ⫾ 2.8 L/min. The comparison between CO-TH and CO-M showed an r2 of 0.86. and the bias was 0.27 L/min (LoA -1.73 to 2.27) with a PE of 29%. The correlation between CO-E and CO-M showed an r2 of 0.84 and the bias was -0.31 L/min (LoA -1.81 to 1.19) with a PE of 24%. These results are similar to comparison between CO-TH and CO-E showing a r2 of 0.85, bias of 0.69 L/min (LoA -1.40 to 2.79), and a PE of 30%. Conclusions: Uncalibrated pulse contour analysis with MostCare device reliably measures cardiac outputin critically ill patients.


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ROLE OF SPLANCHNIC AND/OR RENAL OXYGENATION MONITORING USING NEAR INFRARED SPECTROSCOPY FOR DETECTION OF LOW CARDIAC OUTPUT IN CHILDREN AFTER CARDIAC SURGERY

EFFECT OF VASODILATION ON DIFFERENT COMPONENTS OF PHOTOPLETHYSMOGRAPH

Utpal Bhalala, Akira Nishisaki, The Children’s Hospital of Philadelphia, Derrick Mcqueen, Newark Beth Isreal Medical Center, Duraisamy Balaguru, University of Texas-Houston Medical School, Wynne Morrison, Geoffrey Bird, Vinay Nadkarni, The Children’s Hospital of Philadelphia, Meena Nathan, Children’s Hospital Boston, Joanne Starr, Newark Beth Israel Medical Center

Introduction: Photoplethysmography (PPG) uses light transmission to measure changes in tissue volume. The PPG can be separated into two components, AC and DC. Little is currently known about the effect of decreasing vasomotor tone on the AC and DC components of the PPG signal. Hypothesis: We hypothesized that vasodilation will increase the AC component and decrease the DC component of PPG. Methods: After IRB approval and informed consent we studied ten healthy volunteers. A unilateral axillary brachial plexus block was done to induce peripheral vasodilation. The unblocked arm served as a control. Each subject underwent two sessions during which a different arm was blocked in a random order. Blood volume in the finger was assessed by transmission photoelectric plethysmography using a pulse oximeter (GE Healthcare, Helsinki, Finland). We placed sensors on the index fingers of both hands, and collected composite plethysmographic waveform data at a frequency of 100 Hz. The PPG signal was then separated into its AC and DC components and the ratio of AC to DC (AC/DC) was calculated. Data were recorded from before until 30 min after the end of brachial plexus block. Data (percent change from pre block baseline values) are reported as mean ⫾ SD, with P ⬍ 0.05 signifying statistical significance. We used repeated-measures analysis of variance followed by the Dunnett’s post hoc test to determine the effect of brachial plexus block on PPG measurements. Results: Photoplethysmography DC component values decreased significantly (P ⬍ 0.0001) after brachial plexus block as compared to pre block baseline values. Average decrease in DC values was -52 ⫾ 16%, -50 ⫾ 19% and -51 ⫾ 19% at 10, 20 and 30 min after the block, respectively. The AC component of the PPG and AC/DC did not have statistically significantly changes from pre block baseline values. There were no statistically significant changes in any of the variables in the control arm. Conclusions: DC component of PPG decreased significantly in response to peripheral vasodilation. Unexpectedly, the AC component of PPG and AC/DC did not change significantly in this experimental model.

Introduction: Near Infrared Spectroscopy (NIRS) correlation with measures of Low Cardiac Output (LCO) has not been validated(1). Hypothesis: Splanchnic and/or renal tissue hypoxemia detected by NIRS is a marker of LCO after pediatric cardiac surgery. Methods: In this prospective study, consecutive pediatric patients admitted after cardiac surgery to a PICU over a 9 month period underwent serial splanchnic and renal NIRS measurements until extubation. NIRS values recorded in the first post-operative hour were arbitrarily defined as baseline. A NIRS Event (NE) was prospectively defined as ⱖ20% drop in splanchnic and/or renal NIRS oxygen saturation from baseline during any hour of the study. LCO was prospectively defined as metabolic acidosis (pH ⬎ 2 mmol/L, BE ⬎ -5), oliguria (urine output ⬍1 ml/kg/hr), need for fluid bolus, or escalation of inotropic support. ROC analysis was performed using NE as a diagnostic test for LCO. Results: 20 children were enrolled: Median age 5 mo; median Risk Adjustment for Congenital Heart Surgery category was 3(1-6), Median bypass time was 120 min (45min-300min) and cross clamp time 88 min (17min-157min). 31 episodes of LCO and 273 NEs were observed in 17 patients. The sensitivity of NE as a predictor of LCO was 48% (30%-66%) and specificity was 67% (64%-70%). ROC analysis revealed that neither splanchnic nor renal NE had significant area under the curve (AUC) for prediction of LCO [Splanchnic: AUC 0.45, 95% CI 0.30-0.60; Renal: AUC 0.51, 95% CI 0.37-0.65]. A sensitivity analysis showed that selection of a 5%, 10%, or 15% drop in NIRS value from baseline did not improve diagnostic accuracy of the test. Conclusions: Splanchnic and/or renal tissue hypoxemia as detected by NIRS is a poor predictor of LCO after open heart surgery in children. References:(1) Hirsch JC, Charpie JR, Ohye RG, Gurney JG. Near-infrared spectroscopy: What we know and what we need to know—A systematic review of the congenital heart disease literature. J Thorac Cardiovasc Surg 2009;137:154-159.

Alana Flexman, UCSF, Amir Snapir, Orion Pharma, Matti Huiku, GE, Pekka Talke, UCSF

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CORRELATION BETWEEN B-TYPE NATRIURETIC PEPTIDE AND CENTRAL VENOUS PRESSURE: IS THE RELATIONSHIP USEFUL WHEN MANAGING FLUIDS?

IMPACT OF SEDATION ON CONTINUOUS HEART AND RESPIRATORY RATE VARIABILITY MONITORING IN CRITICALLY ILL PATIENTS

Abdur Baig, Kingsbrook Jewish Medical Center, Karina Muzykovsky, The Brooklyn Hospital Center, Michael Liu, Kingsbrook Jewish Medical Center, Renzo Hidalgo-Cabrera, Kingsbrook Jewish Medical Center, Brooklyn, Henry Cohen, Rajat Mukherji, Kingsbrook Jewish Medical Center

Beverly Bradley, Geoffrey Green, Rajeev Yadav, Izmail Batkin, Tim Ramsay, Ottawa Hospital Research Institute, Andrew Seely, University of Ottawa

Introduction: Central venous catheters that measure central venous pressure (CVP) is the only routinely used method to reliably measure circulating blood volume. B-type natriuretic peptide (BNP) levels may be a rapid method of predicting circulating volume status. Previous studies have not shown that BNP levels correlate with CVPs, however, these studies did not evaluate the correlation between normal BNP levels to normal CVPs. Hypothesis: To test the reliability of BNP in predicting the volume status of critically ill patients when compared to CVP. Methods: All adult, critically ill patients with internal jugular or subclavian central venous catheters in situ were enrolled from June to August 2010. Serum BNP levels were drawn and CVPs were recorded, simultaneously, from lines placed within 48 hours and those providing an appropriate waveform. Demographic data, and severity-of-illness scores [APACHE II, SOFA] were collected. Normal CVP was defined as 8 to 12 mmHg and normal BNP as ⱕ 400 pg/mL. Results: Twenty-two patients were included in our prospective observational study. These were predominantly medical patients with a mean age of 65 years. The incidence of shock was 50% and 84% patients required mechanical ventilation. Fourteen percent had systolic dysfunction (ejection fraction ⬍ 40%). The mean APACHE II and SOFA scores were 22 and 7.4, respectively. CVP and BNP were recorded within an average of 17 hours of catheter insertion. Median BNP and CVP were 339.3 pg/mL and 7 mmHg, respectively. Fourteen patients had a normal BNP (ⱕ 400 pg/dL), 12 of these patients had corresponding CVPs of ⱕ12 mmHg (85.7 %). Only two patients had a CVP ⱖ12 mmHg (14.3%). Three of the eight patients with BNP levels ⬎ 400 pg/dL had a CVP ⱖ12 mmHg (37.5%). (r ⫽ 0.206, Pearson correlation coefficient, p ⫽ 0.479). Conclusions: Most critically ill patients with normal BNP levels had normal CVP, indicating the potential for using BNP as a rapid guide to fluid administration. However, due to a small sample size, only a weak correlation between BNP levels and CVP could be established. Larger trials are necessary to establish the role of BNP as a guide for fluid administration.


Introduction: Given that reduced heart rate variability (HRV) and respiratory rate variability (RRV) are associated with critical illness, and sedation suppresses HRV in healthy subjects, we sought to characterize the potentially confounding impact of sedation on continuously monitored HRV and RRV in critically ill patients. Hypothesis: Sedation reduces HRV and RRV in critically ill patients; the extent of which depends on degree of organ dysfunction, sedative agent, or both. Methods: In this waived-consent, observational pilot study, ECG and end-tidal capnograph waveforms of 34 critically ill adults were continuously recorded from ICU admission to discharge, up to 14 days (11.0 ⫾ 3.6). Inter-beat and inter-breath time-series were constructed, followed by automated removal of artifact and arrhythmias, and comprehensive HRV and RRV analysis (5-minute intervals). Mean HRV and RRV were computed over 2 periods: 4 hours directly prior to a sedation interruption (SI), and the entire duration of SI (3h44m ⫾ 4h39m). Severity of organ dysfunction (Multiple Organ Dysfunction Syndrome (MODS) score: low:0-2, medium:3-4, and high: ⬎ 4) and sedative agent used were recorded for each SI. Variability before and during SI was compared using paired t-tests and analyzed across all levels of MODS and sedative types. Results: A total of 51 SIs in 22 patients were recorded. After data cleaning, 45 SIs from 21 patients had sufficient data for analysis. Both HRV and RRV increased during SI for standard deviation (SD), coefficient of variation (CV), and Poincare´ standard descriptor 2 (SD2) (p ⬍ 0.05). Low MODS patients experienced greater increases in HRV during SI (p ⬍ 0.05 for SD, CV, and Poincare´ SD2) compared to high MODS (all NS). SI led to increased RRV for low MODS patients (p ⬍ 0.05 for SD, CV, and Poincare´ SD2) but a reduction in RRV for high MODS patients. All trends persisted when controlling for sedative agent. Conclusions: Cessation of sedation leads to increased measures of HRV and RRV, with greater restoration of HRV and RRV during SI in low MODS compared to high MODS. The reduction in RRV in high MODS during SI suggests that SI may offer variable benefit to patients depending on degree of organ failure and merits further investigation.

Poster: Cardiovascular – Therapeutics 232

233

EXTRAVASCULAR LUNG WATER DOES NOT INCREASE IN HYPOVOLEMIC PATIENTS AFTER A VOLUME REPLACEMENT PROTOCOL GUIDED BY STROKE VOLUME VARIATION

SLOW PLASMA EXCHANGE WITH CONTINUOUS HEMODIAFILTRATION IS SAFE AND EFFECTIVE THERAPY FOR DILATED CARDIOMYOPATHY IN CHILDREN

Carlos Ferrando, Hospitla Clinico Universitario Valencia, Gerado Aguilar, Hospital Clıńico Universitario Valencia, Javier Belda, Hospital Clinico Universitario Valencia

Takeshi Moriguchi, Kenichi Matsuda, Norikazu Harii, Masahiko Yanagisawa, Daiki Harada, Junko Goto, Minako Hoshiai, Keiichi Koizumi, Hiroaki Kise, University of Yamanashi School of Medicine, Akiyasu Baba, Kitasato Institute Hospital

Introduction: Circulatory failure secondary to hypovolemia is a common situation in critical care units, being the volume replacement the most frequently used initial treatment. A possible complication to the above mentioned overload is the pulmonary edema, quantified at the bedside by the measurement of extravascular lung water (ELWI). Hypothesis: The goal of our study was to demostrated that fluid loading guided by the stroke volumen variation (SVV), in hypovolemic and fully mechanically ventilated patients, does not produce an increase of the ELWI. Methods: In a prospective study 17 postoperative, consecutive patients diagnosed with circulatory failure secondary to hypovolemia were included. Cardiac index (CI), ELWI, SVV and pulmonary permeability vascular index (PVPI) were determined using a PiCCO monitor during the first 12 hours after fluid loading. If CI ⬍ 3, 5 l min-1 m2 and SVV ⬎ 10%, 250 ml of Voluven (Fresenius Kabi, Germany) was administered. If there was an increase in the CI ⬎ 10% and the SVV was ⬎ 10%, another 250 ml was administered and so go on, as long as there was an increase of the CI above 10% and the SVV was greater than 10%. Data was analyzed by the SPSS 15.0 (SPSS Inc., Chicago, IL). To determined differences in the ELWI of 20%, with a potency of 80% and a significance of 95%, a sample size of 17 was calculated. The data was given on average ⫾ typical desviation. To determined if significant differences existed, the information was analyzed ANOVA test of repeated measurements and Bonferroni for multiple comparisons. The interrelation between the administered volume and the ELWI were analysed using the Pearson correlation. Results: Fluid loading produced a significant increase in the CI (p ⬍ 0, 001) and a decrease in the SVV (p ⬍ 0, 001). The ELWI (p ⫽ 0, 993) and the PVPI (p ⫽ 0, 748) did not increase. No correlation was found between the amount of fluids administered and the change in ELWI (p ⫽ 0, 826, r ⫽ 0, 68). Conclusions: Fluid loanding in hypovolemic and fully mechanically ventilated patients guided by the SVV increase CI but does not produce an increase in ELWI

Introduction: Growing evidence suggests that cardiodepressant autoantibodies (CD-Abs), such as beta1-adrenoceptor (␤1AR) antibody, might play an important role in the pathogenesis of dilated cardiomyopathy (DCM). Some reports showed that apheresis, immunoabsorption or plasma exchange (PE), intended to eliminate such CD-Abs, leads to an acute and prolonged hemodynamic improvement in adult patients with DCM. However, apheresis for children with DCM has not been performed because of technical difficulty. We performed slow PE with continuous hemodiafiltration (SPE ⫹ CHDF) on two patients with DCM. One was associated with severe liver dysfunction and another was on cardiogenic shock unresponsive to treatment with medical therapy. The cardiac function of the two patients improved immediately after the adoption of SPE ⫹ CHDF. Hypothesis: We hypothesized that removal of CD-Abs by SPE ⫹ CHDF may accordingly improve the cardiac function and activities of daily living (ADL) in children with DCM. Methods: Four children aged 13.0 ⫾ 4.3 years were included in this study. The body weight was 29.3 ⫾ 7.4kg. Under general anesthesia, the patients were administered SPE 3 times during 3 days. The plasma total of 85.8 ⫾ 6.5mL/kg, which was equal to their blood volume, was exchanged at each procedure. Simultaneously, CHDF was performed in series with the SPE circuit to stabilize hemodynamic status and to minimize the adverse effect of SPE. Results: No severe complications were encountered during any of the procedures. In one patient who had IgG1-4 subclass of ␤1AR antibody, SPE ⫹ CHDF increased the ejection fraction and improved ADL. One of the 2 patients who had IgG3 subclass of ␤1AR antibody was in the early phases of DCM. His hemodynamic state improved and inotropic support discontinued immediately after the adoption of SPE ⫹ CHDF. In another patient, who had mild symptoms, SPE ⫹ CHDF did not clearly improve the patient’s overall condition. In one patient who had no ␤1AR antibody, SPE ⫹ CHDF provided hemodynamic state improvement. However, the improved cardiac function deteriorated again 3 months after SPE ⫹ CHDF. Conclusions: When patients have ␤1AR antibody, SPE should be considered, even in children, as an alternative therapy for DCM.

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ULTRASOUND EVALUATION OF THE EFFECTS OF INHALATION OF NITRIC OXIDE IN CARDIAC SURGERY PATIENTS WITH POSTOPERATIVE SEVERE DIASTOLIC DYSFUNCTION

PERITONEAL DRAINAGE FACILITATES FLUID MANAGEMENT AND PREVENTS FLUID OVERLOAD AFTER SURGERY FOR CONGENITAL HEART DISEASE

Massimo Meco, Marie Allaz, Silvia Cirri, Istituto Clinico Sant’Ambrogio Introduction: Postoperative diastolic dysfunction is a relatively common condition with serious consequences for morbidity and mortality in patients undergoing cardiac surgery. Hypothesis: We evaluated the hypothesis that low doses of nitric oxide (NO) (5 ppm) are able to improve postoperative severe diastolic dysfunction. Methods: 10 patients undergoing cardiac surgery with postoperative restrictive mitral pattern. All patients were monitored with pulmonary artery catheter and diastolic function was assessed by ultrasound. We considered restrictive pattern the following condition: E wave⬎⬎ A, Deceleration time ⬍ 160 ms, and E’wave of mitral annulus TDI ⬍8, propagation velocity (Vp) ⬍50 cm/s, Ar wave of pulmonary veins ⬎ 35 cm/s. We also measured the indices of systolic function (EF, isovolumetric acceleration, and shortening fraction). The hemodynamic and echocardiographic measurements were performed at baseline and during inhalation of NO. Results: All patients showed a decrease in left atrial pressure, improved Deceleration Time (140 vs. 180 ms), an increase of the E ’wave (5.5 vs. 8.9 cm/s), an increase of Vp (31 vs56) and a decrease of ’Ar (70 vs 37cm/s). The cardiac index did not undergo major changes, as well as vascular resistance. Even systolic contractility indices remained unchanged. Conclusions: Inhalation of 5 ppm of NO in patients with severe postoperative diastolic dysfunction has led to a significant improvement in diastolic function of these patients, with normalization of diastolic function and filling pressures. NO, at these doses, does not seem to affect systolic function.

Arun Saini, Children’s Hospital of Michigan, Ralph Delius, Children’s Hospital of Michigan, Christopher Mastropietro, Children’s Hospital of Michigan Introduction: In some centers, peritoneal drainage (PD) catheters are placed intra-operatively in patients undergoing surgery for congenital heart disease to prevent post-operative fluid overload. The utility of this practice has yet to be determined. Hypothesis: PD is a helpful adjunct in preventing post-operative fluid overload in infants undergoing surgery for congenital heart disease. Methods: An IRB-approved retrospective chart review was performed on infants who underwent repair of complete atrioventricular canal defect (AVCD) at our center between 6/07 – 6/10, restricted to one lesion to maintain study homogeneity. Anthropomorphic, peri-operative, and post-operative data in infants with PD were compared to those without using t-tests and Mann-Whitney U tests as appropriate for individual variables. Data are represented as mean ⫾ standard deviation. Results: Thirty-three infants underwent repair of AVCD during the study period, 16 of which had intra-operative PD catheters placed. No complications occurred from catheter placement. Patients with PD had longer duration of cardiopulmonary bypass (214 ⫾ 62 vs. 138 ⫾ 42 min, P ⫽ 0.001) and aortic cross-clamp (149 ⫾ 30 vs. 102 ⫾ 22 min, P ⬍ 0.001) as well as a trend toward higher Aristotle complexity score (12.9 ⫾ 2.4 vs. 11.1 ⫾ 2.9, P ⫽ 0.063). During the first 48 post-operative hours, infants with PD catheters received greater fluid administration (232 ⫾ 63 vs. 168 ⫾ 46 mL/kg, P ⫽ 0.002) yet had more negative fluid balance (-68 ⫾ 56 vs. -0.3 ⫾ 39 mL/kg, P ⫽ 0.002) as compared to those without, in large part due to PD (86 ⫾ 68 mL/kg). Otherwise, groups were similar in age, weight, post-operative urine output, diuretic dosing, creatinine clearance, peak lactate, vasopressor requirements, central venous pressure, duration of mechanical ventilation and ICU length of stay. Conclusions: PD catheters were safe. Further, PD helped to prevent post-operative fluid overload following repair of AVCD as evidenced by greater negative fluid balance and similar hemodynamic profiles at 48 hours post-operatively in those with PD despite more complicated peri-operative courses and more aggressive post-operative fluid resuscitations.


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COMPARISON OF VECURONIUM CONTINUOUS INFUSION AND INTERMITTENT BOLUS DOSING IN SUDDEN CARDIAC DEATH PATIENTS RECEIVING THERAPEUTIC HYPOTHERMIA

CLEVIDIPINE VS. NICARDIPINE; A RETROSPECTIVE EFFICACY AND COST-ANALYSIS

Lesly Jurado, New Hanover Regional Medical Center, Brian Gulbis, Memorial Hermann - Texas Medical Center, Andrea Hall, Memorial Hermann Hospital Introduction: The objective of this study was to compare the effects of vecuronium administered as an intravenous continuous infusion versus intermittent boluses in sudden cardiac death (SCD) patients treated with therapeutic hypothermia. There is limited data to suggest the optimal dosing neuromuscular blockers in these patients. Hypothesis: There will be a difference in the primary objective favoring intermittent boluses. Methods: This was a retrospective, single center, chart review of SCD patients treated with therapeutic hypothermia. Patients were divided into two cohorts, Group 1, patients treated with a vecuronium continuous infusion and Group 2, patients treated with vecuronium intermittent boluses. Primary objectives evaluated were time to achieve goal train of four (TOF) and the percent time the TOF was maintained at goal. Secondary endpoints assessed were the mean total daily dose of vecuronium, the mean dose to achieve goal TOF, the percentage of TOF measurements above or below goal, and the time until a return of spontaneous respirations following the last dose of vecuronium. The chi-square test was utilized for categorical data, while the t-test was used for continuous data. MedCalc software was utilized to analyze the data. Results: There were 123 patients included in the study, 80 in group 1 and 43 in group 2. The goal TOF was achieved significantly earlier in group 2 (5.9 hours vs. 11.3 hours, p-value ⫽ 0.008). The mean total daily dose administered in group 2 was significantly less than group 1 (51.7 mg vs. 76.9 mg, respectively, p-value ⫽ 0.002). The percentage of TOF measurements above goal was higher in group 2 (36% vs. 18%, p-value ⬍ 0.0001) and the percentage of TOF below goal was higher in group 1 (42% vs. 29%, p-value ⫽ 0.02). The time until a return of spontaneous respirations was significantly shorter in group 1 (8.3 hours vs. 14.6 hours, p-value ⫽ 0.04). Conclusions: These findings suggest that vecuronium intermittent boluses were more effective in reaching a goal TOF earlier than and as effective as a continuous infusion in maintaining a goal TOF in patients treated with therapeutic hypothermia. However, bolus administration caused a prolonged time to return of spontaneous respirations.

Allison Campbell, West Virginia University Hospital, Carrie DeFazio, West Virginia University Hospitals, Richard McKnight, West Virginia University Hospital Introduction: Clevidipine was the most recent intravenous dihydropyridine calcium channel blocker.Prior to clevidipine, intravenous nicardipine was the mainstay at our institution for hypertension management in the intensive care unit (ICU). Clevidipine’s pharmacokinetic profile was attractive due to ability to reduce Systolic Blood Pressure by 2–5% within 2– 4 minutes, coupled with a short duration of action of 5–15 minutes after discontinuation. In 2008, clevidipine was added to formulary in hopes to transition patients to oral agents faster and provide a cost effective approach. With the addition, clevedipine was restricted to use in the ICU, emergency department, and operating room. Our protocol for management of stroke in the ICU advocated using nicardipine first line. Hypothesis: Clevidipine and nicardipine will require similar durations of infusion to convert patients to oral agents. Methods: Retrospective review completed in 140 patients, 70 clevidipine and 70 nicardipine. Information collected included: patient age, admitting diagnosis, and ICU length of stay. The endpoints for determination of relative efficacy included the duration of infusion (hours) and the number of oral agents necessary to discontinue the infusion. Additionally, total amount of drug received in milligrams (mg) was obtained as the third endpoint, which was used to extrapolate medication costs. Results: The mean duration of infusion was comparable between the medications. Clevidipine’s mean duration was 27.5 hours vs. 28.1 hours for nicardipine. Clevidipine required a mean of 2.2 oral medications in order to discontinue the infusion compared to 2 for nicardipine. The mean total dose of clevidipine was 128.5 mg vs. 162.8 mg for nicardipine. At a cost of $62.96 for 25 mg of clevidipine, the mean cost per patient was $324. Conversely, nicardipine with a cost of $226.16 for 25 mg, the mean cost per patient was $1473. Conclusions: No difference in clinical outcomes seen between agents. The difference observed was cost $324 vs. $1473. When adding a drug to formulary with restrictions, a thorough review should be performed again at 6 –12 months and restrictions reevaluated, as new drugs do not always correlate to higher costs.

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COST EFFECTIVENESS OF INTRAVENOUS NICARDIPINE VERSUS SODIUM NITROPRUSSIDE FOR POSTOPERATIVE HYPERTENSION AFTER CARDIAC SURGERY

CARDIOPROTECTIVE EFFECT OF SEVOFLURANE VERSUS PROPOFOL DURING ANESTHESIA AND POSTOPERATIVE PERIOD IN CORONARY BYPASS SURGERY

Brian Barnes, Patricia Howard, The University of Kansas Medical Center, Jeffrey Kramer, Emmanuel Daon, George Zorn, The University of Kansas Hospital, Sue Lai, Dennis Grauer, The University of Kansas Medical Center, Greg Muehlebach, The University of Kansas Hospital

Carlos Ferrando, Hospital Clinico Universitario Valencia, Ernesto Pastor, Marina Soro, Gerardo Aguilar, Hospital Clıńico Universitario Valencia, Javier Belda, Hospital Clinico Universitario Valencia

Introduction: Postoperative hypertension (HTN) after cardiac surgery is common and associated with substantial morbidity. Both sodium nitroprusside (SNP) and nicardipine (NIC) are effective in its management. SNP is inexpensive, but associated with labile blood pressure (BP) control, cardiac ischemia, and metabolite toxicity. NIC is well tolerated, provides stable BP control, but is limited by high acquisition cost. Hypothesis: We conducted a cost-effectiveness analysis (from an institutional perspective) of NIC versus SNP in subjects experiencing postoperative HTN after cardiac surgery. Methods: A retrospective, cohort study identified subjects who underwent CABG and/or valve surgery at our institution between 11/2007-12/2009. We included adults experiencing postoperative HTN requiring ⱖ30 minutes of either NIC or SNP. Institutionalspecific data from the Society of Thoracic Surgeons and University HealthSystem Consortium national databases and our financial and electronic medical records were used. Effectiveness was measured by the number of infusion rate changes divided by the infusion duration. Direct costs (using activity-based accounting) were calculated for each subject from post-surgical ICU admission to hospital discharge. Data were compared with t, transformed t, Wilcoxon Rank Sum, chi-square, or Fisher’s exact tests (a priori alpha of 0.05) as appropriate. Results: Of the 119 subjects identified, 76 received NIC and 42 SNP. Demographics including severity of illness, hypertension history, # of preoperative antihypertensive agents, proportion of subjects undergoing CABG or valve surgery, and postoperative length of stay were not significantly different between the groups. NIC required significantly fewer dose changes/hour (1.1 ⫾ 1.5) versus SNP (1.7 ⫾ 1.7, p ⫽ 0.0014). NIC subjects were on average less costly to our institution ($21, 230 ⫾ 8, 738) than those treated with SNP ($22, 007 ⫾ 6, 946, p ⫽ 0.365). Conclusions: NIC use may be limited due to decisions based upon acquisition costs alone. We found that NIC resulted in more stable BP control without increasing postoperative costs. NIC is an economically dominant therapy when compared to SNP in the treatment of postoperative HTN.


Introduction: Volatile anesthetics may have direct cardioprotective properties due to effects similar to ischemic preconditioning and postconditioning. Clinical results in cardiac surgery patients are controversial and may be related to when anesthetics are administered during the intraoperative period. Hypothesis: We hypothesized that the cardioprotective effect of sevoflurane in coronary bypass surgical patients would be greater if administration during anesthesia continued in the ICU for at least 4 h of the postoperative period until weaning from mechanical ventilation. Methods: Double-blind, prospective, randomized, and controlled single-center clinical trial. Seventyfive adult patients were randomly assigned to receive anesthesia and postoperative sedation either with propofol (control, n ⫽ 37) or sevoflurane (n ⫽ 36). Myocardial biomarkers, need for inotropic support, and ICU and hospital lengths of stay (LOS) were recorded. Results: Necrosis biomarkers increased significantly in the postoperative period in both groups (with no differences at any timepoint). Inotropic support was needed in 72.7% and 54.3% of patients in the propofol and sevoflurane groups, respectively (p ⫽ 0.086). There were no significant differences in hemodynamic variables, incidence of arrhythmias or myocardial ischemia, and ICU and hospital LOS between groups. Conclusions: In patients undergoing coronary bypass surgery, continued administration of sevoflurane as a sedative in ICU for at least 4 h of the postoperative period did not yield significant differences in the levels and time course of myocardial damage biomarkers compared to propofol use. However, sevoflurane in this period may improve postoperative myocardial function, as suggested by a tendency toward decreased use of inotropic drugs.

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PROSTAGLANDIN E1 WAS BENEFICIAL TO IMPROVE PERIPHERAL PERFUSION DURING THORACIC AORTIC SURGERY UNDER HYPOTHERMIA

EFFECTS OF FENOLDOPAM MESYLATE INFUSION ON POSTOPERATIVE DIASTOLIC DYSFUNCTION IN CARDIAC SURGERY PATIENTS WITH NORMAL SYSTOLIC FUNCTION

Jun Maki, Our Lady of the Snow Social Medical Corporation, St. Mary’s Hospital, Junko Kaji, Our Lady of Snow Social Medical Corporation, St. Mary’s Hospital, Reiko Makizono, Mariko Hayamizu, Tsukasa Shimauchi, Hiromi Aono, Shogo Nakata, Hideaki Minoda, Yoshimitsu Tsutsumi, Our Lady of the Snow Social Medical Corporation, St. Mary’s Hospital

Massimo Meco, Marie Allaz, Silvia Cirri, Istituto Clinico Sant’Ambrogio

Introduction: Prostaglandin E1 (PGE1) has been shown to possess vasodilator effect, thus improve peripheral perfusion during cardiopulmonary bypass (CPB). During thoracic aorta surgery, protection of vital organs is crucial. Therefore, procedures are performed under moderate to deep hypothermia. However, hypothermia induces increase of systemic vascular resistance and peripheral hypoperfusion. Hence, we have to make every effort to improve peripheral perfusion without any damage to vital organs. Hypothesis: During thoracic aorta surgery under hypothermia, PGE1 will contribute to improve peripheral perfusion protecting vital organs. Methods: We performed retrospective analysis of 12 patients undergoing thoracic aorta surgery under moderate hypothermia. They were divided into two groups, PGE1 (n ⫽ 6) and Control group (n ⫽ 6). Data collected included parameters associated with characteristics of patients, rectal and pharyngeal temperature, pH, BE and lactate. Results: Comparing the characteristics of two groups, duration of CPB and operation of PGE1 group were significantly longer than control group. Although the time necessary for re-warming and pharyngeal temperature just before weaning from CPB were not different between both groups, rectal temperature was significantly higher in PGE1 group (34.8 ⫾ 0.7 vs. 33.4 ⫾ 0.7 °C; p ⬍ 0.05). The value of pH was significantly higher in PGE1 group (7.38 ⫾ 0.03 vs. 7.33 ⫾ 0.02; p ⬍ 0.05) just before weaning from CPB. When operation was finished, pH and BE of PGE1 group were higher than Control group (7.43 ⫾ 0.01 vs. 7.35 ⫾ 0.05 and -1.7 ⫾ 0.3 vs. -2.5 ⫾ 1.7, respectively). Lactate of PGE1 group was similar to Control group (5.91 ⫾ 1.33 vs. 5.90 ⫾ 0.94 mM) just before weaning from CPB. However, lactate of PGE1 group was gradually decreased before operation was finished in contrast to Control group (3.60 ⫾ 0.67 vs. 6.12 ⫾ 1.38 mM). Conclusions: PGE1 improved peripheral perfusion, and thus elevated core temperature promptly. Furthermore, PGE1 maintained blood flow to vital organ, thus enhanced lactate metabolism. As a result, the progression of lactic acidosis was inhibited. In conclusion, PGE1 was efficient to improve peripheral perfusion protecting vital organs during thoracic aortic surgery under hypothermia.

Introduction: Left ventricular diastolic dysfunction is a major problem in thepostoperative period of patients undergoing cardiac surgery. Hypothesis: We tested thehypothesis that fenoldopam mesylate, could be effective to ameliorate thediastolic function of cardiac surgery patiens. Methods: We identified 61 patients with postoperativediastolic dysfunction and preserved systolic function.We considered thediastolic dysfunction situation wherethere was the simultaneous presence of:E wave of TDI of the mitrallateral annuls ⬍ 8 cm/sec, propagation velocity ⬍ 50 cm/sec, Ar wave ofpulmonary veins more than 35 cm/sec.27 patients (Group A) had anabnormal diastolic relaxation, 22 patients (Group B) had a pseudo-normalizedpattern and 12 patients (Group C) had a restrictive pattern. All echocardiographicevaluations were performed at baseline and after 30 minutes after infusion of0.1 mcg/kg/min of fenoldopam. Results: There were nosignificant changes of systolic function indices during infusion of fenoldopamin all three groups. In all patients the infusion of fenoldopam did not involveany change in the indices of afterload, there were no significant changes inheart rate or blood pressure or cardiac index.Infusion of fenoldopam resulted in a significant increasein E wave of TDI in all 3 groups, and involves a significant decrease of E ’/E, and left atrial pressure in all three groups.Fenoldopam induces asignificant improvement of velocity ofpropagation of mitral inflow, and pulmonary vein Ar wave. 33.3% (4/12) of the patientsin group C and 9% (2/22) of patients in group B did not respond to treatmentwith fenoldopam. Conclusions: Fenoldopamis effective in the treatment of postoperative mild to moderate diastolic failure.It seems to be partially effective in the treatment of more serious postoperative diastolic failure.


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EVALUATION OF ADRENAL RESERVE WITH LOW DOSE COSYNTROPIN STIMULATION IN CRITICALLY ILL CHILDREN: A PILOT STUDY

LOW FREE T3 LEVELS ARE ASSOCIATED WITH INCREASED MORTALITY IN SEPTIC CRITICALLY ILL PATIENTS

Claudia Kunrath, Pamela D Reiter, Margaret Clarke, Michael Kappy, Emily L Dobyns, The Children’s Hospital, Aurora, Colorado Introduction: Adrenal dysfunction is common during critical illness and is associated with poor outcomes in adults. Prevalence of adrenal reserve and insufficiency in children, however, remains unclear. Hypothesis: Pediatric adrenal dysfunction is common and correlates with severity of illness/ clinical outcome. Methods: Children were eligible for this prospective, IRB approved study if they had an expected ICU stay ⬎ 24 hrs and were not exposed to chronic steroids within the past 6 mo or acute steroids within the past 4 wks. Baseline blood was collected (total and free cortisol, ACTH, and corticosteroid binding globulin, [cbg]). Patients were stimulated with 1 mcg of IV cosyntropin. Samples were collected again 30 min after stimulation. Adrenal dysfunction was defined as: basal cortisol ⬍ 15mcg/dl; change ⬍ 9; ACTH ⬍ 6 pg/ml or ⬎ 48 pg/ml; free cortisol index ⬍1.27 (infant ⬍1 yr), ⬍0.69 (1-9 yr), ⬍1.3 (⬎10 yr). Mortality, pressor use, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction (MODs), length of stay (LOS) and Pediatric Risk of Mortality Score (PRISM) were recorded. Results: Twenty-seven were enrolled; 24 had complete adrenal profiles [age ⫽ 5.6 ⫾ 5yrs (3 mo-17 yrs); 50% male]. Basal total and free cortisol ⫽ 14.8 ⫾ 8.1 mcg/dl and 6.9 ⫾ 3.7; post-stimulation total and free cortisol ⫽ 27 ⫾ 9.4 mcg/dl and 12.5 ⫾ 4.5. Change in total and free ⫽ 13 ⫾ 7.3 and 5.73 ⫾ 3.4. Basal ACTH and cbg ⫽ 17 ⫾ 14 pg/ml and 2.3 ⫾ 0.8 mcg/dl. PRISM score ⫽ 7.8 ⫾ 6 (0-25). Twenty-three pts were medical, 1 was surgical. Seven patients (29%) required pressor therapy. Seventeen patients (71%) had SIRS and six (25%) had MODs. LOS ⫽ 8.4 ⫾ 6 days (2-26 d). All children survived to PICU discharge. Correlation between PRISM and adrenal function was low (r2 ⬍ 0.2). Laboratory evidence of adrenal dysfunction varied by criteria and was 8-50%. Children with sepsis were more likely to have adrenal dysfunction than children with trauma. Conclusions: Prevalence of adrenal dysfunction ranged from 8-50%. Clinical correlation of laboratory evidence to clinical illness was poor- only 8% of patients had clinical evidence of adrenal dysfunction and required pressors. Adrenal function was not predictive of severity of illness.

Tejal Shah, Nisarg Changawala, Yizhak Kupfer, Chanaka Seneviratne, Sidney Tessler, Maimonides Medical Center Introduction: Nonthyroidal illness syndrome (NTIS) is characterized by low circulating thyroid hormones with low free T3 and low free T4 levels and variable TSH levels. NTIS is commonly encountered in critically ill patients. In the setting of severe sepsis it remains unclear whether NTIS represents a physiological reaction to stress or whether it is another organ failure. We prospectively measured thyroid hormone levels in septic critically ill patients admitted to the medical intensive care unit (MICU) and correlated thyroid hormone levels with patient survival. Hypothesis: To determine the prognostic significance of admission thyroid levels in critically ill septic patients. Methods: Patients diagnosed with severe sepsis or septic shock had free T3, free T4, and TSH levels obtained upon admission to the MICU. Age, gender, medical comorbidities, APACHE IV scores, use of physiologic “stress dose” steroids, use of vasopressors and need for mechanical ventilation were studied. Results: One hundred fourteen severely septic patients admitted to the MICU between September 2009 and December 2009 were studied. The average age was 78.9 ( ⫾ 21) with equal gender distribution. Mean admission APACHE IV score was 51.7 ( ⫾ 11). Ninety nine (87%) of patients had low T3 levels. A free T3 level below 2 was significantly associated with mortality (P ⬍ 0.01). Multivariate analysis revealed that a free T3 of less than 2 was associated with MICU mortality (odds ratio 0.18, P ⫽ 0.003 95% confidence interval 0.06-0.54). Free T3 was inversely correlated with APACHE IV scores (r ⫽ -10.06 with standard error 2.9). Conclusions: Low free T3 levels on admission to the MICU predict a higher mortality for severely septic patients. NTIS represents an organ failure associated with severe sepsis. Research is needed to determine the effect of thyroid hormone therapy on survival in septic critically ill patients with NTIS.

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NUTRITIONAL STATUS AND COMPLICATIONS IN CHILDREN WITH DIABETIC KETOACIDOSIS

DELAYED INTRAVENOUS INSULIN THERAPY INITIATION IS ASSOCIATED WITH MORTALITY IN THE ICU

Jayashree Muralidharan, Post Graduate Institute of Medical Education and Research, Nirmalya Roy Moulik, PGIMER, Sunit Singhi, Post Graduate Institute of Medical Education and Research, Anil Bhalla, Savita Attri, PGIMER

Hanqing Cao, Boyang Li, Philips Research North America, Brian Gross, Philips Healthcare, Rondi Kauffmann, Addison May, Vanderbilt University Medical Center

Introduction: Morbidity and mortality in children with DKA is high in developing economies due to malnutrition and high rate of infections.Malnutrition increases the risk of DKA related complications as shown in previous studies. Hypothesis: To assess the nutritional status of children with DKA and correlate it with the incidence of complications. Methods: It was a prospective study, conducted in a tertiary care hospital in North India over 1 year (2008-09).Thirty three children 1 month to 12 years of age, with DKA were enrolled consecutively and assessed for nutritional status by anthropometry (weight for age ), biochemical parameters (albumin, magnesium and zinc) and pre-illness dietary intake ( Food Frequency Questionnaire).Patients were classified as malnourished or normal based on anthropometry matched for Indian standards. The incidence of complications (electrolyte imbalances, hypoglycemia, sepsis, cerebral edema ) and outcome in terms of survival or death in both were compared with Students’-test for parametric data, Mann-Whitney U test for non-parametric data and Chisquare test for categorical variables. Results: Eleven out of 33 (33.3%) were malnourished. The malnourished and normally nourished groups were similar with respect to demographics, precipitating factors, severity of DKA, treatment and outcome. The incidence of hypokalemia (100 vs. 72.7%; p ⫽ 0.05) and hypoglycemia (63.6 vs13.6%; p ⫽ 0.004) were significantly higher in the former as compared to latter. The admission serum potassium were similar in both , with the former showing a significant fall at 6 hours after start of therapy (2.8 ⫾ 0.8 mEq/L vs. 3.6 ⫾ 0.7 mEq/L; p ⫽ 0.033).The fall in blood glucose (mean ⫾ SD mg/dl) at 12, 24, 36 hours after onset of treatment was also significantly higher in the former compared to the latter (195 ⫾ 69.1 and 272.61 ⫾ 96.3; p ⫽ 0.02, 171 ⫾ 58.5 and 257 ⫾ 96.3;p ⫽ 0.05 and 153.75 ⫾ 49.6 and 241.71 ⫾ 76.3; p ⫽ 0.04 respectively). The incidence of other DKA related complications and outcome were similar in both. Conclusions: The incidence and severity of hypokalemia and hypoglycemia were significantly higher in malnourished DKA. Other DKA related complications and outcome were unrelated to nutritional status.

Introduction: Insulin therapy is initiated to control blood glucose (BG) if it is significantly elevated on intensive care unit (ICU) admission. However, no consensus exists as to specifically when insulin therapy should be initiated. Furthermore, the impact of the timing of insulin therapy initiation on outcomes is unclear. Hypothesis: The timing of insulin therapy initiation is not associated with outcomes in ICU patients. Methods: A retrospective analysis was performed on adult Medical-Surgical ICU patients from the MIMIC II (Multiparameter Intelligent Monitoring in Intensive Care) database collected between 2001 and 2005. Inclusion criteria included intravenous insulin therapy and any BG levels greater than 0 mg/dL. Those patients who were ‘Do Not Resuscitate’ were excluded from the study (N ⫽ 82). Of the 12, 695 patients in the database, 3033 met inclusion criteria. Multivariable logistic regression was used to compare the time of first BG measurements to insulin therapy initiation, the time of maximum BG to insulin therapy initiation, the levels of first BG measurement, and mean and maximum BG levels before insulin therapy initiation. All models were adjusted for diabetes status. Results: The mortality rate was 20.57% (2409 survivors, 47.9% diabetic; 624 non-survivors, 35.4% diabetic). The time of first BG measurements to insulin therapy initiation was significantly higher among nonsurvivors than survivors [median (IQR) 20.10 (6.13, 80.06) vs. 6.75 (3.00, 15. 71) hours, p value ⬍ 0.001]. Likewise, the time of maximum BG to insulin therapy was significantly higher among non-survivors than survivors [median (IQR) 4.07 (1.0, 12.70) vs. 2.58 (0.96, 6.75) hours, p ⬍ 0.001]. The levels of the first BG measurements, mean, and maximum BG before insulin initiation were all statistically significantly higher among non-survivors than survivors [median (IQR) first BG 170 (123, 240) mg/dL vs. 151 (117, 197); mean BG 183 (152, 239) mg/dL vs. 161 (137, 194); maximum BG 269 (219, 346) mg/dL vs. 210 (176, 261), p ⬍ 0.001]. Conclusions: Delayed intravenous insulin therapy initiation in hyperglycemic patients is associated with higher mortality in the ICU.


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IMPACT OF PACKED RED BLOOD CELL TRANSFUSION ON INSULIN REQUIREMENTS IN CRITICALLY ILL PATIENTS

FOURIER ANALYSIS OF NON-CONTINUOUS GLUCOSE MONITORING DATA IN CRITICALLY ILL TRAUMA PATIENTS

Seraj El-Oshar, Ganga Ranasuriya, Phil Elbaum, Cooper University Hospital, Quinn Czosnowski, Philadelphia College of Pharmacy, Karen Vito, Barry Milcarek, Cooper University Hospital, David Gerber, Cooper University Hospital UMDNJ Robert Wood Johnson Medical School at Camden Introduction: Packed Red Blood Cell (PRBC) transfusion and poor glycemic control in critically ill patients are both associated with morbidity and mortality. However, data assessing the impact of PRBC transfusion on glycemic control is lacking. The purpose of this study was to assess the impact of PRBC transfusions on insulin requirements as an index of glycemic control in critically ill adult patients. Hypothesis: PRBC transfusion is associated with increased insulin requirements in critically ill patients. Methods: This was a retrospective study of medical ICU patients admitted to Cooper University Hospital and included in the Project Impact database. IRB approval was obtained with waiver of informed consent. Continuous variables were compared using the Mann-Whitney U test and categorical variables were compared using the chi-square test. Patients receiving PRBC and being treated with insulin were compared for their pre- and post-transfusion insulin requirements. We also assessed the overall frequency with which patients required increased insulin doses post-transfusion compared to pre-transfusion doses. Results: 165 patients admitted to the ICU between April 2009 and March 2010 receiving PRBC were identified, of whom 61 received insulin. At 24 h post transfusion, average daily insulin requirements were significantly greater compared to the 24 hours pre-transfusion (27.5 vs.12.3 units/day, p ⬍ 0.0001). On post transfusion day 2 insulin requirements were numerically higher, but not statistically different (21.5 vs. 12.3 units/day, p ⫽ 0.12). At 24 h 77% of patients had an increased insulin requirement compared to pre-transfusion (p ⬍ 0.0001); by 48 h this had declined to 59% of patients (p ⫽ 0.11). Conclusions: Our results indicate that PRBC transfusion contributes to increased insulin requirements to maintain glycemic control. The state of insulin resistance previously described in critically ill subjects may be exaggerated by PRBC transfusion. This may be the result of inflammatory mechanisms. Alternatively, other unrecognized mechanisms may be responsible. Further investigation is necessary to confirm these findings and elucidate their underlying mechanisms.

Michael Corneille, University of Texas HSC at San Antonio, Jacqueline Richa, University of Texas HSC at San Antonio), Joel Michalek, Yongjiang Ouyang, Ronald Stewart, Steven Wolf, University of Texas HSC at San Antonio Introduction: Tight glycemic control has been described using a variety of discrete parameters including admission glucose value, mean and standard deviation. These parameters fail however to describe glycemic control as a continuous dynamic process. By graphing discrete glucose values over time, a continuous curve is generated. Fourier analysis is a method used to reduce complex curves into simpler series of coefficients. When applied to glucose data, a patient’s glucose curve is reduced to a series of coefficients that can be compared for differences in clinical course and mortality. Hypothesis: We hypothesize that coefficients from Fourier analysis of non-continuous glucose monitoring data is associated with mortality in critically ill trauma patients. Methods: We conducted a single-center 3 year retrospective study of adult trauma patients admitted to the ICU excluding those with ISS ⬍ 9 and ICU LOS ⬍ 3 days. We collected demographics, diagnoses, clinical course and all glucose values. Interpolated curves of glucose values over time were graphed and Fourier models were constructed. We fitted a series of logistic regression models relating 2 Fourier coefficients: Factor 1 and Power 4, with death. The model was adjusted for age, diabetes, admission GCS, ISS, and presence of and first order interactions with head injury. Results: In patients with head injury (n ⫽ 272): admission GCS (p ⫽ 0.001), ISS (p ⬍ 0.001) and age (p ⬍ 0.001) were associated with mortality (AUC ⫽ 0.798); however, no association was found with factor 1, power 4 or diabetes. In patients without head injury (n ⫽ 275): factor 1 (p ⫽ 0.002), power 4 (p ⫽ 0.01) and age (p ⫽ 0.04) were associated with mortality (AUC ⫽ 0.772), but admission GCS, ISS and diabetes were not. Conclusions: Coefficients derived from Fourier analysis of glucose curves are associated with mortality in critically ill trauma patients without head injury. Fourier analysis of interpolated glucose curves may provide additional parameters to assess tight glycemic control.

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EFFECTS OF HYPERGLYCEMIA AND CONTINUOUS INTRAVENOUS INSULIN ON OUTCOMES OF SURGICAL PATIENTS

FEASIBILITY EVALUATION OF A GLUCOSE SENSOR MODIFIED FOR HOSPITAL USE

Andrew Schlussel, Danielle Holt, Eric Crawley, Catherine Uyehara, Tripler Army Medical Center

Rebecca Gottlieb, Ying Luo, Medtronic, Roma Gianchandani, James Blum, University of Michigan Health System, Raju Joshi, Steve Smith, Medtronic

Introduction: Hyperglycemia in critically ill patients has been associated with increased morbidity and mortality. In this study, the degree of glucose control needed to improve outcomes in a mixed surgical population requiring intensive insulin therapy was examined. Hypothesis: Surgical patients whose blood sugar is tightly controlled by continuous insulin therapy have improved morbidity and mortality. Methods: A retrospective chart review of 395 intensive care unit (ICU) patients placed on an intravenous insulin protocol targeted to a blood glucose (BG) of 80-140mg/dL was conducted to compare outcomes of patients with a surgical (n ⫽ 210) vs. medical (n ⫽ 185) diagnosis. Differences in surgical patients with controlled (80-140mg/dL) vs. uncontrolled (ⱖ141mg/dL) blood glucose were examined and the effect of percent time spent in 6 different ranges of BG values during the total time of insulin therapy was evaluated. Results: Blood glucose measurements fell within the target range in medical patients more than in surgical patients (p ⬍ 0.01), however these patients were associated with a higher mortality rate (OR ⫽ 3.6; 95% CI 2.1– 6.0; p ⬍ 0.01). Surgical patients showed a lower ICU and hospital lengths of stay (LOS) (p ⬍ 0.05). Adjusting for covariance in the subgroup of surgical patients demonstrated an increase in mortality in the uncontrolled vs. controlled group (OR ⫽ 4.6, 95% CI 1.4 –18.5; p ⬍ 0.01). Higher mortality was associated with patients who spend greater than 17.6% of their time at BG ⬎ 181mg/dL (OR ⫽ 2.9, 95% CI 1.2–7.3; p ⫽ 0.03). Lower mortality was associated with patients who spend greater than 22% of their time at a BG range of 81–110mg/dL (OR 0.35, 95% CI 0.14 – 0.87, p ⫽ 0.03). Conclusions: Following an insulin protocol does not necessarily result in tight glucose control in all patients. Surgical patients in the uncontrolled blood glucose group were associated with a higher mortality rate compared to patients who were well controlled. This was especially seen when time was spent at BG values ⬎181 mg/dL. These results are comparable to previous studies when blood glucose is controlled below 181mg/dL and further indicate that patients may possibly benefit more by maintaining them within a range of 81–110mg/dL.

Introduction: Glucose control in the critical care environment is a complex paradigm requiring significant effort by hospital staff. Additional tools and methods may be needed to further facilitate glucose management. Hypothesis: Modified interstitial glucose sensors may be used effectively for glucose monitoring in the critically ill. Methods: A study was conducted in a cardiothoracic ICU at the University of Michigan under IRB approval. The investigational sensors were a modified version of the Medtronic SOF-SENSOR™ (Medtronic; Northridge, CA). The modifications focused on interference rejection and increased sensitivity to low glucose. Each subject wore two modified sensors attached to a recording device that collected sensor signals in one-minute intervals. During post-processing, the two sensor signals from each patient were combined to produce a single glucose value output. Reference blood glucose information was collected by ACCU-CHEK® meter (Roche Diagnostics, Mannhein Germany) on an hourly basis, by arterial draw or by capillary sampling. APACHE II score was assessed on a daily basis, and concomitant medication information was collected with time of delivery for post-study analysis. Results: 15 surgical patients were enrolled and completed the study. The average daily APACHE II score for the patient group was 20 (range: 4 – 67). During the study, 512 paired data points between sensor glucose and reference blood glucose were recorded. The Mean Absolute Relative Difference between paired points was 11.0%. The ISO 15197 bias analysis showed 100% of paired points with glucose ⬍ 75 mg/dl within 15 mg/dl (n ⫽ 5), and 87% of paired points with glucose ⬎ 75 mg/dl within the 20% error range. A total of 110 medications were administered and evaluated during the course of this study. Analysis of sensor signal after medication delivery, including acetaminophen, showed no indication of interference with glucose signal. Conclusions: The modified sensor showed good agreement with reference glucose and no drug interference issues in the patients studied. Although a small feasibility study, the results indicate that specialized interstitial glucose sensors may be a promising tool for glucose monitoring in the hospital.


Poster: Endocrine-2 251

252

RISK FACTORS FOR CEREBRAL EDEMA IN DIABETIC KETOACIDOSIS: A PICU EXPERIENCE

AN EVALUATION OF INSULIN GLARGINE USE IN THE MEDICAL INTENSIVE CARE UNIT

Sunit Singhi, Post Graduate Institute of Medical Education and Research, Lokesh Tiwari, PGIMER, Jayashree Muralidharan, Post Graduate Institute of Medical Education and Research

Lindsay Pell, The Ohio State University Medical Center, Kayla Hansen, University of North Carolina Hospitals

Introduction: Cerebral edema (CE) in children with diabetic Ketoacidosis (DKA), has high morbidity and mortality especially in the developing economies due to delay in seeking medical attention and high incidence of sepsis. Hypothesis: To examine the demographic, clinical profile and risk factors for CE and correlate it to the outcome. Methods: Medical records of 77 children with DKA admitted to PICU of a tertiary care hospital in North India between 1st January 2004 and 31st December 2008 were reviewed retrospectively with respect to demographics, clinical features, biochemical profile (blood glucose, osmolality, electrolytes, urea, creatinine, arterial blood gases at admission, 6, 12, 24hours and beyond), complicating CE, septic shock, treatment and primary outcome in terms of survival or death. Patients with and without CE were compared to determine the risk factors for CE. Variables significant on univariate analysis were subjected to multiple logistic regression to determine the most significant predictors. Results: Mean age of the cohort was 5.6 (SD 3.8) years with boys: girls ratio of 1.02. Fifty five (71.4%) had new onset diabetes mellitus.CE was seen in 20 (26%).Admission serum osmolality, blood glucose, rate of fall in glucose and osmolality in first 12 hours and CO2 levels in CE and non CE groups were similar.Univariate analysis revealed younger age (3.9 vs. 6.3 yrs; p ⫽ 0.02), impaired consciousness (90 vs57.9%, OR 6.5; 95% CI 1.3-3; p ⫽ 0.009), prerenal azotemia (80 vs.40.4%, OR 5.9; 95% CI 1.8-20; p ⫽ 0.004) and fluid refractory shock (40% vs.10.5%;OR 5.6;95% CI 1.6-19; p ⫽ 0.003) at admission had higher odds for developing CE. Impaired consciousness(OR 9.8; 95% CI 1.4-66.1; p ⫽ 0.019), fluid refractory shock (OR 4.9; 95% CI 1.1-21.5; p ⫽ 0.037) and pre-renal azotemia (OR 4.8; 95%CI 1.04-22.2; p ⫽ 0.044) were the strongest predictors on multiple logistic regression. The mortality was significantly higher in CE as compared to non CE group (25 vs.3.5%; p ⫽ 0.004). Conclusions: Children with impaired consciousness, fluid refractory hypotensive shock and pre-renal failure at admission were at highest risk for CE. Initial blood glucose, osmolality or rate of fall in both had no association with CE.

Introduction: Long-acting medications are often avoided in the intensive care unit (ICU) due to the rapidly changing clinical status of critically ill patients. Insulin glargine is long-acting with a duration of action of approximately 24 hours. This agent may pose a risk of hypoglycemia to ICU patients who frequently start and stop enteral feedings and have changing doses of corticosteroids. There is currently no published literature reflecting the safety of insulin glargine in the ICU. Hypothesis: The objective of this study was to characterize the use of insulin glargine in the medical ICU (MICU). Methods: This retrospective study included all patients in the MICU who received insulin glargine between January and June 2008. Data collection began on the ICU day of initiation of insulin glargine and continued until insulin glargine was discontinued or the patient was transferred from the ICU, whichever occurred first. Hypoglycemia was defined as glucose ⬍ 74mg/dL. Results: 25 MICU patients (17 male) were included with median age of 66 years and median weight 99kg. 88% had a prior diagnosis of diabetes mellitus type II and 36% were receiving insulin glargine prior to admission. Median MICU length of stay was 18 days (range 2-125). Median day of ICU admission when insulin glargine was initiated was day 11 (range 1–29) and median number of days remaining in ICU upon initiation was 7 (range 1–79). Of the 19 patients who had documentation of insulin dose in the previous 24 hours, 53% received initial glargine dose as ⬍ 60% of previous day’s insulin, 26% received 60-80%, and 21% received ⬎ 80%. 28% of patients experienced hypoglycemia, with a total of 41 hypoglycemic events. Mean hypoglycemic value was 62.5mg/dL ⫹/⫺ 8.9mg/dL. 44% of hypoglycemic events received treatment with IV dextrose. 60% of events were associated with enteral feedings being held or decreased. Conclusions: The use of insulin glargine in MICU patients is associated with a significant incidence of hypoglycemia. The majority of hypoglycemic events are related to intermittent decreases in enteral nutrition. Glargine may have a role as basal insulin coverage, but should not be used as the primary means of controlling hyperglycemia in the MICU.

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PERIOPERATIVE GLUCOSE VARIABILITY AND OXIDATIVE STRESS IN POSTOPERATIVE CRITICALLY ILL PATIENTS

EVALUATION OF THE FREQUENCY OF HYPOGLYCEMIA IN PATIENTS RECEIVING CONTINUOUS INSULIN INFUSIONS

Moritoki Egi, Kazuyoshi Shimizu, Yuichiro Toda, Shiho Takenouchi, Kiyoshi Morita, Okayama University Hospital

Kelly Ennis, Katie Muzevich, Virginia Commonwealth University Health System

Introduction: Swings in glucose levels (GV; glycemic variability) might have biological toxicity. Oxidative stress was higher in the presence of fluctuations from hyperglycemia to normoglycemia when compared with sustained hyperglycemia. Such increased oxidative stress can result in endothelial dysfunction and may contribute to organ damages. Perioperative glucose levels is reported as an independent risk factor for death and morbidity. However, there is few study to assess the impact of glycemic variability on oxidative stress in postoperative critically ill cohort. Hypothesis: There may be significant association of GV, calculated with standard deviation of perioperative glycemia, with postoperative oxidative stress. This association may be comparable with those of mean glycemia (Ave), max and minimum glucose levels (Max and Min). Methods: This prospective observational study conducted in 17 post-esophagectomy patients required intensive care more than 7 days. Blood glucose was measured every 6 hours in ICU. Activation of oxidative stress estimated from measurement of serum asymmetric dimethylarginine (ADMA) at the postoperative 7 days. The correlations of two values were assessed using Pearson’s correlation coefficient. Results: Mean perioperative GV was 14.4 mg/dl (0.8mmol/L) and varied from 10.5 to 22.5 mg/dL (0.6-1.2 mmol/L). Mean glycemic control was 141 mg/dl (7.8mmol/ L). Serum ADMA at 7 was 0.45 micromol/L in average and varied from 0.28 to 0.62 micromol/L. Perioperative GV significantly associated with serum ADMA (R ⫽ 0.57, P ⫽ 0.02). However, Ave, Max and Min were not significantly associated with it (Ave; R ⫽ 0.31, P ⫽ 0.26, MAX; R ⫽ 0.46, P ⫽ 0.07, Min; R ⫽ -0.07, P ⫽ 0.80). Conclusions: Perioperative glycemic variability in postesophagectomy patients required ICU more than 7 days had significant correlation with activation of oxidative stress. These correlations were stronger than mean glucose level. Decreasing variability rather lowering glycemia might be an important dimension of glucose management and and important goal of glucose management.


Introduction: Hypoglycemia is associated with serious consequences including seizure, coma, and death. While the intensity of glycemic control in the critically ill remains controversial, it is clear that the risk of hypoglycemia associated with intravenous insulin infusions increases as goal blood glucose decreases. Hypothesis: At Virginia Commonwealth University Health System, hypoglycemic events have been reported with insulin infusions via the institution’s Patient Safety Net system; however, the incidence of these hypoglycemic events has not been assessed. We hypothesize that hypoglycemic events at a large, academic medical center are underreported; therefore, it is important to conduct an investigation into the true incidence of hypoglycemia in patients receiving intravenous insulin therapy. Methods: An IRB approved, retrospective, single-center medical record review assessed the frequency of hypoglycemia, defined as blood glucose ⱕ 70 mg/dL, in patients receiving insulin infusions for at least one hour. Blood glucose values collected included whole blood samples as well as point-of-care testing. Data was stratified by patient location as well as severity of hypoglycemic event. All data was analyzed using descriptive statistics. Results: Of 583 total patients evaluated, 58.3% (n ⫽ 340) experienced at least one blood glucose measurement ⱕ 70 mg/dL. Additionally, 35.7% (n ⫽ 208) experienced an event ⱕ 60 mg/dL, 14.4% (n ⫽ 84) experienced an event ⱕ 50 mg/dL and 6.7% (n ⫽ 39) experienced an event ⱕ 40 mg/dL. The majority of hypoglycemic events, both ⱕ 70 mg/dL and ⱕ 40 mg/dL, occurred in the Cardiac Surgery Intensive Care Unit, where a lower blood glucose goal is currently targeted. Conclusions: Insulin is a high risk medication; therefore, safe administration is a priority for all health care institutions. Without an objective medical record review, the true incidence of hypoglycemic events may be dramatically underestimated. In this evaluation, more than 50% of all patients receiving insulin infusions experienced at least one hypoglycemic event. These results prompted not only a revision of our institution’s insulin titration protocol, but also consideration of commercially available insulin titration software.

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INSULIN GLARGINE IN THE EARLY MANAGEMENT OF DIABETIC KETOACIDOSIS; A RANDOMIZED PROSPECTIVE PILOT STUDY

GLUCOMETRIC ASSESSMENT OF A MODERATE VERSUS INTENSIVE PAPER-BASED INTRAVENOUS INSULIN PROTOCOL AT A TERTIARY ACADEMIC MEDICAL CENTER

Samir Assaad-Khalil, Akram Fayed, Abeer Abdel Aal , University of Alexandria

Stephanie Wong, Kevin Anger, Bonnie Frawley, Rachel Cyrus, Paul Szumita, Brigham and Women’s Hospital

Introduction: By literature review, insulin glargine was not tested in the early management of diabetic ketoacidosis (DKA) in adults. Hypothesis: To study the effect of early use of glargine insulin on the rate of resolution of acidosis and IV insulin infusion requirement in DKA. Methods: 45 patients with DKA were enrolled when inclusion criteria were met. Patients were randomized into 3 groups. Group A: Standard (regular insulin bolus and Infusion), Group B: Standard protocol plus glargine within 6 hrs of admission, Group C: insulin glargine within 6 hrs of admission along with infusion of regular insulin without a bolus. The groups were compared for the duration of IV insulin infusion, dose of insulin to achieve normal anion gap, duration of acidosis, duration of ICU stay, and hypoglycemia episodes. Composite outcome of death and hypoglycemia were compared between the groups. Results: Insulin requirement was higher in group A than B and C; significant difference. The anion gap normalized in B & C earlier than A ; significant difference. The duration of acidosis was significantly longer in A than B & C. The duration of insulin infusion and ICU stay was significantly longer in A than B and C. There was no significant difference between the groups regarding hypoglycemic episodes.There was no death in the study population Conclusions: Early use of insulin glargine in DKA leads to faster resolution of acidosis, less insulin requirements and shorter ICU stay. It does not increase the incidence of hypoglycemia.

Introduction: New recommendations from American Diabetes Association suggest targeting glucose concentrations ⬍ 180 mg/dl in critically ill adults, prompting many institutions to develop new intravenous insulin protocols to achieve this target. Hypothesis: Evaluate the efficacy and safety metrics of a moderate target (MT) versus intensive target (IT) paper-based multiplication factor intravenous insulin protocol. Methods: A single center retrospective study of clinical practice comparing a MT (110-150 mg/dl) vs IT (80-120 mg/dl) paper-based multiplication factor intravenous insulin protocol was conducted in adult patients admitted to an intensive care unit receiving at least six hours of therapy during May 2007 and December 2009 to February 2010. Baseline data included APACHE II score, age, baseline glucose concentration, and nutritional status. Outcomes included mean glucose concentration and rate of hypoglycemia (⬍60 mg/dl). Results: 100 patients who received insulin according to a MT (n ⫽ 50) and IT (n ⫽ 50) intravenous protocol were included in the analysis. Patient demographics were similar with exception of age and gender. The average duration of infusion was 61.8 ⫾ 67.1 vs 47.68 ⫾ 43.48 hours with 3417 vs 2366 glucose assessments in the MT and IT groups respectively. Mean glucose concentrations was higher in the MT group (145 ⫾ 46.8 vs 115 ⫾ 31 mg/dl; p ⬍ 0.01). The percentage of assessments within target range (48 vs 55.2 % assessments; p ⬍ 0.01) was higher in the IT group. The percentage of patients experiencing hypoglycemia (18 vs 50%; p ⬍ 0.01) and hypoglycemic events (0.4 vs 1.7% assessments; p ⬍ 0.01) was lower in the moderate protocol. None of the hypoglycemic events resulted in documented complications. Conclusions: Implementation of a MT IV insulin protocol increased mean glucose concentrations and reduced the rate of hypoglycemia compared to the IT group.

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ACID-BASE BALANCE IN POSTOPERATIVE CRITICALLY ILL PATIENTS: A QUANTITATIVE ANALYSIS

THE TIME BURDEN ASSOCIATED WITH MAINTAINING TIGHT GYLCEMIC CONTROL

Nana Furushima, Moritoki Egi, Shiho Takenouchi, Hiroshi Morimatsu, Kiyoshi Morita, Okayama University Hospital

Juliane Gartemann, Roche Diagnostics, Ltd., Elizabeth Caffrey, Nandini Hadker, United BioSource Corporation, Jennifer Bittner, Mercy Hospital Fairfield, Sonia Terrell, Carsten Rausch, Roche Diagnostics, Ltd.

Introduction: The acid-base balance may altered in postoperative critically ill patients. Recently, the Stewart-Figge methodology has been found to be useful in explaining and quantifying acid-base changes in various clinical situations. Hypothesis: Strong ion difference calculated using Stewart-Figge methodology may play a major role on the acid-base change in postoperative critically ill patients. Methods: Fifty post-esophagectomy patients required intensive care more than 7days were included in this study. This study was approved by the local institutional ethic committee, which waived the need for informed consent. Patients with chronic renal failure (preoperative creatinine clearance ⬍ 30 ml/min) were excluded. We measured all relevant variables for acid-base analysis according to the Stewart-Figge methodology at every morning from postoperative day (POD) 1 to 6. As Base Excess (B.E.) at POD 6 was median of 4.5mmol/L, we separate patients according to 4.5mmol/L of B.E. level and compare between them. The correlations between delta change of variables and postoperative length of stay in hospital (POLOS) were assessed using Pearson’s correlation coefficient. Results: There are 45 patients (90%) with ⬎ 2.0 mmol/L of B.E. at POD 6. In higher B.E. group, delta change of CO2 from POD 1 was significantly higher in compared with lower B.E. group (delta CO2; ⫹ 7.6 VS ⫹ 0.4, p ⬍ 0.001). However, there is no significant difference in delta pH (p ⫽ 0.69). These differences were caused mainly by change in strong ion difference (delta SID; ⫹ 6.7 VS ⫹ 2.3 ; p ⬍ 0.001). This alternation on SID was caused mainly by change in Na and Cl (delta Na; ⫹ 1.2 VS -1.3 ; p ⫽ 0.03, delta Cl; -4.7 VS -2.8 ; p ⫽ 0.03). Delta Cl was significantly associated with POLOS, but delta Na is not (delta Na; R ⫽ -0.22, p ⫽ 0.14, delta Cl; R ⫽ -0.32, p ⫽ 0.03). Conclusions: Most of post-esophagectomy patients required intensive care more than 7days developed metabolic alkalosis. This was associated with a strong ion alkalosis due to both increased sodium and decreased chloride. This findings may be important to physicians to decide the fluid management or respiratory care in such a cohort.

Introduction: Critically ill medical, post-surgical, and trauma patients are at greater risk for hyperglycemia with associated increase in mortality and morbidity. Tight Glycemic Control (TGC) has been documented as a method to control hyperglycemia by managing blood glucose fluctuations through carefully controlled continuous insulin infusion. Hypothesis: In order to determine the amount of time it takes within practice for critical care nurses to implement effectively a TGC protocol within the cardiovascular unit (CVU), we conducted a pilot time-in-motion study to elucidate the effect on workload. Methods: A time-in-motion study was carried out at Mercy Hospital Fairfield, located in Fairfield, Ohio, to document the time associated with TGC activities. TGC is administered to post-op cardiac patients as stipulated in the institution’s “Open Heart Surgery Post-Operative Clinical Pathway Orders”. A timing workflow, used to capture the key steps involved with TGC implementation when utilizing point-of-care (POC) glucometers for the determination of whole blood glucose (bG) and the time required to complete each step, was designed and validated by CVU staff. CVU staff was trained on the timing workflow and mechanism. Independent observers shadowed CVU nurses, observing when a bG measurement was taken, which steps were completed, and the length of time required to complete each step. Other data such as time of the previous bG measurement and status of the last bG test was collected for analysis purposes. Results: Analysis of the timings showed the TGC protocol is carried out, on average, every 1.2 hours and it takes an average of 3.8 minutes to conduct the protocol. During a standard 12-hour shift, nurses conduct the TGC protocol 9.8 times. Thus, a nurse spends 37 minutes, on average, per shift per patient administering the protocol. This equates to 2 hours and 29 minutes per nurse per week. Conclusions: This pilot study suggests that at the hospital level, nursing time associated with administering the TGC protocol is approximately 128 hours and 58 minutes per nurse per year, which reflects a significant time burden to the institution. This could impact on the financial aspect of an institution and patient care.


Poster: GI/Nutrition 261

262

GHRELIN AND MOTILIN EXPRESSION IN CRITICALLY ILL PATIENTS TOLERANT AND INTOLERANT TO GASTRIC ENTERAL NUTRITION

WEARABLE DEVICE MEASURING ENERGY EXPENDITURE IN CRITICALLY ILL PATIENTS HAS LESS VARIABILITY AND IS COMPARABLE TO INDIRECT CALORIOMETRY

Robert MacLaren, Daniel Crona, University of Colorado School of Pharmacy

Alan Murdock, United States Air Force, Pablo Pizarro, Naval Medical Center Portsmouth, Deborah Mueller, University of Texas Health Science Center San Antonio

Introduction: Endocrine abnormalities may cause gastric motility dysfunction and intolerance to gastric nutrition (GN) in critical illness. The hindered expression of ghrelin and motilin, two promotility hormones, may contribute to gastric hypomotility. Hypothesis: Serum concentrations of ghrelin and motilin are similar in patients intolerant and tolerant to GN and these concentrations do not relate to gastric emptying. Methods: 20 critically ill patients with a gastric residual (GR) ⬎ 150 mL while receiving GEN (intolerant group) and 10 patients with minimal GR (tolerant group) were studied. Patients with intolerance were also assessed one day after prokinetic therapy. Using enzyme-linked immunosorbent assays, serum concentrations of total ghrelin (TG), active ghrelin (AG), and motilin were determined within 24 hours of GR and six hours after fasting. Gastric emptying was assessed concurrently by determining time to peak concentration and 60-minute concentration of acetaminophen after enteral administration of 975mg. Statistical analyses comparing hormone concentrations used paired and unpaired t tests. Associations with motility were examined with linear regression analyses. Results: Patient characteristics were similar between groups. Compared to the tolerant group, the intolerant group had higher TG (285.1 ⫾ 132.5 vs. 1324.8 ⫾ 1204.6 pg/mL; p ⫽ 0.0005), lower AG (208.5 ⫾ 186.9 vs. 43.4 ⫾ 36.8 pg/mL; p ⫽ 0.01), and similar motilin concentrations. Hormone concentrations were similar to baseline values after prokinetic therapy. Gastric emptying parameters were not related to hormone concentrations. Conclusions: Patients tolerant and intolerant to GN display different levels of TG and AG but similar motilin concentrations. Diminished AG expression may contribute to gastric hypomotility and GN intolerance. TG is largely generated in the gastric epithelium and converted to AG by ghrelin O-acyltransferase (GOAT), an enzyme also highly expressed in the stomach. The elevated TG and diminished AG concentrations in the intolerant group suggests gastric hypomotility may be linked to abnormal GOAT activity. Further investigations are needed. Funding: SCCM/Bayer/Joseph F. Dasta Critical Care Pharmacy Outcomes Research Grant

Introduction: Indirect caloriometry (IC) has been considered the gold standard for practical reasons to measure energy expenditure in critically ill patients. However, IC is expensive, requires trained personnel, and has a significant error rate at oxygen requirements based on his methodology. Hypothesis: A commercially available wearable device by Bodymedia, known as the Armband, has been demonstrated to be comparable and reliable to IC in healthy subjects as part of a exercise or weight management program. We hypothesis this device is comparable and potentially more reliable than IC in the critically ill since its methodology is not based on gas exchange. The Armband calculates REE based on galvanic skin response, heat flux, and skin temperature. Methods: Twenty-one mechanically ventilated medical-surgical ICU patients were enrolled in the study. All subjects had the Armband placed for 24 hours for data collection and REE calculation. During this 24 hour period, IC was measured at three different intervals for comparison to the Armband. Additionally, a clinical assessment was performed by a registered nutritionist who estimated REE based on recommendations by the American Society of Parenteral and Enteral Nutrition. Results: Mean provider utilization time for IC, nutritionist, and Armband was 105, 10, and 4 minutes per patient. IC steady state was only achieved 54% of the time in the critically ill population. The results of the RM ANOVA indicated a statistically significant difference of the measurements between the nutritionist and IC, between the nutritionist and the Armband, but not between the Armband and IC. IC showed a greater inter-variability average REE measurement compared to the Armband measurements (SD 151 vs. 29). The Bland-Altman plot for the IC and the Armband demonstrated 95% of the measurement were within 2 SD of the mean. The average cost of the reusable Armband including software analysis was less than $500 compared to most IC machines averaging at least $30,000. Conclusions: The wearable Armband demonstrated comparable results to IC in critically ill patients. Additionally it demonstrated less inter-variability and offered an overall costing savings in dollars and time compared to IC.

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THE RENAL SAFETY OF MRI WITH GADOLINIUM IN DECOMPENSATED CIRRHOSIS

ELECTROMAGNETIC GUIDED FEEDING TUBE INSERTION: ENHANCING PATIENT SAFETY

Sonali Sakaria, Andrew Simpson, Nicole Harlan, Sebastian Perez, Ram Subramanian, Emory University

Steven Trottier, Zohair Karmally, Saint John’s Mercy Medical Center, Margaret Cytron, Kimberly Fowler, Victoria Javaux, St. John’s Mercy

Introduction: Renal function is an established prognostic factor that influences survival in patients with end stage liver disease. Given the potential risk of contrast nephropathy associated with intravenous iodinated CT contrast, alternate contrast modalities for abdominal imaging in advanced cirrhosis need to be examined.Hypothesis: The purpose of this study was to examine the renal safety of MRI with gadolinium during abdominal imaging in patients with advanced liver disease. Methods: The study involved a retrospective analysis of 41 cases of abdominal MRI with gadolinium in patients with end stage liver disease and without renal replacement therapy, at a single academic center during 2008. For each case, a serum creatinine and estimated GFR (as calculated by the MDRD equation) was noted prior to, and within a week after the MRI. The serum creatinine and estimated GFR (eGFR) values before and after the MRI were compared for each case using a paired t-test. In addition, the cases were analyzed for sub-acute complications of nephrogenic systemic fibrosis (NSF), a known complication of gadolinium in end stage renal disease. Results: The age of the patients ranged from 37 to 77 years, with 34% being female. The MELD score ranged from 7 to 33 (average MELD 15). The pre- MRI serum creatinine values ranged from 0.5 to 3.8 mg/dl, with 11 cases having values ⱖ 1.5 mg/dl and corresponding eGFRs ⬍ 60 ml/min. A comparison of the pre and post MRI serum creatinine and eGFR values demonstrated no statistically significant difference, including those cases with a pre MRI serum creatinine ⬎ 1.5 mg/ dl. In addition, no cases of NSF were noted. Conclusions: These observations suggest that MRI with gadolinium is a non-nephrotoxic imaging modality in end stage liver disease. Importantly, the renal safety of this modality extends to cases of advanced cirrhosis with concomitant renal insufficiency, in which contrast enhanced CT may be contraindicated due to the risk of CT contrast nephropathy. Since renal function is an established prognostic factor that influences outcome in advanced cirrhosis, the renal safety of gadolinium as a contrast agent in cirrhosis may establish MRI as the preferred imaging modality in end stage liver disease.

Introduction: Insertion of nasoduodenal feeding tubes (NDFT) typically requires an abdominal radiograph (AR) for placement confirmation. A newly developed device, an electromagnetic guided (EMG) feeding tube, has recently challenged the need for radiographic confirmation of nasoduodenal feeding tubes. Hypothesis: The purpose of this study is to compare the EMG and AR results regarding NDFT placement. Methods: Medical surgical intensive care unit (ICU) patients requiring a NDFT insertion were eligible for the study. The electromagnetic feedings tubes were identical to the standard NDFT except for the electromagnetic tip of the guidewire. The electromagnetic insertion was tracked by a small receiver displayed on a bedside monitor. Three study nurses inserted the EMG NDFT and recorded the location of the distal tip according to the bedside display. AR were obtained following the feeding tube insertion. Demographic data were recorded. Results: Two hundred electromagnetic NDFT insertions were attempted in ICU patients, 128 (64%) males and 72 (36%) females, with and average age 65 ⫹/⫺ 16 years. Ten patients did not receive NDFT due to agitation or anatomical issues. Twenty-one patients had preexisting nasogastric or orogastric tubes and 134 (67%, 101 endotracheal and 34 tracheostomy) patients had an airway in place. The average time for nasoduodenal tube insertion was 30 ⫹/⫺ 17 minutes. Ten patients required repositioning of the NDFT during the insertion as the tube was tracking into the airway. None of the tubes were documented to be in the airway by abdominal radiograph. Compared to AR, EMG correctly documented distal feeding tube tip position in 167 (88%) of 190 patients. EMG correctly documented duodenal tip position in 148 (90%) of 164 patients and gastric position in 19 (73%) of 26 patients. Conclusions: Compared to abdominal radiography, the position of the EMG NDFT was correctly identified in 88% of the patients. One-hundred percent of feeding tubes were located in the duodenum or stomach and airway placement was avoided. Abdominal radiographic confirmation may not be required for electromagnetic guided NDFT placement that is intended to be placed in either the stomach or duodenum.


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INDIRECT CALORIMETRY AS A MEANS OF ASSESSING THE NUTRITIONAL STATUS OF PATIENTS IN THE PEDIATRIC INTENSIVE CARE UNIT

PREVALENCE AND SEVERITY OF VITAMIN D DEFICIENCY IN VETERAN POPULATION IN SURGICAL INTENSIVE CARE UNIT (SICU)

Ryan Taylor, Mattel Children’s Hospital UCLA, Diana Saikali, UCLA, Robert Kelly, Mattel Children’s Hospital UCLA

Kendra Glassman, Mark Wong, John Huang, Mark Prange, Audie L. Murphy VA

Introduction: Indirect calorimetry is a useful instrument to measure a patient’s respiratory quotient (RQ). Anecdotally, a high RQ may be associated with a longer duration of mechanical ventilation dependence. Hypothesis: Mechanically ventilated pediatric patients at our university-affiliated, tertiary-care pediatric intensive care unit (PICU) have a high RQ when receiving full nutritional support. Methods: Pediatric patients receiving mechanical ventilation were enrolled in this IRB-approved study (September 2009-May 2010) when deemed to be receiving full nutritional support (total parenteral nutrition (TPN), enteral feeds only or mixed TPN and enteral feeds) by the clinical team. Once enrolled, an indirect calorimetry study was performed. Patients with a RQ of ⬎ 0.9 were categorized as overfed or undergoing mainly carbohydrate oxidation. Statistical analysis utilized Fisher’s exact test. Results: Twenty-three patients had studies completed. Twelve patients (52%) had a RQ of 0.9-0.99, and 5 patients (22%) had a RQ ⬎ 1. Of the patients with a RQ ⬎ 0.9, 12/17 (71%) were on TPN only and 2/17 (12%) were on enteral feeds only. Of the patients with a RQ ⬎ 0.9, 15/17 (88%) were receiving ⬎ 55% carbohydrates. Of the patients with a RQ ⬍ 0.9, four patients (67%) were on enteral feeds only, and one patient (17%) was on TPN only. A RQ greater or less than 0.9 was found to be associated with nutrition modality (TPN, enteral or mixed) (P ⫽ 0.02). A RQ greater than 0.9 was associated with patients receiving TPN only when compared to patients receiving enteral feeds only (P ⫽ 0.05, Bonferroni correction). Conclusions: A large majority of our mechanically ventilated PICU patients receiving full nutritional support are being overfed or receiving a higher percentage of glucose. Compared to those patients receiving enteral feeds only, patients receiving TPN only appear to be associated with a higher RQ. We speculate that this practice may contribute to increased ventilator days due to increased CO2 production. Further studies are needed to determine whether indirect calorimetry can help practitioners tailor a patient’s nutrition in order to reduce mechanical ventilation dependence.

Introduction: Vitamin D is known to be essential for bone health. It is also associated with decreasing risk of common cancers, autoimmune diseases, infectious diseases, cognitive disorders, and cardiovascular disease and potentially improving pulmonary function and diabetes. In critically ill patients deficiency has been associated with causing severe hypocalcemia. Vitamin D deficiency is often undiagnosed and is frequently not evaluated in hospitalized patients. The purpose of the study was to evaluate 25-hydroxyvitamin D (25-OH D) levels in patients admitted to the SICU. Hypothesis: We hypothesized that the frequency of vitamin D deficiency based on 25-OH D levels were high in patients admitted to the SICU. Methods: We prospectively measured 25-OH D levels in patients admitted to the SICU from January to August 2010. Our inclusion criteria were patients that remained in the SICU for more than 2 days. Patients were excluded from analysis if they were transferred out of the unit before levels were drawn. Patient demographics and calcium levels were also collected. Results were reported as mean ⫹/⫺ standard deviation and correlated using Pearson’s correlation coefficient. The hospital’s reference range for 25-OH D and calcium is greater than 32 ng/ml and 8.6-10 mg/dl, respectively. Vitamin D supplementation was started based on the 25-OH D level. Results: A total of 100 patients were assessed. The average age was 65.7 ⫹/⫺12 years. The 25-OH D range was 5 to 46.4 ng/ml (mean 17.6 ⫹/⫺ 7.8 ng/dl). Vitamin D deficiency was seen in 93% of our population. The mean calcium level was 8.2 ⫹/⫺ 0.61 mg/dl. There were no correlations between age, 25-OH D, and calcium levels. Conclusions: Based on our results, vitamin D deficiency is prevalent in patients admitted to the SICU, but was most likely present prior to the SICU. Though the vitamin D levels were considered severely deficient, patients were only mildy hypocalcemic. More research is still needed to determine if vitamin D deficiency contributes to complications in the intensive care setting and if acute supplementation improves morbidity. Pre-emptive screening may become the standard of practice as more research becomes available.

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SYNBIOTIC THERAPY REDUCES THE COLONIZATION OF PSEUDOMONAS AERUGINOSA IN THE LOWER RESPIRATORY TRACT IN PATIENTS ON LONG TERM MECHANICAL VENTILATION SUPPORT

AN APPLICATION OF ENTERAL NUTRITION PROTOCOL IMPROVES PATIENT CARE AND OUTCOMES IN POSTESOPHAGECTOMY PATIENTS

Mineji Hayakawa, Nobutaka Mukai, Hokkaido University Hospital, Takashi Asahara, Yakult Central Institute for Microbiological Research, Tositeru Ishitani, Atsushi Okamura, Inoue hospital, Koji Nomoto, Yakult Central Institute for Microbiological Research, Satoshi Gando, Hokkaido University School of Medicine Introduction: Several reports have described the effects of probiotic/synbiotic therapy for colonization. However, there is currently insufficient theoretical evidence about how it reduces the pathologic colonization. Hypothesis: We hypothesized that synbiotic therapy could reduce the colonization of P. aeruginosa in the lower respiratory tract in patients on long term mechanical ventilation support. We evaluated our hypothesis and also investigated the changes in the gut flora and the intestinal environment. Methods: The present study was prospective, randomized, controlled trial in a municipal hospital. A total of 47 enteral feeding patients with long term mechanical ventilation support were enrolled in the study. Healthy subjects from previous reports served as reference controls. Patients were randomly assigned to synbiotic and control groups. Patients in the synbiotic group were administrated Lactobacillus casei strain Shirota, Bifidobacterium breve strain Yakult, and galactooligosaccharides as synbiotics for 8 weeks. Patients in control groups were not administered any of these synbiotics. Results: The gut flora and fecal organic acids in the study subjects had been significantly disturbed compared with those of healthy subjects. The characteristics of the patients were not significantly different between the control (n ⫽ 16) and synbiotic (n ⫽ 31) groups. In the synbiotic group, the counts of Bifidobacterium (10.2 ⫾ 0.7 vs. 8.5 ⫾ 1.2 Log10 counts/g, P ⬍ 0.001) and Lactobacillus (7.9 ⫾ 0.5 vs. 5.3 ⫾ 2.2 Log10 counts/g, P ⬍ 0.001) in the gut increased following treatment compared with the control group. The acetic acid concentration increased (71.1 ⫾ 15.9 vs. 46.8 ⫾ 24.1 ␮mol/g, P ⫽ 0.004) and pH decreased (6.91 ⫾ 0.38 vs. 7.31 ⫾ 0.53, P ⫽ 0.007) in the gut in comparison with the control group. The counts of P. aeruginosa in the gut decreased gradually in the synbiotic group (4.1 ⫾ 0.9 vs. 5.4 ⫾ 1.5 Log10 counts/g, P ⫽ 0.002). The amount of P. aeruginosa in the lower respiratory tract synbiotic group decreased significantly after synbiotic therapy (P ⬍ 0.017). Conclusions: Synbiotic therapy reduced the colonization of P. aeruginosa in the lower respiratory tract in the patients on long term mechanical ventilation support.

Akira Hamada, Moritoki Egi, Shiho Takenouchi, Kiyoshi Morita, Yuichiro Toda, Okayama University Hospital Introduction: International guidelines recommended the use of enteral nutrition (EN), an initiation of enteral feeding within the first 24-48 hours following admission and an achieve target goal of EN over the next 48-72 hours. To achieve these goals, EN protocol should be required. However, there is few report to assess the impact and safety of protocol based EN in post esophagectomy patients. Hypothesis: An applocation of EN protocol in post esophagectomy patients improve patients care and outcomes. Methods: In this ‘before-after‘ study, we studied 51patients undergone thoracic esophagectomy and reconstruction for esophageal carcinoma. Among them , EN was continuously administrated. Between 2006 and 2007, there is no feeding protocol (n ⫽ 24). The initiation and adjustment of feeding was decided by attending physicians once per day without any target goal of EN.Between 2008 and 2009, the feeding protocol was used (n ⫽ 27). The initiation of EN was determined at post operative day 2 or 3, and the feeding dose was increased by 20kCal/hour at the morning and evening toward 100% of Basal Energy Expenditure (E100) calculated by Harris-Benedict formula. Results: The median duration to achieve EN administration of E100 was for 3 days with protocol, which is significantly shorter than 6 days without protocol (p ⬍ 0.0001).There is no significant different in the incidence of diarrhea and residual volumes between two groups. The use of parenteral feeding was 0% with protocol, which is significantly lower than 16.7% seen inpatients without protocol (p ⫽ 0.03). The median duration for central line inserted was median of 4 days with protocol, which is significantly shorter in compared with 6 days of no-protocol (p ⬍ 0.01). This might influence the lower trend of incidence of deep venous thromboembolism (20.8% vs. 3.7%, p ⫽ 0.06). The application of protocol was associated with significant independent 32% reduction of postoperative hospital stay when adjusting their age, sex, severity of illness and operation time (p ⫽ 0.048). Conclusions: Our simple EN protocol make the duration to achieve target goal of EN significantly shorter and improve patients care without any harmful side effect.


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SPLANCHNIC SATURATIONS, FEEDING, AND INTESTINAL INJURY IN CHILDREN WITH SEPTIC SHOCK

INTERRUPTION DURING THE INITIATION OF ENTERAL NUTRITION AFTER BURN INJURY DOES NOT RESULT IN INTOLERANCE

Jason Scimeme, Nationwide Children’s Hospital, Kristin Greathouse, The Research Institute at Nationwide Children’s Hospital, Mark Hall, Nationwide Children’s Hospital Introduction: Near infrared spectroscopy (NIRS) is often used to assess tissue perfusion. Concerns about intestinal perfusion often affect feeding decisions in sepsis. Our early work suggested that splanchnic NIRS values drop as feeds are advanced in the septic child. The relationships between splanchnic saturations (SsplO2) and biomarkers of intestinal injury are unknown. Hypothesis: Low SsplO2 will be associated with high plasma levels of intestinal fatty acid binding protein (iFABP), a biomarker of intestinal injury, in enterally fed children following septic shock. Methods: Children with septic shock and non-septic ICU controls are enrolled prior to the initiation of post-pyloric feeds. Splanchnic NIRS sensors are placed in the left peri-umbilical area by ultrasound guidance so that the skin to bowel wall distance is ⬍ 2 cm (children with a greater distance are excluded). NIRS values (blinded to the clinical and study teams) are recorded every 5 seconds for 24hrs. Blood samples are obtained prior to the onset of feeds and again at 12 and 24 hrs thereafter. Average NIRS values are calculated for two hour time periods prior to each blood sampling point. Plasma iFABP is quantified by ELISA. Data are shown as median (range). Results: 5 septic children (age: 0.5 [0.02-9.5]yrs; time from ICU admission to initiation of feeds: 2.5 [0.7-7.6]days; lactate prior to initiation of feeds: 0.9 [0.7-2.6]mmol/L) and 2 non-septic controls (0.4 and 0.7 years) have been studied to date. Controls had SsplO2 ⬎ 70% and undetectable plasma iFABP levels. 2 septic children had undetectable plasma iFABP levels, with a median of 0 (0-154 pg/ml) in the septic group as a whole. The median SsplO2 in the septic children was 61 (19-95)%. SsplO2 were lower as feedings were advanced in the septic subjects (p ⫽ 0.04, linear regression) but not in non-septic controls (p ⫽ 0.91). There was no statistically significant relationship between plasma iFABP levels and SsplO2 by linear regression (p ⫽ 0.48). Conclusions: The preliminary data from this ongoing study suggest that splanchnic NIRS values may not be predictive of intestinal injury in pediatric sepsis patients undergoing enteral feeding. Additional enrollment is warranted to confirm these findings.

271 PREDICTING ENTERAL FEEDING INTOLERANCE Beth Shields, Brooke Army Medical Center, Drew Gibson, USAISR, Steven Wolf, University of Texas Health Science Introduction: The tolerance of enteral nutrition (EN) is extremely important in the hypermetabolic burn patient. Intolerance of EN can lead to caloric deficit and loss of lean body mass. Hypothesis: We sought to determine the tolerance of EN during initiation in a critical care setting and describe the population of patients who did not tolerate the initiation, in an effort to determine if EN tolerance can be predicted. Methods: This was an observational study on adult patients with ⱖ20% total body surface area burns (TBSA) who required EN support. The current standard at our facility is early initiation of enteral nutrition starting at a rate of 20 cc/hr and increasing as tolerated by 20 cc/hr every four hrs to goal. We clinically define high residuals as 300 cc or greater. Results: Data was collected on 93 patients (86% men) with an average age and %TBSA of 41 ⫹/⫺18 years and 43 ⫹/⫺18%, respectively. The majority of patients (76%) did not have high residuals during EN initiation. A small percentage (13%) had had high residuals during the first ten hrs of initiation. This group had a high occurrence (92%) of repeating (3 ⫹/⫺2) high residuals over the first 72 hrs of enteral nutrition. A separate small percentage (12%) had high residuals later in the initiation. This group also had a high occurrence (91%) of repeating (2 ⫹/⫺2) high residuals over the next 72 hrs. The patients with high residuals after ten hrs were examined more closely to describe signs of intolerance prior to the high residual. These patients were found to have sudden increase in residuals by ⬎ 130 cc with a residual of ⬎ 140 cc four hrs prior to the high residual. When we re-examined the entire data set with this criteria along with the criteria of a high residual within the first 10 hrs of initiation, only eleven patients who were in the tolerant group were selected as intolerant. Three of these eleven patients did have high residuals within the next 72 hrs, although after reaching the goal rate. Conclusions: We determined criteria to predict enteral nutrition tolerance. This information can be used for prophylactic treatment of possible impending high residuals or to increase to EN goal more rapidly in patients who meet criteria for tolerating EN.


Drew Gibson, USAISR, Beth Shields, Brooke Army Medical Center, Kevin Chung, USAISR, Steven Wolf, University of Texas Health Science Introduction: Patients with serious burns exhibit elevated metabolic rates and thus have higher nutritional needs. Interruptions such as wound care, surgery, or procedures requiring increased narcotic use can lead to gastric ileus and intolerance of enteral nutrition. Hypothesis: Interruption during the initiation of enteral nutrition is associated with an increased rate of intolerance. Methods: Adult patients admitted to the burn intensive care unit with ⱖ20% total body surface area full thickness burns who received enteral nutrition support were enrolled in this Institutional Review Board approved descriptive study. Patients were divided into two groups: those who had prolonged interruptions (defined as more than six hours for reasons other than high residuals) during the initiation of enteral nutrition and before achieving the goal rate (group 1) and those who did not (group 2). Enteral nutrition intolerance during initiation was defined as gastric residuals (checked every four hours) of greater than or equal to 300 cc at any time prior to reaching the goal rate. Descriptive and comparative statistics were used in the evaluation of the differences in tolerance rate during initiation. Results: Between October 2007 and April 2010, ninety-three patients were enrolled in this study, of which 54% had prolonged interruptions in enteral nutrition prior to reaching goal (group 1) while 46% did not (group 2). Group 1 had an intolerance rate of 28% while group 2 had 23% intolerance (p ⫽ ns). The mean time to reaching the goal enteral nutrition rate in group 1 was significantly longer than group 2 (131⫹/⫺259 vs. 23⫹/⫺11 days, p ⫽ 0.01). Conclusions: The majority of patients in our study tolerated the initiation of enteral nutrition. Approximately half of the patients had prolonged interruptions in enteral nutrition before reaching goal rates. Although these interruptions did not lead to increased incidence of intolerance, they did increase the time to reach the goal rate.

272 DO WE GIVE ENOUGH NUTRITION TO CRITICALLY ILL PATIENTS? Susana Ferreira, Centro Hospitalar Do Porto, Anibal Marinho, General Hospital of Santo Antonio, Heloisa Castro, Centro Hospitalar Porto, Margarida Camara, Hospital Cruz de Carvalho Funchal, Ofelia Afonso, Hospital Infante D Pedro, Paula Castelo˜es, CHVNGaia, Ricardo Marinho, FMUC, Estevaõ Lafuente, Hospital Padre Ame´rico Introduction: Over the past 30 to 40 years advances in enteral feeding techniques, venous access and enteral and parenteral nutritional formulations have made the provision of nutritional support possible for most critically ill patients. Nutritional support has become a routine part of the care of critically ill patients and it is now widely accepted for the treatment and prevention of malnutrition and specific nutrient deficiencies. Hypothesis: The objective of our study was to determine the amount of calories we give to the patients during the first ten days in ICU. Methods: Prospective, observational study, conducted in six portuguese ICU’s. We collected demographic data and total calories administered during the first ten days in ICU. Results: We enrolled 75 patients age - 58, 97 ⫾ 17, 19 (60), weight - 72, 42 ⫾ 18, 12 (70). Total calories administered to these patients were 1019, 05 ⫾ 629, 67 (1012) Kcal /day, with a median value of 14, 45 Kcal/Kg/day in the first ten days in ICU. Days without nutrition – 174 (23, 2%), days in parenteral nutrition – 79 (10, 5%), days in enteral nutrition - 471 (62, 8%) and days in enteral and parenteral – 26 (3, 5%). Conclusions: Ours results show that we give to our patients an insufficient amount of calories in the first 10 days but namely in the first 3 days of stay in ICU. As observed in other studies most of these calories are administrated by enteral route but in the other hand in 23, 2% of the days in our study we didn⬘t supply any nutrition.

Poster: Hematology 274

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PRE OPERATIVE ANEMIA IN SURGICAL INTENSIVE CARE UNIT PATIENTS IS ASSOCIATED WITH HIGHER MORTALITY RATES

DOES PACKED RED BLOOD CELL TRANSFUSION INCREASE THE RATE OF THROMBOTIC EVENTS IN THE CRITICALLY ILL?

Damon Clark, Henry Ford Hospital, Mathilda Horst, Henry Ford, Jordan Jack, Henry Ford Hospital, Roberta Mooney, Henry Ford Health System, Joe Patton, Jennifer Ritz, Ilan Rubinfeld, Henry Ford Hospital

Nitin Puri, Haroon Raja, Karen Vito, Krystal Hunter, Barry Milcarek, Cooper University Hospital, David Gerber, Cooper Hospital/UMC

Introduction: Studies of surgical outcomes have shown that mild preoperative anemia can influence the mortality rates of surgical patients. We sought to investigate implications of this in surgical critical care patients. Methods: We conducted an observational study consisting of four years of data in our single institution National Surgical Quality Improvement Program (NSQIP) database (2005 – 2008). Patients admitted to the Surgical Intensive Care Unit (SICU) were included. Anemia was defined as a hematocrit ⬍ 36% (HCT ⬍ 36) and severe anemia with a hematocrit ⬍ 30% (HCT ⬍ 30). Categorical data was analyzed using Chi-square tests, length of stay was analyzed using Mann-Whitney U. Results: There where 5138 patients in this NSQIP data set; 1526 (29.7%) where admitted postoperatively to the SICU. Preoperative hematocrit levels where analyzed and 749 (50%) had HCT ⬍ 36. Our patients with HCT ⬍ 36 required a mean of 8.8 days (median 4) in the ICU versus those with HCT ⬎ 36 had a mean of 4.75 days (median 3) (p ⬍ 0.001). Patients with HCT ⬍ 30 preoperatively required a mean of 11.43 days (median 6) in the SICU versus a mean of 5.5 days (median 3) for patients with HCT ⬎ 30. Pre operative HCT ⬍ 36 was associated with longer duration of mechanical ventilation, 5.5 days (median 3), in comparison to patients with HCT ⬎ 36 with 3.2 mean days (median 2) (p ⬍ 0.001). Patients with HCT ⬍ 30 preoperatively required a mean 6.3 days (median 3) of mechanical ventilation versus a mean 3.8 days (median 2) for patients with HCT ⬎ 30. Our patients with preoperative HCT ⬍ 36 had higher postoperative mortality 71 deaths (9.5%) versus those with preoperative HCT ⬎ 36 having 30 deaths (4.0%) (p ⬍ 0.001, OR 2.5). Patients with HCT ⬍ 30, the postoperative mortality was 46 (14.2%) versus patients with a preoperative HCT ⬎ 30 had a mortality rate of 55 (4.7%) (p ⬍ 0.001, OR 3.38). Conclusions: Our single institution NSQIP database shows preoperative anemia both mild and more severe to be common in our surgical patients requiring post operative SICU care. These patients also have longer SICU stays and more days on mechanical ventilation. Preoperative anemia is independently associated with higher post operative mortality in SICU patients.

Introduction: Packed red blood cell (PRBC) transfusion is common in the critically ill and is associated with substantial morbidity.Transfusion of PRBC older than 28 days has been associated with deep vein thrombosis in critically ill trauma patients. To our knowledge no data exists on the association between transfusion and thromboembolic disease in a general medical-surgical ICU population. Hypothesis: PRBC transfusion increases the risk of thromboembolic events in critically ill non-trauma patients. Methods: Retrospective study of adult patients (pts) admitted to a Medical-Surgical ICU (7/1/2003-12/31/2009). We identified pts through the Project Impact database with these inclusion criteria: age, gender, mechanical ventilation, history of renal failure, APACHE II score, PRBC transfusion, new thromboembolic events, use of DVT prophylaxis. Patients who received PRBC were compared with those who did not receive PRBC with regard to the above mentioned variables. The groups were compared for the overall incidence of thromboembolic events. Data was analyzed using Chi-square test, Mann-Whitney U test and Friedman’s test. A multivariate analysis including key demographic and clinical factors (age, gender, APACHE II score, history of malignancy, history of hypercoaguable state, mechanical ventilation, use of DVT prophylaxis/anticoagulation) was performed to assess the independent impact of PRBC on the occurrence of thromboembolic events. Results: 8556 pts were evaluated, 1649 transfused and 6907 non-transfused. Univariate analysis demonstrated PRBC transfusion (40% v 19%, p ⫽ 0.001), APACHE II (19.6 v 14.7, p ⬍ 0.0001) and MV (87.5% v 47.8%, p ⬍ 0.0001) to be significantly associated with DVT. Multivariate analysis including all parameters as noted above showed only MV to be a significant risk factor for DVT (p ⬍ 0.0001). When MV was excluded from the multivariate analysis PRBC appeared to be a significant independent risk for DVT (p ⫽ 0.03). Conclusions: Our results suggest that PRBC transfusion may be related to an increased incidence of thromboembolic disease in critically ill patients. This effect may be limited to non-ventilated patients. Further investigation is warranted to evaluate these preliminary findings.

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BARRIERS TO THE EFFECTIVE DIAGNOSIS AND MANAGEMENT OF A RARE UNDIAGNOSED BLEEDING DISORDER PRESENTING TO THE CRITICAL CARE SPECIALIST: RESULTS OF A MULTISPECIALTY, QUANTITATIVE CASEBASED SURVEY

RISK FACTOR ASSESSMENT OF VENOUS THROMBOEMBOLISM (VTE) IN CRITICALLY ILL CHILDREN

Mark Reding, University of Minnesota, Fairview, David Cooper, Novo Nordisk Inc. Introduction: Acquired hemophilia (AH) is a rare but life-threatening bleeding disorder that often presents with acute bleeding, with a consistently prolonged aPTT. Hypothesis: Diagnosis and treatment pose a challenge, given the rarity and general lack of familiarity with AH. Methods: Actively practicing physicians from multiple specialties, including critical care medicine (CCM), were randomly sampled from the AMA Physician Masterfile to complete a 10-minute online, case-based survey to assess barriers to effective diagnosis and management of AH. Results: Physicians (N ⫽ 302) specializing in hematology ⫾ oncology, emergency medicine (EM), geriatrics, internal medicine (IM), rheumatology, and CCM participated. When provided with a case patient presenting with abdominal/back pain and bruising of the arms/flanks, similar to physicians in other specialties, ⬎ 90% of CCM physicians would have ordered both a CBC and coagulation studies. When results revealed an aPTT of 63 seconds, slightly more than half (55%) of CCM physicians would have consulted a hematologist, similar to EM specialists (47%) but in contrast to IM (73%) and geriatrics (75%) specialists. Physicians in all specialties (80%-84%) uniformly selected abdominal CT scan as an initial diagnostic test. When laboratory studies revealed worsening anemia and an aPTT twice the upper normal limit after 12 hours of observation, 90% of CCM physicians would have consulted a hematologist, along with ⬎ 70% of physicians across other specialties. While 380% of physicians in each surveyed specialty would have recommended hospital admission after initial presentation, the proportion who would have favored ICU admission after observation increased, especially among the EM gatekeepers (from 35%-73%). CCM physicians were not surveyed about disposition. Conclusions: Findings suggest that CCM and other physicians placed a higher emphasis on finding the site of bleeding than determining the cause of the abnormal aPTT, given the pattern of hematology consultation. Insights from the survey highlight knowledge/practice gaps that may inform educational or clinical initiatives, including diagnostic algorithms and critical pathways to insure proper work-up of abnormal coagulation studies.

Pamela D Reiter, Beth Wathen, Lynn Schultz, Robert Valuck, Richard Allen, Emily L Dobyns, The Children’s Hospital, Aurora, Colorado Introduction: VTE is a recognized complication in hospitalized adult patients. Risk assessment and prophylaxis is well studied and based on solid principles. Conversely, little is recognized or studied about VTE in children. It has been proposed that the risk of pediatric VTE is increased when ⬎ 1 risk factor is present. Hypothesis: We hypothesize that routine VTE assessment can identify children at risk for developing VTE. Aims of this study were to (1) describe nursing compliance with VTE risk assessment, (2) generate an estimate of VTE risk factors in our population, and (3) state the occurrence of deep vein thrombosis (DVT) and pulmonary embolus (PE). Methods: An IRB approved, prospective, observational trial in children admitted to the PICU during a 6 mo study period (Jan 1, 2010-June 30, 2010) was performed. Using a 12-point, computerbased, VTE risk assessment tool, bedside nurses were asked to evaluate children at admission and again if clinical condition significantly changed. Each VTE risk factor was assigned 1-point and a total VTE risk score was generated for every child. Presence of a documented clot was based on ICD-9 codes. Results: There were 800 admits, representing 742 patients. VTE scores were recorded for 707 admits (88% of total). Mean age ⫽ 6.95 ⫾ 6 yrs, mean weight ⫽ 28 ⫾ 23 kg, 45% female. These 707 admits had a total of 1101 scores. Most admits (74%) did not have any change in their score, 25% had 2-4 changes and 1% had ⱖ 5 VTE changes. The most common risk factor identified was the presence of a central line (45%), followed by infection (43%), age ⬍ 1 yr or ⬎ 14 yrs (33%), trauma (8.6%), immobility (18%), obesity (8.6%), cancer (6%), orthopedic surgery (5.7%), nephrotic syndrome (3.6%), thrombophilia (1.5%), elevated estrogen (0.4%) and burns (0.3%). Sixteen percent of scores were zero, 50% were 1-2, 23% were 3-4, and 2% were ⱖ 5. Eighty-six clots were identified in 40 children. Clots were classified as DVT (76%), PE (13%) and other (11%). Conclusions: Nursing compliance with VTE scoring was high at 88%. Most admits had at least 1-2 risk factors for VTE development, with close to 25% having 3-4 risks. Prevalence of VTE in this study was 5.4%, with DVT as the most common.


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INCIDENCE OF BLEEDING WITH INHALED NITRIC OXIDE VERSUS INHALED EPOPROSTENOL FOLLOWING LEFT VENTRICULAR ASSIST DEVICE PLACEMENT

INTENSIVISTS ARE MORE CONSERVATIVE THAN CT SURGEONS IN TRANSFUSING PRBCS AFTER CARDIOTHORACIC SURGERY

Jennifer Smith, Molly McDermott, Barnes-Jewish Hospital, Richard Fagley, Washington Univesity School of Medicine

David Black, Emory Univ SOM, Robyn Kalwerisky, Emory University, Timothy Buchman, Emory University Hospital, Amy Franklin, University of Texas

Introduction: Inhaled nitric oxide (iNO) and inhaled prostacyclins (iPGI2) are pulmonary vasodilators that are commonly used for the treatment of elevated pulmonary artery pressures and preservation of right ventricular function following left ventricular assist device (LVAD) placement. One potential concern for the use of iPGI2 is its potential effect on platelet aggregation seen with systemic administration that could lead to increased bleeding complications. Hypothesis: iNO and iPGI2 result in similar bleeding rates following LVAD placement. Methods: This was a retrospective analysis of all patients who received permanent LVADs between January 1, 2007 and August 31, 2009 at a large metropolitan academic medical center. Results: Fifty-three patients receiving a LVAD were evaluated, 36 of which received iPGI2 and 17 receiving iNO. Bleeding rates were followed for 48-hours post-operatively through documented chest tube output and transfusion requirements. Baseline characteristics were similar, except for the number of patients whose chest was closed at end of surgery, 10 of 17 (58.8%) in the iNO group vs. 29 of 36 (80.6%) in the iPGI2 group had their chest closed at the end of the case (p ⫽ 0.01). We found no significant difference in total red blood cell transfusions with median of 5 units for the iNO group vs. 3.5 units for the PGI2 group (p ⫽ 0.532). No difference was seen in fresh frozen plasma or cryoprecipitate use, but there was an increased number of platelet transfusions with median of 2 units in the iNO and 0 units in the iPGI2 (p ⫽ 0.012). The iNO group was found to have significantly higher chest tube output than the iPGI2 group with a median output of 3.5L vs. 2L (p ⫽ 0.021). No difference was seen in hospital length of stay, duration of treatment or mortality. Conclusions: iNO and iPGI2 had similar incidence of bleeding events following LVAD placement. Our study suggests that iPGI2 is a safe alternative to iNO and does not confer a higher bleeding risk following LVAD placement.

Introduction: The Society of Thoracic Surgeons (STS) and the Society of Cardiac Anesthesiologists (SCA) offer evidence-based guidelines that outline indications for perioperative and postoperative PRBC transfusion of cardiac surgery patients. Practice may not mirror recommendations. We wanted to ascertain if there is different post-op transfusion behavior between critical care medicine intensivists and CT surgeons in a CT SICU. Hypothesis: The null hypothesis was that there would be no difference between the Hgb level at which intensivists and CT surgeons transfuse after CT surgery. Methods: Lab values and vital signs were extracted from the medical record system for each patient that received a prbc transfusion. We collected data for times immediately before and after transfusion of PRBCs: Hgb, 4hr urine output, 4hr chest tube output, CO/CI, ScVO2, and [lactate]. Simultaneous ethnography was performed to identify the decisionmaker. From the structured observations, we identified who ordered the transfusion and in many cases why. Field notes were collected over 45 clinical days and included the documentation of 514 patient discussions containing 101 transfusion discussions. Two ethnographers coded the same notes to verify identity of the decision-makers. In 52/101 transfusions, the responsible service (CCM vs. surgery) could be unambiguously identified. Results: Intensivist-initiated transfusions (n ⫽ 21) were triggered at a significantly lower Hgb (mean ⫽ 7.9, SD ⫽ 1.1) compared CT surgeon-initiated transfusions (n ⫽ 31), (mean ⫽ 8.7, SD ⫽ 0.95) in the same CT SICU (p ⫽ 0.025, Mann Whitney test). Conclusions: While transfusions were generally prescribed at Hgb levels above evidence-based recommendations, intensivists more closely adhered to the transfusion trigger than operating surgeons when caring for the same patients. Neither anemia nor patient-type completely explain specific transfusion behaviors. It appears that the two specialties have different indications for transfusion. Detailed ethnography to account for these differences is needed.

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BIVALIRUDIN DOSES CORRELATE WITH CREATININE CLEARANCE DURING TREATMENT OF HEPARIN-INDUCED THROMBOCYTOPENIA: A RETROSPECTIVE CHART REVIEW

INFLUENCE OF RENAL FUNCTION ON THE EFFICACY AND SAFETY OF SUBCUTANEOUS DESIRUDIN RELATIVE TO ARGATROBAN IN PATIENTS WITH HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)

Gilles Fraser, Richard Riker, Courtney Runyon, David Redding, Teresa May, David Seder, Katherine Cabral, Maine Medical Center

Belinda Duncan, Michael Kurz, Canyon Pharmaceuticals

Introduction: Dose requirements for bivalirudin (BVR) in the treatment of heparin-induced thrombocytopenia (HIT) have not been extensively studied, particularly in relation to renal function. Methods: We retrospectively evaluated 66 adults treated with BVR for suspected HIT between March 2007 and May 2010 who met steady state conditions: constant BVR infusion dose for ⱖ12 hours, serum creatinine varying ⬍20% in 48 hours with 2 goal activated partial thromboplastin times (aPTT) of 60-80 seconds. Results: Median age was 66 years, weight was 78.4 kg, 64% were male, and 82% were admitted to the ICU. Patients were assigned to 5 groups based on either Cockcroft-Gault estimated creatinine clearance (CrCl) ⬎ 60, (n ⫽ 17); 30-60 (n ⫽ 21); ⬍ 30 ml/min (n ⫽ 13); or renal replacement therapy-HD (n ⫽ 11) or CVVH (n ⫽ 4). For the total cohort, the median [IQR] BVR dose was 0.09 [.05-.15] mg/kg/h. For CrCl ⬎ 60, mean BVR dose was 0.13, median 0.15 [.11-.15] mg/kg/h which was greater than CrCl 30-60 (.096, median 0.10 [.06-0.13], p ⫽ 0.004), CrCl ⬍ 30 (0.07, median 0.08 [.05-.1], p ⬍ .001), CVVH (0.06, median 0.06 [.03-.10] p ⫽ .046), and HD (0.045, median 0.04 [.03-.05] p ⬍ .0001). BVR doses were greater for CrCl ⬍ 30 patients compared to HD (p ⫽ .03). BVR doses correlated with CrCl (Spearman r ⫽ .58, p ⬍ .0001). The aPTT value of 70 [63-75] seconds was similar in all groups. Baseline platelet count of 172, 000 dropped to 71, 000 at BVR initiation 6 [4-11] days after heparin initiation and recovered to 112, 500 over 4 [3-6] days. 68% (45/66) of 4T scores were intermediate (32) or high (13) probability. Thrombosis was present prior to BVR in 25.8% and 3% had thrombosis during BVR. Clinically significant bleeding occurred in 4.5%. The INR increased from 1.4 [1.3-1.6] pre-BVR to 1.9 [1.8-2.1] during BVR (p ⫽ .02) in warfarin naı¨ve patients. Platelet factor 4 antibody assay was ordered in 54 patients and was positive in 43%; repeat testing was positive in 5/14 (36%) 6 [2-8] days after the first negative test. Conclusions: We conclude that since BVR dose requirements increase with creatinine clearance, reasonable initial BVR doses (mg/kg/hour) may be 0.04 for HD patients, 0.06 for CVVH, 0.08 for CrCl ⬍ 30, 0.10 for CrCl 30-60, and 0.15 for CrCl ⬎ 60 ml/min.


Introduction: PREVENT-HIT was a multi-center, randomized comparison of SC desirudin (Desi) vs. aPTT-adjusted argatroban in critically ill patients with clinically suspected and laboratory-confirmed HIT. There was no difference in thrombotic outcomes or major bleeds in patients randomized to Desi. Hypothesis: Since Desi is eliminated by renal mechanisms and renal impairment is common in critically ill patients, a subgroup analysis was performed to evaluate efficacy and safety in patients with renal impairment receiving Desi at standard fixed doses. Methods: Cockcroft-Gault estimates of creatinine clearance (CrCl) were calculated using baseline determinations of sex, age, serum creatinine and ideal body weight. Renal impairment (RI)was defined as CrCl ⬍ 60 ml/min. Major bleeding was defined as a fall in hemoglobin of ⬎ 2 gm/dl requiring transfusion and minor bleeding as all other reported bleeding. Patients randomized to desirudin received a fixed dose of 15 mg or 30 mg (if thrombosis present) SC BID regardless of age, weight or renal function. Results: Efficacy & Safety Argatroban n ⫽ 8 Desi n ⫽ 8 Desi-RI n ⫽ 5 Endpoint CrCl [median (min, max)] 56 (18-94) 46 (24-83) 36 (24-37)New Thrombosis, Amputation or Death 0 0 0 Major Bleed 2 0 0 Minor Bleed 1 1 0 Conclusions: This study supports the recommendation that dose adjustment and aPTT monitoring is not necessary in patients with moderate renal impairment (CrCl 30-60 ml/min) receiving standard fixed doses of desirudin, 15 to 30 mg SC BID. The half-life of desirudin is prolonged to 12 hours or more in patients with severe renal impairment (CrCl 10-30 ml/min) which may necessitate dose reduction and aPTT monitoring. As with all anticoagulants, caution should be used in patients with renal impairment as they have a higher baseline risk for bleeding compared with patients with normal renal function.

282

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TREATMENT OUTCOMES OF HEPARIN-INDUCED THROMBOCYTOPENIA IN SUBARACHNOID HEMORRHAGE PATIENTS: A 4 YEAR, SINGLE-CENTER REVIEW

USE OF THE SUBCUTANEOUS (SC) DIRECT THROMBIN INHIBITOR (DTI) DESIRUDIN (DES) IN PATIENTS WITH HEPARIN INDUCED THROMBOCYTOPENIA (HIT) REQUIRING VENOUS THROMBOEMBOLIC EVENT (VTE) PROPHYLAXIS

Scott Benken, University of Illinois Medical Center At Chicago, Eljim Tesoro, University of Illinois At Chicago, Keri Kim, University of Illinois Medical Center at Chicago, Jeffrey Mucksavage, University of Illinois at Chicago Introduction: Treatment of heparin-induced thrombocytopenia (HIT) is not well described in neurosurgerypatients who have a high bleeding risk if anticoagulated. This study evaluated the treatment for HIT insubarachnoid hemorrhage (SAH) patients and compared outcomes in patients with isolated HIT (iHIT) and HIT with thrombotic syndrome (HITTS). Methods: This was an IRBapproved, retrospective, single-center chart review. Adult patients (⬍18 years old) with SAH discharged from the University of Illinois Medical Center at Chicago (UIMCC) from 2006-2009 were included if they had at least one positive HIT antibody test. Pharmacy records were reviewed for drug therapy information. Baseline characteristics were collected for all patients. Patients were categorized with either iHIT or HITTS based on documented evidence of thrombosis. Primary outcome was the incidence of new thromboses prior to discharge. Secondary outcomes included the incidence of major bleeding, new thromboses up to 3 months after discharge, or hospice/death. A composite “poor outcome” (defined as any secondary outcome) was also evaluated. Results: A totalof 176 patients were screened and 30 patients met inclusion criteria. Eighteen (60%) patients were categorized with iHIT and 12 (40%) with HITTS. There wereno differences in baseline characteristics between the two groups. Twelve (67%)patients with iHIT received prophylaxis with fondaparinuxand nine (75%) of patient with HITTS received anticoagulation with argatroban. Primary outcome occurred in 2 (11%) patients in the iHIT group and 3 (25%) patients in the HITTS group (p ⫽ 0.364).No differences in the incidence of hemorrhage, thrombosis at 3 monthspost-discharge, or hospice/death were found. Patients with iHIT had a 5.5%incidence in composite “poor outcome” compared to 33.3% in patients with HITTS(p ⫽ 0.024). Conclusions: SAH patientswith iHIT and HITTS did not differ in the incidence of new thrombosis afterdiagnosis or after discharge, incidence of hemorrhage, or hospice/death.Patients with iHIT had fewer composite “poor outcomes” than HITTS patients.These findings need further evaluation with larger prospective studies.

Linda Duncan, Michael Kurz, Canyon Pharmaceuticals, Jerrold Levy, Emory University School of Medicine Introduction: VTE prophylaxis is essential in the critically ill patient whose care is frequently complicated by thrombocytopenia, suspicion of HIT or potential heparin allergy. Heparin-based therapies are contraindicated in patients with suspected HIT and should be used with caution in patients with a history of HIT. DES is the only DTI approved for VTE prophylaxis and is the only SC VTE prophylaxis agent without precautions for use in patients with thrombocytopenia. The purpose of this study was to review outcomes of DES for the prevention of DVT, PE and death in a critically ill high risk surgical population with a clinical diagnosis or history of HIT. Methods: This was an observational, single-arm, post-marketing registry in 604 patients undergoing hip and knee replacement surgery. Patients with active bleeding and severe renal impairment were excluded. DES was administered as a 15mg SC injection twice daily. Patients with clinical HIT or a history of HIT were identified from the case report form. Efficacy endpoints included symptomatic DVT or PE and all cause mortality. Major bleeding was defined as transfusion of at least 2 units of blood (including perioperative bleeding). Results: At total of 51 patients were included, 14 patients with clinical HIT (6 confirmed with serology) and 37 patients with a history of HIT. The mean age was 61 ⫹ 16 yrs (range 16-89). Patients received DES for a mean of 12.8 ⫹ 10 days (range 1-57). No patients died or developed a pulmonary embolism. No patient with clinical HIT experienced VTE or death. One patient with a history of HIT developed a DVT. This patient received only 1 dose of DES, switched to heparin for unknown reasons and 10 days later developed a symptomatic DVT confirmed with phlebography. At total of 7 patients had major bleeding events, but none required cessation of study drug. Conclusions: In this post-marketing observational trial, the SC DTI DES appears to be a safe and effective agent for VTE prophylaxis in patients at high risk of VTE who also have a clinical diagnosis or history of HIT. This study is limited by its small sample size and observational nature. These results require confirmation in larger, randomized clinical trials.

284 SEVERITY OF ANEMIA DOES NOT ACCELERATE TRANSFUSION IN CRITICAL CARE Robyn Kalwerisky, Emory University, David Black, Emory Univ SOM, Timothy Buchman, Emory University Hospital Introduction: Transfusions are common in critical care. If transfusions are indicated to stabilize or restore oxygen delivery, it follows that patients with severe anemia (defined as [Hgb] ⬍ 7.6 mg/dl) should have a higher priority for transfusion than patients with mild anemia (defined as [Hgb] ⬎ 8.5 mg/dl) . Hypothesis: The null hypothesis, namely that the lag-time between report of [Hgb] value and corrective transfusion is no different in the two patient groups, was tested in two surgical critical care units at Emory University Hospital in Atlanta, GA. Methods: We obtained the reporting time and value of the immediate pretransfusion [Hgb] and the RBC transfusion time from clinical databases, crosschecking all 126 events by Hgb values analyzed across multiple sources (e.g.blood gas lab, hematology lab). Fewer than 10% of Hgb values were discrepant by more than 0.2 gm/dl. The lag-time was defined as the shortest interval between a [Hgb] determination and initiation of RBC transfusion. Results: The null hypothesis was rejected. Contrary to logic, patients with severe anemia experienced a 1.6 hr longer lag time compared with those who had mild anemia (5.8 vs 4.2 hr, p ⫽ 0.04, one-tailed, unpaired t-test). Conclusions: Severity of anemia does not drive alacrity of RBC transfusions. This suggests that correction of anemia is not the sole or even the major driver of RBC transfusion in critical care. Detailed ethnography to illuminate the logic underlying transfusion is needed.


Poster: Immunology 285

286

SECONDARY SEPSIS AFTER SEVERE TRAUMA: IS IMMUNE RESPONSE GENETICALLY DETERMINED?

REGULATORY T CELLS (TREG) AND ADAPTIVE IMMUNE FUNCTION IN PEDIATRIC SEPTIC SHOCK

Maja Surbatovic, Sonja Radakovic, Miodrag Jevtic, Nikola Filipovic, Predrag Romic, Dragan Djordjevic, Military Medical Academy, Dusko Jovanovic, Military Medical Academy, Belgrade, Serbia

Jennifer Muszynski, Nationwide Children’s Hospital, Kristin Greathouse, Lisa Hanson, Jyotsna Nateri, The Research Institute at Nationwide Children’s Hospital, Mark Hall, Nationwide Children’s Hospital

Introduction: Trauma is one of the main causes of death under the age of 45. There is a high risk of developing immune dysfunction and subsequently sepsis(1). There is tremendous variability seen in the clinical profile and outcome in patients who encounter similar insults. Hypothesis: Augmented serum levels of TNF-alpha, IL-10 and IL-1ra are predictors of sepsis development and fatal outcome in trauma patients. Genotype distributions of TNFalpha308, IL-101082 and IL-1ra gene intron 2 polymorphisms are associated with secondary sepsis development and outcome. Methods: Blood samples were obtained from 112 trauma patients (mean ISS 28.9), 42 developed secondary sepsis. Mortality was 27%. Concentrations of TNF-alpha, IL-10 and IL-1ra were determined in plasma using ELISA assays. Genotyping was performed by PCR – RFLP. Results: When comparing trauma and sepsis (TS) group with trauma (T) group we found that mean values of TNF-alpha were 19-fold, IL-10 34-fold and IL-1ra 11.7-fold higher in TS group (p ⬍ 0.01). When comparing non-survivors with survivors, we found that mean values TNF-alpha were 4.2-fold higher in survivors; mean values of IL-1ra were 6.7-fold and IL-10 5.4-fold higher in nonsurvivors (p ⬍ 0.01). All patients with TNF-alpha308AA survived; RR of death in patients with AG was 3.08 and OR 9.33. When AG and GG were compared, RR for sepsis was 1.23 and OR 1.47. When comparing A1/A1 with A2/A2 IL-1ra, RR of sepsis was 1.76 and OR 2.36, and comparison of A1/A1-4 vs. A2/A2, A3/A3 produced RR of sepsis of 1.68 and OR 2.18. When comparing A1/A1 with A1/A2, RR of death was 4.32, OR 6.19; when comparing A1/A1 with A2/A2 RR of death was 1.44 and OR 1.69. Conclusions: Augmented anti-inflammatory response was detrimental; proinflammatory was beneficial regarding survival but it did not protect trauma patients from developing sepsis. TNF-alpha308 and IL-1ra polymorphisms are associated with sepsis development in trauma patients and outcome. IL-101082 polymorphism showed no association although levels of IL-10 were much higher in TS group and nonsurvivors. Reference: 1. Surbatovic M. et al. Immune cytokine response in combat casualites: blast or explosive trauma with or without secondary sepsis. Mil Med 2007; 172(2): 190-5

Introduction: We have shown that innate immune dysfunction is common in pediatric septic shock. Adaptive (lymphocyte-mediated) immune dysfunction can occur in the subacute phase (week 2) of adult sepsis but is poorly understood in children. Naturally-occurring Treg are immunosuppressive and have been implicated in this process in adults. Hypothesis: Lymphocytes from children with septic shock will shift to production of anti-inflammatory cytokines in the second week of illness and will be characterized by an increased percentage of Treg. Methods: Children with septic shock are enrolled and sampled within 48hrs of shock onset and again at Day 7. The percentage of CD4 ⫹ , CD25 ⫹ , CD127lo (naturally-occurring) Treg among CD4 ⫹ lymphocytes is determined by flow cytometry. CD4 ⫹ T cells are also isolated from whole blood by densitry gradient centrifugation followed by magnetic bead negative selection. 5x105 T cells are incubated with phytohemagglutinin (PHA, 10␮g/ml) for 24hrs at 37°C. Resulting cytokine production is measured by multiplex immunoassay. Data are shown as median (IQR). Results: 10 children have been studied to date (age 4 [2-85] mo, PELOD score 16 [11-21]). PHA stimulation of isolated T cells resulted in a higher ratio of anti-inflammatory interleukin (IL)-10 to proinflammatory interferon (IFN)-g in the Day 7 samples vs initial samples (0.68 [0.52-1.1] vs 0.18 [0.11-0.37], p ⫽ 0.01). This was not true for IL-4, a Th2 cytokine (IL-4/ IFNg ratios: 0.029 [0.008-0.047] vs 0.026 [0.014-0.029], p ⫽ 1.0). Surprisingly, the percentage of naturally-occurring Treg was not different between enrollment (6.3 [2.9-8.1]%) and Day 7 (5.1 [4.3-6.1]%, p ⫽ 0.49). Conclusions: Our preliminary data suggest that the adaptive immune response shifts toward production of anti-inflammatory mediators in the subacute phase of pediatric septic shock. In contrast to adult studies, our subjects did not show an increased percentage of naturally-occurring Treg at this time. Cytokine response profiles do not implicate a simple shift to a Th2 phenotype as an explanation for these findings. Additional enrollment is needed to confirm these findings and explore the role of other adaptive immune cells (Tr1, Th3) in children with septic shock.

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ANALYSIS OF CYTOKINE LEVELS IN CRITICALLY ILL PATIENTS WITH PNEUMONIA WITH RESPECT TO GENDER, ADMISSION DIAGNOSIS, PATHOGEN, AND MORTALITY

EFFECT OF BLOOD COLLECTION METHOD IN INNATE IMMUNE MEASUREMENTS IN NEONATES

Amani Politano, Laura Rosenberger, Tjasa Hranjec, Kimberly Popovsky, University of Virginia, Lesly Dossett, Addison May, Vanderbilt University Medical Center, Robert Sawyer, Univ. of Virginia Introduction: Pneumonia is a serious condition in the ICU with a high associated mortality. Interventions to affect the immune response among these patients have not been successful, perhaps due to the heterogeneity of patients studied in terms of disease, severity of illness, and comorbid illness. Hypothesis: We hypothesized that early cytokine levels could specifically differentiate patients with pneumonia who would survive and would differ between various patient subsets. Methods: 586 patients from 3 trauma/surgical ICUs were identified as having pneumonia. Serum samples were collected within 48 hours of diagnosis of pneumonia and analyzed for levels of IL1, IL2, IL4, IL6, IL8, IL10, IL12, interferon ␥, GMCSF, and TNF by ELISA. The data was divided by patient gender, trauma or non-trauma status, ventilator dependence, pathogen, and mortality; an independent samples t-test was performed for each variable. Results are mean ⫾ SEM. Results: Higher levels of IL6 (623.8 ⫾ 141.2 v 293.6 ⫾ 27.9), IL8 (135.9 ⫾ 20.2 v 59.5 ⫾ 6.4), and TNF (23.4 ⫾ 6.0 v 13.5 ⫾ 1.6) were found in patients who died, compared to those who lived. IL4 was higher in males compared to females (207.7 ⫾ 23.7 v 123.3 ⫾ 21.2) and patients with ventilator-associated pneumonia versus non-ventilator-associated pneumonia (211.5 ⫾ 23.2 v 119.6 ⫾ 28.9). In trauma patients, IL8 (63.1 ⫾ 7.8 v 87.7 ⫾ 10.1) and IL10 (179.2 ⫾ 26.6 v 342.9 ⫾ 78.1) were lower than non-trauma patients. IL1, IL2, and IL12 were lower in Gram-negative compared to mixed infections (6.8 ⫾ 0.8 v 21.1 ⫾ 6.8, 16.1 ⫾ 2.4 v 41.5 ⫾ 12.0, 10.5 ⫾ 1.7 v 37.5 ⫾ 12.9, respectively), and IL1 was also less compared to Gram-positive only infections (6.8 ⫾ 0.8 v 10.4 ⫾ 1.4). In Gram-positive infections, IL4 was lower compared to Gramnegative infections (119.3 ⫾ 23.8 v 202.8 ⫾ 22.1). (All differences significant with p ⬍ 0.05). Conclusions: Our data present the largest study analyzing the predictive value of cytokine levels in pneumonia patients treated in the ICU, and suggests important differences in patient subgroups. Further evaluation of these subgroups is needed before targeted interventions will be successful.


Jeffrey Keyes, Jennifer Muszynski, Nationwide Children’s Hospital, Lisa Hanson, The Research Institute at Nationwide Children’s Hospital, Mark Hall, Nationwide Children’s Hospital Introduction: Innate immune dysfunction is common in pediatric critical illness, but is poorly understood in the neonate. Blood draws are done by heel stick in most neonates outside the first week of life. It is unknown if this method of blood collection affects measurements of innate immune function. Hypothesis: Innate immune function values from neonates (ex vivo LPS-induced TNF␣ production and monocyte HLA-DR expression) will be no different between samples obtained from vascular catheters vs. heel stick. Methods: Concurrently-drawn whole blood samples from vascular catheter and heel stick from NICU patients are analyzed. Ex vivo LPS-induced TNF␣ production is quantified by incubating aliquots of whole blood with LPS (500pg/ml) for 4hr at 37°C. TNF␣ in the resulting supernatant is measured by chemiluminescence. Monocyte HLA-DR expression (molecules/cell) is quantified by flow cytometry. Data are reported as median [IQR]. Pairwise comparisons are made using the Wilcoxon test. Bias between heel stick and catheter samples are evaluated by Bland-Altman analysis. Results: 13 infants have been studied to date (EGA: 33 [27-37.5] weeks, BW: 2.021 [0.765-2.89] kg, Day of life: 5 [3.5-11.5] days). There was no statistically significant difference between ex vivo LPS-induced TNF␣ production between heel stick and catheter-obtained samples (755.5 [548-1986] pg/ml vs. 958 [8072061] pg/ml, p ⫽ 0.34) with a trend toward slightly higher HLA-DR expression in heel stick samples (8452 [3583-10368] molecules/cell vs. 7788 [3341-10147] molecules/cell, p ⫽ 0.07). However, the TNF␣ production assay showed much greater bias upon Bland-Altman analysis (-18%) than did HLA-DR expression (4.7%). Conclusions: Our preliminary data suggest that monocyte HLA-DR expression quantified from heel stick blood samples closely approximates the values obtained from vascular catheters in critically ill neonates, though this was not true for ex vivo LPS-induced TNF␣ production. Given that heel stick is the preferred method of blood collection for most neonates after the first week of life, our data may inform the design of future, longitudinal immune monitoring studies in neonates.

289 THE CYTOKINE RESPONSE TO HEMATOPOIETIC STEM CELL TRANSPLANTATION Paul Kim, Childrens Hospital Los Angeles, Rajni Agarwal, Stanford University, Ami Shah, Childrens Hospital Los Angeles, Laila Cravero, Stanford University, Renna Killen, Childrens Hospital Los Angeles, Yael Rosenberg-Hasson, Stanford University, Joseph DiCarlo, Childrens Hospital Los Angeles Introduction: The cytokine response to hematopoietic stem cell transplantation may be responsible for serious complications in the recipient. Hypothesis: To characterize the cytokine response to stem cell transplantation. Methods: Serum from 27 pediatric transplant recipients was collected weekly for fifteen consecutive weeks. Fifty-one cytokines were quantified by Luminex-based human cytokine assay (Panomics, Fremont, CA); limit of detection ⱕ 1 pg/mL, limit of quantitation ⱕ 10 pg/mL. Results: Peaks of cytokine activity occurred at 7-14 days, 42-49 days, and/or 70-77 days, with each period characterized by a distinct set of cytokines. One-way analysis of variance was employed to detect differences in cytokine concentration at these three milestones, with significance set at p ⬍ 0.05. Unchanging concentrations across time periods were demonstrated for hepatocyte growth factor, ICAM-1, interleukins (IL) 2, 5, 7, and 10, leptin, macrophage inflammatory protein-1B, PAI-1, and VCAM. Peak activity occurred at 7-14 days for CD40, GRO-alpha, and IL-6. At 42-49 days, CD40 remained active and levels of IL-2, IL-12P40, IL-12P70, IL-15, interferongamma, leukemia inhibitory factor (LIF), monocyte chemotactic protein-3 (MCP-3), nerve growth factor (NGF), PDGFBB, resistin, TGF-beta and VEGF were increased as well. Predominant cytokines in the late phase (70-77 days) were IL-2, IL-12P40, IL-12P70, interferon-gamma, LIF, MCP-3, NGF, PDGFBB, resistin, TGF-beta and VEGF. Conclusions: Distinct patterns of cytokine release following transplantation were identified. Ongoing recruitment may allow for identification of cytokine markers that herald complications of stem cell transplantation, such as graft-vs-host disease, veno-occlusive disease and respiratory failure.


Poster: Infection-1 291

292

PROSPECTIVE STUDY OF HERPETIC REACTIVATION IN PATIENTS INTUBATED FOR MORE THAN 48 HOURS

SUSCEPTIBILITY OF CANDIDA SPECIES IN PATIENTS WITH CANDIDEMIA

Krishna Sundar, Utah Valley Pulmonary Clinic, Karl Ludwig, Utah Valley Regional Medical Center, Jeffrey Stevenson, ARUP Laboratories, David Hillyard, University of Utah

Ran Xu, St. Luke’s Episcopal Hospital, Miguel Salazar, Jaye Weston, Dhara Shah, St. Luke’s Episcopal Hospital, Kimberly Putney, St. Luke’s Episcopal Hospital, Kevin Garey, University of Houston College of Pharmacy

Introduction: There is no consensus on the diagnostic methodology for identifying herpes simplex virus-1 (HSV-1) infection of the respiratory tract. The implications of HSV-1 reactivation in the respiratory tract of critically ill patients are unclear. Hypothesis: Quantitative polymerase chain reaction (PCR) done on respiratory secretions of intubated patients results in better diagnosis of respiratory HSV-1 infection. Comparisons of HSV-1 PCR of sputa, bronchoalveolar lavage (BAL), blood may better delineate the extent of HSV-1 bronchopneumonitis. Methods: Quantitative HSV-1 PCR was performed on sputa obtained by endotracheal aspiration every 3 days in patients intubated for more than 48 hours. In patients intubated more than a week or those experiencing a VAP, BAL and blood HSV-1 PCR were carried out to assess viral loads. Study was approved by the Intermountain Health Care IRB in October 2009. Results: Of the 47 patients enrolled so far, 16 patients (34%) were found to have HSV-1 (⬎390 copies/ml; log 2.6) on quantitative PCR of one or more sputa obtained by endotracheal aspiration. The mean age, length of ICU stay and total length of hospital stay of patients with HSV-1 positive sputa was higher than those of patients without HSV-1 in sputa. Mortality in HSV-1 positive patients was 25% as compared to 19.3% in HSV-1 negative patients (p ⫽ 0.46). The finding of HSV-1 on sputum PCR correlated with the finding of HSV-1 on BAL PCR. Respiratory HSV-1 reactivation occurred after 2-9 days of endotracheal intubation. Herpetic facial sores were noted in 50% patients with HSV-1 in sputa. HSV-1 viremia was absent in patients with HSV-1 in BAL or sputum. None of the patients with HSV-1 in BAL had herpetic inclusions noted on endobronchial brush cytology. Out of 7/13 patients with HSV-1 on BAL PCR, only 3/7 had herpetic inclusions on BAL cytology. Conclusions: Quantitative sputum PCR is a novel technique for the diagnosis of respiratory HSV-1 infection. It correlates with BAL PCR for the diagnosis of respiratory HSV-1 infection. Reliance on cytological techniques for diagnosis of herpetic reactivation in respiratory tract may be misleading. Higher morbidity may result from HSV-1 reactivation in ICU patients.Funding: IHC Foundation

Introduction: Candida species are the most common pathogen responsible for fungal bloodstream infections in hospitalized patients with non-C. albicans species increasing in incidence. Reportedly 33% to 55% of candidemia episodes occur in intensive care units with mortality rates as high as 71%. Hypothesis: The purpose of this study was to examine causative species in candidemia patients and assess trends and patterns of Candida susceptibility to echinocandins and azoles. Methods: This was a retrospective cohort study in hospitalized patients with bloodstream Candida infections. All bloodstream cultures positive for Candida were identified from the microbiology laboratory from Sep 2006 to Jul 2009. Patient demographics, Candida species, and antifungal minimal inhibitory concentrations (MIC) for caspofungin and azoles were recorded. Candida infections were categorized as initial or repeat infection, and monthly MIC50 and MIC90 values were calculated. Causative species were determined along with MIC changes over time. Results: A total of 428 cases of candidemia were identified during the study period, with an average of 12 ⫾ 4.7 (mean ⫾ SD) cases per month. The most common causes of initial candidemia were C. albicans (38%), C. glabrata (33%), and C. parapsilosis (14%). Of the 428 cases, 102 (24%) were repeat infections. The most common causes of repeat candidemia were C. glabrata (54%), C. albicans (24%), and C. parapsilosis (11%). Susceptibility of caspofungin (MIC50 range 0.0625-0.5 mcg/ml) and fluconazole (MIC50 range 0.625-64 mcg/ml) did not change significantly over the study period. However, in repeat infections, decreased susceptibility of C. glabrata to caspofungin (MIC90 increased from 0.25 mcg/ml in initial cultures to 8 mcg/ml in repeat positive cultures) and C. albicans to fluconazole (MIC90 increased from 1 mcg/ml in initial cultures to 8 mcg/ml in repeat positive cultures) were observed. Conclusions: C. albicans was the most prevalent causative pathogen of initial Candida bloodstream infections, but C. glabrata was the predominant species found in repeat infections. Decreased susceptibility to fluconazole and caspofungin was observed among Candida species in repeat bloodstream infections.

293

294

USE OF ADJUNCTIVE AEROSOLIZED ANTIMICROBIAL THERAPY IN THE TREATMENT OF PSEUDOMONAS AERUGINOSA AND ACINETOBACTER BAUMANNII VENTILATOR-ASSOCIATED PNEUMONIA

RELATIONSHIPS BETWEEN VIRAL PATHOGEN, BACTERIAL CO-INFECTION, AND OUTCOMES FROM BRONCHIOLITIS IN CRITICALLY ILL CHILDREN

Heather Arnold, Barnes-Jewish Hospital, Amber Sawyer, University of Missouri Hospitals & Clinics, Richard Reichley, Barnes-Jewish Hospital, Scott Micek, Barnes-Jewish Hosptial Introduction: Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of multidrug-resistant (MDR) gram-negative ventilatorassociated pneumonia (VAP), but little is known about their influence on clinical outcomes. Hypothesis: AAA improves clinical outcomes in critically ill patients diagnosed with Pseudomonas aeruginosa (PA) or Acinetobacter baumannii (AB) VAP. Methods: A retrospective study was conducted at Barnes-Jewish Hospital. Critically ill patients who developed PA or AB VAP with positive bronchoalveolar lavage cultures were queried from the pharmacy informatics system. Patient cases were evaluated from 1/1/04 –12/31/09. Outcomes were compared between subjects who received adjunctive aerosolized antibiotics (AAA) and those did not receive AAA (NAAA). Results: 83 patients were included in the NAAA group and 23 in the AAA group (inhaled colistin n ⫽ 13; inhaled tobramycin n ⫽ 10). PA accounted for 77% and 61% of VAP in the NAAA and AAA groups, respectively; AB was responsible for the remainder of cases. 22% of isolates from the NAAA group and 61% of isolates from the AAA group were classified as MDR. NAAA subjects experienced a shorter time from admission to infection (8 vs 12 days, p ⫽ 0.44) and from infection to initiation of appropriate antibiotics (2 vs 4 days, p ⫽ 0.20). Duration of appropriate IV antimicrobial therapy was similar between groups (10 vs 12 days, p ⫽ 0.18). 11% of patients in the NAAA and 17% patients in the AAA group never received appropriate IV therapy (p ⫽ 0.47). In the AAA group, time from infection to AAA was 7 days; duration of inhaled therapy in each arm was 8 days. Hospital and 30 day mortality was similar between groups. However, when time from infection onset to expiration was displayed on a Kaplan-Meier curve, a clear delineation in favor of the AAA group was demonstrated. Despite a log-rank p-value of 0.23, this result was appreciated at 15, 30, 60 and 90 days and was reproducible when MDR-only, PA and AB isolates were evaluated separately. Conclusions: Patients with PA and AB VAP show a trend toward more favorable survival time when treated with AAA. Additional larger, randomized trials are needed to further explore this therapy.


Cesar Mella, Nationwide Children’s Hospital, Asuncion Mejias, Nationwide Childrens Hospital, Jennifer Muszynski, Mark Hall, Octavio Ramilo, Nationwide Children’S Hospital Introduction: Bronchiolitis is a leading cause of morbidity and mortality in infants and children. The relationships between viral pathogen, bacterial coinfection, and outcomes from bronchiolitis are poorly understood. Hypothesis: Critically ill chidren with severe bronchiolitis caused by RSV have increased rates of bacterial co-infection and worse outcomes than those with RSV negative (-) disease. Methods: We reviewed all ICU admissions for bronchiolitis in children ⬍ 2 yrs of age at our center from January to December 2009. Demographic and clinical data were reviewed and compared between patients with RSV ⫹ and RSV- disease. Median data are shown. Results: In 2009, 138/948 (14%) children hospitalized with bronchiolitis required PICU admission, including 125 patients ⬍ 2 yrs of age. 49/125 (40%) patients were premature; of which 41 (33%) were between 32-36 wks GA. RSV was identified in 92 (74%) followed by hMPV (5%), influenza B (5%), rhinovirus (0.08%), and 17% with no virus identified. RSV ⫹ patients were younger(age 1.7 vs 7 mo, p ⬍ 0.001). There were no significant differences between RSV ⫹ and RSV- patients in ICU LOS (5 vs 3 days, p ⫽ 0.7); hospital LOS (8 days, in both groups, p ⫽ 1.0); or need for invasive(50% vs 63%, p ⫽ 0.3) or non invasive mechanical ventilation (47% vs 52%, p ⫽ 0.3). RSV ⫹ patients more frequently had hemodynamic instability (ⱖ 60 ml/kg of fluid resuscitation and/or need for vasoactive agents) on ICU day 1 (30% vs 10%, p ⫽ 0.03) and were more likely to have bacteria isolated from initial airway cultures (80% vs 52%, p ⫽ 0.03)compared to RSV- patients. Among all patients, a positive bacterial airway culture was associated with longer ICU LOS (7.5 vs6 days, p ⫽ 0.02), and a trend toward longer hospital LOS (12 vs 9 days, p ⫽ 0.058). Haemophilus spp and/orMoraxella spp (54%) and pneumococcus (19%) represented the majority of all positive cultures. Conclusions: While resource utilization was not different between groups, critically ill children with RSV ⫹ bronchiolitis appear to be at higher risk of shock and secondary bacterial infection than RSV- patients. The relationships between RSV and secondary bacterial airway infection in critically ill children merit further study.

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EFFECTIVE USE OF A COMBINATION ANTIBIOGRAM TO DETERMINE OPTIMAL EMPIRIC ANTIBIOTICS IN THE MEDICAL INTENSIVE CARE UNIT

BLOOD STREAM ESBL INFECTION IN CRITICAL CARE UNIT: INCIDENCE, RISK FACTORS AND ITS IMPACT ON OUTCOME

Kari Mount, Debra Goff, James O’Brien, The Ohio State University Medical Center

Deven Juneja, Max Super Speciality Hospital, Omender Singh, Max Superspeciality Hospital, Prashant Nasa, Yash Javeri, Rohit Dang, Max Super Speciality Hospital

Introduction: With emergence of multi-drug resistant gram negative organisms (MDRO), infections in the intensive care unit (ICU) are more difficult to treat. Guidelines recommend that ICUs examine their own resistance patterns to guide empiric antibiotics. Our therapy for presumed MDRO is piperacillin/tazobactam (P/T) or cefepime plus an aminoglycoside (AMG). A traditional antibiogram cannot identify which antibiotic combination is optimal. A combination antibiogram reveals how often the organism is resistant to the primary antibiotic but susceptible to the second antibiotic and which combination of antibiotics is most effective. Hypothesis: Creating a combination antibiogram for MDRO will allow identification of the most appropriate empiric antibiotics while minimizing unnecessary antibiotic exposure. Methods: All cultures with gram negative bacteria from a respiratory/ blood culture in the medical ICU between 4/09-4/10 were retrospectively reviewed. Only first isolates were included. As A. baumannii, S. maltophilia, and B. cepacia are not targets for empiric therapy, they were excluded. Susceptibility to each antibiotic was recorded. Appropriate empiric therapy was defined as receiving at least one drug to which the organism was susceptible. Results: 263 isolates were examined. P. aeruginosa (n ⫽ 103), E. coli (n ⫽ 51) and K. pneumoniae (n ⫽ 42) were predominant organisms. Of all isolates, 85% were susceptible to P/T. Adding a second agent to P/T improved susceptibility as follows: tobramycin (97%, p ⬍ 0.0001), amikacin (98%, p ⬍ 0.0001), ciprofloxacin (93%, p ⫽ 0.005). Compared to P/T plus ciprofloxacin, adding tobramycin (p ⫽ 0.05) or amikacin (p ⫽ 0.01) to P/T was statistically better. Of all isolates, 91% were susceptible to cefepime. Adding a second agent to cefepime improved susceptibility as follows: tobramycin (98%, p ⫽ 0.004), amikacin (97%, p ⫽ 0.005), ciprofloxacin (95%, p ⫽ 0.12). Compared to cefepime plus ciprofloxacin, adding tobramycin (p ⫽ 0.059) or amikacin (p ⫽ 0.191) was not statistically different. Adding AMG as a second antibiotic increased the number of patients receiving optimal empiric therapy for MDRO. Conclusions: An ICU combination antibiogram identified P/T or cefepime plus AMG as the most optimal empiric therapy.

Introduction: The incidence of nosocomial infections caused by ESBL producing microbes is increasing rapidly. However, the clinical significance of infections caused by ESBL-producing bacteria in ICU patients remains unclear. Hypothesis: ESBL producing organisms are common causes of blood stream infections in ICU patients and may have an adverse affect on their outcome. Methods: A prospective cohort study was conducted in ICU of a tertiary care hospital in New Delhi, India. Blood cultures were routinely taken at time of admission from all patients suspected to have infection and during the ICU course if there were any signs or symptoms suggestive of infection. Patients, whose blood cultures grew isolates of E. coli and K. pneumonia, during the study period of August 2008 to July 2010, were included for analysis. All patients were managed as per the ICU’s antibiotic policy. For patients at risk of infection with ESBL producing organisms, empirical therapy was initiated with carbapenems in cases of severe sepsis and cefepime or piperacillin/tazobactam for less severe infections.Patients were divided into 2 groups based on the production of ESBL and were compared. Primary outcome measure was ICU mortality. Logistic regression analysis was done to identify risk factors associated with ESBL production. Results: Among the 95 isolates tested, 73 (76.8%) produced ESBL. Transfer from other hospitals or wards (OR 3.65; 95% CI: 1.3 – 10.1 and RR 1.35; 95% CI: 1.05 – 1.73) and previous history of antibiotics usage (OR 3.54; 95% CI: 1.04 – 11.97 and RR 1.5; 95% CI: 0.89 – 2.5) were risk factors for ESBL production. There was no significant difference in ICU mortality (9.6% versus 13.6%; p ⫽ 0.588), need for organ support (vasopressors; p ⫽ 0.796, mechanical ventilation; p ⫽ 0.185 and renal support; p ⫽ 0.343) between ESBL and non-ESBL groups. Conclusions: There is a high incidence of ESBL producing organisms among Enterobacteriaceae causing blood stream infections in critically ill patients. The transfer from other hospitals or wards and previous antibiotic usage are important risk factors for ESBL production. However ESBL production may not be associated with a poorer outcome if appropriate early antibiotic therapy is instituted.

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ANIDULAFUNGIN (ANID) FOR TREATMENT OF CANDIDEMIA/INVASIVE CANDIDIASIS (C/IC) IN SELECTED INTENSIVE CARE UNIT (ICU) POPULATIONS

CLINICAL PROFILE, ICU COURSE AND OUTCOME OF PATIENTS ADMITTED IN ICU WITH DENGUE

Jose A. Paiva, Hospital de Sao Joao, Markus Ruhnke, Charite University Hospital, Wouter Meersseman, University Hospital Leuven, Jan Pachl, University Hospital Kralovske Vinohrady, Ioana Grigoras, University Hospital Sf. Spiridon, Gabriele Sganga, Catholic University Hospital A. Gemelli, Francesco Menichetti, University Hospital Pisa, Philippe Montravers, CHU Bichat Claude Bernard, Georg Auzinger, King’s College Hospital, Georgios Dimopoulos, University Hospital “Attikon” Introduction: ICU patients (pts) are at particular risk of C/IC. ANID is an echinocandin antifungal approved for treatment of C/IC in non-neutropenic pts; it has no dose adjustment requirements and known drug-drug interactions. Prospective trial data on the use of ANID in ICU pts, who commonly present with multiple organ failure and receive a number of concomitant drugs, is lacking. Hypothesis: Safety and efficacy of ANID for the therapy of C/IC in selected ICU populations. Methods: Phase 3b, prospective, open label, multicenter study in adult ICU pts with APACHE II score ⬍25, confirmed C/IC within 96 h before to 48 h after start of study treatment and at least one of these: postabdominal surgery, solid tumor, renal or hepatic insufficiency, solid organ transplant, neutropenia, age ⱖ65 years. Pts received IV ANID (200 mg on day 1, followed by 100 mg/d thereafter) for ⱖ10 days, optionally followed by oral voriconazole/fluconazole, for a total maximum treatment duration of 56 days. The primary efficacy endpoint was global (combined clinical and microbiologic) response at the end of all therapy (EOT) in the modified intent-to-treat (MITT) population. Secondary endpoints included global response at the end of IV therapy (EOIVT) and 2 and 6 weeks after EOT, survival at day 90 and incidence of adverse events (AEs). Results: A total of 216 pts received ⱖ1 dose of ANID. Among MITT pts (n ⫽ 170), 71.2% had candidemia. At baseline, mean APACHE II score was 16.2 (range 4-26), mean SOFA score 7.2 (range 0-20) and mean Candida score 3.4 (95% CI: 3.2, 3.6); the most common pathogens were C. albicans, C. glabrata, C. parapsilosis and C. tropicalis (55.9%, 14.7%, 10.0% and 7.6 %, respectively). Global response was 69.5% (95% CI: 61.6, 76.6) at EOT, 70.7% at EOIVT, 60.2% at 2 weeks post-EOT and 50.5% at 6 weeks post-EOT. Global response at EOT was comparable in pts with or without candidemia, in pts with or without C. albicans, and across the selected subpopulations. Survival at day 90 was 53.8%. Treatment-related AEs occurred in 33/216 (15.3%) of pts, 4 (1.9%) of whom had serious AEs. Conclusions: ANID proved to be an effective, safe and well tolerated agent for the treatment of C/IC in these selected groups of ICU patients.

Deven Juneja, Max Super Speciality Hospital, Omender Singh, Max Superspeciality Hospital, Yash Javeri, Prashant Nasa, Rohit Dang, Max Super Speciality Hospital Introduction: Dengue remains a major health concern in tropical and subtropical countries like India. There have been annual dengue outbreaks in northern India especially in the post-monsoon season. Hypothesis: To assess the clinical profile and ICU course of dengue patients admitted to ICU and to identify the factors related to poor outcome. Methods: All adult patients with dengue infection admitted to ICU during 2 year were included prospectively. Severity of illness was assessed by APACHE II score and presence of organ failure was defined by SOFA score of more than two for that organ system. Primary outcome measure was ICU mortality. Univariate and multivariate logistic regression analysis was performed to assess factors predicting mortality. Results: Data from 114 patients were analyzed. Mean age was 41.95 ⫹ 17.9 years and 70 (61.4%) were males. Commonest presenting complaints were fever (97.4%) and rash (39.5%). Mean admission APACHE II and SOFA scores were 8.38 ⫹ 8.8 and 5.07 ⫹ 3.7, respectively. Commonest organ failure was coagulation (54.4%), followed by cardiovascular (14.9%) and respiratory failure (12.3%). Vasopressor support was required by 14.9% and renal replacement and mechanical ventilation were required by 9.6% and 11.4%, respectively. ICU mortality was 9 (7.9%) and on multivariate analysis, APACHE II score (p ⫽ 0.013) and need for renal support (p ⫽ 0.002), were independent factors predicting mortality. Among the organ system failures, coagulation failure, was least effective in discriminating nonsurvivors (AUROC – 0.231; 95% CI 0.041-0.503) whereas, cardiovascular failure was most effective (AUROC – 0.941; 95% CI 0.891-0.991) followed by respiratory failure (AUROC – 0.893; 95% CI 0.828-0.958). Conclusions: Patients with dengue fever may frequently require ICU admission for organ failure. Their outcome is good if appropriate aggressive care and organ support is instituted early. Patients with high admission APACHE II score and those requiring renal support may be at higher risk of death.



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MRSA INFECTION IN CRITICAL CARE: EFFECT ON MORTALITY

ASSOCIATION OF HEMAGGLUTININ D222 MUTATION IN 2009 INFLUENZA A (H1N1) VIRUS WITH SEVERE RESPIRATORY FAILURE, MICHIGAN 2009-2010

Malcolm Booth, Kate Hamilton, Glasgow Royal Infirmary, John Kinsella, University of Glasgow Introduction: MRSA is a major contributor to healthare infection rates. It represents significant management and prevention challenges and is used as an indicator of infection control standards. MRSA is a source of concern for clinicians, healthcare regulators and the general public. Despite this there is little evidence that MRSA is associated with, or the cause of, poor outcomes in the critically ill. Hypothesis: We hypothesised that in a critical care unit with intense surveillance of MRSA infection rates and audited clinical outcomes that it would be possible to measure the impact of MRSA on critical care mortality. And that MRSA would be associated with an increased length of stay or mortality. Methods: Over seven and a half years ending June 2007 we prospectively collected infection control data for all admissions to a tertiary university hospital critical care unit. Demographics, illness severity including APACHE II and APACHE II predicted motality and outcome data were routinely collected. Patients were classified as: MRSA on admission; critical care acquired MRSA; and MRSA never. These 3 groups were then compared in terms of their severity of illness and outcomes. Patients in whom APACHE II scoring was not possible e.g. burns and re-admissions were excluded. Results: 2528 patients were admitted and 2144 were analysed following the a priori exclusion criteria. Of these 1730 patients were never MRSA culture positive. 307 had MRSA at time of admission and 107 acquired MRSA during their critical care admission. There were no significant differences in APACHE II or APACHE II predicted mortality. No group had a significantly increased standardised mortality ratio: 0.91, 0.93 and 1.04. The patients with acquired MRSA did have a substantially longer mean length of stay at 23.9 days (MRSA never 5.56 days and MRSA on admission 7.9 days). Conclusions: MRSA acquired in the critical care unit or present on critical care admission is not associated with an increase in mortality. MRSA which is acquired in the critical care unit is associated with a prolonged length of stay. The mean time to MRSA acquisition (10 days from critical care admission) indicates that this is a consequence of the prolonged stay rather than its cause.

Pauline Park, University of Michigan, Eden Wells, Susan Peters, Michigan Department of Community Health, Larisa Gubareva, Alicia Fry, Centers for Disease Control, Christy Zalewski, University of Michigan Medical School, Timothy Uyeki, Centers for Disease Control, Lena Napolitano, University of Michigan Introduction: Mutation in the hemagglutinin 222 amino acid (HA 222 AA) of 2009 influenza A (H1N1) virus has been associated with severe clinical illness, but is neither necessary nor sufficient for development of severe infection. Hypothesis: We sought to determine the prevalence of HA 222 AA mutation in a well-characterized US cohort of severely ill patients. Methods: Residual viral samples from patients treated between April 2009 and February 2010 were evaluated by HA 222 AA pyrosequencing. A severely ill cohort, comprised of adult patients with severe respiratory failure transferred for ECMO evaluation (UMSICU), was compared with a concurrentlytested convenience sample (MDCH) referred for diagnostic and epidemiologic testing. 136 samples from 113 patients were evaluated, including 47 samples from 25 UMSICU patients and 89 samples from 88 MDCH patients. Almost all MDCH samples were from the upper respiratory tract; lower respiratory tract samples were more frequent in the UMSICU cohort. Results: A single HA 222 AA mutation (D222E) was detected in the MDCH group; the remainder were identified in the UMSICU cohort (D222G, D222N, combination with wild type). Overall, 10/25 (40%) UMSICU patients vs. 1/88 (1.1%) MDCH patients showed variability at the HA 222 amino acid position (p ⬍ 0.0001), with 10/18 (55%) patients showing multiple codons. The presence of a mutation was not clearly associated with patient age, source of specimen, time from development of symptoms to specimen, or time to institution of antiviral therapy. In severely ill patients with and without HA 222 AA mutations, the incidence of pulmonary hemorrhage, use of ECMO support and overall mortality were similar. Conclusions: Patients with severe H1N1-associated respiratory failure were significantly more likely to have HA 222 AA mutations than a concurrently-studied epidemiologic cohort. However characteristics and mortality were similar in the ICU patients with and without the mutation. Further evaluation of the association, including investigation of potential alterations in host-viral interactions, should be included in future studies of H1N1 influenza.

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COMPARISON OF EARLY-ONSET PATHOGENS AND INFLUENCE OF MULTIDRUG RESISTANT PATHOGEN RISK FACTORS BETWEEN CRITICALLY ILL MEDICAL, SURGICAL, AND TRAUMA PATIENTS WITH SUSPECTED PNEUMONIA

MORTALITY IMBALANCE IN THE TIGECYCLINE PHASE 3 AND 4 CLINICAL TRIALS

Matthew Gauck, UC Health-University Hospital, Neil Ernst, Eric Mueller, UC Health-University Hospital; University of Cincinnati

Introduction: Tigecycline (TGC) is a glycylcycline antibiotic that has been approved for the treatment of complicated intra-abdominal infection (cIAI), complicated skin and skin structure infection (cSSSI), and community-acquired bacterial pneumonia (CABP). In 12 of 13 phase 3 and 4 clinical trials, a numerical increase in all-cause mortality was observed in the TGC group versus comparator. Methods: A pooled analysis of TGC studies that included a comparator was performed using a random effects model. Logistic regression and classification tree analyses were performed to identify risk factors associated with death. Results: In all, 4.0% (150/3788) of TGC subjects and 3.0% (110/3646) of comparator subjects had an outcome of death. The adjusted risk difference in all-cause mortality was 0.6% (95% confidence interval, 0.1–1.2). Cumulative hazard analyses suggested heterogeneity in the risk of mortality across infection types with the greatest risk observed in studies of resistant pathogens and hospital-acquired pneumonia (HAP). The mortality imbalance does not appear to be a function of differential efficacy with the exception of TGC-treated subjects with ventilatorassociated pneumonia (VAP) who had lower cure rates (47.9% vs 70.1%) and greater mortality (19.1% vs 12.3%) than comparator. Increased age, higher APACHE II score (⬎15), and low albumin were identified as risk factors most strongly associated with mortality in both TGC and comparator groups. Baseline bacteremia, driven by the results of one study in HAP, was identified as a risk factor for mortality in the TGC group. In subjects with VAP and baseline bacteremia, mortality was 50% (9/18) for TGC versus 7.7% (1/13) for the comparator group. Additionally, among those who died, more TGC-treated subjects were deemed cured at the test-of-cure visit by investigators (8.2% TGC vs 5.7% comparator) and more TGC subjects died ⬎ 30 days after the last dose of therapy (8.8% TGC vs 1.0% comparator). Conclusions: Infection type, age, severity of illness, and other factors remain important predictors of all-cause mortality in tigecycline clinical trials.

Introduction: Adequate empiric antibiotic therapy for pneumonia depends on local ICU ecology and multidrug-resistant pathogen risk factors (MDRrf). The influence of specific MDRrf on identifying early-onset nonlactose-fermenting Gram-negative bacilli (nlGNB) and MRSA may differ between critically ill populations. Hypothesis: Critically ill trauma patients will have early nlGNB and MRSA less often than critically ill surgical and medical patients despite MDRrf presence. Methods: This was a multi-ICU retrospective study of a prospective culture database at an urban level-1 trauma, academic medical center. Adult critically ill patients suspected of pneumonia who underwent bronchoalveolar lavage (BAL) between Dec06-Jan09 were screened. BALs with bacterial pathogen growth ⱖ10, 000 cfu/mL were included. Early-onset was ⬍ 5 days from hospital admission, thus controlling for hospital length of stay as a MDRrf. Other IDSAdefined MDRrf were obtained from retrospective review of index hospitalization and previous admission histories. Results: 231 patients (trauma n ⫽ 86; medical n ⫽ 78; surgical n ⫽ 49), 275 BALs, and 339 isolates were included. Trauma patients were younger, more often male, and less often had MDRrf. Most common early isolates per group were MSSA/Strep spp. (31%, 20%, 6%), Hemophilus (28%, 7%, 17%), nlGNB (10%, 22%, 28%), Enterobacteriaceae (17%, 12%, 22%) and MRSA (0%, 20%, 6%), respectively. Of all nlGNB/MRSA isolates per group, 7% (n ⫽ 3), 50% (n ⫽ 25), and 16% (n ⫽ 6) were early. In those w/o MDRrf, rates of early nlGNB/MRSA were 5%, 67%, and 13%. Corresponding sensitivity/specificity/positive/negative (NPV) predictive values for MDRrf and early nlGNB/MRSA were 67/40/6/96%, 76/14/50/33%, and 83/27/21/88%, respectively. Removing previous antibiotic exposure increased specificity to 80% in trauma and increased NPV to 42% and 94% in medical and surgical patients, respectively; removing previous healthcare exposure had no effect. Conclusions: Early pathogens differ between critically ill populations despite MDRrf. Initial assessment of MDRrf had moderate sensitivity and poor specificity for early nlGNB/MRSA. Previous antibiotic exposure does not influence the high NPV of MDRrf for early nlGNB/MRSA in trauma patients.


Paul McGovern, Michele Wible, Ahmad El-Tahtawy, Pinaki Biswas, Daniel Meyer, Pfizer Inc.

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CLINICAL IMPORTANCE OF VIRAL RESPIRATORY MARKERS IN A REFERRAL RESPIRATORY ICU

EPIDEMIOLOGY AND OUTCOME OF INFANTS WITH BORDETELLA PERTUSSIS: A FIVE YEAR EXPERIENCE

Seyed Mohammad Hashemian, National Research Institiute of Tuberculosis & Lung Disease, Ali reza Nadji, NRITLD, Hamid Reza Jamaati, Mandana Chitsazan, Golnar Radmand, Mahdi Malekpour, Shahid Beheshti University of Medical Sciences

Ana Lia Graciano, Children’s Hospital of Central California

Introduction: The current data on the load and importance of viral respiratory infection in ICU is scarce. Hypothesis: This study was conducted on the sole referral respiratory ICU nationwide to elucidate the clinical importance of viral markers and viral infection Methods: During the period of two years, all patients with documented diagnosis of VAP and those who stay over 10 days in ICU undergone BAL and the specimen were tested for viral markers using PCR. Specimens were tested for CMV, HSV1, HCV2, RSV and EBV. 65 patients were studied in total. Patients were divided into two groups of viral and non-viral. Results: No significant difference was noted in the clinical condition and severity of diseases reflected through statistically non-significant SAPS II, APACHE II and SOFA scores (all p ⬎ 0.5). Hemodynamic and laboratory findings were same in two groups. Acinetobacter (p ⬍ 0.001) and Pseudomonas (p ⬍ 0.01) bacterial VAP independently and significantly increased the mortality rate in each group. Patients with positive CMV and HSV1 infection showed significant increased in the mortality rates (p ⬍ 0.01) and in cases with co-infection with bacterial VAP, HSV1 and CMV showed an increased mortality rates in comparison with bacterial VAP alone. Conclusions: Our findings show that viral infection either alone or as co-infection with bacterial respiratory infection will increase the mortality in ICU and showed be treated accordingly.

Introduction: In 2010 the Center for Diseases Control declared a Pertussis epidemic in California with 7 reported fatal cases. Our hospital had one of the highest number of cases. We report the clinical characteristics, treatment and outcome of infants ⬍ 12 months of age with confirmed Bordetella Pertussis infection who were admitted to the pediatric intensive care unit between January 1st 2005-August 31st 2010. Hypothesis: We hypothesized that describing the epidemiology of critical Pertussis and the response to available treatments, will provide relevant data for early identification of these high risk infants as well as implementation of appropriate therapeutic modalities to improve their outcomes. Methods: Retrospective chart review as well as review of radiologic studies and echocardiogram reports of all infants admitted to the intensive care unit with confirmed diagnosis of Pertussis by PCR or culture. Results: A total of 40 patients younger than 12 months of age were admitted to the PICU, mean age 8.5 weeks (range 0.6-36). 25/40 (62.5%) patients required mechanical ventilation, including high frequency oscillatory ventilation in 8 patients. Mean white blood count was 40.5 (range 7.7-105.5). Co-Infection at the time of admission was identified in 8 patients. Intubated patients received aggressive pulmonary clearance treatments including dornase and/or hypertonic saline nebulization and bronchoscopy to clear mucus plugging. Four patients with WBC ⬎ 75, 000 underwent double volume exchange transfusion, three survived. 3/40 patients died. There was a significant correlation between mortality, critical hyperleukocytosis and pulmonary hypertension (PAH). PICU length of stay correlated with higher WBC (p ⬍ 0.05) Conclusions: Infants with pneumonia, critical hyperleukocytosis, and PAH have increased morbidity and mortality. Identifying risk factors for critical Pertussis and implementing early therapeutic measures can be crucial in the subsequent management and eventual outcome of this high risk group.

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EXTENSION OF PIPERACILLINE/TAZOBACTAM INFUSION TIME IN THE TREATMENT OF NOSOCOMIAL PNEUMONIA IN THE ICU OF A CANADIAN UNIVERSITY HOSPITAL (EXTEND STUDY)

ANTITHROMBIN III (AT III) ALTERATIONS HAVE A NO RELATION WITH DIC STATUS IN THE EARLY STAGE OF SEPSIS

France Dion, Audrey Buisson, Anne-Genevieve Genest, Marie-Pierre Nolet, Anita Ang, Amine Bouziane, CHUM Introduction: Nosocomial pneumonia is one of the most frequent infections in the intensive care unit (ICU). It is associated with a high mortality and morbidity and an important burden on the health system. Piperacilline/tazobactam (P/T) is often the first line of treatment against this infection. Hypothesis: Beta-lactams present a time-dependant antibacterial activity. Pharmacokinetic and pharmacodynamic simulations showed that a bolus of P/T followed by a continuous infusion could sustain plasma concentrations over the minimum inhibitory concentration (MIC) for a longer period of time than the current practice of intermittent infusions. Therefore, it would be associated with better clinical outcomes of nosocomial pneumonia. Methods: A quasi experimental prospective study was performed with a pre and post design containing a parallel control group. From August 3rd, 2009 to April 25th, 2010, the study evaluated the different infusion methods using surgical and medical ICU adult patients having a hospital-acquired pneumonia treated with P/T and hospitalized at the CHUM. The primary outcome was the clinical resolution of pneumonia at day 10 of treatment. Other efficacy and safety outcomes were also evaluated. Results: P/T infused continuously increased the rate of clinical cure of nosocomial pneumonia by 32% compared to the intermittent infusion (pre 52.6 % vs. post 84.6%, p ⫽ 0.19). Days without mechanical ventilation were increased by three days (pre 3.9 ⫾ 3.9 days vs. post 6.8 ⫾ 3.8 days, p ⫽ 0.04), while the duration of the ICU stay and the recurrence rate of infection were reduced with the continuous infusion (pre 16.7 ⫾ 11.4 days vs. post 15.2 ⫾ 14.1 days, p ⫽ 0.92 and pre 10.5% vs. post 0.0%, p ⫽ 0.70, respectively). Adverse events were comparable between administration methods. Twenty patients were included in the intermittent group (pre) while 15 patients were included in the continuous infusion group (post). Accrual could not be met and the results of the control group were too sparse to be analysed. Conclusions: Results suggest that a continuous infusion of P/T may be more effective and is as safe as intermittent infusions in treating nosocomial pneumonia in an ICU setting.

Masaru Abe, Taijiro Goto, Tomoyuki Harada, Ryuichi Moroi, Mizuho Namiki, Keiko Natori, Noriko Saito, Munekazu Takeda, Arino Yaguchi, Tokyo Women’s Medical University, Terada Takahiro, Tokyo Metropolitan Police Hospital Introduction: Antithrombin III (AT III) has been known to contribute to antiinflammatory response as well as its anticoagulation. In acute inflammatory situations, AT III is consumed or inactivated but this mechanism has not been elucidated yet. Our previous study showed AT III deficiency happened in sepsis. Hypothesis: We hypothesize AT III activity does not relate with DIC status in sepsis. Methods: From January to December 2007, all adult patients admitted to our ICU were included in this study. Trauma patients and patients with hemorrhagic shock were excluded. Serum AT III activity (%) was measured in all patients on admission. The measurement of AT III was using by chromogenics assay (Sysmex®, Kobe) (normal: 80-130%; AT III deficiency ⬍ 80%). Patients were divided into two groups, 1) septic patients and 2) non-septic patients due to primary diagnosis on admission. AT III activity was compared in two groups. Values are expressed as mean ⫾ SD. Data was analyzed by chi-square test, MannWhitney U test and Spearman’s rank correlation. P values less than 0.05 were considered significant. Results: Two hundred and eighty patients (152 men, 128 women; age range 18-94 years [mean 58.2 ⫾ 22.0]) were studied. There were 49 septic patients and 231 non-septic patients on admission. AT III deficiency was present in 69 patients (25%) and 67 % of septic patients had already AT III deficiency on admission. AT III activity was statistically significantly lower in septic patients than in non-septic patients (71.1 ⫾ 20.9 vs. 94.5 ⫾ 17.2 %, respectively, p ⬍ 0.0001). SOFA score was significantly higher in non-septic patients than in septic patients (4.0 ⫾ 3.3 vs. 2.5 ⫾ 2.6, p ⫽ 0.002), while DIC score was higher in septic patients than in non-septic patients (1.0 ⫾ 1.4 vs. 0.4 ⫾ 1.0, p ⫽ 0.004). AT III activity had no correlations with DIC score in septic patients (p ⫽ 0.12), however there was a statistically significant correlation in non-septic patients (p ⫽ 0.006). The mortality was no different between sepsis and non-sepsis. Conclusions: In the early stage of sepsis, AT III deficiency is occurred with a no relation to DIC status, while with good correlations between AT III and DIC in non-septic patients.


307 IMPROVING ANTIBIOTIC DE-ESCALATION PRACTICE IN SUSPECTED VENTILATOR-ASSOCIATED PNEUMONIA: AN OBSERVATIONAL STUDY WITH INTERVENTION David Oxman, Brigham and Women’s Hospital/Harvard School of Medicine, Christopher Adams, Gretchen Deluke, Lauren Philbrook, Peter Ireland, Brigham & Women’s Hospital, Aya Mitani, Christia Panizales, Brigham and Women’s Hospital, Gyorgy Frendl, Brigham & Women’s Hosp./Harvard Med.School, Selwyn Rogers, Brigham & Women’s Hospital/Harvard School of Medicine Introduction: Recommendations for treatment of Ventilator-Associated Pneumonia (VAP) emphasize early broad-spectrum antibiotics. Yet appropriate de-escalation of antibiotics is vital to avoid excessive unnecessary antibiotic use. Once microbiological data is available, or when after re-evalaution the likelihood of pneumonia appears low, guidelines suggest narrowing or discontinuing antibiotics. We examined how often intensivists at our institution appropriately de-escalated antibiotics in suspected VAP and if decision-support could improve practices. Hypothesis: Decision support by ICU-pharmacists can improve intensivists’ antibiotic de-escalation practices in cases of suspected VAP. Methods: Before and after prospective observational study in 4 surgical intensive care units at a university hospital. In phase one, patients with suspected VAP were identified and followed prospectively to see if: 1) Antibiotic coverage was narrowed based on sputum culture results (targeting). 2) Antibiotics were stopped in patients at low-risk of VAP (discontinuation). Likelihood of pneumonia was based on clinical pulmonary infection scores (CPIS) on days #1 and #3 of therapy. In phase two, intensivists were offered decision-support by pharmacists. Results: In the observation phase, 50 cases of suspected VAP were identified. 39 yielded cultures to which antibiotics could be tailored. In only 23 (59%) were antibiotics tailored. Additionally, there were 26 cases in which the likelihood of infection was low, but in only 5 (19%) were antibiotics stopped. During the intervention phase 42 cases of suspected VAP were identified of which 32 yielded cultures to which antibiotics could be tailored. Appropriate tailoring occurred in 29 cases (91%) [p ⫽ 0.005]. In 22 cases with low risk of true infection only in 5 (23%) were antibiotics stopped. Conclusions: At our institution, the rate of appropriate antibiotic de-escalation in cases of suspected VAP was low. However, decision support from ICUpharmacists significantly improved rates of antibiotic targeting. There was no singificant effect on antibiotic discontinuation in patients at low-risk of pneumonia. Additional interventions may be necessary to limit unnecessary antibiotic use in suspected VAP.



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THE RELATIONSHIP BETWEEN STEROID USE AND ACTIVE CYTOMEGALOVIRUS (CMV) INFECTION IN CRITICALLY ILL PATIENTS

SUCCESSFUL CHANGE IN EPIDEMIOLOGY OF ICU MULTIRESISTANT BACTERIA WITH IMPLEMENTATION OF EVIDENCE-BASED INTERVENTIONS

Shinji Uegaki, Mineji Hayakawa, Satoshi Gando, Hokkaido University School of Medicine

Marta Sousa, Isabel Trindade, Hospital Pedro Hispano, Nuno Cortesao, Medical Intensive Care Unit - Hospital Pedro Hispano, Valquiria Alves, Hospital Pedro Hispano, Cristina Granja, Hospital Pedro Hispano; Faculty of Medicine of Porto

Introduction: Recently, many reports have shown that CMV infection in immunocompetent patients is frequent in the ICU, and may be associated with a poor outcome. Hypothesis: We hypothesized that active CMV infection is related to steroid use in the ICU and the lymphocyte count in peripheral blood. Methods: We retrospectively examined patients admitted to the ICU for over 7 days between January 2005 to May 2009. The pp65 antigenemia assay for CMV over the 7 days after admission was performed when a physician suspected a CMV infection. Transplant patients, those who had received long-term administration of steroids, and those younger than 12 years old age were excluded. We compared age, gender, transfusion, CRRT time, days before CMV antigenemia assay, steroid dosage per body weight, lymphocyte counts, ventilator days, ICU stay, APACHE II score, SOFA score, and ICU mortality between the patients and the association with CMV infection. Results: A total of 140 patients were examined using the CMV assay. Sixty-seven patients out of the 140 patients were evaluated using the CMV antigemnemia assay more than 7 days after admission, and were included in this study. Of these 35 patients were antigenemia positive and 32 were negative. The CRRT time, steroid dosage per body weight and SOFA score were significantly different between the two groups. The multivariate analysis showed that steroid dosage per body weight (OR 1.026, 95%CI 1.006-1.045, p ⫽ 0.009) and lymphocyte counts (OR 0.999, 95%CI 0.998-1.000, p ⫽ 0.03 ) are two independent predictors of an active CMV infection. Conclusions: The CMV infections were frequently observed in critically ill patients. Steroid use and lymphocyte counts were two independent risk factors of an active CMV infection.

Introduction: Nosocomial infection due to multiresistant (MR) bacteria is related to a longer length of stay (LOS) and a worse outcome. Hypothesis: To assess the impact of an evidence-based intervention implemented in our ICU in 2007 on MR bacteria epidemiology and related infections. Methods: Retrospective analysis of 194 MR bacteria isolates from culture samples of patients admitted in a 7-bed medical ICU for the past 5 years. MR bacteria considered were meticilino-resistant Staphylococcus aureus (MRSA), multiresistant Acinectobacter baumanni (MRAcibau), vancomycinresistant Enterococcus spp (VRE), extended-spectrum beta-lactamase producers gram negatives (ESBL) and carbapenem-resistant Pseudomonas aeruginosa (CaRPsae). MR bacteria and infections were analysed before and after implementation in 2007 of a set of evidence-based procedures (MRSA and MRAcibau screening protocol, washing hands campaign, central-line (CVC) management and invasive ventilation associated pneumonia (PAVI) protocols). Results: MR bacteria were found in 98 patients, 65% male, mean age 61 yo, 74% with underlying diseases. SAPS 2 was 51, ventilation days 9.5, LOS 14 days and ICU mortality 29.6%. Medical patients accounted for 79%, 16% for surgical and 5% for trauma patients. MR population was 52% MRSA, 30% CaRPsae, 12% ESBL, 4% MRAcibau and 2% VRE. Total bacteria identified decreased after 2007 as well as the rate of MR of all identified bacteria (15% vs. 11% p ⫽ 0.05). Lower rates of MR bacteria were due to MRSA (p ⬍ 0.05) and CaRPsae decrease, despite an increase ESBL (p ⬍ 0.05), VRE and MRAcibau. Infection rate due to MR bacteria has also decreased after 2007 (12% vs. 8% p ⬍ 0.05), including a decrease in MRSA and CaRPsae infections (p ⬍ 0.05) although ESBL, MRAcibau and VRE infections suffered a non-significant increase. MR CVC infection was 2/1000 catheter-days before 2007 and none after this period. MR PAVI has also decreased after 2007 (5.4 vs. 3.7/1000 ventilator-days). LOS of MR bacteria infected patients decreased after 2007 (p ⬍ 0.05). Conclusions: This study suggests that the implementation of a set of evidence-based interventions may contribute to a decrease in MR isolates and that was associated to a reduction in MR infection rates and ICU LOS.

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KLEBSIELLA PNEUMONIAE CARBAPENEMASE PRODUCING ORGANISMS: A RETROSPECTIVE STUDY OF TREATMENT OUTCOMES

CARDIAC TAMPONADE AND SHOCK DUE TO MYOCARDITIS IN A PATIENT WITH H1N1 INFLUENZA INFECTION

Darlene Chaykosky, Claudine El-Beyrouty, Brian Roslund, Thomas Jefferson University Hospital Introduction: Eradication of infections caused by Klebsiella pneumoniae carbapenemase (KPC) producing bacteria is challenging due to the multi-drug resistant nature of these organisms. Aminoglycosides, colistin, and tigecycline may be viable options in treating KPC infections but clinical response can be variable. Currently, there are no guidelines that standardize the treatment of KPC organisms. Hypothesis: A treatment regimen consisting of a combination of antimicrobials is more efficacious in eradicating a KPC organism compared to monotherapy. Methods: This was an IRB approved, retrospective, single center study of all patients with a KPC positive culture between January 2008 and July 2009. An organism was considered a KPC bacterium if the culture showed resistance to ertapenem. Patients were included if they received aminoglycosides, colistin, tigecycline, or a combination of these antibiotics. Patients were excluded if they received antibiotics for ⬍ 24 hours, if they were colonized with a KPC or if they were treated for a KPC infection at an outside facility and were subsequently transferred to our hospital. Results: Of the 74 patient encounters identified, 33 met inclusion criteria. Due to small sample size in the colistin-only arm (n ⫽ 1), this encounter was not included in the analysis. After excluding the colistin-only arm, there was no statistical difference between treatment groups in clinical cure (p ⫽ 0.375) or hospital length of stay (p ⫽ 0.113). There was a statistical difference between treatment groups in intensive care unit (ICU) length of stay (p ⫽ 0.033). Seventy-one percent of encounters in the tigecycline-only arm had an ICU length of stay ⬍ 10 days while 54.5% of encounters in the combinationarm had an ICU length of stay ⬎ 20 days. Differences in eradication rates between treatment arms could not be determined due to small sample sizes in each treatment arm (aminoglycoside-only n ⫽ 7, colistin-only n ⫽ 1, tigecyclineonly n ⫽ 14, and combination n ⫽ 11). Conclusions: Based on our results, it remains unclear if combination therapy is more effective in eradicating KPC organisms compared to monotherapy. Our study suggests combination therapy may be associated with a longer length of stay in the ICU.

Jyoti Assudani, Rahul Kashyap, Guangxi Li, College of Medicine, Mayo Clinic, Chakradhar Venkata, Immanuel St. Joseph’s Hospital-Mayo Health System Case Report – Background: We report an unfortunate case of myocarditis presenting with cardiac tamponade and cardiogenic shock caused by H1N1 influenza infection. In a background of paramount evidence of global spread of H1N1, this uncommon, yet potentially fatal complication needs a vigilant eye among physicians for vital interventions. Case: A 48 year-old woman presented with a 9 day history of influenza-like illness symptoms including fever, cough and myalgias. Her past medical history was significant for hypertension and morbid obesity (BMI ⫽ 42.7). A TTE done at the referring facility, showed global hypokinesis with a large pericardial effusion and an estimated EF of 30%. Troponin was elevated at 0.43. A rapid influenza test obtained in the ER was negative. She was transferred to our institution in cardiogenic shock, for definitive management.On admission, her heart rate was 152 bpm; blood pressure (BP) was 66/42 mm Hg, respiratory rate 20/minute. She required intra-aortic balloon pump and multiple vasopressors to support her BP and mechanical ventilation.A TEE showed a large pericardial effusion and confirmed tamponade with a severe collapse of RA and RV. She was taken to OR. She developed asystole, while being transferred to the OR table, requiring CPR before cardiopulmonary bypass. She had pericardial fluid under pressure relieved and was placed on a right and left ventricular assist device. She was brought to the ICU, where she remained hypotensive and developed multi-organ system failure. She was placed on CVVH. Later on she was declared brain dead due to global anoxic-ischemic brain injury.Autopsy confirmed the diagnosis of lymphocytic type, multifocal, myocarditis. Laboratory diagnosis of H1N1 influenza was made using an influenza real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay performed on respiratory specimens, which was negative for H1N1 in cardiac tissue. Summary: Cardiac involvement with seasonal influenza infection is common. However, fulminant myocarditis associated with novel H1N1 influenza is a very rare but potentially fatal complication. This must be suspected in appropriate settings and must be aggressively treated.


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CHARACTERISTICS OF CLOSTRIDIUM DIFFICILE ACROSS ADULT ICUS IN A TERTIARY HOSPITAL

2009 H1N1 INFLUENZA INFECTION AND SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME: CASE SERIES WITH EMPHASIS ON BRONCHOPLEURAL FISTULAS AND MANAGEMENT APPROACH

Jonas DeMuro, Winthrop University Hospital, Adel Hanna, Withrop University Hospital, David Logan, Winthrop University, Devan Lenhart, William Reed, John McNelis, Winthrop University Hospital Introduction: Clostridium difficile associated disease (CDAD) continues to be a challenge in the critically ill, requiring accurate diagnosis, aggressive medical treatment, and in select patients, surgery. Hypothesis: Increasing use of broad spectrum antibiotics combined with agents given to prevent Stress Ulcer Prophylaxis (SUP) may be associated with CDAD in the ICU. Methods: The medical records of 38 adult ICU patients identified via the infection control data were reviewed retrospectively . Data acquired included demographic data, ICU length of stay (ICULOS), Hospital Length of stay (HOSPLOS), WBC on admission and diagnosis. In addition antibiotics and medications administered as well as surgeries, co-morbid conditions and mortality data. Data is presented as means ⫾ standard deviation. Statistical Analysis is via chi square. Results: The genders were equally divided. The average age was 77 ⫾ 7.6 years , ICU LOS was 15.6 days ⫾ 15.8, and HOSPLOS was 28.0 ⫾ 18.3 days. The observed mortality was 23.7%. The duration from admission to CDAD development was 13.16 days ⫾ 9.98. The WBC at the time of diagnosis averaged 16.1 ⫾ 11.5 . 86.8% of patients were on medications for SUP: 31.6% on famotidine, 21.8% on esomeprazol, and 34.2% both. The incidence of colectomy was 23.7%, with a postoperative hospital mortality of 44.4%. Patients undergoing colectomy were six times more likely to be on metronidazole (p ⬍ .0002). Patients were exposed to a mean of 1.55 ⫾ 1.03 antibiotics before diagnosis with CDAD ( Range 0-4). The common classes included cephalosporins 22.2%, carbapenems 19.4%, fluoroquinolones 16.7%, daptomycin 13.9%, penicillins 8.3%, antifungals 8.3%, tetracyclines 5.6%, and macrolides 2.8%. Conclusions: Antibiotics associated with CDAD in the ICU are changing. Cephalosporins and carbapenems were most associated with CDAD in our study, while no patients were on Clindamycin. While medications for SUP, particularly proton pump inhibitors, remain a potential risk factor a causal relationship could not be deduced from our data . Patients on metronidazole are more likely to require colectomy possibly indicating increasing resistance and treatment failures. Our examination of this important topic is ongoing.

Moussa Yazbeck, Cooper Univeristy Hospital, Woo Jung Lee, Ankur Kalra, Constantine Tsigrelis, Cooper University Hospital, Christa Schorr, Cooper Hospital University Med Ctr, Seraj El-Oshar, Sri-Sujanthy Rajaram, Cooper University Hospital Case Reports: The 2009 H1N1 influenza pandemic affected an estimated 60 million people in the US with 12, 500 deaths. We describe 5 patients with severe H1N1 infection complicated by acute respiratory distress syndrome (ARDS) at our tertiary facility. We also discuss our management of mechanical ventilation, both conventional and high flow oscillatory ventilation (HFOV). Patients’ ages ranged between 20 and 42 years (mean: 28), with 4:1 female to male ratio. Two patients were pregnant upon admission. All patients presented with rapidly progressive respiratory failure requiring mechanical ventilation, and exhibited hypoxemia despite administration of high fractions of inspired oxygen (FiO2). All patients had bilateral diffuse alveolar infiltrates on chest radiography and were treated with broad-spectrum antibiotics and oseltamivir. All cases were confirmed by detection of H1N1 virus from respiratory tract specimens. All patients required very high doses of sedation and 4 required vasopressors at one point during their hospitalization. Four patients had one or more thromboembolic events. Days on mechanical ventilation ranged between 14 and 93 days, and hospital length of stay (LOS) between 14 and 108 days. The patient with the longest LOS survived and 2 died. All patients initially received conventional lung protection strategy with low tidal volumes and high positive end-expiratory pressure (PEEP). All patients received either recruitment maneuvers, prone positioning, inhaled nitric oxide or a combination. Despite this conventional approach, both oxygenation and ventilation became challenging with time. In fact, 3 patients developed pneumothoraces all leading to bronchopleural fistulas (BPFs). Our subsequent mechanical ventilation strategy allowed relative hypoxemia 80-82%, permissive hypercapnia, and prolonged use of HFOV for patients with BPFs. One surviving patient was maintained on a FiO2 of 1.0 intermittently for 16 days in order to wean PEEP, minimize mean airway pressure and facilitate healing of BPFs. In conclusion, patients with H1N1 influenza and ARDS at our institution were young and exhibited high rates of BPFs which require special management approach.

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MINI BRONCHOALVEOLAR LAVAGE AS A METHOD TO DIAGNOSE PNEUMONIA IN A SURGICAL TRAUMA ICU

THE INCIDENCE OF SERIOUS BACTERIAL INFECTION IN INFANTS ADMITTED TO A PICU WITH RESPIRATORY SYNCYTIAL VIRUS

Paul Mahle, University of Central Florida College of Medicine, Matthew Lube, Creighton Fiscina, Jean Tate, Orlando Health Introduction: In 2009 the use of tracheal aspirate in the work up (w/u) of patients (pts) with fever was abandoned in our ICU. It became the standard in our ICU to use either bronchoscopic(BS) guided broncho-alveolar lavage (BAL) or a mini-BAL (mBAL) technique performed by the respiratory therapy (RT) staff without the use of specialized equipment and added costs associated with formal bronchoscopy. This study reports our results with the mBAL technique. Hypothesis: mBAL is an effective tool in the w/u of pts with fever in a surgical/trauma ICU. Methods: All pts having a mBAL as part of a w/u for fever were prospectively followed. The technique involves having the RT staff obtain a right (R) or left (L) sided (depending on xray findings) deep lung specimen with specialized R or L sided catheters for quantitative analysis. Pts with diffuse infiltrates had R sided specimens obtained. mBAL was performed with three separate 20 mL aliquots of saline. 10, 000 or greater cfu/mL were considered positive. BS guided BAL was performed in pts with negative mBAL results with ongoing suspicion for pneumonia. Data are reported as mean ⫾ standard deviation. Results: 105 mBAL’s were performed on 89 pts. Secretions were present in all pts and were purulent in 43. Mean specimen amount was 8 ⫾ 5 mL. Infiltrates were present in 99 cases and were diffuse in 65 and localized in 34. Maximum temperature in the 24 hours preceding mBAL was 38.8 ⫾ 0.7 °C and WBC count 14.7 ⫾ 7.7 x10(3)/␮l. There were 32 positive and 73 negative results. Of the 73 negative results 58 pts had no reason for further w/u for pneumonia in the 7 days following mBAL. 13 pts had persistent suspicion for pneumonia and had a BS BAL performed 4.2 ⫾ 1.9 days after the mBAL and 6 were positive and 7 were negative. 2 pts had their mBAL repeated and both were negative. 10 transient complications occurred in 8 pts: bleeding, hypercapnia(4), desaturation(2), elevated intracranial pressure, bradycardia and vomiting. Conclusions: mBAL is a safe and effective tool for the diagnosis of pneumonia in the ICU. Negative results should be followed up with BS BAL when the clinical suspicion for pneumonia persists.


Linda Thompson, Javier Gelvez, Cook Children’s Hospital Introduction: About 2% of infants hospitalized with Respiratory Syncytial Virus (RSV) progress to respiratory failure (RF).1 Hypothesis: We propose that term infants with RSV and RF have a high incidence of bacterial co-infection, have a higher acuity on presentation, and have a more complicated hospital course. Methods: This retrospective chart review includes 94 infants less than 1 year of age with corrected gestational age of at least 38 weeks hospitalized with RSV and RF over a 3 year period. We used the tracheal aspirate (TA) criteria proposed by Randolph et al in 20042 to distinguish between probable and, possible pneumonias, and no infection by TA. For the primary analysis, we compared patients with bacteremia vs no bacteremia, urinary tract infection (UTI) vs no UTI, probable pneumonia vs no infection by TA, possible pneumonia vs no infection by TA, and probable or possible pneumonia vs no infection by TA. We compared the groups with regard to PICU length of stay (LOS), ventilator days, hospital LOS, and maximum mean airway pressure. The secondary analysis attempted to define signs or symptoms on presentation that were predictive of bacteremia, UTI, probable or possible pneumonia, or any serious bacterial infection (SBI). Results: No patients had meningitis, 4% had bacteremia, 5% had a UTI, 47% and 28% of those with a TA obtained in the first 24 hours had probable pneumonia and possible pneumonia, respectively. The primary analysis showed no difference in PICU LOS, ventilator days, hospital LOS, and maximum mean airway pressure. Patients with UTI were more likely to present with apnea, leukocytosis, or crackles on exam. Patients with possible pneumonia were more likely to present with an abnormal chest radiograph, or leukocytosis. Need for fluid boluses or inotropes were not more predictive of a SBI. Conclusions: SBI on admission in patients with RSV and RF does not prolong their hospitalization course. Randolph’s criteria for bacterial pneumonia showed no clinical relevance in our sample. Apnea on presentation should prompt an evaluation for UTI. References: 1. Behrendt et al. Eur J Pediatr 1998; 157:215-202. Randolph et al. Pediatr Inf Dis J 2004; 23:990-994

Poster: Neurology – Diagnostics 317 IMPACT OF INFLAMMATION MEDIATED HYPERMETABOLISM ON FREE FATTY ACID LEVELS AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE Neeraj Badjatia, Neurological Institute of New York, Columbia University Medical Center, Amanda Carpenter, Neurological Institute of New York, Columbia Unive, Luis Fernandez, J Schmidt, Stephan Mayer, Jan Claassen, Kiwon Lee, E Connolly, Neurological Institute of New York, Columbia University Medical Center, David Seres, Department of Medicine, Columbia University Medical Center, Mitchell Elkind, Neurological Institute of New York, Columbia University Medical Center

⫹/⫺0.18mmol/L, P ⫽ 0.01).In a Cox proportional hazards model adjusting for female sex, the modified Fisher score(HR:3.3, 95%CI:1.3, 8.7, P ⫽ 0.01)and mean FFA levels(HR:1.4 for every 0.1 mmol/L increase, 95%CI:1.1, 1.9, P ⫽ 0.006)were predictive of time to DCI. Conclusions: Inflammation and VO2 are associated with higher FFA levels, and FFA levels predict time to DCI.These findings may indicate a role for interventions that modulate both inflammation mediated VO2 and FFA levels to reduce the occurrence of DCI.

Introduction: The detrimental impact of increased free fatty acid (FFA) levels after subarachnoid hemorrhage (SAH) has been well described in experimental models.Little is known about factors that may contribute to the levels of FFA in SAH patients. Hypothesis: Inflammation mediated hypermetabolism is associated with increased levels of FFA, which play a role in the development delayed cerebral ischemia (DCI) after SAH. Methods: Between November 2008 - December 2009, we measured systemic oxygen consumption (VO2) by indirect calorimetry, high sensitivity C-reactive protein (hsCRP) and FFA levels over four pre-defined time periods in the first 14 days after SAH.Patients with delayed aneurysm repair(⬎48 hours after ictus)or care withdrawn within 7 days from ictus were excluded.Determination of serum non esterified fatty acids(mmol/L) was made using an in vitro enzymatic colorimetric method assay(Wako Diagnostics, Richmond, VA).Multivariable GEE models were used to identify factors associated with VO2 and FFA levels in the first 14 days after SAH. Results: There were 187 serial measurements in 50 consecutive patients(mean age:56 ⫹/⫺14 years old, 66% women) with a median Hunt Hess Score 3(IQR:2, 4) and mean APACHE 2 score 17 ⫹/⫺8.Adjusting for admission APACHE 2 score and age, higher VO2 was associated with higher hsCRP(W-4.2, P ⫽ 0.04), male sex(W5.1, P ⫽ 0.02) , and presence of IVH(W-3.8, P ⫽ 0.05). FFA levels were associated with higher VO2(W-7.8, P ⫽ 0.01), APACHE 2 score(W-8.5, P ⫽ 0.003), and hsCRP(W-7.2, P ⫽ 0.01).Fourteen(28%) patients developed DCI on median post bleed day 7(IQR: 6, 10).A higher proportion of women(86%, P ⫽ 0.1), and higher modified Fisher score(Chi Sq ⫽ 11.4, P ⫽ 0.01)and mean FFA levels were associated with DCI(0.89 ⫹/⫺ 0.46 mmol/L v.0.61

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PERSISTENCE OF MONOAMINES IN ANEURYSMAL SUBARACHNOID HEMORRHAGE PATIENTS WITH MYOCARDIAL INJURY

ANEMIA, TRANSFUSION THRESHOLDS AND INCIDENCE OF VASOSPASM AND INFARCTION AMONG PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE

Marilyn Hravnak, Bhavani Thampatty, Samuel Poloyac, University of Pittsburgh, Jeffrey Yao, Univeristy of Pittsburgh, Elizabeth Crago, Michael Horowitz, University of Pittsburgh

Elizabeth Mauricio, Maisha Robinson, Mayo Clinic, Josh Dajac, University of Florida, Ognjen Gajic, Emir Festic, Mayo Clinic

Introduction: Subarachnoid hemorrhage (SAH) can cause myocardial injury (SAHMI) that can persist for unexplained reasons. Although hypothetically due to a catecholamine surge at the time of aneurysm rupture, the role of monoamines in SAHMI persistence is unexplored. Hypothesis: Using a novel assay for monoamine metabolites in endogenous tryptophan and tyrosine pathways upstream from serotonin and epinephrine respectively, we hypothesized that patients who developed SAHMI [defined as elevated cardiac troponin I (cTnI)], would display persistent monoamine elevations over time. Methods: Prospective longitudinal study recruited 128 SAH patients with Fisherⱖ2 or Hunt/Hessⱖ3. Peak cTnI for days 1-5 post-hemorrhage determined, and patients dichotomized into SAHMI(-) (peak cTnI ⬍ 0.3ng/ml) and SAHMI( ⫹ ) (peak cTnI ⬎ ⫽ 0.3ng/ ml). High-pressure liquid tomography coupled with a colorimetric multi-electrode array system determined tryptophan and its metabolite 5-hydroxyindole3-acetic acid (5-HIAA), and tyrosine and its metabolite homovanillic acid (HVA) levels in 24-hour urine samples for each of days 1-5. Results: Overall SAHMI( ⫹ ) prevalence was 24%. A two-way ANOVA test comparing the equality of means over time showed significant persistently higher levels for SAHMI( ⫹ ) compared to SAHMI(-) groups in tryptophan and 5-HIAA (both p ⬍ 0.01) across all 5 days. A similar analysis revealed significant persistently higher levels for tyrosine and HVA in SAHMI( ⫹ ) compared to SAHMI(-) groups across all 5 days (p ⫽ 0.02 and ⬍ 0.01 respectively). Conclusions: In SAHMI( ⫹ ) patients, tryptophan and its metabolite 5-HIAA, and tyrosine and its metabolite HVA remained significantly and persistently elevated over days 1-5. Monoamine levels are not only higher but persistently so in SAHMI patients, suggesting an ongoing stress state. Funding NHLBI R01HL074316

Introduction: Among patients with aneurysmal subarachnoid hemorrhage (aSAH), anemia due to blood loss, hemodilution and critical illness, is frequently seen. There is no well defined threshold for red blood cell (RBC) transfusion or target hemoglobin (Hb) level for patients with aSAH. Hypothesis: Common Hb threshold for RBC transfusion can be retrospectively identified from the large contemporary cohort and this may impact development of complications among patients with aSAH. Methods: Retrospective, observational study of consecutive patients with aSAH admitted to ICUs at Mayo Clinic in Jacksonville and Rochester over 7-year period. Data included demographics, admit-, nadir-, pre- and post-RBC transfusion Hb and hematocrit (Hct), respective Hct/Hb ratios, RBC transfusion, vasospasm, radiologically confirmed infarction, modified Fisher and WFNS scores. Results: We identified 355 patients, mean age was 56 ( ⫹/⫺14), 222 (63%) were females. Overall, hospital mortality was 14% (49/355). Median admit and nadir Hb levels were: 13.5 (12.5, 14.6) and 10.2 (9, 11.7). Seventythree (21%) of patients were transfused. Median nadir Hb for transfused patients was 8.5 g/dl (8.1, 9.4) versus 10.8 g/dl (9.6, 12) for non transfused. Median pre-transfusion Hb level was 8.7 g/dl (8.1, 9.9), thus “transfusion threshold”. Median post-transfusion Hb was 10.9 g/dl (10.2, 11.4), thus “target Hb level”. Hct/Hb ratio did not significantly change between admission and nadir levels, but did significantly decrease when pre- and post-transfusion levels were compared (2.961 to 2.939, p ⫽ 0.009). This suggested that RBC transfusion relatively increased packed cell volume. Vasospasm was seen in 175 (49%) patients but 111 (31%) had moderate or severe vasospasm. Infarction was seen in 123 (35%) patients. Only nadir Hb level and WFNS were consistently and significantly associated with development of vasospasm and infarctions, in both univariate and multivariate logistic regression analyses. Conclusions: Median Hb threshold for RBC transfusion and Hb target in the large contemporary cohort of patients with aSAH were retrospectively identified. Nadir Hb and WFNS were independently associated with development of vasospasm and/or infarction.


320

321

INFLUENCE OF ATP-BINDING CASSETTE POLYMORPHISMS ON NEUROLOGICAL OUTCOME AFTER TRAUMATIC BRAIN INJURY IN HUMANS

SERUM HS-CRP CONCENTRATION IS ASSOCIATED WITH THE VOLUME OF ISCHEMIC TISSUE IN ACUTE ISCHEMIC STROKE

J’mir Cousar, University of Pittsburgh School of Medicine, Ajit Sarnaik, University Pediatricians, Yvette Conley, University of Pittsburgh School of Nursing, Philip Empey, Ava Puccio, University of Pittsburgh, Patrick Kochanek, University of Pittsburgh Medical Center, David Okonkwo, University of PIttsburgh, Robert Clark, Children’s Hospital of Pittsburgh of UPMC

Soo-Hyun Kim, Chun Song Youn, Sang Hoon Oh, Seung Pill Choi, Kyu Nam Park, College of Medicine, The Catholic University of Korea

Introduction: ATP-binding cassette (ABC) transporters use ATP hydrolysis to translocate solutes across cellular membranes. These include ABCB1 (multidrug resistance protein 1 [MDR1], P-glycoprotein), and ABCC1 and ABCC2 (multidrug resistance associated proteins 1 and 2), recognized as important mediators of solute transport at the bloodbrain and/or blood cerebrospinal fluid barriers. Thus, ABC transporters impact CNS bioavailability of drugs and endogenous solutes, possibly influencing outcome after neurological injury. While several ABCB1/C1/C2 loss or gain-of-function single nucleotide polymorphisms (SNPs) have been identified, their impact on neurological outcome after traumatic brain injury (TBI) is unknown. Hypothesis: ABCB1, C1, and C2 SNPs are associated with Glasgow Outcome Scale (GOS) score after TBI. Methods: DNA samples from 307 adult patients (age 36 ⫾ 15 y; 78% male) with severe TBI (Glasgow Coma Scale score, GCS⬍⫽ 8) were assayed for tagging SNPs of ABCB1 (rs1045642, rs1128503), ABCC1 (rs212093, rs35621, rs4148382) and ABCC2 (rs2273697). For each SNP, patients were dichotomized based on presence of variant allele for multivariate analysis to determine associations with GOS assigned at 6 mo adjusting for initial GCS, age, and sex. Results: The following genotype frequencies were observed for ABCB1: rs1045642 AA (21%), AG (53%), GG (21%); rs1128503 AA (19%), AG (46%), GG (35%); ABCC1: rs212093 AA (30%), AG (49%), GG (21%); rs35621 CC (80%), CT (19%), TT (1%); rs4148382 AA (1%), AG (16%), GG (83%); and ABCC2: rs2273697 AA (3%), AG (31%), GG (3%). These frequencies were similar to published data available through the Intl HapMap Project, Public release #27, 2009-02. Both of the ABCB1 SNPs (but not the others tested) were independently associated with GOS. OR[5-95% CL] for higher (good) GOS: rs1045642 TT vs. TC/CC 0.709[0.547-0.918], P ⬍ 0.01; and rs1128503 CC vs. CT/TT 1.31[1.027-1.67], P ⫽ 0.03. Conclusions: ABCB1/MDR1/P-glycoprotein SNPs are associated with neurological outcome in adults after severe TBI. Further study is necessary to determine whether this is related to CNS bioavailability of ABCB1 drug substrates commonly used in the management of TBI, or brain efflux of endogenous solutes. R01NS069247/T32HD040686

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Introduction: There is growing evidence that inflammation plays an important role in atherogenesis. Previous studies have shown that the concentration of peripheral inflammatory markers, particularly C-reactive protein (CRP), strongly correlates with stroke severity and independently predicts mortality and recurrent vascular events in patients with acute ischemic stroke. The aim of this study was to clarify the relationship between inflammatory markers and stroke severity by means of volumetric measurement of infarct size. Methods: From March 1, 2008 to Feb. 28, 2009, we prospectively analyzed 96 patients who had laboratory investigations and magnetic resonance imaging (MRI) scans. Diffusion weighted imaging (DWI) lesions were outlined using a semiautomatic threshold technique. DWI lesion volumes were measured with MIPAV software (Medical Image Processing, Analysis and Visualization, version 4.1.1, National Institutes of Health, Bethesda, MD.). The relationship between highly selective CRP (hs-CRP) levels and DWI infarct volume quartiles was examined. Results: The median age of patients was 68 years, and 50 patients (51.2%) were male. There was a significant correlation between hs-CRP and DWI volumes (Spearman rho ⫽ 0.239, p ⫽ 0.010). The median hs-CRP values for successive volumes of DWI lesion quartiles (lowest to highest quartile) were as follows: 1.17, 1.14, 1.63, and 3.76 (P for trend ⫽ 0.010). Conclusions: Higher hs-CRP levels were associated with larger infarct volumes in acute ischemic stroke patients. These results suggest that elevated hs-CRP levels, reflecting a large volume of infarct, may serve as a helpful serologic marker in the evaluation of severity of acute ischemic stroke.

323

TERMINOLOGICAL VARIANCE FOR EACH SUBTYPE OF DELAYED CEREBRAL ISCHEMIA AND VASOSPASM AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

ANTIPSYCHOTIC USAGE IN THE INTENSIVE CARE UNIT

Gregory Kapinos, NYPH/Columbia & Cornell U., Pina Sanelli, Angela Hoang, Alan Segal, Axel Rosengart, Matthew Fink, NYPH/Cornell U.

Introduction: Antipsychotic (AP) use in the ICU is appropriate for maintenance of previously diagnosed psychiatric disorders or the acute treatment of delirium. The objective of this study was to describe AP utilization and documentation of mental disorders in ICU patients. Hypothesis: We hypothesized that APs are administered in the ICU without documented diagnoses of mental disorders, including delirium. Methods: This was a retrospective review of all admissions to five ICUs (surgical, medical, neurological, coronary, and cardiovascular surgery) over 6 months ending 6/30/2010 at an academic tertiary care center. Data for AP administration were ascertained from the medical record and validated with the pharmacy database. All formulations of haloperidol and formulary atypical APs were included. Diagnosis codes for mental disorders including delirium (ICD-9 290-319) were collected from the electronic medical record to capture new and previously existing conditions for each hospital admission. Results: We identified 4, 013 patients with 4, 462 unique hospital admissions with an ICU stay. Antipsychotics were administered during 10% (455) of these admissions. Four hundred and thirty seven of these occurred while the patient was in the ICU, with minimal exposure before (n ⫽ 14) or after (n ⫽ 18) the ICU. Mental disorders and delirium were documented in 33% (1, 469) and 2% (81) of these hospital admissions respectively. Of the 437 admissions with AP exposure in the ICU, quetiapine was most frequently used (n ⫽ 259, 59%) followed by haloperidol (n ⫽ 184, 42%), olanzapine (n ⫽ 75, 17%), risperidone (n ⫽ 30, 7%), ziprasidone (n ⫽ 14, 3%), and aripiprazole (n ⫽ 12, 3%). In the ICU, 57% (251) of patients exposed to APs were diagnosed with a mental disorder including 8% (33) diagnosed with delirium. Conclusions: Forty three percent of ICU patients who received AP medication during a 6-month period did not have a previously existing or newly diagnosed documented mental disorder, including delirium. Quetiapine use was more common than haloperidol. Our incidence of documented delirium (2%) in ICU patients is less than published literature (up to 80%). This data indicates potential under-diagnosis and under-documentation of delirium, regardless of AP use.

Introduction: The characterization of delayed cerebral ischemia (DCI) and vasospasm (VSP) after aneurysmal subarachnoid hemorrhage (aSAH) has evolved with the recognition of independent impacts of clinical neurological deficits and infarctions on outcome, even in the absence of narrowed vessel (NV). Hypothesis: Randomized clinical trials (RCT) use dissimilar criteria to define deterioration, delayed ischemic neurologic deficits (DIND), permanent neurologic deficits (PND), symptomatic, sonographic, or angiographic VSP and delayed infarcts. Methods: We systematically reviewed the 38 RCT listed in the AHA 2009 guidelines for aSAH to extract the defining criteria and semantics used for each subtype of ischemic or vasospastic events. Results: Deterioration is defined in 16 RCT, 10 use a coma scale, while others prefer neurologic exams, either standardized (NIHSS for 4) or not, and 5 RCT evoke clinical impression (classic symptoms). DIND, defined in 21 RCT, always implies neurologic changes or deterioration with exclusion of non-ischemic causes, but the lists of excluding syndromes differ. DIND is difficult to appreciate in comatose patients (1 RCT). PND, described in 4 RCT, entails neurologic deficit upon discharge, but “persistent neurologic deficit” should not be equivalent to PND. Symptomatic VSP (6 RCT) varies in definition and is misleadingly interchanged with “clinical VSP” (6 RCT): 13 refer to actual DIND with (10) or without excluding other causes of neurologic decline, while 9 RCT mean DIND with or without evidence of NV, and only 3 RCT require a documented NV. Clinical impression (2 RCT) and hierarchical diagnosis (1 RCT) do aggregate syndromes but with loss in scientific rigor. Both sonographic (13 RCT) and angiographic VSP (5 RCT) have poor consistency in thresholds and stratification, poor concordance and poor sensitivity and specificity for DCI. DCI is referred in 3 RCT as “probable” (clinical) or “definite” (clinico-radiologic), but these terms lack descriptiveness. Delayed infarcts have explicit causal allocation in 7 out of 14 RCT. Conclusions: There is inter- and intra-RCT inconsistency in semantics and specific criteria used for each rubric of DCI, and for the disparate amalgamates of each subtypes of DCI.


Joshua Swan, Kalliopi Fitousis, Jeffrey Hall, Krista Turner, Samual Todd, Methodist Hospital

Poster: Neurology - Monitoring 324

325

EARLY PREDICTORS OF NEUROLOGICAL OUTCOMES AFTER PEDIATRIC HEART SURGERY

VALIDATION OF THE CAM-ICU AS PERFORMED BY BEDSIDE ICU NURSES: A MULTICENTER STUDY

Joan Sanchez de Toledo, Constantinos Chrysostomou, Alicia Au, Richard Orr, Scott Watson, University of Pittsburgh, Steve Lichtenstein, Victor Morell, Ricardo Munoz, Children’s Hospital of Pittsburgh, Michael Bell, University of Pittsburgh

Maarten Van Eijk, University Medical Center Utrecht, Mark Boogaard, Umc St Radboud, Arjen Slooter, University Medical Center Utrecht

Introduction: Brain injury after pediatric heart surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) is common. Early identification of neurological damage is difficult and a clinically-available system to detect such injuries would be a significant advance. Near-infrared spectroscopy (NIRS) has been used to measure brain regional oxygenation saturations (RSO2) and various serological markers of brain injury (neuromarkers) have been proposed. Yet, the ability of these systems to predict relevant outcomes has not been evaluated. Hypothesis: RSO2 and neuromarkers are associated with adverse neurological outcome. Methods: Prospective study of children (n ⫽ 48) undergoing heart surgery with CPB and/or DHCA. Brain RSO2 was measured at baseline and continuously during surgery/postoperatively. Neuromarkers (neuron-specific enolase (NSE), S100␤ and brain-derived neurotrophic factor (BDNF)) were measured at baseline, immediately after surgery and at 16 hpostoperatively. Neurological outcomes were defined as new abnormality on (i) examination, (ii) imaging or (iii) EEG within the first 3 months after surgery. Data presented as mean ⫾ SEM unless otherwise specified. Results: Median age was 8 m [5 d - 17 y], 16 were neonates and 19 had abnormal neurological outcome (39.6%; 6 seizures, 7 abnormal 3 m exam). Time (in min) with RSO2 ⬍ 40% during surgery or postoperatively (214 ⫾ 54 v. 47 ⫾ 17, p ⬍ 0.01; 2671 ⫾ 1114 v. 437 ⫾ 261, p ⬍ 0.01, respectively), BDNF (in pg/ml) immediately after surgery (4460 ⫾ 1192 v. 2539 ⫾ 485, p ⫽ 0.001) and age (45 m ⫾ 26 v. 14 m ⫾ 3, p ⫽ 0.03) were increased in children with abnormal neurological outcomes. In multivariate analysis, time with RSO2 ⬍ 40% during surgery and BDNF were independently associated with outcome. Conclusions: Bedside neurological monitoring of RSO2 and novel neuromarkers may be helpful in assessing neurological injuries after pediatric heart surgery. A comprehensive study to determine the role of these modalities in neurological monitoring is needed.

326 INTERLEUKIN 6 AND DELIRIUM IN ICU PATIENTS Sheila Alexander, Judith Tate, University of Pittsburgh, Dianxu Ren, University of Pittsburgh School of Nursing, Scott Gunn, UPP-CCM, E. Ely, Vanderbilt Vanderbilt Center for Health Services Research and VA-Geriatric Research Education Clinic Introduction: Delirium is a common occurrence associated with poor outcomes in ICU patients. The biological pathways driving delirium are poorly understood. Currently, there are no biomarkers available to predict delirium onset or duration in ICU patients. Hypothesis: The purpose of this project was to describe serum interleukin-6 (IL-6) concentrations over time in the acute period after ICU admission between individuals with and without delirium in the ICU. Methods: Fifty subjects, age 18-75, intubated 24-96 hours and without previous cognitive disorder or acute cerebral/cognitive injury were recruited from a Surgical Trauma and Medical ICU. Delirium was determined daily using the Confusion Assessment Method- for the ICU (CAM-ICU) for 5 days. Subjects were dichotomized into two groups, delirium ( ⫹ ) or delirium (-), based on development of delirium during the study period. Serum was drawn daily for 5 days. Serum IL-6 concentration was quantified with a commercially available ELISA (Invitrogen Corporation, Carlsbad, CA 92008). Data were analyzed using descriptive statistics, t-tests, and ANOVA. Results: The sample was primarily male (n ⫽ 26; 52%) and Caucasian (n ⫽ 46; 92%) with a mean age of 46.94 years old. The delirium ( ⫹ ) group (n ⫽ 21; 41%) had higher serum IL-6 concentrations on day 1 (p ⫽ .027) and over all days (p ⫽ .001) as compared the delirium (-) group (n ⫽ 23; 45.5%). Seven subjects (13.5%) were too unstable to tolerate sedation break and CAMICU assessment; these subjects had IL-6 concentrations that started out lower but rose over time. Conclusions: Serum IL-6 was elevated in most ICU patients. In individuals who developed delirium, serum IL-6 was higher and stayed elevated while in individuals without delirium serum IL-6 concentrations were elevated but decreased over the 5 day period. Our findings suggest that prolonged release of pro-inflammatory cytokine IL-6 an inflammatory pattern worthy of further evaluation in larger cohort investigations as a marker by which to track patterns of brain organ dysfunction. This project was supported by the Society for Critical Care Medicine Norma J. Shoemaker Grant and NIH/NINR R03NR11052.

Introduction: Delirium is a frequent disorder in the Intensive Care Unit (ICU) associated with poor outcome. Several professional organizations, among others the SCCM, therefore recommend standard screening for delirium to improve early diagnosis and treatment. The Confusion Assessment Method for the ICU (CAM-ICU) is the most frequently used delirium detection tool. However, the characteristics of the CAM-ICU have only been studied when the tool was administered by research nurses. Hypothesis: The diagnostic value of the CAMICU in routine practice is unclear, we aimed to investigate the value of the CAM-ICU in daily setting. Methods: Teams of three delirium experts visited ten ICU’s in the Netherlands twice in which the CAM-ICU was incorporated in daily practice. These teams consisted of consultants in psychiatry, geriatric medicine or neurology, together with either the same research physician or nurse scientist. Based on psychiatric examination and DSM-IV criteria for delirium, the teams classified patients as delirious or not delirious. This classification served as gold standard to which the CAM-ICU as performed by the bed-side nurses was compared. Delirium experts and bed-side nurses were blinded to each others assessments. Sensitivity, specificity and positive and negative predicitive values were calculated. Results: 13 delirium experts performed 333 assessments. A total of 108 patients (33%) were not accessible for delirium. Thus 225 patients (67%) could be included in the analysis. Overall, we found sensitivity of 47% (95% CI 35% - 58%), specificity of 98% (95% CI 93% - 100%), positive predictive value of 95% (95% CI 80% - 99%) and negative predictive value of 72% (95% CI 64-79%). Test characteristics varied widely between centres. Conclusions: The sensitivity of CAM-ICU as administered by the bedside nurse in daily practice seems to be lower than in the original validation studies and varied widely between centres. The specificity was excellent. Strengths of this study include the multicenter design, the independent evaluation by various delirium experts with large experience.

327 ELEVATED INTRACRANIAL PRESSURE PREDICTS POOR FUNCTION AND DEATH AFTER SUBARACHNOID HEMORRHAGE Khalil Yousef, Elizabeth Crago, Chien-Wen Kuo, University of Pittsburgh, Michael Horowitz, University of Pittsburgh Medical Center, Marilyn Hravnak, University of Pittsburgh Introduction: Elevated intracranial pressure (ICP) is a serious complication after aneurysmal subarachnoid hemorrhage (aSAH). The impact of elevated ICP on delayed cerebral ischemia (DCI), functional outcome, and death after aSAH is underexplored. Hypothesis: Elevated ICP is associated with DCI, poor functional outcome, and death after aSAH. Methods: Descriptive longitudinal study of 161 aSAH patients; age 18-75 yrs, and Hunt/Hessⱖ3 and/or Fisherⱖ2. ICP measured (mmHg) by intraventricular catheter, and cohorts of: ⬎ 20, ⬎ 30, and ⬎ 40 mmHg developed. DCI defined as neurologic deterioration with abnormal cerebral blood flow. Functional outcome and mortality evaluated at 3 and 12 months by Glasgow Outcome Scale (GOS) [dichotomized as good (4-5) and poor (1-3)]. Results: 80% of patients had ICP ⬎ 20, 47% ICP ⬎ 30, and 22% ICP ⬎ 40. ICP ⬎ 40 was the only significant cohort in the analysis. ICP ⬎ 40 was significantly associated with younger age (p ⫽ .035) and higher Hunt/Hess (p ⫽ .04). 72% of patients with ICP ⬎ 40 developed DCI compared to 52% with ICP ⫽ .044. More patients with ICP ⬎ 40 had poor GOS (61% at 3 months, 56% at 12 months) compared to patients with ICP ⬍40 (30% at 3 and 12 months each); both p ⬍ 0.05. The proportion of mortality was higher in the ICP ⬎ 40 (61% at 3 months, 56% at 12 months) than the ICP ⬍40 group (19% at 3 months and 21% at 12 months); p ⬍ .05. In multivariate logistic regression (controlling for age and Hunt/Hess), ICP ⬎ 40 trended toward predicting DCI (OR 2.3, 95%CI 0.9-5.7; p ⫽ .074), and poor 12-month GOS (OR 2.6, 95% CI 0.9-7.6; p ⫽ .073). However, ICP ⬎ 40 was a significant predictor for poor GOS at 3 months (OR 4.2, 95%CI 1.4-13.1; p ⫽ .012) and mortality at both 3 (OR 10, 95% CI 2.8-35.4; p ⬍ .001) and 12 months (OR 5.3, 95%CI 1.7-17; p ⫽ .005). Conclusions: ICP ⬎ 40 occurs in 1/5 of aSAH patients, and predicts poor functional outcomes at 3 months, and death at 3 and 12 months, even after controlling for age and Hunt/Hess. Clinicians should carefully monitor for ICP ⬎ 40 mmHg, as it is associated with negative consequences. Funding NIH R01HL074316


328 CEREBRAL BLOOD FLOW PATTERNS IN SEVERE HEAD TRAUMA USING TRANSCRANIAL DOPPLER MONITORING Julio Mijangos-Mendez, Guadalupe Aguirre-Avalos, Ana Mendoza-Garibay, Erika Gonza´lez-Navarro, Federico Corona-Jimeńez, Hilario Coronado-Maganã, Servicio de Terapia Intensiva, Hospital Civil de Guadalajara. Universidad de Guadalajara. Me´xico. Introduction: Severe head trauma (SHT) patients represent an average of 20 percent of total admissions to our intensive care unit (ICU). We use transcranial doppler (TCD) monitoring to identify their cerebral hemodynamics. Hypothesis: There are different cerebral blood flow patterns in SHT patients according clinical presentation at admission to the ICU. Methods: We conducted a study to identify cerebral blood flow patterns using TCD, in SHT patients admitted to 14-medical-surgical adult ICU. From May to December 2009, 29 SHT patients were evaluated using TCD (SONARA/tek VIASYS Healthcare Inc. USA), monitoring performed as soon as possible after they were admitted to the ICU and some patients had more than one measure. We identify in middle cerebral arteries mean flow velocity (MCA-FVm) and Pulsatility Index (PI). Clinical variables were registered at the time of TCD. We also recorded APACHE II scale, cerebral computed tomography (CCT) and the needed of a neurological surgery at the admission. Statistical analysis was calculated using SPSS version 17.0 (SPSS Inc. Chicago, USA) Results: Of the 29 patients evaluated, 2 were excluded. Twenty three (85%) were men and 4(15%) women, with a mean age of 26 ⫾ 10.6 yr. There were no differences in clinical variables. The mean Glasgow coma scale was 6 ⫾ 2.9 and APACHE II of 13 ⫾ 2.8. CCT identified subarachnoid hemorrhage (SAH) in 14(52%) and 7(26%) required surgery. We performed 55 TCD, the first measure was on day 3 ⫾ 2.4 after trauma and the values and patterns were as follows: right-MCA-FVm 84.69 ⫾ 41.54 cm.s-1, PI R-MCA 1.14 ⫾ 0.71, left MCA-FVm 81.75 ⫾ 38.88 cm.s-1, PI L-MCA 1.08 ⫾ 0.50. The flow patterns identified were hyperemia 22(43.1%), normal 13 (25.5%), vasospasm 7 (13.7%), intracranial hypertension 6 (11.8%), hypoperfusion 2 (3.9%) and cerebral arrest 1 (2%). SAH and surgery were present at hyperemia, normal and vasospasm patterns in 77%, 69% and 100% respectively. Conclusions: The predominant flow patterns observed after SHT were hyperemia, normal and vasospasm. Hyperemia is observed in the initial days after SHT and all patients with vasospasm pattern had SAH or needed surgery at admission.


Poster: Neurology - Therapeutics 330

331

COMPARISON OF HYPERTENSION, HYPERVOLEMIA, AND TRANSFUSION TO AUGMENT CEREBRAL OXYGEN DELIVERY AFTER SUBARACHNOID HEMORRHAGE

RANDOMIZED COMPARISON OF CEREBRAL PERFUSION PRESSURE (CPP) WITH INTRACRANIAL PRESSURE (ICP) TARGETED THERAPY IN CHILDREN WITH ACUTE CNS INFECTIONS

Rajat Dhar, Michael Scalfani, Allyson Zazulia, Tom Videen, Colin Derdeyn, Michael Diringer, Washington University School of Medicine Introduction: Critical reductions in cerebral blood flow (CBF) and oxygen delivery (DO2) underlie the development of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). If DO2 is not promptly restored then irreversible injury (i.e. cerebral infarction) may result. Induced hypertension (IH) and hypervolemia are the primary means of treating DCI while transfusion has been proposed as an alternate strategy, primarily to improve DO2. The relative effects of these interventions on CBF and DO2 have not been assessed, specifically their ability to restore DO2 to regions where it is impaired. Hypothesis: Transfusion will be as effective as IH and more effective than a fluid bolus in augmenting DO2 to vulnerable brain regions. Methods: We analyzed data from three prospective studies employing PET imaging to measure the effects of: 1) a fluid bolus of 15 ml/kg normal saline (n ⫽ 9); 2) raising blood pressure by 20% (n ⫽ 12); or 3) transfusing one unit of red blood cells (n ⫽ 17), to aneurysmal SAH patients. All patients underwent 15O-PET at baseline and immediately after the intervention. We assessed change in DO2 globally as well as in brain regions with low DO2 at baseline (defined as ⬍ 4.5 ml/100g/min) using repeated-measures ANOVA. Results: The three groups were similar except that the fluid bolus cohort had more patients with symptomatic vasospasm and lower baseline CBF. Global DO2 did not rise significantly after any of the interventions, except when transfusing patients with Hb ⬍ 9 g/dL. All three treatments improved CBF and DO2 to regions with low baseline DO2, but rise in DO2 was greater after transfusion (⫹23%) vs. IH (⫹15%) vs. hypervolemia (⫹10%); p ⬍ 0.001. Similarly, transfusion resulted in a greater reduction in the proportion of brain regions with low DO2 after intervention (39% fewer vs. 13% for IH vs. 7% for fluid, p ⫽ 0.003). Conclusions: Induced hypertension, hypervolemia, and transfusion all improve DO2 to vulnerable brain regions at risk of ischemia after SAH. However, transfusion may provide the greatest benefit, especially amongst patients with anemia. The clinical significance of this difference remains to be established. Supported by grants from the NIH, AHA, and Barnes-Jewish Hospital Foundation.

Sunit Singhi, Arun Bansal, Ramesh Kumar, Anuj Bhatti, Post Graduate Institute of Medical Education and Research Introduction: CPP targeted therapy had shown improved outcome in traumatic brain injury. We compared CPP with ICP targeted therapy in children with acute CNS infections. Hypothesis: CPP targeted therapy may improve outcomes in childhood CNS infections. Methods: In an open label randomized trial approved by Institute’s Ethics Committee, consecutive children, 1 to 12 years, admitted to PICU of a teaching hospital with acute CNS infections and a Glasgow Coma scale Score (GCS) ⬍8 were randomized to receive CPP or ICP targeted therapy, stratified by acute meningitis and encephalitis, after written parental consent. CPP target ⬎60 mmHg was achieved with fluids, vasoactive therapy and osmotic diuretics and ICP target ⬍20 mmHg with osmotic diuretics, deep sedation and mild hyperventilation. Uniform standard care was given to all. ICP was monitored with intraparenchymal micro-transducer (CODMAN®) and mean blood pressure with intra-arterial pressure transducer. Primary outcome measure was improvement in GCS at 72 h post-enrolment and in-PICU mortality. Results: Of the 100 children (CPP n-49; ICP n-51) studied, 62 had acute viral encephalitis, 30 bacterial meningitis and 8 aseptic meningitis. Distribution of diagnostic categories, age (median, interquartile range: 5.5, 2.5-8 years), PRISM III score (22, 16-27) and GCS (5, 4-6) were similar in 2 groups. At 72 h post-enrolment: 88% patients in CPP and 76.5% in ICP gp (P ⫽ 0.14) achieved therapy target; GCS (CPP gp: 9, 8-10 and ICP gp: 8, 5-9, P ⫽ 0.05) and GCS trend were significantly better in CPP gp (P ⫽ 0.044). Nine children in CPP and 15 in ICP gp died ((OR 0.54; 95% CI: 0.2-1.5, P ⫽ 0.2). Of these, 4 in CPP and 11 in ICP gp had refractory raised ICP (P ⫽ 0.07). Neurodeficits were seen in 26% of 38 children in CPP and 45.5% of 33 in ICP group (P ⫽ 0.09) at follow-up 3 months’ post-discharge. Conclusions: CPP targeted therapy was associated with better coma scores at 72 h and a possible trend towards improved survival and neurological outcome as compared to ICP targeted therapy.

332

333

DETERMINANTS OF INTRAVENTRICULAR CATHETER PLACEMENT IN PATIENTS WITH INTRAVENTRICULAR HEMORRHAGE

BLOOD TRANSFUSION IS A PREDICTOR OF HOSPITAL MORTALITY IN ANEURYSMAL SUBARACHNOID HEMORRHAGE

Daniel Herrick, Saman Nekoovaght-Tak, Natalie Ullman, Shannon LeDroux, Daniel Hanley, Wendy Ziai, Johns Hopkins University

Emir Festic, Freeman William, Alejandro Rabinstein, Ognjen Gajic, Mayo Clinic

Introduction: Intraventricular hemorrhage (IVH) and hydrocephalus complicating spontaneous intracerebral hemorrhage (ICH) are associated with poor outcome. Intraventricular catheter (IVC) usage is variable in large clinical trials because the impact is controversial. Hypothesis: To examine factors that predict IVC placement in patients with IVH. Methods: Retrospective analysis of consecutive patients admitted to a University Hospital between 2003-2010 with a primary diagnosis of spontaneous ICH and radiographic identification of IVH. Pre-IVC admission CT scans and clinical data were analyzed. Results: Of 194 patients with IVH, 76 (39%) had an IVC placed of whom 55% had obstructive hydrocephalus. Patients who received an IVC had median age 56 years ( ⫾ 1.1) (SEM), median ICH and IVH volumes of 14.2 cc (iqr 37.4) and 20.9 cc (32.2), respectively, median GCS 5 (4), median Graeb Score 8 (4) and had clinical herniation at presentation in 29%. On univariate analysis IVC placement was associated with [P ⬍ 0.05] younger age, lower admission GCS, lower ICH volume, higher IVH volume, higher Graeb score, presence of clinical herniation at admission, and higher bicaudate index. Independent predictors of IVC placement on multivariate analysis were GCS ⱕ 8 (OR 8.3, P ⬍ 0.001), ICH volume ⬍ 30 cc (OR 4.8, P ⫽ 0.001), Graeb score ⱖ 6 (OR 6.2, P ⬍ 0.001) and age (OR 0.97, P ⫽ 0.05). Loss of hemicisterns, sulcal effacement, and increased bicaudate index were not associated with IVC placement. Obstructive hydrocephalus was present in 36.4% who did not receive an IVC. This group was older with lower Graeb score, larger ICH volume and higher admission GCS compared with patients with obstructive hydrocephalus who did receive an IVC. Mortality was significantly higher in patients with IVC than without (56.6% vs. 41.5%; P ⫽ 0.04). Conclusions: Our audit of clinical practice reveals that IVC placement is most likely to occur in patients with high IVH severity and smaller ICH volumes. Clinical herniation on admission is not a significant deterrent. Radiographic signs of ICP elevation appear to have a less significant impact on decision for IVC insertion. Evidence-based data is needed to define patient selection and clinical benefit for IVC use.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is a condition that carries significant risk of mortality. Red blood cell (RBC) transfusion has been associated with death among patients with aSAH but previous studies may have not adequately adjusted for indication bias. Hypothesis: Transfusion is associated with increased risk of in hospital death in patients with aSAH. Methods: Retrospective study of contemporary cohort of patients with aSAH admitted to ICUs at Mayo Clinic in Jacksonville and Mayo Clinic Rochester over 7-year period. Data included demographics, World Federation of Neurosurgical Societies Scale (WFNS), modified Fisher score (mFisher), admit and nadir hemoglobin (Hb) and hematocrit (Hct), vasospasm, and hospital mortality. Association between RBC transfusion and mortality was evaluated in multivariate logistic regression analysis using the propensity for RBC transfusion as a covariate. Results: We identified 355 patients, mean age was 56 ( ⫹/⫺14), 222 (63%) were females. Hospital mortality was 14% (49/355). Seventy-three (21%) of patients were transfused. Nadir Hb and Hct (p ⬍ 0.001) and vasospasm (p ⫽ 0.012) were important predictors of transfusion and were included in propensity analysis. After adjustment for probability of receiving RBC transfusion (propensity score), WFNS, age and gender in a multivariate logistic regression analysis, RBC transfusion was independently associated with hospital mortality (odds ratio 2.55, 95%CI 1.07 to 6.15, p ⫽ 0.035). Conclusions: In this contemporary cohort of patients with aSAH, RBC transfusion was independently associated with increased mortality. Prospective studies are needed to determine the best threshold for RBC transfusion to minimize potential harm.


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HEMODYNAMIC VARIATIONS OF TWO PENTOBARBITAL COMA LOADING DOSE REGIMENS

EVALUATION OF NICARDIPINE VERSUS LABETALOL FOR BLOOD PRESSURE CONTROL IN ANEURYSMAL SUBARACHNOID HEMORRHAGE

Jennifer Gass, Teresa Allison, Memorial Hermann Hospital, Imo Aisiku, The University of Texas Medical School Introduction: A 2 hour pentobarbital infusion has been proposed as an alternative to Eisenberg’s 4 hour loading dose regimen for the management of refractory intracranial hypertension. There is no data comparing the impact of the different dosing regimens on hemodynamic parameters. Hypothesis: The primary objective was to evaluate differences in mean arterial pressure (MAP) in patients receiving different pentobarbital loading doses. Secondary outcome measures included intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Methods: This was a retrospective cohort study of adult patients who received pentobarbital for the management of refractory ICP from 1/06 to 12/09 in a university hospital. Group 1 (G1) received a loading dose of 30 mg/kg over 2 hours, group 2 (G2) received a loading dose of 10 mg/kg over 1 hour then 15 mg/kg over 3 hours. MAP, ICP, CPP, and medications were collected from 6 hours before to 6 hours after the loading dose. Additional data included baseline characteristics, fluid status, and outcomes. Results: Seventy-three patients were included; 39 in G1 and 34 in G2. Median APACHE II scores were 24 in G1 versus 23 in G2, p ⫽ 1.000. Mean MAP values were higher in G1 during (98 ⫾ 20 vs. 88 ⫾ 18 mmHg, p ⫽ 0.012) and after (101 ⫾ 19 vs. 92 ⫾ 15 mmHg, p ⫽ 0.017), with no difference prior to (98 ⫾ 19 vs. 90 ⫾ 19 mmHg, p ⫽ 0.109) the load. Mean CPP values were higher in G1 after (66 ⫾ 29 vs. 53 ⫾ 30 mmHg, p ⫽ 0.043), with no difference prior to (63 ⫾ 24 vs. 58 ⫾ 28 mmHg, p ⫽ 0.414) or during (62 ⫾ 27 vs. 54 ⫾ 29 mmHg, p ⫽ 0.292) the load. Mean ICP values were not different prior to (48 ⫾ 31 vs. 46 ⫾ 33 mmHg, p ⫽ 0.535), during (45 ⫾ 30 vs. 45 ⫾ 33 mmHg, p ⫽ 0.712), or after (45 ⫾ 34 vs. 47 ⫾ 34 mmHg, p ⫽ 0.505) the load. Vasopressors were used in 27 patients in G1 versus 13 patients in G2 prior to the load (p ⫽ 0.008). There was no difference in vasopressor use during or after the loading dose. There was no difference in the fluid status prior to starting pentobarbital. Conclusions: The alternative dosing regimen achieved equivalent clinical efficacy with less hypotension and reduced CPP. This dosing regimen may be superior due to the side effect profile. Further evaluation is needed to confirm these findings.

Amanda Woloszyn, Mayo Clinic, Karen McAllen, Bryan Figueroa, Robert DeShane, Jeffrey Barletta, Spectrum Health Introduction: AHA/ASA guidelines for management of aneurysmal subarachnoid hemorrhage (aSAH) recommend blood pressure (BP) control, utilizing labetalol or nicardipine, but do not differentiate efficacy between the two agents. Hypothesis: The purpose of this study was to compare BP control between labetalol and nicardipine in patients following aSAH. Methods: Consecutive adult patients admitted to the ICU with a diagnosis of SAH treated with labetalol or nicardipine were retrospectively identified. Patients were included if they received more than one dose of labetalol or a nicardipine infusion for greater than three hours. Patients were excluded if they were ⬍18 years of age, experiencing a non-aneurysmal ICH, acute ischemic stroke or a TIA. Patients were stratified into two groups (labetalol vs. nicardipine) and data was collected for 72 hours. The outcomes compared were time within goal mean arterial pressure (MAP), average MAP/patient, MAP variability, response to therapy, and treatment failure. Goal MAP was defined as 70-110mmHg. MAP variability was defined using the standard deviation of the mean for all MAP values/patient during treatment. Response to therapy was evaluated by time averaged means calculated for MAP in one hour blocks for those patients not within the goal MAP at baseline. Treatment failure was defined as a change to an alternative agent and/or MAP that was never within goal. Results: There were 103 patients evaluated (labetalol n ⫽ 43; nicardipine n ⫽ 60). Demographics were similar between the two groups. There was no difference in baseline MAP between the nicardipine and labetalol groups (117 ⫾ 12 vs. 117 ⫾ 18 mmHg, p ⫽ 0.998), respectively. Nicardipine was associated with a longer time within goal MAP (78 ⫾ 24% vs. 58 ⫾ 36%, p ⫽ 0.001) and lower average MAP/patient (93 ⫾ 11 vs. 106 ⫾ 12 mmHg, p ⬍ 0.001). There was no difference in MAP variability between the nicardipine and labetalol groups (13 ⫾ 5 mmHg vs. 11 ⫾ 4 mmHg; p ⫽ 0.137). Nicardipine led to a more rapid response to therapy (F ⫽ 8.1; p ⫽ 0.005) and fewer treatment failures (0% vs. 28%, p ⬍ 0.001). Conclusions: Nicardipine is associated with superior blood pressure control versus labetalol and should be the preferred agent for blood pressure control in aSAH.

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PROLONGED EMERGENCY DEPARTMENT LENGTH OF STAY DOES NOT INCREASE RESOURCE UTILIZATION IN PATIENTS WITH INTRACEREBRAL HEMORRHAGE

DIFFERENTIAL EFFECT OF HYPOTHERMIA BY OPERATIVE STATUS IN SEVERE TRAUMATIC BRAIN INJURY: CAN IT BE EXPLAINED BY DIFFERENCES OF CEREBRAL AND SYSTEMIC PHYSIOLOGY?

Jonathan Elmer, Massachusetts General Hospital and Brigham and Women’s Hospital, Daniel Pallin, Brigham and Women’s Hospital and Children’s Hospital Boston, Shan Liu, Catherine Pearson, Yuchiao Chang, Steven Greenberg, Jonathan Rosand, Joshua Goldstein, Massachusetts General Hospital Introduction: Longer emergency department length of stay (EDLOS) has been associated with poorer outcomes in critical illness. In a prior study of a cohort of intensive care unit (ICU)-admitted patients with intracerebral hemorrhage (ICH), we found no association between EDLOS and neurologic outcome, despite the accepted benefit of care for these patients in specialty units. In the present work, we analyzed the same cohort to determine the association of EDLOS with hospital resource utilization. Hypothesis: Longer EDLOS correlates with higher costs, longer ICU length of stay (LOS) and longer hospital LOS. Methods: We retrospectively analyzed a prospective cohort of consecutive ICU-admitted patients with spontaneous ICH at a single academic center, excluding patients whose goals of care were made comfort only in the ED. The primary exposure variable was EDLOS. Outcomes of interests were ICU LOS, hospital LOS and hospital costs. We used a non-parametric mixed model to quantify the association of EDLOS with each outcome. We identified biologically plausible confounders a priori, and included them in multivariate modeling if they were associated with EDLOS and the outcome of interest (with a p-value of ⱕ 0.20). Results: The cohort consisted of 574 subjects, admitted from February 2005 to October 2009. Median EDLOS was 5.1h (IQR 3.7-7.1h); 18.5% had an EDLOS greater than 8h. In bivariate analysis, increased EDLOS was associated with shorter ICU LOS (Spearman’s r ⫽ -0.29, p ⬍ 0.01), shorter hospital LOS (r ⫽ -0.08, p ⫽ 0.04) and lower hospital costs (r ⫽ -0.22, p ⬍ 0.01). Covariates included in the final multivariate model were age, initial Glasgow Coma Scale score, initial hematoma volume and need for intubation. Controlling for these, no association was found between EDLOS and any outcome. Conclusions: We sought evidence that prolonged EDLOS increases overall resource utilization. Bivariate analysis suggested the opposite, but this was proven to be due to confounding. Controlled analysis showed no association between EDLOS and resource utilization. Our work does not demonstrate that EDLOS affects resource utilization, but rather shows that among this cohort, sicker patients are rushed to the ICU from the ED faster.


David Zygun, University of Calgary, Alex Valadka, Seton Brain and Spine Insitute, David Okonkwo, University of Pittsburgh, Sierra Fourwinds, Silverwind Research , Guy Clifton, University of Texas Medical School at Houston Introduction: To investigate physiologic parameters that may account for the differential effect of hypothermia (H) on outcome by operative status observed in NABIS:H II Methods: NABIS:H II was a RCT of very early cooling to 33°C for 48h in patients with severe TBI. The study was terminated for futility after 97 patients. Early induction of H did not improve outcome. Patients with operatively removed hematomas treated with H had a marginally improved rate of good outcomes. GEE analysis was employed. Results: 39% of patients had surgery to remove hematomas and 54% were randomized to H. ICP in the H group was higher throughout the first week, reaching significance only on day 1 (p ⫽ 0.04) and day 2 (p ⫽ 0.02). CPP on day 0 was higher in the H group compared to the normothermia (N) group (88 vs 81 p ⫽ 0.007). On day 2 the reverse was true (79 vs 85 p ⫽ 0.004). During H, PbtO2 was lower compared to N patients on days 0 (20 vs 26 p ⫽ 0.03), day 1 (19 vs 25 p ⫽ 0.01) and day 2 (21 vs 25 p ⫽ 0.05). CVP did not differ between H and N groups. PAOP did not differ between groups except day 6 (18 vs 5 p ⫽ 0.02). Cardiac index (CI) was lower in H patients on day 0 (3.05 vs 3.82 p ⬍ 0.01) and day 1 (3.31 vs 4.21 p ⬍ 0.01). ICP was non-significantly higher in operative patients on days 2, 3 and 4. CPP, PbtO2, CVP and CI did not differ between operative and nonoperative patients. PAOP was lower in operative patients on days 4-7. In operative patients, H treatment had no effect on ICP but was associated with higher CPP but lower PbtO2 on day 0. In operative patients, the H group had higher PbtO2 on days 6 and 7. CVP and PAOP did not differ but CI was lower in H compared to N patients on day 0 and day 1 in operative patients. In nonoperative patients, ICP was higher in H patients on days 1, 2 and 3. CPP was significantly lower in nonoperative H patients only on day 2. H was associated with little effect on PbtO2, CVP, and PAOP but was associated with suppression of CI in nonoperative patients. Conclusions: The differential effect of H on outcome by operative status is not obviously explained by cerebral or systemic hemodynamic parameters. Further investigation into the cardiosuppressive and PbtO2 effects of H is warranted.

Poster: Pulmonary - Diagnostics 340

341

ECONOMIC IMPACT OF USING A HAND-CARRIED ULTRASOUND FOR DIAGNOSTIC THORACENTESIS IN PATIENTS WITH PARAPNEUMONIC EFFUSIONS

BILATERAL AUSCULTATION IS NOT THE BEST BEDSIDE TEST TO DETECT ENDOBRONCHIAL INTUBATION – A PROSPECTIVE RANDOMISED TRIAL

Pankaj Patel, GE Healthcare, Manan Shah, Anna DSouza, Xcenda, Haesuk Park, University of Texas at Austin

Christian Sitzwohl, Harald Herkner, Angelika Langheinrich, Andreas Schober, Stephan Kettner, Medical University of Vienna, Daniel Sessler, Cleveland Clinic

Introduction: Delays in access to diagnostic modalities in the hospital setting such as a standard ultrasound can add significantly to the total cost of a hospitalization. Hand-carried ultrasound (HCU) including pocket-sized ultrasound devices offers the convenience of rapid assessment due to their portable nature. Hypothesis: The study purpose was to develop a model to assess the economic impact of using a HCU versus the current standard of care for diagnostic thoracentesis in patients with parapneumonic effusions (PPE). Methods: The model was developed from a U.S. hospital perspective, and timeframe was during the hospitalization stay. In the HCU strategy, all diagnostic thoracentesis procedures were guided with the HCU, whereas the current standard of care reflects only 55% of procedures with standard ultrasound guidance. Model inputs included total number of patients hospitalized in the U.S and diagnosed with PPE, proportion requiring a diagnostic thoracentesis, risk and cost of pneumothorax, and per diem cost of a complicated pneumonia hospitalization. Outcomes included cost due to delays in access to ultrasound and risk of pneumothorax. One-way sensitivity analyses were done varying key model inputs. Results: The model population included a total of 967, 266 patients hospitalized for pneumonia in the U.S. of which 50% were diagnosed with a PPE. Use of ultrasound for all diagnostic thoracentesis procedures with the HCU strategy avoided 207, 375 days of hospitalization annually translating to a cost-savings of $291 million USD ($301 per hospitalized pneumonia patient). Additionally, a 71.2% reduction in risk of pneumothorax was found for the HCU strategy (2%) compared to the current standard of care (7%). After accounting for the cost reduction from pneumothorax and the additional cost of thoracentesis using ultrasound guidance, the total cost-savings were $282 per hospitalized pneumonia patient. Sensitivity analyses showed the cost-savings to range from $84 to $358, and a minimum risk reduction of pneumothorax of 44.3%. Conclusions: The convenience of the HCU for guiding diagnostic thoracentesis procedures in hospitalized pneumonia patients will potentially result in total cost-savings of $273 million USD per year.

Introduction: Endotracheal intubation is performed by a wide variety of critical care clinicians with different levels of experience in airway management. Serious complicationscan result from misplacement of an endotracheal tube (ETT) in a main stembronchus. The beside ‘gold standard‘ to detect such a misplacement is bilateral auscultation of the lungs; but this method frequently provides inconclusive results. Other routinely used tests to verify correct ETT placement include observation of symmetric chest movements, and inserting the ETT to a specific depth. Hypothesis: We designed this study to determine which bedside method has the highest sensitivity and specificity for detecting endobronchial intubation and whether these increase with experience. Methods: Patients were randomly assigned to eight study groups. In four groups, an ETT was fiberoptically positioned 2.5-4.0 cm above the carina, whereas in the other four groups the tube was positioned in the right mainstem bronchus. The four groups differed in the bedside test used to verify the position of the ETT. First-year residents and experienced anaesthesiologists performed one of the following bedside tests in each patient: 1) bilateral auscultation of the chest (Auscultation); 2) observation and palpation of symmetric chest movements (Observation); 3) estimating the position of the ETT by the insertion depth (Tube Depth); and, 4) a combination of all three mentioned tests (All Three). Results: 160 patients (118 female/ 42male) with 320 observations by 32 experienced and 22 inexperienced anesthesiologists were included in the study. Tube Depth and All Three were significantly more sensitive for detecting endobronchial intubation than the other methods including auscultation (p ⬍ 0, 001). First year residents missed endobronchial intubation by auscultation in 55% versus only 10% of experienced anesthesiologists did so. Conclusions: Our results suggest that the hierarchy of the methods used to assess the correct ETT insertion depth should be changed and that clinicians should rely more on depth of ETT insertion than on auscultation. This is especially true for physicians with less experience in airway management.

342 CARDIAC MARKERS N-TERMINAL-PROBNP, TROPONIN T AND TROPONIN I LEVELS OVER THE FIRST WEEK AND ITS RELATION TO 30 DAY SURVIVAL IN ARDS PATIENTS WITH STRUCTURALLY NORMAL HEARTS Yasser Nassar, Dina Monsef, Gamal Hamed, Sanaa Abdelshafy, Cairo University Introduction: Cardiac enzymatic elevation occurring in ARDS may be associated with increased mortality. Hypothesis: Cardiac markers N-terminal-ProBNP , Troponin T and Troponin I levels are sampled from all patients on day zero , day two and day seven of ARDS diagnosis, then patients are grouped after 30 days into survivors and nonsurvivors and their first week cardiac markers levels are compared to identify its relation to 30 day outcome survival. Methods: The study was conducted in cairo university between 1 June 2008 and 1 April 2009. Inclusion criteria was any adult patient diagnosed to have ARDS according to the criteria of the American-European Consensus Conference in 1994. Exclusion criteria was any structural heart disease by echocardiography, pulmonary embolism, atrial fibrillation, renal insufficiency, age less than 18. All patients benefited from Lung protective ventilation strategy. Plasma levels of Cardiac markers including N-terminal-proBNP, troponin I and troponin T were measured on day zero and on day two and day seven of ARDS diagnosis. According to outcome mortality patients were classified after 30 days of ARDS diagnosis into Survivors group and Nonsurvivors group. Results: The study comprised 20 patients with mean age of 58.9 ⫾ 20.69 yrs, 11 men vs 9 women (p ⬎ 0.05)30 day Survivors were (7, 35%) patients while Nonsurvivors were (13 , 65%) patients. N-terminal Pro-BNP mean values were on day zero 712.0 ⫾ 188.13 vs 8975.9 ⫾ 9360.6 ( p ⬍ 0.001) , day two 995.57 ⫾ 594.28 vs 4545.92 ⫾ 1384.82 (p ⬍ 0.001) and on day seven 1007.67 ⫾ 716.74 vs 13732.07 ⫾ 13363.14 ( p ⬍ 0.001) in Survivors vs Nonsurvivors respectively.Troponin I mean values were on day zero 0.2 ⫾ 0.0 vs 4.57 ⫾ 9.33 (p ⬍ 0.001), day two 0.2 ⫾ 0.0 vs 3.29 ⫾ 8.12 (p ⬍ 0.001) and day seven 0.2 ⫾ 0.0 vs 2.09 ⫾ 5.25 (p ⬍ 0.001) in Survivors vs Nonsurvivors respectively. Troponin T mean values were on day zero 0.0 ⫾ 0.0 vs 0.51 ⫾ 0.7 (p ⬍ 0.001), day two 0.0 ⫾ 0.0 vs 0.97 ⫾ 1.81 (p ⬍ 0.001) and day seven 0.0 ⫾ 0.0 vs 0.72 ⫾ 1.24 (p ⬍ 0.001) in Survivors vs Nonsurvivors respectively. Conclusions: Survivors of ARDS with structurally normal hearts had significantly lower first week levels of cardiac markers N-terminal Pro-BNP, Troponin I and Troponin T than Nonsurvivors.


Poster: Pulmonary – Mechanical Ventilation-1 343

344

EFFECT OF ENDOTRACHEAL TUBE WITH TAPER SHAPED CUFF AND SUBGLOTTIC SECRETION (SGS) SUCTION PORT INTUBATION DAYS IN AN URBAN ICU

REAL-TIME MEASUREMENTS OF INSPIRATORY PLATEAU PRESSURE (PPLT), RESPIRATORY SYSTEM COMPLIANCE (CRS), AND RESISTANCE (RRS) DURING VENTILATORY SUPPORT*

Torillo Flores, New York Downtown Hospital, Ulf Borg, Covidien Introduction: Introduction Ventilator associated pneumonia (VAP) is seen in patients receiving mechanical ventilation (MV) for more than 24 hrs. One cause of VAP is microaspiration of secretions/fluid around the endotracheal tube (ETT) cuff. A comprehensive study on healthcare resource utilization found that patients with VAP had on average 11 more MV days and 6 more ICU days. After introducing the standard VAP bundle with only marginal result we changed our ETTs from Hi-Lo endotracheal tube with barrel shaped cuff (Covidien) to a tube with a taper-shaped cuff and subglottic secretion suction channel (SealGuard™ EVAC, Covidien). We compared the intubation days and VAP rate before and after conversion. Hypothesis: Hypothesis Taper-shaped cuff and SGS management will decrease number of days intubated and rate of VAP. Methods: Methods ICU data for 19 months starting in January 2009 with conversion to tapershaped cuff with SGS in November 2009: intubation days, VAP rate and adherence to VAP bundle, weaning protocol and to sedation vacation protocol. Extubation considered successful after 24 hrs of unassisted breathing. Results: Results Mean intubation days decreased from 6.5 SD ⫾ 2 (n ⫽ 214) before conversion to 5.2 ⫾ 2 (n ⫽ 134) days after conversion. Adherence to VAP bundle and sedation vacation and weaning protocol was the same before and after conversion at 95%. VAP rate was 5.7/1000 MV hrs prior to conversion and 0 after. Conclusions: Conclusion After conversion to taper-shaped cuff and SGS management reduction in days intubated and VAP rate was achieved.. This difference was observed in spite of strong adherence to standard VAP prevention measures. Adoption of ETTs with taper-shaped cuffs and SGS management may result in decreased morbidity and significant cost reduction since every MV/ICU day cost ⬃$5500. Continued data collection will further elucidate the effects of the endotracheal tube conversion.

Nawar Al-Rawas, University of Florida, Michael J. Banner, University of Florida College of Medicine, Neil R. Euliano, Convergent Engineering, A.Joseph Layon, Andrea Gabrielli, University of Florida College of Medicine Introduction: Real-time Pplt, Crs, and Rrs allow understanding of pulmonary mechanics of patients with respiratory failure. Pplt, needed for calculations of Crs and Rrs, is obtained by applying an end-inspiratory pause (EIP) immediately following a tidal volume during controlled mechanical ventilation (CMV) or intermittent mandatory ventilation (IMV). Applying an EIP with IMV may interfere with patient/ventilator synchrony and predispose to erroneous measurements of Pplt. Thus, repeated measurements of Pplt, and therefore Crs and Rrs, are difficult to obtain using an EIP. Hypothesis: We hypothesize that real-time Pplt may be accurately estimated from a method using the expiratory time constant (tE) during passive deflation of the lungs combined with the equation of motion of the respiratory system. Methods: Adults (n ⫽ 30, 86% heterogeneous causes of respiratory failure and 14% normal pulmonary function; age 51 ⫾ 18.7 yrs; 26 males, 4 females; wt 83 ⫾ 37.7 kg) in an IRB-approved study were ventilated with CMV and EIP 0.5 sec, allowing for measurement of Pplt, which, in turn, permitted calculations of Crs and Rrs. Subsequently, Pplt was derived using the tE method, and Crs and Rrs were recalculated. Data were analyzed with regression analysis and Bland-Altman plots. Results: Pplt during CMV with EIP was 21.56 ⫾ 7.51 cm H2O, and Pplt from the tE method was 21.56 ⫾ 7.59 cm H2O. Relationships using both ways of determining Pplt were: r2 ⫽ 0.99, 0.97 and 0.92 for Pplt, Crs and Rrs, respectively (p ⬍ 0.05). BlandAltman plots for Pplt, Crs and Rrs showed essentially zero bias at .01, .01 and .01, respectively, and high precision at ⫾ 1.35, ⫾ 1.37 and ⫾ 2.15 for Pplt, Crs and Rrs, respectively. Conclusions: Pplt may be accurately and continuously derived using tE from passive deflation of the lungs without the need for EIP. This method can be employed with other modes in which spontaneous ventilation is mechanically supported, for example, pressure support ventilation. Knowledge of these data allows for real-time monitoring of pulmonary mechanics and a dynamic means of assessing the risks of overdistension or overpressurization during ventilatory support(1). 1. ARDS network protocol 2008 *Patent pending

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AUTOPEEP IN RELATION TO TIME CONSTANT IN AIRWAY PRESSURE RELEASE VENTILATION (APRV)

NEURALLY TRIGGERED BREATHS REDUCE TRIGGER DELAY, RESPONSE TIMES, AND WORK OF BREATHING IN PEDIATRIC PATIENTS WITH BRONCHIOLITIS

Aanchal Kapoor, Ehab Daoud, Robert Chatburn, Cleveland Clinic Introduction: Airway Pressure Release Ventilation (APRV) is a form of “open lung approach” ventilation strategy used for acute respiratory distress syndrome (ARDS). This non-conventional mode of ventilation commences at an elevated baseline pressure (P-high) followed by a short release time (T-low) to a lower pressure (P-low) to accomplish tidal ventilation. Optimal T-low allows for adequate ventilation and impedes complete exhalation and hence generating autoPEEP to prevent alveolar collapse. There is an exponential change in volume during the release time which is a function of the time constant (TC) of the respiratory system. The autoPEEP level can be predicted theoretically using a simple model. Predicted autoPEEP ⫽ (P-high – P-low)(exp –t/TC). The purpose of this study was to compare autoPEEP levels, and flow decay profiles at different TCs and at different levels of P-low during simulated ventilation. Hypothesis: The predicted autoPEEP under-estimates the actual autoPEEP, and that the P-low value affects this relation. Methods: A passive ARDS patient was modeled with a lung simulator (IngMar ASL 5000): compliance ⫽ 30 mL/cm H2O, resistance ⫽ 10 cm H2O/L/s, with time constant (TC) of 0.3 seconds. An Avea Ventilator was set as follows: Experiment 1: P-high ⫽ 25 cm H2O and P-low ⫽ 0 cm H2O, T-low was varied from 1 to 4 TC. T-high was held constant at 5.6 seconds. Experiment 2: same settings except P-low ⫽ 10 cm H2O. We measured autoPEEP (volume at the end of T-low/compliance) and flow as % of peak expiratory flow (PEF) at each TC. Mean values from at least 5 breaths were compared with t tests. Actual values of autoPEEP were expressed as percent increase above predicted. Results: For both experiments, the actual autoPEEP was higher than predicted (P ⬍ 0.001). Experiment 1: actual vs predicted autoPEEP (cm H2O) was 1TC: 14 vs 9, 2TC: 8 vs 3, 3TC: 4 vs 1, 4TC: 2 vs 0.5. Experiment 2: 1TC: 9 vs 6, 2TC: 4 vs 2, 3TC: 2 vs 0.8, 4TC: 1 vs 0.3. Conclusions: Setting T-low based on predicted autoPEEP may not be reliable and results in higher than expected auto PEEP. This may be due to nonlinear resistance of the ventilator system. The addition of P-low reduces the amount of auto PEEP.


Katherine Clement, University of North Carolina, Shirley Holt, UAMS/ACH, Tracy Thurman, UAMS/ACHRI, Mark Heulitt, UAMS/ACH Introduction: Patient-ventilator interaction typically occurs when the ventilator responds to a pneumatic trigger from a patient’s airway. Neurally Adjusted Ventilatory Assist (NAVA) is a mode of ventilation designed to improve patientventilator interaction by interpreting a diaphragmatic signal to trigger a supported breath. Hypothesis: We hypothesized that neurally triggered breaths would reduce trigger delay, ventilator response times, and work of breathing (WOB) in pediatric patients with bronchiolitis. Methods: Thirty subjects aged 0 to 24 months with bronchiolitis were enrolled. Subjects were studied in volume support (VSV - pneumatic trigger) and NAVA (pneumatic and neural trigger). Airway flow and pressure waveforms were obtained with a pneumotachograph and computerized digital recorder. Data were recorded for 120 seconds for each experiment and analyzed for trigger delay, ventilator response time, and pressure time product (PTP), a measure of WOB. Results: Nineteen subjects completed both VSV and NAVA arms of the study. Eleven subjects had inadequate data. Mean age was 1.6 ⫾ 1 months. Mean weight was 4.2 ⫾ 1.4 kg. Neurally triggered breaths had less trigger delay (ms) (40 ⫾ 27 vs. 98 ⫾ 34; p ⬍ 0.001) and reduced ventilator response time (ms) (20 ⫾ 18 vs. 36 ⫾ 34; p ⬍ 0.001) compared to pneumatically triggered breaths. WOB was extrapolated from the change in the area under the curve of the pressure-time waveform. WOB was decreased with neurally triggered breaths, as suggested by reduced PTP Area A (cmH2O*sec), the area of the pressure curve from initiation of breath to start of ventilator pressurization (0.013 ⫾ 0.010; p ⬍ 0.001), and reduced PTP Area B (cmH2O*sec), the area of the pressure curve from start of ventilator pressurization to return of baseline pressure (0.008 ⫾ 0.006 vs. 0.023 ⫾ 0.009; p ⫽ 0.003). Conclusions: Neurally triggered breaths reduce trigger delay, improve ventilator response times, and decrease WOB in children with bronchiolitis. Further analysis will determine if neurally triggered breaths reduce patient-ventilator asynchrony, which may increase length of ventilation and hospital stay. Funding: Children’s University Medical Group grant, Arkansas Children’s Hospital Research Institute

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COMBINED ANTICOAGULANT AND FIBRINOLYTIC THERAPY DECREASES THE VENTILATOR DAYS IN AN OVINE MODEL OF CUTANEOUS BURN AND SMOKE INHALATION INJURY

CORRELATES OF PERIPHERAL MUSCLE WEAKNESS IN MECHANICALLY VENTILATED PATIENTS

Sven Asmussen, Yusuke Yamamoto, Daniel L Traber, Hiroshi Ito, Lillian D Traber, David N Herndon, Perenlei Enkhbaatar, Dept. of Anesthesiology, Univ. of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX Introduction: Aim of this study was to investigate the longterm effects of recombinant human antithrombin (rhAT), heparin (hep) and tissue plasminogen activator (tPA) in our established model of acute lung injury, resulting from burn and smoke inhalation injury (BSII). Hypothesis: We hypothesised that this triple therapy decreases the requirement of ventilation and reduces the ventilation days. Methods: Eight female sheep (31-42 kg) were operatively prepared for chronic study, and were randomly allocated either to control or treatment group (n ⫽ 4 each). After tracheostomy, BSII (48 breath of cotton smoke) and 3rd° burn of 40% total body surface area was performed under deep anesthesia. The sheep were mechanically ventilated and fluid resuscitated for 96h in awake state. The treatment group received combined therapy of rhAT (0.7mg/kg/h, continuous IV infusion starting 1 h post-injury), nebulized heparin (5000IE, every 4 h, starting 2h post-injury), and nebulized tPA (2mg every 4 h, starting 4h postinjury). The treatment was stopped at 48h. Ventilator weaning was started at 48 h, if PaO2/FiO2 ratio was ⱖ 250. The control group received the vehicle. Measurements were taken in intervals ranging from 3 to 12 hours. Statistical analysis: two-way ANOVA and Bonferroni post hoc comparison. Data are expressed as mean ⫾ SEM. Significance P ⬍ 0.05. Results: The PaO2/FiO2 ratio was significantly decreased in control group vs. baseline (BL:517 ⫾ 16 vs. 96h: 214 ⫾ 58). The ratio was significantly higher in treatment vs. control group (96h: 391 ⫾ 36). All treated sheep survived and were weaned from the ventilator. The tracheostomy tube was removed in 3 of 4 treated sheep at 72 h. Three out of 4 control sheep survived, however none of the survived sheep could be weaned from the ventilator. Conclusions: The triple therapy with nebulized heparin and tPA and intravenous rhAT may be a novel and efficient therapeutic option in management of burn patients with smoke inhalation injury.

Linda Chlan, University of Minnesota School of Nursing, Mary Fran Tracy, University of Minnesota Medical Center, Fairview, Kay Savik, Jill Guttormson, University of Minnesota, Debra Skaar, University of Minnesota College of Pharmacy Introduction: Immobility leads to muscle weakness yet little is known about which specific risk factors contribute most to weakness in ventilated ICU patients. Hypothesis: The purpose of this study was to determine the contributions of known correlates to peripheral muscle weakness in ventilated patients. Methods: A sample of 95 patients (50% male) who had been mechanically ventilated an average of 9 days (⫹7.8; median 7.0) prior to enrollment participated in this descriptive, correlational study for 7.1 days (⫹7; median 4.2) from 5 ICUs in the urban Midwest. Subjects were 60.1 years old (⫹15.1; median 64) with APACHE III scores of 62.2 (⫹21; range 15-113); 35% received insulin infusions, 57% steroids, and 8% neuromuscular blockers (NMBs) while in ICU. Results: Hand dynamometry, a marker of peripheral muscle strength, was performed daily with the Jamar grip device. Baseline grip strength was 12.3 pounds-force (⫹17.9; range ⫽ 0-102); standardized adult male range 101-121. Mixed models analysis was used to examine known correlates of muscle weakness. Level 1 model indicated significant unexplained variance in both grip strength over time (z ⫽ 5.41; p ⬍ .001) and in initial grip strength (z ⫽ 5.37 p ⬍ .001) indicating further analysis being appropriate. Level 2 modeling indicated sedation frequency [␤-.31(.14); p ⫽ .03], female gender [␤ -7.3(3.0; p ⫽ .02], age [␤-.28(.10); p ⫽ .01], and days enrolled [␤ -.45(.12); p ⫽ .0004] explained a significant amount of variance in grip strength over time. APACHE III scores [␤ -.12(.07); p ⫽ .12], receipt of insulin, steroids, or NMBs did not contribute to an explanation of grip strength beyond the significant variables. Age, female gender, prolonged ventilator support, and frequency of sedative administration contribute to diminished grip strength in this sample, regardless of illness severity. Conclusions: Interventions are needed that directly modify risk factors to reduce immobility and weakness. Sedative regimens that manage symptoms yet reduce the frequency of medication administration are needed, particularly for those patients requiring prolonged periods of mechanical ventilatory support. [Supported by grant NR009295]

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INFLAMMATORY EFFECTS OF A RECRUITMENT MANOEUVRE

USE OF BLADDER PRESSURE RECORDING TO AID IN THE INTERPRETATION OF PLATEAU AIRWAY PRESSURES DURING ACTIVE EXPIRATION

Giuseppe Mancino, Michele Collareta, Matteo Franchi, Roberto Topini, Francesco Forfori, Francesco Giunta, Universita` di Pisa Introduction: Acute respiratory failure (ARF) is a common cause of admission to ICU: ventilatory support is crucial to many critically ill patients. Nowadays ventilatory strategies use low tidal volumes and low pressures and periodic derecruitment of the dependent lung unit. The cyclic collapse and decollapse of the lung damages it, causing release of cytokines. Alveolar recruitment manoeuvres (RM), consisting of a transient increase of respiratory pressure, have been proposed to prevent collapse of the lung, and to improve oxygenation, but it is still unknow if RM can cause an increase in systemic levels of proinflammatory cytokines, so contributing to VILI. Hypothesis: The aim of this trial was to demonstrate that a protective ventilatory strategy associated to a RM improves gas exchange, not causing or worsening a significant inflammatory reaction. Methods: We recruited 10 patients admitted to our ICU for ARF and ARDS. After 24 hrs of a protective ventilatory strategy, a RM was performed in CPAP mode, and PEEP was raised to 40 cmH2O for 30”. Before and after the RM, data regarding lung mechanics, gas exchange, hemodynamics and plasmatic levels of IL-1b, IL-6, IL-8, IL-10, TNF-a and NO were recorded. We measured proinflammatory cytokines in the BAL or in the tracheobrochial lavage before and after the RM. Results: The RM caused a slight and transient increase of the PaO2/FiO2 ratio from the baseline mean level of 207 ⫹ - 78 mmhg to 220 ⫹ -83 at T30’’ (p ⫽ 0.83) without a significant change in hemodynamics and lung mechanics. The RM did not cause a statistically significant change in plasmatic levels of pro and anti inflammatory cytokines at 3 and 12 hours. Nonetheless, we observed a significant increase of TNF-a/IL-10 ratio at 3 hours (7.79 ⫹ -7.46 vs 6.12 ⫹ 5.80, p ⬍ 0.05) and a reduction of plasmatic levels of NO 24 hrs after the RM (12.3 ⫹ -6.6 umol/l vs 18.7 ⫹ - 8.5 umol/l, p ⬍ 0.05). Conclusions: So, the RM, performed by setting PEEP to 40 cmH20 for 30’’ caused an unbalance of the citokyne profile in favour of proinflammatory ones, evident at 3 hrs, but no longer significant at 12 hrs. An immunologic effect of the RM is also shown by the decrease of plasmatic levels of NO.

Ramiro Saavedra Romero, Robert Shapiro, James Leatherman, Hennepin County Medical Center Introduction: It is recommended that plateau airway pressure (Pplat) be measured with relaxed respiratory muscles. Active expiration during the end-inspiratory pause may cause measured Pplat to greatly exceed relaxed Pplat, leading to the use of deep sedation or neuromuscular paralysis to accurately assess respiratory system mechanics. Hypothesis: In the presence of active expiration, subtracting the expiratory change in intra-abdominal pressure (⌬IAP) from the measured Pplat would provide a close estimate of relaxed Pplat. Methods: We studied 13 mechanically ventilated patients who had clinical evidence of active expiration. Pplat and bladder pressure (IAP) were measured simultaneously using a 2 channel recorder. Pplat was measured with a pressure transducer connected via an adaptor to the endotracheal tube. When possible, a series of three measurements were obtained. Relaxed Pplat was then measured after abdominal expiratory muscle activity was abolished with deep sedation or paralysis. ⌬ IAP was defined as the expiratory rise in bladder pressure from baseline. Results: ⌬ IAP during active expiration was 14.0 ⫹ 7.4 cmH2O. Pplat during active expiration was 34.5 ⫹ 8.8 cmH2O. The corrected Pplat (measured Pplat- ⌬ IAP) was 20.5 ⫹ 6.6 cmH2O and relaxed Pplat was 23.4 ⫹ 6.7 cmH2O. The absolute difference between corrected Pplat and relaxed Pplat was 3.7 ⫹ 2.1 cm H20. Conclusions: With active expiration, the measured Pplat greatly overestimates the relaxed Pplat. Subtracting ⌬ IAP from measured Pplat provides a much better approximation of relaxed Pplat. This approach might obviate the need for repeated deep sedation or paralysis for serial measurements of Pplat in some patients.


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IS CUMMULATIVE VENTILATION GREATER THAN 48 HOURS AN IMPORTANT PARAMETER IN MECHANICAL VENTILATION?

PROSPECTIVE COMPARISON OF SPO2 AND PAO2 BASED MARKERS OF LUNG DISEASE SEVERITY IN MECHANICALLY VENTILATED CHILDREN

Manpreet Chadha, Subhash Reddy, Mathilda Horst, Jack Jordan, Ilan Rubinfeld, Henry Ford Hospital

Robinder Khemani, Childrens Hospital Los Angeles, Christopher Newth, Children’s Hospital of Los Angeles, Patrick Ross, Children’s Hospital Los Angeles, Tyler Berutti, Vanderbilt Children’s Hospital, Neal Thomas, Penn State Children’s Hospital, Jason Scimeme, Children’s Hospital/Ohio State University, Mark Hall, Nationwide Children’s Hospital, James Schneider, Cohen’s Children’s Medical Center, Vani Venkatachalam, Douglas Willson, University of Virginia Health Sciences Center

Introduction: In the National Surgical Quality Improvement Project (NSQIP) prolonged ventilation (PV)as an adverse event is defined as cumulative ventilation over 48 hours. We sought to better understand the ventilatory and critical care outcomes associated with this parameter and see if this adverse event serves as a herald for other more serious adverse outcomes. Hypothesis: We hypothesized that PV is associated with increased serious post operative adverse outcomes. Methods: We utilized 4 years of NSQIP Public use files under the data use agreement and after the approval of our IRB. The years 2005-2008 were combined and assessed for prolonged ventilation and associated critical care outcomes. Adverse events of particular interest to Critical Care were reviewed in based on relationships to the prolonged ventilation outcome variable. Data was analyzed in SPSS (Chicago). Univariate categorical chi-square analysis was utilized as well as binary logistic regression. Acuity adjustment of variables for regression were based on multiple year review of NSQIP annual reports. Results: Of 635265 patients, 15311 patient (2.4%) had the adverse event of PV. This was associated with an increase in organ space infections: 11.3% vs 1.1% in non-PV (OR 11.7, p ⬍ .001). Similarly, dehiscence occurred at an increased rate of 5.8% vs 0.5% (OR 11.8, p ⬍ .001). Pneumonias occurred in 36% of the patients as opposed to .9% of the rest (OR 62.3, P ⬍ .001). Due to the cumulative nature of the definition it is not surprising that reintubation is highly associated with PV: 37.5% vs0.6% (OR 106, P ⬍ .001). Pulmonary embolism was also associated with PV: 2.1% vs 0.3% in non-PV patient (OR 8.0, p ⬍ .001). Infections tracked in NSQIP were combined as one dichotomous variable and highly associated with PV: 52.4% vs 6.4% (OR 16, p ⬍ .001). Most significantly, mortality was associate with PV: 24.9% vs 1.2% (OR 28, p ⬍ .001). Results were confirmed using binary logistic regression with consistently similar odds ratios. Conclusions: In our review we do find a significant associate with this concept of cumulative ventilation time as a marker and potential predictor, for further adverse events. Further work validating this as a guide in clinical ventilation is warranted.


Introduction: Given that pulse oximetry is increasingly substituting for arterial blood gas monitoring, non invasive surrogate markers for lung disease severity are needed to stratify patient risk. Hypothesis: We sought to prospectively validate the comparability of SpO2/FiO2 (SF) and Oxygen Saturation Index (OSI) to PaO2/FiO2 (PF) and Oxygenation Index (OI) in children. Methods: Prospective, six-site observational study from mechanically ventilated children with SpO2 ⱕ 97% and an arterial catheter. Data were divided into derivation and validation datasets, and linear regression was used to derive predictive equations. Results: 825 blood gas, SpO2 and ventilator settings from 94 patients were included. The median PF was 135 with a median OI of 13.5. OSI had a strong linear association with OI in both derivation (R2 ⫽ 0.86) and validation (R2 ⫽ 0.85) datasets. SF had a fair linear association with PF in both derivation (R2 ⫽ 0.57) and validation (R2 ⫽ 0.62) datasets. SF criteria for ARDS and ALI were 208 (204, 212) and 268 (260, 276). 509 observations were available with SpO2 ⱕ 95%. SF had a much stronger linear correlation with PF in this range (R2 ⫽ 0.71), with higher SF criteria for ARDS 233 (229, 239) and ALI 324 (315, 334). Conclusions: In children with respiratory failure, SpO2 can be reliably substituted for PaO2 to calculate markers of lung injury severity, but this relationship stronger when SpO2 ⱕ 95%. SpO2 should be targeted between 88-95% to best apply non invasive lung disease severity markers to characterize risk, increase enrollment in clinical trials, and inform therapy decisions.


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THE POTENTIAL TO MAKE MECHANICAL VENTILATION FOR PEDIATRIC ALI MORE LUNG PROTECTIVE BY USING A COMPUTER PROTOCOL

IMPACT OF ELECTRONIC NOTIFICATIONS ON INTRAOPERATIVE VENTILATOR PARAMETERS FOR PATIENTS WITH ACUTE LUNG INJURY

Robinder Khemani, Childrens Hospital Los Angeles, Katherine Sward, J Michael Dean, University of Utah, Alan Morris, Intermountain Medical Center, Christopher Newth, Children’s Hospital of Los Angeles

Michael Maile, Krishnan Raghavendran, James Blum, University of Michigan Health System

Introduction: Reproducible ventilator protocols decrease variability and may shorten mechanical ventilation for children in Pediatric Intensive Care Units (PICUs). Hypothesis: We sought to evaluate the potential benefit of computerized pediatric ventilation protocols adapted from the ARDS Network. Methods: We conducted a retrospective cohort study in a tertiary care PICU which included 402 intubated and mechanically ventilated children with PaO2/FiO2 (P/F) ratio ⬍300. For eligible children admitted from Jan 2000 - Jul 2007, arterial blood gas values (ABG) and ventilator settings were analyzed against a computer pediatric mechanical ventilation protocol adapted from the ARDS Network. Changes to PEEP, FiO2, PIP and ventilator rate (VR) recommended by the protocol were compared to actual changes. Results: 2, 719 ABGs from 402 patients were associated with 6, 017 ventilator settings. Median P/F ratio was 140, with 24.4% mortality. The protocol recommended decreasing FiO2 for 54.3% of clinician decisions; however, FiO2 was actually decreased in only 29.3% of these decisions. In the mid (55 to 68 mmHg) and low (⬍55 mmHg) PaO2 ranges, the protocol recommended more PEEP than was used in actual practice, 42% and 67% of the time respectively. The protocol’s recommended changes to PIP or VR after an ABG were followed 42% of the time, but clinicians made no change to either PIP or VR 46% of the time when the protocol recommended a change. This was true even for pH ⬎ 7.45 and PIP ⱖ 30 cmH2O. Conclusions: Although pediatric intensivists have claimed to embrace lung protective ventilation, there are many lost opportunities to minimize potentially injurious levels of ventilator support. A reproducible computer pediatric mechanical ventilation protocol can recommend ventilator changes consistent with lung protective ventilation, and might standardize clinician decisions.

Introduction: Evidence currently supports the use of lung protective ventilation strategies (LPVS) for patients with acute lung injury (ALI). However, when patients with ALI present for surgery, LPVS are often not utilized in the operating room. Hypothesis: We hypothesized that sending anesthesia providers an automated reminder regarding the use of LPVS before they started a case with a patient who had a low PaO2/FiO2 ratio would lead to decreased tidal volumes (Vt) and increased levels of positive end expiratory pressure (PEEP) intraoperatively. Methods: If a patient had an arterial blood gas with a PaO2/FiO2 ratio ⬍ 300 within 24 hours of surgery, the anesthesia providers were randomized either to receive or not to receive paged alerts regarding the potential presence of ALI. The page also contained a suggested tidal volume to use intraoperatively along with recommended levels of PEEP. Suggested tidal volumes of 6 mL/kg predicted body weight (PBW) were calculated from data in the electronic anesthesia record. Median values for Vt, PEEP, and peak inspiratory pressure (PIP) were then analyzed using the t-test. A sample size of 16 in each group was calculated to have 80% power to detect a difference in means of 2.1 (the difference between a group 1 mean of 8.6 mL/kg PBW and a group 2 mean of 6.5 mL/kg PBW) assuming that the common standard deviation is 2.0 using a two group t-test with a 0.05 two-sided significance level. Results: Data from 46 cases were available for analysis. There were 22 cases in which alerts were sent and 24 cases without alerts. The average Vt for patients that received an alert was 7.1 mL/kg PBW vs 7.8 mL/kg PBW in the no alert group (P ⫽ 0.36). The average median PEEP was 6.1 cmH2O in the alert group and 6.3 cmH2O in the no alert group (P ⫽ 0.91). The average median PIP was 23.6 cmH2O in both groups (P ⫽ 1.0). Only 3 of 22 patients in the alert group received a median Vt of ⱕ 6 mL/kg PBW. Conclusions: Cases with alerts showed a trend toward reduced tidal volumes, but did not result in a statistically significant reduction in Vt, increase in PEEP, or decrease in PIP. Based on these data, further study on the reasons why anesthesia providers avoid LPVS in patients with high risk of ALI is required.

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SECRETION-RELATED ENDOTRACHEAL TUBE OBSTRUCTIONS: REMOVAL OF OBSTRUCTING LUMINAL SECRETIONS USING NEW COMPLETE AIRWAY MANAGEMENT (CAM) CATHETERS™

SURVEY OF PEDIATRIC AND NEONATAL INTENSIVISTS REGARDING TREATMENT OF TRACHEAL CULTURES

Orlando Morejon, Mariners Hospital, Stephen Bricknell, Bob Stone, Saint Francis Medical Center

Introduction: Ventilator Associated Pneumonia(VAP) is the second most common nosocomial infection in pediatric intensive care unit (PICU) in the United States. The specific clinical criteria for VAP includes: fever, leukocytosis, evidence of infection based on airway cultures and radiologic changes after 48 hours of mechanical ventilation (MV). Empiric therapy for VAP accounts for about 50% of antibiotic use in PICUs.Hypothesis: Pediatric and neonatal intensivists provide variable management to MV patients with positive tracheal cultures. Methods: A Web based survey sent to pediatric and neonatal intensivists practicing in a university hospital setting about individual practice and management of MV patients. Results: A total of 159 responders completed the survey. Of these 73 were pediatric and 86 were neonatal intensivists. The majority of intensivists do not perform surveillance cultures (97% and 94% respectively). Fever was the most common indication (81%) for pediatric, and clinical suspicion/septic work up (43%) for neonatal intensivists, to request tracheal cultures. Most pediatric (89%) and neonatal intensivists (88%) would not treat isolated tracheal culture showing gram negative bacteria; but would treat with: new infiltrates on the radiographs (88% and 93%); increased ventilator requirements (82% and 93%), leukocytosis (76%, 81%), elevated CRP (47% and 60%), gram stain with polymorphs (57% and 43%) and bacteria (19% and 20%). Intensivists choose intravenous antibiotics (⬎90%) ahead of aerosolized or direct instillation of antibiotics (30%). Conclusions: This survey indicates that most intensivists rely on clinical indicators to obtain tracheal cultures. Fever and suspected sepsis are the most common factors leading to airway cultures. Most do not treat isolated gram-negative tracheal cultures; there is a variable response to additional factors leading to antibiotic treatment. Antibiotic treatment of patients is the most common choice if associated with new radiologic changes and increased ventilator requirements.It is unclear whether this variable management leads to antibiotic overexposure or affects the incidence of VAP. Further studies are needed to determine the safest and most cost effective practice.

Introduction: Endotracheal tube (ETT) secretions cause luminal obstructions that increase work of breathing (WOB) and life-threatening scenarios. Suctioning (SXN) is ineffective at ETT secretion removal. We evaluated a mechanical cleaning (MC) method using new CAM Catheters™ for ETT secretion removal. Hypothesis: We hypothesized that MC would significantly improve the patency of ETTs previously managed by SXN. Methods: 21 ETTs were collected from patients mechanically ventilated (MV) for 1-27 days. ETTs (7-8.5 mm) were cut to 26.5 cm lengths and set in a mock trachea. Each ETT was SXN with the patient’s own 14 Fr. SXN catheter to remove secretions coughed into them during extubation, so the post-SXN (pre-MC) patency would more closely reflect ETT patency during MV. ETT cross-sectional area was determined using acoustic reflectometry (AR) (Hood Labs, Pembroke MA) following: extubation, SXN, MC using CAM Rescue Cath™ and CAM Endotrach Cath™ (Omneotech™, Tavernier FL) in sequence to mimic a new anticipated clinical practice for removal of secretion-related ETT obstructions. AR readings were scaled to patency using new ETT reference data. Results: ETT patency % (range, [p value only for difference between SXN and MC]) following each step in the protocol was reported for average for entire ETT length, narrowest point at baseline and narrowest point after each intervention, respectively: post-extubation ⫽ 87% (4697%), 72% (4-90%), n/a; post-SXN ⫽ 90% (61-98%), 78% (48-98%), 77% (4790%); post-MC ⫽ 97% (92-100%, p ⫽ 0.0041), 94% (83-100%, p ⫽ 0.0004), 90% (83-98%, p ⫽ 0.0012). Conclusions: The severity of secretion-related ETT obstruction detected at the single point of greatest obstruction (which determines resistance and WOB) was considerably greater than the average obstruction throughout the entire length of the ETT. Removal of secretion-related ETT obstructions by MC using the CAM Catheters™ significantly improved ETT patency throughout the length of the ETT and at the point of greatest obstruction compared to patency resulting from conventional clinical SXN practices. Restoration of ETT patency with expectant reduction of resistance and WOB may facilitate weaning from MV. This novel concept warrants further investigation.

Srinivasarao Badugu, Thianchai Bunnalai, University of Florida College of Medicine, Tara Smith, University of Florida-Shands Hospital


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THE IMPACT OF DELIRIUM ON MECHANICAL VENTILATION IN THE PEDIATRIC INTENSIVE CARE UNIT

PREDICTION OF EXTUBATION FAILURE IN LONG-TERM MECHANICALLY VENTILATED MEDICAL ICU-PATIENTS

Kevin Madden, Robinder Khemani, Childrens Hospital Los Angeles, Jeffrey Gold, Childrens Hospital of Los Angeles

Bernd Saugel, Philipp Rakette, Veit Phillip, Roland Schmid, Wolfgang Huber, Klinikum Rechts der Isar der Technischen Universita¨t Mu¨nchen

Introduction: In adults delirium is an independent predictor of increased mortality, length of stay and worse functional and cognitive outcome; yet little is known about delirium in critically ill children. Hypothesis: Mechanically ventilated children diagnosed and treated for delirium will have a longer length of ventilation before treatment of delirium compared to after treatment of delirium. Methods: Retrospective review of children in a tertiary care PICU and CTICU diagnosed with delirium while mechanically ventilated during a 92-month period. Results: 81 patients were diagnosed with delirium while being mechanical ventilated. The mean age was 11.6 years, mean weight was 38.8 kg. Patients were 59.3% male, and 40.4% Latino. Respiratory distress/failure was the most common reason for admission (45.7%). The median time between start of mechanical ventilation and diagnosis of delirium was 94 hours. The mean cumulative dose of narcotics (standardized to morphine) pre-treatment of delirium was 332.41 mg and post-treatment was 222.97 mg yet this difference is not statistically significant (Mann–Whitney U ⫽ 3589, n1 ⫽ n2 ⫽ 81, P ⫽ 0.30 two-tailed). The mean cumulative dose of benzodiazepines (standardized to lorazepam) pre-treatment of delirium was 145.14 mg and post-treatment was 84.60 mg yet this difference is not statistically significant (Mann–Whitney U ⫽ 3656, n1 ⫽ n2 ⫽ 81, P ⫽ 0.20 two-tailed). Olanzapine (58%) was the most common anti-psychotic. The median length of mechanical ventilation pre-treatment of delirium was 94 hours and post-treatment of delirium was 93 hours. There was no statistically significant difference in length of ventilation between any subgroups of patients (BiPAP, tracheostomy). Overall mortality was 22.2%. Conclusions: The treatment of delirium does not appear to affect the length of mechanical ventilation or to decrease the cumulative dose of narcotics and benzodiazepines.

Introduction: Early pulmonary weaning resulting in extubation is a crucial goal in critical care. However, extubation failure results in risks associated with reintubation (re-ITN). Hypothesis: The aim of the study was to identify predictors for extubation success/failure in long-term mechanically ventilated medical ICUpatients. Methods: Prospective trial. University hospital. 70 extubations/patients, MV ⬎ 48h. Collection of demographic, pulmonary, hemodynamic and neurologic variables before/after extubation. Estimation regarding extubation success by the nurse. Extubation failure was defined as the need for re-ITN within 48h. Results: Patients: age 64 ⫾ 13 years. Days of MV 8.2 ⫾ 6.2. GlasgowComa-Scale (GCS) 13.0 ⫾ 2.0; Cook-Palma-Score (CPS) 16.0 ⫾ 1.3; Clinical pulmonary infection score (CPIS) 1.3 ⫾ 1.6; Acute Physiological Assessment and Chronic Health Evaluation II score (APACHE II score) 14.7 ⫾ 3.6; Sequential Organ Failure Assessment score (SOFA Score) 5.5 ⫾ 2.3; Extra-vascular lungwater index (EVLWI) determined using transpulmonary thermodilution 10.9 ⫾ 3.9. Extubation success/failure: Out of 70 extubations 58 (83%) were successful and 12 (17%) resulted in re-ITN within 48h (18.3 ⫾ 14.2h, min 2h, max 48h). Estimation regarding extubation outcome by the nurse did not correlate with actual success/failure of extubation. There was no significant correlation between extubation success/failure and age, duration of MV, pre-extubation blood gas analysis, EVLWI, GCS, CPS, CPIS, APACHE II score, SOFA score, cough strength, swallowing reflex or secretions. Airway occlusion pressure after 0.1 seconds (P0.1) and negative inspiratory force (NIF) - both determined using the artificial respirator Evita XL (Dra¨ger, Germany) - were also not able to predict extubation outcome. Compared to patients with successful extubations, in patients with extubation failure significantly higher pre-extubation pCO2 values were observed (46.7 ⫾ 10.8 vs. 39.4 ⫾ 11.1; p ⫽ 0.045). Conclusions: In long-term mechanically ventilated medical ICU patients prediction of successful extubation using traditional pulmonary weaning parameters is difficult. Higher pre-extubation pCO2 might be used as a predictor for extubation failure.

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FLOW DECAY IN RELATION TO TIME CONSTANT IN AIRWAY PRESSURE RELEASE VENTILATION (APRV)

NONINVASIVE WORK OF BREATHING PER MINUTE (WOBN/MIN) DURING WEANING IMPROVES PREDICTION OF POSTEXTUBATION OUTCOME

Aanchal Kapoor, Ehab Daoud, Robert Chatburn, Cleveland Clinic Introduction: Airway Pressure Release Ventilation (APRV) is a form of “open lung approach” ventilation strategy used for acute respiratory distress syndrome (ARDS). This non-conventional mode of ventilation commences at an elevated baseline pressure (P-high) followed by a short release time (T-low) to a lower pressure (P-low) to accomplish tidal ventilation. Optimal T-low allows for adequate ventilation and impedes complete exhalation and hence generating autoPEEP to prevent alveolar collapse. There is an exponential change in volume during therelease time which is a function of the time constant (TC) of the respiratory system. The purpose of this study was to compare flow decay profiles at different TCs and at different levels of P-low during simulated ventilation. Hypothesis: The flow decay is inconsistent between each TCs, and that the P-low value affects this relation. Methods: A passive ARDS patient was modeled with a lung simulator (IngMar ASL 5000): compliance ⫽ 30 mL/cm H2O, resistance ⫽ 10 cm H2O/L/s, with time constant (TC) of 0.3 seconds. An Avea Ventilator was set as follows: Experiment 1: P-high ⫽ 25 cm H2O and P-low ⫽ 0 cm H2O, T-low was varied from 1 to 4 TC. T-high was held constant at 5.6 seconds.Experiment 2: same settings except P-low ⫽ 10 cm H2O. We measured flow as % of peak expiratory flow (PEF) at each TC. Mean values from at least 5 breaths were compared with t tests. Results: Flow decay was inconsistent between each TC in both experiments: 81% vs 92% for the 1st TC, 52% vs 46 for the 2nd TC, 54% vs 46% for the 3rd TC, and 48% vs 55% for the 4th TC. While the predicted change in volume is 63% at 1TC, 86.5% at 2TC, 95% at 3TC and 98% at 4TC. Conclusions: Setting T-low based on predicted flow decay may not be reliable.This may be due to nonlinear resistance of the ventilator system.The addition of P-low increases the amount of flow decay.


Andrea Gabrielli, Michael J. Banner, University of Florida College of Medicine, Neil R. Euliano, Convergent Engineering, Steve Bonett, University of Florida College of Medicine, Nawar Al-Rawas, Anatole D. Martin, University of Florida, Carl W. Peters, A.Joseph Layon, University of Florida College of Medicine Introduction: WOBn/min obviates an esophageal balloon(1) and reflects the total load on inspiratory muscles to spontaneously inhale. Increased values of WOBn/min, while receiving minimal pressure support ventilation (PSV) and positive end expiratory pressure (PEEP) as during a weaning trial, predisposes to inspiratory muscle fatigue and weaning failure. Conversely, appropriate values of WOBn/min under same conditions may predict weaning success. Hypothesis: WOBn/min during weaning may be a predictor of extubation outcome. Methods: Adults for weaning were divided into 2 groups: Training group (n ⫽ 64, 39么, 25乆, age 58.6 ⫾ 17.2 yrs, wt 84 ⫾ 27 kg) and Prospective-Validation group (n ⫽ 33, 26么, 7乆, age 55.3 ⫾ 18.4 yrs, wt 87 ⫾ 27 kg). Data from a combined pressure/flow sensor, positioned between endotracheal tube and ventilator breathing circuit, were directed to a respiratory monitor (NICO, Respironics) and laptop computer. WOBn/min, spontaneous breathing frequency (f), tidal volume (Vt), and f/Vt were measured. Following a weaning trial, the decision to extubate was made using routine practice standards at minimal ventilator settings (PSV 10 cm H2O, PEEP 5 cm H2O) by clinicians blinded to the study. Data were analyzed using area under ROC curves (AUC) and standard formulae. Results: For Training group of 52 successes and 12 extubation failures, AUC for WOBn/min ROC curve was 0.86 using a cut point of 9.8 Joules/min. For Prospective-Validation group of 26 successes and 7 failures, indices to predict weaning were: WOBn/min f Vt f/VtAUC 0.94* 0.78 0.61 0.73 Sensitivity 0.92 0.92 0.54 0.88 Specificity 0.86 0.67 0.50 0.50Pos. Predictive Value 0.96 0.92 0.82 0.88Neg. Predictive Value 0.75 0.67 0.20 0.50 *p ⬍ .05 compared to f, Vt and f/Vt. Conclusions: The predictive power of WOBn/min of 10 Joules/min was ⬎ traditional indices. AUC was significantly greater for WOBn/min ROC curve compared to AUC for f, f/Vt and Vt, indicating that WOBn/min was a more accurate model for predicting weaning outcome. Reference: 1.Crit Care Med 2006; 34:1052

361 COMPARISON OF ENDOTRACHEAL TUBE INTRINSIC SUCTION RATES AND CUFF SEAL PERFORMANCE Peter Lichtenthal, University of Arizona, Paul Batchelder, Clinimark Introduction: Pulmonary microaspiration remains a serious complication of tracheal intubation. The ability to prevent microaspiration by tracheal suction and cuff integrity could reduce the incidence of microaspiration. Therefore, we evaluated the subglottic suctioning ports and cuff integrity of available endotracheal tubes (ETTs) from 3 different manufacturers. Hypothesis: There is a difference in subglottic suction and cuff leak rates in ETTs. Methods: Using an approved invitro test fixture mimicking the human trachea (ISO 5361 Annex B) we investigated the suction performance and cuff leakage of 3 sizes of endotracheal tubes (ETTs) (6mm, 7.5mm, 9mm) from 3 different manufacturers who offer the suctioning option (TaperGuard EVAC, Tyco Health Care, Pleasanton, CA, Blue line SACETT, Portex, Smith Medical Keene NH, Teleflex ISIS HVT, Teleflex, Research Triangle Park, NC). The suctioning performance at intermittent (15 seconds on and 8 seconds off) suction of 150 mmHg and leakage rate was measured using liquids of 3 viscosities (500cP, 5000cP, 12500cP). During each test a reservoir was used to collect liquid suctioned from the EVAC lumen of the endotracheal tube and weigh boat under the inflated cuff was used to collect any drips that leaked past the cuff. Pre and post test weights were recorded as was time elapsed to calculate suction and leak rates. In this setup the suction rate was dependent on suction rate and 18 results were obtained for each tube size. Results: Overall the Teleflex ISIS (ISIS) had the best suction performance (.2- 5.3 ml/sec) at all viscosities and the TaperGuard EVAC (TGE) had the lowest leak rate (0-.8 ml/hour). In the 7.5mm and 9mm ETTs the order of suction rate was ISIS, TGE (.6-3.4 ml/sec) and SACETT (.3-2.9 ml/sec). In the 6mm tube the suction rates were comparable. The lowest leak rate order was TGE, SACETT (.3-1.3 ml/hour) and ISIS (.3-1.6 ml/hour). Conclusions: In our model the ISIS proved to have the most efficient suction while the TGE demonstrated the best leak protection. The clinical significance of theses findings should be tested in controlled human trials.



363

NON-INVASIVE ASSISTED RAPID SHALLOW BREATHING INDEX FOR PREDICTION OF FAILURE OF NON- INVASIVE VENTILATION

HIGH FREQUENCY OSCILLATORY VENTILATION IN CHILDREN-ONE INSTITUTION’S EXPERIENCE

Jerry Lang, Katherine Berg, Eske Bak, Justin Salciccioli, Michael Cocchi, Ray Ritz, Michael Donnino, Beth Israel Deaconess Medical Center Introduction: Non-invasive ventilation (NIV) can reduce the need for intubation in acute respiratory failure (ARF), and may therefore reduce the morbidity and mortality associated with invasive mechanical ventilation. There is currently no standard physiologic parameter to predict success or failure with NIV. The rapid shallow breathing index (RSBI) is a validated tool used to predict success of extubation after mechnical ventilation. We evaluated the effectiveness of the RSBI to predict failure of NIV early in the course of ARF. Hypothesis: We hypothesize that a RSBI ⬎ 105 will be predictive of the need forintubation and increased in-hospital mortality. Methods: We performed a prospective observational trial of patients with ARF in the emergency department and intensive care units at an academic tertiary care center. Patients were started on NIV at the discretion of the clinical team and the RSBI was calculated regardless of the level of ventilatory support. RSBI was defined by the ratio of the frequency to the exahaled tidal volume ratio and was determined at initiation of NIV. The primary endpoint of the study was the need for intubation and mechanical ventilation, and the secondary endpoint was in-hospital mortality. We compared the high RSBI (105 or higher) group with the low RSBI group (less than 105) using a Chi Square with p value of 0.05 representing statistical significance. Results: We evaluated 101 patients with ARF. The average age of the cohort was 70 ⫹/⫺ 16 years, and all causes of ARF were included. DNI/DNR patients were excluded from analysis. Among 83 patients with a RSBI ⬍ 105, 26 (31%) required intubation, compared to 10/18 patients (55%) with a RSBI ⬎ ⫽ 105 (P ⫽ 0.06). When comparing mortality, 7/83 patients (8.4%) with a RSBI ⬍105 died compared to 6/18 (33%) patients in the group with a RSBI ⬎⫽105 (p ⫽ 0.01). Conclusions: A RSBI of ⬎ ⫽ 105 was statistically significantly associated with increased in-hospital mortality with an associated strong trend toward increased need for intubation. Validation of this concept in a larger patient population is warranted.

Christopher Babbitt, Miller Children’s Hospital, Michael Cooper, The University of California at Irvine Medical Center Introduction: High frequency oscillatory ventilation (HFOV) has been advocated for respiratory failure in children based on experience from small studies. Our institution has been utilizing it for many years for a variety of conditions. Hypothesis: By reviewing our experience with over 100 patients, characteristics can be identified that predict who is likely to benefit from HFOV. Methods: A retrospective chart review was performed on all patients admitted to a 20 bed PICU that were managed with HFOV over an eight year period. Survivors and non-survivors were analyzed in separate groups and compared. Patient characteristics that were reviewed include: age, PRISM score, cause of respiratory failure, incidence of MODS, oxygenation index (OI), duration of ventilation, length of stay, and use of vasoactive agents. Student’s T testing and Fisher’s exact test were used and P values ⬍ 0.05 were considered significant. Results: 104 patients underwent HFOV during the 8 year period with an overall mortality rate of 42%. The annual number of patients on HFOV increased from 9 during 2001 to a high of 34 during 2008. 9 patients died from hypoxia or hyperacapnia and 5 went on to ECMO. OI at initiation of HFOV was 28 (6-51). Non-survivors had a higher incidence of extrapulmonary ARDs (60% vs. 30%), MODS (77% vs. 33%), and a greater need for an epinephrine infusion (60% vs 34%). Survivors had a higher incidence of bronchiolitis (21% vs 2.8%) and a greater LOS (30 vs. 11 days). There was no difference in age, PRISM score, time before initiating HFOV, duration of HFOV, length of mechanical ventilation, or OI prior to HFOV. Survivors had a lower OI after 4 hours of HFOV (23 vs 30) and 12 hours (16 vs. 30) and their OI decreased significantly after 12 hours when compared with that at initiation. After 24 hours of HFOV, 86% of the non-survivors had died, gone on to ECMO, or had an OI ⬎ 25. Only one survivor had an OI greater than 25 after 24 hours, compared with 36 at initiation of HFOV. Conclusions: Survival is lower in HFOV patients who develop MODs and have an extrapulmonary cause of ARDs. Patients that show improvement in their OI at 12 hours and have an OI less than 25 after 24 hours of HFOV are likely to survive.

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AN UNEXPECTED BENEFIT FROM A CLOSED ICU MODEL AND A WEANING PROTOCOL IN THE INTENSIVE CARE UNIT

USE OF PRONE VENTILATION IN NON-HYPOXEMIC RESPIRATORY FAILURE REQUIRING PROLONGED MECHANICAL LUNG VENTILATION

Kristin Fless, Edward Gray, Fariborz Rezai, Paul Yodice, Saint Barnabas Medical Center

Afzal Azim, Sanjay gandhi Postgraduate Institute of Medical Sciences-LucknowIndia, Arvind Baronia, Sanjay Gandhi Postgraduate Institue of Medical Sciences

Introduction: Protocol-driven weaning with daily spontaneous breathing trial (SBT) is superior to physician-initiated weaning. Institution of protocols often follows transition from open intensive care unit (ICU) models to closed ICUs where all care is delivered by on-site critical care trained physicians. Hypothesis: We evaluated the effect of a protocol-driven closed ICU on respiratory outcomes and resource utilization. Methods: Average ventilator length of stay (AVLOS) and arterial blood gas (ABG) sampling were compared for two years prior to (2004 and 2005) and following (2008 and 2009) full implementation of the closed ICU and weaning protocol. Years 2006-2007 represent the transition period from open to closed model and were excluded from analysis. All patients receiving mechanical ventilation in the medical-surgical ICU at our academically affiliated community hospital were included. Following implementation of the closed ICU patients were weaned according to a protocol developed by intensivists and respiratory therapists which required daily screening and SBT. Patients meeting criteria were extubated. The protocol did not include routine ABG measurements prior to extubation. Results: For two years prior to the closed ICU model AVLOS was 3.94 days (3.45 and 4.44 respectively). 3, 855 and 3, 978 ABGs were performed in 2004 and 2005 respectively. Following implementation of the closed ICU, AVLOS decreased to 3.0 days (2.82 and 3.18 in 2008 and 2009) with 2, 172 and 2, 220 ABGs performed, respectively. Conclusions: We demonstrated a decrease in AVLOS of nearly one full day and over 3, 400 fewer blood gases following institution of the closed ICU and weaning protocol (24% reduction in AVLOS and 44% reduction in ABG sampling). Although protocolassociated AVLOS reduction is well recognized in the literature, we have found no reports of reduction in ABG sampling associated with closed ICU and weaning protocols. ABGs are associated with morbidities, utilize respiratory therapy manpower and add to the cost of care. Our experience suggests that routine ABG sampling is not necessary for weaning from mechanical ventilation when a closed ICU model with robust weaning protocols is implemented.

Introduction: Mechanical lung ventilation in the prone position helps to enhance oxygenation, improves ventilation-perfusion mismatch, prevents ventilator-induced lung injury (VILI) and increases postural drainage of secretions. Patients of Guillain Barre Syndrome usually have a good outcome but they suffer mortality due to nosocomial infections and ventilator associated pneumonia (VAP) is the leading nosocomial infection. We studied the use of prone ventilation to reduce the incidence of ventilator associated pneumonia in these patients. Hypothesis: Elective prone ventilation may reduce the complications of prolonged mechanical lung ventilation in patients of non-hypoxemic respiratory failure. Methods: Over a period of three years we used prone ventilation in 40 patients of Guillain Barre Syndrome requiring prolonged mechanical ventilation as a preventive strategy for ventilator associated pneumonia. Patients requiring mechanical ventilation for more than 21 days were only analyzed. Elective biweekly prone ventilation was used in addition to other standard practices for prevention of ventilator associated pneumonia. We gave prone ventilation for planned duration of 8 hours (range 8 ⫹ 1.5 hrs) during each session. Results: The mean age of patients was 32.4years.The average length of ICU stay for our patients was 40 ⫹ 6 days. Only 2 out of 40 patients suffered from ventilator associated pneumonia. 13 patients with clinical and radiological evidence of basal collapse and atelectasis at ICU admission responded well to early prone ventilation therapy. No major complication of prone position ventilation was noted in any patient. There were minor complications like pressure sore in 06 patients Conclusions: Prone ventilation can be a useful adjunct strategy to prevent ventilator associated pneumonia in patients with non-hypoxemic respiratory failure requiring prolonged mechanical ventilation.


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TIMING OF TRACHEOSTOMY: COMPARISON OF MEDICAL, SURGICAL, AND TRAUMA PATIENTS

A SIMPLE METHOD TO ENHANCE USE OF LOWER TIDAL VOLUME MECHANICAL VENTILATION

Lindsay Fairfax, Carolinas Medical Center, A. Christmas, FH Sammy Ross Trauma Center, Vaughn Braxton, Klint Janulis, Ronald Sing, Carolinas Medical Center

Mark Mazer, Thomson Pancoast, East Carolina University, Charles Bangley, Pitt County Memorial Hospital, Qiang Wu, East Carolina University

Introduction: The timing of tracheostomy has been shown to vary widely across hospitals and individual intensivist practice, with earlier tracheostomy being associated with decreased intensive care unit length of stay. Hypothesis: We hypothesized that timing to tracheostomy would differ between groups, with trauma and surgical patients receiving earlier procedures. Methods: The procedures database was quiered for all tracheostomies performed in 2009. A retrospective chart review was then performed to determine the indication and timing of tracheostomy. Demographics and outcomes were also recorded. Timing to tracheostomy, length of stay, and length of stay post-tracheostomy was then compared with a p ⬍ 0.05 considered significant. Results: In 2009, there were 407 tracheostomies performed at our institution. Pediatric (29), emergent (26), and elective/ENT (43) procedures were excluded. Patients were then divided by service into medical (n ⫽ 111, 35%), surgical (n ⫽ 79, 24%) and trauma (n ⫽ 133, 41%) groups. Trauma patients were significantly younger (49 ⫾ 18 years) than medical (54 ⫾ 17 years) and surgical (60 ⫾ 12 years) patients. Timing to tracheostomy was signifcantly shorter in trauma patients (8 ⫾ 5 days) compared to the other two groups (surgical 15 ⫾ 11 days, medical 15 ⫾ 14 days). However, overall length of stay was similar between trauma (30 ⫾ 16 days) and medical (31 ⫾ 16 days) patients and longer in surgical patients (46 ⫾ 30 days). Time to hospital discharge following tracheostomy varied significantly between groups, with the shortest being medical (17 ⫾ 13 days), followed by trauma (22 ⫾ 16 days) and surgical (29 ⫾ 55 days). Conclusions: Trauma patients, who are younger and more often male, underwent significantly earlier tracheostomy as compared to medical or surgical patients. Time to discharge post-tracheostomy varied between the three groups, with surgical patients having a longer overall length of stay. However, despite undergoing earlier tracheostomy, trauma patients had a similar overall length of stay compared to medical patients. Future work will concentrate on differences in ICU length of stay and patient outcomes.

Introduction: Implementation of evidenced based concepts into clinical practice is a challenge for critical care practitioners. Evidence suggests that use of lower Vts (tidal volume) is beneficial for patients with lung injury and those without underlying lung disease. Unfortunately lower Vt ventilation is under-utilized in routine practice.We surveyed the use of Vts in our medical intensive care unit (MICU). Despite conceptual support, use of standard order sets, ventilator protocols and a safety checklist, at baseline most patients were ventilated with Vts in excess of 8 ml/kg PBW. This prompted efforts to comprehend the cause of the gap between intended and actual practice. The respiratory flow sheet had a designated field for absolute Vt, but did not have fields to record PBW or Vt expressed as ml/kg PBW, though ad hoc annotation was permitted. Hypothesis: We hypothesized that adding fields for PBWand Vt ml/kg PBW to the respiratory flow sheet would increase the use of Vts less than 8 ml/kg PBW. Methods: The respiratory flow sheet was checked for documentation of PBW and Vt ml/kg PBW before and after intervention. Baseline data was collected from 29 patients, and from 30 patients receiving any mode of invasive mechanical ventilation after intervention. If missing, Vt ml/kg PBW was calculated at data collection. Results: At base line PBW was charted for 19/29 (66%) patients; none had Vt ml/kg PBW noted. The mean tidal volume of the controls was 8.28 ⫹/⫺ 2.18 ml/kg PBW. Seventeen (59%) patients received Vt in excess of 8 ml/kg PBW. After intervention 24/30 patients (80%) had PBW and 27/30 (90%) had Vt ml/kg PBW recorded. The mean tidal volume fell to 7.50 ⫹/⫺ 2.28 ml/kg PBW. This 9.1% reduction of 0.78 ml/kg PBW was significant (p ⫽ .037). The number of patients receiving Vt in excess of 8 ml/kg PBW dropped to 9 (30%). Conclusions: Ultimately failure to use lower Vts in our MICU is related to how practitioners think and communicate. A change of environment to obligate recording PBW and Vt as ml/kg PBW serves as a mental prompt, and helps practicioners conceptualize in terms of PBW-adjusted rather than absolute Vts. The intervention worked, as most patients are now ventilated with Vts less than 8 ml/kg PBW.

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HIGHER RESPIRATORY COMPLIANCE IS ASSOCIATED WITH MORE BALANCED APEX/BASE LUNG SOUND DISTRIBUTION

DEMOGRAPHICS AND OUTCOMES OF A REGIONAL WEANING CENTRE, CANADA

Clarence Finch, MD Anderson Cancer Care Center, Laura Withers, Quan Nguyen, MD Anderson Cancer Center, Joseph Nates, MD Anderson Cancer Center/University of Texas

Introduction: Various studies describe organizational models and outcomes for patients experiencing protracted weaning, though none include data from Canada. Hypothesis: To characterize the population of a specialized 6-bed weaning centre admitting medically stable patients ventilated for ⱖ 21 days from intensive care units (ICUs) in Ontario, Canada and to report outcomes and discharge disposition. Methods: Retrospective cohort study. Data were extracted from the medical record and independently verified. Results: A total of 118 patients were admitted from Jan 2004 to Jul 2009. Seven (5.9%) patients received only noninvasive ventilation (NIV), 16 (13.6%) were weaned to mask oxygen via tracheostomy prior to admission, and 95 (80.5%) were invasively ventilated. Mean age was 67 ⫾ 13.4 years; 63 (53.4%) were male. The number of pre-morbid conditions ranged from 0 to 8. Median ICU length of stay prior to admission was 50.9 (interquartile range [IQR] 35.1 to 82.2) days. Most frequent indications for prolonged mechanical ventilation were: COPD with (33, 28.0%), and without (11, 9.3%), infective exacerbation; pneumonia (24, 20.3%); neuromuscular disease (15, 12.7%); and acute respiratory distress syndrome (13, 11.0%). Of the 95 patients receiving invasive ventilation on admission, 62 (65.3%) achieved 24 hours of spontaneous breathing by a median 13.5 (IQR 7.9 to 27.1) days.The Kaplan-Meier estimated median duration of stay in the weaning centre was 54.0 (IQR 28.1 to 91.0) days. For patients discharged alive, 51 (43.2%) were discharged back to the referral institution, 29 (24.6%) to a rehabilitation facility, 22 (18.6%) to home, and 2 (1.7%) to a long term ventilation centre. Of the 95 invasively ventilated patients, 42 (44.2%) were weaned and decannulated, 9 (9.5%) were weaned with tracheostomy retained, 4 (4.2) required part-time NIV, 23 (24.2%) remained ventilator dependent, 4 (4.2 %) required part time ventilatory support, and 13 (13.7%) died. Conclusions: Despite a prolonged ICU stay prior to referral, weaning outcomes were similar to those previously reported in other countries and organizational care models. Funding: TEGH Foundation

Introduction: Shift of lung sounds distribution towards the diaphragmatic lung areas has been associated with increase in positive end-expiratory pressure (PEEP) in PEEP-responder patients. In the present study, we explore the correlation between apex/base lung sound distribution and dynamic compliance in mechanically ventilated cancer patients. Hypothesis: We hypothesize that vibration response imaging can be used in determining flow characteristics in mechanically ventilated cancer patients. Methods: Thirteen lung sound measurements were obtained with the Vibration Response Imaging (VRI) lung sound monitoring system in nine mechanically ventilated cancer patients (six males, three females, age 59 ⫾ 11). Chest radiograph findings included pneumonia in five patients and atelectasis or pleural effusion in 4 patients. Respiratory compliance was obtained at the time of the lung sound measurement and was correlated with the apicodiaphragmatic ratio (ADR) calculated as the ratio between lung sound recorded at the apex and at the base at peak inspiration. Two variant data observations highlighted in the Figure were eliminated from the statistical analysis. Results: ADR was significantly lower (1.5 ⫾ 0.4 versus 2.4 ⫾ 0.4, p ⫽ 0.01, Mann Whitney U-Test) in patients with higher compliance (⬎40mL/cmH 2 O) than in patients with lower compliance (⬍40mL/cmH 2 O). Moreover, a strong correlation was obtained between respiratory compliance and ADR (r ⫽ 0.85) as shown in the Figure. Conclusions: More homogeneous lung sound distribution, illustrated by a more balanced apex/base lung sound ratio, was correlated with higher respiratory compliance in mechanically ventilated cancer patients.

Louise Rose, University of Toronto, Ian Fraser, Toronto East General Hospital


370 MECHANICAL VENTILATION FOR PEDIATRIC AND YOUNG ADULT PATIENTS UNDERGOING HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY Rizalina Mauricio, MD Anderson Cancer Center, Regina Okhuysen-Cawley, MD Anderson, Andrea Hayes- Jordan, Holly Green, Lianchun Xiao, Jose Cortes, MD Anderson Cancer Center, Rodrigo Mejia, University of Texas MD Anderson Cancer Center Introduction: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin appears to be a promising therapy for peritoneal carcinomatosis due to desmoplastic small round cell tumor and other sarcomas. Extensive peritoneal resection followed by thermal destruction residual tumor cells is thus an essential component of this operation and is accompanied by significant fluid shifts. Hypothesis: We speculated that older patients with shorter procedures would extubate early (within the first 48 hours) vs. late (beyond 48 hours). Methods: The medical records of 19 patients referred to MD Anderson Cancer Center for this procedure to undergo 21 procedures and spanning from January 2005 to October 2009 were reviewed following IRB approval. Perioperative management included bowel preparation, laparotomy for cytoreduction with HIPEC with cisplatin, and indicated supportive care in the intensive care unit, including conventional mechanical ventilation in all cases. The mean intraoperative fluid balance and time under anesthesia were 5005 ml and 790 min respectively. Results: We were unable to define any correlation between length of mechanical ventilation (LMV) and cumulative fluid balance on statistical analysis, as depicted in table 1. However, there was a tendency towards earlier extubation for older and heavier patients. Table 1 displays the Spearman correlation coefficients of LMV with the other three variables. The analysis suggested a tendency negative correlation of LMV with age (Pho ⫽ -0.40, p ⫽ 0.07) and weight (Pho ⫽ -0.39, p ⫽ 0.08), however the correlation was not statistically significant. No significant correlation was detected between LMV and cumulative fluid either (p ⫽ 0.83). Conclusions: Small children undergoing HIPEC may be at higher risk for prolonged mechanical ventilation. Further study of patient characteristics is needed in order to optimize ventilatory management in this complex patient population. This information may be of value for the anticipatory guidance of families preparing for this procedure.


Poster: Pulmonary - Therapeutics 371

372

RANDOMIZED COMPARISON OF MAGNESIUM SULFATE, TERBUTALINE AND AMINOPHYLLINE INFUSION IN ACUTE SEVERE ASTHMA IN CHILDREN

SEVOFLURANE MAINTAINED BETTER OXYGENATION AND IMPROVES LUNG DAMAGE IN A MODEL OF SEVERE ARDS COMPARED TO PROPOFOL

Sunit Singhi, Post Graduate Institute of Medical Education and Research, Arun Bansal, Kapil Chopra, Sudhanshu Grover, PGIMER

Carlos Ferrando, Hospitla Clinico Universitario Valencia, Joaquin Moreno, Marina Soro, Hospital Clıńico Universitario Valencia, Javier Belda, Hospital Clinico Universitario Valencia

Introduction: Intravenous (IV) magnesium sulfate (MgSO4), terbutaline and aminophylline infusions, all are used in treatment of acute severe asthma in children; published data to determine the most effective option among these are scanty. We have compared efficacy of the three drugs in acute severe childhood asthma unresponsive to standard firstline treatment. Hypothesis: IV Mg SO4 is more effective than IV aminophylline and terbutaline. Methods: In a randomized open label study in a tertiary care teaching hospital, we enrolled 100 consecutive children, 1 to 12 years, with acute severe asthma unresponsive to standard first-line treatment (oxygen, 3 doses of nebulized salbutamol, budesonide and ipratropium bromide and one dose of systemic corticosteroid within one hour). They were randomized to receive IV Mg SO4 (50 mg/kg over 20 mins), terbutaline (10 mcg/kg bolus over 30 mins then 0.1 mcg/kg/min) or aminophylline (5 mg/kg loading then 0.9 mg/kg/h) for one hour. Respiratory rate, oxygen saturation (in room air), retractions, wheeze and dyspnea were monitored. Clinical Asthma Severity Scores (CASS) was calculated from the above at 1, 2, 4, 8 and 12 hours. Primary outcome measure was treatment success, defined as improvement in CASS of ⱖ 4 at the end of 1 hour, and secondary outcome was CASS score trend over 12 hours. Informed written parental consent was obtained. Study was approved by Institute Ethics Committee. Results: All groups were similar; mean CASS were 9.9 in MgSO4, 10.7 in terbutaline and 10.8 in aminophylline group; p ⫽ 0.06. Treatment success was noted in 33 (97%) of 34 patients in MgSO4, 23 (70%) of 33 in terbutaline and 23 (70%) of 33 in aminophylline group (P ⫽ 0.006). MgSO4 group had lowest CASS scores over 12 hours (p ⬍ 0.001), least number of patients with retractions, wheeze, and dyspnea, and higher mean oxygen saturations after one hour of treatment(P ⬍ 0.05). No side effects was noted with MgSO4, two patients had hypokalemia with ECG changes with terbutaline and 9 had nausea and/or vomiting with aminophylline group, P ⫽ 0.001. Conclusions: Magnesium sulfate was more effective than terbutaline and aminophylline in treatment of patients with acute severe asthma unresponsive to standard first line treatment.

Introduction: Respiratory distress syndrome (ARDS) is characterized by hypoxemia due to shunting, increased pulmonary edema (ELWI) and pulmonary vascular permeability (PVPI). The potential inhibition of hypoxic pulmonary vasoconstriction (HPV) caused by sevoflurane could limit its use in anesthesia for patients with ARDS. However there is no evidence about the use of sevoflurane in lungs with ARDS. It has been recently shown that sevoflurano improves oxygenation and attenuates lung damage in a model of mild lung injury (ALI) compared to propofol. Hypothesis: The goal of this study was to show that, in a model of ARDS, sevoflurane produced better oxygenation , lung function and haemodynamics compared to propofol. Methods: An experimental, prospective, randomized and controlled study was carried out in 16 pigs. The number of animals was based on previous studies.They were randomized to receive a anesthetic doses of propofol (P) (AstraZeneca, Wedel, Germany) 5-7mg kg-1 h-1 or sevoflurane (S) (Abbott Laboratories) using the Anaconda device (ACD) (Sedan Medical, Uppsala, Sweden) to obtain endtidal concentration of 1.5 vol%. Monitoring and anesthetic management were identical for both groups except for sedation. The ARDS was made through multiple saline lavage. Respiratory/pulmonary parameters: PaO2, ELWI and PVPI and haemodynamicparameters: cardiac index (CI), mean arterial pressure (MAP) and global endiastolic volume (GEDI) were collected at 10 and 240 min after confirmation of ARDS (PaO2/FiO2 ⬍ 200 mmHg). We used SPSSTM 15.0 (SPSS Inc., Chicago, IL) for statistical test (ANOVA) and Bonferroni for multiple comparisons, significance when p ⬍ 0, 05. Results: The group S showed better PaO2/FIO2 (p ⫽ 0.04) (95 CI 0.54 to 72.45), less ELWI (p ⫽ 0.04) (95 % CI 0.12 to 12.12) and PVPI (p ⫽ 0.04) (95 % CI 0.07 to 3.32) compared to propofol. There were no differences in IC (p ⫽ 0.09), MAP (p ⫽ 0.2) and GEDI (p ⫽ 0.7). Conclusions: In this model of severe ARDS, sevoflurane preserves better oxygenation levels as a result of fewer pulmonary edema (ELWI) due to a less impairment of alveolar membrane permeability (PVPI) compared to propofol. There were no haemodynamic differences between the two anesthetics.

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FEASIBILITY OF PERCUTANEOUS VAGAL ELECTRICAL STIMULATION FOR THE TREATMENT OF ACUTE ASTHMA EXACERBATION

HIGH FLOW NASAL CANNULAE OXYGEN THERAPY REDUCES THE RATE OF TRACHEAL INTUBATION IN INFANTS WITH ACUTE LUNG INJURY

James Miner, Hennepin County Medical Center, Lawrence Lewis, St. Louis University Hospital, Giselle Mosnaim, Rush University Medical Center, Joseph Varon, The University of Texas, Thomas Hoffmann, ElectroCore LLC

Beth Forst, Tracey Herstich, Kathleen Taylor, Donna Carroll, David Gothard, Michael Forbes, Akron Children’s Hospital

Introduction: In certain asthmatic patients, current pharmacological treatments may be insufficient resulting in prolonged Emergency Department (ED) monitoring or hospital admission. Hypothesis: A vagal electrical stimulator could improve airflow limitation in patients with acute asthma exacerbation. Methods: This was a prospective multicenter observational study of adult patients undergoing treatment for asthma with a measured FEV1 between 25%-70% of predicted following one hour of standard of care (SOC) treatment in the ED without improvement. SOC included inhaled beta agonists, corticosteroids, and supplemental oxygen. Consenting patients had a percutaneous electrode placed near the carotid sheath using ultrasound guidance. Patients were monitored for adverse events, perceived work of breathing, and FEV1. Treatment success was determined by the percentage who responded with a clinically meaningful increase in FEV1 of at least 12% compared to baseline. Patients reported dyspnea using a 100mm visual analog scale (VAS). 24 patients were enrolled. Devices were placed with patients in a semirecumbant position using local anesthesia. The mean insertion time was 10 min. Stimulation (25Hz, 0.2ms pulse width) was administered for 60 minutes within a range of 1-12volts with adjustments in voltage guided by symptomatic improvement, muscle twitching or patient discomfort. Results: At 15, 30, and 60 min, 54.2%, 66.7%, and 76.2% of patients had achieved the 12% improvement in FEV1, respectively. The median FEV1 improvement for the responders vs. non-responders was 30.9% vs. 3.0% at 15 min, 39.4% vs. 6.2% at 30 min, and 42.5% vs. 8.3% at 60 min. Sixteen patients provided dyspnea VAS evaluations. The median VAS improvement from baseline at 15, 30, and 60 min was 20mm (53.9%), 31mm (69.1%), and 34mm (81.0%), respectively. There were no episodes of increased tachycardia, bradycardia, hypotension, or diaphoresis during or post treatment. No patient discontinued stimulation due to pain or muscle twitching. Conclusions: Our study suggests that percutaneous vagal electrical stimulation safely improves airflow limitation and may offer a new therapeutic approach to the treatment of patients with an acute asthma exacerbation.

Introduction: Noninvasive positive pressure ventilation (NIPPV) has been used with increased frequency to treat acute cardiac & respiratory failure in infants, children & young adults. While there is a growing body of evidence in adult ED and ICU care, the pediatric evidence base remains sparse. Adding to the data dearth are the complex variables of patient size, pathophysiology & the numerous NIPPV modalities (BiPAP, CPAP, etc.). The optimum application of each modality to specific disease process & populations remains incompletely understood. The delivery of high flow nasal cannula oxygen therapy using the Vapotherm® system (Vapotherm, Inc Troy, MI, USA) [VT] has been used in our urban med/surg PICU (23 beds, 1400 annual discharges) since 2005. From 2/2006 to 2/2007 the device was unavailable due to bacterial contamination. Since FDA re-approval, it has been used regularly. Hypothesis: Capitalizing on the historically convenient withdrawal and reintroduction of the device, we hypothesized that VT makes no difference in the rates of mechanical ventilation (MV) in infants ⬍ 24 mos admitted to the PICU to treat acute lung injury (ALI) due to bronchiolitis or pneumonia. Methods: Using local data from the Virtual Pediatric Systems (VPS, LLC Alexandria, VA, USA; https://www.portal.myvps.org) we identified all infants ⬍ 24 mos admitted with ICD-9 codes 466, 480, 480.1, and 487. Outcomes were compared among the 3 VT epochs (VT-intro [VT-1], VT-withdrawal [VT-0], VT-return [VT-2]). Significance was defined as p ⬍ 0.05. Results: During VT-1, VT-0, and VT-2, 68, 90 and 305 patients, respectively, met criteria. The rates of MV were 52.9%, 70% and 42.9%, respectively. Comparison between VT successes and non VT successes, 77/93 (82.8%) and 100/212 (47.2%) using the z test of binomial proportions showed a highly significant (z ⫽ 6.84, p ⬍ 0.001) difference. Conclusions: Our analysis rejected the null hypothesis that VT has no impact on the rates of MV in infants with ALI due to bronchiolitis or pneumonia. There was a nearly 30% actual reduction in MV rates between VT-0 & VT-2. Further studies are needed to compare severity of illness and NIPPV modalities to optimize the application of VT and other promising NIPPV modalities.


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SEVOFLURANE AMELIORATES LUNG INFLAMMATORY RESPONSE AND IMPROVES OXYGENATION IN A MODEL OF SEVERE ARDS COMPARED TO PROPOFOL

SERIAL CARDIAC TROPONIN LEVELS AS MARKER OF CARDIAC TOXICITY IN CHILDREN WITH STATUS ASTHMATICUS TREATED WITH INTRAVENOUS TERBUTALINE

Carlos Ferrando, Hospitla Clinico Universitario Valencia, Joaquin Moreno, Hospital Clıńico Universitario Valencia, Jose Carbonell, Hospital Clinico Universitario de Valencia, Gerardo Aguilar, Marina Soro, Hospital Clıńico Universitario Valencia, Javier Belda, Hospital Clinico Universitario Valencia

Meena Kalyanaraman, Children’s Hospital of New Jersey, Utpal Bhalala, The Children’s Hospital of Philadelphia, Michael Leoncio, Miami Childrens Hospital

Introduction: Respiratory distress syndrome (ARDS) is a lung disease characterized by an activation of the inflammatory cascade. The only treatment that reduces mortality is lung-protective ventilation. This ventilation requires patient sedation. The intravenous sedation is the most commonly used, an alternative is inhalational sedation with halogetaned agents. Recently, sevoflurane has been shown to modulate the lung inflammatory response in a model of mild lung injury (ALI) compared to propofol. Hypothesis: The goal of this study was to show that, in a model of a severe ARDS, sevoflurane ameliorates the inflammatory response and improves oxygenation compared to propofol. Methods: An experimental, prospective, randomized and controlled study was carried out in 16 pigs. The number of animals was based on previous studies. They were randomized to receive a anesthetic doses of propofol (P) (AstraZeneca, Wedel, Germany) 5-7mg kg -1 h -1 or sevoflurane (S) (Abbott Laboratories) using the Anaconda device (ACD) (Sedan Medical, Uppsala, Sweden) to obtain endtidal concentration of 1.5 vol%. Monitoring and anesthetic management were identical for both groups except for sedation. The ARDS was made through multiple saline lavage. PaO 2 /FiO 2 and cytokines in bronchoalveolar lavage (BAL) were determined at 10 and 240 min after confirmation of ARDS (PaO 2 /FiO 2 ⬍ 200 mmHg). We used SPSS 15.0 (SPSS Inc., Chicago, IL) for statistical U the Mann Whitney test (PMN neutrophils) and ANOVA test (Cytokines and PaO 2 /FiO 2 ), significance when p ⬍ 0, 05. Results: Levels of cytokines in the S group were lower than those in P group. IL-1␤ (p ⫽ 0, 04) (95% CI 5, 1 to 736, 6), TNF-␣ (p ⫽ 0, 04) (95% CI 3, 9 to 598, 8) and IL-6 (p ⫽ 0, 03) (95% CI 19, 6 to 587, 7). PMN neutrophil count was lower in S group (p ⫽ 0, 007). The S group showed a better PaO2/FiO2. Conclusions: In this model of severe ARDS, sevoflurane ameliorates lung inflammatory response compared to propofol. This could be the reason for a better oxygenation in the sevoflurane group.

Introduction: There is lack of a consistent data on the occurence of cardiotoxicity from intravenous (IV) terbutaline and there is lack of guidelines for its monitoring in children with status asthmaticus. Hypothesis: Cardiac troponin I (cTnI) level is a marker of cardiotoxicity from IV terbutaline in children with status asthmaticus and correlates with asthma severity and risk factors for severe asthma. Methods: In this prospective study, 20 consecutive pediatric patients with status asthmaticus who received IV terbutaline admitted to the PICU over a 21 month period were enrolled for the study. Asthma severity, BMI, epinephrine and steroid use and occurence of metabolic acidosis were noted for each patient. cTnI levels were obtained half hour before and 4 hours after terbutaline bolus and then every 24 hours until discontinuation of the continuous IV terbutaline. EKG was performed in patients with elevated cTnI. Data was analyzed using 2 tailed Student t test or Mann -Whitney test. Results: cTnI levels ⬎ 0.03 ng/ml was seen in 50% of patients with peak cTnI post-terbutaline bolus in 6 patients, during terbutaline infusion in 3 patients and pre-terbutaline use in 1 patient. EKG changes of myocardial injury normalized upon discontinuation of terbutaline in one patient who had significantly high cTnI (up to 3.79 ng/ml). All other patients with elevated cTnI had normal EKG. There was no statistical difference in terbutaline dose (p ⫽ 0.82) or duration (p ⫽ 0.85), asthma severity (p ⫽ 0.26), BMI (p ⫽ 0.24), steroid (p ⫽ 0.73) and epinephrine (p ⫽ 0.73) use, metabolic acidosis (p ⫽ 0.73) in patients with or without elevation of cTnI. Conclusions: Cardiac TnI does not correlate with dose or duration of terbutaline, asthma severity, BMI, epinephrine and steroid use and metabolic acidosis in children with status asthmaticus and can be found prior to terbutaline use. Clinically significant cardiotoxicity is rare with terbutaline use and is reversible upon discontinuation of terbutaline.

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USE OF RESCUE THERAPIES FOR ARDS PATIENTS: POPULATION-BASED STUDY IN OLMSTEAD COUNTY, MINNESOTA

AMINOPHYLLINE TREATMENT MAY INCREASE DURATION OF PEDIATRIC INTENSIVE CARE UNITS (PICU) ADMISSION FOR PATIENTS WITH SEVERE STATUS ASTHMATICUS

Sonal Rachmale, Guangxi Li, Adil Ahmed, Rahul Kashyap, Thomas Bice, Michael Wilson, Ognjen Gajic, College of Medicine, Mayo Clinic

Abdallah Dalabih, Donald Arnold, Rick Barr, Vanderbilt Children’s Hospital

Introduction: Salvage therapies for severe hypoxemia in ARDS includeHigh Frequency Oscillation (HFO), ECMO, inhaled vasodilators (nitric oxide-iNO and inhaled prostacyclin- iPCI), and prone positioning. Degree of utilization for these therapies in the population is not clearly documented. Mayo Clinic provides ready and exclusive access to rescue therapies to Olmsted County population allowing for detailed clinical epidemiologic studies. Hypothesis: In this population-based study we describe the use of the ARDS rescue therapies and associated outcomes in a defined suburban population. Methods: This is a retrospective review of patients with ARDS admitted from the Olmstead County from 2004 to 2008. The presence of ALI and ARDS was independently confirmed according to the AECC criteria. The use of rescue therapies, severity of illness and hospital outcomes was abstracted from electronic medical records using standard criteria. Outcomes of ARDS patients who did and did not use rescue therapies were compared using univariate and multivariate logistic regression analysis. Results: Among 270 ARDS patients from 2004 to 2008, 34 (12%) received at least one of the above rescue therapies. Among these 34, HFO only was used in 12 (35%), prone positioning in 11(32%), iNO in 19 (55%) and inPCI in 5 (14, 7%) patients. Ten patients among the group received some combination of therapies (HFO ⫹ iNO ⫽ 7, HFOV ⫹ PP ⫹ iNO ⫽ 2, iNO ⫹ PP ⫽ 1). None of the patients received ECMO. Patients getting rescue therapies were younger (54 vs. 67, p ⫽ 0.005) and had lower PaO2/FIO2 (65 vs. 95 p ⫽ 0.001). Severity of illness (APACHE IV scores) was similar between two groups (68 vs. 58, p ⫽ 0.15) There was no difference in hospital (38% vs 39%, p ⫽ 0.93) and one year mortality (47% vs 49%, p ⫽ 0.86), 28 ventilator-free days (12 vs 14, p ⫽ 0.77) and ICU length of stay (8 vs.7, p ⫽ 0.11). When adjusted for age, APACHE IV and nadir PaO2/FIO2, the use of rescue therapies did not influence hospital mortality (OR 0.64, 95% CI 0.26-1.52). Conclusions: In this population-based study rescue therapies were used in a minority of ARDS patients. They are preferred for younger patients and worse hypoxemia with similar outcomes compared to patients without these therapies.


Introduction: Aminophylline is not recommended by the National Heart, Lung and Blood Institute and there is limited information regarding the benefit of it in contemporary treatment algorithms of severe asthma exacerbation. However it continues to be used in some PICU’s. Hypothesis: For severe asthma exacerbations, aminophylline added to systemic corticosteroid and inhaled albuterol decreases length of stay (LOS) in the PICU. Methods: We retrospectively compared patients admitted to our PICU with severe asthma (Pediatric Asthma Scores [PAS] of 12-15) who received aminophylline infusion with patients matched by PAS score who did not, from Jan.2007-Jan.2010. Respiratory Therapists scored PAS and administered albuterol treatments by protocol. The primary outcome measure was functional length of stay (FLOS, time from admission to PICU to q2 hour albuterol), the time at which patients could be transferred to a floor bed. A secondary outcome was time to symptom relief (PAS ⬍ 7). We used Cox proportional hazards to examine associations of aminophylline treatment with these time-to-event outcomes, adjusted for baseline PAS, age, race and gender. We considered two-sided P values of ⬍ 0.05 to be statistically significant. Results: FLOS was longer for the 49 subjects who received aminophylline than for the 47 who did not (hazard ratio for FLOS in PICU: 2.526, CI 1.563, 4.082 P ⬍ 0.001). Within the aminophylline group, those with drug level ⬎ 10 mcg/ml had longer FLOS (2.186 Hazard ratio, P ⫽ 0.0225) than those with drug level ⬍ 10 as well as time to symptom relief (2.481 Hazard ratio, P ⫽ 0.0085). There was a trend toward an association of increasing drug level and FLOS (P ⫽ 0.068). Conclusions: Adding aminophylline to corticosteroid and inhaled albuterol treatment regimens is associated with statistically and clinically significant increases in FLOS and time to symptom relief in the PICU when adjusted for relevant subject characteristics. To our knowledge, this study is the first to demonstrate an association of aminophylline use with increased PICU LOS and time to symptom relief. Aminophylline should be used prudently in this setting.

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PROTOCOLIZED PICU MANAGEMENT OF STATUS ASTHMATICUS

STANDARDIZED ARDS ALGORITHM IMPROVES SAFE TRANSPORT OF CRITICALLY ILL PATIENTS FOR ECMO EVALUATION AT A REGIONAL ARDS CENTER

Todd Karsies, Margaret Chase, Nationwide Children’s Hospital/The Ohio State University College of Medicine Introduction: Status asthmaticus is a common PICU admission. Many standard therapies have significant toxicities and little evidence to support their use. Consequently, there is wide practice variability, even within an ICU, that may increase morbidity, cost, and resource utilization. Hypothesis: A standardized management protocol will improve PICU status asthmaticus outcomes. Methods: We retrospectively evaluated a PICU asthma protocol developed as a QI project. Data including medications used, respiratory and hemodynamic support, fluid requirements, LOS, and total charges were collected for 7 months after implementation on all PICU patients admitted with status asthmaticus, All PICU patients with status asthmaticus during the same time period the previous year were used for comparison. Results: 151 protocol patients were compared with 87 controls. The protocol patients were older (median 61 vs 39 months; p ⫽ 0.02) with a trend toward more patients with previous ICU admissions (23% vs 14%; p ⫽ 0.09). No differences were seen in ICU or hospital LOS, nor in fluid requirement, need for pressors or intubation. BiPap use significantly increased post-protocol from 21% to 48% (p ⬍ 0.0001) and terbutaline use decreased from 31% to 19% (p ⫽ 0.03). For patients requiring BiPap, protocol patients had significantly decreased ICU LOS (4 vs 5 days; p ⫽ 0.01) and cost ($29107 vs $41641; p ⫽ 0.048) compared to controls. Finally, while no prospective severity score was used during the study, there appeared to be differences in overall severity of illness, as only 50% of controls required escalation of therapy beyond albuterol, steroids, and ipratropium compared to 67% of protocol patients (p ⫽ 0.02). Conclusions: Implementation of a protocol altered the PICU management of status asthmaticus but had unclear effects on outcomes. Differences in age or illness severity may account for perceived lack of benefit. For patients requiring BiPap, treatment per protocol did decrease LOS and cost, suggesting a greater benefit in patients with higher illness severity. Further work is needed to assess the benefit of this protocol as a clinical tool.

Muhammad Masood, Thomas Jeffrey, Pauline Park, Mark Lowell, University of Michigan, Craig Meldrum, Univeristy of Michigan Medical School, Carl Haas, Jonathan Haft, University of Michigan, Lena Napolitano, University of Michigan School of Medicine Introduction: Transport of critically ill patients with severe acute respiratory distress syndrome (ARDS) is challenging related to severe hypoxemia, hypercarbia, and hemodynamic instability. An ARDS algorithm was created for stabilization of critically ill patients prior to air transport to our regional ARDS center. Hypothesis: The use of a standardized ARDS algorithm will facilitate safe transport of ARDS patients. Methods: Retrospective review was performed of all Extracorporeal Membrane Oxygenation (ECMO) referrals transported to our institution over a 5 year period (7/2005–7/2010). This data serves as an update to previously reported 72 patients. The ARDS algorithm was initiated by the critical care air transport team on arrival at the referring institution with direct communication with the fellow/attending intensivist, and included recruitment maneuvers, advanced mechanical ventilation, inhaled nitric oxide, correction of respiratory acidosis with NaHCO3 and/or tromethamine, and critical care management. Optimal endpoints to initiate transport included target PaO2 60 mm Hg and arterial pH 7.30. Results: 162 patients with severe ARDS were successfully transferred by the critical care air transport team. 157 patients (96.9%) were successfully transported on first attempt; 5 patients (3.1%) failed initially and were transported after a second attempt. Patients were 47% female and 53% male; mean age was 39 (range, 8-80) years. 36 patients had 2009 Influenza A (H1N1) virus infection. Median (range) laboratory values: PaO2/ FiO2 ratio 66 (43–261), arterial pH 7.29 (6.90 –7.50), PaCO2 47 (20 –104) mmHg, PaO2 75 (42–290) mmHg, oxygen saturation 89% (63 – 100%), FiO2 1.0 (.90-1.0), PEEP 14.4 (5–32) cm H2O, peak inspiratory pressure 38 (18 –72) cm H2O. 59% of patients were on vasopressors, 3 were on drotrecogin alpha and 4 patients were pregnant. 28 patients received inhaled nitric oxide; 5 were nonresponders. 8 patients were transported on ECMO following cannulation at the referring hospital. No deaths occurred during air transport. Conclusions: Development and use of an ARDS algorithm for critical care air transport standardized management and facilitated safe transport of severe ARDS patients to definitive care.

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HUMIDIFIED HIGH-FLOW THERAPY VIA NASAL CANNULA FOR ACUTE RESPIRATORY FAILURE

ENDOBRONCHIA TRACHEAL STENT PLACEMENT AS ALTERNATIVE TREATMENT FOR IATROGENIC TRACHEAL TEAR DUE TO ENDOTRACHEAL INTUBATION

Steven Johnson, University of Maryland School of Medicine, Robin Smith, Jeff Ford, Daniel Herr, University of Maryland Medical Center, John Straumanis, Deborah Stein, University of Maryland School of Medicine, Carl Shanholtz, Univ. of Maryland School of Medicine Introduction: High-flow therapy (HFT) provides improved humidification and warmth to allow nasal cannula therapy to achieve flows up to 40 liters/minute thereby providing inspiratory assistance and expiratory resistance. Although used in neonatal populations, little has been published on its use in older children and adults. Hypothesis: HFT will reduce the need for intubation or BiPAP in pediatric and adult patients with acute respiratory failure. Methods: Retrospective review of prospectively collected data obtained from consecutive patients undergoing HFT (Vapotherm) at a large academic medical center. Indications, prior type of ventilatory assistance, alternatives to HFT considered, and subsequent outcome including need for intubation or BiPAP were collected over a 10 month period. Results: 211 adult ICU patients (trauma: 92, SICU: 73, MICU: 46) and 120 PICU patients were administered HFT of which 221 (64%) were successfully weaned to low flow (⬍4 liters/minute) nasal cannula. Hypoxia (59.7%) was the most common indication followed by increased work of breathing/shortness of breath (23.6%) and hypoventilation with hypercarbia (13.1%). After initiating HFT, 67% of patients with hypoxia were weaned and 25% intubated; 75% with increased work of breathing/shortness of breath were weaned and 21% intubated; and 56%with hypoventilation and hypercarbia were weaned and 28% intubated. If HFT had not been used, intubation would have occurred in 63 (19.0%) of which 37 (59%) avoided intubation and were successfully weaned from HFT. Similarly 188 (56.8%) would have been placed on BiPaP mask of which 120 (64%) were successfully weaned from HFT and only 41 (22%) were intubated. Only 23 (7%) of HFT patients subsequently required BiPAP. Of the 37 patients on BiPAP prior to HFT, 24 (65%) were weaned successfully on HFT and only 5 (13.5%) were returned to BiPAP. Only 4 (1.2%) patients did not tolerate HFT. Conclusions: High-flow humidified therapy via nasal cannula can safely reduce the need for intubation and provides a more comfortable and effective alternative to BiPAP in patients with acute respiratory failure. HFT is a significant improvement in non-invasive ventilation for patients with acute respiratory failure.

Karina Pambukhchian, Mark Vollenweider, University of Florida, Rakesh Gupta, OrlandoHealth Case Reports – Introduction: The incidence of iatrogenic tracheal tear is approximately 1:20, 000 intubations. Surgical repair is associated with a high incidence of morbidity and mortality. We report a case of a patient with an iatrogenic tracheal tear who undersent successful repair with a tracheal stent with subsequent liberation from mechanical ventilation and discharge from the ICU. Case Presentation: 79 year old female intubated in ED for a diagnosis of aspiration pneumonia. After two days she developed hemodynamic collapse and a CXR demonstrated the new findings of extensive pneumomediastinum, subcutaneous emphysema and subdiaphragmatic air. CT scan showed the distal end of the endotracheal tube through the posterior membrane at the opening of the right mainstem (RMS) bronchus. Bronchoscopic evaluation revealed a 6cm tear from her subglottis to proximal RMS. Her posterior membrane had completely infolded and her esophagus was protruding into the tracheal lumen. Pt was deamed high risk surgical candidate secondary to the extensive injury and co-morbidities. A 20mm ⫻ 80mm covered tracheal stent was deployed and successfully closed her tear. She was transported back to the ICU and over a period of two weeks she progressively improved, without evidence of mediastinitis. She was then successfully liberated from mechanical ventilation. She was eventually discharged to a specialty care hospital for rehabilitation without pulmonary sequela. Discussion: Fatal complications occurs in 30% of patients with traumatic bronchial injuries. TBI should be considered in the right clinical presentation. Radiographic findings can include a completely normal radiograph in 10% of cases when the tear is incomplete. Pneumomediastinum and/or pneumothorax is common. Surgical repair confers a high morbidity and mortality. Tracheal stents offer an alternative treatment. Known complications from covered airway stents include migration, perforation, central and distal airway obstruction and granulation tissue formation. Conclusions: Iatrogenic TBI is a devastating injury that can be successfully treated with endobronchial deployment of tracheobronchial stents.(3 images available-xray ⫹ bronch)


Poster: Renal 383

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THE RENAL SAFETY OF MRI WITH GADOLINIUM IN CRITICAL CARE

PREDICTIVE POWER OF CYSTATIN C TO DETECT ACUTE KIDNEY INJURY IN PEDIATRIC CARDIAC SURGERY PATIENTS

Nicole Harlan, Vikas Kumar, Sonali Sakaria, Andrew Simpson, Sebastian Perez, Ram Subramanian, Emory University Introduction: Intravenous contrast enhanced imaging enhances the detection of pathology in critical illness. Given the risk of contrast nephropathy associated with iodinated CT contrast, alternate contrast modalities need to be examined, particularly in the setting of renal insufficiency. Hypothesis: The purpose of this study was to examine the renal safety of MRI with gadolinium in critically ill patients. Methods: The study involved a retrospective analysis of 222 ICU patients at a single academic center during 2007 and 2008, who received an MRI imaging study with gadolinium in the absence of renal replacement therapy. For each case, a serum creatinine and estimated GFR (as calculated by the MDRD equation) were recorded prior to, and 48 and 72 hours after the MRI. The serum creatinine and estimated GFR (eGFR) values before and after the MRI were compared for each case. In addition, the cases were analyzed for sub-acute complications of nephrogenic systemic fibrosis (NSF), a known complication of gadolinium in end stage renal disease. Results: The age of the patients ranged from 16 to 97 years, with 51% being female. The pre- MRI serum creatinine values ranged from 0.3 to 4.5 mg/dl, with 51 cases (25%) having values ⱖ 1.5 mg/dl and corresponding eGFRs ⬍ 60 ml/min. A comparison of the pre and post MRI serum creatinine and eGFR values demonstrated no statistically significant difference (P ⬍ 0.05), including those cases with a pre MRI serum creatinine ⱖ 1.5 mg/ dl. In addition, no cases of NSF were noted. Conclusions: These observations suggest that MRI with gadolinium is a non-nephrotoxic imaging modality in critically ill patients. Importantly, the renal safety of this modality extends to cases of renal insufficiency, where contrast enhanced CT may be contraindicated due to the risk of CT contrast nephropathy. These findings suggest that MRI with gadolinium can be a useful contrast enhanced imaging modality in critical care, especially in the setting of renal insufficiency.

Amanda Brooks, Jerome Lane, Shannon Haymond, Carl Backer, Eric Wald, Children’s Memorial Hospital Introduction: Acute kidney injury (AKI) is a frequent complication of pediatric cardiopulmonary bypass (CPB) that carries significant morbidity and mortality. The clinical standard uses serum creatinine (SCr) and urine output to detect AKI. However, SCr is a delayed, inadequate marker of acute changes in renal function and may not allow for intervention before permanent renal injury. Cystatin C (cysC) has emerged as a promising renal biomarker. Hypothesis: Cys C is a more sensitive predictor of AKI than SCr after pediatric cardiac surgery involving CPB. Methods: We analyzed data from 100 prospectively enrolled patients (95 complete datasets), aged 2 weeks to 18 years old after cardiac surgery involving CPB. SCr and cysC were followed pre-operatively and at 0, 8, 24, 48, 72 and 96 hours post-operatively. The primary outcome of AKI was defined by an increase in SCr ⬎ 50% from preoperative baseline. Secondary outcomes included length of stay in the ICU and hospital, length of mechanical ventilation and need for renal replacement therapy. We performed post-hoc analysis to assess the performance characteristics of both biomarkers according to pediatric-modified RIFLE criteria for R-risk, I-injury and F-failure. Results: 28.4% of patients (n ⫽ 27) developed AKI. CysC was not superior to SCr when predicting AKI. Both CysC and SCr had fair predictability for AKI at all time points, with CysC most sensitive at 48 hours, ROC-AUC 0.666 (95% CI 0.545-0.787) [p ⫽ 0.012]. Baseline cysC levels were elevated in patients with pre-existing renal insufficiency (p ⬍ 0.001). 30.5% of patients (n ⫽ 29) were classified as “Risk” and 5% (n ⫽ 5) developed “Injury.” CysC was a stronger predictor of the development of “Injury” compared to SCr at all time points studied. CysC was most sensitive at 24 hours AUC-ROC 0.897 (95% CI 0.797-0.996) [p ⫽ 0.001] vs SCr at the same time point AUCROC 0.668 (95% CI 0.383-0.953) [NS]. Conclusions: Both SCr and cysC are fair predictors of AKI after pediatric cardiac surgery. Preoperative cysC may be useful to risk-stratify patients with pre-existing renal insufficiency. Cys C may be an earlier, more sensitive predictor of kidney “Injury” as defined by pRIFLE classification when compared to conventional renal biomarkers.

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TIMING OF INITIATION OF RENAL REPLACEMENT THERAPY IN ACUTE KIDNEY INJURY: A META-ANALYSIS

FLUID STATUS AND CLINICAL OUTCOMES IN CRITICALLY ILL CHILDREN WITH SEPSIS: A RETROSPECTIVE ANALYSIS

Constantine Karvellas, University of Alberta, Maha Farhat, Massachusetts General Hospital, Imran Sajjad, Harvard University, Simon Mogensen, Hvidovre Hospital, Sean Bagshaw, University of Alberta Hospital Division of Critical Care Medicine

Joseph Angelo, University of Texas Medical School At Houston, Eric Williams, Jeanine Graf, Curtis Kennedy, Baylor College of Medicine, Stuart Goldstein, Cinncinnati Children’s Medical Center

Introduction: The purpose of this study was to systematically review the literature on the effect of timing of initiation of renal replacement therapy (RRT) in critically ill patients on clinical outcomes. Hypothesis: Earlier initiation of RRT in the critically ill will result in a decrease in 28-day mortality. Methods: PUBMED, EMBASE, Web of Science, Scopus and Cochrane Controlled Clinical Trials register amongst other sources were searched. Only studies with adult (over 18) critically ill patients with acute kidney injury were included. The exposure of interest was early vs. late initiation of RRT. The primary outcome of interest was 28-day mortality. Secondary outcomes were renal recovery and length of ICU/hospital stay. Results: We identified 14 unique controlled trials (5 prospective, 9 retrospective out of 1, 493 citations). One randomized trial (out of n ⫽ 2) fulfilled all quality indicators while none of the cohort studies (n ⫽ 12) met all quality indicators assessed. Early initiation of RRT was associated with a significant improvement in 28-day mortality (odds ratio 0.39, 95% confidence interval, 0.23 to 0.65). However, there was significant heterogeneity between the 14 pooled studies (I-squared ⫽ 77%). In sensitivity analysis, stratifying for patient population (surgical, n ⫽ 8 or mixed, n ⫽ 6) or study design (prospective, n ⫽ 5 or retrospective, n ⫽ 9) did not impact on the overall effect estimate (p ⬎ 0.2 for both). Meta-regression controlling for severity of illness on admission (APACHE II), baseline creatinine and urea did not impact on the overall effect estimate (p ⬎ 0.15 for both). We were unable to pool an effect estimate for renal recovery or length ICU/hospital stay (incomplete data). Conclusions: Early institution of RRT in critically ill patients with acute kidney injury may have a beneficial impact on survival. However, this conclusion is based on heterogeneous, poorly designed studies with a paucity of randomized controlled trials. Currently, a conclusive treatment recommendation can not be made.


Introduction: Maintenance of fluid balance is an important component of care for children in the pediatric intensive care unit(PICU). Previous studies show that degree of fluid balance in PICU patients affects multiple organ systems. However, limited supporting data has led to variability in fluid management strategies and the epidemiology of current fluid management practices in the PICU is not well described. Hypothesis: Lesser degrees of fluid overload (%FO) may improve outcomes in septic PICU patients. Methods: Retrospective review of patients with sepsis admitted to Texas Children’s Hospital (TCH) PICU during 2009 (n ⫽ 38). Demographics, anthropometric measures, vital signs, lab data and fluid balance at specified time points were obtained by integration of PICU database and medical records. Predictor variables were acute resuscitative fluids(defined as 60cc/kg in first 1 hr of admission) and late fluid administration (defined by percentage of fluid overload (FO) validated from the Prospective Pediatric CRRT registry). Pulmonary outcomes were FiO2, mean airway pressure, and PEEP. Cardiac outcomes were SBP, heart rate, shock index and administration of pressors. Serum creatinine changes defined kidney function using pRIFLE and AKI criteria. Hospital LOS and survival data were obtained. Data were controlled for disease severity by PRISM-III. Results: Mean volume of fluid received during the first 24 hrs of admission was significantly greater in non-survivors than survivors (257.6 vs 160.4 cc/kg; p ⫽ 0.004). Non-survivors achieved a significantly higher degree of %FO during the first 24 hrs of admission than survivors (17.5% vs 5.6%; p ⬍ 0.001). Overall median (25-75%ile) PRISM-III was 1.3 (0.4-5.0) and shock index was 1.6 (1.1-2.2). In sub-group analysis of patients in the upper 50th%ile of PRISM-III, the mean %FO remained significantly higher in nonsurvivors than survivors (p ⫽ 0.008). Conclusions: Mean fluid volume received and %FO at 24 hrs after admission were associated with mortality in septic PICU patients. Results of this study could inform treatment guidelines for optimal fluid administration and management of fluid overload in septic children.

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PREDICTIVE VALUE OF ASYMMETRICAL DIMETHYLARGININE LEVELS FOR ACUTE KIDNEY INJURY IN PEDIATRIC CARDIAC SURGERY PATIENTS WHO UNDERGO CARDIOPULMONARY BYPASS

DOES A SMALL INCREASE IN PLASMA CREATININE INCREASE ICU LENGTH OF STAY FOLLOWING THE ARTERIAL SWITCH OPERATION?

Amanda Brooks, Jerome Lane, Shannon Haymond, Children’s Memorial Hospital, Mark Wainwright, Northwestern University Feinberg School of Medicine, Carl Backer, Eric Wald, Children’s Memorial HospitaL Introduction: Asymmetrical dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is an emerging independent risk marker for endothelial dysfunction, adverse cardiovascular events and progression of chronic kidney disease. ADMA has not been investigated in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) in pediatric congenital heart surgery patients. Hypothesis: ADMA levels will be elevated in those patients who develop post-CPB AKI and will be associated with worse overall outcomes. Methods: We analyzed data from 100 prospectively enrolled patients (complete datasets for 95), aged 2 weeks to 18 years who underwent cardiac surgery involving CPB. AKI was defined as a peak serum creatinine (SCr) ⬎ 50% above a pre-operative baseline during the first 4 post-operative days. Our secondary outcomes: mortality, need for renal replacement therapy (RRT), length of stay in the intensive care unit and in the hospital and heart failure were also analyzed. Results: 28% (n ⫽ 27) patients developed AKI. There was no association with ADMA levels at any time point in the study and the development of AKI. The median preoperative ADMA level was 0.66 ␮M/L (IQR 0.58-0.85). Immediately post-operatively, median ADMA was 0.79 ␮M/L (IQR 0.48-1.1) in patients who developed AKI vs median 0.69 ␮M/L (IQR 0.40-0.98) in non-AKI patients (p ⫽ 0.59). In patients with pre-existing renal insufficiency (GFR ⬍ 60ml/ min/m2), median preoperative ADMA levels were elevated, 0.76 ␮M/L (IQR 0.421.1) [p ⫽ 0.01]. Median preoperative ADMA levels were greater in patients who developed the composite outcome of heart failure and need for RRT (p ⫽ 0.02). These patients also had a higher peak ADMA and a greater incremental change in ADMA levels from immediately post-operatively to peak levels (p ⫽ 0.016). Conclusions: ADMA levels are not associated with AKI after pediatric CPB and thus unlikely to be useful as a biomarker in this setting. They are significantly elevated in patients with pre-existing renal insufficiency, and may be useful as a risk-stratification tool. Elevated preoperative ADMA levels and larger increases in ADMA in the immediate post-CPB period may be associated with poorer cardiac and renal outcomes.

Derek Wheeler, Cincinnati Children’s Hospital Medical Center, Anne Lintzenich, Medical University of South Carolina, Erika Stalets, Cincinnati Children’s Hospital, Rajit Basu, Cincinnati Childrens’s Hospital, Catherine Krawczeski, Peter Manning, Cincinnati Children’s Hospital Medical Center, Prasad Devarajan, Cincinnati Children’s Hospital Nephrology Introduction: Acute kidney injury (AKI) is an independent risk factor for increased morbidity and mortality in critically ill children and adults. Some studies suggest that even modest elevations in plasma creatinine (Cr) are associated with increased complications and length of stay (LOS) in the ICU. We have previously shown that fluid overload is an important risk factor for increased postoperative ICU LOS following the arterial switch operation (ASO). Hypothesis: We hypothesized that relatively modest elevations in plasma Cr are associated with increased postoperative ICU LOS in children following the ASO. Methods: With IRB approval, we collected demographic data and clinical data for 85 infants undergoing the ASO between 19972008. We collected baseline Cr, daily Cr until POD #7, peak Cr (defined as highest Cr during hospital stay), discharge Cr, and the need for renal replacement therapy (RRT). Our local practice is to begin aggressive diuresis on POD #1, thus we chose not to analyze urine output as a marker for AKI. We conducted univariate and multivariate linear regression analysis to determine factors that were independently associated with prolonged postoperative ICU LOS. A p-value ⬍ 0.05 was significant. Results: All 85 infants (52 M:33F) in our cohort survived to hospital discharge. The median baseline Cr was 0.6, CPB time 184 mins, and aortic cross-clamp (XC) time 112 mins. 43 infants underwent concomitant VSD repair (50%), and 15 (18%) required arch repair for coarctation or interrupted aortic arch. The median peak Cr was 0.9 mg/dL, delta Cr 0.3 mg/dL, and discharge Cr 0.5 mg/dL. The median postoperative ICU LOS was 5 days. Several factors were associated with postoperative ICU LOS, including CPB time, XC time, net POD #1 fluid balance, peak Cr, delta Cr, and postoperative infections. These factors were included in multiple regression analysis - only CPB time was independently associated with postoperative ICU LOS (p ⫽ 0.008). Conclusions: The results of our retrospective analysis suggest that small changes in plasma Cr are not independently associated with prolonged postoperative ICU LOS in a relatively uniform cohort of 85 infants undergoing the ASO.

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DIFFERENCES IN RISK FACTORS FOR ACUTE KIDNEY INJURY BY CREATININE VERSUS URINE OUTPUT CRITERIA

DOES NGAL REDUCE COSTS? A COST ANALYSIS OF URINE NGAL (UNGAL) AND SERUM CREATININE (SCR) FOR ACUTE KIDNEY INJURY (AKI) DIAGNOSIS

Michael Shashaty, Robert Gallop, Nuala Meyer, University of Pennsylvania, Paul Lanken, Hospital of the U. of Pennsylvania, Daniel Holena, Hospital of The University of Pennsylvania, A Localio, Scarlett Bellamy, Sandra Kaplan, University of Pennsylvania, Jason Christie, University of Pennsylvania School of Medicine Introduction: Acute Kidney Injury Network (AKIN) consensus criteria define acute kidney injury (AKI) by changes in serum creatinine (Cr) and reduced urine output, but many studies define AKI by Cr criteria alone. It is unknown how this may affect conclusions about AKI risk factors. Hypothesis: Risk factors for AKI differ using a Cr-only versus a urine output-only definition of AKI. Methods: We analyzed a prospective cohort of patients admitted to the trauma ICU of an urban academic medical center. Demographic and clinical characteristics were evaluated as potential risk factors for AKI during the first 5 days of admission. AKI was defined as having satisfied Cr criteria only (AKI-Cr) or urine output criteria only (AKI-UO). A multinomial logistic regression model was created to determine independent risk factors for each category of AKI. Results: Of 418 subjects included for analysis, AKI-Cr occurred in 75 (18%) and AKI-UO in 67 (16%). On univariate analysis, AKI-Cr (v. no AKI) was associated with African American race (65% v. 47%), BMI (27.7 v. 25.6), penetrating trauma (44% v. 26%), AIS score for abdomen (2.3 v. 1.4), surgery prior to ICU admission (73% v. 50%), and administration of fluid (5.0L v. 3.7L) and PRBC (5.4u v. 2.3u), FFP (3.5u v. 1.2u), and platelets (0.5u v. 0.2u). AKI-UO (v. no AKI) was associated with hypertension (30% v. 13%), diabetes (13% v. 3%), age (47y v. 38y), BMI (32.9 v. 25.6), and administration of FFP (2.1u v. 1.2u). In the multinomial logistic regression model, independent risk factors for AKI-Cr were BMI, AIS score for abdomen, and PRBC administration while those for AKI-UO were BMI and diabetes mellitus. Hospital mortality rates for AKI-Cr, AKI-UO, and no AKI were 14.7%, 11.9%, and 3.8%, respectively. Conclusions: In this cohort of critically ill trauma patients, AKI defined by Cr had an incidence similar to AKI defined by reduced urine output. Both univariate and multinomial analyses identified significant differences in risk factors for AKI by criteria used. The study results suggest that a Cr-only AKI definition may not identify all risk factors associated with full AKIN criteria, and raise the possibility that Cr change and urine output may reflect different underlying pathophysiology.

Amay Parikh, Columbia University Medical Center, John Rizzo, Stony Brook University, Donald Chalfin, Abbott Diagnostics, Thomas Nickolas, Columbia Univeristy Medical Center Introduction: We previously demonstrated that uNGAL is a sensitive & specific test for detecting AKI in the emergency dept (ED), but its costs have not been established. Hypothesis: We hypothesized that uNGAL used with Scr would reduce costs in diagnosis & management of AKI in ED patients (pts) vs. Scr. Methods: We analyzed 1, 120 pts from EDs at 2 US hospitals from 2007-8. uNGAL measurements were recorded but unavailable to physicians. A simulation model was developed for 2 competing strategies of Scr vs. uNGAL plus Scr (uNGAL ⫹ Scr). Patients were classified into diagnoses of Normal, PreRenal, AKI, Stable CKD. Outcomes included costs for timely, delayed, or unnecessary AKI diagnosis, ICU admission & length of stay. Model inputs were derived from the data & literature. Regional DRG reimbursements were used to quantify costs. Results: For a hypothetical cohort of 10, 000 pts per center, treatment costs were $900 per patient (pp) in the Scr arm & $950 in the uNGAL ⫹ Scr arm. At center 1, uNGAL ⫹ Scr resulted in 1, 987 fewer pts with delayed diagnosis & treatment than Scr alone (448 vs. 2, 435 pts), while uNGAL ⫹ Scr identified 535 more pts who received unnecessary further testing. Similar findings were observed in center 2 (7, 829 more pts with delayed diagnosis & treatment; 311 more pts treated unnecessarily). Although initial evaluation costs at each center was $50 pp higher in the uNGAL ⫹ Scr arm, total cost declined as fewer pts had delayed diagnosis & treatment or unnecessary treatment (Center 1-$233 pp; Center 2-$3, 229 pp). Conclusions: uNGAL in addition to Scr improves patient management & reduces costs. uNGAL is a reliable, cost-saving test for evaluating suspected AKI, & savings are particularly high when Scr specificity is low.


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THE FIRST POSTOPERATIVE SERUM CREATININE PREDICTS SUSTAINED KIDNEY INJURY IN PATIENTS UNDERGOING SURGICAL TREATMENT FOR MALIGNANT MESOTHEOLIMA

LOW-INTENSITY CRRT MAY LEAD TO BETTER OUTCOMES IN SEPTIC AKI IN ICU

Annette Mizuguchi, Aya Mitani, Sushrut Waikar, Joseph Bonventre, David Sugarbaker, Brigham and Women’s Hospital, Gyorgy Frendl, Brigham & Women’s Hosp./Harvard Med.School Introduction: Cancer patients admitted to the intensive care unit with acute kidney injury (AKI) have higher mortality rates than non-cancer patients (Curr Opin Crit Care 2008; 14: 635-646; Crit Care 2005; 9: R700-709). However, it is unclear how AKI relates to the development of sustained kidney injury present 2-4 weeks after surgery. Sustained postoperative kidney injury has serious implications for cancer patients as many require additional treatment and follow-up diagnostic tests with potentially nephrotoxic agents. The identification of early biomarkers that predict sustained kidney injury is desirable as our current ability to detect AKI in a timely manner is limited. Hypothesis: Small acute changes in serum creatinine (sCr) measured immediately after surgery and during the subsequent 24-48 hours, will predict development of sustained kidney injury (50% loss of kidney function). Methods: Retrospective study of 313 patients who underwent extrapleural pneumonectomy. Results: Comparison of mean sCr values for patients who developed sustained kidney injury and those who did not develop it show a distinct time course and pattern of sCr elevation that persisted up to 100 days. We found that patients with a sCr increase ⱖ0.1 mg/dl immediately after surgery are at increased risk of developing sustained kidney (OR 3.01, CI95% [1.49-6.06]). Similarly, sCr elevation of ⱖ0.3 mg/dl during the first 24-hour and the subsequent 24-hour period reliably predicted sustained kidney injury. Conclusions: Small sCr changes in the immediate postoperative period (at the time of arrival to the ICU) are predictive of sustained injury (50% loss of kidney function). As one of the earliest diagnostic tests described thus far in identifying patients prone to sustained kidney injury, our sCr elevation-based diagnostic strategy will enable enrollment of patients into well-powered interventional studies to test new strategies for the salvage of kidney function.


Tomoko Fujii, St. Marianna University, Yoshitomo Namba, Showa University Fujigaoka Hospital, Shigeki Fujitani, St. Marianna University, Jun Sasaki, Kentarou Narihara, Showa University Fujigaoka Hospital, Yasuhiko Taira, St. Marianna University Introduction: Acute kidney injury (AKI) is a common condition in the intensive care unit (ICU). BEST Kidney study revealed hospital mortality of patients treated with continuous renal replacement therapy (CRRT) was over 55% and that of septic AKI on RRT was 68%. There is continuing controversy about the intensity of CRRT, high dose as 35-40mL/kg/hr vs. low dose as 20-25mL/kg/hr. Hypothesis: This study is to evaluate whether low-dose CRRT is adequate for survival of AKI patients in ICU. Methods: We conducted a retrospective multicenter observational study in two ICUs for patient in emergency room (ER) from January 2005 to July 2010. Delivered dose was calculated in patients treated with CRRT in the form of post-dilution continuous veno-venous hemodiafiltration. The main outcome measures were ICU mortality and hospital mortality. Results: Of the 165 patients treated with CRRT, 32 patients were excluded from analysis due to end-stage renal disease on hemodialysis before admission. All the patients were admitted from ER and the prevalence of sepsis was 55% (74/133). 23% of the patients (32/133) admitted after emergency surgical operation. The median delivered dose of CRRT was 16.8 mL/kg/hr (interquartile range (IQR) ⫽ 14 to 19). ICU mortality was 35% (43/122) and hospital mortality was 42% (56/132). Of note, hospital mortality of the septic patients was 45.9% (34/74). The median length of ICU stay was 10 days (IQR ⫽ 5 to 36.5) and of hospital stay was 36 days (IQR ⫽ 6.5 to 92). Data of baseline serum creatinine and urine output before the initiation of CRRT were available for 108 patients, and 28% fell in a RIFLE category of injury and 55% in failure at the CRRT initiation. The indication for CRRT initiation were RIFLE category of failure, severe acidemia, serum creatinine ⬎ 3.4 mg/dL, blood urea nitrogen ⬎ 70 mg/dL, hyperkalemia ⬎ 6.0mmol/L in descending order. Conclusions: The intensity of CRRT in this study was lower than published data. As our study includes only patients from ER, it is likely to be more reflective of actual clinical practice of septic AKI. This study supports that the intensity of CRRT for AKI as low as 17 mL/kg/hr could be contributive to survival of critically ill patients especially with sepsis.

Poster: Sepsis – Guidelines and Bundles 393

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IMPROVING OUTCOMES IN SEVERE SEPSIS AND SEPTIC SHOCK IN THE SURGICAL PATIENT POPULATION FOLLOWING IMPLEMENTATION OF AN EARLY SEPSIS INITIATIVE

TRANSFUSION OF PACKED RED BLOOD CELLS IS NOT ASSOCIATED WITH IMPROVED CENTRAL VENOUS OXYGEN SATURATION IN PATIENTS WITH SEPTIC SHOCK

Garrett Coyan, Niaman Nazir, Chad Cannon, Steven Tenny, Steven Simpson, Carla Braxton, Charles Richart, Michael Moncure, University of Kansas Medical Center Introduction: The development of severe sepsis or septic shock (SS/SS) is associated with significant morbidity and mortality in the surgical patient population. The initiation of sepsis quality initiatives has been shown to significantly reduce mortality in patients with SS/SS. While there have been extensive publications reporting benefit for medical patients with SS/SS managed with the sepsis bundles, few studies evaluate the potential benefit of a sepsis initiative in surgical patients who develop SS/SS. Hypothesis: The use of an early sepsis initiative based on best practice guidelines may reduce the mortality and healthcare resource consumption in the surgical patient population with SS/SS. Methods: A retrospective review of 2831 patients who developed SS/SS (sepsis with organ dysfunction and/or refractory hypotension) after major surgery was examined from June, 2003 through December, 2009 in an academic medical center. Mortality, length of hospital stay (LOS), intensive care unit (ICU) days, and duration of mechanical ventilation were compared between the pre-intervention group (June 2003-December 2005, N ⫽ 720) and the post-intervention group (January 2006-December 2009, N ⫽ 2111). Statistical analysis was conducted using T-test for continuous variables and chi-squared analysis for categorical variables. A p-value of 0.05 or less was considered significant. Results: The in hospital mortality rate decreased from 15.83% to 11.42% after implementation of the early sepsis initiative (p ⫽ 0.002) for an actual relative risk reduction of 27.9%. LOS was reduced by 6 days (30.70 ⫾ 33.24 to 24.70 ⫾ 24.63, p ⬍ 0.001). ICU LOS was decreased by 4.5 days (19.15 ⫾ 28.46 to 14.64 ⫾ 20.00, p ⬍ 0.001). Duration of mechanical ventilation was reduced by 4.3 days (16.34 ⫾ 20.52 to 12.06 ⫾ 12.82, p ⫽ ⬍ 0.001). Conclusions: The implementation of an early sepsis initiative leads to significant reduction in mortality, hospital LOS, ICU days, and ventilator days in the surgical patient population. In addition to promoting improved patient outcomes, the use of sepsis bundles in the surgical patient leads to decreased healthcare resource consumption.

Brian Fuller, Washington University School of Medicine, Mithil Gajera, Cooper University Hospital, Christa Schorr, Cooper Hospital University Med Ctr, David Gerber, Cooper Hospital/UMC, R. Dellinger, Cooper University Hospital, Joseph Parrillo, Cooper University Hospital/UMC, Sergio Zanotti-Cavazzoni, Cooper University Hospital Introduction: The exact role of packed red blood cell (PRBC) transfusion in the setting of early resuscitation in septic shock is unknown. Hypothesis: The transfusion of PRBCs does not improve cellular oxygenation as determined by central venous oxygen saturation (ScvO2) ⬎ 70%. Methods: Retrospective cohort study (n ⫽ 93) of patients presenting with septic shock treated with early goal directed therapy (EGDT). Data was collected on patients identified via the Surviving Sepsis Campaign Chart Review database and linked to the Project IMPACT database. Pearson chi square and Fisher’s exact test were used to test for clinical significance. Primary outcome was the achievement of ScvO2 of ⬎ 70%. Secondary outcomes included improved sequential organ failure assessment (SOFA) score, achievement of central venous pressure (CVP) ⬎ 8 mmHg and a mean arterial pressure (MAP) ⬎ 65 mmHg. Results: 34/93 patients received at least one PRBC transfusion. The two groups were well balanced with respect to age, gender, APACHE II, and baseline lactate levels. The ScvO2 goal ⬎ 70% was achieved in 71.9% of the PRBC group and 66.1% of the no PRBC group (p ⫽ 0.30). There was also no difference in change in SOFA score within the first 24 hours in the PRBC group vs. the no PRBC group (8.6 to 8.3 vs. 5.8 to 5.6, p ⫽ 0.85), time to achievement of CVP ⬎ 8mmHg (732 minutes vs. 465 minutes, p ⫽ 0.14), or use of norepinephrine to maintain MAP ⬎ 65mmHg (81.3% vs. 83.8%, p ⫽ 0.77). Conclusions: In this study, the transfusion of PRBC was not associated with improvement in cellular oxygenation, as demonstrated by a lack of improved achievement of ScvO2 ⬎ 70%. Also, the transfusion of PRBC was not associated with improved organ function, or improved achievement of the other goals of EGDT. These results are consistent with data from previous studies that suggest that PRBC transfusion does not improve oxygen utilization. Further studies are needed to determine the impact of transfusion of PRBC within the context of early resuscitation of patients with septic shock, as the beneficial effects gained by an early and goal oriented approach to resuscitation may be lost by the negative effects associated with PRBC transfusion.

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IMPACT OF ORDER SET UTILIZATION ON SEPTIC SHOCK PATIENTS IN THE MEDICAL INTENSIVE CARE UNIT

JUMPING THE HURDLES - BARRIERS DURING IMPLEMENTATION OF A SEPSIS PROGRAM

Daniel Malcom, Sullivan University College of Pharmacy, Barbara Faircloth, Bradley Davis, Chenoah Gudel, University of Tennessee Medical Center

Laszlo Hoesel, Nicolas Mouawad, Lora Silverman, Mary-Margaret Brandt, Mary-Anne Purtill, Joseph Bander, Patricia Posa, St. Joseph Mercy Hospital

Introduction: Bundled care for septic shock has been widely associated with reduced mortality. To our knowledge, no study has evaluated the impact of an order set developed after release of the 2008 Surviving Sepsis guidelines. In late 2008, our institution developed an order set including recommendations from the update. Hypothesis: Order set utilization will be associated with improved survival. Methods: A retrospective cohort study (IRB-approved) was designed comparing septic shock patients receiving the pre-printed order set to those who received traditional care with handwritten orders at presentation. All patients admitted to the critical care service from July to December 2009 with an ICD-9 diagnosis of septic shock (785.52) were evaluated. Patient demographic data, order set utilization, and APACHE II scores (with associated laboratory values) were recorded. The primary endpoint was in-hospital mortality, and a multivariable regression analysis was performed to identify predictors of survival. Results: Of 131 patients evaluated, 25% (n ⫽ 33) received the pre-printed order set and 75% (n ⫽ 98) received traditional care. Average age in the order set group was 62.1 ⫾ 15.9 versus 62.0 ⫾ 14.4 in the traditional care group (p ⫽ 0.98). APACHE II scores for the order set group averaged 28 ⫾ 7.8 while the scores averaged 27.7 ⫾ 9.0 (p ⫽ 0.72). With regards to sex, 57.6% (n ⫽ 19) were male in the order set group and 55% (n ⫽ 54) were male in the traditional group (p ⫽ 0.81). In the multivariable regression model including age, sex, APACHE II score, and serum lactate level, patients who received order set driven care were significantly more likely to survive (OR 2.75, 95% CI 1.01-7.44, p ⫽ 0.05). Serum lactate levels differed significantly between survivors and non-survivors, averaging 3.8 ⫾ 3.6 mmol/L in non-survivors versus 2.6 ⫾ 2.0 mmol/L (p ⫽ 0.04) in survivors, and increased lactate was found to be associated with a reduction in survival (OR 0.84, 95% CI 0.71-0.99, p ⫽ 0.05). Conclusions: Order set driven care was associated with a higher likelihood of survival in patients presenting to our institution with septic shock. We hope these results encourage further utilization of the preprinted order set for patients presenting with septic shock.

Introduction: Guidelines for the care of septic patients have been widely accepted but compliance with these guidelines has been variable. We report our experience in identifying and overcoming barriers to implementation of a sepsis program and compliance with the guidelines. Hypothesis: We hypothesized that a systematic approach to identify and overcome barriers to compliance with sepsis guidelines will improve the outcome of septic patients. Methods: In 2006, a multidisciplinary team designed and implemented a hospital-wide sepsis program using a 4-tier process. It consisted of organizational commitment, identification of septic patients, bundle implementation, and outcome measurement with feedback. If adult patients in the hospital or ED screened positive for severe sepsis, interventions were initiated followed by transfer to an intensive care unit with standardized care. The sepsis team monitored compliance, barriers and other outcomes during implementation. A pre-implementation cohort (n ⫽ 60) was compared with a post-implementation cohort (n ⫽ 1329) for compliance, inhospital mortality, length of stay and direct costs. Results: Three key barriers were identified: correct identification of septic patients, personal variations in adhering to the treatment bundles, and reluctance to insertion of central lines. To overcome these barriers, unit-based frontline staff (‘sepsis champions‘) provided realtime assessment and feedback to caregivers. Daily rounds by a sepsis team member helped staff increase adherence to the treatment protocol. New sepsis protocols initiated by nurses helped avoid variations by physicians and delays in treatment. This increased overall compliance with the sepsis bundles from 0% to 64% and decreased in-hospital mortality from 45% to 26%. Similarly, length of stay and direct cost decreased. Conclusions: Successful implementation of sepsis guidelines requires a multidisciplinary approach based on a structured and supervised process. Key barriers must be addressed and may be overcome by ongoing monitoring, constant feedback and teaching which can increase compliance and survival of septic patients. This study may benefit other institutions in their initiation of new interventions.


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OUTCOMES IN OCTOGENARIANS ADMITTED TO A COMMUNITY HOSPITAL WITH A DIAGNOSIS OF SEPSIS

EARLY GOAL-DIRECTED THERAPY IMPROVED SURVIVAL OF PATIENTS WITH SEPTIC SHOCK IN KOREA

Armand Tanase, Western Reserve Care System, Kanwaljit Waraich, Western Reserve Care System/ NEOUCOM, Hardeep Rai, Western Reserve Care System, Abhijit Duggal, Sunnybrook Health Care Sciences

Myung Hee Park, Jae Seong Kim, Gil Joon Suh, Woon Yong Kwon, Jae Hyuk Lee, Kyung Su Kim, Department of Emergency Medicine, Seoul National University College of Medicine

Introduction: After the implementation of early goal directed therapy several trial have shown that age is not a factor in mortality and morbidity in patients admitted with sepsis. Hypothesis: To evaluate differences in clinical characteristics, co-morbid conditions and mortality of octogenarians admitted with sepsis compared to younger patients in a community hospital. Methods: We retrospectively analyzed a cohort of 230 patients with a diagnosis of sepsis. Results: 58(25.21%) of the total admissions were octogenarians. This group was more commonly coming from extended care facilities (55%vs34%, p0.005) and had a higher proportion of white patients (88%vs74%, p0.02). There was no statistical difference between the presenting APACHE II scores (22 ⫾ 6.28vs 21 ⫾ 6.26, p 0.29) or underlying cardiac(57%vs46%, p0.17) or pulmonary pathology (16%vs0.23%, p0.26) between the two groups. Both groups had no significant difference between rates of bacteremia (40%vs42%, p0.87), shock (55%vs47%, p0.28), ARDS (0%vs5%, p0.11) or thrombocytopenia (16%vs26%, p0.14).There was a higher mortality in the octogenarian group, but is was not statistically significant. (48%vs35%, p0.08) Patients in the octogenarian group had a lower rate of intubation rates (17%vs31%, p0.06) and renal replacement therapy (9%vs20%, p0.06).But the rates of use of activated protein c, steroids, insulin infusion and vasopressors were similar in both the groups. There was no difference in the length of stay in the ICU(4.56 ⫾ 5.20vs5.86 ⫾ 6.34, p0.16) and hospital (9.12 ⫾ 8.58vs11.03 ⫾ 8.28, p0.13) between the two groups. Patients younger that 80 were more likely to be discharged home(25.58%vs12.06, p0.04). Conclusions: Octogenarians admitted to a community hospital with a diagnosis of sepsis have no difference in the mortality and rates of complications. This is despite the fact that octogenarians have a lower likelihood of undergoing mechanical ventilation and renal replacement therapy. The length of stay in the ICU and hospital is very similar to younger people, but octogenarians have a much lower rate of discharge directly to home. Thus aggressive initial management is appropriate in patients over the age of 80 who are admitted with a diagnosis of sepsis

Introduction: Many previous clinical data have reported the beneficial effects of the early goal-directed therapy (EGDT) on the patients with severe sepsis and septic shock. Hypothesis: We performed this study to determine whether the EGDT improves survival of patients with septic shock in Korea. Methods: This was a prospective before and after study conducted at an emergency ICU in one tertiary hospital in Seoul, Korea. We enrolled consecutive patients with suspected infection who met two or more criteria for systemic inflammatory response syndrome and showed sustained hypotension even after volume resuscitation. We compared the patients before (the non-EGDT group) and after (the EGDT group) the application of EGDT with respect to demographic features, APACHE II score, achievement of early goals, and outcomes including 28-day mortality. To adjust the severity differences between the two groups, matched pairs using APACHE II score were selected and compared. Data were analyzed by the Kaplan-Meier survival analysis with log-rank test, paired t-test, and McNemar or sign test, where appropriate. Results: Among 138 enrolled patients, 88 patients were categorized as the non-EGDT group and 50 were as the EGDT group. The patients in the EGDT group achieved the early goals more frequently, had shorter time from diagnosis to antibiotics, and received larger volume for initial 6 hrs than those in the non-EGDT group. The patients in the EGDT group had higher APACHE II score (29.06 ⫾ 9.10 vs. 25.53 ⫾ 9.57, p ⫽ 0.034) than those in the non-EGDT group and did not show any improvement in 28-day mortality (42.0% vs. 44.3%, p ⫽ 0.792). However, when matched pairs were compared (n ⫽ 47/group), significant reduction of 28-day mortality was observed in the EGDT group (40.4% vs. 61.7%, p ⫽ 0.039). Conclusions: The EGDT improved 28-day survival of patients with septic shock in Korea.

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ARE OFF-HOURS ADMISSIONS TO THE ICU ASSOCIATED WITH DECREASED COMPLIANCE WITH THE SEPSIS RESUSCITATION BUNDLE?

OUTCOMES OF AN ELECTRONIC ALERT ON IMPLEMENTATION OF THE SEPSIS RESUSCITATION BUNDLE AND OUTCOMES: A PILOT STUDY

Ogbonna Ogbu, Razaq Badamosi, Henry Ford Hospital

Lynne Bustraan, Florida Hospital East Orlando, Mary Sole, University of Central Florida, Christine Higgins, Florida Hospital Altamote

Introduction: Implementation of the 6-hour sepsis resuscitation bundle has been shown to improve outcomes in severe sepsis and septic shock. Off-hours are associated with changes in physician staffing levels in the ICU. Admissions to hospitals during the off-hours have been associated with poorer outcomes and delays in procedures and treatment. Hypothesis: There is decreased compliance with elements of the sepsis resuscitation bundle in the ICU for patients with severe sepsis and septic shock admitted during off-hours. Methods: In this singlecenter retrospective study, we analyzed data on patients admitted to the medical ICU from December 2008 through January 2010 extracted from the hospital’s medical record database. We excluded patients who were not admitted with an initial diagnosis of severe sepsis or septic shock and who had appropriate central lines placed in the emergency department. Patients admitted between 6:30 AM and 5:00 PM Monday – Friday were classified as on-hours admissions. All other admissions were considered off-hours. We evaluated the following elements of the sepsis resuscitation bundle: blood cultures obtained before antibiotics, administration of broad spectrum antibiotics, CVP monitoring, Svo2 measurement, use of pressors and use of dobutamine and/or packed red blood cell (PRBC) transfusion. We compared implementation for on- and off-hours admissions using chisquare or Fischer’s exact test as appropriate. Results: The study population consisted of 155 patients of which 106 (70%) were off-hours admissions. Compliance in the two groups (off-hours vs. on-hours), was highest for lactate measurement [102 (96%) vs. 48 (98%)], and use of pressors [86 (81%) vs. 38 (78%)]. It was lowest for use of dobutamine ⫹/⫺ PRBC [46 (43%) vs. 17 (35%)]. There were no statistically significant differences in compliance between on- and off-hours admissions for any of the bundle elements. Conclusions: Off-hours admission was not associated with decreased compliance with the sepsis resuscitation bundle. The changes in staffing between on- and off-hours do not appear to affect bundle compliance in the ICU. Research is needed to improve the observed low level of compliance with specific elements of the sepsis bundle.


Introduction: This study evaluated an electronic alert system on implementation of the Surviving Sepsis Campaign (SSC) resuscitation bundle at two community hospitals in the Southeast. Hypothesis: Implementation of the alert system will 1) accurately identify patients with sepsis; 2) improve implementation of the SSC bundle; and 3) reduce intensive care (ICU) and hospital length of stay (LOS). Methods: A pre-test, post-test design was used following IRB approval and waiver of consent. Prior to activation of the alert system, data were collected retrospectively for a 3-month period identifying 62 subjects with a DRG of sepsis. A sepsis initiative was led by clinical nurse specialists (CNS) at both sites. The sepsis alert feature was activated on the ICU monitor after in-service. Data from 64 subjects with a positive alert were analyzed after implementation. Results: The groups were not different (p ⬎ .05) in age (mean 67 ⫾ 17 years) or gender (male 56%). A DRG of sepsis was documented in 37 subjects post alert (58%), yielding a false positive trigger of 42%, rejecting hypothesis 1. Nurses placed the alert on “standby” for 30% of subjects. Completion of the SSC bundle in confirmed septic patients increased from 19% to 32% following the alert, but was not significant (chi2; p ⫽ .14), rejecting hypothesis 2. Fluid resuscitation for hypotension increased from 52% to 92% (chi2; p ⫽ .001), and vasopressor administration without fluid resuscitation decreased from 34% to 4% (chi2; p ⫽ .004). Fluid volume administered increased from 1063 mL to 1439 mL, but was not significant (t-test; p ⫽ .19). No one had central venous pressure or ScvO2 measured. No differences were found in ICU and hospital LOS between groups (t-test; p ⬎ .05), rejecting hypothesis 3. Conclusions: Nurses play an important role in early detection and management of sepsis. An electronic alert may be beneficial; however, the trigger needs to be accurate and the nurse must find the prompts easy to follow. Findings may have been stronger had prompts been followed all of the time. Fluid administration improved after the alert system was activated. The contributions of education and CNS follow-up to the results are not known. Study funded by unrestricted grant from Philips Medical.

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SEPSIS ALERT SYSTEM IN THE EMERGENCY DEPARTMENT EXPEDITES SEPSIS BUNDLE CARE

RESULTS OF A SEPSIS MANAGEMENT PROTOCOL IMPLEMENTATION AFTER THREE YEARS IN A VENEZUELAN HOSPITAL

Aaron Trammell, Stephan Russ, Keith Wrenn, Ian Jones, Arthur Wheeler, Michael Hooper, Todd Rice, Vanderbilt University Medical Center Introduction: The Surviving Sepsis Campaign (SSC) guidelines are focused on early detection, resuscitation and proper antimicrobial selection in patients with sepsis. Hypothesis: We hypothesized that a protocolized pathway with early alerting system for patients presenting with severe sepsis to our emergency department would result in expedited achievement of the SSC goals. Methods: Patients presenting to the adult emergency department meeting SIRS criteria requiring admission to the MICU for a diagnosis of septic shock or respiratory failure before and after implementation of an optional sepsis notification protocol was implemented in the ED were included. This protocol includes increased nurse availability, standardized volume resuscitation, guidelines for antimicrobial selection and early notification of MICU charge nurse and fellow. Data was collected for standard care (n ⫽ 190) and protocol groups (n ⫽ 15) regarding baseline characteristics, initial laboratory results, and timing of interventions (antibiotics, vasopressor use, CVP measurement, volume of fluids given, transfer to MICU, total time hypotensive, total time in the MICU). Means (s.d.) were used to compare baseline data. Medians (IQR) were used to compare duration of time to specific interventions. Results: The groups were similar in demographics with a trend towards higher mean arterial pressure in standard care vs sepsis protocol patients (76.9 ⫾ 20.2 mmHg vs. 68.3 ⫾ 14.9 mmHg; P ⫽ 0.10). There was no significant difference between the standard care and protocol groups in percentage requiring vasopressors (34.2% vs. 26.7%; P ⫽ 0.55) or baseline lactate (2.8 ⫾ 2.5 mEq/L vs. 2.9 ⫾ 2.6 mEq/L; P ⫽ 0.98). The protocol significantly decreased time to transfer to MICU (240 min vs. 190 min; P ⫽ 0.03), time to antibiotics (60.5 min vs. 20 min; P ⫽ 0.01), time to CVP measurement (9.3 hr vs. 5.3 hr; P ⫽ 0.001). The protocol also demonstrated a trend toward improvement in time from arrival until labs and blood cultures were obtained, time from arrival until vasopressors were initiated and total time hypotensive. Conclusions: We conclude that patients initiated on a sepsis protocol in the emergency department receive more timely appropriate medical care.

Pablo Perez , Sunnybrook Health Sciences Centre, Juan Pal , Stevens Salva , Fernando Perez, Margory Ojeda, Arelys Quintero, Gabriel d’Empaire, Hospital de Clinicas Caracas Introduction: Using protocols for sepsis management according the Surviving Sepsis Campaign (SSC) has been used to improve outcomes in septic patients over the last years. Hospital de Clinicas Caracas ICU was the first center in Venezuela to launch a protocol like this three years ago. Hypothesis: Implementing a sepsis management protocol according to SSC recommendations will improve bundle goals compliance, will reduce mortality and length of stay over time. Methods: Retrospective analysis of the SSC database including all the patients with severe sepsis and septic shock admitted to the Hospital de Clinicas Caracas ICU between 2007 May and 2010 May. Educational sessions were done every six months as part of the protocol for training and retraining. After each year ended the results were evaluated and the protocol implementation was continued without any modifications. Bundle goals compliance, hospital mortality, ICU and hospital length of stay were compared between the third and the first year. Results: 190 consecutive patients were included. Demographic and severity characteristics were similar in all years. Patients from the third year had better lactate measurement compliance (92.30% vs. 71.72%, p ⫽ 0.004); better antibiotic administration ⬍ 3 hours compliance (88.46% vs. 60.60%, p ⫽ 0.01); better initial resuscitation bundle goals compliance (46.15% vs. 30.30%, p ⫽ 0.02); lower hospital mortality (21.15% vs. 36.36%, p ⫽ 0.1); lower ICU length of stay (4.67 ⫾ 3.26 vs. 5.28 ⫾ 5.01, p ⫽ 0.76) and lower hospital length of stay (11.49 ⫾ 7.19 vs. 12.61 ⫾ 8.13), p ⫽ 0.54) than the first year. Conclusions: Implementing a sepsis management protocol according to the SSC recommendations was effective to improve earlier antibiotic administration and better resuscitation bundle goals compliance. Also it showed a decrease in hospital mortality and lower ICU and hospital length of stay. Being a retrospective single center study is limited for definite conclusions


Poster: Sepsis – Nosocomial (VAP, BSI, UTI) 403

404

A COMPARISON OF VAP RATES AS IDENTIFIED ACCORDING TO NATIONAL HEALTHCARE SAFETY NETWORK (NSHN) AND AMERICAN COLLEGE OF CHEST PHYSICIANS (ACCP) CRITERIA IN A MEDICAL/SURGICAL ICU POPULATION

SUSTAINED REDUCTION OF VENTILATOR ASSOCIATED PNEUMONIA: USE OF AN INNOVATION SYSTEM PROCESS IN A TERTIARY CARE CENTER

Lee Skrupky, Barnes-Jewish Hospital, Kevin McConnell, John Dallas, Washington Univ. School of Medicine, Kathleen McMullen, Banes-Jewish Hospital, Walter Boyle, Marin Kollef, Washington Univ. School of Medicine Introduction: Given the significance of VAP in the ICU it is important that there be some agreement between criteria utilized to survey the incidence of VAP and criteria used to assess patients at the bedside. However, CDC NHSN criteria for VAP that are often used for surveillance appear more stringent than the ACCP criteria applied in clinical practice. Hypothesis: We hypothesized that VAP rates identified according to NHSN criteria would be significantly lower than rates identified using ACCP criteria. Methods: MICU and SICU patients requiring mechanical ventilation for ⬎ 48 hrs were prospectively screened for VAP from Jan 2009 to Jan 2010 using both the NHSN and ACCP criteria. The presence or absence of a new or progressive radiographic infiltrate was based on the interpretation of the chest radiograph by radiologists who were blinded to the study. All ACCP classifications, including the corresponding radiographs and laboratory data, were reviewed by one investigator (J.D.) and confirmed by a second investigator (M.H.K.). All NHSN classifications were made by the hospital infection prevention department. Patients were excluded if they had a tracheostomy in place at time of VAP suspicion, were significantly immunosuppressed, or if a concurrent source of infection was obvious. Both endotracheal tube aspirates and BAL samples were assessed to determine culture positivity. Results: Over one year, 2060 patients met the inclusion criteria. Of these, 83 patients (4%) had VAP according to the ACCP criteria, as compared to 12 patients (0.6%) using the NHSN criteria. The 12 patients meeting NHSN criteria were also identified in the ACCP group. Agreement of the two sets of criteria was poor (kappa statistic, 0.26). The median CPIS score was 6 in both groups. Cultures were positive in 88% (n ⫽ 73) of patients in the ACCP group as compared to 92% (n ⫽ 11) in the NHSN group. All patients identified by ACCP criteria received treatment for VAP as decided by the ICU team. Conclusions: There is poor agreement between the ACCP and NHSN diagnostic criteria for VAP. Although there may be some benefit to using more stringent criteria for surveillance of VAP, utilization of the NHSN criteria may underestimate the scope of the clinical problem.

Omar Rahman, Geisinger Health System, Doyle Ashburn, Mitchell Craft, Lisa Esolen, Janet Comrey, Debra Gardill, Lani Kishbaugh, Geisinger Medical Center Introduction: Ventilator Associated Pneumonia (VAP) has significant impact on healthcare costs, morbidity and mortality. Prevention guidelines have been proposed and implementation of the IHI ventilator bundle has shown to reduce VAP rates. Compliance with guidelines and sustaining low infection rates in tertiary care centers remains a problem. Using information technology to develop reliable processes and translation to bedside application has been demonstarted to improve clinical microsystems. Hypothesis: Using an innovative multimodality approach incorporating Electronic Medical Records (EMR) & quality improvement ‘smart’ tools with traditional clinical team plan-do-study-act (PDSA) cycles would lead to reliable adherence to prevention guidelines and sustained reduction of VAP. Methods: Prospectively collected data from 2006 to 2010 was reviewed retrospectively. Setting: Med-surg, trauma, cardiothoracic ICU mechanically ventilated ⬎ 48 hrs. Process relaibility measures were IHI bundle components and guidelines. Stepwise interventions were introduced over 4 years and implemented via EMR and web-based tools:1) Information from nurses’ electronic flowsheets to pharmacy & respiratory care for oral care with chlorhexidine, weaning & subglottic drainage. 2) Endotracheal tubes with subglottic suction for all emergency surgery, trauma, code and ICU intubations. 3) Best practice alerts. 4) Education campaigns for physicians, nurses and respiratory personnel. 5) Analysis of every VAP case with remedial action. 6) Compliance monitoring & data collection.VAP team meetings every 2 weeks composed of intensivist, respiratory, nursing, infection control, innovations, quality and executive personnel. Results: VAP rates 1998-2005 range: 8.7 to 15.5/ 1000 MV days. Post process rates: 2006 ⫽ 5.6/1000; 2007 ⫽ 3.6/1000; 2008 ⫽ 0.49/1000; 2009 ⫽ 0.75/1000; 2010 ⫽ 0.23/1000 MV days. Relative risk reduction of 95.9 % at end of study period. Bundle complaince improved by 24 %. Conclusions: Innovation systems approach results in sustained reduction of VAP. Similar multimodality approach is applicable to other quality initiatives. VAP related cost savings were in excess of $ 1 million.

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DAILY BATHING WITH 2% CHG WASHCLOTHS LEADS TO ALMOST TOTAL ELIMINATION OF MRSA BACTERAEMIA

EMPIRIC ANTIBIOTIC THERAPY WITH INHALED TOBRAMYCIN VS. INTRAVENOUS TOBRAMYCIN FOR LATE-ONSET VENTILATOR-ASSOCIATED PNEUMONIA IN CRITICALLY ILL SURGICAL PATIENTS: IT-VAP PILOT STUDY

Duncan Wyncoll, Guy’s & St Thomas’ Foundation Trust, Manu Shankar-Hari, Guy’s & St Thomas’ NHS Foundation Trust, Richard Beale, Saint Thomas’ Hospital Introduction: Optimal infection control (IC) practice is vital in the intensive care unit (ICU) if quality care is to be provided. An internationally recognized marker of quality is the rate of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia, and acquired colonisation. Hypothesis: Over the last decade our IC strategy and patient bathing protocol changes have led to sustained improvements in quality and the rate of MRSA bacteraemia. Methods: A number of initiatives have been added sequentially in an attempt to control MRSA bacteraemia and acquired colonization in a 30-bed mixed tertiary ICU. These initiatives have included guidelines for the insertion and care of central lines (CVCs) and a tool to encourage early CVC removal, hand hygiene interventions, and daily triclosan washes, In addition, MRSA colonized patients have chlorhexidine gluconate (CHG) 1% applied nasally and to the tracheostomy site (if applicable) and CHG powder is also applied to the axillae, groin and skin folds. In January 2007, 2% CHG bathing cloths were introduced as a further intervention against MRSA and have been used continuously since. The cloths are warmed and used to bathe the patients once daily. Results: Annual ICU admission rates and severity of illness has remained constant over the same period. In 2002, the number of patients developing bacteraemia was 31 out of 1, 188 patients admitted to ICU, of whom 115 were colonized with MRSA at ICU admission. A further 109 patients became colonized with MRSA ⬎ 48 hrs after admission. In 2007, when the 2% CHG bathing cloths were introduced, there were just 6 MRSA bacteraemia out of 1, 125 admissions. In 2008 & 2009 there was 1 MRSA bacteraemia in each year; 24 & 12 patients became colonized with MRSA ⬎ 48hrs after admission in 2008 & 2009 respectively. Conclusions: We conclude that, although the reduction in the rate of MRSA bacteraemia and ICU acquired MRSA colonization suggests the combined effectiveness of the many infection control procedures initiated, the introduction of the 2% CHG bathing cloths has been associated with almost total elimination in MRSA bacteraemia.


Molly Moore, UC Health-University Hospital; University of Cincinnati, Ashley Bedel, Unviersity of Cincinnati College of Pharmacy , Neil Ernst, Eric Mueller, UC Health-University Hospital; University of Cincinnati Introduction: Ventilator-associated pneumonia (VAP) requires adequate empiric antibiotic therapy with sufficient pulmonary drug concentrations. With high potency, local delivery, and limited systemic exposure, inhaled (INH) aminoglycosides have gained interest. However, studies are limited by inconsistent diagnostic criteria, no standard regimens, and late initiation of INH therapy. Hypothesis: Patients with VAP treated with empiric INH tobramycin (INHt)based therapy will have similar or lower 96-hour clinical pulmonary infection scores (CPIS) compared to patients treated with empiric IVt-based therapy. Methods: This retrospective cohort study included adult surgical ICU patients at an urban, level-1 trauma center who received adequate empiric antibiotic therapy for late-onset VAP. Included patients received protocolized empiric therapy with anti-pseudomonal B-lactam plus either INHt (300mg Q12h) or IVt (5-7mg/kg daily) for at least 48 hours. Late-onset VAP was CPIS ⱖ5 and pathogen growth ⬎ 10, 000 cfu/mL on bronchoscopic bronchoalveolar lavage ⬎ 5 days from admission. Results: Eleven patients received INHt and 7 IVt. There were no differences in patient demographics, severity of illness, or baseline renal function. Pathogens included Enterobacteriaceae (58%) and Pseudomonas aeruginosa (24%). At 96 hours, 82% of INHt patients had a decrease in CPIS of at least 2 points and total score ⬍ 5 v 29% of IVt patients (p ⫽ 0.049). The median decrease in CPIS score at 96 hours was 3 (IQR 2-4.5) in the INHt patients compared to 1 (IQR 0.5-2) in IVt patients (p ⫽ 0.042). No INHt patients had measurable tobra plasma concentrations. There were no differences in CPIS score at the end of definitive therapy, duration of definitive therapy, VAP relapse or recurrence, duration of mechanical ventilation, hospital or ICU lengths of stay, in-hospital mortality, or adverse events. Conclusions: INHt-based empiric combination therapy was associated with greater decrease in CPIS at 96 hours compared to IVt-based therapy in patients with bacteriologically diagnosed, late-onset VAP. Randomized studies using standardized VAP diagnostic criteria and empiric antibiotic regimens are needed.

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CENTRAL LINE-ASSOCIATED BLOODSTREAM INFECTIONS IN CHILDREN AFTER CARDIAC SURGERY: SURVIVAL ANALYSIS OF INCIDENCE AND RISK FACTORS

CATHETER- RELATED BLOODSTREAM INFECTION (CRBSI) ARISING FROM SHORT TERM VASCULAR ACCESS-A COMPARATIVE ASSESSMENT OF TWO IN SITU DIAGNOSTIC METHODS

Ryan Moran, Thomas Talbot, Vanderbilt University Medical Center, Patrick Arbogast, Vanderbilt University, Bradly Strohler, Neal Patel, Vanderbilt University Medical Center Introduction: Previous studies have identified potential risk factors for central line-associated bloodstream infections (CLABSIs) that are related to the operative and post-operative course in children after cardiac surgery. However, prior studies have not taken into account variable follow-up time. Survival analyses may help determine if previously identified associations are truly related to differences in the rate of CLABSIs after cardiac surgery or instead reflect a greater number of post-operative central venous catheter (CVC)-days. Hypothesis: Specific characteristics related to cardiac surgery in children are associated with higher rates of CLABSIs in the post-operative period. Methods: Retrospective review of patients from birth to 18 years admitted after cardiac surgery from March 2008 through June 2009 at a large tertiary care children’s hospital. Subjects were followed from the day of surgery until central lines were discontinued for at least 72 hours or until a CLABSI event occurred. CLABSIs were defined by the Centers for Disease Control and Prevention/National Healthcare Safety Network criteria. Data analysis was by proportional hazards. Logistic regression was also performed for comparative purposes to prior studies. Results: 377 subjects were included, providing 4117 CVC-days. 19 CLABSIs were identified, giving a rate of 4.6 events per 1000 CVC-days (95% CI: 2.9 - 7.2). Several significant associations were identified through logistic regression, including cardiopulmonary bypass time ⬎ 140min (OR: 4.44, 95%CI 1.65-12), risk adjustment for congenital heart surgery score ⬎ 3 (OR: 8.08, 95%CI 2.96-22) and weight ⬍ 5kg (OR: 21, 95%CI 4.76-92.4). No associations were identified after accounting for follow-up time using proportional hazards. Conclusions: Findings were consistent with previous studies when ignoring variable follow-up. However, when properly accounting for variable follow-up, these findings suggest that previously identified risk factors may describe longer CVC exposure time rather than higher rates of CLABSIs. This study highlights the importance of considering variable follow-up time when assessing the risk for CLABSIs in children after cardiac surgery.

John Gowardman, Royal Brisbane and Womens Hospital, Paula Jefferies, Royal Brisbane and Women’s Hospital, Graeme Nimmo, Royal Brisbane and Women’s Hopsital and Queensland Pathlogy, Narrelle George, Royal Brisbane and Women’s Hospital, Queensland Pathology, Matthew McGrail, Monash University, Claire Rickard, Griffith University Introduction: Recognition of catheter-related bloodstream infection (CR-BSI) remains difficult. Diagnosis requires device removal with isolation of an identicle organism from blood and tip (Gold Standard). Hypothesis: Two “in situ” diagnostic methods, differential time to positivity (DTP) and semi-quantitative superficial cultures (SQSC) of catheter entry site and hubs, perform well for the diagnosis of both CR-BSI and catheter tip colonisation (CTC) in short term vascular access. Methods: IRB approved prospective study in adult ICU. Both arterial (AC) and central venous (CVC) catheters were studied. On clinical suspicion of CR-BSI, SQSC were obtained from the skin site and device hubs along with cultures from all catheter lumens, peripheral blood and tips (semi quantitative ). DTP was positive if growth from lumen blood occurred 120 minutes before peripheral blood. SQSC and tip cultures were positive if ⱖ 15 CFUs were grown. The 2 methods were compared against the gold standard (isolation of a matched organism from peripheral blood and tip). Diagnostic validity values (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy) and their 95% CI were calculated using Vassar Stats and methods compared using the McNemar test and Fisher’s exact test. A p ⬍ 0.05 was significant. Results: 120 CVCs and 93 ACs were studied in 101 patients with a mean (SD) age of 50.9 y (16.8) and APACHE II score 21.0(6.9). For both AC and CVC combined, diagnostic validity values (95% CI) of the SQSC technique for CR-BSI were sensitivity 80% [44-96]; specificity 74% [67-80]; PPV 13% [6-25]; NPV 99% [95-100] and accuracy 74% [68-80] and for CTC; sensitivity 82% [65-93], specificity 82% [75-87], PPV 46% [33-59], NPV 96% [93-98] and accuracy 82% [76-87]. Validity values for DTP were; sensitivity 40% [14-73], specificity 99% [96-100], PPV 67% [24-94], NPV 97% [93-99] and accuracy 96% [92-98]. Conclusions: For diagnosis of CR-BSI and CTC in short term vascular access, DTP and SQSC displayed high specificity, NPV and accuracy. These results may assist in excluding the intravascular device as a source of sepsis.

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IMPACT OF INAPPROPRIATE EMPIRIC ANTIMICROBIAL THERAPY FOR TREATMENT OF VENTILATOR-ASSOCIATED PNEUMONIA ON PATIENT OUTCOMES IN A RURAL TRAUMA POPULATION

VENTILATOR-ASSOCIATED TRACHEITIS (VAT) IN CRITICALLY ILL CHILDREN: A CASE SERIES

Wesley McMillian, Fletcher Allen Health Care, Jayde Bednarik, UMASS Memorial Medical Center, Joseph Aloi, John Ahern, Bruce Crookes, Fletcher Allen Health Care

Introduction: Critically ill children admitted to the PICU with acute respiratory failure are at significant risk for ventilator-associated respiratory infections (VARI), including ventilator-associated pneumonia (VAP) and ventilator-associated tracheitis (VAT). Our group has shown that VAP increases PICU LOS, costs, and mortality. However, there are relatively few studies on the impact of VAT in critically ill patients, and these have been limited to adults. We report the first case series of critically ill children with VAT. Hypothesis: We hypothesized that VAT has become more common in our PICU coincident with the successful reduction of VAP. Methods: With IRB approval, we identified all children with VAT in our PICU from January 1, 2004 - June 30, 2010. VAT was diagnosed according to the CDC as the presence of at least 2 of the following: fever, cough, new or increased sputum production, rhonchi, wheezing AND a positive respiratory culture in the absence of clinical or radiographic evidence of pneumonia. Demographic information, length of ventilation, PICU and hospital LOS, and mortality were recorded. The VAT rate was calculated as the number of VAT cases divided by the total number of ventilator days ⫻ 1, 000. Continuous, non-parametric data were expressed as median (IQR). Results: During the period of study, 77 children were diagnosed with VAT (3.0 per 1, 000 ventilator-days). The VAT increased over time from 1.96 to 3.19 per 1, 000 ventilator-days. Concurrently, our VAP rate decreased from 5.6 per 1, 000 ventilator-days to 2.13 per 1, 000 ventilator-days. Most of the VAT cases were female (57%), with age 1.93 months (1.96, 25.2), weight 11 kg (11.25, 93.3), and PRISM-III 8 (8, 30). The majority of VAT cases were due to a single microorganism (56/77, 73%), most commonly Pseudomonas aeruginosa (25/56, 45%). The duration of ventilation was 21 days (20.5, 121), PICU LOS 26 days (26, 186), and hospital LOS 66 days (66, 460). Hospital mortality in the cohort was 14.3%. Conclusions: VAT is a significant problem in critically ill children admitted to the PICU and may be a precursor for VAP. Future studies will determine whether VAT is indepedently associated with increased hospital costs, LOS, and mortality.

Introduction: Inappropriate empiric antimicrobial therapy (IEAT) has been associated with increased morbidity and mortality in ventilator-associated pneumonia (VAP) in a medical ICU population. However, IEAT does not appear to confer the same mortality risk in surgical ICU patients diagnosed with VAP. Hypothesis: IEAT in treatment of VAP will not adversely impact morbidity or mortality outcomes in our rural trauma population. Methods: A retrospective cohort study was completed on all adult (⬎18 years) trauma patients on mechanical ventilation (MV) admitted to our rural level-1 trauma center between 1/03 and 12/08 who were diagnosed with VAP. Patient demographics, duration of MV, time until VAP development, respiratory cultures and sensitivities, risk factors (RF) for multi-drug resistant pathogens (MDRPs), ICU and hospital length of stay (LOS), and in-hospital mortality were assessed. IEAT was defined as documented bacterial resistance to empiric antimicrobial therapy. Appropriate empiric therapy was subdivided into patients who had treatment de-escalation or no change to their antibiotic therapy. Results: One hundred twenty-one patients were diagnosed with VAP. IEAT was found in 30 (25.6%) patients. Ninety-one patients received appropriate therapy; 78 (85.7%) had therapy de-escalated and 13 (14.3%) continued empiric therapy for the duration of treatment. Baseline characteristics including age (p ⫽ 0.136), male gender (p ⫽ 1.00), ISS (p ⫽ 0.238), APACHE II (p ⫽ 0.491), RF for MDRPs (p ⫽ 0.590), and organ injury were similar between groups. Patients in the IEAT group received prolonged antimicrobial therapy (10.9 vs 8.6 days, p ⫽ 0.008). No difference was found in time to VAP development (5.5 vs 5.0 days, p ⫽ 0.862), ICU LOS (27.4 vs 23.6 days, p ⫽ 0.507), hospital LOS (38.8 vs 33.8 days, p ⫽ 0.319), duration of MV (19.4 vs 18.9 days, p ⫽ 0.808) or mortality (6.7 vs 9.9%, p ⫽ 0.730) when comparing the IEAT group with the appropriate therapy group. Conclusions: IEAT does not appear to appear to influence morbidity or mortality outcomes in a trauma population diagnosed with VAP. However, antibiotic duration is prolonged by approximately 2 days.

Derek Wheeler, John Whitt, MaryJo Giaccone, John Butcher, Marion Schulte, Cincinnati Children’s Hospital Medical Center


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VENTILATOR-ASSOCIATED PNEUMONIA (VAP) CAN BE ERRADICATED. SUCCESFUL VAP PREVENTION PROGRAM IN A COMPREHENSIVE CANCER CENTER SURGICAL ICU

IMPACT OF MULTIPLE EPISODES OF VENTILATOR-ASSOCIATED PNEUMONIA ON PATIENT OUTCOMES IN A RURAL TRAUMA POPULATION

Joseph Nates, The University of Texas at M D Anderson Cancer Center, Cheryl Perego, Clarence Finch, Roy Chemaly, Victoria Jordan, John Terrell, Selvaraj Pravinkumar, Issam Raad, Kristen Price, The University of Texas M D Anderson Cancer Center

Joseph Aloi, Wesley McMillian, Fletcher Allen Health Care, Jayde Bednarik, UMass Memorial Health Care, John Ahern, Fletcher Allen Health Care, Bruce Crookes, Medical University of South Carolina

Introduction: In August 2002, the ventilator-associated pneumonia (VAP) rate in our ICU was 34.2 per 1000 ventilator days (VD). Although there is no benchmark for Oncological-ICUs, our rate was double the National Nosocomial Infection Surveillance Trauma ICU mean VAP rate (17 cases/1000 VD). In 2003, aggressive multidisciplinary strategies to reduce VAP rate were implemented and annually revisited, and new evidence-based (EB) strategies added as fast as identified in the literature. Hypothesis: An effective infection control program combined with EB interventions can reduce VAP rates. Methods: From 8/1/2002 to 6/31/2010, prospective surveillance data using the Centers for Disease Control (CDC) definitions were collected in our 28-bed adult surgical ICU. VAP rates and VD were tracked and improvement processes were assessed monthly. Interventions included education of multidisciplinary team on infection prevention strategies, implementation of the 2003 revised CDC Prevention of HealthcareAssociated Pneumonia Guidelines, and the Institute of Healthcare Improvement ventilator bundle initiative including aggressive ventilator weaning protocol, head elevation, and others. In 2008 and early 2009, daily sedation holidays and spontaneous breathing trials were mandated. The VAP rates were measured by statistical process control charts. Results: During the study period, the VAP rate per 1000 VD was reduced from 34.2 in 2002 to 0 in 2010 (p ⬍ 0.000). The VAP rates per 1, 000 VD were 19.8 in 2003, 17 in 2004, 10.1 in 2005, 8.6 in 2006, 9.2 in 2007, 8.5 in 2008, 2.2 in 2009, and 0 in 2010. The most frequently isolated microorganisms were Ps. aeruginosa and S. aureus. A zero VAP rate has been maintained for the last 12 months. The cost avoidance associated with VAP reduction surpassed $1.5 million. Conclusions: As a result of the above interventions, VAP was successfully controlled and the rate has remained at zero for 12 months. The results of our ICU infection control program indicate that the entity recognized as VAP today is clearly preventable. A multidisciplinary team approach that combines continuous education and aggressive implementation of EB interventions can eradicate VAP while impacting outcomes and healthcare costs.


Introduction: The development of ventilator-associated pneumonia (VAP) is the leading cause of infection related cause of death in the ICU, as well as prolonged mechanical ventilation (MV), ICU and hospital length of stay (LOS). The impact of multiple episodes of VAP in the same ICU and hospital stay is not as well described in current literature. Hypothesis: The development of multiple VAPs will not impact morbidity or mortality outcomes in a rural trauma population. Methods: A retrospective cohort study was completed on all adult (⬎18 years) trauma patients on MV admitted to a rural level-1 trauma center between 1/03 and 12/08 who were diagnosed with VAP. Patient demographics, duration of MV, time to initial (1VAP) and subsequent VAP (2VAP) development, respiratory cultures and sensitivities, risk factors (RF) for multi-drug resistant pathogens (MDRPs), ICU and hospital LOS, and in-hospital mortality were assessed. Results: One hundred twenty-one patients were diagnosed with 1VAP and 26 (21.5%) developed 2VAP. Baseline characteristics, including age, gender, APACHE-II, smoking history, RFs for MDRPs, ISS, and outside intubation were similar between the groups. Trauma-induced organ failure was similar between the groups, with the exception of pulmonary involvement (43% with 1VAP vs. 73% with 2VAP; p ⫽ 0.008). Mortality was similar between 1VAP and 2VAP (9.5% vs. 7.7%; p ⫽ 1.0). Duration of MV, ICU and hospital LOS were significantly longer in the 2VAP group (mean difference duration of MV 17.2 days; ICU LOS 17.4 days; hospital LOS 14.6 days; all p ⬍ 0.05). The mean duration of antimicrobial therapy for treatment of first episode of VAP was similar between 1VAP and 2VAP (9.3 vs. 8.8 days, p ⫽ 0.564). Conclusions: The development of 2VAP did not appear to increase mortality in this population of trauma patients. However, 2VAP was associated with longer duration of MV and a subsequent prolongation of ICU and hospital LOS.

Poster: Sepsis- Diagnostics 413

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DECREASED PLASMA ASYMMETRIC DIMETHYLARGININE AND ALTERED ARGININE METABOLISM IN PEDIATRIC SEPSIS

ELEVATED SOLUBLE CD163 LEVELS ARE ASSOCIATED WITH THROMBOCYTOPENIA-ASSOCIATED MULTIPLE ORGAN FAILURE (TAMOF) IN PEDIATRIC SEPSIS PATIENTS

Scott Weiss, Shannon Haymond, Hantamalala Ralay-Ranaivo, Mark Wainwright, Children’s Memorial Hospital, Northwestern Feinberg School of Medicine

E. Halstead, Children’s Hospital of Pittsburgh, Mark Hall, Nationwide Children’s Hospital, Raj Aneja, Jennifer Jones, Joseph Carcillo, Children’s Hospital of Pittsburgh

Introduction: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, has shown promise as a biomarker in adult vascular disease. Altered availability of NO and its precursor, arginine, may also contribute to organ dysfunction in sepsis, but the role of ADMA in pediatric sepsis is unknown. Hypothesis: Plasma ADMA is altered in pediatric sepsis and is a sensitive biomarker for diagnosis and to predict outcomes. Methods: In a prospective study of 83 children—30 severe sepsis/shock, 24 febrile/non-septic, and 29 healthy age-matched controls—we measured plasma ADMA, arginine, citrulline, and ornithine using tandem mass spectrometry once for controls and daily for seven days for septic patients. Data are presented as median (IQR) ␮mol/L and compared using Kruskal-Wallis, Friedman, and Spearman’s rho tests. ROC analysis determined the ability of ADMA to identify septic children. Results: ADMA was lower in sepsis (0.38, 0.30-0.56) compared with febrile (0.46, 0.40-0.83) and healthy controls (0.57, 0.52-0.66; p ⬍ 0.001). Over time, ADMA levels in sepsis increased above control values (day 7: 0.64, 0.50-0.79, ptrend ⫽ 0.02). While arginine and citrulline were also decreased in sepsis, the citrulline:arginine ratio (measure of NO synthase activity) did not differ between groups (p ⫽ 0.53). However, the arginine:ornithine ratio was decreased in sepsis compared with febrile and healthy controls (0.44, 0.24-0.56 vs 0.53, 0.37-0.76 vs 0.66, 0.52-0.87; p ⫽ 0.03), indicating increased arginase activity. The area under the ROC curve for ADMA to identify patients with sepsis was 0.69 (95% CI 0.53-0.85). The ADMA cut-point 0.65 ␮mol/L yielded sensitivity 92%, specificity 35%, PPV 69%, NPV 75%, ⫹ LR 1.4, and -LR 0.2. ADMA was inversely correlated with organ dysfunction by PELOD score (p ⫽ 0.01) and interleukin-6 level (p ⫽ 0.02). However, ADMA was not associated with mortality, length of stay, or inotrope duration (all p ⬎ 0.05). Conclusions: Plasma ADMA and arginine are decreased in pediatric sepsis. Low ADMA may maintain NO synthase activity despite diminished arginine availability and increased arginine metabolism by arginase. ADMA may be limited as a biomarker to identify children with sepsis or to predict outcomes.

Introduction: CD163, the haptoglobin-hemoglobin scavenger receptor, is expressed on activated monocytes/macrophages. CD163 is shed in its soluble form (sCD163) in the presence of LPS, Fc-gamma cross-linking and oxidative stress. Very high levels (⬎20 mg/L) are indicative of macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH), and high levels are a negative predictor of outcome in adult patients with pneumococcal sepsis. We have previously described several pediatric sepsis phenotypes:immunoparalysis (ex vivo LPS-stimulated TNF production ⬍200pg/ml), TAMOF (organ failure index [OFI] ⬎ 1, platelets ⬍ 100, 000/ml), and sequential multiple organ failure (SMOF, OFI ⬎ 2, renal and hepatic involvement). Hypothesis: There will be differences in plasma soluble CD163 levels across pediatric sepsis phenotypes. Methods: PICU patients with sepsis were prospectively enrolled. Blood samples were collected Mondays and Thursdays. Whole blood ex vivo LPS-induced TNF production and plasma soluble CD163 levels were assayed by ELISA. Clinical data included OFI scores and outcomes. Statistical analyses included t-Test, Wilcoxon test and logistic regression. Results: Forty-nine (49) of a goal of 100 sepsis patients have been enrolled to date. Thirty-five (71%) patients had sepsis-associated MOF (OFI ⬎ 2). The incidences of the previously described sepsis phenotypes were not mutually exclusive: 7 (14%) patients had immunoparalysis, 10 (20%) patients had SMOF and 11 (22%) patients had TAMOF. Soluble CD163 levels ranged from 0.3 to10.2 mg/L and were increased in MOF patients compared to those without (4.8 ⫾ 0.53 vs. 2.5 ⫾ 0.44, p ⬍ 0.002, t-Test). Only TAMOF was independently associated with increased sCD163 levels (p ⬍ 0.0002). Soluble CD163 levels in non-survivors (n ⫽ 3, 6.47 ⫾ 1.59) were not statistically different from survivors (n ⫽ 46, 3.25 ⫾ 0.43). Ex vivo LPS-stimulated TNF production did not correlate to plasma sCD163 levels. Conclusions: Although sCD163 levels did not reach thresholds indicative of HLH or MAS (20 mg/L), higher levels were associated with TAMOF. Further work is in progress to investigate the mechanism of elevated sCD163 levels in TAMOF.

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416

CIRCULATING NUCLEOSOME AS A PREDICTOR OF SEPSIS AND ORGAN DYSFUNCTION IN CRITICALLY ILL PATIENTS

LOW SERUM SELENIUM LEVEL WAS ASSOCIATED WITH POOR PROGNOSIS OF PATIENTS WITH SEPTIC SHOCK

Xiangming Fang, Qixing Chen, Baoli Cheng, Yue Jin, Zhejiang University

So Young Ha, Gil Joon Suh, Woon Yong Kwon, Kyung Su Kim, Myung Hee Park, Department of Emergency Medicine, Seoul National University College of Medicine

Introduction: Sepsis is a leading cause of death in critically ill patients, in which apoptosis plays a major role in the pathophysiology of sepsis. Elevated levels of circulating nucleosomes released by apoptotic cells have been detected in patients with severe sepsis and septic shock. Hypothesis: The circulating nucleosomes in sepsis may have diagnostic/prognostic value. Methods: Newly admitted patients who were estimated to stay for more than 48 hours in intensive care unit were prospectively enrolled. Levels of circulating nucleosomes within 24-hour of admission were measured and analyzed for the capacity of predicting sepsis. Results: In total, 64 patients were recruited. The nucleosomes levels on admission in 50 patients with sepsis were significantly higher than those in 14 non-septic patients (P ⫽ 0.015). The area under the receiver-operating-characteristic curve was 0.72 (95% confidence interval, 0.57 to 0.87). The optimal cutoff value for circulating nucleosomes to distinguish sepsis from non-sepsis is 2.64 arbitrary unit with 51% sensitivity and 92% specificity. Multiple logistic regression analysis confirmed circulating nucleosomes as an independent predictor for sepsis. Furthermore, the levels of circulating nucleosomes on admission were significantly correlated with the immunosuppressive response and organ dysfunction in sepsis, while not associated with the fatal outcome of sepsis. Conclusions: The present study demonstrates that serum circulating nucleosomes have a predictive value in sepsis and organ dysfunction, and may serve as a candidate biomarker for diagnosis/prognosis of sepsis.

Introduction: Recent clinical data have shown that low selenium level is associated with poor prognosis of critically ill patients. However, few studies have investigated whether serum selenium level is associated with prognosis of patients with septic shock. Hypothesis: This study was performed to determine whether low serum selenium level is associated with the poor prognosis of patients with septic shock. Methods: This was a prospective, observational study conducted in an emergency intensive care unit (ICU) of a tertiary referral hospital. We enrolled consecutive patients who were admitted to the emergency ICU with septic shock from February 2006 to May 2010. We collected data with respect to demographic findings, diagnosis, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Mortality was defiled as death occurring during hospital stay. According to the mortality, the enrolled patients were divided into two groups, the survivors and the non-survivors. We obtained blood samples through an arterial catheter at admission to the ICU and measured serum selenium levels. We compared the data between the survivors and the non-survivors using chisquare test or student t-test. Then, the area under the receiver operating characteristics curve (AUC) was measured to evaluate the discrimination ability for the hospital mortality. Results: Among 147 patients, 88 were the survivors and 59 were the non-survivors. The APACHE II score of the survivors were lower than that of the non-survivors. Serum selenium level of the survivors was higher than that of the non-survivors (p ⫽ 0.043). The APACHE II score (AUC [95% confidence intervals], 0.847 [0.628-1.000]) and serum selenium levels (AUC [95% confidence intervals], 0.889 [0.706-1.000]) were discriminative for the hospital mortality. Conclusions: Low serum selenium level was associated with the poor prognosis of patients with septic shock.


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418

PREDICTORS OF ICU TRANSFER IN PATIENTS WHO DEVELOP MODIFIED SIRS CRITERIA

EVALUATION OF THE INDIVIDUAL SIRS CRITERIA FOR THE DETECTION OF SEPSIS IN THE MEDICAL INTENSIVE CARE UNIT

Michael Young, Michael Hooper, Supriya Gowda, Gordon Bernard, Arthur Wheeler, Lisa Weavind, Todd Rice, Vanderbilt University Medical Center Introduction: Sepsis is defined as the systemic inflammatory response syndrome (SIRS) secondary to infection, and it commonly occurs in hospitalized patients. Patient characteristics which predict transfer to an ICU in patients with SIRS are not entirely understood. Hypothesis: We hypothesized that demographics, baseline characteristics, and physiologic parameters would predict the need for ICU transfer in a cohort of general medical patients with modified SIRS criteria. Methods: We studied 207 patients on medical wards at Vanderbilt Hospital who met modified SIRS criteria (at least one abnormal criterion being temperature or WBC count). We compared 117 consecutive patients who required transfer to the MICU with 90 consecutive patients who did not. We collected data on baseline demographics, comorbidities, physiologic condition, severity of illness, and clinical outcomes. Results: Patients transferred to the ICU were similar in age to those not transferred (54 vs. 58y, p ⫽ 0.11). Transferred patients were more likely to be male (p ⫽ 0.049) and on chronic dialysis (p ⫽ 0.026), and less likely to be immunosuppressed (p ⬍ 0.001) or have chronic lung disease (p ⫽ 0.025). At the time they met SIRS criteria, patients transferred to the ICU were more likely to be septic (p ⫽ 0.014) and in shock (p ⬍ 0.001) with higher WBC count (13.8 vs. 7.4, p ⬍ 0.001), heart rate (120 vs. 94, p ⬍ 0.001), respiratory rate (31 vs. 20, p ⬍ 0.001), and temperature (37.6 vs. 37.1, p ⬍ 0.001). The rate of positive blood cultures after enrollment was similar between groups (p ⫽ 0.375). In regards to outcome, patients requiring ICU transfer were more likely to be transferred to a skilled-nursing facility (p ⫽ 0.001) or die during the 28-day study period (p ⬍ 0.001). Conclusions: Our data suggests that in hospitalized patients meeting modified SIRS criteria at a tertiary care medical center, male gender and more severe derangements of individual SIRS criteria were associated with ICU transfer. Chronic dialysis was also associated with ICU transfer, but other comorbidities were not. We propose that additional studies of patients in other hospital settings may lead to improved models for predicting which patients with modified SIRS criteria should be transferred to an ICU.

Matthew Semler, Michael Hooper, Vanderbilt, Lisa Weavind, Gordon Bernard, Arthur Wheeler, Vanderbilt University Medical Center, Todd Rice, Vanderbilt University Introduction: The systemic inflammatory response syndrome (SIRS) represents a collection of physiologic and laboratory indices widely used to identify patients with sepsis. The criteria were developed by consensus without evaluation of sensitivity and specificity of the individual variables for detecting sepsis. Hypothesis: We hypothesized that modified SIRS was highly sensitive, but not specific, for sepsis and that elevated temperature and elevated WBC were specific for sepsis. Methods: We prospectively evaluated 536 consecutive patients admitted to our MICU for the presence of modified SIRS criteria (ⱖ 2SIRS criteria with one being abnormal WBC or Temperature). The presence of sepsis was determined by retrospective chart review. The sensitivity, specificity, positive and negative predictive value for each individual SIRS criterion were calculated. Receiver operating characteristic (ROC) curves for each variable were determined. Results: Of the 536 patients, 478 (89%) met modified SIRS criteria and 203 (38%) had sepsis. Modified SIRS criteria had a sensitivity of 99%, specificity of 17%, PPV of 42%, and NPV of 97% for the presence of sepsis. In patients with modified SIRS criteria, 201 (42%) had sepsis. The current SIRS criteria demonstrated a sensitivity, specificity, PPV, and NPV respectively of: 34%, 90%, 72%, 65% for elevated temperature; 26%, 50%, 27%, 48% for low temperature; 73%, 33%, 44%, 64% for elevated heart rate; 65%, 27%, 55%, 36% for elevated respiratory rate; 46%, 42%, 40%, 46% for elevated WBC; and 84%, 6%, 39%, 36% for low WBC. Using ROC curves, the variables discriminating the presence of sepsis were elevated WBC (AUC 0.686; 95% CI 0.634 to 0.739), elevated heart rate (AUC 0.640; 95% CI 0.589 to 0.692), elevated respiratory rate (AUC 0.641; 95% CI 0.590 to 0.692), and elevated WBC (AUC 0.570; 95% CI 0.512 to 0.627). Conclusions: Modified SIRS criteria had a high sensitivity but poor specificity for sepsis upon admission to the MICU. Elevated temperature was highly specific for sepsis (90%), while the remainder of the individual variables were not specific for sepsis.

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BASELINE CHARACTERISTICS, COMORBIDITIES, AND OUTCOMES OF PATIENTS WITH SIRS BASED ON ROUTE OF ADMISSION TO THE MEDICAL INTENSIVE CARE UNIT

CANDIDA SCORE COMBINED WITH PROCALCITONIN TO DIAGNOSE INVASIVE CANDIDIASIS IN SURGICAL CRITICALLY ILL PATIENTS: A RETROSPECTIVE STUDY

Supriya Srinivasa Gowda, Michael Hooper, Matthew Semler, Lisa Weavind, Arthur Wheeler, Gordon Bernard, Todd Rice, Vanderbilt University Medical Center

Xiangdong Guan, Xiaoyue Li, Rongyao Wu, Juan Chen, the First Affiliated Hospital of Sun Yat-sen University

Introduction: The route of hospital admission may be associated with different clinical outcomes in patients with Systemic Inflammatory Response Syndrome (SIRS) admitted to the ICU. Hypothesis: We hypothesized that the route of admission to the ICU is associated with significant differences in patient demographics, physiologic characteristics, comorbidities, and outcomes in patients with SIRS. Methods: Medical ICU patients admitted from either the emergency room (ER), an outside facility (OF), or from an in-hospital medical ward (MW) were screened for the development of “Modified SIRS Criteria” (2 SIRS criteria with one being either an abnormal temperature or WBC count). Results: Among 466 consecutive admits to the MICU who met modified SIRS criteria, 207 (44%) were admitted from the ER, 142 (30.5%) from OF and 117 (25%) from MW. Mean age of patients was 52 years with no difference between groups (p ⫽ 0.282) and 54% were male (p ⫽ 0.353). Black patients represented a higher percentage of patients admitted via the ER compared to OF or MW transfers (p ⬍ 0.001). MW transfers were more likely to have chronic lung disease, chronic dialysis, and immunosuppression compared to patients transferred from ER or OF. Physiologic parameters differed between groups, with patients from MW having higher temperatures (p ⫽ 0.016), heart rates (p ⫽ 0.012), and respiratory rates (p ⫽ 0.003). Mean WBC did not differ between groups, but MW patients were more likely to be neutropenic (p ⫽ 0.001). The proportion of patients in shock at the time of transfer was similar between groups. The incidence of sepsis was 54% among MW patients, 39% for those from OF and 38% from the ER (p ⫽ 0.094). The rates of positive blood cultures in the MICU were similar between groups (p ⫽ 0.170; cumulative rate of 21.5%). The mortality rate for patients presenting from the ER (7.2%) was significantly lower than for patients from OF (14%) or from MW (17%; p ⫽ 0.018). Conclusions: Our study shows that the route of admission to MICU is associated with significant differences in the baseline characteristics, physiologic status, and outcomes of patients with SIRS. Differences in comorbidities between groups may be responsible for much of the differences in physiology and outcome.


Introduction: Invasive candidiasis (IC) has become a leading cause of sepsis and septic shock in critically ill patients. However, it can be difficult to accurately and quickly diagnose IC because conventional microbiological, histological, and radiological methods are relatively insensitive, and time-consuming. Hypothesis: the Candida Score (CS) and procalcitonin (PCT) level could be used in combination to predict IC in surgical critically ill patients. The diagnostic efficacy of PCT is better than that of beta-1, 3-D-glucan (BG) for IC. Methods: It was a retrospective, observational study. We conducted a cohort review of critically ill patients with CSⱖ2 points who had cotemporaneous PCT and BG levels in the Surgical ICU of a tertiary care university hospital from June 2008 to December 2009. Diagnosis value of PCT and BG were assessed and compared. Results: Compared with control group patients (n ⫽ 101), observation group patients (n ⫽ 54) had higher 1PCT48h (1.10 ⫾ 0.34 ng/ml vs. 0.42 ⫾ 0.21 ng /ml, )and 2BG48h (22.94 ⫾ 10.57 pg/ml vs. 10.89 ⫾ 5.17 pg/ml). The area under the receiver operating characteristic (ROC) curve for PCT48h and BG48h were 0.960 (95% CI: 0.933 to 0.986) and 0.859 (95% CI: 0.793 to 0.926) respectively. With a cut-off value of 0.55 ng /ml, PCT48h had a sensitivity of 92.59% and a specificity of 88.12%. Conclusions: Our study suggests that CS can be used in combination with PCT to diagnose IC among surgical critically ill patients. For diagnosing IC, PCT has an advantage over BG.

421 PREDICTORS OF ICU LENGTH OF STAY IN PATIENTS WITH MODIFIED SIRS CRITERIA Michael Hooper, Lisa Weavind, Supriya Gowda, Arthur Wheeler, Gordon Bernard, Todd Rice, Vanderbilt University Medical Center Introduction: The Systemic Inflammatory Response Syndrome (SIRS) is common in hospitalized patients. Understanding factors associated with outcomes in patients with SIRS may help clinicians identify high risk patients and provide more intensive treatments. Hypothesis: We hypothesized that the individual SIRS criteria would independently predict ICU length of stay after adjustment for baseline patient characteristics and severity of illness. Methods: We prospectively evaluated 479 consecutive patients with modified SIRS criteria (defined as 2 SIRS criteria with at least one being temperature or WBC) admitted to the MICU at Vanderbilt University Hospital. Demographics, vital signs, and baseline characteristics were recorded via chart review by study personnel. Each patient was followed until the earlier of death, discharge, or study day 28. ICU length of stay was defined as the total number of days during the 28 day study period that a patient was under the care of an ICU team. Patients who died were assigned an ICU length of stay of 28 days.We used a stepwise method to construct a linear regression model to predict ICU length of stay. Individual SIRS criteria, age, shock, mechanical ventilation, RASS, and a diagnosis of infection at the time of enrollment were considered as variables for the model. Results: Our cohort had an average age of 54 ⫾ 18 years. 55% of patients were male and 42% were retrospectively determined to be septic at the time of enrollment. The median ICU length of stay was 3 days [IQR 2 to 7]. Stepwise linear regression predicted ICU length of stay (days) ⫽ -2.354 ⫹ 1.4 *[abs value RASS] ⫹ 2.9*presence of shock ⫹ 3.3*presence of elevated pulse(y/n) ⫹ 2.1*presence of elevated respiratory rate(y/n) ⫹ 0.062*age (r2 ⫽ 0.15;P ⬍ 0.001). Conclusions: In a single center cohort of 479 MICU patients with modified SIRS criteria, elevated pulse, elevated respiratory rate, shock, age, and RASS were independently predicted an increased ICU length of stay.


Poster: Sepsis- Therapeutics 422

423

ACE INHIBITION REDUCES MORTALITY IN PATIENTS WITH SEVERE SEPSIS

THE EFFECT OF ANTIPYRETIC EXPOSURE ON CLINICAL OUTCOMES IN GRAM-NEGATIVE SEPSIS

Paul Dobesh, Donald Klepser, Timothy McGuire, Margaret Hitzeman, Keith Olsen, University of Nebraska Medical Center College of Pharmacy

Nicholas Mohr, Hawnwan Moy, Robert Alunday, Washington University School of Medicine, Scott Micek, Barnes-Jewish Hospital, Richard Fagley, Washington University School of Medicine, Lee Skrupky, Barnes-Jewish Hospital

Introduction: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have demonstrated the ability to have a positive effect on a number of inflammatory markers in patients with diabetes, heart failure, and hypertension. Animal models suggest that ACE inhibitors/ARBs may be able to protect against the excessive inflammatory response observed in sepsis. Therefore, we evaluated the effect of ACEIs/ARBs on in-hospital mortality in patients with severe sepsis. Hypothesis: Determine the effect of ACE inhibitors and ARBs on mortality in patients with severe sepsis. Methods: This retrospective cohort study included all patients over age 40 with a diagnosis of severe sepsis and an ICU admission at our academic medical center from 1/1/2005 to 12/31/2008. ACE inhibitor/ARB use, patient demographics, and APACHE II score at the time of sepsis were collected from patient charts. We used a multivariable logistic regression model to evaluate the association between ACEI/ARB use and in-hospital mortality after controlling for age, gender, and severity of illness. Results: We identified 547 patients who met the inclusion criteria for this study. Of those patients, 245 (44.8%) had exposure to an ACE inhibitor/ARB. ACE inhibitor/ ARB and non-ACE inhibitor/ARB patients were similar in gender (53%) and APACHE II scores (21 ⫾ 6.9), while ACE inhibitor/ARB patients were older (67 ⫾ 12 vs. 63.2 ⫾ 13.4 years; p ⫽ 0.001). In the univariate comparison, ACE inhibitor/ARB users had a 40% relative reduction in mortality compared to non-ACE inhibitor/ARB users (23.3% vs. 38.7%; p ⬍ 0.001). In the multivariable regression, ACE inhibitor/ARB use had a protective effect (OR 0.40 CI 0.25-0.63, p ⬍ 0.001), while age (OR 1.04 CI 1.02-1.06), APACHE II score (OR 1.10 CI 1.06-1.13), existing coronary artery disease (OR 2.17 CI 1.313.59), heart failure (OR 1.89 CI 1.08-3.33), and liver disease (OR 2.88 CI 1.58-5.25) were associated with increased mortality. Conclusions: In this analysis, the use of an ACE inhibitor/ARB had a protective effect on patients with severe sepsis by significantly reducing mortality compared to patients not receiving an ACE inhibitor/ARB.

Introduction: Fever is a common response to life-threatening infection and has prognostic implications in critically ill patients. Animal trials suggest that fever may be important to survival in severe sepsis, but human data conflict on the use of antipyretic medications for critically ill adults. Hypothesis: Antipyretic administration early in severe sepsis is associated with increased mortality. Methods: Single-center, retrospective cohort study of 278 adult patients with gramnegative severe sepsis or septic shock and fever at a 1, 111-bed academic center from January 2002 through February 2008. Early antipyretic therapy was defined as administration of acetaminophen or ibuprofen within 6 hours of presentation. Results: Patients were treated with an early antipyretic agent (129 with acetaminophen, 4 with ibuprofen) in 47% of cases. Patients in the early antipyretic group had a higher incidence of neutropenia (32% vs. 21%, p ⬍ 0.05) and a higher Tmax (39.3 vs. 39.0 deg. C, p ⬍ 0.01), but were otherwise well matched. Significantly fewer patients receiving antipyretics required admission to an ICU (62% vs. 78%, p ⬍ 0.01), mechanical ventilation (32% vs. 54%, p ⬍ 0.01), or vasopressor support (32%vs. 50%, p ⬍ 0.01) within 3 days of presentation. While antipyretic use was associated with lower in-hospital mortality (26% vs. 37%, p ⫽ 0.05) in univariate analysis, it was not independently associated with survival (OR 1.31, 0.67-2.51) in multivariate logistic regression. Independent predictors of mortality were APACHE-II score, mechanical ventilation, neutropenia, and hospital steroid use. Conclusions: In this retrospective study of patients with severe gram-negative sepsis, in-hospital mortality was significantly lower in patients receiving early antipyretic therapy. Antipyretic use was not independently associated with survival in multivariate regression, potentially as the result of confounding variables. These findings are hypothesis-generating for future clinical trials, as the role of fever control has been largely unexplored in severe sepsis. This study was made possible by Grant Number UL1 RR024992 from the NIH-National Center for Research Resources.

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REAL-LIFE EXPERIENCE WITH DROTRECOGIN ALFA ACTIVATED FOR SEVERE SEPSIS: AN EFFECTIVENESS AND SAFETY META-ANALYSIS

28-DAY ALL-CAUSE MORTALITY IN PATIENTS RECEIVING ERITORAN WITH SEVERE SEPSIS AND HIGHER RISK OF MORTALITY BY INFECTION TYPE (BACTEREMIC VS NONBACTEREMIC): ANALYSIS OF DATA FROM A PHASE II TRIAL

Andre Kalil, University of Nebraska, Steven LaRosa, Brown University Introduction: Drotrecogin alfa activated (DAA) has been approved since 2001, but controversies about its real-life effectiveness outside clinical trials remains. Hypothesis: We aim to evaluate the effectiveness (hospital mortality) and safety (serious bleeding) in all studies that evaluated DAA in the last 9 years and compare it with the PROWESS APACHE II ⬎ 25 trial results. Methods: A systematic review was performed for all controlled and single -arm studies that evaluated DAA in patients with severe sepsis. The pooled results were analyzed by randomeffects models. Risk Ratios, 95%CI, and p-values were reported. Results: Effectiveness: 8 controlled (N ⫽ 42, 258) and 8 single-arm (N ⫽ 2, 370) trials; Safety: 18 single-arm (N ⫽ 7, 376) studies. Relative risk (RR) of hospital mortality was reduced by 17% with DAA compared to controls (RR ⫽ 0.83[95%CI 0.79, 0.87]; p ⬍ 0.0001; I2 ⫽ 39%). This mortality reduction was similar to PROWESS ⬎ 25 (RR ⫽ 0.71[95%CI 0.59, 0.85]; p ⫽ 0.0002). Both propensityadjusted studies (RR ⫽ 0.85[95%CI 0.81, 0.89]; p ⬍ 0.0001) and unadjusted studies (RR ⫽ 0.78[95%CI 0.70, 0.88]; p ⬍ 0.0001) showed a significant, but smaller relative mortality reduction, 15% and 22%, respectively, compared to PROWESS ⬎ 25 (29%). A metaregression showed higher DAA benefits with increasing control mortality (p ⫽ 0.00002) and higher APACHE II scores (p ⫽ 0.03). The DAA hospital mortality for single-arm studies (46% [95%CI 4250%]) was significantly (p ⬍ 0.0001) higher than that for PROWESS ⬎ 25 (31% [95%CI 27-36%]). Serious bleeding with DAA in the 18 studies was 6.0% (95%CI 4.9-7.4 %), which was significantly (p ⫽ 0.002) higher than that of PROWESS ⬎ 25: 3.5% (2.5-5.0%). Metaregression did not show association between serious bleeding and APACHE II (p ⫽ 0.63). Conclusions: Compared to PROWESS APACHE II ⬎ 25, real-life use of DAA was associated with higher hospital mortality rates in both controlled and single-arm trials, and significant, but smaller reduction in the risk of death (17%). Propensity-adjusted trials suggested smaller benefits than unadjusted studies. The rate of serious bleeding was significantly higher in real-life use of DAA than PROWESS. The benefit/risk ratio with DAA remains higher in sicker patients.


Steven Opal, The Warren Alpert Medical School of Brown University, Mark Tidswell, Baystate Medical Center Introduction: An animal study published in 2006 (Solomon JID 2006:193: 634) suggested that eritoran may be more effective in the treatment of bloodstream than extravascular infections; we explored the differences in eritoran and placebo (PBO) treatment outcomes in patients with severe sepsis caused by bacteremic vs non-bacteremic infections. Hypothesis: We expected that higher doses of eritoran may be required for patients with extravascular infection. Methods: For this post-hoc analysis, we examined data from a phase 2, randomized, PBO-controlled trial of 45 mg or 105 mg of eritoran tetrasodium in pts with severe sepsis. This trial enrolled pts aged 18-85 with severe sepsis. Our analysis focused on pts in the 105-mg arm who had Acute Physiology and Chronic Health Evaluation (APACHE)-II scores of ⬎ 20 stratified by causative infection type: bacteremic vs non-bacteremic. Results: 142 pts with baseline APACHE II ⬎ 20 received eritoran tetrasodium 105 mg or PBO and were included in this analysis. Among 44 subjects with bacteremia, the rates of 28-day all-cause mortality were 48% (11/ 23) for eritoran and 33% (7/21) for placebo; the difference was not statistically significant. Among 98 subjects with non-bacteremic infection, the rates of 28-day all-cause mortality were 24% (11/46) for eritoran and 48% (25/52) for placebo; the difference was statistically significant (P ⫽ 0.0138). The Breslow-Day test suggested that treatment outcomes were affected by whether or not the infection was bacteremic (P ⫽ 0.0258). In patients with bacteremia, the relative risk of all-cause mortality for eritoran tetrasodium 105 mg versus placebo was 1.43 with 95% confidence interval of 0.68 to 3.01; in patients with non-bacteremic infection, the relative risk of all-cause mortality for eritoran tetrasodium 105 mg versus placebo was 0.50 with 95% confidence interval of 0.28 to 0.90. Conclusions: In contrast to the findings of Solomon et al, humans with high-risk severe sepsis caused by extravascular infections appeared to show greater benefit from treatment with the higher dose of eritoran than did patients with bacteremic infection. Given the small sample size of this subanalysis, this result would need confirmation in larger trials.

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THE EFFECT OF LOADING DOSE TIMING OF ERITORAN ON 28-DAY MORTALITY IN PATIENTS WITH SEVERE SEPSIS AND HIGHER RISK OF MORTALITY: ANALYSIS OF DATA FROM A PHASE II TRIAL

EFFICACY OF ERITORAN IN HIGHER-RISK PATIENTS WITH SEPSIS BY BASELINE ENDOTOXIN LEVEL: ANALYSIS OF DATA FROM A PHASE II TRIAL

Roland Schein, University of Miami Miller School of Medicine, Mark Tidswell, Baystate Medical Center Introduction: Since toll-like receptor 4 (TLR4) activation occurs at the earliest stage of the systemic inflammatory response cascade, we explored the impact of the timing of the first dose of eritoran, a TLR4 antagonist, on patient (pt) survival in pts at higher risk of mortality. Hypothesis: We expected that earlier administration of eritoran would be associated with reduced mortality. Methods: We examined data from a phase 2, randomized, placebo (PBO)-controlled trial of 45 mg or 105 mg of eritoran tetrasodium in pts with severe sepsis. This trial enrolled pts (18-85 years) within 12 hours of identification of severe sepsis. Our analysis focused on pts in the 105-mg arm with APACHE II scores of ⬎ 20 (the entry criterion and dose adopted for the phase 3 trial of eritoran) to determine the effect on all-cause 28-day mortality of receiving the initial loading dose ⱕ6 hrs after diagnosis of severe sepsis compared to receiving it ⬎ 6 hrs after diagnosis. Results: 142 pts with baseline APACHE II ⬎ 20 received eritoran tetrasodium 105 mg or PBO and were included in this analysis. Among 31 pts who began treatment ⱕ6 hrs of diagnosis, mortality was 29% (4/14) for eritoran and 47% (8/17) for PBO. Mortality for the 111 pts who began treatment ⬎ 6 hrs after diagnosis was 33% (18/55) for eritoran and 43% (24/56) for PBO. The differences in rates of mortality were not statistically significant overall or by timing of first dose. Differences among mean baseline APACHE II scores for the 4 groups were not statistically significant: eritoran ⱕ6 hrs 26.1, PBO ⱕ6 hrs 27.1, eritoran ⬎ 6 hrs 26.7, PBO ⬎ 6 hrs 27.5. The Breslow-Day test suggested timing of the first dose had no effect on mortality (p ⫽ 0.6709). The relative risk of all-cause mortality for eritoran tetrasodium 105 mg vs PBO was 0.73 with 95% confidence interval of 0.47 to 1.12 using Cochran-Mantel–Haenszel statistics stratified by timing of first dose. Conclusions: Within the constraints of a limited sample size, we found that the reduction in mortality rate of eritoran vs PBO in higher-risk pts who initiated treatment ⬎ 6 hrs after diagnosis of severe sepsis did not significantly differ from that of pts who initiated treatment ⱕ6 hrs of enrollment.

Mark Tidswell, Baystate Medical Center, Steven Opal, The Warren Alpert Medical School of Brown University Introduction: We analyzed a subgroup of patients from the modified intent-totreat population of a phase II, randomized, placebo (PBO)-controlled trial of eritoran, a toll-like receptor 4 antagonist, to determine if eritoran efficacy correlated with baseline levels of endotoxin, a frequent mediator of sepsis, in patients (pts) with severe sepsis and higher risk of mortality. Hypothesis: We expected that pts with higher baseline endotoxin levels would respond best to treatment with eritoran. Methods: Pts with severe sepsis in the eritoran tetrasodium 105 mg arm and PBO arm with Acute Physiology and Chronic Health Evaluation (APACHE)-II scores of ⬎ 20 were stratified into 2 groups: those without elevated baseline endotoxin (⬍0.2 EU/mL) and those with elevated endotoxin (ⱖ0.2 EU/mL). We compared 28-day all-cause mortality among pts receiving eritoran and PBO to determine if response to eritoran correlated with baseline endotoxin. Results: Of the 111 pts who had baseline APACHE II ⬎ 20 and recorded baseline endotoxin values, 52 received eritoran and 59 PBO. Eighteen of the eritoran pts had normal baseline endotoxin, and of these 5 (28%) died; 34 of the eritoran pts had elevated endotoxin, and of these 13 (38%) died. Twenty-six of the PBO pts had normal endotoxin, and of these 11 (42%) died; 33 PBO pts had elevated endotoxin, and of these 17 (52%) died. Favorable but not statistically significant trends toward lower mortality rates were observed in pts receiving eritoran tetrasodium105 mg within each baseline level of endotoxin. The relative risk of all-cause mortality for eritoran vs PBO was 0.71 with 95% confidence interval (CI) of 0.45 to 1.13 using Cochran-Mantel–Haenszel statistics stratified by baseline endotoxin. The Breslow-Day test suggested no statistically significant difference in the treatment effect on mortality between baseline levels of endotoxin (P-value ⫽ 0.8985). Conclusions: Although no significant correlations between treatment effect and baseline endotoxin levels were observed, higher risk pts with severe sepsis appear to benefit from treatment with eritoran, regardless of the baseline level of endotoxin. Given the small sample size, this result will need to be confirmed in a larger trial.

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COMPARATIVE EFFICACY OF ERITORAN, A TOLL-LIKE RECEPTOR 4 ANTAGONIST, IN PATIENTS WITH SEVERE SEPSIS AND HIGHER RISK OF MORTALITY BY TYPE OF CAUSATIVE PATHOGEN

DOPPLER ASSESSMENT OF THE EFFECTS ON SPLANCHNIC AND RENAL PERFUSION OF LOW DOSES OF VASOPRESSIN IN SEPTIC SHOCK PATIENTS.

Steven LaRosa, Rhode Island Hospital , Mark Tidswell, Baystate Medical Center

Introduction: Septic shock is a condition in which the splanchnic hypoperfusion is common and potentially harmful. Hypothesis: We tested the hypothesis that the infusion of low doses of vasopressin may be able to increase splanchnic perfusion in septic shock patients Methods: 11 patients in septic shock with infusion of norepinephrine and mean arterial pressure ⬍ 70 mmHg. We started the infusion of low dose vasopressin (max ⫽ 0.05 IU/kg/h) to reach an average pressure of 70 mmHg. All patients were monitored with pulmonary artery cater and splanchnic perfusion was assessed using the Doppler technique. Ultrasound measurements of flow and resistance of the celiac artery, superior mesenteric artery, portal vein and hepatic artery were performed at baseline and after 30 minutes after the infusion of vasopressin. Results: All patients had the following hemodynamic changes: a decrease in cardiac index and heart rate, and increased systemic vascular resistance. The pulmonary resistance have not undergone major changes. The flow in the celiac trunk is significantly increased (TAVM 20cm/s vs 31cm/s) while the vessel vascular resistance significantly decreased. Same phenomenon was recorded in the superior mesenteric artery (TAVM 19cm/s vs 37cm/s), the effect of vasopressin was greater in the superior mesenteric artery than in the celiac trunk. The portal vein flow increased during infusion of vasopressin (TAVM 7.8cm/s vs 9 cm/s). The interlobular renal artery pulsatility index decreased significantly (0.79 vs. 0.69). Conclusions: Infusion of low dose vasopressin (0.05 IU/kg/h), used to arrive at an average pressure of 70 mmHg in patients in septic shock, induces an increase in splanchnic perfusion and renal perfusion.

Introduction: We sought to determine if the type of causative pathogen was associated with differences in 28-day all-cause mortality in patients (pts) with a higher risk of mortality receiving eritoran for severe sepsis. Hypothesis: We expected that eritoran would be efficacious across a broad range of pathogen types. Methods: Our analysis was based on data from a randomized, doubleblind, placebo (PBO)-controlled study conducted in the US and Canada in pts aged 18-85 with severe sepsis. PBO, eritoran tetrasodium 45 mg, or 105 mg were administered every 12 hrs for 6 days. The primary efficacy variable was 28-day all-cause mortality. For this analysis, we examined 28-day all-cause mortality in patients with APACHE II scores ⬎ 20 receiving eritoran tetrasodium 105 mg/d or PBO by pathogen type: gram negative, gram positive, mixed, and other/ unknown. Results: 142 pts with baseline APACHE II ⬎ 20 received eritoran tetrasodium 105 mg or PBO and were included in the analysis. One eritoran pt was excluded from analysis because pathogen type was missing. Overall mortality rates were 31% (21/68) for eritoran and 44% (32/73) for PBO. Among 39 pts with gram negative pathogen, mortality rates were 43% (9/21) for eritoran and 50% (9/18) for PBO. Among 48 pts with gram positive pathogen, mortality rates were 35% (7/20) for eritoran and 43% (12/28) for PBO. Among 17 pts with mixed pathogen type, mortality rates were 0% (0/8) for eritoran and 33% (3/9) for PBO. Among 37 pts with pathogen type as other or unknown, mortality rates were 26% (5/19) for eritoran and 44% (8/18) for PBO. The relative risk of all-cause mortality for eritoran vs PBO was 0.69 with 95% confidence interval of 0.45 to 1.08, and odds ratio was 0.55 with 95% CI of 0.27 to 1.12, using Cochran-Mantel-Haenszel test stratified by pathogen type. The Breslow-Day test suggested that eritoran treatment outcomes were unaffected by pathogen type (P-value ⫽ 0.4834). Conclusions: Within the constraints of a limited sample size, 28-day all-cause mortality did not appear to be correlated with type of identified pathogen in pts with severe sepsis and higher risk of mortality. Future clinical trials of eritoran should include pts with all types of infecting pathogen.

Massimo Meco, Marie Allaz, Silvia Cirri, Istituto Clinico Sant’Ambrogio


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RETROSPECTIVE EVALUATION OF THE RELATIONSHIP BETWEEN VASOPRESSOR DOSAGE AND DURATION AND IN-HOSPITAL MORTALITY IN SEPTIC SHOCK: THE RESPONSE STUDY

DOES DELAY IN VASOPRESSOR ADMINISTRATION AFFECT MORTALITY IN PATIENTS WITH SEPTIC SHOCK?

Suzanne Conyne-Rapin, UC Health-University Hospital; University of Cincinnati, Christopher Roberts, University of Cincinnati, Neil Ernst, Eric Mueller, UC Health-University Hospital; University of Cincinnati

Introduction: Earlier treatment of patients with septic shock, particularly with antibiotics has been shown to reduce mortality. Hypothesis: We hypothesized that earlier initiation of vasopressor medication would similarly improve survival in septic shock patients with refractory hypotension. Methods: Approval for this project was attained from the local research ethics board. Retrospective data of time to vasopressor administration after the onset of septic shock was collected on 8, 640 adult patients from 24 intensive care units in Canada and the United States. Survival to hospital discharge was analyzed using multivariate logistic regression analysis with backward elimination of significant variables. Demographic data was dichotomized into ’early’ and ’late’ treatment groups based on the median time of delay to vasopressors for the entire cohort (2.92 Hrs). The groups were compared using the Chi Squared Test. Results: The main outcome was survival to hospital discharge. In total, 8, 640 patients met the definition of septic shock and received vasopressors. The overall unadjusted mortality rate was 47%. 1933 observations were removed due to incomplete data capture. The demographic data analysis showed significant differences between ‘early’ and ‘late’ groups with acute coronary syndromes, COPD, emergency surgery, and liver failure. Of these, only liver failure was an independent predictor of mortality and thus entered into the final analysis.Independent mortality predictors were liver failure (OR 3.38, 95% CI, 2.66-4.29), metastatic cancer (OR 1.66, 95% CI, 1.36-2.02), AIDS (OR 2.01, 95% CI, 1.39-2.89), malignancy (OR 1.87, 95% CI, 1.48-2.36), and neutropenia (OR 1.83, 95% CI, 1.33-2.52). Also, analyzed as continuous variables, antibiotic delay (OR 1.071, CI, 1.06-1.08), age (OR 1.03, CI, 1.02-1.03), and Apache Score (OR 1.11, 95% CI, 1.10-1.12) were also found to be significant. After adjustment, the odds for survival were 0.83, 0.73, 0.74, 0.77, 0.87, 0.68, 0.68, 0.87, and 1.09 for increasing time delays of 0.12, 0.5, 1.16, 2, 2.9, 4, 5, 0.75, 8.45, and 14.1 hours respectively. Conclusions: Earlier treatment with vasopressor does not convey a survival benefit in patients with septic shock.Case Reports:

Introduction: Catecholamine (CA) vasopressors are commonly used for hemodynamic support in patients with septic shock. Although adverse physiologic effects (e.g., impaired microvascular circulation) are well described, the relationship between CA dosage and mortality is poorly defined. CA dosage over time likely represents vascular smooth muscle dysfunction. Hypothesis: CA dosage over time is higher in nonsurvivors and independently associated with mortality in patients with septic shock. Methods: This single-center, retrospective, casecontrol study evaluated adult critically ill surgical and medical patients with septic shock admitted between Jan 2009 and Mar 2010. Patients with guideline-defined septic shock were included. The primary outcome was difference in daily maximum vasopressor index (VI) between in-hospital nonsurvivors (cases) and survivors (controls) [VI ⫽ (dopamine) ⫹ (epinephrine ⫻ 100) ⫹ (norepinephrine ⫻ 100) ⫹ (phenylephrine ⫻ 10); dosages in mcg/kg/min]. Stepwise multivariate logistic regression (MVLR) was performed to determine the independent association between daily CA dosage and in-hospital mortality. Results: 142 patients (nonsurvivors n ⫽ 67; survivors n ⫽ 80) were included (in-hospital mortality 54.4%). Baseline characteristics were similar between groups except increased CA initiation SOFA and chronic hepatic failure in nonsurvivors. Over 98% of all patients received norepinephrine-based CA regimens. Nonsurvivors required significantly higher CA dosages on days 1-6 (p ⬍ 0.032 for all). Areas under the receiver operating characteristic (ROC) curves for predicting mortality were 0.72 and 0.82 for worst daily: maximum VI and SOFA, respectively. Best predictive thresholds on ROC analysis were 31 and 14, respectively. On MVLR controlling for respective daily SOFA, vasopressin, and clinically relevant factors affecting mortality, CA dosage was independently associated with mortality (dichotomous VI ⬎ 33 on day 3 [OR 17.8, CI 1.6-198.5] or continuous VI on day 3 [1.07, 1.0131.14]). Duration of CA alone was not associated with mortality. Conclusions: CA dosage and response over time likely reflects prolonged vascular smooth muscle failure and is independently associated with mortality in septic shock.

Vance Beck, University of Ottawa, Anand Kumar, University of Manitoba, Greg Bryson, Ottawa Hospital

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RECOMBINANT THROMBOMODULIN (RTM) MAY BE EFFECTIVE FOR SEPSIS WITH DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

RANDOMIZED CONTROLLED TRIAL OF RECOMBINANT HUMAN SOLUBLE THROMBOMODULIN FOR SEPSIS AND DISSEMINATED INTRAVASCULAR COAGULATION PATIENTS

Yoshitomo Namba, Jun Sasaki, Makoto Hayashi, Kazumasa Watanabe, Munetaka Hayashi, Kentarou Narihara, Showa University Fujigaoka Hospital Introduction: To investigate the therapeutic effect of rTM for DIC associated sepsis. DIC is a serious complication that can occur during treatment of sepsis. Conventional treatment of DIC consists of the adminstration of heparins as well as platelet transfusion or FFP supplementation. rTM has become commercially available for patient with septic DIC in Japan 2008. rTM has been developed as a novel treatment that inhibits activated factors V and VIII by activating protein C and binding high morbility group box 1 protein (HMGB1). Hypothesis: This study is to evaluate whether rTM is effective for septic DIC in the intensive care unit (ICU). Methods: We conducted a retrospective study in our emergency room (ER) and ICU. Subjects were 40 patients with septic DIC who were administered rTM between August 2008 and August 2010 (rTM group) and 20 patients who were not administered rTM between August 2007 and August 2008 (Control group). All patients were admitted from ER. DIC was diagnosed by Japanese Association for Acute Medicine (JAAM) DIC Criteria. rTM was administered for six consecutive days in rTM group. In both groups, data was measured at day 0 (before treatment of DIC), and day 7. (1) Changes in severity score (APACHE II, SOFA), coagulation and inflammatory markers (PTINR, D-dimer, AT III, PIC, TAT, PAI-1, CRP, procalcitonin, IL-6, IL-1 beta, HMGB1, etc) in rTM group were investigated. (2) DIC resolution rate, ICU mortality, hospital mortality, and changes in severity score and coagulation and inflammatory markers were compared between two groups. Results: (1) Significant improvements were observed in APACHE II, SOFA, PTINR, D-dimer, AT III, PIC, TAT, CRP, procalcitonin, and IL-6 (p ⬍ 0.05). (2) The baseline characteristics were almost similar between two groups. Although not statistically significant, rTM group had higher DIC resolution rate and lower mortality rate as well as greater improvements in each marker. Conclusions: In patients administered with rTM, severity score improved significantly. In addition, rTM group tended to have lower mortality rate. This study supports that rTM could be effective for septsis with DIC.


Hiroto Ushizawa, Eiji Isotani, Yasuhiro Otomo, Tokyo Medical and Dental University Introduction: It is expected that recombinant human soluble thrombomodulin (rTM) not only reverses hyper-coagulative status through activating protein C but also prevents multiple organ failure. We started and a randomized controlled trial of rTM for sepsis and disseminated intravascular coagulation patients. We introduce the preliminary report in this paper. Hypothesis: rTM improves both physiological scores and the amount of mediators, and reduces the mortality of sepsis and DIC patients in 28 days. Methods: We enrolled and analyzed 19 patients who were treated for DIC accompanied by sepsis from October 2008 to August 2010. They were randomized into rTM-treated group or placebo-treated group (9 to 10). Our primary endpoint was mortality in 28 days. As composite outcomes, We compared Acute Physiology and Chronic Health Evaluation (APATCHE II) score, Sequential Organ Failure Assessment (SOFA) score, acute phase DIC score, and serum soluble thrombomodulin, TNF-␣, IL-1␤, IL-6, HMGB-1, protein C, protein S levels among both groups in 10 days. Statistical analysis was performed by Wilcoxon rank-sum test. P ⬍ 0.05 was regarded as statistically significant. Results: We found that all scores and mediators improved after administration of rTM in Day 10, but there was no significant differences among both groups. Neither was mortality in 28 days. Median of each score or mortality was as follows; APATCH II score: rTM group 22, control group 17.5 (p ⫽ 0.27), SOFA score: rTM 8, control 5.5 (p ⫽ 0.52), acute phase DIC score: rTM 3.5, control 3.5 (p ⫽ 0.69), SIRS score: rTM 2.5, control 1.5 (p ⫽ 0.23), mortality in 28days: rTM 0.44, control 0.20 (p ⫽ 0.27). Significant adverse effects such as gastrointestinal bleeding, cerebral hemorrhage, and bronchial hemorrhage by using rTM were not observed in this trial. Conclusions: Further investigation will be needed to ascertain whether rTM is effective for DIC accompanied by sepsis.This work was supported by a grant from Asahi-Kasei pharmaceutical co. ltd. Referrence: H. Saito, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5: 31-41.

434 REBOUND HYPOTENSION AFTER HYDROCORTISONE DISCONTINUATION IN SEPTIC SHOCK Katri Abraham, Lisa Hall Zimmerman, Janie Faris, Detroit Receiving Hospital, Ghulam Saydain, Wayne State University Internal Medicine, Pulmonary Medicine, Linda Browning, Detroit Receiving Hospital Introduction: Septic shock is associated with a mortality rate up to 80%. Previous studies and guidelines advocate the use of hydrocortisone (HC) in septic shock patients who remain hypotensive despite fluid resuscitation and vasopressor therapy. Limited data exists regarding hypotensive events after HC discontinuation. Hypothesis: To evaluate rebound hypotension (RH) after discontinuation of HC in patients with septic shock. Methods: This retrospective study evaluated adult patients admitted to the MICU with septic shock from Jan 08-May 10 who received HC 50 mg IV q 6 hours. Patients were divided into two groups: RH vs no rebound hypotension (NRH). RH was defined as systolic blood pressure (SBP) decrease ⬎ 40 mmHg or SBP ⬍ 90mmHg within 24 hours of HC discontinuation. P-value ⬍ 0.05 was considered significant. Data are expressed as mean ⫾ SD. Results: This study evaluated 32 patients (16 RH vs 16 NRH) with septic shock, primarily respiratory source, with a mean age of 61 ⫾ 13 years and APACHE II of 27 ⫾ 8. Half of the patients (16) had HC tapered upon discontinuation. There were no significant differences in baseline characteristics between RH vs NRH. A trend towards higher in-hospital mortality was seen in RH vs NRH (63% vs 31%, p ⫽ 0.08) with no differences in those patients that survived in hospital length of stay (LOS) [30 ⫾ 28 vs 25 ⫾ 14 days, p ⫽ 0.6] and ICU LOS [18 ⫾ 11 vs 14 ⫾ 10 days, p ⫽ 0.43]. No differences were found in taper vs abrupt discontinuation for RH vs NRH. Higher in-hospital mortality was seen in RH patients who did not receive vasopressin for shock (77% vs 18%, p ⫽ 0.006) and who were age ⱖ50 (23% vs 69%, p ⫽ 0.02). Conclusions: In-hospital mortality tended to increase in patients who experienced RH after discontinuation of HC. In-hospital mortality was higher in those patients with RH who did not receive vasopressin and those who were older. Further study is needed to identify risk factors associated with RH.


Poster: Sepsis-Antimicrobials 435

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COMBINATION EMPIRIC THERAPY FOR GRAM-NEGATIVE HEALTHCARE-ASSOCIATED INFECTIONS: ADEQUACY OF AMINOGLYCOSIDES VERSUS FLUROQUINOLONES IN THE SETTING OF BETA-LACTAM RESISTANCE

RISK OF ACUTE KIDNEY INJURY (AKI) ASSOCIATED WITH SINGLE DOSE AMINOGLYCOSIDE (SDA) ADMINISTRATION IN PATIENTS WITH SEVERE SEPSIS AND SEPTIC SHOCK

Marcus Dortch, Vanderbilt University Medical Center, Rondi Kauffmann, Vanderbilt University Medical Ctr, Patrick Norris, Vanderbilt Univ. Med. Center - Div. of Trauma and Surgical Critical Care, Addison May, Vanderbilt University Medical Center Introduction: Inadequate antibiotic therapy is associated with mortality in critically-ill patients with sepsis. To increase the probability of adequate therapy against potential multi-drug resistant gram-negative pathogens, empiric combination therapy comprised of broad-spectrum beta-lactams (BL) with an aminoglycoside (AMG) or fluoroquinolone (FQ) is recommended. However, widespread use of FQs may be leading to increased resistance. Hypothesis: AMGs provide adequate antibiotic therapy more than FQs in the setting of BL resistance. Methods: A retrospective analysis of infection control data collected 2001 to 2008 was conducted in a single center’s trauma and surgical intensive care units. For diagnosed healthcare-associated infections, antimicrobial susceptibility data was collected for isolated gram-negative pathogens. Susceptibility to AMGs and FQs was assessed for pathogens resistant to broad-spectrum BLs including 3rd/4th generation cephalosporins (CEPH), beta-lactamase inhibitor combos (BLIC), or carbapenems (CARB). Pathogens were grouped by susceptibility; FQ-R (FQ-resistant/AMG-sensitive) or AMG-R (AMG-resistant/FQ-sensitive). Proportional differences of study groups were assessed using ⌾2 test with Bonferroni correction (p-value ⱕ0.008). Results: 1, 794 gram-negative pathogens were isolated from 2, 374 health-care associated infections. Resistance to BLs was: CEPH 31% (559); BLIC 37% (644); and CARB 10% (172). For BLIC-resistant pathogens, AMGs would have provided adequate therapy significantly more than FQs [FQ-R (7.1%) vs. AMG-R (5.0%), p ⫽ 0.005]. For CEPH & CARB resistant pathogens, AMGs would have also provided adequate therapy more than FQs; however these observations were not statistically significant [CEPH resistant: FQ-R (8.8%) vs. AMG-R (5.2%), p ⫽ 0.068]; [CARB resistant: FQ-R (17.4%) vs. AMG-R (10.5%), p ⫽ 0.167]. Conclusions: For BL-resistant pathogens isolated from healthcareassociated infections, combination therapy consisting of BL ⫹ AMG would have provided adequate therapy more often compared to combination therapy consisting of BL ⫹ FQ. Unless contraindicated, empiric therapy consisting of BL ⫹ AMG should be considered as 1st line in the setting of suspected gram-negative healthcare-associated sepsis.

Ana Avram, Tampa General Hospital, Robert Handzel, SUNY Upstate Medical University, Babak Sarani, Trauma Center At Penn, William Schweickert, University of Pennsylvania, Amanda Ball, Cassandra Bellamy, Hospital of the University of Pennsylvania, Seema Sonnad, University of Pennsylvania, Todd Miano, Hospital of the University of Pennsylvania Introduction: Inadequate empiric antimicrobial therapy is associated with a twofold increase in hospital mortality. Retrospective studies have established inadequate therapy most commonly occurs with nosocomial infections and resistant gram negative rods are the most common pathogen. Aminoglycosides (AG) are often effective against these resistant pathogens. However, the concern for nephrotoxicity, especially in patients with compromised circulation, may prompt clinicians to withhold aminoglycosides. Whether single doses of AG in critically ill patients with severe sepsis and septic shock increases the risk of acute kidney injury is unknown. Hypothesis: SDA administration will not affect the risk of AKI in patients with severe sepsis and septic shock. Methods: Retrospective cohort analysis of adult ICU patients with severe sepsis or septic shock given SDA as part of empiric therapy compared to those not receiving any AG. The primary endpoint was the incidence of AKI, defined as either an absolute increase in serum creatinine concentration of ⬎ 0.5 mg/dL or an increase from baseline of ⬎ 50%, whichever was greater. Secondary endpoints were the incidence of AKI according to the RIFLE criteria (without assessment of urine output) and the need for dialysis. Continuous data were assessed using student’s t-test or Mann-Whitney test as appropriate. Categorical data were assessed with the chi square test. Results: 448 patients were included (AG n ⫽ 164, control n ⫽ 284). Baseline serum creatinine, comorbidities, and age were similar between groups. SDA patients had longer lengths of stay prior to infection, higher APACHE II scores, a higher rate of shock, received more fluids, and more concomitant nephrotoxins compared to control patients (all p ⬍ 0.05). Despite SDA patients having greater severity of illness, there was no difference in study defined acute kidney injury: 46/164 SDA (28%) compared to 71/284 control (25%), p ⫽ 0.5. There was no difference in RIFLE-AKI or the need for dialysis. Conclusions: SDA administration as empiric therapy for severe sepsis and septic shock did not affect the risk of AKI in patients with severe sepsis and septic shock.

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IMPACT OF PREVIOUS ANTIMICROBIAL EXPOSURE ON GRAM-NEGATIVE SEPSIS: ANALYSIS OF SUSCEPTIBILITY AND MORTALITY

TIMING OF ANTIBIOTIC ADMINISTRATION IN GRAMNEGATIVE SEPTIC SHOCK

Michael Johnson, UIC-College of Pharmacy, Reichley Reichley , BJC Healthcare, Scott Micek, Barnes-Jewish Hospital, Marin Kollef, Washington Univ. School of Medicine Introduction: Appropriate selection of antimicrobial therapy has been associated with improved survival in septic shock. Optimizing empiric therapy based on the patient’s risk for resistant pathogens is imperative. Hypothesis: Previous exposure to anti-pseudomonal agents in the last 90 days may result in decreased Gram-negative susceptibility and subsequent reutilization as empiric therapy may increase mortality. Methods: Retrospective study of patients with GN bacteremia complicated by septic shock over six years (01/02-12/07). Results: Data from 752 patients with 846 GN organisms isolated from the bloodstream were evaluated. E. coli (25%), K. pneumoniae (24%), and P. aeruginosa (16%) were the most common organisms isolated. 41% (n ⫽ 310) of the patients had previous antibiotic exposure. Cefepime was the most common agent with previous exposure (26%), followed by ciprofloxacin (17%) and carbapenems (13%). Resistance was greater in cases with previous exposure versus no exposure for the following agents: cefepime (41% v. 10%), piperacillin/tazobactam (non-Pseudomonas isolates) (39% v. 21%), carbapenems (41% v. 7%), ciprofloxacin (38% v. 14%) and gentamicin (41% v. 14%) (all P ⬍ 0.05). High MIC values (within two dilutions of the MIC break point) were more common with prior exposure to cefepime (26% v. 9%, P ⬍ 0.001) and carbapenems (29% v. 9%, P ⬍ 0.001). Empiric reutilization had a higher rate of mortality when compared to patients treated with a new antibiotic (55 v. 38%, P ⬍ 0.001). Reutilization was associated with a 1.89-fold increase in mortality (CI 1.20-2.96, P ⫽ 0.005) via multivariate analysis. Conclusions: Reutilization is associated with increased mortality in GN sepsis. Previous antibiotic exposure should receive careful consideration during prescribing of empiric therapy.


Heather Rouse, Penn State Hershey Medical Center, Stacy Voils, Virginia Commonwealth University Health System Introduction: Each hour delay in administration of appropriate antibiotics in patients with septic shock has been shown to decrease survival. Hypothesis: It is hypothesized that if potential barriers to antibiotic administration are present, then there will be a significant delay in antibiotic administration leading to worse outcomes in patients with gram-negative (GN) septic shock. Methods: This was a retrospective cohort study including adult intensive care unit (ICU) patients with positive cultures for a GN organism who required vasopressor support and met the definition of septic shock. Barriers assessed with the potenial to impact antibiotic administration were ‘routine‘ order status, pharmacy verification ⬎ 15 minutes, prescribing errors, and ordering a non-formulary medication. The time of antibiotic administration from the initial onset of hypotension and septic shock was collected and analyzed by the presence of these barriers. Results: A total of 123 patients were screened and 41 patients met inclusion criteria. Fifty-six percent were male with a mean age of 60.1 years ( ⫾ 13.7) with an overall hospital mortality rate of 56%. The median time to antibiotic administration from the onset of hypotension was 7 hours (IQR, 3.1-13) and the time to appropriate antibiotic administration (based on susceptibilities) was 7.1 hours (IQR, 3.816.6). The most commonly identified barrier was ordering antibiotics as ‘routine‘ (n ⫽ 16, 39%). An ANOVA analysis showed the barriers did not have a significant impact on the timing of antibiotic administration. The timing of any GN antibiotic did not have a significant impact on mortality at discharge (p ⫽ 0.16), length of hospital stay (p ⫽ 0.4), ICU stay (p ⫽ 0.9), or length of mechanical ventilation (p ⫽ 0.82), a finding confirmed by multivariate analyses. Conclusions: We found a 7 hour delay in antibiotic administration from the onset of hypotension in patients with GN septic shock. However, none of the identified potential barriers were associated with a significant impact on time to antibiotic administration.

Poster: Sepsis-Cardiovascular 439 ATRIAL FIBRILLATION IN THE INTENSIVE CARE UNIT Tara Quasim, University of Glasgow, Lee Riddell, Glasgow Royal Infirmary, John Kinsella, University of Glasgow Introduction: Atrial Fibrillation (AF) is a common arrhythmia in the critically ill population. It is associated with an increased severity of illness, longer length of hospital stay and worse mortality. The aim was to determine the incidence and outcomes of patients with new onset atrial fibrillation or those with a pre-existing history, in a cohort with detailed, prospectively collected data. Patients who did not experience any type of AF were used as a comparator. We also examined the role of the inflammatory response in the development of AF. Hypothesis: We hypothesised that patients with AF had an increased severity of illness and greater degree of inflammation than those who did not develop AF. In addition we hypothesised that patients with chronic AF would exhibit a different oucomes to those that developed it acutely. Methods: This was a retrospective cohort study of all patients admitted between 27/04/2006 - 05/09/2009 to a 9 bedded, level 3 tertiary referral ICU within the West of Scotland, UK. Baseline data recorded included age, APACHE II, predicted hospital mortality, actual ICU and hospital mortality and the highest CRP recorded during the critical illness. Results: The data of 1056 consecutive patients was analysed. The incidence of new onset AF was 13.9% whilst 4.4% of patients had a pre-existing history. The hospital mortality rate was 31.7% in those who did not experience AF compared to 48.2% in those who did (p ⬍ 0.001). The hospital mortality was 30.4% in those with a prior history of AF and 53.7% in the new onset group (p ⫽ 0.006). The peak CRP was higher in those with AF (p ⬍ 0.001) and higher in those with new onset AF as opposed to those with a prior history of AF (p ⫽ 0.044). Conclusions: Patients with AF in ICU were older, more unwell, had a longer ICU stay and higher hospital mortality. They had higher peak CRP corroborating previous hypotheses that inflammation may have a role in the aetiology of AF. Patients with chronic AF do not have worse outcomes than predicted and do exhibit a different response to those who develop it acutely. Future research on AF in the critically ill should differentiate between those patients with new onset and those with a prior history.

440 CHANGES IN CATECHOLAMINE REQUIREMENTS AFTER ADDITION OF VASOPRESSIN PREDICTS SURVIVAL IN PATIENTS WITH SEPTIC SHOCK Maggie Mechlin, University of Cincinnati College of Medicine, Suzanne Conyne-Rapin , Shaun Keegan, Eric Mueller, UC Health/The University Hospital, Steven Lisco, University of Cincinnati College of Medicine Introduction: Septic shock is a common and perilous disease. Vasopressin may diminish catecholamine requirements, but how this impacts patient outcome is unknown. Hypothesis: Change in catecholamine dosage after vasopressin initiation is a predictor of survival in patients with septic shock. Methods: This retrospective case-control study included adult patients with guideline-defined septic shock receiving catecholamines and at least 12 hours of vasopressin admitted to an academic medical center from January 2009 to March 2010. Catecholamine dosage was expressed as vasopressor index (Vi) (Vi ⫽ dopamine ⫹ dobutamine ⫹ 100*epinephrine ⫹ 100*norepinephrine ⫹ 100*phenylephrine [units mcg/kg/min]). Patients were divided into survivors and non-survivors. The primary outcome was comparison of daily and %change in Vimax between groups. Results: 30 survivors and 54 non-survivors were included (64% mortality). Median SOFA score on vasopressin day 0 was higher in non-survivors (11 vs 14; p ⬍ 0.001). A trend toward survival was seen in surgical ICU compared to medical ICU patients (50% vs 28%; p ⫽ 0.07). Median daily Vimax was similar between non-survivors and survivors on vasopressin day 0 (44 vs 25; p ⫽ 0.07); however, median daily Vimax was lower in survivors on vasopressin days 1, 2, and 3 (48 vs 10; p ⫽ 0.03; 28 vs 9;p ⫽ 0.021; 17 vs 5; p ⫽ 0.01). The %change in Vimax from vasopressin day 0 to 1 and vasopressin day 1 to 2 was greater in survivors (-0.06 vs -0.47; p ⫽ 0.02; -0.10 vs -0.50; p ⫽ 0.007); there was no difference in %change Vimax after 2days (-0.25 vs -0.58; p ⫽ 0.06). A decrease in Vimax by 30% or more between vasopressin days 0 and 2 had a 93% sensitivity and a 57% specificity for predicting survival. Positive and negative predictive values were 55% and 93%, respectively. Conclusions: Survivors required lower catecholamine doses and more often had a significant decrease after vasopressin initiation. Based on high sensitivity and negative predictive value, a ⬎ 30% decrease in Vimax from vasopressin day 0 to 2 may differentiate those who survive septic shock from those who do not.

441

442

EVOLUTION OF HEMODYNAMICS IN COMMUNITY ACQUIRED AND HOSPITAL ACQUIRED PEDIATRIC SEPSIS

A NON PHARMACOLOGIC APPROACH FOR THE TREATMENT OF SEPTIC SHOCK: THE INTRA-AORTIC BALLOON PUMP

Akash Deep, King’s College Hospital, Joe Brierley, Great Ormond St, London Introduction: To study the evolution of fluid refractory septic shock after PICU admission. Hypothesis: Evolution of shock necessitates regular hemodynamic assessment to permit appropriate vasoactive therapy. Methods: Prospective observational study of 18 children with fluid-resistant septic shock (despite ⬎ 40 mls/kg fluid ) admitted to 2 tertiary UK PICU. Hemodynamics assessed by ultrasonic cardiac output monitor (USCOM) with CI, SVRI, SVCO2 & CVP measured sequentially. Assessment at PICU admission and regularly thereafter, especially around interventions. Results: At presentation children categorized into 2 hemodynamic groups: A (n ⫽ 9) high CI, low SVRI (warm shock) and B (n ⫽ 9) with low CI, high SVRI (cold shock). 7/9 warm shock admitted to PICU from hospital due to hospital-acquired infection (vascular access device or surgical site infection), 8/9 cold shock community acquired sepsis. 6 warm shock children Gram-positive sepsis as opposed to 2 cold shock. Apart from 1 warm shock fungaemia all other cultures gram negative. All Group A started on vasopressor alone (nor-epi). Within median of 8 hours, 5 had inotrope added due to falling CI. 2 progressed to frank cold shock requiring vasopressor substitution with inotrope (1 in 2 hrs, 1 in 14 hrs) and 1 needed inodilator. Mean SCVO2 in group A: 58 ⫹/⫺ 5 %. Both vasopressor substitution with inotrope children had concurrent SCVO2 drop to mean 50 %9 in B had a mean SCVO2 of 54 ⫹/⫺ 3.0 % and were initially started on inotropes. Within median of 10 hrs, 3 required vasodilator adding and an additional patient after 24 hours had large rise in CI and fall in SVRI and was weaned off inotropes support and started on norepi.There was 1 death in each group, 1 with severe catecholamine resistant cold shock at presentation, the other the early warm to cold shock child, both had ECMO contraindications. Remaining 16 discharged intact at 30 days. Conclusions: The hemodynamic status of children in septic shock changes over time necessitating hemodynamic assessment to guide addition or changes of inotrope/ vasopressor therapy. If a child in septic shock is not improving or deteriorates after an initial response, repeat hemodynamic measurements should allow optimization of therapy.

Lora Silverman, Nicolas Mouawad, Ajay Gupta, Mary-Margaret Brandt, MaryAnne Purtill, St. Joseph Mercy Medical Center Introduction: The Food and Drug Administration has approved the use of the intra-aortic balloon pump (IABP) in cardiogenic shock and septic shock, most recently in 2006. Significant yet temporary myocardial dysfunction is a known complication of septic shock. Case reports of IABP use in septic shock in human subjects are more than 30 years old. These data were collected prior to the development of the bedside percutaneously inserted device and long before standardized management goals for sepsis were developed. Hypothesis: Percutaneously inserted IABP can be successfully used to provide cardiac support in patients suffering from temporary sepsis-induced myocardial dysfunction. Methods: We describe two cases of patients in their mid-50’s with no known cardiac history presenting to our surgical intensive care unit in profound septic shock. We resuscitated the patients, and obtained source control. Despite compliance with the Surviving Sepsis Campaign guidelines, both patients remained unresponsive to fluid resuscitation, vasoactive agents, and steroid administration. We monitored vital signs and cardiac parameters. Bedside echocardiography was obtained. Percutaneous IABP was placed after evolving myocardial ischemia and infarction was ruled out. Results: Echocardiography obtained in both patients revealed ejection fractions (EF) of 22% and 10% with severe global hypokinesis. Follow-up echocardiogram demonstrated EF of 50% and 60%, respectively, with no residual left ventricular dysfunction. Both had considerable improvements in systolic blood pressure, significantly lower vasopressor requirements within 24 hours, and made meaningful recoveries. Conclusions: IABP use is a viable option for the subpopulation of septic patients suffering from severe septic shock with myocardial suppression refractory to fluid, vasoactive agents, and steroids.


Poster: CPR/Resuscitation-1 444

446

WIN 55, 212-2 INDUCED HYPOTHERMIA AND IMPROVED MYOCARDIAL FUNCTION THROUGH ACTIVATION OF CB1 RECEPTOR IN RAT MODEL OF CPR

PRESERVATION OF LEFT VENTRICULAR MYOCARDIAL DISTENSIBILITY BY A NOVEL NHE-1 INHIBITOR BIX WITH NO EFFECT ON CASPASE-3 ACTIVITY

Yinlun Weng, Institute of Critical Care Medicine, Shijie Sun, Institute of Critical Care Medicine;Keck School of Medicine of the University of Southern California, Sen Ye, Jeonghyun Park, Institute of Critical Care Medicine, Max Harry Weil, Wanchun Tang, Institute of Critical Care Medicine; Keck School of Medicine of the University of Southern California

Jeejabai Radhakrishnan, Iyad Ayoub, Madhav Upadhyaya, Raul Gazmuri, Rosalind Franklin University of Medicine and Science

Introduction: We have previously demonstrated that WIN 55, 212-2, the nonselective cannabinoid (CB) 1/2 receptor agonist, produced hypothermia and improved outcomes of CPR. In this study, we investigated whether those effects were regulated through activation of CB1 or CB2 receptor in a rat model of CPR. Hypothesis: The hypothermia and resulting beneficial effects following the use of WIN 55, 212-2 are mediated by activating CB1 rather than CB2 receptors. Methods: Ventricular fibrillation (VF) was induced in 20 male S-D rats weighing between 450-550g. CPR was initiated after 6 min of untreated VF. Defibrillation was attempted after 8 min of CPR. Resuscitated animals were randomized into four groups: 1) placebo control; 2) WIN 55, 212-2; 3) selective CB1 receptor antagonist plus WIN 55, 212-2; 4) selective CB2 receptor antagonist plus WIN 55, 212-2. Animals randomized to receive intramuscular injection of placebo, CB1 or CB2 receptor antagonist at 5 min post resuscitation. Thirty min after injection, animals in groups 2, 3 and 4 received intravenous infusion with WIN 55, 212-2 at a dose of 1.0 mg/kg/h for 4 h while animals in group 1 received placebo of the same amount. Blood temperature and myocardial function, including the ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured and recorded. Results: Blood temperature was significantly decreased in both WIN 55, 212-2 and CB2 receptor antagonist treated animals. However, the temperature in the CB1 receptor antagonist and placebo treated animals remained at baseline value. EF, CO and MPI at 4 h after infusion were significantly better in both WIN 55, 212-2 and CB2 receptor antagonist treated animals compared to the other two groups (p ⬍ 0.05). Conclusions: WIN 55, 212-2 induced mild hypothermia and resulted in improved myocardial function by activating the CB1 receptor but not the CB2 receptor in the rat model of CPR.

Introduction: We have previously reported that caspase-3 activation is associated with resuscitation from cardiac arrest. Caspase-3 activation might lead to myocardial dysfunction linked to cleavage of contractile proteins and genomic DNA. We have also demonstrated in other studies that NHE-1 inhibitors preserve left ventricular myocardial distensibility and ameliorate post-resuscitation myocardial dysfunction. Hence, we examined whether myocardial protection exerted by NHE-1 inhibition involves reductions in caspase-3 activity using a novel NHE-1 inhibitor BIX. Hypothesis: We hypothesized that BIX administration during resuscitation will preserve myocardial distensibility and ameliorate caspase-3 activity. Methods: VF was electrically induced and left untreated for 10 minutes in two groups of four rats each. Rats were randomized to receive a new NHE-1 inhibitor (BIX, 1-mg/kg) or vehicle control into the right atrium at the start of chest compression. Defibrillation was attempted after 8 minutes of chest compression. Rats were monitored for 60 minutes post-resuscitation. Caspase-3 activity was measured in left ventricular tissue at 60 minutes post-resuscitation using a fluorescence based assay which measures the cleavage of the caspase-3 substrate DEVD-AFC. AFC released after cleavage was measured at 360/40 nm excitation and 528/20 nm emission wavelengths and activity was expressed as pmoles AFC released/min.mg protein-1. Results: Administration of the BIX at the beginning of chest compression was markedly effective in preserving myocardial distensibility, enabling a chest compression depth of 17 mm (maximal safe depth) to generate a forward blood flow that resulted in a coronary perfusion pressure 23 mmHg higher (45 ⫾ 12 vs 22 ⫾ 10, p ⬍ 0.05) and a mean aortic pressure 28 mmHg higher (62 ⫾ 15 vs 34 ⫾ 10, p ⬍ 0.05) than control rats. However, BIX did not affect caspase-3 activity as demonstrated by comparable activities in the BIX treated and control rats (3.6 ⫾ 2.3 vs 2.9 ⫾ 0.4). Conclusions: BIX preserved myocardial distensibility without affecting caspase-3 activity.

447

448

STERNAL WALL PRESSURE COMPARABLE TO LEANING DURING CPR IMPACTS INTRATHORACIC PRESSURE AND HEMODYNAMICS IN ANESTHETIZED CHILDREN DURING CARDIAC CATHETERIZATION

THE FIRST QUANTITATIVE REPORT OF VENTILATION QUALITY DURING THE RESUSCITATION OF OLDER CHILDREN AND ADOLESCENTS

Andrew Glatz, Dana Niles, Brian Hanna, Children’s Hospital of Philadelphia, Joar Eilevstjonn, Laerdal Medical AS, Laura Diaz, Children’s Hospital of Philadelphia, Matthew Gillespie, The Children’s Hospital of Philadelphia, Jonathan Rome, Robert Berg, Vinay Nadkarni, Children’s Hospital of Philadelphia Introduction: Force due to leaning (incomplete chest recoil) during cardiopulmonary resuscitation (CPR) negatively affects hemodynamics and intrathoracic airway pressures (ITP) in animal models and adults. The effect of leaning force on hemodynamics and ITP has not been studied in children. Hypothesis: In anesthetized children during cardiac catheterization, application of sternal force (SF) up to 20% of subject’s body weight (comparable to heavy leaning during CPR) will significantly increase central venous pressure and ITP. Methods: An IRB-approved pilot study of healthy, anesthetized, paralyzed, mechanically-ventilated children (6 mos-8 yrs) for routine hemodynamic cardiac catheterization ⬎ 6 mos after cardiac transplant was undertaken. Central hemodynamic measures via right heart and arterial catheters and ITP (peak proximal endotracheal tube pressure) via pneumotach were measured before and during incremental increases in SF of 10 and 20% of body weight. Primary outcomes include changes in central venous pressure (mean right atrial pressure (mRAP, mmHg) and ITP (cmH2O). Differences were compared by repeated measures ANOVA, then paired t-test as appropriate. Results: 14 subjects (mean age: 5.4 ⫾ 1.6 yrs, range: 3.1-7.9 yrs; weight: 18.5 ⫾ 3.5 kg) were studied. mRAP increased significantly with SF application of 10%: 7.1 ⫾ 1.8 vs 5.9 ⫾ 1.6 mmHg (p ⬍ 0.0001); and 20%: 7.7 ⫾ 1.8 vs 5.4 ⫾ 1.7mmHg (p ⬍ 0.0001); with greater increase at 20% (p ⬍ 0.0001). ITP increased significantly with SF application of 10%: 18.4 ⫾ 5.1 vs 16.5 ⫾ 4 cmH2O (p ⫽ 0.018); and 20%: 20.1 ⫾ 5.2 vs 17 ⫾ 4.2 cmH20 (p ⫽ 0.0001); with greater increase at 20% (p ⫽ 0.0004). In addition, coronary perfusion pressure (aortic diastolic – mRAP) decreased significantly with SF application of 10%: 41.3 ⫾ 6.7 vs 42.7 ⫾ 7.2 mmHg (p ⫽ 0.05) and 20%: 40.3 ⫾ 5.9 vs 42.8 ⫾ 6 mmHg (p ⬍ 0.0001). No significant differences were detected for other hemodynamic measures. Conclusions: In healthy, anesthetized children, sternal forces comparable to leaning forces previously reported during CPR elevate ITP and central venous pressure and decrease coronary perfusion pressure. These hemodynamic effects may be clinically important during CPR and warrant further study.


Andrew McInnes, Robert Sutton, Children’s Hospital of Philadelphia, Alberto Orioles, Children’s Hospital of Philadlephia, Akira Nishisaki, University of Pennsylvania School of Medicine, Dana Niles, Children’s Hospital of Philadelphia, Benjamin Abella, University of Pennsylvania Health System, Matthew Maltese, University of Penn/Children’s Hospital, Vinay Nadkarni, Robert Berg, Children’s Hospital of Philadelphia Introduction: Excessive ventilation is associated with worse clinical outcome after adult cardiac arrest. This study is the first to characterize ventilation rate adherence to American Heart Association (AHA) guidelines during in-hospital pediatric cardiac arrest. Hypothesis: We hypothesized that during pediatric CPR events, ventilation rates exceeding AHA guidelines would be common, occurring during at least 30% of the resuscitative time. Methods: Ventilation rate (breaths per minute [bpm]), determined via changes in chest wall impedance (CWI), was prospectively recorded during resuscitation of children and adolescents (ⱖ 8 years of age) who suffered a cardiac arrest in a pediatric intensive care unit (PICU) or emergency department (ED) of a tertiary-care pediatric hospital. Resuscitative time was divided into equal 30s epochs for analysis. Excessive ventilation was defined as a ventilation rate ⬎ 10 bpm (AHA-defined). Results: Twenty-six consecutive cardiac arrest events were screened; 24 (92%) provided interpretable CWI waveforms resulting in 588 thirty-second CPR epochs. The proportion of CPR with ventilation rates exceeding AHA guidelines was 63% (CI95 59-67%), significantly higher than our a priori hypothesis (p ⬍ 0.01). The proportion of CPR epochs with a ventilation rate exceeding 20 bpm was 20% (CI95 17-23%). After controlling for location of arrest and initial event rhythm, CPR epochs that occurred on nights/weekends were 3.6 times (CI95: 1.6 – 7.9, p ⬍ 0.01) more likely to have a ventilation rate exceeding AHA guidelines. Conclusions: During in-hospital pediatric cardiac arrest, rescuers frequently provide artificial ventilations at rates in excess of AHA guidelines, with twenty percent of CPR time having ventilation rates double that recommended. Excessive ventilation was particularly common during CPR events that occurred on nights/weekends. Funding: The Laerdal Foundation for Acute Care Medicine and the Endowed Chair of CCM at CHOP

449

451

FIRST DOCUMENTED CARDIOPULMONARY ARREST RHYTHM OFTEN DIFFERS FROM TELEMETRY RHYTHM AT THE TIME OF CODE BLUE CALL IN HOSPITALIZED ADULTS

ANTECEDENT BRADYCARDIA IS COMMON AND ASSOCIATED WITH POOR OUTCOME IN ADULT CARDIOPULMONARY ARREST PATIENTS HOSPITALIZED OUTSIDE THE ICU

Christian Coletti, Christiana Care Health Services, Utpal Bhalala, Christopher Bonafide, The Children’S Hospital of Philadelphia, Penny Rathmanner, Anita WITZKE, Melody Kasprzak, Christiana Care Health System, Vinay Nadkarni, Robert Berg, Children’s Hospital of Philadelphia, Marc Zubrow, Christiana Care Health System Introduction: The initial CardioPulmonary Arrest (CPA) ECG rhythm documented on hospital code records (1DOC) is reported to the National Registry of CPR (NRCPR) as a surrogate for etiology of arrest. We assessed ECG telemetry (TELE) records of monitored non-ICU patients at the time of CPA to evaluate their agreement with first documented rhythm. Hypothesis: The agreement between the 1DOC ECG rhythm reported to NRCPR and TELE ECG rhythms immediately prior to CPA will be less than 80% beyond that predicted by chance (kappa ⬍ 0.8). Methods: Descriptive analysis of 92 CPA non-ICU telemetry adult patients. 5 events were excluded due to missing data. CPA were defined as resuscitation events requiring ⬎ 1 minute of chest compressions or defibrillation. The CPA rhythm was determined by reviewing the first documented (1DOC) rhythm on the code sheet at time of CPR initiation. TELE ECG rhythm at the time of code call was independently determined by reviewing the 10 minutes of telemetry prior to the call. PEA arrest rhythms on the code sheet were considered “in agreement” with rhythms at the time of the code blue call that were organized and did not represent ventricular tachyarrhythmias (VTA). The primary outcome was the kappa statistic for agreement between 1DOC and TELE rhythms. Results: Of the 87 CPA events with complete data, 1DOC rhythms at the time of CPA were asystole (20%), VTA (23%), and PEA (57%). TELE rhythms at the time of code call were asystole (5%), VTA (37%), and other organized rhythms (59%). Agreement between TELE and 1DOC rhythms was 57% (kappa ⫽ 0.25, 95%CI 0.09-0.42). Among events with 1DOC recorded as asystole at time of code team arrival, the TELE rhythm at the time of the code call was asystole in only 18%, with VTA in 24%, and other organized rhythm in 59%. Conclusions: First documented CPA ECG rhythm from the code record reported to NRCPR had only fair agreement with TELE ECG rhythms at the time of the code blue call. VTA and organized rhythms will often degenerate to asystole by the time the code team arrives. Targeted interventions to facilitate rapid defibrillation and respiratory interventions to prevent asystole in hospitalized patients should be considered for future study.

Utpal Bhalala, Christopher Bonafide, The Children’s Hospital of Philadelphia, Christian Coletti, Penny Rathmanner, Christiana Care Health System, Vinay Nadkarni, Robert Berg, Children’s Hospital of Philadelphia, Anita Witzke, Melody Kasprzak, Marc Zubrow, Christiana Care Health System Introduction: In-hospital cardiopulmonary arrests (CPA) that are precipitated by respiratory insufficiency often exhibit bradycardia before the arrest. The purpose of this study was to determine the prevalence and association of antecedent bradycardia with outcome in adult patients with CPA occurring outside the ICU setting. Hypothesis: (1) Bradycardia often occurs in the 10 min preceding CPA. (2) Patients with bradycardia prior to CPA are more likely to have poor outcome than patients without antecedent bradycardia. Methods: Prospective cohort study of 92 CPA outside the ICU in patients monitored by telemetry. CPA were defined as requiring ⬎1 min of chest compressions or defibrillation. The arrest rhythm was the first documented rhythm on the code sheet at the time of CPR initiation. Two independent experts reviewed the telemetry data and measured the heart rate (HR) at 1-min intervals for the 10 min preceding CPA. The mean HR between observers was used for each interval. Bradycardia (HR 1-59) occurring at least 3 min before the code blue call was considered “antecedent” a priori. Good (versus poor) outcome was defined as survival with discharge to home or with no change from pre-arrest function. The association between antecedent bradycardia and poor outcome was evaluated using logistic regression. Results: Of the 92 CPA events, arrest rhythms included pulseless electrical activity (PEA, 54%), asystole (19%), ventricular tachyarrhythmia (23%) and undocumented (4%). The overall rate of survival to hospital discharge was 40% and good outcome was 38%. Among all CPA events, 57% (95%CI 46-67%) were preceded by bradycardia on telemetry between 3 and 10 min prior to CPA. Antecedent bradycardia was associated with poor outcome (OR⫽2.78, 95%CI 1.16-6.70, p⫽0.02). Conclusions: In a cohort of hospitalized adult patients with CPA outside the ICU, antecedent bradycardia was common and predicted poor outcome. Future studies should evaluate the association between antecedent bradycardia and respiratory insufficiency, which may be an under-recognized cause of preventable CPA.

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453

DURATION OF CPR AND ILLNESS CATEGORY IMPACT INHOSPITAL PEDIATRIC CARDIAC ARREST OUTCOMES

DEEP CHEST COMPRESSIONS >50MM IMPROVE HEMODYNAMIC OUTCOMES DURING ACTUAL PEDIATRIC AND ADOLESCENT ARREST

Renee Matos, Children’s Hospital of Pittsburgh, Robert Watson, University of Pittsburgh School of Medicine Children’s Hospital of Pittsburgh, Vinay Nadkarni, Children’s Hospital of Philadelphia, Hsin-Hui Huang, University of Pittsburgh, Peter Meaney, Children’s Hospital of Philadelphia, Christopher Carroll, Connecticut Children’s Medical Center, Robert Berg, Children’s Hospital of Philadelphia, Richard Berens, Children’s Hospital of Wisconsin, Amy Praestgaard, University of Pennsylvania, Philip Spinella, University of Connecticut Introduction: The effect of duration of CPR, accounting for illness category, on survival after in-hospital pediatric cardiac arrests (IHCA) is unknown. Hypothesis: Survival to hospital discharge and neurologic outcome following IHCA are associated with CPR duration, and modified by patient illness category. Methods: We analyzed all index pulseless IHCA ⬍18 years reported to the AHA National Registry of CPR (NRCPR) from 2000-2009 with CPR duration 1-180 minutes, excluding those in the NICU or delivery room. Illness category definitions of Surgical Cardiac (SC), Medical Cardiac (MC), General Medical (GM), General Surgical (GS), and Trauma were pre-defined. Stepwise multivariate logistic regression (SPSS 18.0, SAS 9.2) was used to adjust for factors associated withoutcome.FavorableneurologicoutcomewasdefinedasadischargePediatricCerebral Performance Category score of 1, 2 or 3, a priori. Results: Of 3396 patients, survival to hospital discharge was 28.1%. Survival decreased with CPR duration: 1-15 minutes (44%, n⫽1386), 16-35 minutes (18%, n⫽1037), and 36-180 minutes (16%, n⫽973), p⬍0.001. Between 1 and 15 minutes of CPR, survival decreased linearly by 2.4% per minute. SC patients had better survival 273/703 (39%) than GS 102/268 (38%), MC 173/570 (30%), GM 367/1466 (25%), or Trauma 38/389 (10%) patients, p⬍0.001. At CPR durations ⬍15 minutes, SC had the best survival compared to all other groups (p⬍0.001). SC also had better survival than GM at 1-15 minutes, adjOR 1.9 (95% CI 1.3-2.6); 16-35 minutes, 1.9 (1.2-3.2); and 36-180 minutes, 2.1 (1.3-3.6). Neurologic outcome was better for patients who received 1-15 minutes of CPR when compared to those who received 16-35 minutes (adjOR 0.26, 95%CI 0.20-0.34) or 36-180 minutes (0.19, 0.14-0.25), ⬍0.001. SC patients also had more favorable neurologic outcomes (32.8%) than all other groups: GS 27.2%, MC 21.2%, GM 14.3%, and Trauma 5.3%, p⬍0.001. Conclusions: Shorter duration of CPR is strongly associated with better survival and neurologic outcome after IHCA, even when accounting for potentially confounding variables. In addition, illness categories further impact adjusted survival and neurologic outcomes, independent of CPR event duration.

Robert Sutton, Akira Nishisaki, Dana Niles, Jessica Leffelman, Children’s Hospital of Philadelphia, Matthew Maltese, University of Penn/Children’s Hospital, Kristy Arbogast, Andrew McInnes, Robert Berg, Vinay Nadkarni, Children’s Hospital of Philadelphia Introduction: Existing pediatric cardiopulmonary resuscitation (CPR) guidelines are developed by expert consensus, extrapolating animal and adult data to children. Evidence collected from real children during cardiac arrest associating quality of CPR with improved hemodynamic outcomes has not been established. Hypothesis: Chest compressions (CCs) delivered to a depth of ⬎50mm will achieve prospectively targeted hemodynamic outcomes (SBP ⱖ100 mmHg, MBP ⱖ50mm Hg, and DBP ⱖ40 mmHg). Methods: With IRB approval, CPR monitoring/feedback enabled defibrillators captured CPR quality during consecutive in-hospital CC events in children ⱖ8 yrs with existing arterial BP catheter monitoring. Data included: CC depth (mm), CC force (kg), residual leaning force (kg), and arterial blood pressure (BP; mmHg). Simultaneous arterial BP associated with the force/depth of each CC was determined. Generalized estimating equations, adjusting the standard errors for within-event correlation between CCs, were used to determine the relationship between CC depth/force and arterial BP. A priori targeted hemodynamic outcomes were SBP ⱖ100 mmHg, MBP ⱖ50mmHg, and DBP ⱖ40 mmHg. Results: Analysis yielded 2915 evaluable CCs during 7 arrests (age range 13.5-17 yrs). After controlling for significant residual leaning force (⬎2500grams) between CCs, systolic and mean BP were related to CC depth (SBP ⫽ 22 ⫹ 1.12*CC depth (mm); MBP ⫽ 28 ⫹ 0.3*CC depth (mm); p⬍0.01 for both). Similarly, systolic and mean BP were related to CC force (SBP ⫽ 40 ⫹ 1.14*CC force (kg), p⬍0.01; MBP ⫽ 31⫹ 0.4*CC force (kg), p⫽0.04). Compared with CCs ⬍50mm depth, CCs ⱖ50mm depth were 3.7x (CI95 1.8 - 7.7) more like to achieve SBP ⱖ100 mmHg, 2.1x (CI95 1.3 3.4) more likely to achieve MBP ⱖ50 mmHg, and 2.1x (CI95 1.2 - 3.6) more likely to achieve a DBP ⱖ40 mmHg (p⬍0.01 for all). Conclusions: Chest compressions delivered to a depth of ⱖ50mm during real in-hospital pediatric CPR achieve targeted hemodynamic outcomes significantly more often than CCs ⬍50mm depth. These data support that during pediatric resuscitation attempts, providers should push hard to achieve hemodynamic goals.



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FORENSIC ANALYSIS OF CRIB MATTRESS PROPERTIES ON PEDIATRIC CPR QUALITY - CAN WE BALANCE SKIN INTEGRITY WITH CPR EFFECTIVENESS?

PROTOCOLIZED USE OF SEDATION AND PARALYSIS WITH THERAPEUTIC HYPOTHERMIA FOLLOWING CARDIAC ARREST

Dana Niles, Children’s Hospital of Philadelphia, Matthew Maltese, University of Penn/Children’s Hospital, Akira Nishisaki, Children’s Hospital of Phildelphia, Jessica Leffelman, Children’S Hospital of Philadelphia, Larissa Hutchins, Children’s Hospital, Nancy Schneck, The Children’s Hospital of Phildelphia, Robert Sutton, Kristy Arbogast, Robert Berg, Vinay Nadkarni, Children’s Hospital of Philadelphia

Timothy Ellender, Indiana University, Methodist Hospital/Indiana Clinic, Elizabeth Taber, Methodist Research Institute, Michelle Deckard, Dustin Spencer, Judith Jacobi, Methodist Hospital/Clarian Health

Introduction: Standard (Std) pressure reduction (PR) crib mattresses prevent skin injury yet large mattress deflection during CPR chest compressions (CC) are evident. New high-density (HD) PR crib mattress technology might provide similar PR for skin, with less mattress deflection during CC. Hypothesis: HD crib mattress will have less deflection during CC compared to current Std mattress. Methods: Epochs of 50 high quality CCs (target CC depth 38-51mm) guided by real-time internal potentiometer feedback were delivered to a CPR manikin with realistic CC characteristics on two crib mattress surfaces: Std vs HD. CCs were performed with/without a standard CPR backboard (each condition weight:12.6kg). Mattress displacement (mm) was measured using surface accelerometers. PR qualities of mattresses were assessed by mattress industry standard: qualitative time-lapse thermal density mapping. Analyses comparing force and displacement during CC for the two mattress types by t-test with two-tailed alpha⫽0.05. Data expressed as mean⫾SD. Results: Std and HD had equivalent PR characteristics by qualitative time-lapse thermal density mapping. During high quality CPR achieving target CC depth 38-51mm, the Std mattress had significantly more mattress displacement compared to HD mattress (Std 26.5⫾1.0mm vs. HD 9.8⫾0.7mm, p⬍0.0001). This difference was greater when backboard was not used (Std 42.0⫾1.5mm vs. HD 10.3⫾1.0mm, p⬍0.0001). Std mattress had lower applied force compared to HD on backboard (Std 42.3⫾1.5kg vs.44.5⫾ 2.8kg, p⬍0.0001). Conclusions: Chest compressions delivered on HD PR crib mattresses resulted in less mattress deflection compared to Std PR mattress. Forensic engineering analysis of crib mattress properties suggest characteristics of mattresses impact pediatric CPR quality, and that it is possible to balance skin PR qualities with CPR effectiveness. Mattress CPR quality testing should be done as hospitals move to PR mattress design.

Introduction: Therapeutic hypothermia (TH) has been shown to improve the neurologic recovery of cardiac arrest patients who experience return of spontaneous circulation (ROSC). It remains unclear as to how earlier cooling and treatment optimization influence outcomes. Hypothesis: Protocolized use of early sedation and paralysis improves cooling optimization and clinical outcomes. Methods: A 3-year (2008-2010), pre-post intervention study of patients with ROSC after cardiac arrest treated with TH was performed. Those patients treated with a standardized order-set which lacked a uniform sedation and paralytic order were included in the pre-intervention group, and those with a standardized orderset which included a unifrom sedation and paralytic order were included in the post-intervention group. Patient demographics, initial and discharge Glasgow Coma Scores (GCS), resuscitation details, cooling time variables, severity of illness as measured by the APACHE II score, discharge disposition, functional status, and days to death were collected and analyzed using Student t-tests, ManWhitney U tests, and the Log-Rank test. Results: 232 patients treated with TH after ROSC were included, with 107 patients in the pre-intervention group and 125 in the post-intervention group. The average time to goal temperature (33°C) was 227 minutes (pre-intervention) and 168 minutes (post-intervention) (p⫽0.001). A 2-hour time target was achieved in 38.6% of the patients (postintervention) compared to 24.5% in the pre-group (p⫽0.029). Twenty-eight day mortality was similar between groups (65.4% and 65.3%) though hospital length of stay (10 days-Pre & 8 days post-intervention) and discharge GCS (13 preintervention & 14-Post) differed between cohorts. More Post patients were discharged to home (55.8%) compared to 43.2% in the pre-intervention group. Conclusions: Protocolized use of sedation and paralysis improved time to goal temperature achievement. These improved TH time targets were associated with improved neuroprotection, GCS recovery, and disposition outcome. Standardized sedation and paralysis appears to be a useful adjunct in induced TH.

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7.5% NACL WITH ADENOSINE, LIDOCAINE AND MG2ⴙ REDUCES FLUID REQUIREMENT AND IMPROVES KIDNEY FUNCTION FOLLOWING ⬃75% BLOOD LOSS IN A PIG MODEL OF SEVERE HEMORRHAGIC SHOCK

RELATION BETWEEN MAGNETIC RESONANCE IMAGING (MRI) FINDINGS AFTER RESUSCITATION AND PROGNOSIS DIFFER DEPENDING ON THE TIME THAT MRI WAS PERFORMED

Asger Granfeldt, Torben Nielsen, Christoffer Sølling, Aarhus University, Geoffrey Dobson, James Cook University, Lise Wogensen, Jørgen Frøkiær, Aarhus University, Jakob Vinten-Johansen, Emory University, Else Tønnesen, Aarhus University

Toshiaki Mochizuki, St. Luke’s International Hospital

Introduction: Re-establishment of circulation with fluid or blood following hemorrhagic shock triggers ischemia-reperfusion (I/R) injury and multi-organ dysfunction. Excessive fluid therapy in the pre-hospital setting further worsens outcomes. The combination of adenosine, lidocaine, and magnesium (ALM) stabilizes cardiovascular function and hemodynamics after I/R. Hypothesis: Treatment with 7.5% NaCl ALM at resuscitation: 1) improves hemodynamic stability, 2) reduces fluid requirements during permissive hypotension, and 3) restores kidney function after re-infusion of shed blood. Methods: Anesthetized pigs (38kg) were randomized to 4 groups: Sham (n⫽5), Sham ⫹ ALM (n⫽5), Hemorrhage ⫹ placebo, (n⫽11) and Hemorrhage ⫹ ALM (n⫽9). Blood was withdrawn to a MAP of 30-35mmHg. After 90 min at this MAP, Ringers acetate and 20ml 7.5% NaCl ⫾ ALM (adenosine,0.23mg/kg; lidocaine, 0.64mg/kg;Mg2⫹,0.4mg/kg) was infused to achieve a target MAP of 50 mmHg (permissive hypotension). After 30 minutes 75% of the drawn blood was re-infused ⫾ ALM (adenosine, 0.82mg/kg);lidocaine, 1.66mg/kg ) and the pigs were observed for 6 hours. Glomerular filtration rate(GFR) was estimated hourly by the renal clearance of 51Cr EDTA, and tissue blood flow was quantified by neutronactivated microspheres. Results: 1.9⫾0.3 L of blood (75% of total blood volume) was withdrawn to maintain a MAP of 30-35mmHg. In the placebo group 46.7⫾ 24 ml/kg of Ringers acetate were needed to maintain a MAP of 50-55mmHg for 30 min while the volume needed in the ALM group was significantly less (25.9⫾ 9.0 ml/kg, p⫽0.03). Two pigs in the placebo group developed irreversible shock and could not be resuscitated with fluid, while no pigs developed irreversible shock with ALM. Despite an increase in fluid volume in the placebo group there was no difference in hematocrit, regional myocardial or renal blood flow among groups. In the ALM group GFR returned to 83% of baseline, (baseline: 66⫾20ml/min vs. end of experiment: 51⫾15ml/min), whereas GFR in the placebo group only returned to 54% of baseline (98⫾39ml/min vs. 51⫾19 ml/min)(p⫽0.01). Conclusions: 7.5% NaCl with ALM reduced fluid requirements during permissive hypotension and restored kidney function to near baseline levels.


Introduction: Positive findings on head magnetic resonance imaging (MRI) after resuscitation suggest an unfavorable prognosis. Hypothesis: The relation between positive findings on MRI after resuscitation and neurological prognosis may differ depending on the time that MRI was performed. Methods: We retrospectively analyzed electronic medical records to examine intensive care unit admission after resuscitation from out-of-hospital cardiac arrest. Head MRI was conducted before discharge or death. Patients were excluded from the study if they had head trauma, cerebral vessel disease or were aged 16 years or younger, and if MRI was not performed before discharge or death. We assumed the judgment of hypoxic brain injury with diffusion weighted imaging (DWI) or T2weighted imaging by two radiologists to be positive MRI findings. The time when MRI was performed was divided into eight from A to H 4-day periods. Clinical outcome was assessed at the time of discharge by using the Pittsburgh cerebral performance category (CPC). We defined good neurological prognosis as CPC1 and an unfavorable prognosis as CPC2–5. The positive predictive value and the negative predictive value concerning the relation between prognosis and MRI findings were calculated for each period. Results: For 1057 cases of out-ofhospital cardiac arrest, 296 were resuscitated and admitted to our intensive care unit; following the exclusion of 245, we were left with a study sample of 51 patients. The number of MRIs for periods A to H were 7, 15, 14, 6, 4, 2, 0, and 3, respectively. The positive predictive value was 85.7%, 93.3%, and 92.9% for periods A to C, respectively, and was 100% for all periods from D onwards. The negative predictive value was 71.4%, 73.3%, 85.7%, and 66.7% for periods A to D, respectively, 100% for E to F, and 33.3% for H. Conclusions: Positive findings on head MRI until post-resuscitation day 12 does not necessarily suggest unfavorable prognosis. MRI performed after resuscitation day 13 is suitable for predicting prognosis.

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IMPACT OF THE ARTERIAL HYPEROXIA AFTER IN-HOSPITAL CARDIAC ARREST

DOES PERFORMING CARDIOPULMONARY RESUSCITATION ON A HUMAN PATIENT SIMULATOR ELICIT A STRESS RESPONSES?

Younghwan Lee, Tae Gun Shin, Min Seob Sim, Ik Joon Jo, Hyoung Gon Song, Samsung Medical Center, Sungkyunkwan University School of Medicine Introduction: Current American Heart Association guidelines for adult cardiopulmonary resuscitation advocate 100% inspired oxygen during resuscitative efforts because this may maximize the likelihood of achieving return of spontaneous circulation (ROSC). But, hyperoxia after ROSC may have potentially detrimental effects. Hypothesis: This study was to determine whether high oxygen delivery in the early post cardiac arrest setting has adverse effects on survival. Methods: We retrospectively reviewed patients with in hospital cardiopulmonary arrest from 2003 to 2009 according to the Utstein style guidelines. Exclusion criteria included ages less than 17 years and traumatic cardiac arrest. The subjects were divided into three groups based on PaO2 on arterial blood gas analysis (ABGA) values after return of spontaneous circulation (ROSC); hyperoxia (PaO2 ⱖ 300mmHg), normoxia (300mmHg ⬎ PaO2 ⱖ 60mmHg), or hypoxia (PaO2 ⬍60 mmHg or ratio of PaO2 to fraction of inspired oxygen ⬍300). We evaluated the first PaO2 values obtained regardless of location and the first intensive care unit (ICU) PaO2. The primary outcome was in-hospital mortality. Results: There were 541 patients that met the inclusion criteria. Median time between ROSC and the first PaO2 was 14 minutes (IQR⫽5-40) and median time between ROSC and the first ICU PaO2 was 44 minutes (IQR⫽12-137). In the first PaO2 categories, 379 had hypoxia (83 %) and 30 had normoxia (7%), 45 had hyperoxia(10%). There were no significant differences in the survival discharge rate. In the first ICU PaO2 categories, of 346 patients, 275 had hypoxia (79%) ,37 had normoxia (11%), and 34 had hyperoxia (10%). The hyperoxia group had an odds ratio for in-hospital mortality of 2.70 (95% CI, 1.11-6.66) in a multivariable regression analysis adjusting confounders (age, sex, comorbid condition, no flow time, sepsis related organ failure assessment score, initial rhythm, percutaneous cardiopulmonary support). Conclusions: Arterial hyperoxia in the first ICU PaO2 after ROSC was associated with in-hospital mortality. However, the first PaO2 after ROSC regardless of loctaion, which was obtained faster than that in the ICU had no asssociation with in-hospital mortality.

Monica Alba, University of Florida Introduction: The effects of stress on decision making and performance of rescuers during cardiopulmonary resuscitation (CPR) are unknown. To begin studying the effects of stress, we first sought to understand which types of currently used teaching tools elicited the strongest stress response. Hypothesis: Performing CPR on a human patient simulator will elicit stress response in the rescuer leader measured by an increase in salivary cortisol and heart rate (HR) when compared to static mannequin and paper test. Methods: Salivary cortisol and HR were used as stress physiologic markers. 10 second year pediatric residents were enrolled and each performed a mock resuscitation using 3 different methods: paper test, static mannequin and human patient simulator. Salivary cortisol samples were collected at baseline, 20, 40 and 60 min. HR was recorded at 5 seconds intervals for 5 min prior to testing (baseline), during testing and 3 min after each test using a Polar HR monitor. Salivary cortisol analyzed by ELISA (SALIMETRICS®). The design was a randomized complete block design with repeated measures. Statistics performed using SAS. Results: The average heart rate increased during the testing period compared to baseline when using the mannequin and simulator (81.68bpm SE ⫹/⫺3.3 bpm to 93.89 bpm SE ⫹/⫺ 4.4bpm; p⬍0.0001); (89.57bpm SE ⫹/⫺3.3bpm to 97.8bpm -SE ⫹/⫺ 4.2bpm for simulator; p⬍ 0.001) respectively. There was an increase in salivary cortisol at all testing times when comparing to baseline for all modes of testing (p⬍ 0.0001). Salivary cortisol concentration peaked at 20 minutes when using paper (0.222 microgram/dL, SE ⫹/⫺ 0.03) or static mannequin (0.290 microgram/dL SE ⫹/⫺0.03). When testing with the human patient simulator, the increase in cortisol level at 20 min was comparable to the other two testing methods (0.249 microgram/dL SE ⫹/⫺0.03) but a peak was not reached until 40min (0.259 microgram/dL SE ⫹/⫺ 0.02). Conclusions: Performing CPR as rescuer leader during mannequin and simulator testing increases heart rate and salivary cortisol, surrogate markers for stress. CPR on a human patient simulator induces a significant and sustained increase in salivary cortisol when compared with static mannequin and paper testing

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EFFECT OF THERAPEUTIC HYPOTHERMIA VS ⌬-OPIOID RECEPTOR AGONIST ON POST RESUSCITATION MYOCARDIAL FUNCTION IN A RAT MODEL OF CPR

GOOD NEUROLOGICAL OUTCOME AT ICU DISCHARGE OF NON-VF PATIENTS TREATED WITH RESUSCITATIVE HYPOTHERMIA AFTER CARDIAC ARREST-DATA FROM A GERMAN CPR REGISTRY

Sung Phil Chung, Gangnam Severance Hospital, Feng-Qing Song, Tao Yu, Yinlun Weng, Shijie Sun, Max Weil, Wanchun Tang, Institute of Critical Care Medicine Introduction: The ⌬-opioid receptor (DOR) agonist, D-Ala2-D-Leu5 enkephalin (DADLE), has been shown to limit myocardial infarct size in models of cardiac ischemia and reperfusion. This study is to compare the effect of DADLE with therapeutic hypothermia on post resuscitation myocardial function, 72-h survival in a rat model of cardiac arrest and resuscitation. Hypothesis: The activation of DOR with DADLE has the same effect on post resuscitation myocardial, neurologic function and 72-hr survival rate as therapeutic hypothermia in a rat model of cardiac arrest and CPR. Methods: Ventricular fibrillation (VF) was induced in 15 male Sprague-Dawley rats. After 8 min of untreated VF, cardiopulmonary resuscitation was performed for 8 min before defibrillation. Animals were randomized to three groups of five: a) normothermia; b) hypothermia (32°C); and c) normothermia with DADLE intravenous infusion (1 mg/kg/h). Hypothermia and drug infusion were started after successful defibrillation. Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured echocardiographically together with neurologic deficit scores and duration of survival. Results: The 72-h survival was significantly greater in the hypothermic group (4/5) than in both DADLE (1/5) and normothermic (0/5) group. However, the survival time of the DADLE treated animals was significantly longer than that of the normothermia group (51.8⫾18.9 vs 18.8⫾10.1 h). Both the DADLE and hypothermic group showed significantly better myocardial function than the normothermic group during the first 4 h after resuscitation. The neurologic deficit scores at 72 h were better in the hypothermia group than in both DADLE and control groups. Conclusions: DADLE attenuated post resuscitation myocardial dysfunction and increased short term survival time. However, the 72-h survival and neurologic deficit scores were not comparable with those of therapeutic hypothermia.

Markus Foedisch, Andreas Bartsch, Andreas Viehoefer, Evangelische Kliniken Bonn Introduction: Resuscitative hypothermia therapy (RHT) significantly reduces mortality and neurological impairment after cardiac arrest (CA) in patients presenting with VF/VT as initial rhythm and is incorporated in the AHA and ERC resuscitation guidelines for postresuscitation care. Only little data exist regarding neurological outcome in patients with asystole/PEA treated with RHT after CA in preceeding investigations. Hypothesis: RHT improves neurological outcome in surviors of CA presenting with initial non-VF rhythm. Methods: RHT was implemented as standard care after succesful CPR for all patients suffering from CA independent from origin and initial rhythm in 2003 in our hospital. Comatose patients after CPR underwent RHT for minimum 24 hours immediately after admission in the ED following a standard treatment protocol. Initial BLS and ACLS data, cooling techniques, course of temperature and other baseline data were documented in a database (CoolBrain Registry). Neurological outcome was quantified using the Pittsburgh cerebral performance category scale (CPC) at ICU discharge. Results: 150 patients included in the registry showed ROSC after CPR at ICU admission and received RHT between June 2003 and June 2010. 108 (72%) had asystole/PEA as initial rhythm and were retrospectively analysed regarding overall and neurological outcome. CA was witnessed in 19 of those patients (17,6%), out-of-hospital resuscitation was performed in 70 patients (64,8%), 38 of the CA (35,2%) were located in-hospital. 48 of the patients (44,4%) showed a CA of non-cardiac origin, 60 of the patients (55,6%) had a CA of supposed cardiac origin. Good neurological recovery at ICU discharge (CPC 1/2) was seen in 39 (36,2%), 15 patients (13,9%) showed severe neurological impairment and 54 of the patients (49,9%) died during ICU stay. In the group of survivors 72,2% of the non VF patients showed a CPC of 1/2, 27,8% a CPC of 3/4 at ICU discharge. Conclusions: Mild RHT significantly improves neurological outcome independent of the origin of cardiac arrest and of initial rhythm. The high rate of favourable neurological outcome in patients with initial non-VF rhythm underlines the necessity to perform RHT in every patient suffering from CA.


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OUTCOMES IN COMATOSE CARDIAC ARREST PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION TREATED WITH THERAPEUTIC HYPOTHERMIA AND PERCUTANEOUS CORONARY INTERVENTION

INCREASED BLOOD PRESSURE AND DEPTH OF CHEST COMPRESSIONS DOES NOT IMPROVE CARDIAC OUTPUT OR ORGAN PERFUSION IN A SWINE MODEL OF PEDIATRIC CARDIAC ARREST

Michael Kelley, Robert Huang, Quinn Wells, Carol Scott, Joseph Fredi, John McPherson, Vanderbilt University

Chad Mao, Children’s Healthcare of Atlanta, Emory University, Mark Clay, University of Texas Southwestern Medical Center, Clarence Bone, Jakob VintenJohansen, Emory University, Kevin Maher, Children’s Healthcare of Atlanta, Emory University

Introduction: The mortality from cardiac arrest remains very high, and many of these patients (pts) present with STEMI. However, little is known about outcomes of STEMI pts treated with TH and primary PCI, and the decision to perform primary PCI with uncertain neurological injury can be difficult. Hypothesis: Cardiac arrest patients with STEMI treated with TH benefit from early PCI but ongoing evidence of cardiogenic shock despite intervention strongly supports a poor prognosis. Methods: We retrospectively analyzed 88 consecutive comatose pts treated at our institution with TH after cardiac arrest. Our protocol offered TH to unselected pts, regardless of hemodynamics, length of resuscitation, time to return of spontaneous circulation, or presenting cardiac rhythm. A total of 23 TH pts (26%) had evidence of STEMI at presentation and all underwent emergent coronary angiography; detailed clinical data was obtained on each. Results: Overall, 13 pts (57%) survived to hospital discharge. Mechanical support was required in 10/23 (43%) pts with a survival rate of 2/10 (20%). Survival in pts not requiring support was 11/13 (85%; p ⫽ 0.003). Pts requiring support had no significant differences in age, gender, time to institution of TH, door-toballoon time, anterior location of MI, initial rhythm or intervention (PCI or CABG) compared with pts not requiring support. Among the 13 pts not requiring mechanical support, 2 required inotropes and died while 5 required vasopressors and survived. The cause of death in the mechanical support group was determined to be cardiac in 5 pts and neurologic in 3 pts. Among all 13 survivors, 12 (92%) had a Cerebral Performance Category of 1 at discharge. Conclusions: Survival of comatose STEMI pts treated with TH and primary PCI after cardiac arrest was low, primarily due to the very poor survival in the mechanical support group. In STEMI pts not requiring support, survival was high. Among survivors of STEMI complicated by cardiac arrest treated with TH and primary PCI, neurologic outcomes were excellent. Thus, comatose STEMI pts after cardiac arrest should be strongly considered for emergent primary PCI and TH, particularly if the need for mechanical support is unlikely.


Introduction: Guidelines for depth of chest compressions in children are based on consensus from expert panels and limited data. Compressions are performed to provide blood pressure and perfusion; however the significance of the blood pressure generated during chest compressions on tissue perfusion, CO and survival is unknown. Hypothesis: Performing chest compressions (CC) to generate higher blood pressure will result in improved survival, CO and tissue perfusion in an animal model of pediatric cardiac arrest. Methods: Domestic swine, 8-12 kg, were anesthetized and instrumented. VF was induced and continued for 3 mins at which time CPR was initiated. Animals were randomized to CCs with a targeted systolic BP of 40 or 80 mmHg, correlating to a compression depth of approximately 1⁄3 and 1⁄2 the chest diameter, respectively. After 7 mins of compressions, defibrillation and cardiac drugs were employed until ROSC or 25 mins of CPR. Central venous, LV, arterial pressure and ECG were recorded continuously and brain near-infrared spectroscopy (NIRS) data was recorded at 1 min intervals. Blood flow to LV, RV, kidney, liver and brain were determined by labeled microspheres injected at baseline, 5 mins into CPR, and 15 mins after recovery, if applicable. Arterial and venous blood gases were sampled at the same time intervals as the microspheres. A p-value ⱕ 0.05 was considered statistically significant. Results: ROSC was achieved in 5/17 animals, 3/8 in the 40 mmHg cohort and 2/9 in the 80 mmHg cohort (p ⫽ 0.62). Microspheres demonstrated greater perfusion to the brain in the 40 mmHg cohort (0.22 vs 0.05 ml/kg/min, p ⬍ 0.0001). Cerebral NIRS were 33% higher in the 40 mmHg group (37.9% vs 28.6%, p ⫽ 0.03). Microsphere data suggested improved perfusion to the LV, RV, and liver in the 40 mmHg cohort however did not reach statistical significance due to sample size. CO was similar in both cohorts during CPR (3.94 vs 3.25 L/min, p ⫽ 0.21). Conclusions: Increased blood pressure does not improve survival, CO, or vital organ perfusion. In fact, direct and indirect metrics of tissue perfusion, particularly brain perfusion, suggest that a lower blood pressure generated during CCs may provide better organ perfusion during CPR.


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ABSM OF ELECTROCARDIOGRAM PREDICTS SUCCESSFUL DEFIBRILLATION ON RATS DURING CPR

TRACHEAL INTUBATION OF A DIFFICULT AIRWAY USING IN-DIRECT LARYNGOSCOPES, AIRWAY SCOPE®, AIRTRAQ® AND GLIDESCOPE:® A COMPARATIVE MANIKIN STUDY OF INEXPERIENCED PERSONNEL

Xiaobo Wu, Weil Institue of Critical Care Medicine, Joe Bisera, Weil Institute of Critical Care Medicine, Shijie Sun, Institute of Critical Care Medicine, Max Weil, Weil Institute of Critical Care Medicine, Wanchun Tang, Institute of Critical Care Medicine Introduction: Early investigations indicated that amplitude spectrum area (AMSA) based on amplitude and frequency was a good indicator of successful defibrillation. The present study introduces a more simple method also based on amplitude for predicting success of defibrillation. This method is called the sum of the absolute magnitude (ABsM), following the equation: ABsM ⫽ |A1|⫹|A2|⫹|A3|⫹. . .⫹|Ai|⫹. . .⫹|An|, where Ai is the amplitude value at the ith sample point of ECG waveform. Hypothesis: This study was designed to assess the efficacy of ABsM in predicting success of defibrillation. We hypothesized that ABsM may also predict success of defibrillation during CPR. Methods: Ventricular fibrillation (VF) was induced in 25 male rats, weighing between 450-550g, CPR was initiated after 6 min of untreated VF. Precordial compression was adjusted to achieve coronary perfusion pressure at 24⫾2 mmHg. Defibrillation was attempted after 6 min of CPR. Results: The ABsM of a 5-second strip was calculated during CPR prior to the electrical shock. The results indicated that ABsM of successful defibrillation was significantly higher than in the failed defibrillation (128.5⫾50.3 mV versus 66.8⫾17.5 mV, p⬍0.001). The positive predictive value was 83.30%, the negative predictive value was 80.00%, the sensitivity was 79.00%, and the specificity was 84.20%. Conclusions: We concluded that the ABsM could predict the success of defibrillation during CPR.

Tomoko Tamura, Koichi Tanigawa, Nobuyuki Hirohashi, Yasumasa Iwasaki, Taku Takeda, Ryu Tsumura, Tadatsugu Otani, Takuma Sadamori, Grad. School of Biomed. Sci., Hiroshima Univ. Introduction: The AirwayScope® (AWS), the Airtraq® (ATQ) and Glidescope®(GS) are newly developed in-direct laryngoscopes to ease tracheal intubations including difficult airways. The purpose of this study was to evaluate the effecacy of these devices by inexperienced personnel in a simulated manikin difficult airway. Methods: Eight medical students with no previous experience in tracheal intubation participated in this study. Following a brief instruction of the devices, the students were asked to intubate a simulator. We used an advanced patient simulator (SimMan®, Laerdal Medical, Stavanger, Norway) to simulate normal and difficult airway scenarios including cervical spine rigidity, limited mouth opening, pharyngeal obstruction and swollen tounge. The sequences in selecting devices and scenarios were randomized. Success rates for tracheal intubation, and the time required for visualization of the glottis (T1, sec), tracheal intubation (T2), and inflation of the lungs (T3), as well as the number of optimization maneuvers and dental click sounds were analyzed. Results: The students performed a total of 120 tracheal intubations. The AWS had the highest success rates of tracheal intubation compared with ATQ and GS (AWS 100%*; ATQ 85%; GS 88%; *P ⬍ 0.05 AWS vs. ATQ and GS). T1, T2 and T3 with three devices are as follows: AWS; T1 5.0 ⫾ 5.1 s*, T2 9.7 ⫾ 14.1 s**, T3 14.5 ⫾ 13.7 s***, ATQ; T1 7.5 ⫾ 12.1 s, T2 20.4 ⫾ 39.4s, T3 25.4 ⫾ 39.5 s, GS; T1 10.7 ⫾ 25.2 s, T2 17.7 ⫾ 35.2 s, T3 24.7 ⫾ 35.5 s (*p⬍0.05 vs. GS,** p⬍0.05 vs.ATQ,***p⬍0.05 vs. ATQ, GS). The number of audible dental click sounds with the GS was significantly greater than with the AWS and ATQ. Conclusions: The AWS achieved successful intubations in all scenarios, and the times required for intubations were shorter than the ATQ and GS. These results indicate that the AWS may be a suitable device for tracheal intubation including difficult airways by inexperienced personnel. Further studies in a clinical setting are necessary to confirm these findings.

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CHEST COMPRESSION CHARACTERISTICS OF CPR MANIKINS, ‘OBJECTS OF DAILY LIVING,‘ AND REAL CARDIAC ARREST PATIENTS

PATTERN OF THORACIC COMPLICATIONS RELATED TO STANDARD MANUAL CPR

Jessica Leffelman, Children’s Hospital of Philadelphia, Matthew Maltese, University of Penn/Children’s Hospital, Dana Niles, Children’s Hospital of Philadelphia, Akira Nishisaki, University of Pennsylvania School of Medicine, Kristy Arbogast, Children’s Hospital of Philadelphia, Sriram Balasubramanian, Drexel University, Jennifer Mendelson, The University of Arizona, Vinay Nadkarni, Children’s Hospital of Philadelphia Introduction: Realistic manikins are used to teach CPR “muscle memory” for AHA recommended chest compression (CC) force and depth. Our objective was to identify “objects of daily living” (ODL) that mimic CC characteristics of manikin and human chests, to facilitate ease of access to CPR training. Hypothesis: Common “objects of daily living” can mimic manikin and human CC characteristics, for potential use as surrogates for learning the force necessary to reach recommended CC depth. Methods: Sixty CC at metronome paced 100 CC/min were delivered to manikins, humans in cardiac arrest, and 8 ODL: tennis ball, soccer ball (7psi), American football (13 psi), life jacket, toilet paper roll, empty polyethylene terephthalate 2L soda bottle (#1 recycling), pool polyethylene “noodle” and a Nerf football. A load cell with accelerometer interposed between the CC provider’s hands and the ODL recorded the applied force and calculated depth. Each CC cycle was mathematically modeled as a parallel spring-damper model with second order spring and linear depth-dependent damping elements. The mean spring (elastic) force required to achieve 38mm depth CC was quantified for each ODL. These force-deflection measures were compared to spring force data obtained from pediatric manikins (Laerdal Medical), and real children in cardiac arrest. Data expressed as mean⫾SD. Results: The mean spring forces at 38 mm of CC from real children in cardiac arrest were: 8-11yrs: 21.3 ⫾7.7 kg, 12–15 yrs: 33.8 ⫾10.9 kg, 16-19yrs: 23.6 ⫾9.1kg, 20-23yrs: 35.9 ⫾1.4 kg. The mean spring force for pediatric manikins representing 5 year old children at 38mm depth was 33kg. Six ODLs (tennis ball, American football, life jacket, toilet paper, pool noodle, Nerf football) were ⬎ 20kg force different from manikins and humans. At 38mm, the 7psi inflated soccer ball had a spring force of 10.8 ⫾2.7kg and the 2L plastic soda bottle 33.8⫾7.8kg, close to the manikin and real children’s CC characteristics, respectively. Conclusions: Several “objects of daily living”, such as soccer balls and 2L plastic soda bottles, can mimic manikin and human CC characteristics, and have potential for use as surrogates to teach AHA recommended CC force/depth “muscle memory”.

Kyoungchul Cha, Ynosei University, Wonju College of Medicine, Sung Oh Hwang, Ho Kyung Won, Yong Won Kim, Deuk Hyun Park, Hyung Jin Shin, Yonsei University, Wonju College of Medicine Introduction: External chest compression during CPR is, not infrequently, associated with injuries to the thorax. Several reports have been made about thoracic complications after CPR, but details of the pattern of thoracic complications related to standard CPR remain to be investigated. Hypothesis: This prospective observational study was conducted to evaluate the pattern of thoracic complications caused by external chest compression during standard CPR in patients with cardiac arrest. Methods: Chest CT scan was performed within a day after resuscitation in 114 patients (67 males, mean age: 51 year-old) who received standard CPR and resuscitated from out-of-hospital cardiac arrest. We divided both hemithoraces into 6 regions to allocate the site of injury (anterior, anterolateral, upper lateral, lower lateral, posterolateral and posterior). Results: Median time from collapse to ROSC and total duration of CPR were 25.0 (IQR: 12.0-34.0) minutes and 14.5 (IQR: 8.0-24.0) minutes, respectively. Thoracic injuries were observed in 83 patients (73%). Rib fracture was noted in 56 cases (49%) and lung contusion in 47 cases (41%). Sternal fracture (12 cases, 11%), hemothorax (11 cases, 10%), pneumothorax (9 cases, 8%), retrosternal hematoma (3 cases, 3%), pericardial effusion (3 cases, 3%), hemomediastinum (3 cases, 3%) were also noted. No pneumomediastinum or aortic injury was found. Rib fractures were frequently observed at 3rd through 6th rib on both sides (right: 81%, left: 80%). Rib fractures were noted only in upper part of the hemithorax (anterior: 34%, anterolateral: 59%, upper lateral: 7%). On the contrary to the injury pattern of rib fracture, most of lung contusion (79%) was developed in lower part of thoraces. Age, sex, thoracic circumference, time from collapse to ROSC, or total duration of CPR had no relationship with the development of rib fracture or lung contusion. Conclusions: Significant proportion of the patients who received standard CPR had various thoracic injuries including skeletal injuries on the anterior and lateral region of the thoracic cage and lung contusions on the posterior region of the thorax.


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PUSH HARD. . . AND THEN HARDER? SHALLOW CHEST COMPRESSIONS ARE MORE COMMON DURING LATER PERIODS OF PEDIATRIC AND ADOLESCENT RESUSCITATION ATTEMPTS

EFFICACY OF PERIPHERAL EPINEPHRINE INFUSIONS DURING PEDIATRIC AND NEONATAL INTERFACILITY TRANSPORTS

Robert Sutton, Carleen Zebuhr, Dana Niles, Kristy Arbogast, Akira Nishisaki, Children’s Hospital of Philadelphia, Matthew Maltese, University of Penn/Children’s Hospital, Aaron Donoghue, The Children’s Hospital of Philadelphia, Mette Stavland, Laerdal Medical, Vinay Nadkarni, Children’s Hospital of Philadelphia Introduction: Rescuers often do not adhere to CPR guidelines during resuscitation of adults and children. Risk factors associated with CPR error should be identified in an effort to improve quality during resuscitation attempts. Hypothesis: Even with provision of automated feedback, providers will be more likely to perform chest compressions outside AHA guideline recommendations during later periods of pediatric and adolescent resuscitation attempts. Methods: CPR monitoring/feedback enabled defibrillators were used to evaluate CPR quality during consecutive patients ⱖ8 yrs receiving chest compressions (CCs) during PICU/ED resuscitations. In each event, CCs were numbered consecutively: “early” CCs were #1 to 100; late were #1001 to 1100. Data sets included: CC depth (mm); CC force (kg); and CC depth guideline compliance (depth ⱖ38mm). All CC depths reported are corrected for mattress deflection (i.e, represents actual chest deflection). Audiovisual feedback was given to drive CPR performance toward the AHA target CC depth (ⱖ 38mm). Generalized estimating equations, adjusting the standard errors for within-event correlation between CCs, were used to determine the relationship between CC depth/force and period of resuscitation (early vs. late). Results: Between October 2006 and December 2009, fifty consecutive CC events were enrolled in our ongoing study of pediatric CPR quality; 21 index events had at least 1100 CCs delivered and were used for this analysis. Average age was 14 ⫾ 4 yrs. Late CCs were 1⁄2 as likely to be guideline compliant (ⱖ 38mm) compared to the early CCs (OR 0.5; CI95 0.26 – 0.98, p⫽0.043). This decreased CC depth was associated with a non-significant decline in applied CC force of 1.9kg (CI95 -5.4 – 1.7, p⫽0.3). Conclusions: Chest compressions performed later in resuscitation events are less likely to meet guideline recommendations. Future studies should evaluate patient factors (i.e., chest compliance / molding) and team dynamic factors (i.e., perception of futility) that could lead to poorer resuscitation quality during later portion of resuscitation events.

Emily Miller, University of Pittsburgh, Bradley Kuch, Kathryn Felmet, Children’s Hospital of Pittsburgh Introduction: The ACCM recommends inotropes for fluid refractory shock in children via peripheral IV (PIV) if central venous access is not available. There is no data supporting the efficacy or safety of epinephrine (EPI) via PIV in children. Hypothesis: We hypothesize that PIV EPI will increase systolic blood pressure (SBP) similar to EPI via CVL. Methods: In a retrospective cohort study, the medical records of 50 patients aged 0-18 who received EPI via PIV or CVL during interfacility transport were evaluated for changes in SBP and for PIV dysfunction. Patients were excluded if bolus dose EPI was given or if the route of EPi was changed during transport. SBP data was analyzed as % change from pre-EPI baseline. Differences in continuous variables were analyzed using MW rank sum and are presented as medians. Results: 36/50 received EPI via PIV, and 14/50 received EPI via CVL. SBP was increased by time index 2 and at all subsequent time points after initiation of EPI via CVL (p⫽0.001, 0.004, ⬍0.001, 0.008 for T2,3,4,5 respectively) and PIV (p⫽0.02, ⬍0.001, ⬍0.001, ⬍0.001 for T2,3,4,5 respectively). There was no difference in the % change from baseline between CVL and PIV groups at any time point. Patients in the CVL group were younger (0.1m (CVL) vs 14m (PIV), p⫽0.01) and had higher PRISM scores compared with the PIV EPI group (18 (CVL) vs 9.5 (PIV), p⫽0.005). CVL patients received higher doses of EPI compared with PIV patients (0.1mcg/kg/min [range 0.05-0.08] by CVL vs 0.07 mcg/kg/min [range 0.05-0.48] by PIV, p⫽0.04). Median cumulative bolus fluid given did not differ between groups (CVL: 44ml/kg [range 5-200] vs PIV: 52 ml/kg [range 4-132]). 1/36 patients who received PIV EPI had a documented EPI infiltrate; it caused a local reaction which resolved within 48 hours. Conclusions: In this small retrospective study, PIV EPI was as effective as CVL EPI at raising SBP. No lasting adverse effects resulted from delivery of PIV EPI. Further research is needed to determine the relative effectiveness of PIV and CVL EPI, and the risk of serious infiltrations from PIV EPI. Adherence to ACCM guidelines should not be delayed by lack of central access.

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IMPACT OF OBJECTIVE GUIDANCE ON ANESTHESIOLOGY RESIDENT RESUSCITATION SKILLS

WHEN SPACE IS AN ISSUE: USE OF VIDEO ASSISTED LARYNGOSCOPY BY CRITICAL CARE PERSONNEL IN AEROMEDICAL TRANSPORT

Matthew Chakan, Scharukh Jalisi, Ruben Azocar, Boston University School of Medicine Introduction: Manual ventilation and cardiopulmonary resuscitation (CPR) are commonly performed, using subjective assessment by the provider. Recommended guideline targets are frequently not met. To increase objective guidance, a hand-held electronic device, the Exact Instrument of Resuscitation (EIR), was designed to couple with a bag-valve and display real-time tidal volumes, while providing ventilation and chest compression cadence. Hypothesis: EIR use during manual ventilation and CPR will improve guideline target compliance and ventilation and CPR parameters. Methods: Randomly chosen Anesthesiology residents (n⫽7) completed two sets of one-minute rescue ventilation followed by two cycles of CPR: the first without guidance, and the second while using the EIR, after EIR familiarization and guideline review. Trials were done on a Laerdal SkillReporter manikin using a bag-valve-mask. Added in-line airflow and pressure sensors analyzed with Matlab computation software measured: tidal volume, ventilation period, breath duration, and average breath pressure. Laerdal PC SkillReporting software measured the chest compression rate. SAS JMP statistical software was used for repeated measures ANOVA analysis. Results: Rescue breathing ventilation period improved (3.49⫾1.15 to 4.66⫾0.69 sec; p⬍0.05) from below target without the EIR (p⬍0.05), to no difference from target using the EIR (p⬎0.05). EIR use did not change (p⬎0.05) the tidal volume (400.⫾99 to 425 ⫾46 mL), breath duration (1.37⫾0.23 to 1.37⫾0.34 sec), or average pressure (15.6⫾3.9 to 17.5⫾2.3 cmH2O), and the tidal volume and breath duration were not different (p⬎0.05) than target regardless of EIR use. For CPR, EIR use increased the breath duration (1.00⫾0.12 to 1.29⫾0.24 sec; p⬍0.05), and decreased the average pressure (26.2⫾9.1 to 17.1⫾2.7 cmH2O; p⬍0.05). There was no change (p⬎0.05) in the tidal volume (555⫾167 to 422⫾73 mL) or compression rate (102⫾18 to 106⫾13 per min). Tidal volume, breath duration, and compression rate were not different than their respective target (p⬎0.05), regardless of EIR use. Conclusions: Use of a device for objective timing and tidal volume guidance improves ventilation timing, without improvement of tidal volume or chest compression rate.


Robert Cambridge, Rose Haisler, OSF St. Francis Medical Center Introduction: During critical care transport of a patient in a standard civilian helicopter, airway management is hindered due to cramped conditions.Video assisted (VA) laryngoscopy may offer an advantage over traditional directly visualized (TDV) laryngoscopy for in-flight airway placement. Hypothesis: Endotracheal intubation success and procedural time is improved using VA laryngoscopy as compared to TDV laryngoscopy in a suboptimal placed simulated patient. Methods: Study participants were asked to attempt intubation twice (medical and trauma scenarios) on a mannequin airway simulator in a civilian helicopter (Bell 230). Participants were randomized to the VA or TDV group and sat in the forward facing seat with the simulator’s head against the rear bulkhead preventing standard operator positioning. Participants attempted airway visualization and indicated when they noted the best view of the larynx (based on the modified Cormack-Lehane scale). The participant then attempted endotracheal intubation, calling out when they completed their attempt. Tube location was verified by investigators after the attempt, and larynx view and attempt completion times were recorded. Results: Thirty subjects of varying training levels (EM residents, CCRNs, and paramedics) participated (17 in VA group, 13 in TDV group). No significant differences in training levels between the groups was noted (p⫽2.85). The VA group was more successful than the TDV group in endotracheal intubation (33/34 (97.1%) vs. 21/26 (80.8%); p⫽0.037). While VA provided a faster mean optimal view of the larynx (8.8 seconds vs. 18.5 seconds; p⫽19.7), the confidence intervals overlapped. The mean time to intubation completion was similar for both methods (VA 25.87 seconds vs. TDV 25.64 seconds; p⫽0.01). There were no significant differences in time to best view (p⫽0.65) or time to intubation completion (p⫽0.18) for scenario type. Conclusions: VA laryngoscopy provided a greater likelihood of successful tracheal intubation as compared to TDV in a simulated helicopter patient. VA laryngoscopy had no time advantage over TDV laryngoscopy for laryngeal view or subsequent endotracheal tube placement.

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IMPLEMENTING THERAPEUTIC HYPOTHERMIA(TH) FOR CARDIAC ARREST(CA) USING TIME TARGETS CAN IMPROVE CLINICAL OUTCOMES

EXTRACORPOREAL CARDIOPULMONARY RESUSCITATION IN A PEDIATRIC CARDIAC CENTER IS EFFECTIVE EVEN AFTER 60 MINUTES UNSUCCESSFUL CONVENTIONAL CARDIOPULMONARY RESUSCITATION

S Pai, F Rivera, B Kanna, R Loganathan, LHC Introduction: It is estimated that ⬍15% US hospitals are currently using mild TH for CA patients. This low level of utilization is attributed to barriers like triage for prompt screening and inability to apply multiple interventions consistently to achieve timely target temperature. Hypothesis: Implementation of a bundle of interventions with time targets may help overcome barriers and help achieve desired temperature. Methods: An observational outcomes study was conducted on patients who suffered In-hospital(IH) or Out of Hospital(OH) CAs between Jan’06 and March’10. An intensivist who was present 24/7 implemented “TH bundle” using specific time targets was implemented in Jan’09. It included screening patients after return to spontaneuous circulation(ROSC) achieved using predetermined criteria(10mins), labs send out & starting cold saline(15mins), start surface cooling(30mins), achieving target temperature(4hours). Outcomes including hospital mortality and Cerebral Performance Scores (CPS) were collected and analyzed. Statistical analysis was performed to compare the differences in before and after implementation of TH. A p value ⬍0.05 was considered significant. Results: In pre-TH group, 34 CAs(25⫽OH) were admitted to the ICU. In the post-TH group, 76 CAs were screened, TH bundle was implemented in 26 patients(22/58 OH; 12/18 IH). 22/26 had 100% compliance with TH bundle. 3 had Vtach/Vfib, 18 asystole/PEA & 5 had mixed rhythms as their initial presentation. Mean time to reach target temp was 3.2 hours from ROSC. 11/ 26(42.3%) survived to hospital discharge with no differences across initial rhythm. 10/26 had CPS of 1/2 (good neurological outcomes). While comparing pre and post TH patients, survival to discharge showed a non-statistical but clinically significant improvement from 29% to 42% (OR1.76, 95%CI 0.5-5.9, p⫽0.3) Conclusions: Our experience suggests that maintaining time targets can help implement TH, achieve timely target temperature and improve clinical outcomes. Presenting cardiac rhythm did not predict clinical outcomes supporting previous studies that mechanisms of brain injury are similar across various cardiac rhythms. This is the first study to describe the implementation and utilization of a TH bundle.

Akira Yoshimoto, Masaki Osaki, Ikuya Ueta, Shizuoka Children’s Hospital Introduction: Extracorporeal cardiopulmonary resuscitation (E-CPR) has been used for patient refractory to conventional cardiopulmonary resuscitation (CCPR). These results and reports, however, were from big pediatric cardiac centers with enough medical staffs and little is known about the benefits of E-CPR in medium-sized pediatric cardiac centers where ECMO team is not always on site. Furthermore there is a controversy about risk factors of E-CPR in pediatric population. At our institution, a medium-sized pediatric cardiac center dealing with 300 cardiac surgeries, we introduced a policy to activate ECMO team if in-hospital cardiac patients are refractory to C-CPR for 10 minutes. Hypothesis: In this study, we sought to evaluate effectiveness of our E-CPR strategy and to find potential risk factors for mortality of E-CPR. Methods: All patients‘ records who had E-CPR from December 1998 to June 2010 were retrospectively reviewed. Results: Of 76 ECMO runs, 26(34%) E-CPR were identified. Median age and weight were 3.4 months (range from day 5 to 13 years) and 5 kg (range from 2.3 to 41kg) respectively. Median CPR time before ECMO was 59.5 minutes (30-150minutes) and median ECMO duration were 129 hours (14-324 hours). The survival rate more than one-month was 69%. Neurological complications were common, affecting 61% of survivors. There was no significant difference between survivors and nonsurvivors in age, weight, duration of CPR, ECMO support time, pH, or lactate level by Mann-Whitney U test. Conclusions: This results encourage us to promote our E-CPR strategy to activate ECMO team after 10 minutes unsuccessful C-CPR. There is room for improvement in survival rate and in neurological outcomes. However, considering these patients could not be rescued without E-CPR, E-CPR should be initiated when establishment of ECMO is anticipated within 60 minutes.



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BUILDING A POST CARDIAC ARREST THERAPEUTIC HYPOTHERMIA PROGRAM

COMPARING THE GLIDESCOPE RANGER AND VENNER AP ADVANCE VIDEO-LARYNGOSCOPES IN A DIFFICULT PREHOSPITAL LARYNGOSCOPY SIMULATION

Michelle Deckard, Timothy Ellender, Methodist Hospital/ Clarian Health, Judith Jacobi, Methodist Hospital/Clarian Health, Dustin Spencer, Methodist Hospital/ Clarian Health Introduction: Since 2005, induced therapeutic hypothermia (TH) has been recommended by the American Heart Association for cardiac arrest survivors who remain comatose after return of spontaneous circulation (ROSC). Our institution began to implement TH for post cardiac arrest patients in 2006; however only 56% of eligible patients received appropriate TH due to systems variability. In 2008 we implemented a standardized treatment algorithm through the work of a multi-professional team and have since worked to maintain continuous quality improvement initiatives. Hypothesis: A standardized treatment protocol that targeted earlier cooling would increase the use and efficiency of TH and improve patient outcomes. Methods: A multi-professional team, led by a cardiac registered nurse who oversees program performance, was assembled. A TH protocol and detailed order set was created and implemented for TH use in all eligible in-hospital and out-of-hospital arrests. System wide education regarding appropriate use of TH, hypothermia physiology, cooling techniques, pharmacologic considerations, patient monitoring, and recognition of potential adverse effects was provided to all critical care and emergency medical physicians, nurses, and pharmacy staff. Patient demographics, cooling techniques, timing variables, and outcomes data were collected for quality analysis. Results: The volume of eligible cardiac arrest patients with ROSC who receive standardized TH increased by 98% with protocolized care. The time from initiation of cooling to target temperature was reduced from 293 minutes to 143 minutes. The time from return of spontaneous circulation (ROSC) to target temperature was reduced from 436 minutes to 284 minutes. This translated to a more consistent mortality reduction to 65% and full neurologic recovery in over 80% of survivors. Conclusions: Multi-professional initiatives to implement therapeutic protocols can be successful and can be enhanced through continuous quality improvement. Standardization of TH therapy can improve therapeutic delivery and timing which appears to affect patient outcome.

Angus Butchart, Queen Elizabeth Hospital, Christine Tjen, Norfolk & Norwich University Hospital, Atul Garg, Peter Young, Queen Elizabeth Hospital Introduction: Difficult and failed intubation are leading causes of morbidity and mortality in anaesthetic practice, but occur more frequently in the pre-hospital and emergency setting. Video-laryngoscopy may provide advantages over traditional direct laryngoscopy by permitting indirect visualisation of the laryngeal inlet. The Glidescope Ranger (GSR; Verathon, WA, USA) and the Venner AP Advance (APA; Venner Medical, Singapore) are new video-laryngoscopes in clinical use. The GSR has a hockey-stick shape and requires learning a new technique and the use of a stylet. The APA is based on a standard Macintosh blade, has a guiding mechanism that foregoes the need for stylet and offers a familiar technique to those trained in direct laryngoscopy (DL). Hypothesis: These new devices demand different intubating techniques. We wished to assess their efficacy in a simulated difficult pre-hospital airway. Methods: Thirty qualified paramedics received a short demonstration of the APA and GSR and were asked to intubate a modified Grade III difficult laryngoscopy mannequin placed on the floor. Time to achieve optimal view and tracheal intubation were recorded and potential trauma assessed by number of discrete forward advances of the endotracheal tube and by visual analogue scale. DL was used as a comparator. Results: Participants declared a median 60 (20-300) previous intubations. There was no difference in time to achieve optimal view between APA and GSR, but tracheal intubation was significantly more rapid when the APA was used (p ⬍ 0.0001). Potential trauma was reduced for the APA compared to the GSR for number of discrete forward advances (p ⬍ 0.0001) and by visual analogue scale (p ⬍ 0.001). Conclusions: APA and GSR provided a faster intubation than DL in this difficult laryngoscopy simulation, however the APA demonstrated both earlier intubation and a more favourable trauma profile than the GSR. The APA may provide a more intuitive method for indirect visualisation of the larynx. Both devices warrant further investigation in the clinical environment.

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SUPRAGLOTTIC AIRWAY DEVICES FOR RESCUE DURING EMERGENCY AIRWAY MANAGEMENT IN THE REMOTE LOCATION

IMPROVING QUALITY AND SAFETY FOR A HOSPITAL EMERGENCY RESPONSE SYSTEM THROUGH IN SITU SIMULATION TRAINING

Jeff Keck, University of Connecticut, Thomas Mort, Hartford Hospital

Elizabeth Mack, Palmetto Health Children’s Hospital, Mary Patterson, Tom LeMaster, Jennifer Manos, Michael Moyer, Brian Pio, Derek Wheeler, Cincinnati Children’s Hospital Medical Center

Introduction: The laryngeal mask airway (LMA) is a valued asset in routine and emergency airway management. It provides ventilation when conventional efforts fail. It also offers a conduit to intubate when other methods are inadequate. Previously, Ferson et al, have shown a high success rate using the intubating LMA (iLMA) for the known difficult airway. Hypothesis: The LMA is an effective tool to achieve a patent airway in the ‘Can’t ventilate, can’t intubate‘ (CVCI) situation in remote locations. Methods: A QI database of remote intubations was reviewed (n⫽1515). The number of LMA insertions and the ability to establish ventilation was analyzed. All intubations via the classic LMA (cLMA) or iLMA were reviewed. Data on demographics, physiological status and anatomy were reviewed. Operator success rates were also analyzed to ascertain the impact of experience on placement. Results: 297 cases using the cLMA or the iLMA were reviewed. The iLMA was the most used device to rescue the ‘CVCI‘ case. Of LMAs used, 17% were cLMA and 83% were iLMA. The ability to ventilate with an LMA was great, 92%: 1st pass- 71.4%, 2nd pass- 89%. Ventilation occurred in 94% of cLMA and 91.5% of iLMA insertions, but 24 cases (21 iLMA and 3 cLMA) could not establish ventilation despite reseating or size change. LMA failures were rescued by Combitube (n⫽6), FOB (n⫽2), Bougie (n⫽1) and video laryngoscopy (n⫽15). A surgical airway was needed in two cases. 271 patients had intubation by iLMA with a success rate of 86.3%. Blind intubation via the iLMA (n⫽174) was successful in 88% (⬍4 attempts). FOB for rescue was successful in 16 of 23 attempts. FOB via the LMA as a primary method had a high success rate for both iLMA (21 of 28) and cLMA (44 of 46). An airway catheter was used for 29 of the cLMA⫹FOB attempts. Rates of missed intubations were 8.1% for staff and 17.9% for residents. There was a recognized difference in success rates and level of training (CA1- 41%, CA2- 9.5%, CA3- 12.2%). Conclusions: LMAs have a proven record for managing the DA in the CVCI situation, either as a primary means of ventilation or a conduit for endotracheal intubation. Experience with an LMA for rescue in the remote location is paramount and must be immediately available.


Introduction: Crew resource management training (CRM) is an effective method to reduce errors and improve safety, especially when focusing on nontechnical skills, such as teamwork, leadership and communication. A potential weakness of CRM is that it takes place in the artificial setting of a simulation lab. Conversely, in situ simulation training is conducted on actual patient care units and involves actual members of the health care team and is thus a more realistic and effective method of training. Hypothesis: We hypothesized that in situ simulation training will identify latent safety threats and improve care delivered to children suffering from cardiopulmonary arrest. Methods: With IRB approval, we reviewed our experience with in situ simulation over the past 2 yrs. In situ simulations were conducted using standardized scenarios 2x/month on the ward and 1x/month in PICU, alternating between day and night shifts. All scenarios involved clinical deterioration to cardiopulmonary arrest and were conducted in the actual clinical environment, in real time, and included bedside staff and personnel from the code team. Simulations were limited to 20 mins, including a debrief which reviewed technical and non-technical skills. All simulations were videotaped and analyzed later for quality improvement purposes. Results: We conducted approx 45 in situ simulations over the 2 yrs and identified 17 potential latent safety threats, which we categorized as medication, equipment, and/or resource/system threats. Identification of these errors resulted in modification of systems to reduce the risk of error. The in situ simulations also reinforced teamwork behaviors, including the use of assertive statements, role clarity, frequent updating, shared mental models, independent double checks of high risk medicines, and overcoming authority gradients. Conclusions: Our in situ simulation training program identified several latent safety threats in each of 3 major categories – medication, equipment, and resource/system and reinforced teamwork behaviors necessary for optimal resuscitation. We believe that in situ simulation training plays an important role in patient safety and quality improvement efforts.

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BISPECTRAL INDEX MAY BE A USEFUL SCREENING TOOL TO IDENTIFY PATIENTS FOR THERAPEUTIC HYPOTHERMIA AFTER CARDIAC ARREST: A RETROSPECTIVE STUDY

BREAKING THE CODE: THE DEVELOPMENT OF EDUCATIONAL VIDEOS TO IMPROVE RESUSCITATION PREFERENCE DISCUSSIONS WITH HOSPITALIZED PATIENTS AND SURROGATE DECISION MAKERS

Richard Riker, David Seder, Barbara McCrum, Gilles Fraser, Maine Medical Center Introduction: Therapeutic hypothermia (TH) is a standard treatment for comatose patients after cardiac arrest, but determining “coma” is often difficult in patients intubated and sedated prior to evaluation, often with TH already initiated. The bispectral index (BIS), a processed electroencephalographic variable between 0 and 100, appears useful for prognostication in this population during neuromuscular blockade (NMB), but has not been studied as a potential tool to assist with screening appropriate candidates for TH after cardiac arrest. Hypothesis: We propose that patients that awaken during TH would have high BIS values. Methods: We reviewed our TH database of 204 patients treated between July 2005 and August 2010, identifying 5 patients who awoke and followed commands during TH. Our TH protocol uses surface cooling (Arctic Sun) x 24 hours with 12 hour rewarming and includes intermittent NMB for shivering, infusions of fentanyl and propofol, and intermittent lorazepam. Results: All 5 had TH interrupted and recovered to a Cerebral Performance Category score of 1. The median (IQR) age was 58 (55-66) years, 60% were male. Cardiac arrest was witnessed in 5, 3 were transferred from another hospital, and arrest location was out-of-hospital in 4 and in-hospital in 1. Time from arrest to return of spontaneous circulation was 18 (13-24) minutes, including 1 min of no flow (no CPR) and 15 (8-20) mins of low flow (CPR). Initial rhythm was ventricular fibrillation in 3 and pulseless electrical activity in 2. The first BIS values after NMB were 63, 52, 43, 52, and 54, (median 52, 95% confidence interval 46-59) at a propofol dose of 30 (0-50) mcg/kg/min and fentanyl dose of 15 (0-35) mcg/h. The median BIS1 value in our database was 18 (6-36); only 10% were ⬎43. Conclusions: We conclude that an early BIS score ⬎43 during NMB after cardiac arrest may be associated with wakefulness. This small sample provides only a crude estimate of a possible BIS cutoff for TH. It is not known whether these patients may benefit from TH, nor whether the converse (BIS ⬍43 is an appropriate threshold for TH) is correct, but further study of the potential role of the BIS for the often difficult decision of whether to initiate TH is warranted.

Michael Wilson, Artur Krupa, Mayo Clinic, John Litell, Mayo Clinic (CCM), Ognjen Gajic, Mayo Graduate School of Medicine(Rochester), Keith Swetz, Kianoush Kashani, Mayo Clinic Introduction: Resuscitation preferences among patients and surrogate decision makers are typically assessed at hospital and ICU admission. Standards for these conversations are lacking or poorly enforced. Hospitalized patients often have scant knowledge and high levels of uncertainty when making decisions about cardiopulmonary resuscitation. Several authors have called for strategies to improve decision making. Video-based education tools have been successfully employed in other clinical settings to aid in decision making. Hypothesis: Key elements are important in the design and production of a video-based education tool to improve resuscitation preference decision making among hospitalized patients and surrogate decision makers. Methods: We searched the literature for existing tools to improve patient and surrogate comprehension of resuscitation status decision making. We also conducted focus groups and interviews of providers, patients, and members of the public. Data were compiled to guide the production of a video-based educational tool, which was reviewed by clinicians and patient representatives for appropriateness and accuracy. Results: Few tools to assist hospitalized patients in making resuscitation decisions are described in the literature. We identified the following elements as important in the video design: visual representation of the components of cardiopulmonary resuscitation, an explanation of “full code” and “do not resuscitate” status, and a presentation of the risks, benefits and alternatives of each resuscitation status choice. Other important design characteristics include short duration, repetition of key points, ease of comprehension, inclusion of elements designed to reduce anxiety and promote confidence, and deferral of specific recommendations to the patient and their provider. Conclusions: More strategies are needed to prepare patients and surrogates to establish resuscitation preferences. Videos with key components may help address this need. Subsequent studies should assess the impact of videos on patient comprehension and quality of decision making in the outpatient, inpatient, and critical care settings. Supported by a grant from the Mayo Foundation.

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HYPOTHERMIA THERAPY FOLLOWING PEDIATRIC CARDIAC ARREST: CLINICAL FACTORS CORRELATING WITH FAVORABLE NEUROLOGIC OUTCOMES

IF YOU BUILD IT, THEY WILL CALL: VOLUME, CHARACTERISTICS, AND OUTCOMES OF PEDIATRIC MEDICAL EMERGENCY TEAM CONSULTATIONS SIX MONTHS POSTIMPLEMENTATION

Sandra Buttram, Pamela Garcia-Filion, Korwyn Williams, Phoenix Children’s Hospital, Bentley Bobrow, Arizona Department of Health Services Bureau of EMS and Trauma System, Heidi Dalton, Phoenix Childrens Hospital Introduction: Post-cardiac arrest (CA) care goals include optimizing physiologic variables and minimizing secondary insults. Temperature control with hypothermia therapy (HT) improves neurologic outcome in adults and neonates after CA. Insults which increase cerebral metabolism such as hyperthermia (T⬎38 C) and seizures (SZ) may contribute to poor outcome. The efficacy of HT after pediatric CA is unknown. Hypothesis: We report the outcomes of HT compared to standard therapy (ST) following pediatric CA and clinical factors that correlate with favorable neurologic outcome. Methods: Patients (1d-18y) with out-ofhospital CA were prospectively identified by the AZ Dept. of Health Services Registry while in-hospital CA patients were identified retrospectively. A chart review of patients presenting from Jan. 2007–Aug. 2009 was performed. HT was used at attending discretion with goal temperature 32-34 C. A pediatric cerebral performance category (PCPC) scale score ⱕ 3 at hospital discharge defined a favorable neurologic outcome. Fisher’s exact test and logistic regression were used to evaluate the association between outcome and clinical characteristics. Results: We studied 46 patients; 33 received HT after CA. Overall survival to hospital discharge was 39% for the HT group versus 23% for ST (p⫽0.49). Compared to ST, hyperthermia was less common (21% vs 54%) and, when present, shorter in duration (hours) (2.8 ⫾ 2.5h vs 7.6 ⫾ 7.4h) in the HT group (p⫽0.04 and p⫽0.16, respectively). SZ tended to be less frequent in the HT (24%) group compared to ST (39%) (p⫽0.47). Favorable outcome was 50% more likely in the HT group compared to ST (OR 1.48; 95% CI 0.24, 7.6), and less likely when hyperthermia (0.23; 0.03, 2.1) and SZ (0.26; 0.03, 2.3) were present. In the HT group, patients that underwent slow (⬎8h) rewarming were 5.6 times more likely to experience favorable neurologic outcome (p⫽0.059). Conclusions: HT following pediatric CA trended towards improved outcome compared to ST. The incidence of secondary neurologic insults such as hyperthermia and SZ may be decreased by HT. Rewarming after HT should occur slowly. The efficacy of HT after pediatric CA should be evaluated in a randomized controlled trial.

Kathryn Roberts, Christopher Bonafide, Kathleen McLaughlin, Emily Huang, Carrie Silver, Donna Czaplicki, Jessica Wellner, Melissa Duva, Margaret Priestley, The Children’s Hospital of Philadelphia Introduction: The objective of this quality improvement evaluation was to analyze medical emergency team (MET) call volume, characteristics of patients receiving assistance from the MET, and outcomes of patients transferred to the ICU during the 6-month period post-implementation. Methods: A multidisciplinary team implemented a rapid response system (RRS) to improve early recognition and response to deteriorating patients on the non-ICU units of a 460-bed urban children’s hospital in February 2010. The RRS includes both afferent and efferent limbs. The afferent limb consists of an early warning score (EWS) and guidelines for escalating response. The efferent limb is a MET staffed by a physician or nurse practitioner, nurse and respiratory therapist who respond within 30 minutes of activation. Any bedside clinician can call the MET for increased EWS, concerning change in respiratory, cardiovascular or neurologic status, parent/family concern, staff concern or “gut feeling”. Six months post-implementation, we evaluated MET call volume, the proportion of calls occurring shortly after arrival on the inpatient unit, and critical outcomes occurring among patients transferred to the ICU. Results: The MET was activated 361 times over 6 months (14 calls/ week; 9.8 calls/1000 patient-days). 14 calls were escalated to a code blue before the MET arrived. 20% occurred within 6 hours of admission and 4% occurred within 12 hours after transfer out of the PICU or NICU. The call resulted in ICU transfer in 35%. Within 12 hours of arriving in the PICU, 2% of the patients transferred experienced a cardiopulmonary arrest, 16% required intubation, 7% required initiation/escalation of BiPAP and 10% required vasopressor administration. Conclusions: Pediatric MET call volume was high and may be sufficient to justify a stand-alone team. One-fifth of calls occurred less than 6 hours after admission, suggesting that systems to improve the prediction of deterioration in high risk patients at the time of admission may be of value. Few patients who were transferred experienced critical outcomes in the 12 hours after arriving in the PICU, suggesting that most transfers occurred before the patient experienced life-threatening deterioration.


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THE ATTITUDES TOWARD THE PERFORMANCE OF AUTOMATED EXTERNAL DEFIBRILLATOR (AED) IN JAPAN IN 2010

PREDICTIVE FACTORS FOR MORTALITY IN TRAUMATIC CARDIAC ARREST PATIENTS

Takumi Taniguchi, Masaki Okajima, Kanazawa University Hospital Introduction: The importance of the performance of cardiopulmonary resuscitation (CPR) and use of automated external defibrillator (AED) by bystanders is increasingly being recognized, and a large number of training courses for CPR and the use of AEDs are being conducted in USA, Europe, and Japan. Our previous study in 2006 showed that many non-medical people in Japan are unwilling to operate AEDs because they are not familiar with the concept of AED and/or with the method of using an AED, unlike medical personnel. Therefore, the present study was conducted to assess the current trend (i.e., in 2010) in the attitudes of Japanese people toward using AEDs if they witnessed a cardiac arrest. Hypothesis: We hypothesis that the non-medical Japanese people who are familiar with the concept of AED and have claimed their willingness to use AED will be greater than that in 2006. Methods: Participants of the study included high school students, teachers, medical nurses, and medical students; they were asked to respond to a questionnaire to assess their familiarity with the concept of AEDs and their willingness to use AEDs. These data were compared with those obtained in 2006. Results: A total of 2785 individuals (men, 45%) completed the questionnaire. About 71% of them had undergone training for CPR more than once. Further 47% of high school students, 89% of teachers, 93% of nurses, and all medical students were familiar with the concept of AEDs and how to use them; the percentages of high school students, teachers, and nurses in 2010 were significantly greater than those in 2006. Among the participants, 73% of high school students, 87% of teachers, 98% of nurses, and all medical students claimed they would ‘definitely’ use AEDs if required; the rates of high school students, teachers, and nurses in 2010 were significantly more than those in 2006. Conclusions: These findings suggest that the current number of non-medical Japanese people who are familiar with the concept of AED and have claimed their willingness to use AED is considerably greater than that in 2006. However, more non-medical Japanese people should be made aware of AEDs and how to use them.

Hyung Jin Shin, Tae Hoon Kim, Kyoung Lok Lee, Yonsei University, Wonju College of Medicine Introduction: Traumatic cardiac arrest patients have very poor prognosis. We sought to determine the predictive factors for mortality in trauma patients who received cardiopulmonary resuscitation. Hypothesis: There will be the specific predictive factors for mortality in traumatic cardiac arrest patients. Methods: We conducted a retrospective study of 560 patients with traumatic cardiac arrest (392 males [70%], mean age 48 ⫾ 21 years) who visited our ED from January 1997 to April 2010. We divided the patients based on length of survival: longer than 24 hours or shorter. Results: 212 patients (38%) recovered spontaneous circulation. 62 patients (11%) survived for longer than 24 hours. The patients who were discharged alive were 12 patients (2%). Among the immediate causes of cardiac arrest, hypovolemia was the most frequent (255 patients [46%]); CNS injuries was the cause in 198 patients (35%), and tension pneumothorax in 34 patients (6%). The odds ratio of the recovery of spontaneous ventilation was 23.036 (95% confidence interval [CI] ⫽ 5.452-97.336). Ratio of hypovolemia (⬎24h-survival group, 38% (24/62); ⬍24h-survival group, 60% (91/150) [p ⫽0.015]), head and neck trauma (⬎24h-survival group, 39% (24/62); ⬍24h-survival group, 29% (44/150) [p ⫽ 0.017]) and chest trauma (⬎24h-survival group, 15% (9/62); ⬍24h-survival group, 37% (56/150) [p ⫽ 0.007]) was significantly different between groups. Conclusions: Among ⬎24h-survival patients with traumatic cardiac arrest, there was higher incidence of head and neck trauma and less incidence of chest trauma and hypovolemia. The recovery of spontaneous ventilation was a predictive factor of survival according to our study.

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CARDIAC ARREST IN SURGICAL PATIENTS: EVALUATING OUTCOMES WITH A 24 HOUR, IN-HOUSE INTENSIVIST MODEL

A COMMUNITY HOSPITAL’S THERAPEUTIC HYPOTHERMIA TREATMENT OF ANOXIC BRAIN INJURY; RESULTS

Alyssa Chapital, William Stone, Daniel Johnson, Michelle Anderson, Joel Larson, Samuel Money, Mayo Clinic Introduction: One in five patients will survive to discharge after an in-hospital cardiopulmonary arrest (CA) and of those that survive approximately 15% of those will experience a significant insult where they are unable to independently care for themselves. There is also recent evidence that survival after CA is lower in the evenings and weekends with asystole being the first documented rhythm. Hypothesis: The aim of this study was to evaluate if a 24 hour in-house, board certified intensivist model had any affect on diurnal variation in outcome after CA. All patients with a documented in-hospital CA since 2001 were reviewed.Isolated respiratory arrests were excluded. Methods: This was a retrospective analysis performed at a university, tertiary care referral center. All patients with a documented in-hospital CA since 2001 were reviewed. CA was defined as loss of spontaneous circulation. Patients undergoing general or vascular surgery were included. Isolated respiratory arrests were excluded.. Results:212 patients were identified with CA. 38 patients represented the surgical cohort. Mean age was 64 yrs, 59% were male. Median post-op day for arrest was day 2. 74% experienced return to spontaneous circulation (RTSC). Of that group only 32% survived to discharge with 50% leaving to dependent care. RTSC was more likely if the code occurred during the day shift. PEA was the most commonly encountered rhythm followed by pulseless VT/VF during the evening shift. Despite 50% of evening patients generating a RTSC, mortality during that shift remained at 100%. Conclusions: It has been previously shown that survival rates from in-house cardiac arrest are lower during the evening shifts. The initial documented rhythm in the evening was asystole suggesting a difference in patient vigilance. While we found that patients with CA during the evening suffered from a higher mortality, PEA was the most commonly encountered rhythm. Despite that the 24 hour intensivist model perhaps produced a higher RTSC than quoted in the literature, this did not reflect in outcome during the evening shift. This suggests that monitoring is not the only factor in the disparate outcome in these surgical patients.


Kathleen Ledwick, Christine Sommers, Bradley Prior, Kadlec Regional Medical Center, Jeremy Blanchard, Kadlec Medical Associates Introduction: The objective was to share our results as a rural community hospital in treating anoxic brain injury associated with ventricular fibrillation (VF) cardiac arrest using mild hypothermic therapy (MHT). The design used was retrospective, observational, and a single center study. The study setting was a 188 bed community hospital. Hypothesis: A protocol developed based on the two landmark studies from Australia and Europe but, adapted to fit our facilities philosophy and mission would improve neurologic outcomes in patients with anoxic brain injury from a cardiac arrest. Methods: The study group included all out of hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless ventricular tachycardia who arrived at our facility and received MHT. The observations were from January 2006 to August 2010. The protocol includes chilled fluid resuscitation and a surface cooling device to reach a goal core temperature of 33 degrees Celsius. Hypothermia was maintained for 24 hours with a controlled 12 hour re-warming period. Key measurements for the study were: (1) witnessed OHCA with presenting arrhythmias of ventricular fibrillation or pulseless ventricular tachycardia, (2) CPR performed within 15 minutes, (3) return of spontaneous circulation (ROSC) within 30 minutes, (4) MHT duration in hours, (5) episodes of hypothermia below 32, (6) abortion of the protocol and reasons and (7) status at discharge. Results: The Glasgow-Pittsburgh Cerebral Performance Categories (CPC) was used as the measurement tool for outcome status at discharge. Patients’ outcomes were considered favorable with a score of 1-2 upon discharge from the hospital. A poor outcome was defined as a CPC score of 3-5. The results were that 58.3% (n⫽28) of the patients had a good/moderate outcome with a CPC score of 1-2; 41.6% had a poor outcome with a CPC score of 3-5. Conclusions: Our results were similar to the large academic centers. Hospitals of all sizes can institute a mild hypothermia protocol for the treatment of anoxic brain injury associated with cardiac arrest and have good results.

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TEACHING ADVANCED AIRWAY MANAGEMENT SKILLS: USING SIMULATION TO ACCELERATE THE FIBEROPTIC INTUBATION LEARNING CURVE

IMPACT OF RURAL HOSPITAL OUTREACH EDUCATION ON RECOGNITION AND MORTALITY IN PATIENTS TRANSFERRED WITH SEVERE SEPSIS AND SEPTIC SHOCK

Rana Latif, Alexander Bautista, Xinyuan Duan, Aurel Neamtu, Anupama Wadhwa, Dongfeng Wu, University of Louisville, Mary Carter, Medicine, Ozan Akca, University of Louisville

Cynthia Coleman, Audis Bethea, Robert Crisalli, Carol Morreale, David Seidler, Charleston Area Medical Center

Introduction: The importance of fiberoptic intubation (FOI) is well established for management of difficult airway. Teaching FOI to first responders might reduce airway-related complications in critically ill patients. Hypothesis: Training with fiberoptic simulator enables novices to acquire FOI skills comparable to experienced anesthesiologists. Methods: 8 attending as Experts and 15 medical students as Novices pre- and post-training were video taped while performing oral and nasal FOI on human anatomy simulator (Laerdal Medical, NY). Identities were concealed during recordings. Training comprised of practicing fiberoptic bronchscope skill on virtual reality simulator (Immersion Medical, MD), viewing a video presentation about FOI, and performing oral and nasal FOI on human anatomy simulator until reaching satisfactory performance. Two blinded faculty rated video clips using binary scoring with Pass ⫽ 1 (no further training required) and Fail ⫽ 0 (more training required). Time required to complete the procedure and the number (#) of attempts were documented. Paired and unpaired t-tests, the z-test comparing proportions, and the likelihood ratio test were applied as appropriate. Results: Experts performed better than pre-training Novices in 1) Pass/fail scores: 0.88 ⫾ 0.34 vs. 0.27 ⫾ 0.45; P⬍0.0001; 2) Duration of oral FOI: 48 ⫾ 22 vs 261 ⫾ 134 sec, P⬍0.0001; 3) Duration of nasal FOI: 50 ⫾ 21 vs 112 ⫾ 58 sec, P⫽0.0015; 4) # of oral attempts: 1.1 ⫾ 0.4 vs 5.8 ⫾ 1.7, P⬍0.0001; and 5) # of nasal attempts: 1.1 ⫾ 0.4 vs 4.3 ⫾ 2.1, P⬍0.0001. There was a statistically significant increase in the performance of Novices post-training in Pass/Fail score (0.27 ⫾ 0.45 vs 1.00 ⫾ 0.00, P⬍0.0001), duration of oral (260 ⫾ 134 vs 45⫾18 sec, P⬍0.0001) and nasal FOI (112 ⫾ 58 vs 43 ⫾ 9 sec, P⫽0.0004), # of oral attempts (5.8 ⫾ 1.7 vs 1.1 ⫾ 0.4, P⬍0.0001), and # of nasal attempts (4.3 ⫾ 2.1 vs 1.5 ⫾ 0.9, P⬍0.0001). The performance of Novices posttraining was not statistically different from that of Experts in any category. Conclusions: The simulation setting can be used to accelerate attainment of FOI skills among novices. Such a training approach may improve airway management outside of the perioperative environment.

Introduction: Charleston Area Medical Center’s (CAMC) sepsis team utilizes a multidisciplinary process to promote the identification and early implementation of appropriate clinical interventions in patients with sepsis. This approach has resulted in a decrease in mortality of approximately 15% since its implementation in 2007 and an overall mortality rate of 25% in 2009. Despite significant overall improvements, mortality rates associated with patients transferred from outside facilities remained high (45% in 2008). As a result, outreach education programs were organized and provided to rural facilities frequently transferring patients to CAMC. Hypothesis: Implementation of outreach education to rural institutions will result in improved recognition and mortality associated with sepsis. Methods: Since the implementation of outreach education in January of 2009, data has been retrospectively collected to assess its impact on the number of transfers (as a marker of recognition) and mortality rates. Comparisons between the groups were performed using t-tests with an ␣ of ⬍ 0.05 to determine statistical significance. Results: Outreach education was completed at 5 rural institutions. Institutions were provided screening tools, order sets and educated on resuscitation and management bundles. Additional support was provided through repeat onsite visits and telephone consultations throughout 2009. Patients transferred with the diagnoses of severe sepsis and septic shock increased from 75 in 2008 to 200 in 2009 (p ⬍ 0.001). Monthly patient transfers increased from 6 in 2008 to 16 in 2009 per month. Mortality rates decreased from 45% in 2008 to 35% in 2009 and through the first 7 months of 2010 were approximately 30% (p⫽0.171). Conclusions: Onsite outreach education provided to rural institutions improved identification of severe sepsis and septic shock patients as evidenced by a significant increase in patient transfers to CAMC. While not reaching statistical significance, mortality has drastically improved over the 19 months since implementation of educational efforts. Further data collection will continue over the remainder of 2010 and into 2011 in order to determine if this trend in improved mortality will continue.

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USE OF THE SCCM MULTIDISCIPLINARY CRITICAL CARE KNOWLEDGE ASSESSMENT PROGRAM (MCCKAP) EXAM TO IMPROVE THE QUALITY OF EDUCATION IN CRITICAL CARE FELLOWSHIPS

IMPACT OF COMPUTER-BASED SIMULATION ON PATIENT SURVIVAL IN MANNEQUIN-BASED ADVANCED CARDIAC LIFE SUPPORT SIMULATED CASES

David Machado, University of Michigan, James Blum, University of Michigan Health System, Pauline Park, Andrew Rosenberg, University of Michigan, Lena Napolitano, University of Michigan School of Medicine Introduction: The SCCM MCCKAP exam is administered to fellows to assess critical care knowledge. We sought to assess the impact of using this exam to modify our core curriculum annually to improve quality of education in our critical care (surgery and anesthesiology) fellowships. Hypothesis: The MCCKAP exam identifies areas of weakness in fellow critical care knowledge, enabling revision of the core curriculum, with resultant improvement in subsequent MCCKAP exam performance. Methods: The MCCKAP Adult exam was administered to all surgical and anesthesiology critical care fellows; performance in the specific component areas were reviewed. Areas with poor performance were identified, curriculum was revised annually to include new lectures to address these areas. Local and national data for the MCCKAP exam were reviewed for 5 years (2006-2010). Results: Total fellows taking the MCCKAP exam annually were 449, 441, 457, 459 and 475 respectively from 2006-2010. Primary medicine training was 62% of the cohort in 2006 and 52% in 2010. Fellows from nonMedicine backgrounds (including surgery and anesthesiology) has increased from 38% in 2006 to 48% in 2010. National examination scores have improved significantly, with an increase in the total number of correct answers from 58.9% in 2006 to 66.7% in 2010. A total of 35 surgery/anesthesiology fellows (6-9/annually) took the exam at our institution. Examination scores for our fellows were lower than national (48.9% vs. 58.9% correct) in the initial year (2006). With curriculum redesign based on review of the MCCKAP results, our fellow MCCKAP performance improved, with increases in raw scores for the total exam (48.9% in 2006 vs. 60.42% in 2010) and in specific subcategories . In the last 5 years, 94.1% of our fellows passed the American Board of Surgery surgical critical care examination. Conclusions: Use of the SCCM MCCKAP exam improved education in our critical care fellowship program and serves as a pivotal component for curriculum redesign. These curriculum changes resulted in improved exam performance and a high board certification exam pass rate. The increasing participation of fellows from non-Medicine background affirms the multidisciplinary nature of this exam.

Lindsay Palkovic, Quinn Czosnowski, Craig Whitman, Laura Finn, Michael Cawley, Philadelphia College of Pharmacy Introduction: Multidisciplinary Rapid Response Teams (RRT) require advanced training in advanced cardiac life support (ACLS) to improve patient survival. Limited data is published to determine if computer-based simulation used before mannequin-based simulation enhances learning to improve simulated patient survival. Hypothesis: Computer-based simulation completed prior to mannequin-based simulation will improve survival outcomes in mannequinbased ACLS cases compared to mannequin-based simulation alone.. Methods: Subjects were students in the Doctor of Pharmacy (PharmD) practice laboratory course at a large, private pharmacy school. Subjects were randomized to two sections and then to RRTs. Section A completed mannequin simulation before computer simulation, and Section B completed computer simulation cases before the mannequin simulation. Teams with members with ACLS certification or that completed simulation in the previous 6 months were excluded. One instructor documented all outcomes and used a rubric to determine survival. Case outcomes were reviewed blindly by two ACLS certified critical care pharmacists. Categorical data were compared with chi-square test in SPSS®. Results: There were 228 subjects in 40 RRTs. Many subjects had BLS certification (68%), but none had ACLS certification. Five teams were excluded due to members’ recent completion of simulation. Mannequin survival was greater in Section B than Section A (41.2% vs. 5.6%; p⫽0.018). More teams in Section B correctly completed all BLS skills (52.9% vs. 0%; p⬍0.001). Section B teams more frequently opened the airway (15 vs. 9; p⫽0.027), assessed breathing (17 vs. 13; p⫽0.045), and gave rescue breaths (16 vs. 4; p⬍0.001). All teams correctly selected the first medication, dose, and route. Few subjects in Section B (5%) would have preferred mannequin simulation first; however, most subjects in Section A (80%) would have preferred computer simulation first. Conclusions: Computer-based simulation prior to mannequin-based simulation improves survival in ACLS cases and improves BLS skills compared to mannequin-based simulation alone. Participants prefer computer-based simulation prior to mannequin-based simulation.


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IMPROVING NEONATAL ADMISSION TEMPERATURE FOLLOWING INTRODUCTION OF A SIMULATION TRAINING PROGRAMME

IMPACT OF ACUTE STRESSORS ON RESIDENT PERFORMANCE DURING SIMULATED RESUSCITATION

Ezam Mat Ali, Northwick Park Hospital, London, Dieudonne Birahinduka, Northwick Park Hospital Introduction: Hypothermia in premature infants is strongly associated with increased morbidity and mortality. Suboptimal admission temperature to neonatal units is largely a consequence of management at delivery. Studies of intervention in thermoregulation at birth have shown that neonatal admission temperature can be improved by the use of plastic or polyethylene bags at delivery.However, regardless of available published evidence in the medical literature, there is still discordance in its translation into clinical practice. Despite the use of polyethylene bags, many neonatal units in the UK still record admission temperatures of less than 36°C. Hypothesis: Simulation training on admission temperature of preterm babies leads to a decrease in the number of babies admitted with hypothermia. Methods: In October 2006 we designed a guideline on thermal care at birth and undertook workshops for neonatal doctors and neonatal nurses to simulate the management of newborn babies in delivery room on a weekly rolling system. The target admission axillae temperature was 36.5°C to 37.5°C. We collected data for admission temperature, gestation, gender, birth weight and time from birth to admission to our neonatal unit from January 2005 to December 2007. All babies born at less than 31 weeks gestation were included in this study. Results: There was a statistically significant increase in admission temperature after the simulation training when compared to before the workshop started (mean 35.7°C; SD 0.89 vs 37.0°C; SD 0.47 respectively, p⬍0.0005, Independent student t-test).There was a significant reduction in the number of neonates with admission temperatures of less than 36.0°C after the simulation workshop when compared to before the training (52.6% vs 1.8% respectively; Pearson Chi-Square p⬍0.0005). There was no significant increase in admission temperature of more than 37.9°C after the introduction of simulation workshop (0% vs 1.8% respectively; Pearson Chi-Square p⫽0.24). Conclusions: Multiprofessional simulation training in thermoregulation of preterm babies at delivery together with a comprehensible and realistic guideline on thermal control can reduce the likelihood of them being hypothermic on admission.

Dominique Piquette, Sunnybrook Health Sciences Centre - Department of Critical Care Medicine, Jordan Tarshis, Tasmin Sinuff, Sunnybrook Health Sciences Centre, Robert Fowler, Sunnybrook Hospital, Vicki LeBlanc, Wilson Centre for Research in Medical Education Introduction: Health care professionals have identified stress as a contributor to medical errors committed in the intensive care unit (ICU). Residents’ clinical performance may be more susceptible to the effects of stress because of their lack of experience. Hypothesis: The objective of this study was to determine the residents’ stress responses and clinical performance during simulated, high acuity ICU scenarios. Methods: Each resident completed two simulated scenarios. For each scenario, they were exposed to one of two stress conditions (high vs. low) created by adding external stressors (noise, distractors) to the baseline scenarios. Psychological (anxiety, cognitive appraisal) and physiological (heart rate, cortisol) measures of stress were collected pre and post scenario. Two assessors independently evaluated residents’ videotaped performance using the Ottawa global rating scale (GRS). The primary analysis was conducted on the Ottawa GRS score, using a 2x2x2 between subject analysis of variance with stress condition (low, high), scenario (A-unstable atrial fibrillation; B-abdominal sepsis), and order of stress exposure as the independent variables. Twenty-six participants per group were required to provide a power of 80% at 5% significance level to detect a difference of 1 point with a standard deviation of 1.25 on the Ottawa GRS. Results: Overall, the scenarios triggered significant psychological and physiological stress responses among the 54 study participants. However, these responses often peaked before the beginning of the scenario. The experimental ‘high-stress’ condition did not elicit greater stress responses than the ‘low-stress’ condition. No difference in performance was found between the high-stress and low-stress condition (F value⫽2.84, p⫽0.098). Post-hoc analyses revealed no association between stress measures and performance. Conclusions: Resuscitation simulations evoked significant stress responses that appeared mostly related to anticipatory stress rather than external stressors occurring during the scenarios. We did not observe an association between stress responses and performance. Factors that modulate clinicians’ stress responses and their impact on performance should be further explored.

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THE EFFICACY OF AN ONLINE TRAINING AND SIMULATION-BASED COMPETENCY PROGRAM FOR THE USGUIDED PLACEMENT OF CENTRAL VENOUS CATHETERS AND ITS HOSPITAL-WIDE IMPLEMENTATION

A HIGH-FIDELITY SIMULATOR LEARNING ENVIRONMENT IMPROVES CARDIOVASCULAR CRITICAL CARE KNOWLEDGE GAIN AND RETENTION

Lauren Philbrook, Allan Kachalia, Marcy Carty, Kimberly Matzie, Aya Mitani, Marie Gerhard-Herman, Charles Pozner, Gyorgy Frendl, Brigham and Women’s Hospital Introduction: Although ultrasound (US) guidance reduces central venous catheter (CVC) related complications, it remains a recommended but not widely implemented practice. Standardization of images, the development of scalable hospital-wide training, competency and quality control programs will be necessary to gain wider implementation. Hypothesis: Web-based training for USguided CVC placement will not be inferior to traditional classroom training and will be preferred by trainees. It may save time and reduce costs. Methods: 133 participants were randomly assigned to classroom-based (65) or web-based (68) training (with identical content) via computer-generated randomization, stratified by specialty and training level. A narrated PowerPoint lecture was supplemented by mentored hands-on practice (classroom) or a video (web-based) demonstrating all aspects. Completion required the trainees to pass an online, multiple choice test and a 1-hour simulator-based test (US-guided CVC placement into a mannequin (Blue PhantomTM)). Participants completed an online survey (©SurveyMonkey) on the effect of this training on their clinical practice. Results: The mean scores of the knowledge test (scale: 100) were 72.9 (CI: 70.1-75.5; classroom n⫽65) and 74.0 (CI: 71.0-77.0; web n⫽68). A one-sided non-inferiority t-test (defined as web group no more than 3 points below the classroom group) shows that web-based learning is not inferior to classroom based learning (p⫽0.0205 for non-inferiority, power: 0.656). Survey response rate was 86.4% (web) and 88.9% (classroom). Both groups agreed that US-guidance made the procedure safer (p⫽0.43), 87% recommend mandatory training for all (p⫽0.71), and felt that this course has changed the way they perform CVC placement; use of US-guidance increased to 80-90%. Conclusions: Our webbased program proved to be as effective as traditional methods for teaching US-guided CVC placement. A web-based system is a safe, cost-effective, and scalable means of training large numbers of individuals, but adjuncts must be developed to provide trainees hands-on practice. Our program, fully implemented, will train and certify 300-500 clinicians annually.


Paul Dobesh, Keith Olsen, Donald Klepser, Patricia Carstens, Dean Collier, Julia Reffert, University of Nebraska Medical Center Introduction: There is increasing interest in the value of learning with highfidelity human patient simulators (HPS). Several studies have reported improved task performance and participant satisfaction, but few have examined HPS as an adjunct to the classroom and evaluated its effect on long-term knowledge retention. Hypothesis: Exposure to an HPS learning environment in cardiovascular critical care will result in improved scores on both immediate and follow-up objective examinations. Methods: 126 third year pharmacy students were assigned to either traditional classroom (n⫽64) or HPS (n⫽62) settings over 2 academic years. Both groups were presented the same series of cases involving code and shock situations, and a single instructor followed a script to facilitate student learning and discussion. Three days after the experience, a 10 question multiple-choice examination was administered. Exam questions were categorized as patient assessment, selection of therapy, or the evaluation of therapy. Students also completed a Likert scale survey to assess their impression of each learning experience. The multiple-choice examination was repeated three months later to assess retention. Results: Overall, the students exposed to HPS performed significantly better on both examinations. These students correctly answered 7.07⫾1.39 questions out of 10, while classroom students had an average score of 6.53⫾1.45 (p⫽0.0395). A similar result was observed in the follow-up examination, with scores of 7.29⫾1.52 vs. 6.53⫾1.69 (p⫽0.0091). The primary difference between the groups was observed with the higher level learning questions on evaluation of therapy for both the initial and follow-up exams (p⫽0.0016 and p⫽0.0032). The results of the Likert scale survey were also in strong favor for the HPS environment over the classroom experience. Conclusions: Incorporation of high-fidelity simulation enhances learning and leads to significant, sustained increases in knowledge.

494 OBJECTIVELY EVALUATING PEDIATRIC RESIDENT PERFORMANCE USING CLOSED MALPRACTICE CLAIMS IN A SIMULATOR BASED TESTING ENVIRONMENT Chelsie Byrnes, Brian Cummings, Wayne Stathopoulos, Natan Noviski, James Gordon, Massachusetts General Hospital Introduction: Ensuring that pediatric residents have the practical skills they need to become independent practitioners is a challenge. Standardized testing does not capture the nuances associated with practical skills. Simulation is an alternative means of evaluating residents in real life scenarios. Hypothesis: It is feasible to objectively evaluate pediatric residents in a simulation based testing environment, using closed malpractice claims, to ensure residents meet the minimum standards for acceptable patient care. Methods: Two claims out of 198 provided by our malpractice carrier were developed into pediatric simulation scenarios. Cases were standardized through a written protocol and computer programming of the simulator. Twelve subjects participated as a clinical leader in both scenarios. Two physicians evaluated each resident using a clinical performance evaluation tool, previously found to perform equally well to the OSCE scoring system. The scoring system encompasses eight competencies consistent with those endorsed by the ACGME. Both examiners evaluated and scored a test subject to standardize the evaluation scale. After each scenario, each resident was debriefed on the case. Residents completed a follow up survey to get their impressions about their experience. Results: The evaluation tool showed consistency with low interobserver variability. Clinical scores increased in relation to training level of the pediatric resident. The majority of residents reported the simulation as a positive experience, citing that it was helpful to individually deliberate through the scenarios and make independent decisions. All of the residents requested simulation training to be mandatory as part of residency training. Conclusions: This pilot project demonstrated that using simulation based testing is a feasible means of objectively evaluating residents’ performance. It provides a practical and objective complement to standardized testing as a mechanism to ensure that pediatric residents meet specific expectations upon completion of their residency training. The trend of increasing performance with increasing experience shows that this may be a potential mechanism for assessing the knowledge at various training levels.


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SURVEY OF CRITICAL CARE EDUCATIONAL EXPERIENCES IN US MEDICAL SCHOOLS

SUCCESSFUL PROVISION OF ICU DIDACTIC EDUCATION IN AN ACGME COMPLIANT MANNER

Oveys Mansuri, Harvard Medical School / Brigham and Women’s Hospital

Lisa Hollett, Kazuhide Matsushima, Scott Armen, Penn State Hershey Medical Center, Heidi Frankel, Penn State College of Medicine

Introduction: As reports of predicted workforce shortages in primary care capture the attention of the public, the shortage of ICU physicians is often overlooked. Outcomes research has demonstrated that critical care specialists can improve morbidity and mortality, and reduce healthcare costs. Medical schools offer many elective ICU experiences to their students, but the timing and availability of these are limited. Hypothesis: Performing a review of critical care experiences available to medical students provides both a portrait of the current state of critical care exposure at the undergraduate medical education level, as well as insight into reasons for decreased interest in critical care postgraduate training. Creating mandatory critical care clerkships early in training may be a method of increasing recruitment into ICU training programs. Methods: The study reviewed available curriculum for the 133 US medical schools represented by the AAMC during the M3 and M4 years with special attention to ICU experiences, and any requirements for an ICU rotation prior to graduation. The experiences were categorized into anesthesia, medicine, surgery, pediatric, neurological, emergency medicine, and required ICU clerkships. The data was then analyzed for preliminary staging of critical care education in medical schools. Results: Only 15 critical care clinical experiences were available to 3rd year students between 121 medical schools, the majority being in medical, surgical, and pediatric ICUs. During the M4 year there were 440 ICU rotations available between 116 medical schools. 21% of medical schools required a critical care experience prior to graduation. Again, the majority of the clinical experiences were in medical, surgical, and pediatric ICUs. Conclusions: During a time when ICU training programs are finding innovative curriculum models to recruit intensivists, the undergraduate medical curriculum remains unchanged. This limited survey of medical schools supports that allowing for early exposure to ICU rotations and making critical care education in medical school a national standard would increase interest, potentially help reduce the workforce shortage, and improve the critical care background of all physicians.

Introduction: It is difficult to provide a structured didactic curriculum to novice learners in the ICU compliant with current ACGME regulations. Hypothesis: Our hypothesis is that it is possible to deliver a curriculum that will result in performance improvement over the course of a rotation. Specifically, post scores will improve over pre scores utilizing combined self study/formalized classroom approach. Methods: All surgical, anesthesia or emergency medicine residents and medical students on a rotation in the adult SICU of an academic medical center were enrolled in a Monday-Friday curriculum at 1100 covering topics in the SCCM Adult Intensive Care Unit Curriculum for Residents (RICU). Pre and post test scores were compared. Home access was given to the online PowerPoint presentations. Pre-testing was completed prior to the course using the RICU pretest. The post test was completed within one week of the end of the rotation. A minimum passing score of 70% was required for satisfactory rotation completion. Duty hours were logged. The 30 bed SICU was staffed by 2 teams of 3-5 residents each and a board certified intensivist; AM rounds were concluded to allow lecture attendance. Paired student’s T testing compared pre-and post-test values. Results: There were 63 participants from January-June, 2010. 22 paired pre and post tests were analysed. Pre-test scores ranged from 22-95 and post-test scores from 54-100. One resident required two attempts to successfully pass the post. The total mean pre-test score for all was 57.23. At post-test this score increased to 90.34 (⬍0.001). The sole group that had a statistically significant change from pre to post was medical students, 46.67-93.75 (p⬍0.001). This group also had the highest attendance rate at live sessions. No violations of ACGME duty hours (self-reported) were logged over the study. Conclusions: Providing a formalized, structured critical care education program utilizing RICU with bedside teaching results in measured knowledge improvement for novice critical care providers that is ACGME compliant. Further implementation in other settings and utilizing other modalities including skills sessions, and asssessment of knowledge retention should be investigated.

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ERRORS, INCIDENTS, AND ATTITUDES OF PHYSICIANSIN-TRAINING FOLLOWING ELIMINATION OF LONG DUTY PERIODS IN THE ICU

IMPROVING ADVERSE DRUG EVENT DETECTION IN CRITICALLY ILL PATIENTS THROUGH INTENSIVE CARE UNIT TRANSFER SUMMARY SCREENING

Walter Boyle, Richard Fagley, John Mazuski, Douglas Schuerer, Robert Southard, Washington University in St. Louis

Ananth Anthes, University of Pittsburgh Medical Center, Lisa Harinstein, The Cleveland Clinic, Pamela Smithburger, University of Pittsburgh School of Pharmacy, Amy Seybert, University of Pittsburgh, Sandra Kane-Gill, University of Pittsburgh School of Pharmacy

Introduction: Long duty periods (DPs) for physicians-in-training (PITs) can result in fatigue-related medical errors, and dangerous work- and driving-related incidents. We assessed these and other training-related issues before and after changing from 30 hr to 14 hr DPs in a busy 24-bed ICU at a major medical center. Methods: PITs with 30 hr DPs on the ICU service from 1/1-4/30/09 completed an anonymous 45 item ‘pre-change’ survey at rotations end. Following implementation of 14 hr DPs on 7/1/09, PITs on service from 1/1-4/30/10 completed the same ‘post-change’ survey. Results: 36 PITs completed the prechange survey, and 28 PITs completed the post-change survey. There were decreases in the % of PITs who self-reported medical errors from pre-change to post-change, including errors affecting care (27.7% vs. 16.7%) and errors not affecting care (50.0% vs. 8.3%), and in the total number of errors reported (55 vs. 16). Fewer PITs reported ‘near-miss’ traffic events (30.6% vs. 17.9%), traffic tickets (13.9% vs. 0%), and MVCs (5.6% vs. 3.6%), and there were fewer total driving events reported (36 vs. 15). The PITs’ rating of DPs duration as “too much” decreased (69.4% vs. 10.7%), while rating of the DPs duration as “about right” increased (30.6% vs.75.0%). The rating of sleep time as “about right” similarly increased (25.0% vs. 67.9%). Handover time increased from “⬍1 hr” (69.4% vs. 21.4%) to “1-2 hr” (30.6% vs. 67.9%). Didactic lecture time decreased from “1-2 hrs” (72.2% vs. 32.1%) to “⬍1 hr” (5.6% vs. 60.7%). Most PITs in both surveys (⬎90%) rated “critical care training in professional development” and “the role of the Intensivist” as “important” or “very important”. Conclusions: These findings suggest long DPs in the ICU are more risky for patients and PITs alike. Shorter DPs appear to improve safety and PITs attitudes about the duration of DPs and sleep time. An increase in the number of handovers with shorter DPs may increase risk, and the increased handover time observed in this study should be expected. Decreased didactic lecture time related to an inability of PITs on nighttime DPs to attend mid-day didactic offerings can be addressed by moving these offerings to “peri-handover” periods.


Introduction: Current ADE detection relies heavily on voluntary reporting which results in underreporting. Hospital discharge notes have been studied as a form of surveillance; however, ICU transfer summaries have not been studied for this purpose. Improving ADE prevention strategies relies upon improving detection. Hypothesis: ICU transfer summaries are an effective tool for ADE detection. Methods: A retrospective electronic medical record review was conducted among medical ICU patients. Inclusion criteria included patients ⱖ18 years of age admitted between January through April 2009 with an ICU length of stay ⱖ24 hours. Two scales were utilized to assess chart documentation for ADEs: 1) Harvard Medical Practice Scale (MPS) and 2) Leonard Evidence Assessment Scale. The Harvard MPS was used to rank the strength or confidence of the wording in the medical record with a score of 4 (more than 50-50 but close), 5 (moderate/strong) or 6 (virtually certain) indicating the presence of an ADE. The Leonard scale was used to score causality and included objective markers such as presence of symptoms or if an antidote or counteracting procedure occurred. Leonard scores of 1 out of 4 indicated unlikely ADE, 2 of 4 possible, 3 of 4 probable and 4 of 4 a certain ADE. Results: Preliminary demographic information indicates 50% of the patients were male with a mean age of 60.3 years (⫹/⫺ 16). 258 unique patients had ICU transfer summaries screened and evaluated for ADEs. 105 patients had at least 1 ADE with a total of 139 ADEs. The Harvard MPS scores collected were 4 (39.6%), 5 (51.8%) and 6 (7.9%). The Leonard scores were 2 of 4 (17.3%), 3 of 4 (54.7%) and 4 of 4 (28.1%). Most common medications associated with an ADE were furosemide, ciprofloxacin, warfarin and heparin. Most common ADEs were Clostridium difficile, hypotension, acute kidney injury and hyperglycemia. Conclusions: 41% of ICU transfer summaries contained a description of an ADE; therefore, reviewing ICU transfer summaries is a useful method of detecting ICU-specific ADEs and should be considered as part of an ADE surveillance system. Understanding contributing medications and resulting reactions of ADEs will aid in future prevention strategies.

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EFFICACY OF A PROGRAM DESIGNED TO TEACH AIRWAY SKILLS TO PEDIATRIC RESIDENTS

CAN A MULTIMEDIA EDUCATIONAL PROGRAM FOR A PEDIATRIC SUBSPECIALTY TEAM IMPROVE THEIR KNOWLEDGE AND MODIFY CLINICAL OUTCOMES?

Richard Mink, Nicole Baier, Harbor-UCLA Medical Center & LABioMed, Christopher Babbitt, Miller Children’s Hospital, Khahn-Van Le-Bucklin, University California, Irvine, Esther An, Harbor-UCLA Medical Center, Tom Kallay, Harbor-UCLA Medical Center & LABioMed Introduction: Upon completion of training, pediatric residents are expected to be competent in endotracheal intubation (ET). However, the opportunity to learn this skill has recently decreased. In order to improve resident airway skills, we created a program comprised of didactic sessions, simulation, an anesthesia rotation with supervised patient encounters and a test to reinforce knowledge. Hypothesis: The purpose of this study was to determine the effectiveness of the program in improving trainee airway knowledge, skills and attitude. Methods: Pediatric interns from 2 different pediatric residencies were evaluated. One group was given the course, the other was not. Knowledge, skills and attitude were assessed in both groups in the middle of the 1st year of training (pre-course) and at the start of the 2nd year (post-course). Measurements included tests of airway knowledge (multiple-choice and case scenario questions), evaluation of bag-mask ventilation and ET performance (checklists), and a confidence questionnaire. These tools were previously shown to be reliable and valid. Questions and skills were scored as percent correct; the questionnaire used a 5-point Likert scale. Analyses used the Student’s t-test and compared baseline scores and change from baseline. Data are mean⫾SD. Results: Nine residents who completed the program and 11 who did not participated in both testing sessions. The groups were similar (p⬎0.05) in all baseline assessments except those who did not take the program scored slightly better (p⬍0.05) in ET than those who took the course (48.3%⫾0.09 vs.40.1%⫾0.07). Course participants showed a greater improvement (p⬍0.05) in multiple-choice questions (19.3%⫾12.2 vs.3.3%⫾15.8), ET (34.1%⫾13.5 vs. -6.3%⫾16.5), and greater airway confidence (1.1⫾0.3 vs. -0.02⫾0.5). There was improvement in the case questions (12.0%⫾13.3 vs. 1.7%⫾13.5) and bag-mask ventilation (11.3%⫾18.7 vs. -4.3⫾20.4) but these were not significant (p⫽0.11 & 0.10, respectively). Conclusions: An airway skills program that uses multiple methods of teaching can successfully improve pediatric trainee airway knowledge, skills and attitude. Further evaluation is needed to determine if these improvements are maintained.

501 QUALITY OF VENTILATION SUPPORT DURING ACLS TRAINING SITUATIONS UNDER HIGH STRESS CONDITIONS IN A HUMAN MANIKIN MODEL OF CARDIAC ARREST Markus Foedisch, Evangelische Kliniken Bonn, Alexander Boscher, Michael Reith, Ludwig-Maximilians-University Munich Introduction: Although sufficient ventilation is a key requirement during CPR and the AHA 2005 resuscitation guidelines suggest expansion of airway management options, only little data exist regarding ventilation quality in simulated cardaiac arrest (CA) scenarios under high stress conditions. Hypothesis: Ventilation quality is substandard predominantly under high stress conditions. Methods: The CA scenarios were performed in a full-scale cabin simulator at the Lufthansa Flight Training Center under simulated flight conditions using standard emergency equipment. A team of three rescuers (primary care physicians) experienced in mask ventilation, treated 15 min CA scenarios of a collapsed flight passenger. A computerized manikin (Ambu CCT simulator) and a custom-made recording program were used to measure ACLS data focussing on performance of ventilation quality. Ventilation was considered to be sufficient with a rate of 3-6/min and a tidal volume between 250 and 400 ml. Results: 100 CPR sessions were recorded and evaluated. Bag-mask ventilation and endotracheal intubation, but no supraglottical device were provided in the standard airline emergency equipment. First mask ventilation was established 0,5-10,3 min (median 2,76 min) after start of ACLS. Endotracheal intubation was performed in 51% of the scenarios, mean time to succesful intubation was 7,3 min. Sufficient mask ventilation over the whole CA scenario course could be achieved in only 46%, oxygen application was missing in 22%. If endotracheal intubation was performed, ventilation rate and volume were classified sufficient in 89%. Some factors contributing to insufficient ventilation were seen to be human factor related (team performance, mask and head postioning). Analyzing the whole CA scenarios it got obvious that ventilation skills are highly variable and appeared to be correct half the time. Conclusions: Overall ventilation quality in ACLS training scenarios has to be judged poor especially under mask ventilation conditions even from experienced caregivers. This underlines the importance of implementing alternative airway management strategies like use of a supraglottical airway device to optimize ventilation performance during CPR.

Hemant Agarwal, Vanderbilt Children’s Hospital, benjamin saville, Vanderbilt University, Frederick Barr, Vanderbilt Children’s Hospital, Zena Harris, Johns Hopkins University and School of Medicine, Jayant Deshpande, Vanderbilt Children’s Hospital Introduction: A multi-disciplinary team approach to sub-specialty care requires development of an educational program to reinforce quality care concepts. Hypothesis: Our primary objective was to assess quality and beneficence of multimedia educational program (MMEP) developed for the entire clinical team working in Pediatric Intensive Care Unit (PICU) & Pediatric Heart Institute (PHI). Secondary objective was to correlate implementation of the MMEP with improvement in clinical outcomes in the PICU and PHI. Methods: MMEP using standardized format similar to case-based scenarios was delivered every week to the clinical team. All patients undergoing cardiac surgery were assessed for outcomes before and during the program’s implementation period. The quality of MMEP and its beneficence for each clinical team member was assessed using Likert scale (1 to 5) responses in an anonymous survey following one year of continuous education. Clinical outcomes including mortality and morbidity variables for patients were assessed for the study period and compared with those of the pre-study period. Results: 86% of 259 clinical team members responded to the survey. Quality of the MMEP was excellent (mean response on the Likert scale 4.4⫾0.6) with no difference in responses across clinical team (p⫽0.3). It had excellent beneficence (mean response of 4.3⫾0.7) with Cronbach’s alpha of 0.93 revealing high internal consistency among responses with maximum benefit to the residents (p⫽0.006). The MMEP r esulted in reduction in length of mechanical ventilation for 3 of 10 commonly operated cardiac defects (tetralogy of fallot (TOF): p⫽0.02, bidirectional Glenn shunt (BDG):p⫽0.057 and atrial septal defect(ASD): p⫽0.09). Conclusions: Development of a high quality multimedia educational program in pediatric subspecialty is beneficial for the entire clinical team in particular resident physicians. Provision of such an educational program is associated with a trend towards improved clinical outcomes.

502 EVALUATION OF A PEDIATRIC RRT PROGRAM Beth Wathen, Jennifer Goode, Emily Dobyns, The Children’s Hospital Introduction: Our pediatric tertiary care hospital implemented a rapid response team (RRT) in February 2007. The RRT is comprised of the ICU fellow and charge RN, house supervisor and respiratory therapy supervisor. The RRT responds to requests from both inpatient and outpatient areas. A separate Code Blue Team responds to all medical emergencies. The RRT responds to an average of 30 calls per month. In November 2008, we implemented a program to allow family members to request an RRT. Hypothesis: Objectives were threefold: 1. Evaluate staff acceptance of RRT program 2. Identify ongoing barriers encountered with the current RRT program between disciplines and 3. Identify additional methods staff feel will improve our RRT program Methods: A 13 question Zoomerang survey was developed and sent to all members of the clinical staff. Staff were given three weeks to respond and multiple email reminders were sent out. Results: 325 staff members completed the survey (76 physicians/mid-level providers, 211 RNs, 16 RTs, and 22 other clinical staff). 32% of responding staff knew the appropriate timeframe for the RRT response. 28% thought the RRT response should be immediate, thus highlighting the continued confusion between our code blue and RRT response teams. 70% of staff stated that 75% of time or greater they were comfortable in escalating concerns if other team members disagree. 87% of staff were satisfied with current RRT program at least three quarters of the time. 30% reported they have encountered a negative response from another staff member when requesting an RRT. Data was analyzed between disciplines to identify discipline specific barriers and concerns. The main barriers identified with the current RRT program include communication concerns between disciplines and ‘fear of appearing as if they did not know what they were doing‘. Across all disciplines, standardized simulated codes and communication/ teamwork training were the most requested areas for additional focus. Conclusions: Evaluating our 3 year old RRT program provided valuable insight into current acceptance of the program, identified barriers across disciplines, and provides direction for further initiatives to enhance the program.


503 NEW METHOD DIAGNOSTICS COAGULATION DISORDERS AFTER SURGERY Ivan Tyutrin, Siberian State Medical University, Oleg Tarabrin, Odessa State Medical University, Alexandr Stecenko, Siberian State Medical University, Sergii Shcherbakov, Dmytro Gavrichenko, Odessa State Medical University Introduction: Despite the evidence of perioperative hypercoagulability in cancer patients, there are no consistent data evaluating the extent, duration, and specific contribution of platelets and procoagulatory proteins by in vitro testing. This study compared efficacy of haemoviscoelastography versus thromboelasthgraphy for monitoring of coagulation imbalance. Methods: 241 Patients undergoing surgery for abdominal cancer we examined the efficacy of a variety of coagulation tests. A complete coagulation screening, thromboelasthgraphy (TEG) and haemoviscoelastography (HVG) were performed before and at the end of surgery. Results: We calculated the elastic shear modulus of standard MA (Gt) and HVG MA (Gh), which reflect total clot strength and procoagulatory protein component, respectively. The difference was an estimate of the platelet component (Gp). There was a 16% perioperative increase of standard MA, corresponding to a 51% increase of Gt (P ⬍ 0.05) and an 79%-87% contribution of the calculated Gp to Gt. We conclude that serial standard thromboelastography and HVG viscoelastic test may reveal the independent contribution of platelets and procoagulatory proteins to clot strength. Using multiple linear regression, all coagulation, TEG and HVG variabities were used to model postoperative hypercoagulation. Results showed that some components of the TEG failed to identify hypercoagulation (r ⬍ 0.2, P ⬎ 0.75). All components of the HVG test reflect postoperative coagulopaties. Conclusions: Hypercoagulability is not reflected completely by standard coagulation monitoring and TEG and seems to be predominantly caused by increased platelet reactivity. HVG provides a fast and easy to perform bedside test to quantify in vitro coagulation, may be usefull in determining the coagulation status of cancer patients perioperatively.


Poster: Education-3 504 PFCCS AND INTERN PERCEPTIONS OF SELF-EFFICACY Jason Werner, Cardinal Glennon Children’s Hospital, Daniel Bruzzini, US Air Force Center for Susstainment of Trauma and Readiness Skills, Jeremy Garrett, Cardinal Glennon Children’s Hospital, Heidi Sallee, Saint Louis University School of Medicine Introduction: Graduating pediatric interns are asked to supervise the care of increasingly ill children, but have received little formal training in the recognition and management of these patients. Hypothesis: Teaching the Society for Critical Care Medicine’s Pediatric Fundamentals of Critical Care Support course with the addition of high-fidelity simulation scenarios to graduating pediatrics PL-1s will increase feelings of self-efficacy when managing critically-ill children. Methods: All research was approved by the St. Louis University (SLU) School of Medicine IRB. All pediatrics residents at the SLU School of Medicine completing their intern year were taught the PFCCS course in May of 2010. The course included four high-fidelity simulations after the conclusion of the didactic part of the course. Learners were asked to complete a survey of 10 5-point Likert scale questions on their feelings of preparation for managing critical children before and after the course and were given the opportunity to provide feedback on their feelings about the course. Areas assessed included caring for critical pediatric patients, monitoring patients during intubation, operating a ventilator, making decisions about mechanical ventilation, choosing medications for rapid-sequence intubation, leading a medical code, evaluating and correcting electrolyte abnormalities, arranging transport for a critically-ill child, providing sedation and analgesia, and recognition and initial management of shock states. Results: 13 pediatrics interns were taught the PFCCS course. All interns completed both surveys. Results were compared using a paired Student’s t-test. Learners’ reported feelings of preparation increased by an average of 0.97 points. The improvement in seven items were significant at or below p ⫽ 0.02. 10/11 interns indicated they thought the course was “extremely helpful”. 8/11 said lectures were the least helpful part of the course, and 8/11 said the simulations were the most helpful. Conclusions: Being taught the PFCCS course reliably improved pediatric interns’ feelings of preparation for recognition and management of critically-ill children. Interns found high-fidelity simulation more helpful and lecture sessions less helpful.

505 PRESENTATION OF PATIENTS DURING ROUNDS BY NURSES IN A PICU TO IMPROVE COMMUNICATION AND CARE Meena Kalyanaraman, Cheryle Aizley, Derrick McQueen, Children’s Hospital of New Jersey Introduction: The pediatric intensive care units (PICU) are frequent sites where medical errors occur secondary to involvement of multiple health care providers, complex disease pathologies and the use of various technologies and laboratory tests. Many of these errors are secondary to poor communication between physicians and nurses. Hypothesis: Nurse presentation of patients during morning rounds will improve the perception of the role of nurses in the PICU by physicians and nurses and will be good for patient care. Methods: A knowledge, attitude and practice survey (KAPS) of resident physicians (RP) and nurses (RN) was done prior to initiation of nurse presentation (NP) of patients during morning rounds, 3 months after initiation of NP and 15 months after initiation of NP. The initial survey was taken by all RP with first year RP taking only the attitude component of KAPS. The other 2 KAPS were taken only by RP who rotated through the PICU. All RNs in the PICU took the surveys. The responses were graded on the Likert Scale from 1 to 5 with 1 being ‘strongly disagree’ and 5 being ‘strongly agree’. RP, RN and attending physicans (AP) ranked the overall perception of NP for improvement of patient care with Likert Scale during these 3 survey time periods. Results: 100% of RP completed the survey during the 3 time periods. 89%, 85% and 93% of RN completed the survey during the 3 time periods. All 3 components of the KAPS showed statistically significant improvement (p⬍0.005, ANOVA) from the pre-NP survey to the post-NP survey for RP and RN. The overall perception of NP also showed improvement which was statistically significant for RP, RN and AP. Conclusions: Nurse presentation of patients during morning rounds is well received by RP, RN and AP and can improve communication and care in the PICU.

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PRACTICING PEDIATRIC CRITICAL CARE MEDICINE AFTER A NATURAL DISASTER: LESSONS LEARNED FROM THE EARTHQUAKE IN HAITI

USE OF ULTRASOUND IN PEDIATRIC INTENSIVE CARE UNITS

Reinhard Hopfner, Thy Tran, Nadia Khan, Michael Nares, University of Miami, Miller School of Medicine Introduction: The 2010 earthquake in Haiti was one of the worst natural disasters in recent history. The University of Miami, Miller School of Medicine and Project Medishare, an affiliated nonprofit healthcare organization, established a field hospital after the earthquake at the Port-au-Prince airport. The hospital quickly became a major healthcare facility in Haiti. Hypothesis: Beyond the immediate aftermath of the earthquake, when admissions to the hospital were almost exclusively earthqake related injuries, children with severe nonsurgical conditions needing intensive care became increasingly frequent. Methods: We describe the implementation of a neonatal and pediatric ICU at a field hospital in Port-au-Prince after the earthquake. We present the patient characteristics and the challenges in sustaining effective critical care medicine under the conditions of a field hospital with limited resources. Results: The implementation of critical care medicine started 12 days after the earthquake. The post-operative recovery area was used as an ICU for the first intubated patients who could not be transferred out of the country. The increasing number of ICU-patients and the complexity of cases soon required the separation into an adult and a pediatric and neonatal ICU. Due to the fact that our facility was best equipped for the care of intubated pediatric patients in the Port-au-Prince area, many children were sent from other facilities. The characteristics of patients transitioned from earthquake related injuries to the medical-surgical spectrum of a large general hospital. Many patients presented with hypovolemic or septic shock as well as severe infections. The supplies and staffing were adjusted accordingly. Nurses with varying degree of experience came mostly from the US, individually or as part of a team. One critical care trained physician directed the unit. Haitian volunteers worked as ancillary staff. Medical focus was adequate use of available resources and appropriate monitoring despite a lack of equipment. Conclusions: Practicing pediatric critical care medicine in the setting of a field hospital after a natural disaster is possible with highly motivated volunteers, flexibility and corresponding resourcefulness.

Iris Toedt-Pingel, Archana Verma, Kathryn Scharbach, The Children’s Hospital at Montefiore Introduction: Accurate assessment and rapid decision-making are essential in the critical care setting. Ultrasound has become an invaluable tool in the management of critically ill patients. Despite the widespread use of bedside ultrasound, generally accepted standards for ultrasound training of pediatric intensivists are lacking. While there seems to be a movement towards establishing such standards and a formal training process for adult intensivists, similar efforts have not been reported for pediatric intensivists.We surveyed pediatric critical care fellowship directors in US training programs to ascertain current ultrasound usage and training in the pediatric academic ICU setting. Methods: An anonymous, voluntary, online 22-question survey was used to collect data pertaining to hospital and setting, ultrasound usage and training and opinions regarding the establishment of a training curriculum for ultrasound usage in the PICU setting. The survey was electronically distributed via Survey Monkey to all PICU fellowship program directors in the USA. Results: 24 of the 61 PICU fellowship directors completed the survey. 95 % of responders have access to bedside ultrasound. All use it for central line placement and ⬎50% use it for pleural fluid evaluation. Only 54% of PICU personal report formal training in ultrasound use. Most of the training consisted of a 1-2 day course and/or a company in-service session. 75% of those performing ultrasounds report following up their findings with a trained sonography technician. 91% of participants support a formal ultrasound curriculum for PICU fellowship training. Conclusions: Despite nearly 100% availability of bedside ultrasound in pediatric intensive care units in academic institutions the comfort level of PICU physicians in using the ultrasound other than for central line placement is very low. This is likely a result of limited training in usage and interpretation. Support for a formal training curriculum for fellows and attendings was expressed by the majority of PICU fellowship directors. Such training could improve ultrasound usage in the pediatric critical care setting. Further research is necessary to explore whether this improves patient outcomes.


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A MULTIDISCIPLINARY EDUCATIONAL STRATEGY FOR ENHANCING TEAMWORK AND COLLABORATION TO IMPROVE PATIENT CARE

METABOLIC CHANGES IN NEUROSURGICAL PATIENTS RECEIVING HYPERTONIC SALINE INFUSION THERAPY

Daniel Haller, Rebecca Honor, Todd Slesinger, Narendra Singh, John Platz, North Shore University Hospital Introduction: Communication between team members in the intensive care unit is critical in achieving a group understanding of the direction and details of daily patient care. Positive outcomes have been shown to improve with a multidisciplinary approach. There needs to be a cultural change in the way the team members view each others role in patient care. Hypothesis: We hypothesize that we can enhance nursing education in an evidence based manner and create an atmosphere that will facilitate expanding the role of the critical care nurse during ICU rounds. Methods: To investigate this, we started a quality improvement project that subsequently received IRB approval. Intensivists rotating through the SICU gave critical care lectures to the nursing staff at least twice weekly. Surveys were administered to 33 full-time SICU nurses who had more than 2 years of bedside experience. Surveys were handed out prior to the commencement of these lectures. After 3 months of lectures a second survey was given to the same group of nurses. The surveys consisted of 3 questions graded on a 5-point Likert scale to determine the effectiveness of communication, leadership and team decisionmaking in the SICU. Approximately 60% of surveys were returned in both the pre and post period. Results: Analysis using an exact Mann-Whitney test to compare the pre and post surveys (sample size of n⫽22 and n⫽20 respectively), found statistically significant differences for all three questions. Median responses for the pre-survey in communication, leadership, and team decision making were 2, 3 and 3.5 respectively and in the post survey were 4, 4 and 4.5 with p-values of 0.02, ⬍0.01 and 0.02. Conclusions: The significance of this project will hopefully lead to more effective multidisciplinary rounds in which both nurse and physician have equal opportunity to practice evidence based medicine in the SICU. We expect that this collaboration will not only enhance nursing education but also create an environment in which the nurse, and other healthcare professionals, will feel empowered to participate in critical care rounds thereby increasing the effectiveness of communication between physicians and nurses.

George Coritsidis, Suganda Phalakornkul, Kayode Lawrence, Nechama Diamond, Salwa Rhazouani, Elmhurst Hospital Center/ Mt Sinai School of Medicine Introduction: Hypertonic saline (HTS) infusions are commonly used in neurosurgical intensive care units as a treatment for reducing cerebral edema. Data as to the effects of these infusions is lacking, and indeed HTS may be associated with hyperchloremic metabolic acidosis, hypokalemia, hypernatremia and diuresis. Hypothesis: We were interested in comparing the metabolic effects of neurosurgical patients who received HTS infusions and those that did not. Methods: A retrospective study was performed on all adult critically ill neurosurgical patients between 2007-2010. Data was reviewed for changes in electrolytes, metabolic profile, and urine output. Results were compared between patients who received HTS for 48 hours and control group. Results: 168 patients were identified 100 of which received HTS. Pathology of HTS patients vs. control group was as follows: traumatic brain injury 52% vs. 53%; CVA 35% vs. 25%; tumor 8% vs. 9%; mass effect by CT scan 47% vs. 60%, respectively, all nonsignificant. Serum sodium was not changed in the control group but significantly increased with HTS at 48 hrs (136 ⫾ 0.7 vs. 144.6 ⫾ 1.0 mEq/L, P⫽0.0001, respectively). Serum potassium did not change at 48 hrs in the control but decreased in HTS (3.91 ⫾ 0.05 vs. 3.6 ⫾ 0.05 mEq/L, P ⫽ 0.0037). Though serum bicarbonate did not significantly change in either group at 48 hrs, the bicarbonate levels in the HTS group was significantly lower than in the control (23.4 ⫾ 0.39 mg/dL vs. 25 ⫾ 0.46 mg/dl, P⫽0.006). There was no significant difference in urine output from start of study to 48 hours after correcting for diuretic use. Conclusions: Electrolyte abnormalities are seen with as little as 48 hours of HTS infusion. A significant decrease in serum potassium was seen even after correcting for diuretic use. In specific cases or during longer HTS infusion these metabolic changes may become clinically significant.

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IMPLEMENTATION OF A CHECKLIST REGARDING INSERTION OF CENTRAL VENOUS CATHETER IN THE INTENSIVE CARE UNIT OF A UNIVERSITY HOSPITAL

MEDICAL AND TEAM TRAINING IN A PEDIATRIC INTENSIVE CARE UNIT THROUGH A MULTIDISCIPLINARY, IN SITU SIMULATION PROGRAM

Erick Santos, Divisaõ de Terapia Intensiva,, Mayra Gonçalves Menegueti, Divisaõ de Terapia Intensiva, HCFMRP, Universidade de Saõ Paulo, Ribeiraõ Preto, SP, Brasil, Gil Cezar Alkmim-Teixeira, Jaciara Viana, Edson Antoˆnio Nicolini, Divisaõ de Terapia Intensiva,, Anibal Basile-Filho, Maria AuxiliadoraMartins, Divisaõ de Terapia Intensiva, HCFMRP, Universidade de Saõ Paulo, Ribeiraõ Preto, SP, Brasil

Phoebe Yager, Josephine Lok, James Gordon, Kathryn Beauchamp, Brian French, Lois Parker, Patricia English, Robert Simon, Wayne Stathopoulos, Natan Noviski, Massachusetts General Hospital

Introduction: The use of increasingly more invasive techniques in Intensive Care Units(ICU) has raised patient exposure to hospital-acquired microorganisms, predisposing individuals to hospital-acquired infections.The central venous catheter(CVC) is an example, and the way it is inserted greatly boosts the risk of patient infection. Hypothesis: To employ a checklist in order to evaluate the impact of CVC insertion practices in the ICU of a University Hospital, taking into account the recommendations made by Centers for Disease Control(CDC), before and after specific staff training. Methods: A checklist containing CDC recommendations for CVC insertion was designed, in order to assess the use of individual protection equipment, hand antisepsis, insertion site antisepsis and asepsis, and use of sterile fields.The checklist was applied before and after specific staff training regarding CVC insertion. Results: One hundred and four checklists were filled in before staff training.Results reveal that 70% of the staff did not wear protection goggles, 2% did not carry out hand antisepsis, and 8% accomplished antisepsis inadequately.All the staff performed insertion site antisepsis and asepsis; however 5% employed PVPI and Chlorhexidine in the same procedure.As for the insertion site, 43% were done on the subclavian vein, 43% on the internal jugular vein, and 14% on the femoral vein.Concerning the use of sterile fields, 73% utilized wide fields, whereas 27% covered the insertion site only.After staff training, forty-five checklists were analyzed. It was found that 44% of the staff did not wear protection goggles, and 100% carried out correct hand antisepsis.All the staff performed insertion site antisepsis and asepsis. As for the insertion site, 78% of the punctions were accomplished on the subclavian vein and 22% on the internal jugular vein.As for the use of sterile fields, 80% utilized wide fields, while 20% covered the insertion site only. Conclusions: Implementation of the checklist enabled better observance of routine procedures, and specific staff training contributed to improved compliance with measures aiming at the prevention of infections related to CVC insertion, as recommended by the CDC.


Introduction: Simulated case exercises teach residents and fellows how to manage critical events in the Pediatric Intensive Care Unit (PICU); however exercises at an off-site location make interdisciplinary participation and team training a challenge. Hypothesis: A multidisciplinary, in situ PICU simulation program will allow core members of the care team – nurse, pharmacist, physician, respiratory therapist – to manage cases together in the same environment in which they practice and to reflect on their teamwork. Methods: In 2010, leadership from disciplines that make up the PICU care team developed an interdisciplinary program in which simulated cases occur in the PICU in real patient rooms utilizing an interactive mannequin and the same human and technological resources made available during actual critical events. Participants are asked to act as they would in real life, e.g. perform needed procedures, use the code cart. A trained physician facilitator stays out of sight during the case, then leads an interactive debriefing focusing on self and team reflection, analysis and synthesis of information. Leadership from nursing, pharmacy and respiratory therapy routinely participate in the debriefings. Teaching points encompass medical management and principles of crisis resource management. Results: To date, 56 in situ cases have been conducted in the PICU with over 300 participants, including pediatric and emergency medicine residents, PICU fellows, respiratory therapists, pharmacists, PICU nurses, social workers, chaplains and unit administrative support staff. Many participants report a similar surge of adrenaline as during a real emergency. With minimal direction, participants identify suggestions to improve team work. Several real resource utilization issues have come to light as a result of the program, leading to operational improvements, e.g. implementation of a Celsius to Fahrenheit conversion table in every patient room following a simulated case involving active cooling. Conclusions: Implementation of an in situ PICU simulation program facilitates an interdisciplinary approach to medical and team training and creates a realistic environment to fully engage participants physically, conceptually and emotionally.

512 IMPORTANCE AND POTENTIAL OF THE FUNDAMENTAL CRITICAL CARE SUPPORT (FCCS) IN JAPAN Kazuaki Atagi, Osaka City General Hospital, Shigeki Fujitani, St.Marianna University School of Medicine, Takamitsu Kodama, St. Marianna University, Shinichi Nishi, Hyogo College of Medicine, HIdeki Shimaoka, Osaka City General Hospital Introduction: With regard to the intensive care of critically-ill patients, the uniformity and consistency of medical treatment is important; therefore, it is necessary to provide critically-ill patients with fundamental medical care initially combined with specialized treatment.On the contrary, treatment is based on a guidance by senior physicians in many medical institutions. In 2009, we held FCCS courses in Japan and have had feedback with various opinions from participants . We have evaluated the importance of courses on FCCS courses in Japan using the surveillance. Hypothesis: Combining the skill station, FCCS course is a valuable tool for education for the basis of critical care medicine in Japan. Methods: Ten FCCS courses have been held in Japan since February 2009. Courses were provided in the form of lectures and skill stations in accordance with the slides and curriculum designed by SCCM. After the end of the course, we conducted a survey to study the ratio of residents among the participants and those hoping to participate, the motive of attending the course, and the satisfaction level of each lecture and skill station. Results: Approximately 1/2 of the all participants were in the category of attending class; approximately the remaining 1/2 were in the category of residents, nurses, and clinical engineers. With regard to the motive for participation, several attendings had expressed their hope for standardization providing trainee doctors with the guidance; on the other hand, several residents, participants had raised questions with regard to managing seriously-ill patients and expressed their dissatisfaction with the management, which varies from one advising doctor to another. In the evaluation of lectures and skill stations, almost all the participants had answered that they were satisfied; particularly, the satisfaction rating of skill stations for the Mechanical Ventilation. Conclusions: Also in Japan, attendings and residents at the site of intensive care, hope for the making of a guideline of “standard treatment,” for which the course on FCCS is considered to be useful. Furthermore, the course is most suitable for the training of the Rapid Response Team through initial assessment and treatment.


Poster: Epidemiology/Outcomes (Predictors, Quality of Life, Safety)-1 518

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EPIDEMIOLOGY AND OUTCOMES IN PATIENTS WITH SEVERE SEPSIS ADMITTED TO THE HOSPITAL WARDS: AN OBSERVATIONAL COHORT STUDY TO IDENTIFY PATIENTS AT INCREASED RISK OF ADVERSE OUTCOMES

THE TIME TAKEN TO ACHIEVE NORMOTHERMIA DOES NOT PREDICT SURVIVAL IN HYPOTHERMIC TRAUMA PATIENTS

Mark Mikkelsen, Hospital of the Univ. of Pennsylvania, David Gaieski, Jason Christie, Hospital of the University of Pennsylvania, Munish Goyal, Washington Hospital Center, Nuala Meyer, Hospital of the University of Pennsylvania, Scarlett Bellamy, University of Pennsylvania School of Medicine, Barry Fuchs, Hospital of the University of Pennsylvania Introduction: Severe sepsis is associated with significant mortality. Many patients with severe sepsis will be admitted through the Emergency Department (ED) to hospital wards. The outcomes of these patients will vary, and it is possible that factors present in the ED could be used to identify patients at high risk of adverse outcomes, including death. Hypothesis: We hypothesized that we could identify factors in the ED that would be associated with adverse outcomes in severe sepsis patients admitted to a non-Intensive Care Unit (ICU) setting. We limited our hypothesized risk factors to sociodemographics, comorbidities (hematological malignancy, organ transplantation, and chronic liver disease), the presence of hypotension or elevated serum lactate levels in the ED, severity of illness, and etiology of sepsis. Methods: Retrospective cohort study of severe sepsis patients admitted from the ED to the wards of an academic medical center between 2005 and 2007. The primary outcome was in-hospital mortality. The secondary outcome was ICU transfer within 48 hours of admission. Multivariable logistic regression was used to adjust for potential confounding in the association between risk factors and in-hospital mortality. Results: 309 patients with severe sepsis were admitted to a non-ICU setting over 2 years; the mortality rate was 6% (95% CI: 3 to 9%) and 5% (95% CI: 3 to 8%) required ICU transfer within 48 hours of admission. ICU transfer was associated with in-hospital mortality (OR⫽4.65, 95% CI: 1.18, 18.26, p⫽0.028). Independent risk factors for increased risk of death included: patients with hematological malignancy (OR⫽5.14, 95% CI: 1.86, 14.18, p⫽0.002) and patients with high (⬎⫽ 4 mmol/L) serum lactate levels (OR⫽5.17, 95% CI: 1.30, 20.51, p⫽0.02). Intermediate (2 - 3.9 mmol/L) serum lactate levels were not associated with in-hospital mortality, nor were any of the other factors tested. Conclusions: We found that patients with hematological malignancy and patients with an elevated serum lactate upon presentation to the ED are at increased risk of adverse outcomes when admitted to a non-ICU setting. Early recognition of these at-risk groups, combined with targeted interventions, may improve patient outcomes.

Jorge Con, Kelly Hager, Christopher Piercecchi, Kara Synder, Randall Friese, University of Arizona, Narong Kulvatunyou, University of Arizona College of Medicine, Peter Rhee, Terence O’Keeffe, University of Arizona Introduction: Hypothermia on arrival has been shown to be a predictor of morbidity and mortality in trauma patients. We have examined the effect on outcome of the length of time taken by a hypothermic patient to achieve a normal core body temperature. Hypothesis: Our hypothesis was that the time required to achieve normothermia is a better predictor of mortality than the initial core body temperature. Methods: All trauma patients admitted to a surgical Intensive Care Unit (ICU) at a level I trauma center between 2007 to 2009 were retrospectively analyzed to identify their presenting core body temperature in the Emergency Department (ED). We defined hypothermia as an initial temperature of less than 36 degrees Celsius (°C). Time taken to achieve normothermia was calculated from data extracted from the electronic medical record. We compared crude mortality between hypothermic and normothermic patients using Chi-square analysis, and then used a multivariate logistic regression model to adjust for confounders. Results are presented as proportions or means ⫾ Standard Deviation. Results: Of the 2407 patients admitted to the surgical ICU over this period, 509 were hypothermic on presentation to the ED with an overall mortality of 6.0%. Hypothermic patients were more likely to be hypotensive in the ED (9.3% vs. 2.9%, p⬍0.001), be comatose [GCⱕ8] (39.6% vs. 20.2%, P⬍0.001), be intubated (43.0% vs. 27.6%, P⬍0.001), and have a higher injury severity score (24 ⫾ 12 vs. 17 ⫾ 11, P⬍0.001). Mortality rates were higher in hypothermic patients, and declined stepwise as temperature increased. In the multivariate logistic regression model, independent predictors of mortality included age, Head AIS, shock (SBP⬍90 mmHg), and temperature less than 34°C. Time to achieve normothermia was NOT a predictor of mortality. Conclusions: Even mild hypothermia of ⱕ36°C was associated with decreased survival in trauma patients admitted to the ICU. Initial Emergency Department core body temperature was a better predictor of mortality than the length of time taken to achieve normothermia. Pre-hospital measures aimed at temperature conservation in a trauma patient may be more important than in-hospital warming time.

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EFFECT OF ANNUAL CHANGES IN HOSPITAL VOLUME ON RISK-ADJUSTED MORTALITY FOR MECHANICALLY VENTILATED PATIENTS

PEDIATRIC INTENSIVE CARE UNIT (PICU) OUTCOMES FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT)– A CONTEMPORARY SINGLE CENTER EXPERIENCE

David Wallace, Derek Angus, University of Pittsburgh Medical Center, CRISMA Center, Matthew Rosengart, University of Pittsburgh Medical Center, Theodore Iwashyna, University of Michigan Health System, Jeremy Kahn, University of Pittsburgh Medical Center, CRISMA Center

Ranjit Chima, Sonata Jodele, John Butcher, John Whitt, Stella Davies, Derek Wheeler, Cincinnati Children’s Hospital Medical Center

Introduction: Cross-sectional volume-outcome relationships are well established in critical care. However, whether changes in volume over time are associated with concomitant changes in outcome is unknown, and has important implications for understanding the mechanism of this often-used policy tool. Methods: We performed a retrospective cohort study using Pennsylvania state discharge data. All adult intensive care discharges between July 1, 2004 and June 30, 2008 with procedure codes for mechanical ventilation were eligible. We used hierarchical logistic regression models to determine the association between annual changes in volume and annual changes in 30-day risk-adjusted mortality, controlling for patient characteristics and severity of illness. Results: 147 hospitals reported 136,543 discharges involving mechanical ventilation during the four year period. The mean and distribution of discharges remained stable over time. The mean yearly change in hospital volume was 2 patients (range:-198 to 200). Unadjusted 30-day mortality was 33.3%. Admission to a hospital in the highest quintile of overall volume was associated with a significant reduction in the odds of death (odds ratio: 0.76, p⬍0.0001). However, within hospitals, annual changes in volume were not associated with changes in outcome (odds ratio for an annual absolute increase in volume of 50 patients: 0.98; 95%CI: 0.96-1.01; odds ratio for an annual relative increase in volume of 10%: 1.0, 95%CI: 0.99-1.02). Hospitals that consistently grew over the four year period (n⫽16) had similar riskadjusted mortality over time compared to hospitals that shrunk over the four year period (n⫽15), (p-value for interaction between volume changes and time⫽0.69). Conclusions: For critically ill patients receiving mechanical ventilation, simple changes in hospital volume are not associated with changes in risk-adjusted mortality. A more complex relationship between changes in hospital volume and subsequent outcomes is possible, but was not apparent over the study period. These findings suggest that observed volume-outcome relationships in critical care may be due to specific care processes and structural factors rather than clinical experience.NIH T32-HL07820


Introduction: Clinical outcomes for children admitted to the PICU following HSCT are improving. Prior studies in this population have demonstrated up to 56% survival at ICU discharge. In comparison to most programs, children undergoing HSCT at our center represent a higher risk group as they are dominated by grafts from unrelated donors, many with significant HLA mismatch. Hence, we reviewed outcomes for children undergoing HSCT admitted to our PICU. Hypothesis: We hypothesized that survival to PICU discharge for HSCT admissions has improved compared to published data. Methods: A retrospective review of our PICU clinical and HSCT databases was performed from July 2004 through June 2009. Continuous data were analyzed using either Student’s t-test for parametric or Mann-Whitney Rank Sum test for non-parametric data. A p value of ⬍0.05 was considered significant. Results: Over this period, 136 HSCT recipients accounted for 260 PICU admissions and the rate of survival to PICU discharge was 82% (213/260). To date, 43% (59/136) of the HSCT patients are still alive with a median follow up of 2.9 years (1.1-6.1 yrs). The median PRISM II score and length of stay (LOS) for this cohort was 8 (0-47) and 4 days (1-172 days), respectively. Patients required intubation and mechanical ventilation during 39% (100/260) of these admissions and the rate of successful extubation and discharge from the ICU was 58% (58/100). Patients required inotropes or vasopressor support during 42% (109/260) of these admissions with a 66% (72/109) survival to ICU discharge. Renal replacement therapy was utilized during 14% (36/260) of admissions with a 50% (18/36) survival to ICU discharge. The LOS, PRISM II score, and ventilator days were all significantly lower for patients who survived to ICU discharge compared to patients who died during their ICU admission [LOS (median 3 vs. 13 days, p⬍0.001), PRISM II score (median 7 vs. 13, p⬍0.001), ventilator days (median 5 vs. 12 days, p⬍0.002)]. Conclusions: We report 82% survival to PICU discharge, with overall 43% survival at a median follow-up of nearly 3 years for all HSCT patients admitted to our PICU. Hence, our data suggest improved survival outcomes for this high risk patient population.

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EFFECT OF 24-HOUR IN-HOSPITAL PEDIATRIC CRITICAL CARE ATTENDING PHYSICIAN PRESENCE ON PROCESS OF CARE AND PATIENT OUTCOME

THREE-YEAR SURVIVAL FOLLOWING ICU SEVERE SEPSIS IN AGED MEDICARE BENEFICIARIES

Akira Nishisaki, Vinay Nadkarni, The Children’s Hospital of Philadelphia, Jesse Pines, University of Pennsylvania, Robert Berg, Mark Helfaer, The Children’s Hospital of Philadelphia, Richard Lin, Children’s Hospital of Philadelphia Introduction: In-hospital attending models for large tertiary Pediatric ICUs are increasingly popular, but impact on process of care and patient outcome is unclear. Our ICU transitioned to a 24-hour in-hospital model in January 2004. Hypothesis: Implementation of 24-hour in-hospital critical care attendings in a large, tertiary ICU is associated with more ventilator-free hours, and improved patient survival. Methods: With IRB approval, our 45-bed Pediatric ICU from 2000-2008 and ventilation billing database from 2003-2006 was analyzed. A 2 month transition from Traditional 12-hour (12hA) to 24-hour (24hA) in-hospital attending call system in Dec 2003- Jan 2004 was excluded. Severity was adjusted for PRISM 24 score. Univariate analysis by T-test and chi2 test with multivariate linear and logistic regression to adjust for covariates, where appropriate. Results: 24,903 patients were admitted:10,395 with 12hA and 14,508 with 24hA. ICU mortality was significantly higher during 12hA in univariate analysis (12hA: 2.53% vs. 24hA:2.07%, p⫽0.016), but not with multivariate analysis adjusting for 5 covariates and PRISM 24 predicted mortality (Odds Ratio:1.17, 95%CI 0.94-1.47,p⫽0.16). 3,515 patients required invasive mechanical ventilation: 810(33.1%) during 12hA vs.2705 (31.5%) during 24hA,p⫽0.13. For patients who required mechanical ventilation, ventilator-free hours to day 14 were significantly longer for 12hA (263⫾100 hrs) vs. 24hA (229⫾123 hrs, p⬍0.0001). Differences in ventilator-free hours remained significant (coefficient:-33.7,95% CI:-42.5, -24.8,p⬍0.0001) after adjusting for covariates and predicted mortality. Conclusions: Implementation of 24-hour inhospital critical care attending coverage in a large, tertiary Pediatric ICU was not associated with improved patient ICU survival. Surprisingly, it was associated with shorter ventilator-free hours. Further studies to evaluate the effect on process of care and patient outcomes are needed.

Walter Linde-Zwirble, Z D Associates, Hannah Wunsch, Columbia University Medical Center, Sachin Yende, University of Pittsburgh, Carmen Guerra, Columbia University, Derek Angus, University of Pittsburgh Critical Care Medicine CRISMA Laboratory Introduction: Long-term survival is a keyclinical outcome and necessary in the health economics ofcritical illness. Prior VA work showed that severe sepsis (SS)hospital survivors have their life expectancies reduced by half. But, theVA may not be represent other populations of interest andmisrepresent the impact of SS on survival afterhospitalization. We analyzed Medicare beneficiarieswith ICU SS (ISS) compared to hospital and population controls matchedby age/race/gender to determine whether long-term survival after SS in the agedMedicare population is different from results in the VA population. Hypothesis: Medicarebeneficiaries will have reduced survival compared to controls and willbe reduced by more than reported VA results. Methods: We identified SS andselected the first ISS hospitalization in 2003 for Medicare beneficiaries in a2.5% sample of Medicare fee for service beneficiaries aged 66⫹y, using theAngus methodology. Control groups (hospitalized non-SS [HOS] and generalpopulation [GEN]) were matched by age/race/gender and were selected from anindependent 2.5% sample. Survival through 3 years was analyzed. Life tables were used to calculate the expectedsurvival of the ISS cohort by age/gender. Death was categorized as: hospital;Early⬍180d; Later-⬍3y. Survival was modeled as a two componentexponential decline. Results: We identified 7468 ISScases with hospital mortality of 30.4% compared to 2.2% in HOS controls. Of ISShospital survivors, 33.4% died Early and 26.8% more Later, leaving 39.7% aliveat 3y. Of HOS hospital survivors, only 14.2% died Early and 22.2% Later,leaving 63.7% alive at 3y. Of matched GEN controls, only 2.8% died Early with85.7% alive at 3y compared to the life table expected 82%. At 3y the ISS cohorthad 1.65y mean survival compared to 2.30y for HOS controls and 2.61y by lifetable. ISS modeled survival was 3.7y, reduced by 65% compared to life table(10.6y) and 52% compared to HOS (7.7y). Conclusions: ISS hospital survivors have reduced survival compared to matched controls, keeping only 1/3 of expectedsurvival, much reduced compared to VA estimates. Since 1/3 die within 6m ofdischarge, better coordination of end of life care could help improve qualityof life.



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THE DISCHARGE REVISED ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION SCORE AS A PREDICTOR OF READMISSION AFTER DISCHARGE FROM SURGICAL INTENSIVE CARE UNIT

A DAILY CHECKLIST CAN CHANGE INTENSIVE CARE UNIT HAND HYGIENE CULTURE.

Hee-Pyoung Park, Han-Na Lee, Ji-Hyun Lee, Yoon-suk Jeon, Young-Jin Lim, Seoul National University Hospital, Jung-Won Hwang, Seoul National University Bundang Hospital Introduction: Intensive care unit (ICU) readmission rates range from 3% to 12%, in spite of initial recovery from critical illness. Previous researches report that the Revised Acute Physiology and Chronic Healty Evaluation (APACHE II) score at either admission or discharge is an important predictor for readmission after ICU discharge. However, there are a few papers concerning the association of discharge APACHE II score with readmission after discharge from surgical intensive care unit. Hypothesis: We compared the ability of the discharge APACHE II score with that of the admission APACHE II score in predicting readmission, especially early readmission within 48 hours, after discharge from ICU. Methods: A retrospective cohort study and a review of patient records for all patients admitted to the 32-bed tertiary surgical intensive care unit(SICU) from October 2007 to March 2010 were conducted. Results: Of 4257 adult(ⱖ 18 yr) admitted to the SICU, 271(6.4%) were readmitted to the SICU during the same hospital stay. Age (OR 1.01, 95% confidence interval [CI] ⫽ 1.00-1.02, P ⫽ 0.025), male(OR 1.36,[1.04-1.78],P ⫽ 0.007), admission route from other ICUs(OR 1.78, [1.08-2.94],P ⫽0.024), both admission (OR 1.04,[1.02-1.06],P ⫽ 0.000)and discharge APACHE score(OR 1.04,[1.02-1.06],P ⫽ 0.001)and length of stay in SICU(OR 1.04, [1.02-1.05],P ⫽ 0.000) were significant independent factors in predicting readmission. Readmitted patients had longer LOS and higher mortality than those not readmitted (55⫾ 75 vs. 15 ⫾ 23 days, 13% vs. 0.5%, P ⫽ 0.000 respectively). With regard to early readmission within 48 hours, the discharge APACHE II score, not the admission APACHE II score, was the only significant predictor (OR 1.06,[1.00- 1.12],P ⫽ 0.046). Conclusions: This study showed that both discharge APACHE II score and admission APACHE II score are useful predictors for readmission after ICU discharge, but discharge APACHE II score is only independent factor in predicting early readmission within 48 hours after ICU discharge.

Jeremy Pamplin, BAMC, Roderick Kuwamoto, STICU Brooke Army Medical Center, Harry Bradstreet, John Linfoot, BAMC, Kevin Chung, USAISR, Kurt Grathwohl, San Antonio Uniformed Services-Health Ed Introduction: Hand washing compliance remains a major challenge to sustain in many hospitals. Many human factors and ergonomic approaches have been taken to enhance provider compliance with hand washing prior to and after touching patients and their proximate environments. Daily patient checklists in the intensive care unit (ICU) have previously been shown to improve compliance with a variety of evidence based interventions. Hypothesis: Adding a question to the daily ICU checklist about hand washing compliance before touching patients will improve healthcare team members’ compliance and reduce central line associated bloodstream infections (CLABSI). Methods: This process improvement project was conducted in a 20-bed surgical ICU in a 450-bed academic military medical center. Data was collected for the three months before and three months after adding the following question to our daily ICU checklist: “Has anyone seen anyone else touch the patient without washing their hands in the past 24 hours?” Only two answers were allowed, “yes” or “no.” The question was asked during multidisciplinary ICU rounds (MDR) for every patient as a part of our daily review checklist. If the question was answered “yes,” we subsequently asked for a name of the offender and recorded it. Hand washing or alcohol dispenser usage prior to touching a patient or his immediate surroundings was considered compliant. The “offender list” was not published. Results: Hand washing compliance as measured by a third party observer from infection control significantly increased from 69% to 88% (p ⬍ 0.0001). We also observed a cultural shift in team member interactions: team members – including nurses, attendings, residents, technicians – began stopping each other from entering patient rooms unless they had confirmation that the provider had used alcohol hand cleanser or had washed their hands. The intervention was associated with a decline in CLABSI rates/1000 central line days (⬍13.7 vs. 2.7, p ⫽ 0.09). Conclusions: A simple intervention can drastically improve overall hand-washing compliance in an intensive care unit and is thus far associated with a short term decrease in CLABSI.

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BUN IS PREDICTIVE OF BLOOD CULTURE POSITIVITY AND MORTALITY IN CRITICALLY ILL PATIENTS INDEPENDENT OF ‘NORMAL’ CREATININE

HYPOTHERMIC EVENTS IN A BURN ICU INCREASE MORTALITY RISKS

Kevin Beier, Harvard Medical School, Sabitha Eppanapally, Brigham and Women’s Hospital, Heidi Bazick, Massachusetts General Hospital, Domingo Chang, Karthik Mahadevappa, Brigham and Women’s Hospital, Fiona Gibbons, Massachusetts General Hospital, Kenneth Christopher, Brigham and Women’s Hospital Introduction: Elevated BUN level is correlated with increased mortality in patients with heart failure and is predictive for ICU stay and survival in acute necrotizing pancreatitis. Hypothesis: We hypothesized that elevated BUN is associated with all cause mortality independent of creatinine in the ICU. Methods: Multicenter observational study of 209 medical and surgical intensive care unit beds in two teaching hospitals in Massachusetts. The cohort consisted of 26,288 patients, age ⱖ 18 years, hospitalized between 1997 and 2007 with creatinine 0.80-1.30 mg/dl at ICU admission.BUN at ICU admission was categorized as 10-20, 20-40 and ⬎40 mg/dl. Logistic regression examined death at days 30, 90 and 365 post-ICU admission as well as in hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Results: BUN at ICU admission is predictive for short term and long term mortality independent of creatinine. 30 days following ICU admission, patients with BUN ⬎40 mg/dl have an Odds Ratio for mortality of 5.12 (95% CI, 4.30-6.09; P⬍.0001) relative to patients with BUN 10-20 mg/dl. 30 days following ICU admission, patients with BUN ⬎40 mg/dl have an multivariable Odds Ratio of 2.78 (95% CI, 2.27-3.39; P⬍.0001) relative to patients with BUN 10-20 mg/dl. 30 days following ICU admission, patients with BUN 20-40 mg/dl have an OR of 2.15 (95% CI, 1.98-2.33; ⬍.0001) and a multivariable OR of 1.53 (95% CI, 1.40-1.68; P⬍.0001) relative to patients with BUN 10-20 mg/dl. Results were similar at 90 and 365 days following ICU admission as well as in-hospital mortality. A subanalysis of patients with blood cultures (n⫽ 7,482), demonstrated that BUN at ICU admission was associated with the risk of blood culture positivity (BUN⬎40 mg/dl adjusted OR 2.18 (95% CI, 1.65-2.89; ⬍.0001); BUN 20-40 mg/dl adjusted OR 1.52 (95% CI, 1.31-1.76; ⬍.0001.)). Conclusions: Among critically ill patients with Cr 0.8-1.3 mg/dl, an elevated BUN at ICU admission is associated with increased mortality, independent of serum creatinine. BUN at ICU admission is associated with the risk of blood culture positivity which may reflect decreased immune function related to the extent of catabolism and may impact mortality.


Amani Jambhekar, Alejandra Mora, John Jones, United States Army Institute of Surgical Research, Charles Wade, University of Texas Health Science Center at Houston, Steven Wolf, University of Texas Health Science Center at San Antonio Introduction: The purpose of this study was to determine the incidence of hypothermic events and their association with outcomes in critically injured patients with severe burns in the ICU. Hypothesis: We hypothesized the severity of hypothermia would be associated with mortality and poor outcomes. Methods: In a retrospective study of a single ICU, we examined core body temperatures of 338 subjects with severe burns (ⱖ20% TBSA burned), who stayed at least 3 days in the ICU, and had a minimum of 100 temperature measures. Subjects with at least one temperature ⬍34.7°C were considered hypothermic (n⫽29); all others (ⱖ34.7°C) were considered non-hypothermic (n⫽309). Hypothermia within a 24-hour period counted as one hypothermic event. Groups were compared using t-tests with adjustments for heterogeneity of the data and chi square analysis. Results are reported as mean⫾SD [median; IQR] and a p⬍0.05 was considered significant. Results: Hypothermic and non-hypothermic patients did not differ in age (33⫾16.3 vs. 35⫾16.9 yrs [25; 21-46 vs. 28; 22-45]) or ISS (31⫾12.7 vs. 27⫾11.6 [25; 25-34 vs. 25; 17-34]) but had significantly greater TBSA burned (60⫾18.0, vs. 42⫾17.0% burn [59; 50-73 vs. 36; 29-51]). Mortality rates for hypothermic subjects were more than twice that of non-hypothermic subjects (52% vs. 21%; p⬍0.005). Adjusting for age and TBSA hypothermic subjects had an increased risk of mortality (OR, 2.72; 95% CI, 1.08-6.86). TBSA, age, and temperature were assessed using ROC analysis (AUC⫽0.843). Patients who experienced recurrent hypothermic events had more than twice the mortality rate of patients who experienced only one incident of hypothermia (88% vs. 38%; p⬍0.01). Additionally, non-hypothermic subjects experienced more ICU free days (9⫾11.3 vs. 2⫾6.2; p⬍0.0001) and a greater number of mechanical ventilation free days (18⫾14.4 vs. 7⫾9.8; p⬍0.01) compared to hypothermic subjects. Conclusions: After adjusting for differences in age and TBSA, hypothermia in subjects with severe burns was an independent risk factor for mortality and poor outcomes.

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INSTITUTION OF QUALITY IMPROVEMENT PROCEDURES INCLUDING ROUTINE SPONTANEOUS AWAKENING TRIALS AND SPONTANEOUS BREATHING TRIALS MAY IMPROVE OUTCOMES IN PEDIATRIC CRITICAL ILLNESS

PSOAS MORPHOMICS: CORRELATES OF MORTALITY IN SURGICAL INTENSIVE CARE UNIT PATIENTS

Catherine Preissig, Medical Center of Central Georgia Introduction: National societies have recently made recommendations for quality improvement procedures geared to improve patient outcomes in the critical care setting. While these recommendations may be applicable to critically ill patients of all ages, few studies have directly evaluated the impact of such procedures in children. Our pediatric ICU recently implemented as standard care quality improvement procedures including spontaneous breathing trials (SBTs) and spontaneous awakening trials (SATs) in mechanically ventilated (MV) patients. Hypothesis: We hypothesized that the implemetation of such measures in our pediatric ICU would improve patient outcomes without increasing adverse events. Methods: We implemented daily SBTs and SATs as standard care in MV patients in our pediatric ICU in October 2009. We performed retrospective chart analysis of 50 MV patients admitted between April-Sept 2009 prior to implementation, designated group A, and 50 MV patients admitted after initiation of these measures, designated group B. We excluded patients with tracheostomies. Patients were evaluated for outcome measures including hospital and ICU length of stay, MV days, adverse events, demographic, and clinical data. Results: There were no significant differences in age, weight, gender, or ethnicity between the 2 groups. Mean age was 6.1 years and 5.5 years for groups A and B, respectively. Patients that recieved daily SBTs demonstrated a 6.7% reduction in MV days compared to group A, had a 95.2% extubation success rate compared to 91% success rate for group A, and ⬍3% suffered unplanned extubations (comparable to group A). Patients that received daily SATs had decreased maximum and average sedation requirements compared to group A, and had similar accidental extubation rates (⬍3% in both groups). ICU length of stay was decreased by 1.8 days in group B compared to A, but hospital length of stay was not significantly different between the 2 groups. Conclusions: The implementation of SBTs and SATs in critically ill children may lead to decreased mechanical ventilation days and decreased sedation requirements without increasing incidence of unplanned extubations.

Constance Mobley, Rachel Lee, University of Michigan, Craig Meldrum, Univeristy of Michigan Medical School, Sven Holcombe, Stewart Wang, University of Michigan, Lena Napolitano, University of Michigan School of Medicine, Pauline Park, University of Michigan Introduction: Frailty is emerging as an important determinant of patient outcomes in the critically ill. Specific markers to measure frailty have not been delineated and reproducible and quantitative methods to assess this measure remain limited. Computerized volumetric determination of core muscle mass has been evaluated as a marker of adverse outcomes in hospitalized patients. We evaluated psoas muscle morphomics in a subset of critically ill patients transferred to the University of Michigan surgical intensive care unit for tertiary care. Hypothesis: We aimed to determine if psoas muscle size is relevant as a marker of frailty in critically ill patients. Methods: Between July 2005 and June 2010, 162 patients were transferred to the UM SICU with severe ARDS. A cohort of 65 patients with torso CT scans was identified. Quantitative image analysis data was linked with clinical data. 50.8% of patients received scans within 72 hours of admission to the ICU. Results: Overall mortality in the cohort was 35.8%. Survivors and non-survivors were similar in age, BMI, ICU length of stay and hospital length of stay. Psoas measurements were analyzed independently in men and women due to baseline gender differences in muscle mass. Patients with a smaller mean area psoas muscle size had an increased mortality rate compared to those who survived. Patients were grouped in terciles based on calculated psoas muscle morphomics. Mortality in the lowest tercile was 66.7% and was significantly higher compared to mortality in the middle tercile (66.7% vs. 22.7%, p⬍ 0.004) and highest tercile (66.7% vs. 14.3%, p⬍ 0.0001). Patients in the lowest tercile also had high mean APACHE III scores, however these were not statistically significant across groups (APACHE III score by lowest to highest tercile 77.7, 65.3, 63.8). This suggests that mean psoas muscle size may be a better predictor of mortality in our patient cohort. Conclusions: Frailty as measured quantitatively by psoas muscle size correlates with increased mortality in critically ill patients. Core muscle mass screening on ICU admission may help to identify a subgroup of patients at greater risk of mortality who may benefit from strategic critical care interventions.

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IMPACT OF A SURGICAL INTENSIVIST TEAM ON ICU OUTCOMES

HEALTH-RELATED QUALITY OF LIFE IN CHILDREN WITH CARDIAC DISEASE WHO PREVIOUSLY REQUIRED EXTRACORPOREAL MEMBRANE OXYGENATION SUPPORT

Steven Gannon, Maxwell Mayer, Wayne State University School of Medicine, LaToyia Johnson, Phyllis Oxley, Harper University Hospital, Yehudis Tawil, Wayne State University, Pawel Galecki, Wayne State University School of Medicine, Steven Tennenberg, Wayne State University School of Medicine, Dept of Surgery Introduction: Intensivist-directed ICU teams are promoted to implement evidence-based care and lead to improved patient outcomes. While they have been shown beneficial in a closed and medical ICU (MICU) model, their role in an open surgical ICU (SICU) model is less well studied. The goal of this study was to determine the impact of an intensivist team on ICU length of stay (LOS) and mortality in an open, collaborative surgical ICU environment. Hypothesis: Implementation of a surgical intensivist team in an open SICU will decrease LOS and mortality. Methods: In April 2007, a multidisciplinary, intensivist-directed, Leapfrog-compliant, ICU team was initiated to care for surgical patients in Harper Hospital’s adult ICUs. This is a 4 unit, 40 bed, medical/surgical ICU of a tertiary care teaching hospital. The SICU functions as an open unit, with care of patients shared by the intensivist and primary surgical teams. A MICU intensivist team, functioning in a closed unit model, cares for all medical ICU patients. We retrospectively analyzed all admissions to the ICU from Jan. 1, 2006 to Dec. 31, 2008. Data were grouped as before the initiation of the SICU team (PRE) and after (POST). Unpaired t-tests (LOS) and Chi square analysis (ICU mortality) were used to compare results in the two groups. Results: There were 7436 ICU admissions during the study period. SICU MICU N LOS (days) Mortality (%) N LOS (days) Mortality (%) PRE 1289 5.40 ⫾ 8.4 4.0 1787 3.66 ⫾ 5.4 9.8 POST 1659 5.02 ⫾ 7.6 * 4.0 2701 3.81 ⫾ 5.2 10.0 N ⫽ number of patients. Data are mean ⫾ SD. * P ⫽ 0.198 vs PRE LOS. Conclusions: During both periods, LOS was significantly higher and mortality significantly lower in the SICU patients. This reflects the differences in these patient populations. While there was no decrease in LOS in MICU patients, there was a weak trend toward decreased LOS in the SICU after the intensivist team was started. The SICU intensivist team had no impact on mortality. More significant benefit from a surgical intensivist team may require a closed unit model.

John Costello, Molly O’Brien, David Wypij, Joana Shubert, Joshua Salvin, Jane Newburger, Peter Laussen, John Arnold, Francis Fynn-Thompson, Ravi Thiagarajan, Children’s Hospital Boston Introduction: Little is known about health-related quality of life (QOL) in children with cardiac disease who previously required ECMO. Hypothesis: Children with heart disease who survived ECMO and their parents will describe decreased QOL when compared to a U.S. population sample. Methods: In this single institution cross-sectional study of cardiac ECMO survivors who were 5-18 years of age at the time of the study, QOL was assessed by parent-proxy report using the Child Health Questionnaire (CHQ) PF-50. For patients 10-18 years of age, patient-reported QOL was also assessed using the CHQ CF-87. Physical (PHS) and psychosocial summary scores (PSS) from the CHQ PF-50 were compared to those of a U.S. population sample and other cardiac populations. Associations were identified between exposure variables and PHS and PSS ⬍1 standard deviation below those of the general population. Results: CHQ-PF50 was completed for 41/98 eligible patients (42%) at age 10 years (6-18) and 7 years (1-16) after ECMO. There were no differences in demographics, procedural or ECMO-related variables between responders and non-responders. PHS for ECMO survivors were lower than the mean of the population sample (42 ⫾ 16 vs. 53 ⫾ 9, p⬍0.001), but similar to children with Fontan physiology or an AICD. PSS in ECMO patients were not different than the general population (48 ⫾ 12 vs. 51 ⫾ 9, p⫽0.11) or other cardiac samples. Placement on ECMO for post-cardiotomy failure, more non-cardiac operations, total ICU and hospital days, non-cardiac medical conditions, current medications, and the need for physical, occupational or speech therapy were associated with low PHS. More non-cardiac operations, non-cardiac medical conditions, and the need for special education, physical, occupational or speech therapy were associated with low PSS. QOL as reported by 17 children on the CHQ CF-87 was similar to that of a school-based population with the exception of the physical functioning concept. Conclusions: In children with cardiac disease who previously required ECMO, physical QOL is lower than the general population but similar to patients with complex cardiac disease, whereas psychosocial QOL is similar to the general population and other cardiac populations.


533 EXPLORING NSQIP IMPLICATIONS IN CRITICAL CARE: WHAT FACTORS ARE ASSOCIATED WITH THE ADVERSE EVENT OF “PROLONGED VENTILATION” IN SURGICAL PATIENTS? Subhash Reddy, Mathilda Horst, Huang Yung, Manpreet Chadha, Jack Jordan, Ilan Rubinfeld, Henry Ford Hospital Introduction: Cumulative ventilation time ⬎48 hrs, over a patient’s entire hospital stay, is defined in National Surgical Quality Improvement Program (NSQIP) of the American College of Surgeons as prolonged ventilation. This is considered an adverse outcome and is reported as a respiratory complication in NSQIP. Hypothesis: The purpose of study is to identify and analyze pre- and peri-operative factors associated with prolonged ventilation (PV) in surgical patients. Methods: Under the data use agreement and with the approval of our IRB, we reviewed 4 years (2005-2008) of NSQIP Public Use Files. Those with prolonged ventilation (PV) were labeled and evaluated in comparison to the rest of NSQIP patients who did not have prolonged ventilation. Odds ratio (OR), Chi square, uni-variate logistic regression were performed using SPSS (SPSS,Chicago). Data reported here was significant at p⬍.001. Results: Of 635265 patients, 15311(2.4%) were PV. The highest risk was seen with wound class 3(4%) and 4(10.5%). CHF (12.3OR) is the highest risk among cardiac conditions. The proportion of patients with PV increased with rising ASA class 1-5 (0%, 0.4%, 2.6%, 17% & 43% respectively) and p⬍0.001. Pre operative wound infection (5.3OR), pneumonia (28.1OR), preoperative SIRS (6.5OR), previous sepsis (15.2OR) and septic shock (94.6OR) increased likelihood of PV. Of the preoperative neurologic conditions impaired sensorium (24OR) and coma (40OR) were associated with PV. Dialysis (4.5OR) was less risky than acute renal failure (18.7OR). We report these additional odds ratios of factors found to be highly significant (OR⬎2.0 & P⬍0.001): bleeding disorders (4.7), transfusion (23.9), IDDM (2.89), ETOH (2.4), functional status of “dependent” (5.5), COPD (9.1), ascities (11.63), esophageal varices (6.8), steroid use (3.3) and weight loss (3.7). Interestingly, context was also important: elevated risk occurred with prior surgery (30 days) (8.3OR) and emergency surgery (7.3OR). Conclusions: This descriptive analysis demonstrates an association between many preoperative factors leading to the prolonged ventilation. Preoperative identification of modifiable risk factors may allow interventions to improve ventilation outcomes.



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TIME DEPENDENCY IN THE ASSOCIATION OF TRANSFUSION AND ACUTE LUNG INJURY IN THE INJURED PATIENT

IMPACT OF THE VIRAL RESPIRATORY SEASON ON POSTOPERATIVE OUTCOMES IN CHILDREN UNDERGOING CARDIAC SURGERY

Daniel Holena, Hospital of The University of Pennsylvania, Giora Netzer, University of Maryland Medical Ce, Russell Localio, Robert Gallop, University of Pennsylvania, Scarlett Bellamy, University of Pennsylvania School of Medicine, Nuala Meyer, Hospital of the Hospital of the University of Pennsylvania, Michael Shashaty, Paul Lanken, Patrick Reilly, Jason Christie, Hospital of the University of Pennsylvania Introduction: Blood transfusion is recognized as an important risk factor for development of ALI after trauma, but previous studies have not determined whether this relationship varies based on the timing of transfusion with respect to the initial trauma. Hypothesis: We hypothesized that the strength of the relationship between PRBC transfusion and ALI varies by the temporal proximity of transfusion to the initial trauma. Methods: Data were collected as part of a prospective cohort study from 1999 to 2006 to determine clinical and genetic factors associated with the development of ALI. Inclusion criteria were age ⬎ 13 years, SICU admission, and severe trauma as defined by injury severity score (ISS) ⱖ 16. All patients were followed prospectively from admission for the development of ALI during the first 5 days after trauma. Discrete time models were fit to test the association of timing of PRBC delivery with development of ALI, adjusting for age, ISS, type of trauma, gender, admission APACHE III scores, and amount of crystalloid delivered. Results: At total of 609 patients were available for analysis. Patients tended to be young (median age 33 years), male (77%), and were equally split between African American and Caucasian. Using a discrete time-survival model, the relationship between the amount of daily PRBC delivered on subsequent development of ALI was found to vary significantly by time-window of transfusion (p⬍0.0001), The major effect of PRBC delivery on ALI risk was driven transfusion in the first 24 hours of after trauma (OR⫽1.08 per unit; 95% CI 1.04,1.13, p⬍0.001). This finding persisted after controlling for age, ISS, gender, mechanism of trauma, APACHE III score, and total fluids delivered during the first 24 hours (adjusted OR ⫽ 1.07 per unit; 95% CI 1.02,1.11, p⬍0.001). The cumulative incidence of ALI over 5 days was nearly 50% in patients receiving ⬎ 6 units of PRBCs in the first 24 hours. Conclusions: The association between PRBC transfusion and the development of ALI in trauma patients is time-dependent, with the amount of PRBC delivery in the first 24 hours driving the overall relation. Each unit of PRBC during this time period increases the odds of subsequent ALI development by 7%.

Michael Spaeder, Children’s National Medical Center, Kathryn Carson, Johns Hopkins University School of Public Health, Luca Vricella, Diane Alejo, Kathryn Holmes, Johns Hopkins Hospital Introduction: Few studies have investigated the impact time of year has on morbidity and mortality outcomes of pediatric cardiac surgical patients. Of concern in performing cardiac surgery in the winter months is the community or hospital acquisition of viral respiratory illnesses. Hypothesis: We hypothesized that post-operative outcomes in children undergoing cardiac surgery are worse during the viral respiratory season. Methods: All patients under the age of 18 years who underwent cardiac surgery at our institution between 10/02 and 9/07 were identified. Patients were assigned to either viral (November to March) or non-viral (April to October) season based on operative date and were stratified by complexity of cardiac disease. The primary outcome was post-operative length of stay (LOS). We performed a matched case-control analysis on the subset of patients with laboratory confirmed viral respiratory infection (respiratory syncytial virus, influenza, parainfluenza or adenovirus). Results: A total of 744 patients were included in the analysis; 262 patients in the viral season and 482 patients in the non-viral season. Thirteen patients (1.7%) had viral respiratory infection. There was no difference in baseline patient characteristics, post-operative LOS, ICU LOS, hospital charges or risk of mortality between the seasons. Patients undergoing surgery during the viral season were more likely to have viral respiratory infection (p⬍0.01). Patients with viral respiratory infection were more likely to have a longer post-operative LOS, ICU LOS and hospital charges (all p⬍0.01) as compared with matched controls. Conclusions: We identified no difference in post-operative outcomes based on season in patients undergoing cardiac surgery. While the number of patients with viral respiratory infection was low, these children have significantly worse outcomes than matched controls. Our findings strengthen the call for universal influenza vaccination and palivizumab administration to appropriate groups and strict adherence to isolation procedures in hospitalized patients. Pre-operative testing for respiratory viruses should be considered during the winter months for children undergoing elective cardiac surgery.

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FACTORS ASSOCIATED WITH READMISSION IN CHILDREN WITH STATUS ASTHMATICUS

OUTCOMES OF SEVERE SEPSIS IN SOLID ORGAN TRANSPLANTS - A NATIONWIDE ANALYSIS

Christopher Carroll, Kathleen Sala, Yen-Shin Tang, Aaron Zucker, Connecticut Children’s Medical Center

Gagan Kumar, Puneet Sood, Ankit Sakhuja, Amit Taneja, Sandeep Markan, Thomas Kaleekal, Medical College of Wisconsin, Abhishekh Deshmuk, University of Arkansas, Rahul Nanchal, Medical College of Wisconsin

Introduction: Status asthmaticus is a frequent cause of hospitalization in children. A subset of children hospitalized for status asthmaticus has multiple readmissions over the course of their childhood, little research has explored the characteristics underlying readmission in this population. Hypothesis: In a cohort of children admitted to the ICU with status asthmaticus, there are specific characteristics that predict future hospital readmission. Methods: We conducted a retrospective chart review of all children aged 2 to 18 years admitted to the pediatric ICU for status asthmaticus from 2003-2006. Predictors and outcomes of children readmitted to the hospital for an asthma exacerbation were compared to those without readmission. Results: One hundred and fifty-six children were admitted to the pediatric ICU for status asthmaticus between 2003-2006, 44 (28%) of whom were readmitted to the hospital (ward or ICU) through April 2010. Median time to readmission was 0.9 years, with 25% and 75% quartiles of 0.5 and 1.7 years, respectively (range 0.1 – 6.2 years). Children readmitted to the hospital following an ICU admission were significantly more likely to be nonCaucasian (OR 2.4, 95% CI 1.1-5.5; p⫽0.04), to have persistent asthma (OR 3.0, 95% CI 1.3-6.9; p⫽0.01), to have been previously hospitalized for asthma (OR 4.0, 95% CI 1.9-8.4; p⬍0.001), and to have had pneumonia during their ICU admission (OR 2.4, 95% CI 1.1-5.5; p⫽0.03) compared to children who were not readmitted. The predicted probability of readmission ranged from 6% in patients with none of these risk factors to 66% in children with all 4 risk factors. No other factors, including age, gender, race, or ICU length of stay were associated with future readmission. A regression model containing the variables that were significantly associated with readmission in univariate analyses proved to have good model fit. Conclusions: Almost 30% of children admitted to the pediatric ICU with status asthmaticus were subsequently readmitted to the hospital for asthma. Non-Caucasian race, persistent asthma, pneumonia and a history of previous hospitalization are significant predictors of future readmissions for an asthma exacerbation in children admitted to the ICU.

Introduction: Solid-organ transplant recipients (SOT) are a growing population of immunocompromised hosts. Over 24,000 SOT are now performed in the U.S. annually. However, there is a paucity of literature on the nationwide outcomes of severe sepsis in SOT recipients. We sought to examine these outcomes using a large administrative database. Hypothesis: Given the immune-compromised state, outcomes of severe sepsis in SOT recipients are worse when compared to the general population. Methods: Using the Nationwide Inpatient Sample 2007, patients older than 18 years, discharged with any diagnosis of severe sepsis were identified using ICD-9-CM codes. SOT patients were also identified using appropriate ICD-9CM codes. Transplants included in the study were - kidney, liver, heart and lung. The primary outcome studied was all cause in hospital mortality and secondary outcomes were rate of mechanical ventilation and length of stay (LOS). Chi square test and t tests were used to compare the variables for unadjusted analysis. Multivariate logistic regression was used to obtain adjusted odds ratios. ␣ was set at 0.05. Results: There were total of 338,456 estimated adult discharges with severe sepsis in 2007. Of these 4325 were SOT. The frequency of severe sepsis was significantly higher in SOT when compared to those who did not have transplants (2.4% vs. 1.0%). However, in-hospital mortality in patients admitted with severe sepsis was significantly lower in SOT when compared to the general population (25.9% vs. 36.5%). This difference persisted after adjustment for age, co-morbid conditions and severity of sepsis (OR 0.79; 95% CI 0.65-0.95). Rates of mechanical ventilation were also significantly lower in SOT group (OR 0.63; 95%CI 0.54-0.74). LOS was not significantly different in severe sepsis patients with SOT. Conclusions: Solid organ transplant patients have higher frequency of severe sepsis when compared to general population but paradoxically the mortality is significantly lower. These patients also have significantly less respiratory failure requiring mechanical ventilation. Prospective studies are investigate the reason for our findings.


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VARIATION IN THE TREATMENT OF PATIENTS WITH SEPTIC SHOCK

ARE PATIENT CHARACTERISTICS AND CLINICAL OUTCOMES OF 2009 H1N1 INFLUENZA INFECTION DIFFERENT FROM THAT OF SEASONAL INFLUENZA INFECTION?

Tara Lagu, Baystate Health, Jay Steingrub, Baystate Medical Center, Michael Rothberg, Baystate Health, Brian Nathanson, OptiStatim, LLP, Penelope Pekow, Peter Lindenauer, Baystate Health Introduction: There is limited evidence for many of the treatments administered to patients with septic shock. Little is known about the use of sepsis treatments in settings outside of clinical trials. Hypothesis: Treatment of septic shock will vary across hospitals and patient groups, and the degree of variation will depend on the strength of the supporting evidence. Methods: We conducted a retrospective study of 192 hospitals that treated at least 50 adult medical patients with vasopressor-dependent sepsis between 2004-2006. We examined hospital use of a comprehensive set of therapies and calculated the median, 25th, and 75th percentiles rates of treatment. We developed multilevel (hierarchical) mixed effects logistic regression models to evaluate the association between patient and hospital characteristics and selected treatments. Results: 22,702 patients were included in the study. Use of mechanical ventilation varied little across hospitals (median 52% [IQR 44, 60], while administration of hydrocortisone (23% [IQR 15, 34]), activated protein C (APC) (4.0% [IQR 1, 8]), and central venous pressure (CVP) monitoring (25% [IQR 12, 44]) showed greater levels of variation. After adjusting for patient case-mix differences, we observed no consistent association between the treatment rates for these four therapies and hospital characteristics such as size, teaching status, geographic region, or urban/rural setting. However, when compared to patients ⬍ 45 years old, patients ⱖ 75 years were less likely to receive APC (OR⫽0.35 [95% CI 0.27-0.45]), hydrocortisone (OR⫽0.65 [95% CI 0.56-0.75]), or CVP monitoring (OR⫽0.73 [95% CI 0.63-0.84]. When compared to whites, black patients were more likely to be mechanically ventilated (OR⫽1.15 [95% CI 1.05-1.25]), but blacks were less likely to receive hydrocortisone (OR⫽0.86, [0.78-0.95]) or APC (0.70, [0.58-0.86]). Conclusions: The treatment of patients with septic shock varies widely across hospitals. In contrast to mechanical ventilation, there is more between-hospital variation for treatments with weaker supporting evidence (level 2 recommendations or below). Black and elderly patients are less likely to receive therapies with weaker supporting evidence.

Rahul Kashyap, Jyoti Assudani, Priya Sampathkumar, Adil Ahmed, College of Medicine, Mayo Clinic, Chakradhar Venkata, Immanuel St. Joseph’s HospitalMayo Health System, Ognjen Gajic, Guangxi Li, College of Medicine, Mayo Clinic Introduction: As of August 2010, the Centers for Disease Control and Prevention estimates that about 61 million cases of 2009 H1N1 occurred between April 2009 and April 2010 in the United States, resulting in about 274,000 H1N1-related hospitalizations and 12,470 deaths.There is paucity of literature comparing the patient characteristics and clinical outcomes of the 2009 H1N1 infection to that of seasonal influenza infection in a single hospital environment. Hypothesis: We sought to evaluate the differences in patient characteristics and clinical outcomes of 2009 H1N1 influenza from that of seasonal influenza. Methods: This retrospective cohort study includes chart review of hospitalized adult patients with laboratory proven influenza in three consecutive seasons (October-May) during 2007-2010 at a tertiarycare medical center.Laboratory diagnosis of influenza was made using an influenza real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay performed on respiratory specimens. Patient characteristics and clinical outcomes of influenza, including ICU admissions, development of ALI/ARDS and hospital mortality were compared. Results: A total of 270 adult patients met inclusion criteria (N; 2009 H1N1 influenza ⫽ 74, Seasonal influenza ⫽ 196). Compared with seasonal influenza, 2009 H1N1 influenza patients were younger (Median age (in years) (IQR) 47(31-58) vs. 67(51-82), p⬍0.01) and less often Caucasian 58(78%) vs. 178 (91%) (p⬍0.01). Asthma was more prevalent in 2009 H1N1 influenza patients 11(15%) vs. 8(4%) (p⬍0.01). Amongst patients with 2009 H1N1 influenza, 26(35%) required ICU care compared to 53(27%) patients with seasonal influenza (p⫽0.19). More patients from 2009 H1N1 influenza infection developed ALI/ARDS (13 (18%) vs. 15 (8%), p⬍0.02). No significant difference in mortality was observed between 2009 H1N1 influenza 4(5.4%) and seasonal influenza 7(3.5%) (p⫽0.49). Conclusions: Compared to seasonal influenza, hospitalized patients with 2009 H1N1 influenza were younger, non-Caucasian and were more likely to have a history of asthma. Significantly higher number of H1N1 influenza patients developed ALI/ARDS. No difference was observed in ICU admissions and hospital mortality between the two groups.

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ALBUMIN AND C-REACTIVE PROTEIN HAVE PROGNOSTIC SIGNIFICANCE IN PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA

VALUE OF TARGETING HIGHER MEAN ARTERIAL PRESSURE IN CRITICALLY-ILL PATIENTS WITH CHRONIC KIDNEY DISEASE

Jae Hyuk Lee, Kyuseok Kim, You Hwan Jo, Joong Eui Rhee, Seoul National University Bundang Hospital

Vivek Punjabi, Dan Fabius, Jean-Sebastien Rachoin, Barry Milcarek, Christa Schorr, Sergio Zanotti-Cavazzoni, Cooper University Hospital

Introduction: Biochemical markers are associated with severity of disease, inflammatory condition and underlying nutritional status. However, these are not included in severity assessment tools in community-acquired pneumonia (CAP). Hypothesis: Biochemical markers such asalbumin and C-reactive protein (CRP) might be associated with mortality and when combined with pneumonia severity index (PSI), these markers could improve the prognostic performance for mortality in patients with CAP. Methods: The data were gathered prospectively in hospitalized patients with CAP via emergency department. Laboratory values including CRP and albumin, clinical variables and PSI were measured. Major outcomes were 28-day mortality and survival times. Results: 424 patients were included. The 28-day mortality was 13.7%. CRP and albumin were significantly different between survivors and non-survivors. In logistic regression analysis, CRP and albumin were independently associated with 28-day mortality (p ⬍ 0.05). ROC curve showed improvement of mortality prediction by adding CRP or albumin toPSI scale. The Cox Proportional Hazard analysis shows high serum albumin( ⱖ 3.3mg/dL) had a hazard ratio of 0.5 (95% CI, 0.3 to 0.9) and high CRP (ⱖ 14.3 mg/dL) had a hazard ratio of 2.0 (95% CI, 1.1 to 3.4). Conclusions: Biochemical markers such as albumin and CRP were associated with 28day mortality in hospitalized patients with CAP and these markers increased prognostic performance when combined with PSI scale

Introduction: Current guidelines for treatment of critically-ill patients recommend aiming for a MAP of 65. This has been based on small studies that did not show a difference in hemodynamic parameters measured at different MAP targets in patient with preserved vascular auto regulation.We analyzed the association between MAP and SVO2 in a well characterized population of critically-ill patients with CKD. Hypothesis: Patients with chronic kidney disease (CKD) have impaired vascular auto regulation and require higher blood pressure to maintain adequate organ perfusion. Methods: We performed a retrospective study of patients admitted to the Medical/Surgical ICU between July’03 and December’08. Patients were identified through the PI database. Inclusion criteria were Age⬎17, CKD and presence of PA catheter. We recorded demographical data as well as the following hemodynamic parameter: CO, CI, CVP, PCWP, SVR and SVO2 at three different times – this first time the MAP was in the range of 60-69, 70-79 and 80-89, all of which were within 12 hours of the first measurement. We analyzed the data using Chi-square test and Friedman’s test. Results: 184 patients we initially considered for enrollment of which 59 had incomplete data. The average age was 70 y [57-76], and there were 37% female. There were 21.6% COPD, 32.8% CHF, 92.8% HTN, 72.8% CAD, and 44.8 % ESRD. Only 66 patients had all data at the three predefined MAP ranges. 33 of those patients were ESRD. We performed a Friedman test on these patients which revealed no difference for CVP (p⫽0.103), CO (0.377) or CI (0.577). The PCWP was greater in the G3 (p⫽0.032) so was the SVR (p⬍0.001). Conclusions: In patients with chronic kidney disease and ESRD, higher MAP (80-89) are associated with significantly higher SVO2 thus suggesting a better tissue oxygen delivery. There may be a need for targeting a higher MAP in patients with impaired vascular auto regulation. Prospective controlled trials should be performed to ascertain the validity of these findings.


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RESOURCE-EFFICIENT MOBILIZATION PROGRAMS IN THE ICU: WHO STANDS TO WIN?

RED CELL DISTRIBUTION WIDTH AND MORTALITY IN CRITICAL ILLNESS

Clifford Perez, John Mah, Ilene Staff, David Fichandler, Karyn Butler, Hartford Hospital

Heidi Bazick, Massachusetts General Hospital, Domingo Chang, Karthik Mahadevappa, Brigham and Women’s Hospital, Fiona Gibbons, Massachusetts General Hospital, Kenneth Christopher, Brigham and Women’s Hospital

Introduction: Prolonged immobilization in critically ill patients is associated with muscle atrophy, weakness and pulmonary complications. Hypothesis: The purpose of this study was to evaluate the feasibility of a resource-efficient early mobilization program (REMP) on improvement in motor performance in the surgical intensive care unit (SICU). Methods: Consecutive SICU admissions between April 2009 and May 2010 underwent physical therapist (PT) evaluation and participation in REMP (one PT, one PT aide, the dedicated SICU respiratory therapist, and the patients’ bedside nurse). Motor evaluations in the SICU were compared with evaluations at SICU and hospital discharge. Sitting balance (SB), transfer from bed-to-chair and ambulation were assessed using the Functional Independence Measure scale (FIM motor domain, 1-7). Age, gender, APACHE II, SICU, hospital and ventilator lengths of stay, extubations, hemodynamic instability, and falls were recorded. SICU patients prior to REMP initiation served as controls. Data are expressed as median for performance evaluations and mean ⫾ SEM for continuous variables. Analysis utilized c2, Friedman or Wilcoxon ranks, or t-test. Results: Twenty-eight patients entered the REMP and 31 patients served as controls. There were no differences in age, APACHE II or initial FIM for ambulation or SB (median ⫽ FIM 1). Bed-to-chair evaluation was higher in the controls (p⬍0.024). Both groups improved across the three time periods on all measures; however, more REMP patients improved SB (higher FIM score) at SICU and hospital discharge (75% vs.36.7%, p⫽0.004). Among patients with initial FIM ⬎4, more REMP patients improved to FIM ⬎5 (supervision or independence) for SB (60% vs. 30%, p⫽0.05) and ambulation (23% vs. 0%, p⫽0.01) at ICU discharge. No adverse events occurred. Conclusions: A resource-efficient approach to early mobilization is feasible in the SICU and has a favorable safety profile. Early mobilization significantly improves SB and ambulation at discharge from the SICU for patients with initial low motor performance. FIM assessment may be useful in allocating resources to patients who ‘stand’ to benefit from REMP in the ICU.

Introduction: Red Cell Distribution Width (RDW) is a predictor of mortality in the general population of adults ⱖ 45 years. Hypothesis: We hypothesized that there is an association between RDW at the initiation of critical care and all cause mortality. Methods: We performed a multicenter observational study of 51,413 patients, age ⱖ 18 years, who received critical care between 1997 and 2007. The patients were treated in 209 medical and surgical intensive care beds in two hospitals in Boston, Massachusetts. The exposure of interest was RDW on ICU admission and categorized a priori in quintiles as ⱕ13.3%, 13.3-14.0%, 14.014.7%, 14.7-15.8%, and ⬎15.8%. Logistic regression examined death by days 30, 90 and 365 post-ICU admission, in-hospital mortality and blood culture positivity. Adjusted odds ratios were estimated by multivariable logistic regression models. Adjustment included age, sex, race, Deyo-Charlson index, CABG, MI, hematocrit, WBC, MCV, BUN, sepsis and creatinine. Results: RDW was a particularly strong predictor of all cause mortality 30 days following ICU admission with a risk gradient across RDW quintiles following multivariable adjustment: RDW 13.3-14.0% OR 1.19 (95% CI, 1.08-1.30; P⬍.0001); RDW 14.014.7% OR 1.28 (95% CI, 1.16-1.42; P⬍.0001); RDW 14.7-15.8% OR 1.69 (95% CI, 1.53-1.87; P⬍.0001); RDW ⬎ 15.8% OR 2.62 (95% CI, 2.39-2.88; P⬍.0001); all relative to patients with RDW ⱕ13.3%. Similar significant robust associations following multivariable adjustments are seen with death by days 90 and 365 post-ICU admission as well as in-hospital mortality. In a sub-analysis of patients with blood cultures drawn (n⫽ 18,525), RDW at ICU admission was associated with the risk of blood culture positivity and remained significant following multivariable adjustment. The adjusted risk of blood culture positivity was 1.4- and 1.5-fold higher in patients with RDW values in the 14.7-15.8% and ⬎15.8% quintiles, respectively, compared with those with RDW ⱕ13.3%. Conclusions: RDW is a significant predictor of the risk of all cause patient mortality and blood culture positivity in the critically ill.

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TRADE OFF BETWEEN DUTY HOURS AND NUMBER OF PATIENT HAND-OFFS: COMPARISON OF PROVIDER SCHEDULING OPTIONS IN THE INTENSIVE CARE UNIT

THE UTILIZATION OF RED BLOOD CELLS TRANSFUSION AND THE MORTALITY OF OLDER PATIENTS WITH CANCER ADMITTED TO THE ICU

Chris Janish, Mayo Clinic, Anil Patel, Mayo Foundation For Medical Education and Research, Bjorn Berg, North Carolina State University, Kianoush Kashani, Mayo Clinic (CCM), Cassie Kennedy, Mayo Graduate School of Medicine, William Dunn, Mayo Clinic, Ognjen Gajic, Mayo Graduate School of Medicine(Rochester), Yue Dong, Mayo Clinic

Marylou Cardenas-Turanzas, Kristen Price, Joseph Nates, The University of Texas MD Anderson Cancer Center

Introduction: New Accreditation Council for Graduate Medical Education (ACGME) duty-hours regulations are designed to address resident sleep deprivation, leading to a trade-off with an increased number of “provider shift-changes” (PSC). Each PSC, leads to the possibility of communication breakdown during each patient hand-offs (PHO), contributing to medical errors and poor patient outcomes. Future duty-hour restrictions pose further challenges to resident scheduling in intensive care units that require 24-hour coverage. The primary metric taken into consideration when determining the schedule is duty-hours set by the ACGME . The relationship between duty-hours, numbers of shift-changes and hand-offs has not been well studied. Hypothesis: The resident duty-hours reduction is associated with significant increased number of PHO due to more frequent PSC. Methods: Each critical care fellow is working within a team (attending, senior and junior medical residents) at a medical ICU in a tertiary medical center. Patient care is provided by two teams during the day which alternate at night. A new fellow’s schedule was implemented in July 2010 using 5 instead of 4 fellows to cover the unit during each month. It was designed to reduce duty-hours in line with the ACGME’s recommendations and improve their education experience. Total weekly ICU coverage hours, each fellow’s weekly dutyhours and number of PSC were calculated for both old and new schedules. Using Discrete Event Simulation modeling, we were able to calculated actual number of PHO between old and new schedules for fellows. Results: The new schedule reduced total weekly duty-hours for each fellow (73.5h vs. 62.4h), but it resulted 33% more PSC (112 vs. 84) and PHO (860 vs. 650) compared to the old schedule. Conclusions: This preliminary study investigated the trade off between duty-hours and number of PSC, PHO. Future consideration of provider scheduling metrics should include duty-hour regulation, service coverage and potential increased hand-offs. Our study purposed a new patient centric scheduling in order to provide continuous patient care with minimal interruption and still meet the resident duty-hour requirement.

Introduction: Transfusion is a common procedure in the ICU. Hypothesis: We evaluated the relative impact of determinants of ICU mortality adjusting for the amount of red blood cells (RBC) units transfused during the stay, in the oldest group of patients with cancer admitted to a comprehensive cancer center. Methods: A retrospective chart review of patients ⬎79 years old was conducted from September 1, 2001 to August 31, 2005. We collected sociodemographic data, amount of RBC units transfused, hemoglobin (Hb) level, modified SOFA score, hospital and ICU length of stay (LOS). The outcome of study was the ICU discharge status. We used logistic regression to determine independent factors associated with mortality including a priori the amount of RBC units transfused during the stay as well as the factors with p-value ⬍.20 in the bivariate analysis. Results: A total of 196 patients were included, 63.3% received transfusions at the unit and the ICU mortality rate was 8.7%. The mean Hb level at admission was 10.9 (range 5.1 –15.9) and the majority 57.7% were transfused during the first 48 hrs of admission. The mean (sd) number of units utilized per patient was 2.3 (2). Patients who did not survive the ICU stay received a mean of 3.8 RBC units compared to only 2.2 units utilized by patients who were discharged alive, and the difference was marginally significant (p ⫽ .05). The factors independently associated with mortality were medical admissions (Odds Ratio [OR] ⫽ 3.78, 95% CI 1.18, 12.11), increased modified SOFA score (OR ⫽ 1.27, 95% CI 1.04, 1.57), and increased ICU LOS (OR⫽ 1.12, 95% CI 1.03, 1.21). We observed Whites were 74% less likely to die than non-Whites (OR⫽ .26, 95% CI .07, .92, p ⫽ .04). The amount of RCB units utilized during the stay did not remain a significant determinant of mortality. Conclusions: Although this study supports findings of long stays in the unit associated with higher utilization of transfusion, our results do not support findings about transfusion associated with ICU mortality. To avoid error in hypothesis testing, a larger sample is needed. The observation of race independently associated with ICU mortality in the oldest population of patients with cancer, deserves further investigation.



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EFFECT OF 24-HOUR MANDATORY VERSUS ON-DEMAND CRITICAL CARE SPECIALIST PRESENCE ON LONG-TERM SURVIVAL AND QUALITY OF LIFE OF CRITICALLY ILL PATIENTS IN THE INTENSIVE CARE UNIT OF A TEACHING HOSPITAL

OUTCOMES OF SEVERE SEPSIS IN PATIENTS WITH CIRRHOSIS

Martin Reriani, Michelle Biehl, Jeff Sloan, Michael Malinchoc, Ognjen Gajic, Mayo Clinic

Introduction: Patients with cirrhosis are at increased risk of developing infectious complications. Since the liver is a major immune organ, infections in patients with cirrhosis may lead to greater cytokine imbalances, higher risk of organ failure and subsequent death. Indeed, infections are a main cause of the newly described entity of acute on chronic liver failure leading to multiple organ failure. However literature describing the incidence and outcomes of severe sepsis in patients with cirrhosis is scarce. The goals of our study were to describe the outcomes of severe sepsis in cirrhotics. Hypothesis: Cirrhosis independently predicts worse outcomes in patients with severe sepsis Methods: Using the Nationwide Inpatient Sample 2007, patients older than 18 years, discharged with any diagnosis of severe sepsis (995.92) were identified using ICD-9-CM codes. The cirrhotics were also identified using appropriate ICD-9CM codes. Outcome variables included frequency, in-hospital mortality and length of stay. Chi square test and t tests were used to compare variables for unadjusted analysis. Logistic regression model was developed to find if cirrhosis was independent predictor of mortality. The model was adjusted for demographic and hospital characteristics, co-morbidities and severity of severe sepsis. ␣ was set at 0.05. Results: There were total of 6,648,184 adult discharges in 2007. The frequency of severe sepsis was significantly higher in cirrhotics when compared to those who did not have cirrhosis (2.7% vs. 1.0%). In-hospital mortality in patients admitted with severe sepsis was significantly higher in cirrhotics when compared to those without (53.8% vs. 35.5%). Cirrhosis was found to be independent predictor of mortality in patients with severe sepsis (OR 1.98; 95%CI 1.70-2.31).The length of stay was significantly higher in severe sepsis patients with cirrhosis (mean: 17 days vs. 15.4 days). Conclusions: Patients with cirrhosis have 2.7 times higher frequency of severe sepsis when compared to non-cirrhotics. Cirrhosis is an independent predictor of mortality in patients admitted with severe sepsis.

Introduction: Intensive care unit (ICU) staffing by critical care physicians has been shown to improve patient outcomes. Mandatory compared to on-demand intensivist presence further improves processes of care and decreases ICU complication rate and hospital length of stay. The effect of continuous mandatory intensivist coverage on long-term patient mortality and quality of life (QOL) has not been studied. Hypothesis: We hypothesized that 24-hour on-site presence of a critical care specialist will improve long-term survival and QOL of critically ill patients. Methods: In this prospective study we obtained long-term survival and QOL of patients admitted to a medical ICU before (year of 2005) and after (year of 2006) a staffing model change from on-demand to mandatory 24-hour critical care specialist presence in the medical ICU. Long-term survival was ascertained on 3279 patients (1582 before and 1697 after staffing model change) from hospital discharge to June 2010. In a subset of patients admitted in the last two months of the control period and the first two months of the intervention period, QOL was assessed using the SF-36 survey administered both at baseline and at six months after ICU discharge. Results: The baseline characteristics did not differ significantly between the two groups except for race and APACHE III score (median 30 vs 37, P⬍0.001, before and after the staffing model change respectively). Long-term survival was not significantly different before and after the staffing change - HR 1.05 95% CI(0.95-1.16); P⫽0.3. SF-36 physical functioning composite score improved significantly at six months compared to baseline in patients after the staffing model change - delta (SD) 8(14) vs 2(11), P⫽0.03. There was no difference in the overall and mental composite score of the SF-36 between the two groups. Conclusions: Introduction of an additional night shift to provide mandatory as opposed to on-demand 24-hour staff critical care specialist coverage did not affect long-term survival of medical ICU patients. In survivors who underwent baseline and follow up QOL surveys, physical function improved to a greater extent after the staffing change, but this finding requires further confirmation.

Muhammad Ali, Shahryar Ahmad, Gagan Kumar, Nilay Kumar, Rahul Nanchal, Medical College of Wisconsin

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ELDERLY TRAUMA PATIENTS SHOULD BE EVALUATED FOR PRE-EXISTING URINARY TRACT INFECTION

REVISED TIGHT GLYCEMIC CONTROL PROTOCOL FOR CRITICAL CARE PATIENTS AT A COMMUNITY HOSPITAL

Lois Sakorafas, Micheal Horst, Roxanne Chandler, Tracy Evans, John Lee, Matthew Edavettal, Daniel Wu, Jo Ann Miller, Frederick Rogers, Lancaster General Hospital

Nicki Roderman, Gita Patel, Medical Center of Plano

Introduction: With advancements in technology particularly Computer Tomography scans, the reliance on simple tests like presence of blood in urinalysis plays significantly less important role and may prompt skipping this test in trauma patients. This may result in missing the diagnosis of pre-existing Urinary Tract Infection (UTI) in elderly trauma patients at the time of admission. Hypothesis: Pre-existing UTI is prevalent in elderly trauma patients. Methods: Retrospective review of a robust prospectively collected trauma database of a community hospital was performed to identify the prevalence of pre-existing UTI in elderly trauma patients. Results: From Jan 2009 to July 2010, 3167 patients were admitted to our trauma service of a community hospital and of these 912 (28.8%) were 65 years or older. Pre-existing UTI was diagnosed and treated in 6.5% of patients 65 years or older compared to 0.7% in patients less than 65 years (p⬍0.001; OR ⫽ 7.4; 95%CI for OR ⫽ 3.3-16.4). The rate of preexisting UTI was almost double among elderly patients whose mechanism of injury was a fall, compared to other mechanisms of injury; but this did not reach statistical significance (7.2% versus 4.1%; p ⫽ 0.100; OR ⫽ 1.8; 95%CI for OR ⫽ 0.9-3.8). For all trauma patients, unadjusted mean (SD) hospital length of stay (LOS) was longer in patients with pre-existing UTI when compared with those without pre-existing UTI [4.6 (standard deviation 3.6) days versus 3.4 (standard deviation 4.7) days; p ⫽ 0.006. Conclusions: There is a significant prevalence of preexisting UTI in elderly trauma patients and unadjusted hospital length of stay was longer in all trauma patients with pre-existing UTI. Possible implications of missing this diagnosis on admission, such as untreated infection especially in those requiring prosthetic materials; as well as subsequent mis-classification as hospital acquired infection should be investigated.


Introduction: Tight glycemic control in the critically ill has been an ongoing controversial therapeutic issue. Optimal target blood glucose levels for critically ill patients have been greatly debated. Multiple publications have advocated looser target blood glucose ranges for critically ill patients due to concerns of hypoglycemia and associated increased mortality. Hypothesis: The purpose of this study was to investigate the effect of loosening the tight glycemic control (TC) range in the medical/surgical critical care unit from 81-110 mg/dL to 90-140 mg/dL at a community hospital. Methods: A retrospective review of data from 47 patients treated with the TC algorithm to attain blood glucose (BG) measurements of 81-110 mg/dL were compared to 70 patients that were treated with the revised TC algorithm to attain BG measurements of 90-140 mg/dL. Data collected included demographics, APACHE-II scores, co-morbidities, starting BG, time to goal, mean BG at goal, percentage of patients with hypoglycemia (BG⬍40 mg/ dL), length of stay (LOS), and mortality. Results: Demographics were similar between the groups, although the APACHE-II score was higher in the 81-110 mg/dL group (30.5 ⫹ 10.9) versus the 90-140 mg/dL group (25.1 ⫹ 8.3, p⫽0.003). There were more trauma and general surgery and fewer medical patients in the 81-110 mg/dL group. Hospital and critical care unit lengths of stay, starting BG, and hours to goal were similar between both groups. The median BG at goal was 125.7 mg/dL (99.1-200.5 mg/dL) in the 90-140 mg/dL group versus 110.3 mg/dL (88-280 mg/dL) in the 81-110 mg/dL group (p⬍0.0001). Percentage of patients with a BG ⬍40 mg/dL was 8.5% in the 81-110 mg/dL group versus 4.3% in the 90-140 mg/dL group (p⫽0.44). Mortality was similar between the tighter 81-110 mg/dL (34%) and the 90-140 mg/dL (34.3%) groups (p⫽1.0). A multivariate logistic regression analysis revealed a BG ⬍ 40 mg/dL was a predictor of mortality (p⫽0.038). Conclusions: There were no appreciable differences in hypoglycemia and mortality with the range of 90-140 mg/dL versus the tighter range of 81-110 mg/dL; however, there is an increased risk of mortality associated with severe hypoglycemia.

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THE IMPACT OF COMPLEX CHRONIC CONDITIONS ON CHILDREN ADMITTED TO A NATIONAL SAMPLE OF U.S. PICUS

A MULTICENTER COLLABORATIVE APPROACH TO REDUCING PEDIATRIC CODES OUTSIDE THE ICU

Jeffrey Edwards, Amy Houtrow, Roberta Rehm, UCSF, Barry Markovitz, Childrens Hospital Los Angeles, Robert Graham, Children’s Hospital Boston, R. Dudley, UCSF Introduction: Children with complex chronic conditions (CCC) are a vulnerable population who may frequently require intensive care. To date, no studies have estimated the risks associated with CCC for children admitted to PICUs using regression methods modeled on a nationally representative sample. Hypothesis: Complex chronic conditions put children at increased risk for death during their PICU admission, even after adjusting for other factors and compared to children with chronic, but non-complex, conditions. Methods: A cross-sectional cohort study of all patients admitted in 2008 to 46 PICUs throughout the U.S. that participate in the Virtual Pediatric Intensive Care Unit Performance System (VPS) database. Modified Delphi method was used to identify CCC diagnoses. Hierarchical mixed-effects logistic regression models were used to examine the association between CCC and death during PICU admission and other secondary outcomes. Results: Of the 43,384 PICU patients admitted in 2008, 23% had a documented CCC. After adjusting for age, gender, severity of illness, length of stay, admission type, and other factors, having a CCC increased the odds of death during PICU admission by 43% (adjusted odds ratio [AOR] 1.43, 95% CI 1.22-1.67, P⬍0.001), compared to not having a CCC. Chronic, non-complex, conditions, were associated with decreased risk of death (AOR 0.79, P⫽0.027). Having a CCC diagnosis also increased the odds of a previous PICU admission (AOR 1.64, P⬍0.001), extended [ie, ⬎95%] length of PICU stay (AOR 1.55, P⬍0.001), and extended duration of positive pressure respiratory support (AOR 1.39, P⬍0.001). In contrast, having only a non-complex, chronic condition was associated with decreased odds of these same outcomes. Having a CCC decreased the odds of a subject’s admission being unscheduled (AOR 0.62, P⬍0.001) and of the need for respiratory support (AOR 0.93, P⫽0.036). Conclusions: Children with complex chronic conditions are a sizeable proportion of children admitted to US PICUs, with disproportionate health risks and needs. Because PICUs are a locus of care for this vulnerable group, intensivists must continue to devote efforts to study and mitigate the impact of complex chronic conditions on children.

Leslie Hayes, The Children’s Hospital of Alabama, UAB, Emily Dobyns, the Children’s Hospital Denver, Bruno DiGiovine, Wayne State University, AnnMarie Brown, Akron Children’s Hospital, Sharon Jacobson, Texas Children’s Hospital, Beth Wathen, The Children’s Hospital Denver, Heather Richard, Children’s Healthcare of Atlanta, Tina Logsdon, Matthew Hall, CHCA, Barry Markovitz, Children’s Hospital Los Angeles Introduction: The Child Health Corporation of America (CHCA) formed a multicenter collaborative to decrease the rate of pediatric codes outside the ICU by 50%, double the days between these events and improve patient safety culture scores by 5 percentage points. Hypothesis: Working in a collaborative model would facilitate reduction in pediatric codes outside the ICU and improve patient safety scores across multiple institutions. Methods: A multidisciplinary pediatric advisory panel developed a comprehensive change package of process improvement strategies and measures for tracking progress. Learning Sessions, conference calls and data submission facilitated collaborative group learning and implementation. Twenty CHCA hospitals participated in this 12 month improvement project. Each hospital identified at least one non-critical care ‘target‘ unit in which to implement selected elements of the change package. Strategies to improve prevention, detection and correction of the deteriorating patient ranged from relatively simple, foundational changes to more complex, advanced changes. Each hospital selected a broad range of change package elements for implementation using rapid-cycle methodologies. The primary outcome measure was codes per 1000 patient days. Secondary outcomes were days between codes and change in patient safety culture scores. Results: The code rate for the collaborative as a whole did not decrease significantly (3% decrease, p ⫽ 0.284). However, twelve hospitals reported additional data post-collaborative; these 12 hospitals saw significant improvement in code rates (24% decrease, p ⫽ 0.039). Patient safety culture scores improved by 4.5 - 8.5% across all 20 hospitals, but only reached significance in one domain, ‘non-punitive response to error‘ (39% positive response baseline, 47% positive response post-collaborative, p ⫽ 0.02). Conclusions: A complex process, such as patient deterioration, requires sufficient time and effort to achieve improved outcomes and create a deeply embedded culture of patient safety. For quality improvement projects of large magnitude, use of a collaborative model can facilitate goal acheivement.

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ASSOCIATION BETWEEN NUCLEATED RED BLOOD CELLS AND IN-HOSPITAL MORTALITY IN PATIENTS WITH SURGICAL SEPSIS

UNPLANNED DEVICE REMOVAL IN THE PICU: QUIT BLAMING THE FLOAT NURSE

Sapana Desai, Jeffrey Hall, Frederick Moore, Krista Turner, Laura Moore, The Methodist Hospital

Jean Christopher, Christine Perebzak, Akron Children’s Hospital, Michael Forbes, Children’s Hospital Medical Center of Akron, Michael Bigham, Akron Children’s Hospital

Introduction: Nucleated red blood cells (NRBCs) are present in certain nononcological disease states and are associated with a poor prognosis. The purpose of this study is to evaluate NRBCs as an early prognostic marker for mortality in patients with surgical sepsis. Hypothesis: Surgical sepsis patients with detectable NRBCs are at increased risk of mortality compared to those with non-detectable NRBCs. Methods: This IRB approved retrospective evaluation of prospectively collected data was conducted in the surgical intensive care unit (SICU) at an academic tertiary care center from 9/07 to 12/09. Adult SICU patients managed using our sepsis computerized decision support protocol were eligible. NRBC values were collected at any time point during SICU admission, with a subset (iNRBC) gathered at sepsis protocol initiation. NRBC values above 0/uL were defined as positive [⫹], whereas non-detectable NRBCs were negative [-]. Statistical analyses were performed using chi-squared tests with an alpha value set at 0.05. Results: At sepsis protocol initiation, 48/275 patients (17.5%) were iNRBC[⫹] and 227/275 (82.5%) were iNRBC[-]. Mortality was greater in patients that were iNRBC[⫹] compared to iNRBC[-] for both ICU (25% vs. 11.9%, p⫽0.018) and hospital stay (31.3% vs. 14.5%, p⫽0.006). When all NRBC values are considered, 116/275 patients (42.2%) were NRBC[⫹] and 159/275 (57.8%) were NRBC[-]. Mortality was greater in patients that were NRBC[⫹] compared to NRBC[-] for both ICU (22.4% vs. 8.2%, p⫽0.001) and hospital stay (28.4% vs. 9.4%, p⬍0.001). Hospital and ICU mortality increased with increasing NRBC concentration. For patients with severe sepsis (n⫽153), NRBC positivity at any time point was associated with increased ICU mortality (20% versus 3.2%, p⫽0.001). Significant mortality differences did not occur between NRBC[⫹] and NRBC[-] patients classified with sepsis (n⫽48) or septic shock (n⫽74). Conclusions: Surgical sepsis patients with detectable NRBCs are at increased risk of ICU and hospital mortality compared to those with nondetectable NRBCs. The mortality difference is underscored in surgical patients with severe sepsis. This study suggests NRBCs may be a biomarker of outcomes in patients with surgical sepsis.

Introduction: The Institute of Medicine has described 6 characteristics of highquality healthcare systems, one of which is safety. Unplanned device removal (UDR) has been identified as safety risk due to the critical nature of many devices. In 2009 we recognized an increase in UDR rates. In response, we sought to identify whether a relationship exists between the incidence of UDRs and the nurse shift worked, nurse position (dedicated PICU nurse or float nurse), or nurse:patient staffing ratios. Hypothesis: We hypothesized that night shift, float nurse assignment, and 1:2 (nurse:patient) staffing ratio are risk factors for UDR in the PICU. Methods: The setting of this improvement project was a med/surg PICU with 1300 annual admissions. The improvement data tracking period was 9 months (6/09-3/10). A PICU Critical Incident Review team was created to 1)study reasons for an increase in UDR, 2)collect detailed data for UDRs, 3)review incidents in real time with nursing/medical staff, 4)and meet monthly to review events for the purpose of identifying/implementing improvement strategies. Results: There were 38 UDRs identified during the tracking period. Central venous catheter unplanned removal rates were highest (8.7/1000 device days), followed by tracheostomy UDRs (8.0/1000), feeding tube (7.0/1000), arterial line (4.2/1000), ETT (1.6/1000), and PICC line (1.5/1000). UDR rates were equally distributed between day and night shifts (50% day, 50% night) and more device removals were noted in higher acuity nurse:patient staffing ratios (1:1, p⬍0.001). Float nurses trended toward fewer device removals per hours worked than PICU nurses (0.17 vs 0.24 UDRs per 1000 hours worked). Conclusions: Unplanned device removals are common in our PICU cohort but we did not identify a relationship between increases in UDR and night shift or float nurse staffing. As such, quality improvement efforts to reduce rates of UDRs in the PICU should not focus on these issues. 1:1 (nurse:patient) staffing ratios in this PICU were associated with increased UDRs when compared with lower acuity 1:2 staffing. PICU Critical Incident Review teams provide valuable information surrounding UDRs and allow for longitudinal tracking to direct improvement efforts.


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DO DAILY GOAL SHEETS STILL SERVE AS AN EFFECTIVE COMMUNICATION TOOL IN THE ICU?

PREDICTORS OF COSTS IN THE PEDIATRIC INTENSIVE CARE UNIT: RELATIONSHIP TO THE PEDIATRIC RISK OF MORTALITY SCORE

Sandra Swoboda, Johns Hopkins Medical Institutions, Dauryne Shaffer, Samantha Young, Jennifer Simmons, Johns Hopkins Hospital, Pamela Lipsett, Johns Hopkins Medical Institutions Introduction: The daily goal sheet (DGS) is a communication tool to ensure all members of the healthcare team (HCW) understand patient goals and plans of care. Early studies indicated HCW communication and patient specific goals of care were improved with DGS. They have been in place in our surgical ICU’s since 2003. Hypothesis: Providers and prescribers may differ in their attitudes about DGS and this difference may influence the perceived or actual utilization of DGS. Methods: Randomly over a 4 week period in 2 surgical ICU’s, DGS were collected and surveys were prospectively given to HCW eliciting their attitudes about the DGS. HCW included providers (RN’s grouped into years of experience) and prescribers. Data was analyzed by unit, within and between groups using Fishers exact. Results: 115 surveys were completed (84 providers, 31 prescribers). 95% of all HCW understood patient daily goals at the end of rounds. RN’s were more likely to refer to the DGS at least once a day vs. prescribers (60% vs. 37%, p⫽0.01). Only 44% of RN’s felt the DGS was helpful in communicating goals of patient care with the ICU team vs. 73% of prescribers, p⫽0.01. Neither providers (27%) nor prescribers (42%) felt the tool useful in communication of goals to the primary surgical team, p ⫽0.17. RN years of experience were divided into 3 categories (⬍1 year (N ⫽7), 1-5 years (N⫽31), ⬎6 years (N⫽45)). RN’s with ⬍1 year and ⬎6 years of experience found the DGS helpful in communicating daily goals with ICU staff compared to RN’s with 1-5 years experience (p ⫽0.01). Similarly, the least and most years of experienced RNs found the DGS helpful in communication to the primary surgical service vs. RN’s with 1-5 years (38% vs. 6%) p⫽0.01. Conclusions: While the DGS serves to determine and map the plan of care for the day; HCW infrequently refer to it during their shift (37% to 60%). Touted as a tool for communication of patient goals, there is a discrepancy by users of its communication value. Years of RN experience impact its utilization with the least and most experienced RN’s finding benefit. The impact of RN experience and the utility of the DGS as a means to communicate patient plan of care is an area of continued research.


Benson Hsu, Thomas Brazelton, University of Wisconsin - American Family Children’s Hospital Introduction: US healthcare expenditure is rapidly increasing with end of life costs representing 10-12% of the total US healthcare budget and up to 27% of the Medicare budget. However, the relationship between spending and end of life care has not been shown in the pediatric population. Hypothesis: The Pediatric Risk of Mortality (PRISM III) score has a positive predictive relationship to total hospital costs and physician charges. Methods: Examined all patients hospitalized in an academic pediatric critical care unit between 01/01/09 and 12/31/09. PRISM III scores, clinical and demographic data from an internal division database were cross-referenced with cost and charge data from hospital and physician group decision support databases. Cost and charge data underwent log transformation for the regression analysis. Results: 850 patients were identified with 48 patients (5.6%) excluded due to lack of financial data. Those excluded differed statistically in PRISM III scores (0.94 versus 3.18) and length of stay (LOS) (1.5 versus 6.1) using the Mann-Whitney Test. Of the study population, 52.6% were male and 45.0% were medical. The average PRISM III score, age, and LOS were 3.18, 8.0, and 6.1. Total and average daily physician charges and hospital costs were $52,283.43 and $9,647.89. Univariate regression analysis against total physician charges and hospital costs showed statistically significant coefficients for PRISM III scores, age, LOS, surgical patients, and death of 0.04, -0.01, 0.06, 0.56, and 1.22. The adjusted r2 values ranged from 0.007 (age) to 0.364 (LOS). Multivariate regression analysis against total physician charges and hospital costs showed statistically significant coefficients for PRISM III scores, age, LOS, male, and surgical patients of 0.04, -0.01, 0.06, -0.12, and 0.81. The adjusted r2 value was 0.508. Conclusions: PRISM III scores have a weak relationship to total physician charges and hospital costs in both the univariate and multivariate analysis. The goodness of fit was poor in the univariate regression but improved somewhat with the multivariate regression predicting slightly more than of 50% of total physician charges and hospital costs.


557

PREDICTORS OF FUNCTIONAL OUTCOME AFTER LARGE HEMISPHERIC INFARCTIONS TREATED WITH HYPEROSMOLAR HYPOTHERMIC NORMOGLYCEMIA (H2N)

EXTERNAL VALIDATION OF THE ARDS NETWORK SHORTTERM MORTALITY PREDICTION MODEL FOR ACUTE LUNG INJURY (ALI)

Katja Wartenberg, Martin-Luther-University Halle-Wittenberg, Christoph Reichelt, Technical University of Dresden, Stephan Mayer, Neurological Institute of New York

Abdulla Damluji, Pennsylvania State University School of Medicine, Elizabeth Colantuoni, Pedro Mendez-Tellez, Jonathan Sevransky, Eddy Fan, Johns Hopkins University School of Medicine, Carl Shanholtz, University of Maryland School of Medicine, Margaret Wojnar, Pennsylvania State University School of Medicine, Peter Pronovost, Dale Needham, Johns Hopkins University School of Medicine

Introduction: Large hemispheric infarctions carry a mortality rate of 40 – 80% and lead to moderate-severe disability in 60-80% of the surviving patients. Potential prognostic factors to determine outcome in these patients are poorly defined. Hypothesis: Independent predictors of poor functional outcome assist to determine prognosis after large hemispheric infarction. Methods: Patients with large hemispheric infarctions were treated with the combination of insulin infusion (target glucose 4.6-6.1 mmol/L), mild hypothermia (33-35°C), and hypertonic saline (goal sodium 150-155 mmol/L) within 72 hours of symptom onset and were prospectively enrolled in the Large Hemispheric Infarction Outcome Project between August 2006 and March 2009. We analyzed impact of demographic, clinical, radiological variables and hospital complications on outcome using forward stepwise multiple logistic regression analysis. Poor functional outcome, assessed at 3 and 12 months, was defined as modified Rankin Scale (mRS) of 4 to 6. Results: Of the 50 patients enrolled 22 had right-sided infarctions and median age was 64 (range 36-83) years. Baseline NIHSS was 18.3⫾5.7. At 3 months, 28 patients had died (56%); 17 had a mRS of 4 and 5 (34%). In the univariate analysis, advanced age (63.9⫾1.9 vs 46.0⫾3.6 years), infarction caused by atrial fibrillation (51 vs 0%), and uncal herniation (55 vs 13%) were more common among the patients with poor outcome, whereas rebound fever (43 vs 88%), tracheobronchitis (53 vs 100%), and hemicraniectomy (31 vs 80%) occurred less often (p⬍0.05). Older age was the only significant predictor of poor functional outcome at 90 days (1.14 (1.02-1.27), P⫽0.019) and 12 months (1.12 (1.03-1.21), P⫽0.006). Conclusions: Advanced age is independently associated with poor functional outcome at 3 and 12 months after large hemispheric infarction. Complications did not affect long term outcome, and hemicraniectomy did not have a protective effect in our patient population. Prognostication and management decisions should include the age of the patient. Long term studies evaluating the quality of life after large hemispheric stroke are needed.

Introduction: A recent study (1) used data from two ARDS Network (ARDSNet) trials (2, 3) to develop and internally validate a simple multivariable prediction model for inhospital mortality of non-trauma, Acute Lung Injury (ALI) patients. Hypothesis: Our purpose was to evaluate the external validity of this prediction model. Methods: Data for external validation were obtained from a prospective cohort study of ALI patients from 13 ICUs at four teaching hospitals in Baltimore, Maryland. The primary outcome was inhospital mortality. Results: Of the 508 non-trauma, ALI patients eligible for this analysis, 234 (46%) died in-hospital. Discrimination of the prediction model, evaluated by the area under the receiver operator characteristics curve (AUC), was 0.67 using the external validation dataset vs. 0.68 using the ARDSNet internal validation dataset (3). In evaluating calibration of the prediction model, predicted vs. observed mortality using the external validation dataset was similar for both low risk (prediction model score ⫽ 0) and high risk (score ⫽ 3 or 4⫹) patient strata. However, for intermediate risk (score ⫽1 or 2) patients, observed in-hospital mortality was substantially higher than predicted mortality (25.3% vs. 16.5% and 40.6% vs. 31.0% for score ⫽ 1 and 2, respectively). Sensitivity analyses limiting our external validation data set to only those patients meeting the more restrictive ARDSNet trial eligibility criteria and to those who received mechanical ventilation in compliance with the ARDSNet ventilation protocol did not substantially change the model’s discrimination or calibration. Conclusions: Evaluation of the ARDSNet mortality prediction model using an external ALI patient cohort demonstrated similar discrimination properties, but substantial differences in observed vs. predicted mortality among intermediate risk ALI patients. Further external validation and/or model refinement may be beneficial before use of the mortality prediction model outside of ARDSNet trials. References: 1. Crit Care Med 2009;37(6):1913-1920.2. N Engl J Med 2000;342(18): 1301-1308.3. N Engl J Med 2004;351(4):327-336.

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IMPACT OF HOSPITALISTS AND A RAPID RESPONSE TEAM ON ICU READMISSIONS

ANTITHROMBIN III DEFICIENCY IN PATIENTS WITH SEVERE BURNS

Sinoj John, Dartmouth-Hitchcock Medical Center, Howard Corwin, Cynthia Robison, Donna Houston, Stephen Surgenor, Dartmouth Hitchcock Medical Center

JOHN CAMACHO OVIEDO, Hospital Universitario La Paz

Introduction: Approximately ten percent of patients who survive intensive care are readmitted to the intensive care unit (ICU) during the same hospitalization. These ICU readmissions are associated with significant morbidity and mortality. We compared the impact of a hospitalist program and a rapid response team on ICU readmissions. Hypothesis: Implementation of strategies to identify high risk ICU discharges will improve outcome of ICU readmissions. Methods: This was a retrospective observational study of all patients admitted to the medical surgical ICU at Dartmouth-Hitchcock Medical Center from 07/03 to 06/08. Over the study period, two interventions were initiated: a hospitalist program (2005) and a rapid response team (2006). ICU readmission rate, mortality, and length of stay before and after each intervention were compared. Results: The patient demographics, admission diagnosis, admission source and APACHE II scores were comparable between all time periods. Total readmission rate prior to and following the initiation of a hospitalist service or a rapid response team were not significantly different (11.1% versus 10.3% versus 12.5%, p ⫽ 0.26). On the other hand, ICU readmissions within 48 hours of discharge increased significantly after the implementation of a rapid response team (2.7% versus 3.8% versus 5.2%, p ⫽ 0.002). There was no significant difference in mortality with the rapid response team (27% versus 25%, p ⫽ 0.86) however the hospital length of stay for ICU readmissions was significantly reduced (50 ⫹ 40 days to 42 ⫹ 36 days, p ⫽ 0.02).Conclusions: Implementation of a rapid response team resulted in an increase in early (⬍ 48 hours) readmission to the ICU. While there was no reduction in readmission mortality, there was a significant reduction in hospital length of stay with the rapid response team. The initiation of a hospitalist program had no impact on ICU readmissions or outcome.

Introduction: Antithrombin III (AT) is an endogenous anticoagulant with antiinflammatory properties. Previous studies describe AT deficiency (plasma levels of AT ⬍70%) in 50% of patients with severe burns. Hypothesis: To evaluate the incidence of AT deficiency and determine its relationship with age, sex ABSI score, markers of inflammation, Mechanical Ventilation (MV), LOS in the ICU and multiorgan failure (SOFA). Methods: We performed a cross-sectional study of the AT levels in critical burn patients from January 2009 to July 2010. The AT deficiency and the quantitative variables was analyzed with the U Mann-Whitney and the Student’s t test and the qualitative variables with Chi-Square and the Fisher‘s exact test. A p-value ⬍.05 was considered statistically significant. Results: A total of 94 patients were included. AT deficiency was observed in 29% of patients, at base-line or within the first 15 days of admission. The age was 47⫾19 years,72% were male, the mean ABSI score was 6 and the total body surface burn was 19⫾14%. Inhalation was present in a 17% of patient and 9% had associated trauma. A 44% developed sepsis and 47% required MV, median 11 days (range 4-26). The median LOS in ICU was 13 days (range 7-26). The ICU mortality was 13%. Analyzing the groups with/without AT deficiency, we found an inverse relationship between the levels of AT with the levels of CRP (158⫾72 mg/L vs. 111⫾72 mg/L, r⫽-0.462, p⫽0.002) and the ABSI score (7⫾2 vs. 5⫾2, r⫽0.448, p⫽0.001). We also found the AT levels to be an independent predictor of the need and duration of MV (70 vs. 37%, 23 vs. 13 days, p⫽0.006), sepsis (70 vs. 33%, p⫽0.001) and mortality (26 vs. 13%, p⫽0.035). Low AT levels are associated with more severe burns, as observed with the inverse relationship of initial AT and SOFA (SOFA at 24h⫽ 4⫾2 vs. 2⫾2, s⫽-0.423, p⫽0.002) as well as on follow (SOFA at 7 day⫽ 5⫾2 vs. 1⫾2, s⫽-0.511, p⫽0.002). Conclusions: Severe burn is associated with AT deficiency and this correlates with increases in inflammatory markers like CRP. Low AT levels were found in the most critical ill patients (higher ABSI and SOFA) and are a predictor of need of MV, sepsis and mortality.


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LESION LOCALIZATION IN PAROXYSMAL SYMPATHETIC HYPERACTIVITY

A PILOT STUDY OF THE EPIDEMIOLOGY AND ASSOCIATIONS OF PULSE PRESSURE VARIATION IN CARDIAC SURGERY PATIENTS

Holly Hinson, Josh Duckworth, Robert Kowalksi, Hans Puttgen, Wendy Ziai, Johns Hopkins Hospital Introduction: Current theory regarding the etiology of Paroxysmal Sympathetic Hyperactivity(PSH) following Traumatic Brain Injury(TBI) describes dysregulation of the autonomic nervous system due to disconnection of cortical centers. While the brain stem controls sympathetic outflow, right hemisphere strokes have been associated with unchecked sympathetic activity. The purpose of this study was to examine the anatomic location of lesions encountered in TBI patients with PSH. Hypothesis: We hypothesized that TBI patients withPSH would have lesions along tracts connecting the right cortical hemisphere to the brain stem. Methods: We cross-referenced a retrospective query of a University Hospital Trauma Registry (2001-2008) to identify TBI patients with Glascow Coma Scores(GCS) of ⱕ12, with pharmacy databases of patients receiving bromocriptine or propranolol (treatments for PSH) to identify patients who met criteria for dysautonomia. Patients meeting physiologic criteria for PSH were matched 1:1 by admission GCS, age and gender to TBI patients without PSH. Radiographic findings on brain CT or MRI scans were compared between cases and controls. Results: Sixteen patients metcriteria for dysautonomia (cases). Cases and controls were similar in age(mean⫾SEM) (32⫾2.1 years, P⫽0.65), gender (P⫽0.63) and race(P⫽0.77). Imaging severity as reflected by the Rotterdam and Marshall Scores were significantly worse in the cases (P⫽0.001, P⫽0.003). All PSH patients exhibited structural brain injury vs. 10 controls (P⫽0.007). The number with brain stem injury was not statistically different (7 vs. 3, P⫽0.13). Right hemispheric lesions were significantly more common in the PSH group (15 vs. 6, P⫽0.001). There was a trend toward worse outcome in the PSH group, with 44% dead or vegetative at hospital discharge, vs. 25% in the non-PSH group (P⫽0.08). Conclusions: Our audit of routine neuroimaging data suggests that right hemispheric lesions may be more common inpatients who develop PSH after TBI. Consistent with previous work, our cohort of PSH patients had worse outcomes than those without PSH. Prospective sophisticated imaging analysis is needed to better define the anatomic localization and pathophysiology of this condition.

Inbyung Kim, Emergency Department, Rinaldo Bellomo, Austin Hospital Introduction: Pulse pressure variation (PPV) is an accepted measure of intravascular filling. It can now be estimated automatically. However, there is limited knowledge of the epidemiology and associations of such estimates in cardiac surgery patients. Hypothesis: We aimed to assess the incidence of PPV values in the likely fluid responsiveness range and their association with other relevant parameters in patients immediately after cardiac surgery. We hypothesized that a PPV value in the likely fluid-responsive range would be relatively common and that such value would show logical correlations with relevant hemodynamic, fluid-related and mechanical ventilation-dependent variables. Methods: We conducted a pilot prospective observational study of the epidemiology and associations of automatically estimated PPV in 30 cardiac surgery patients admitted to the intensive care unit of a university hospital. Results: We collected automated monitor-estimated PPV values every 15 min during mandatory ventilation in patients after cardiac surgery. Clinicians were not informed of the PPV value and did not use it for patient management. Simultaneously, we collected data on all relevant hemodynamic values, fluid balance (FB) hourly, tidal volume (TV) and peak airway pressure. We studied 30 patients for a total 205 measurements. The PPV value was ⬎ 13% in 38% of measurements and the average duration of this physiological state was 38 minute per patient. A higher PPV value correlated with negative fluid balance (p⬍0.001), lower pulmonary atrial pressure (PAPmean) (p⫽0.018), lower cardiac index (CI) (p⫽0.013), higher peak airway pressure (p⬍0.0001) and higher TV (p⬍0.0001). Conclusions: In a tertiary ICU, after cardiac surgery, an automated PPV greater than 13% was present in more than one third of patients and showed logically correlation with other hemodynamic values. These findings support the value of automated PPV measurements.

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VALUE OF PREVALENT CLINICAL GRADING SCALES FOR PREDICTING OUTCOME AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

ACUTE LUNG INJURY IN COMBAT CASUALTIES RECEIVING MASSIVE BLOOD TRANSFUSIONS

Sachin Agarwal, Matthew Vibbert, Luis Fernandez, Michael Schmidt, Jan Claassen, Stephan Mayer, Kiwon Lee, E. Sander Connolly, Neeraj Badjatia, Columbia University Medical Center Introduction: Several admission clinical rating scales delineating the severity of injury after subarachnoid hemorrhage (SAH) have been proposed; however, it is not clear whether any one scale is superior in predicting outcome after SAH. No SAH grading scale has approached universal acceptance. Hypothesis: There are no differences in the ability of three commonly used scales, Glasgow Coma Scale (GCS), Hunt and Hess Scale (H&H), and World Federation of Neurological Surgeons scale (WFNS) on admission after SAH to predict short and long term outcomes, as defined by death or the modified Rankin Scale (mRS) score. Methods: Patients enrolled in a prospective SAH outcomes project between August 1996 and July 2009 were analyzed. The mortality at discharge, mRS at 14 days, 3 months, and 12 months were the primary outcome measures. Poor outcome was defined as a mRS ⬎⫽ 4. Logistic regression and Receiver operating characteristic (ROC) curves were used to assess predictive accuracy for the outcomes. The extent to which the grading scales assigned the same grade to an individual patient i.e. the level of agreement between the scales, was assessed using a kappa statistic. Results: There were 1109 SAH patients (age: 53.5⫹/⫺ 14.2 years, 77% women) admitted during the study period. The median Hunt Hess score was 3 (IQR: 1-3), median GCS 15 (IQR: 10-15), and median WFNS score was 1 (IQR: 1-4). There was no difference in the ROC curves among the grading scales for predicting poor outcome (H& H: 0.79; GCS: 0.79; WFNS: 0.78). Each scale independently predicted mortality at discharge and poor outcome (mRS ⬎⫽ 4) at 14 days, 3 months, and 12 months (P ⬍ 0.001) after adjusting for age, sex, race, aneurysm size, Modified fisher scale, and acute physiological score. The kappa statistic was 0.48. Conclusions: There was poor overall agreement between the three grading scales. There was no significant difference in the ability of each scale administered at the time of admission to predict poor outcome at 14 days, 3 months and 12 months after SAH.


Chee Chan, Andrew Shorr, Washington Hospital Center, Jeremy Perkins, Walter Reed Army Institute of Researh Military Casualty Research Introduction: Trauma patients often require massive transfusion (MT) and are at risk for Acute Lung Injury (ALI). It is unclear if utilization of Warm Fresh Whole Blood (WFWB), rather than blood component therapy, alters rates of ALI in MT. Hypothesis: We hypothesized that WFWB is associated with lower rates of ALI in MT. Methods: We retrospectively analyzed rates of ALI in patients undergoing MT while at a Combat Support Hospital in Iraq (Jan 2004-Dec 2006). We studied subjects receiving ⱖ 10 u of pRBCs over a 24 hr period. ALI was defined based on discharge ICD-9 codes. We compared patients with ALI to those not developing ALI with respect to demographics, trauma type, severity of illness (SOI), crystalloid volume given, and exposure to WFWB and various blood components. We employed logistic regression to identify variables independently associated with ALI. Results: The cohort included 591 subjects (mean age: 28⫹/⫺8.1 yrs; male: 96.7%; 92.6% penetrating trauma) and the mean Trauma Injury Severity Score was 2.2⫹/⫺2.2. We observed ALI in 11.2% and 34.4% of these individuals had been given WFWB. After adjusting for type of trauma, SOI, volume of crystalloid administered, and other covariates, WFWB remained independently associated with ALI (AOR:1.06; 95%CI:1.00-1.13). Despite the nexus between WFWB and ALI, nearly 2/3rds of persons with ALI had never received WFWB. Hence, we examined independent factors associated with utilization of WFWB. We determined that SOI (AOR:1.18; 95%CI:1.021.35), volume of crystalloid for resuscitation (AOR:1.12; 95%CI:1.06-1.18), use of recombinant factor VIIa (AOR:1.94; 95%CI:1.06-3.57), and US Citizenship (vs other national) [AOR:3.06; 95%CI:1.74-5.37] correlated with WFWB treatment. Conclusions: ALI is uncommon following MT; patients treated with WFWB are more severely ill than those given only component therapy. Despite an independent association between WFWB and ALI, that nearly 2/3rds of patients with ALI never received WFWB indicates that WFWB is neither a necessary nor sufficient casual step in the evolution of ALI following MT. WFWB may be associated with increased risk of ALI, but this is confounded by increased injury and crystalloid use in patients receiving WFWB.

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ANOTHER BURDEN FOR THE CRITICALLY ILL WITH SEVERE SEPSIS: HEALTHCARE COSTS AND MORBIDITY

LIMITING BLOOD LOSS FROM ROUTINE PHLEBOTOMY PRACTICES IN THE ICU

Gagan Kumar, Amit Taneja, Jayshil Patel, Puneet Sood, Thomas Kaleekal, Sandeep Markan, Nilay Kumar, Medical College of Wisconsin, Rumi Ahmed Khan, Orlando Regional Medical Center, Rahul Nanchal, Medical College of Wisconsin

Kathleen To, Washington University School of Medicine, Carrie Sona, Marilyn Schallom, Lee Skrupky, Jessica Bowles, Barnes-Jewish Hospital, Steve Jarman, Robert Southard, Bradley Freeman, Douglas Schuerer, John Mazuski, Washington University School of Medicine

Introduction: Severe sepsis has intense demands on the physicians, equipments and facilities which subsequently places a significant burden on healthcare resources. The loss of work hours and morbidity after the resolution of severe sepsis is another facet of economic burden and challenges on the limited available resources. The goal of our study was to examine the healthcare costs of severe sepsis over time using nationally representative data. Hypothesis: With the improvements in management of severe sepsis, though the mortality and lengths of stay have improved, the total charges and transfers to long term care facilities have increased. Methods: The Nationwide Inpatient Sample (NIS) database from 2000 to 2008 was used to examine the mortality, total charges, length of stay (LOS) and dispositions of patients admitted with diagnosis of severe sepsis . ICD-9-CM codes in adults aged 18 and above as described in literature were used to identify severe sepsis. Survey commands in STATA were used to find national estimates. Chi-square and t-tests were used to compare categorical and continuous variables between the 2 groups, respectively. Results: A total of 5,247,400 estimated hospital admissions were identified with severe sepsis during 2000 to 2008 period in United States. While the mortality decreased over time from 37.5% in 2000 to 26.5% in 2008, the discharge disposition to home also proportionally decreased by a similar number - from 36.4% in 2000 to 27.1% in 2008. Survivors had significantly increased rates of discharges to long term care facility or with home health care.After adjusting for inflation since 2000 total charges in 2008 were $90,648 as compared to $70,336 in 2000. The LOS decreased from 16.1 days in 2000 to 14.1 days in 2008. The daily total charges increased from $4370 to $6430 in the same period. Conclusions: We conclude that while the mortality rates and LOS in severe sepsis have improved, the total charges have gone up by $20,000. Significantly higher proportions of survivors are being discharged to outside facilities and with home health care thereby increasing costs even further. Increased attention to this phenomenon is warranted.

Introduction: Anemia and blood transfusions are associated with increased morbidity and mortality. In the critically ill patient population with prolonged ICU length of stay, frequent phlebotomy for laboratory studies may be a significant contributor to iatrogenic anemia. Implementation of a standard protocol for ordering and obtaining laboratory tests would therefore decrease phlebotomyrelated blood loss (PEBL) and blood transfusions. Methods: A practice-improvement protocol designed to reduce PEBL was implemented in a tertiary care academic Surgical ICU in Jan, 2010. Four areas were targeted: 1) Minimization of daily laboratory tests; 2) Minimization of blood wasted by nursing staff when blood was drawn from indwelling catheters; 3) Temporal clustering of laboratory studies; and 4) Increased use of whole blood point of care studies. From Sept 1-Dec 31, 2009, and from Feb 1-June 30, 2010 (Periods 1 and 2, respectively, before and after protocol implementation) patients admitted to the SICU whose length of stay were ⱖ5 days were selected for analysis. PEBL was estimated from the number of laboratory tests obtained per patient per day, and the amount of blood required for these tests. For a 30-day period in each group, the amount of blood drawn but not used for laboratory testing was collected separately and quantified. Blood transfusions were tallied; transfusions for active hemorrhage were excluded. Results: Patients in Period 1 (n⫽118) and Period 2 (n⫽105) were similar with regard to age, modified APACHE II, and reasons for admission. There was no difference in the units of blood transfused for anemia (1.26 ⫾ 2.1 units vs. 1.37 ⫾ 2.0 units, P⫽0.512), nor in the daily total amount of blood utilized for testing (16.71 ⫾ 5.34 ml vs. 17.57 ⫾ 7.40ml, P⫽0.721) in Periods 1 and 2. The amount of wasted blood, however, did significantly decrease in Period 2 with the intervention (11.9 ⫾ 3.9 ml vs. 6.2 ⫾ 2.0 ml, P⬍0.0001). Conclusions: Implementation of this protocol resulted in only a small decrease in PEBL, with the major effect observed in nursing procedures. While potentially valuable for improving resource utilization, physician compliance would be needed to significantly impact unnecessary PEBL.



567

NOISE POLLUTION LEVELS IN THE PEDIATRIC INTENSIVE CARE UNIT

DEATHS IN THE PICU: DOES TIME TO DEATH MATTER?

Bree Kramer, Women & Children’s Hosp of Buffalo, Christopher Heard, Children’s Hospital of Buffalo

Introduction: PICU mortality rates, clinical and PICU parameters associated with risk, and predictive models of mortality are well-defined. What is unknown is whether those who die quickly have unique characteristics for whom therapies may be more or less effective. Hypothesis: A substantial portion of deaths occur quickly, and these patients are a unique population which can be described by clinical and systemic factors. Methods: 5034 consecutive patient deaths from 1/1/2006-12/31/2008 from the VPS, LLC national database. Patients were dichotomized as early or late deaths. Descriptive statistics compared patient and hospital system variables for significant associations with early death which became candidate variables for modeling. Due to significant covariance, logistic regression was not feasible. Classification and Regression tree analysis (CART) identified strata of patients explaining early death for which adjusted odds ratios were calculated; Cox regression modeled time to death. Results: 31% (the first tertile) of patients died within the first 36 hours and were defined as early deaths. Early death was associated with younger age, race, patient diagnosis, surgical procedures, and systems issues in unadjusted analysis. Adjusted odds ratios revealed patient characteristics (race, patient origin and operative status), lack of clinical interventions (ventilation, renal replacement therapy), CPR, and systemic issues (non-teaching status) as significantly associated with early death. Cox proportional hazards model identified similar predictors as well as night coverage and patient diagnosis Conclusions: Patients who die early in their PICU course are significantly different from those who die later, representing a unique cohort of patients. These findings may inform timing of enrollment in clinical trials and interpretation of outcomes of specific interventions.

Introduction: There are many sources of noise in a PICU, patients and staff may experience both short and long term adverse effects resulting from exposure to excess noise levels. Hypothesis: The aim of the study is to assess noise levels over 24 hrs in the PICU and evaluate both the families’ and nurses’ opinions of noise level at the bedside. Methods: After IRB approval and informed consent the noise levels at a bedside were recorded using a NoisePro® DLX noise logger. After the NoisePRO® was calibrated, the microphone was placed 1m from the child’s head. The noise level was averaged each minute and a peak noise level occurring each minute if ⬎100dB was recorded. Patient demographics and bed location were recorded. A parent questionnaire regarding time spent at the bedside and their evaluation of noisiness of the room was completed. Both the day and night bedside nurse completed a questionnaire about their view of the noise level. For each patient, the maximum, minimum and average decibel levels were calculated. Results: We have recruited 40 patients in the study. The average patient age was 6 yrs (range: 1 month to 41 years). 49% of the patients were male. The average maximum dB for all patients was 83 (range: 74.1 to 90.2). The average minimum dB for all patients was 51.8 (range 42.5 to 61.4). The average daily bedside noise level for all patients was 63.3dB (range: 58 to 68). The average % time where the noise level was ⬎70dB was 3.7% (range: 0.2 to 14.4%). 6 patients experienced no time with a noise level ⬎80dB. For the other 34 patients, the average percent of time that the noise level was ⬎80dB was 0.2% (range: 0 to 1.21%). In addition, all patients experienced an average of 115 minutes/day (range 13 to 393 minutes) where the peak noise level for any minute during 24 hr period was ⬎100dB (average peak 134.7dB, range: 113.5 to 145.1). Our parents reported an average noise level of 3.8 (using a scale of 0 to 10, 0 being no noise). Our nursing staff reported an average noise level of 4.4. Conclusions: The majority of patients in our PICU experience levels of noise at some time greater than the recommended 80dB. Plus, most of our patients experience peak noise levels in excess of 100dB during their PICU stay.

Amanda Levin, Deli Wang, Denise Goodman, Children’s Memorial Hospital

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TRENDS IN UTILIZATION USE OF INVASIVE AND NON-INVASIVE MECHANICAL VENTILATION IN ASTHMA

THE BURDEN OF POTENTIALLY AND ACTUALLY INAPPROPRIATE MEDICATION IN ELDERLY ICU SURVIVORS

Gagan Kumar, Amit Taneja, Jayshil Patel, Nilay Kumar, Sandeep Markan, Thomas Kaleekal, Medical College of Wisconsin, Rumi Ahmed Khan, Orlando Regional Medical Center, Rahul Nanchal, Medical College of Wisconsin

Alessandro Morandi, Eduard Vasilevskis, Timothy Girard, Laurence Solberg, Erin Neal, Vanderbilt University School of Medicine, Renee Torres, Vanderbilt University, Donna Fick, Pennsylvania State University, E Ely, Sunil Kripalani, Pratik Pandharipande, Vanderbilt University School of Medicine

Introduction: The role of non invasive ventilation (NIMV) in acute exacerbations of asthma is controversial. Smaller studies and a recent metanalysis failed to show any benefits of NIMV in these patients. The use of NIMV is increasing worldwide especially in exacerbations ofchronic obstructive pulmonary disease to prevent intubation. The nationwide trends of mechanical ventilation particularly NIMV for asthma are largely unknown. Hypothesis: Despite limited data, the use of NIMV in asthma is increasing while the use of invasive mechanical ventilation (IMV) is declining. Methods: Nationwide Inpatient Sample database from 2000 to 2007 was used to examine the trends of mechanical ventilation in asthma hospitalization in adults aged 18 and above. ICD-9-CM code 493.0 was used to identify primary asthma. We excluded patients with pneumonia, severe sepsis, COPD and ILD. Survey commands in STATA were used to estimate frequency of IMV and NIMV. Chi-square and t-tests were used to compare categorical and continuous variables between the two groups, respectively. ␣ was set at 0.05. Results: A total of 2,178,376 hospital admissions were identified with principal diagnosis of asthma in adults over 18 years of age during 2000 to 2007 period in United States. A total of 4880 (2.1%) patients underwent IMV in 2000. This number steadily decreased overtime such that by 2007, only 2692(1%) of asthmatics underwent IMV. However, the use of NIMV increased more than 5 times, from 0.4% in 2000 to 2.2% in 2007. All cause in hospital mortality for acute asthma did not change significantly from 2000 to 2007, however the proportion of patients undergoing IMV was significantly lower and accordingly their mortality was proportionately higher (7.4% in 2000 and 11.4% in 2007). Conclusions: We conclude that while the rates of NIMV in acute asthma are increasing, the rate of invasive mechanical ventilation are decreasing. The mortality has remained similar for patients undergoing NIMV but has proportionally increased for IMV.


Introduction: Elderly patients are often prescribed medications in the hospital that are considered potentially inappropriate medications (PIMs). It is unknown whether these PIMs are initiated in the ICU or if they are stopped or continued across transitions in care beyond the ICU. Furthermore, it is unclear if these PIMs are actually inappropriate medications (AIMs), given the patients’ underlying medical condition. Hypothesis: To describe PIMs and AIMs in elderly ICU survivors. Methods: This prospective cohort included ICU patients (age ⱖ60) who survived to discharge after septic/cardiogenic shock or respiratory failure. We collected patients’ home medications, actual medications administered while in the ICU and the ward (via our electronic medication administration record) and medications prescribed at ICU and hospital discharge. PIMs were identified using the validated 2003 Beer’s criteria. Additional PIMs were added based on recent medication safety literature. A hospitalist, geriatrician and clinical pharmacist evaluated whether discharge PIMs were also AIMs based on their indication, effectiveness, dosages and drug interactions. Results: We enrolled 120 patients, whose median age was 68 years (IQR, 66-74), and APACHE II was 27 (20-32). The proportion of patients receiving ⱖ 3 PIMs increased from 16% at preadmission to 38% at hospital discharge. Of the patients with at least one PIM at discharge (N ⫽ 104), 59% were considered to have at least one AIM. When analyzing medications, the total number of PIMs increased from 159 at preadmission to 253 at discharge. The median pre-admission PIMs was 1(0-2) versus 2 (1-3) at hospital discharge (p⬍0.001). Importantly, 49% of the discharge PIMs and 58% of discharge AIMs were initiated in the ICU. Conclusions: The prescription of potentially and actually inappropriate medications is an extremely common practice among the elderly that significantly increases after critical illness. Importantly, half of the potentially and actually inappropriate medications were newly initiated in the ICU, providing an opportunity to improve medication safety in survivors of critical illnesses.

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PROSPECTIVE INDEPENDENT VALIDATION OF IMPACT MODELING AS A PROGNOSTIC TOOL IN SEVERE TRAUMATIC BRAIN INJURY

EARLY INTEGRATION OF PALLIATIVE CARE IN CRITICAL CARE UNITS OFFERS TIMELY SUPPORT FOR PATIENTS AND REVEALS REGIONAL NETWORKING OPPORTUNITIES

Ava Puccio, David Panczykowski, Bobby Scruggs, David Okonkwo, University of Pittsburgh

Kelly Becker, Michael Trexler, Susan Hanna, Loraine Jenkins, Jeanette Meyer, Paul Lange, Sharon Curran, Borgess Health

Introduction: Clinical trials in traumatic brain injury (TBI) have been unsuccessful owing in large part to pathologic injury heterogeneity and insensitive outcome measurements. The International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic model has been purposed as a means of risk adjustment and mortality prediction for use in trial design and analysis. Hypothesis: Our hypothesis is the discriminitive ability of the IMPACT model in predicting 6-month functional outcome and mortality is equivalent to using prospectively collected data at a large, Level 1 center. Methods: Severe TBI patients ⱖ18 years of age admitted with a GCS ⱕ8 to our trauma center between July 1994 and May 2009 were included. Clinical data was prospectively collected and linked to 6-month functional outcome (GOS) and mortality. Discriminatory power of 3 versions of the IMPACT model (Core; Core⫹CT; Core⫹CT⫹lab) were assessed using multiple regression analyses and indicated by the area under the receiver operating characteristic curve (C statistic). Results: A total of 587 patients were available for analysis; the mean age was 37.8 ⫾17. The median 6-month GOS was 3 (IQR 3); 6-month mortality was 41%. The prognostic models were composed of age, motor score, and pupillary reactivity (core model), Marshall grade on head CT and secondary insults (core⫹CT), and laboratory values (core⫹CT⫹labs); all of these displayed good prediction ability for mortality and unfavorable outcome (Cmort⫽0.78, 0.83, 0.82; CGOS⫽0.76, 0.83, 0.79 respectively). Both Cmort and CGOS were significantly different between models (p⫽0.01 and 0.02, respectively). Conclusions: Prospective, independent validation supports the IMPACT prognostic model’s discrimination of patient 6-month functional status and of mortality after severe TBI. This model is an effectual instrument to assist TBI study design and analysis.

Introduction: Rising healthcare costs force hospitals to use rescources efficiently while supporting best practices. Early integration of palliative care (PC) in the intensive care unit (ICU) is a clinical practice guideline, regardless of prognosis. Hypothesis: The establishment of an interdisciplinary team (IDT) and defined PC consultation criteria will increase PC utilization and offer timely support for patients and their families. Methods: Concurrent and retrospective APACHE IV data were evaluated over 18 months, using APACHE methodology (diagnoses, comorbidities, treatments, length of stay, and APAHCE/APS scores). At weekly IDT meetings patients who met PC triggers (or whose families needed additional support) were discussed with palliative and ICU medical staff. Records of those seen by PC were evaluated for admission source, timing of consultation and outcomes. Results: From January 2009 through June 2010, 227 of 3037 total ICU patients (7%) received PC services in the ICU, and 90 (40%) of these were seen within 24hrs of admission. Sources were: Emergency Department (ED) 36%, regional hospitals 33%, medical floors 25%, OR 5%, other 1%. Nearly half (45%) referred from regional hospitals received a PC consult within 24hrs. Of the 494 ICU patients who died in the hospital, 130 (26%) of these patients were seen by PC while in critical care. Of the 305 patients who died in the ICU, 59 (19%) were seen by PC while in critical care. Of the 189 patients who died after transfer to medical floors, 71 (38%) were seen by PC in the ICU. Conclusions: The IDT and use of PC triggers facilitates PC consultations, providing timely support for patients and families. However, underutilization in ICU patients who ultimately died there suggests opportunities for earlier collaboration between critical care and PC. Referral patterns indicate a need for end-of-life education in the ED and at regional referral hospitals.

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VALIDATION OF A MODEL THAT USES ENHANCED ADMINISTRATIVE DATA TO PREDICT MORTALITY IN CRITICALLY ILL PATIENTS WITH SEPSIS

EXTENDED SHIFTS FOR ATTENDING PHYSICIANS IN THE PEDIATRIC, CARDIOVASCULAR, AND NEONATAL INTENSIVE CARE UNIT

Tara Lagu, Baystate Medical Center, Peter Lindenauer, Baystate Health, Brian Nathanson, OptiStatim, LLP, Penelope Pekow, Michael Rothberg, Baystate Health, Jay Steingrub, Thomas Higgins, Baystate Medical Center

Katri Typpo, University of Arizona College of Medicine, Hossein Tcharmtchi, P. Kelly, Baylor College of Medicine, Eric Thomas, University of Texas-Houston Medical School, Leticia Castillo, University of Texas Southwestern Medical Center, Hardeep Singh, Baylor College of Medicine

Introduction: Existing ICU risk adjustment models rely on physiologic measurements that require manual data collection and entry. A validated model that uses detailed administrative data to adjust for severity of illness among sepsis patients treated in the ICU would reduce the burden of data collection and permit severity adjustment even when physiologic measurements are not available. Hypothesis: A model using detailed treatment information will have similar discrimination as existing mortality prediction models such as APACHE, SAPS, and MPM. Methods: We previously developed a model to predict mortality in patients with sepsis using administrative and billing data from 166,931 patients treated at 309 hospitals between 2004-2006. The model incorporates information about patient age, sex, source and site of infection, comorbid conditions and receipt of vasopressors and mechanical ventilation during the first 2 hospital days. In the development cohort, the AUROC of the model was 0.78. To validate the model, we analyzed data from 300 adult sepsis patients who were enrolled in Project IMPACT at Baystate Medical Center between 2002-2009. Patients were included in the validation if they were admitted to the ICU by hospital day 2 and had valid APACHE II, MPM II, and SAPS scores recorded in the Project IMPACT Database. We used our model to calculate a predicted mortality for each patient and compared model performance by calculating AUROC for each model. Results: All models had acceptable discriminatory ability and the AUROC of all models were statistically similar (APACHE-II ⫽ 0.71, SAPS-II ⫽ 0.74, MPM-II ⫽ 0.69, administratively derived model ⫽ 0.69, p-value that the AUROCs are equal ⫽ 0.35). Conclusions: A model using detailed administrative data has similar discriminatory ability as existing severity scores based on physiologic measures derived from chart abstraction. This model may be a useful tool for severity adjustment when conducting large epidemiologic and outcomes studies in sepsis where richer clinical information is not available.

Introduction: Attending physicians in the pediatric, cardiovascular, and neonatal intensive care units (ICU) are increasingly asked to provide 24 hour, in-house coverage to enhance resident supervision and improve care quality. This may lead to longer shifts for these physicians and may impact fatigue and error rates. Hypothesis: Evaluate how often attending physicians in the pediatric,cardiovascular, and neonatal intensive care unit are working more than 16 consecutive hours while providing direct patient care. Methods: We administered an anonymous 26 item web-based survey to 688 attending physicians from fellowship programs in the pediatric critical care fields across the United States to determine perceptions regarding their own extended duty hour shifts. Participants received two reminder emails to complete the survey. Results: Our overall survey completion rate was 52.3%. Of respondents, 14.2% worked in the CVICU, 35.5% in the PICU, and 60.5% in the NICU. Most (91.4%), of physicians reported use of other allied healthproviders in their ICU, although this was most common in the NICU (98.2%). Of those who work in CVICU, PICU, and NICU, 56.0%, 61.9%, and 38.1%, respectively, had an in-house mandate for overnight call. Overall, 37.5% of the respondents reported providing direct patient care after working for more than 16 consecutive hours (clinical and non-clinical duties) at least once weekly, although the frequency of those reporting these extended shifts varied greatly by specialty. With 70.0%, 47.3%, and 29.2% of attendings in CVICU, PICU,and NICU, respectively, reporting at least once weekly extended shifts. Increased frequency of extended shifts was associated with an in-house mandate for overnight call (p⫽0.02). Conclusions: Physicians in the pediatric critical care fields are often providing direct patient care for extended shifts greater than 16 hours, often as a night-shift after working a full day. This raises concerns regarding fatigue, the ability to supervise residents, and error rates for attending physicians in these fields who are increasingly asked to provide 24 hour in-house coverage.


574 CLINICAL OUTCOMES ASSOCIATED WITH ADJUNCTIVE AEROSOLIZED ANTIBIOTIC THERAPY IN GRAM-NEGATIVE VENTILATOR-ASSOCIATED PNEUMONIA Amber Sawyer, University of Missouri Hospital, Heather Arnold, Richard Reichley, Barnes-Jewish Hospital, Scott Micek, Barnes-Jewish Hosptial, Marin Kollef, Washington University School of Medicine Introduction: Treatment of gram-negative ventilator-associated pneumonia (VAP) is often limited to antimicrobials with high risk for toxicity. Utilizing locally administered antibiotics via nebulization as an adjunct to systemic therapy has emerged as a practical attempt to provide adequate antimicrobial coverage while minimizing toxicity. Data regarding the use of aerosolized antibiotic therapy in VAP is limited and its impact on patient outcomes remains inconclusive. Hypothesis: The object of this study is to evaluate clinical outcomes associated with adjunctive aerosolized antibiotic therapy in the setting of gram-negative VAP. Methods: This retrospective, comparative cohort study included 56 medical and surgical intensive care unit (ICU) patients in a 1250-bed academic medical center. Patients with bronchoalveolar-lavage (BAL) positive Pseudomonas aeruginosa or Acinetobacter baumannii VAP were assessed for resolution of clinical signs and symptoms of pneumonia. Two treatment groups were compared and included patients receiving systemic antibiotics plus adjunctive aerosolized tobramycin or colistin (IV ⫹ inhaled group) versus systemic therapy alone (IV group). The primary outcome was clinical resolution of VAP based on changes in a modified clinical pulmonary infection score within 7 days from BAL. Results: Resolution of VAP occurred in 21 of 29 and 6 of 19 patients in the IV and IV ⫹ inhaled groups, respectively (72.4 vs. 81.8%; p⫽0.005). Within 7 days of BAL, 62% of the IV group had a decrease in score by ⱖ 2 points versus only 21.1% of the IV ⫹ inhaled group (p⫽0.005). Duration of mechanical ventilation and hospital length of stay were significantly longer in the IV ⫹ inhaled group. Conclusions: Utilization of adjunctive aerosolized antibiotics to systemic therapy did not influence the rate of clinical resolution of gram-negative VAP.



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A SURVEY ON BEHALF OF USCIITG-LIPS INVESTIGATORS: TOWARD STANDARDIZATION OF A CHECKLIST FOR LUNG INJURY PREVENTION (CLIP)

RISK FACTORS FOR HYPOTENSION FOLLOWING URGENT INTUBATION IN A BURN INTENSIVE CARE UNIT

Peter Hou, Jason Cohen, Brigham and Women’s Hospital, Marie Elie-Turenne, Univerity of Medicine and Dentistry, New Jersey, Daniel Talmor, Beth Israel Deaconess Medical Center, David Murphy, Johns Hopkins University Hospital, Charles Cairns, University of North Carolina, Gyorgy Frendl, Brigham and Women’s Hospital, Ognjen Gajic, Mayo Graduate School of Medicine (Rochester), Michelle Gong, Montefiore Medical Center Introduction: In 2009, 22 centers performed an observational cohort study and enrolled 5584 hospitalized patients with predisposing conditions for acute lung injury (ALI). Incidence of ALI was 6.8% and varied significantly across hospitals from 2 to 13%. Hypothesis: The variation in ALI development may be contributed by practice variation among specialists with suboptimal communication at diverse clinical settings in the intensive care unit (ICU), emergency department (ED), and operating room (OR). Methods: Questionnaire with potential elements for acute lung injury prevention was sent to site-investigators. Results: 16 of 22 (72%) responses represented hospitals with 30 to 166 ICU beds and 17,000 to 100,000 annual adult ED visits. Protocols exist for severe sepsis: in the ICU (11/16), ED (5/16), OR (1/16); vent bundles: in the ICU (13/16), ED (1/16), and OR (2/16); restrictive transfusion: in the ICU (8/16), ED (2/16), and OR (1/16). Estimated frequency of utilizing rapid sequence intubation for airway control: 72% (25-96%) in ICU, 77% (21-100%) in ED, 37% (4-87%) in OR; initial tidal volume set at less than 8 cc per kg of predicted body weight: 73% (29-99%) in ICU, 42% (5-84%) in ED, 52% (8-100%) in OR; positive end-expiratory pressure immediately instituted in intubated patient: 87% (26-100%) in ICU, 73% (12-100%) in ED, and 38% (13-81%) in OR; conscious effort to minimize inspired oxygen in intubated patients: 67% (31-98%) in ICU, 39% (0-88%) in ED, and 38% (13-81%) in OR. Regarding patient care, frequency of direct communication between ED and ICU staff is 35% (6-85%), between ED and anesthesia staff is 24% (0-87%), between ED and surgical staff is 56% (17-92%), between anesthesia and ICU staff is 36% (5-99%), and between surgical and ICU staff is 36% (7-88%). Regarding handoffs, standardized protocols exist at 2 sites for ED patients admitted to ICU, at 1 site for ED patients transferred to OR, and at 3 sites for OR patient admitted to ICU. Conclusions: Variation among clinical practices in the management of critically ill patients may contribute to the variation in the incidence of acute lung injury development. A checklist for lung injury prevention may be warranted.

578 CONSULTATION IN THE ICU: A QUALITATIVE STUDY Jennifer Stevens, Anna Johansson, Mara Schonberg, Michael Howell, Beth Israel Deaconess Medical Center Introduction: More than 20 million inpatient consultations occur every year according to Medicare data. These consultants are involved for many of our most complex ICU patients. No standard approach exists to measure the quality of consultation and research efforts are correspondingly limited. Hypothesis: Qualitative methods would identify consistent thematic elements associated with the quality of consultation. Methods: We conducted a qualitative study with indepth, semi-structured interviews of attendings of two medical ICUs and one mixed medical-surgical ICU, and of subspecialists who frequently consult in these ICUs. Interviews were transcribed verbatim and systematically coded. Preliminary results are presented here. Results: We invited 18 ICU attendings to participate; 12 (66%) completed the interview. ICU attendings broadly conceived of consultation in two thematic categories: ‘cognitive‘ and ‘procedural‘. Reasons for obtaining consults included the need for expert advice (noted by n⫽12 respondents), medical-legal reasons (2), a request for prognostic information about the patient (2), and interest in expanding the education of the primary or consulting service (3). Both ICU attendings and consultants identified communication (noted by n⫽12 respondents), responsiveness (10), timeliness (9), and expertise (6) as features important in an effective consult. Major obstacles to a high quality consult were temporal (time of day or week), physical (location of the patient or ICU), and cultural (e.g., surgical services that are more hierarchical than their medicine counterparts). The consulting services themselves have their own incentives that may not align with the needs of the primary team. Respondents identified several opportunities for improvement. Conclusions: Formal qualitative methods identified several themes related to the quality of consultation in the ICU. This work provides a basis for the future development of a standardized, quantitative tool with which to measure consult quality.

Christopher Dennis, San Antonio Military Medical Center, Brian Yoon, Touro College of Osteopathic Medicine, Seth Holland, Daun Milligan, San Antonio Military Medical Center, Kevin Chung, United States Army Institute of Surgical Research Introduction: In the setting of urgent intubations in the burn intensive care unit (BICU), most commonly performed secondary to sepsis, various induction agents are utilized that may induce hemodynamic instability. Hypothesis: The use of propofol as an induction agent for urgent endotracheal intubation for respiratory failure in septic burn patients is associated with clinically significant hypotension. Methods: A retrospective review of consecutive critically ill burn patients who underwent urgent endotracheal intubation during their BICU course was performed. Basic burn related demographic data, indication for intubation and induction agents utilized were recorded. The primary outcome of interest was the presence of clinically significant hypotension, defined as hypotension requiring at least one fluid bolus, a new vasopressor agent, or escalation of current vasopressors immediately after intubation. Secondary outcomes included ventilator associated pneumonia, acute respiratory distress syndrome, length of stay, and in-hospital mortality. Results: Between January 2003 and August 2010, 279 consecutive patients with a mean percent total body surface area (%TBSA) burned of 38⫹/⫺23 underwent urgent endotracheal intubation while in our BICU. Of these, 168 patients (60%) were determined to have sepsis. After intubation, 117 patients (42%) experienced clinically significant hypotension. Propofol (51%) was the most commonly utilized induction agent followed by etomidate (23%), ketamine (15%), and versed (11%). On multiple logistic regression, %TBSA (OR 1.016, 95% CI 1.004-1.027, p⬍0.001) and sepsis (OR 1.852, 95% CI 1.100-3.117, p⫽0.02) were found to be the only significant predictors of hypotension. None of the other induction agents, to include propofol, were significantly associated with hypotension in patients with or without sepsis. There was no significant correlation between hypotension and any of the secondary outcomes. Conclusions: In critically ill burn patients undergoing urgent endotracheal intubation, specific induction agents, to include propofol, were not associated with clinically significant hypotension. The presence of sepsis and %TBSA were the most important risk factors.

579 A TALE OF TWO ERAS: 10 YEARS OF SURGICAL CRITICAL CARE AT A UNIVERSITY AFFILIATED HOSPITAL Paul Chugay, James Krinsley, Kevin Dwyer, Timothy Hall, Stamford Hospital Introduction: Over the past decade a significant amount of research has resulted in recommendations on how to improve the care of critically ill patients, such as intensive glycemic management, protocol guided sepsis protocols, ventilator weaning and de-escalation therapy in the setting of ICU infections. The purpose of this study is to evaluate key clinical outcomes of surgical service patients admitted over a 10 year period to a single highly protocol and data driven ICU. Hypothesis: Implementation of patient care protocols, adherence to expert critical care recommendations, and the advent of a surgical critical care service was associated with improved outcomes of surgical ICU patients. Methods: This study is a retrospective analysis of prospectively collected data from 3,564 consecutive surgical service admissions between 1/1/00 and 12/31/09 to the 16 bed adult ICU of a university affiliated hospital. Information was abstracted from the ICU’s comprehensive clinical database. Results: 1455 and 2109 patients were admitted between 2000-04 (E1) and 2005-09 (E2) respectively. The number of admissions/day increased from 0.80 to 1.16 (p⫽0.0027). Median (IQR) age of the cohorts increased from 64 (47-76) to 66 (49-78) (p⫽0.0027).APACHE II (APII) (E1 11 [8-16] vs. E2 11 [8-15], p⫽0.9920) and Charleson comorbidity scores (mean [SD]) (E1 1.1 [1.8] vs. 1.2 [1.9], p⫽0.2543) did not change significantly.ICU LOS decreased from 1.7 (0.9-3.1) to 1.1 (0.8-2.1) (p⬍0.0001).MORTALITY (%) E1 E2 Overall 11.3 6.0 (p⬍0.0001) AP II 0-9 1.1 0.7 AP II 10-19 7.8 3.8 AP II 20⫹ 47.8 33.1 Trauma 14.6 7.4 Vascular 9.7 6.5 Respiratory 8.8 2.8 GI 19.9 9.6 OrthoNeuro 10.8 5.6Grouped by two year intervals 2000-01 12.4 2002-03 11.6 2004-05 7.1 2006-07 6.3 2008-09 6.0 Conclusions: Implementation of standardized care using best practice patient care guidelines in a data driven and intensivist staffed university affiliated hospital was associated with significant decreases in mortality and LOS among a large heterogeneous cohort of surgical ICU patients.


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SEVERITY AND PREVENTABILITY OF DRUG INDUCED HYPOTENSION

MODIFICATION OF A VALIDATED INDEX TO PREDICT DEATH OR READMISSION FOLLOWING ACUTE-CARE HOSPITALIZATION TO OUTCOMES OF CRITICAL ILLNESS

Sandra Kane-Gill, University of Pittsburgh School of Pharmacy, Jaclyn LeBlanc, Atlantic Health Sciences Corporation, Joseph Dasta, University of Texas, CPP Hypotension Research Group, University of PIttsburgh Introduction: While hypotension is common in intensive care unit (ICU) patients, the occurrence of drug-induced hypotension has not been reported. By identifying hypotension as a drug-related hazardous condition, prevention strategies could be developed to minimize hypotention-related injury. Hypothesis: The occurrence of drug-induced hypotention is high, often caused by medication errors, and hence may be preventable. Methods: In this observational study, clinical pharmacists in 53 ICUs from 23 hospitals recorded episodes of hypotension during a 24-hour period. Hypotension was defined as SBP ⬍ 90 mm Hg or a decrease in SBP of 30 mm Hg over two hours in a previously non-hypotensive patient. Each hypotensive episode was assessed for the degree of a drug-related cause using the Kramer algorithm. Each episode of drug-induced hypotension was further evaluated whether it was due to a medication error. Results: Of the 690 patients evaluated, 238 (34.5%) experienced at least one episode of druginduced hypotension. SBP ⬍ 90 mmHg occurred in 42% of episodes and 55% were from a decrease in SBP of 30 mm Hg over two hours. Fifty six percent of episodes were possibly related to a drug, and 10.2% were considered probable or definite. The most common identified drugs were beta-blockers, narcotics, propofol, furosemide, benzodiazepines and hydralazine. 36.4% resulted from a medication error of which 4.3% reached the patient but resulted in no harm, 3.5% caused no harm but required monitoring or intervention to prevent harm, 3.5% may have resulted in harm, and 0.3% may have contributed to patient’s death. The most common error types were improper dose (54%), wrong time (19%), and prescribing (16%). Approximately 75% of patients required intervention for this episode of hypotension including crystalloids, norepinepherine, colloids, dopamine and phenylepherine. Conclusions: Drug-induced hypotension occurs in one-third of ICU patients, often requires active intervention and can result in harm. One-third of drug-induced hypotensive events are therefore preventable.

Vanessa Ho, Weill Medical College of Cornell, Lynn Hydo, New York Presbyterian Hospital, Philip Barie, Weill Cornell Medical College Introduction: Accurate prediction of mortality (M) or ICU re-admission (R) associated with critical illness has long been sought, but remains elusive. A new scoring system (LACE) has been validated to predict the risk of M or hospital re-admission (composite variable) within 30 days of discharge from acute-care hospitalization, incorporating length of stay (L), acuity (A), co-morbidity (C), and emergency department use in the preceding 6 mos. (E). Hypothesis: We hypothesized that LACE would predict M or R accurately in association with critical illness. Methods: The LACE system (0-19 points) was not designed for critical illness prognostication and requires a complex calculation, so the system was modified to utilize raw data readily available in ICUs (continuous data for L and A (APACHE) II score]) categorical binary data for C and E), and applied retrospectively to a 12,116-patient database. Primary outcome variables: M and R. Statistics: X ⫹ SEM, ANOVA, logistic regression (LR); p⫽0.01. Results: Age was 63.1 ⫹ 0.2 years; APACHE II score was 15.2 ⫹ 0.1 pts.; ICU-L was 5.9 ⫹ 0.1 days; hospital-L was 20.8 ⫹ 0.3 days. 47% had C, 52% were emergency admissions. M was 10.9%, R was 8.8%. By LR (dependent variable⫽R), A, C, and E (all, p⬍0.0001) were independent predictors of R, whereas ICU-L was not. Model chi-square: 138, p⬍0.0001, 91.2% of cases were predicted accurately, but the c-statistic for the four parameters ranged from 0.54-0.61. By contrast (dependent variable⫽M), A, E, and ICU-L (all, p⬍0.0001) were independent predictors of M, whereas C was not. Model chi-square: 2365, p⬍0.0001, and 90.4% of cases were predicted accurately, but the c-statistics were modest for L, C, and E (range, 0.57-0.68); only the c-statistic for A was in the clinically meaningful range (0.86). Conclusions: This modified LACE system has little utility for prediction of R following critical surgical illness, and performed better for prediction of M only because the APACHE II score dominated the model. Most of the descriptive utility of LACE as described may come from non-critically ill or non-surgical patients, or additional modification (e.g., weighted C scores) may be necessary to improve the model for critical illness prognostication.

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A CONSULTATIVE TELEMEDICINE SERVICE IMPROVES COMPLIANCE WITH BEST PRACTICE GUIDELINES IN A HIGHLY STAFFED INTENSIVE CARE UNIT

A CAUSE-AND-EFFECT RELATIONSHIP BETWEEN MUSCLE INJURY AND ACUTE KIDNEY INJURY IN RHABDOMYOLYSIS: A 5-YEAR SURVEY

Asad Latif, Mark Romig, The Johns Hopkins Medical Institutions, Peter Pronovost, Johns Hopkins University, Adam Sapirstein, Johns Hopkins School Of Medicine

Tetsuhiro Takei, Hiroko Fukushima, Yokohama City Minato Red Cross Hospital

Introduction: Telemedicine in the intensive care unit (ICU) is in the nascent stages of its development and usage. Little is known about its potential to improve quality of care in the ICU environment. Hypothesis: A consultative ICU telemedicine service improves compliance with best care practices in a highly staffed ICU of an academic medical center. Methods: We conducted a prospective study over a 10 week period. Best practice measures were defined relating to mechanical and pharmacological deep venous thrombosis (DVT) prophylaxis, gastric and decubitus ulcer prophylaxis, and prophylaxis against ventilator associated pneumonias (VAP). Baseline rates were collected during the first 2 weeks of the study period. A remote, consultative ICU telemedicine service was then implemented using two-way audio-visual communication, existing electronic documentation and real-time physiologic monitoring. Staffing was by an intensivist and nurse between 7p-7a daily. Compliance with the best practice measures was checked and recommendations to improve observed deficiencies were made for the 8 week intervention period. Pre and post-intervention data was analyzed using the Chisquare test. Results: Baseline metrics were gathered for 125 patients pre- and 605 patients post-intervention. Compliance was defined as either adherence to best practice or presence of a therapeutic contraindication. Compliance improved for both mechanical (93.6% vs 98.2%; p⬍0.01) and pharmacological (80.8% vs 88.8%; p⬍0.05) DVT prophylaxis. Patients ventilated ⬎24 hours were assessed for VAP prophylaxis. Compliance to sedation holidays (69.7% vs 85.5%; p⬍0.05) and regular oral care (69.7% vs 90.9%; p⬍0.01) significantly improved, while there was no improvement in daily spontaneous breathing trials (66.7% vs 77.6%; p⬎0.05). There were no differences in compliance for stress ulcer prophylaxis (86.4% vs 81.5%; p⬎0.05), regular repositioning for decubitus ulcer prophylaxis (85.6% vs 90.9%; p⬎0.05) or elevation of the head of the bed ⬎ 30 degrees (75.2% vs 73.6%; p⬎0.05). Conclusions: A consultative ICU telemedicine service made clinically significant improvements in adherence with and documentation of best care practices in a highly staffed academic ICU.


Introduction: There is no clear evidence supporting the cause-and-effect relationship between muscle injury and acute kidney injury (AKI) in patients with rhabdomyolysis. Hypothesis: A value of creatine kinase (CK), a surrogate measure for quantifying muscle injury, correlates with the development of AKI in rhabdomyolysis. Methods: Patients who visited to our hospital from April 2005 to March 2010 and whose value of CK exceeded 10,000 IU/L were enrolled in this study. We evaluated the relationship between a peak CK value and the delta creatinine which was defined as difference between a baseline creatinine value obtained on the day CK reached its peak and a maximal creatinine value within subsequent 7 days. Patients whose baseline creatinine value had already exceeded 1.2 mg/dL were excluded from the study because a cause-and-effect relationship between muscle injury and AKI seemed unclear in these subjects. AKI was defined as an increase of a serum creatinine value more than or equql to 0.3 mg/dL, or a 50% increase over baseline. Results: After excluding 104 patients, 81 patients finally met the inclusion criteria. A mean value of peak CK was 50,428 (10,230621,912) IU/L. We found no significant correlation between a peak CK value and the delta creatinine in these 81 patients (rs⫽0.11, p⫽0.31). Although 7 patients developed AKI, none of them required renal replacement therapy. Acute physiology and chronic health evaluation II and the sequential organ failure assessment scores in the AKI group were significantly higher than those in the non-AKI group (p⬍0.01), whereas a peak CK value and the total amount of 48-hour fluid administration were not significantly different between the two groups. Conclusions: Not the severity of muscle injury, but other factors such as systemic inflammation contribute to the development of kidney injury in rhabdomyolysis.

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585

THE DOMAINS OF GLYCEMIC CONTROL IN CRITICALLY ILL PATIENTS: IMPACT OF STEROID TREATMENT

CHARACTERISTICS AND OUTCOME OF CRITICALLY ILL PATIENTS WITH 2009 H1N1 INFLUENZA A INFECTION IN SYRIA

Bethany Lussier, James Krinsley, Stamford Hospital Introduction: Although systemic corticosteroid treatment (CS) is associated with hyperglycemia, the impact of CS on the domains of glycemic control - mean glucose level (MGL), glycemic variability (GV) and hypoglycemia (HYPO) - in critically ill patients (pts) has not been well described. Hypothesis: CS is associated with changes in all three domains of glycemic control in critically ill pts. Methods: This is a retrospective study of prospectively collected data involving 4,463 pts admitted to the 16 bed adult ICU of a university affiliated hospital between 10/1/05 and 5/31/10. Data were abstracted from the unit’s comprehensive clinical database. All pts were treated with an intensive glycemic protocol targeting 80-140 or 80-125 mg/dL (before or after 1/12/07). Pharmacy charges were used to identify 680 pts who received any dose of CS during ICU stay (CS⫹). MGL, severe HYPO (SH, ⬍40 mg/dL), and GV (for patients with 3⫹ blood glucose [BG]values), reflected by coefficient of variation (%) (CV) were calculated for each patient. Multivariable logistic regression analysis included APACHE IV predicted mortality. Results: Data: CS- CS⫹ P value DM (%) 20.9 18.4 0.1469APIV pred mort (%) 19.0 21.4 ⬍0.0001Mortality 13.9 20.6 ⬍0.0001MGL (mg/dL) 120.3 129.4 ⬍0.0001 SH (%) 2.5 4.1 0.0258CV (%) 20.5 24.3 ⬍0.0001Low GV was associated with reduced risk of MORT and increased GV and HYPO were associated with increased risk of MORT in CS⫹ pts. Regression analysis: mortality (CS⫹ cohort) OR (95% CI) P valueCV ⬍ 15%* 0.27 (0.12-0.59) 0.0013CV ⬎ 35% * 2.28 (1.45-3.59) 0.0004Minimum BG ⬍ 60 3.25 (1.70-6.22) 0.0004*univariable multivariable . Conclusions: Treatment of critically ill pts with CS results in higher MGL, higher GV and higher rates of HYPO. The changes in GV and HYPO are associated with increased risk of MORT. Heightened efforts to improve these domains of glycemic control in pts receiving CS may improve their outcomes.

Reem Alsadat, Al-Mouassat University Hospital, Abdulrahman Dakkak, Ibn Alnafees Hospital, Mouna Mazloom, Damascus Hospital, Ghassan Ghadhban, Shadi Fattoom, Assad University Hospital, Nabil Abouchala, Mazen Kherallah, King Faisal Specialist Hospital and Research Center Introduction: The objective of this study was to describe the epidemiological characteristics, clinical features, and outcome of severe cases of 2009 H1N1 influenza A infections who were admitted to the intensive care units (ICU) in Damascus, Syria. Methods: Retrospectively, we collected demographic data, clinical presentation, risk factors and outcome data on all patients who were admitted to the ICU with confirmed or suspected diagnosis of severe 2009 H1N1 influenza A with respiratory failure at 4 major tertiary care hospitals in Damascus, Syria. Acute Physiology and Chronic Health Evaluation (APACHE) II system was used to assess the severity of illness within the first 24 hours after admission. Outcome was overall hospital mortality. Results: Total of 80 patients were admitted to ICU with severe 2009 H1N1 infection of whom 60% were males. The mean age was 40.7 years with 50% of the patients were in the age group of 25-49 years. 20% of patients were asthmatics, 23.8% had obesity defined as BMI ⬎30, 5% of patients were pregnant and 30.2% had no risk factors. Median duration from start of symptoms till hospital admission was 3 days. Patients were admitted to ICU with the diagnosis of respiratory failure in 86.2%, 58 patients (72.5%) had acute lung injury or adult respiratory distress syndrome, 10 patients (12.5%) had viral pneumonitis, 34 patients (42.5%) had secondary bacterial pneumonia and 12 patients (15%) had exacerbation of airflow disease. Mechanical ventilation was required in 59 patients (73.7%) for an average duration of 10.6 days, 47 out of 59 patients (79.7%) were placed on muscle paralysis. Mean hospital length of stay was 11.7 days. Overall mortality rate of 51% for an average APACHE II score of 15.2 with a predicted mortality of 21% (standardized mortality ratio of 2.4, 95% confidence interval: 1.7-3.2, P value ⬍ 0.001). Mortality was 0% for APACHE II group of 0-9, 54% for 10-19 group and 67% for above 20 group. Conclusions: Critically ill patients with severe 2009 H1N1 infection in this limited resource country had a much higher mortality rate than the predicted APACHE II mortality rate or when compared to the reported mortality rates for severe cases in other countries during this pandemic.



587

DISTRIBUTION AND CHARACTERISTICS OF PEDIATRIC RAPID RESPONSE TEAMS IN THE UNITED STATES

QUALITY OF LIFE BEFORE, 3 MONTHS AND 1 YEAR AFTER ICU DISCHARGE

Jerome Chen, Arnold Palmer Hospital for Children, Alex Kemper, Duke University Medical Center, Fola Odetola, University of Michigan, David Turner, Duke University Medical Center

Sandra Oeyen, Dominique Benoit, Ghent University Hospital , Lieven Annemans, Ghent University , Johan Decruyenaere, Ghent University Hospital

Introduction: Hospitals that care for children have begun to implement rapid response teams (RRTs) or medical emergency teams in an effort to improve patient safety. However, the distribution and characteristics of pediatric RRTs are unknown. Hypothesis: RRTs are prevalent but vary in characteristics such as mechanisms of activation and team composition. Methods: We performed a cross-sectional survey study of pediatric intensive care unit (PICU) Medical Directors in the United States regarding RRTs. Eligible hospitals were identified through the National Association of Children’s Hospitals and Virtual PICU websites. Results: We mailed surveys to 210 hospitals. After three survey waves, the response rate was 64% (n⫽134). Most hospitals (79%, 103) had a RRT, 85% (88) of which were implemented within the past 5 years. Institutions with RRTs were more likely to have larger PICUs compared to institutions without RRTs (median 19 vs. 9 beds respectively, p ⫽ 0.00), have fellowship training programs (94% vs. 69%, p⫽0.00), and have residency training programs (83% vs. 63%, p⫽0.05). All RRTs were available on nights and on weekends. A two-tiered model with the code team separate from the RRT was present in 80% of cases. Families could activate the RRT in 69% of cases, and automatic activation triggers for vital sign criteria were present in 34% of cases. The team included nurses in 100%, respiratory therapists in 89%, and physicians in 77% of hospitals. The team leader was a physician in 63%, a nurse in 29%, and a nurse practitioner in 3% of hospitals. 96% of institutions tracked the number of RRT activations, while 84% tracked mortality, codes, and unplanned intubations. In opinion data, 86% of respondents believed that RRTs decrease the frequency of codes on the wards, 72% believed that they are essential for patient safety, and 67% believed that they decrease mortality. Conclusions: Pediatric rapid response systems are common, but differ considerably in methods of activation, the presence of automatic triggers, and team composition. Attitudes and beliefs regarding RRTs vary about PICU physicians. Future research should focus on specific characteristics of RRTs that may be associated with improved patient outcomes.

Introduction: Quality of life (QOL) after critical illness is partly dependent on pre-ICU QOL. However, studies including assessment of QOL before ICU admission are scarce. We investigated QOL 3 months and 1 year after ICU discharge, and compared it with QOL before ICU admission. Methods: A prospective observational cohort analysis was performed. Between March 3rd 2008 – March 3rd 2009, all consecutive patients admitted to the surgical ICU (SICU), medical ICU (MICU) and burn unit (BU) were screened for inclusion. Demographic, comorbidity, severity of illness, organ failure, and outcome data were collected. Standardized questionnaires (EuroQoL-6D (EQ-6D), Medical Outcomes Study 36-item Short Form Health Survey (SF-36)) were used to assess pre-ICU QOL (face-to-face interview), 3 months (regular mail) and 1 year (regular mail or phone if no answer) after ICU discharge. Results: Of 2414 patients, 1953 (1269 SICU, 614 MICU, 70 BU patients; 62% males) were included. Mean age was 57.2 years (SD 16.8), mean APACHE II score 16.9 (SD 8.2), and mean Charlson comorbidity index 2.6 (SD 2.8). ICU, hospital, 3 months and 1 year mortality were 8.6 % (N⫽167), 14.6% (N⫽285), 17.4% (N⫽340), and 26.4% (N⫽515) respectively. Three months after ICU discharge (response rate 69.6% (N⫽1139)), QOL was significantly lower on all SF-36 domains (P⬍0.001), especially the physical domains, compared with baseline QOL. Significantly more patients reported problems on the EQ-6D (P⬍0.001; anxiety P⫽0.006). After 1 year, overall response rate was 91.2% (N⫽1373). Compared with QOL 3 months after ICU, QOL increased significantly on all SF-36 domains (P⬍0.001), but remained lower than baseline QOL, particularly on physical level (P⬍0.001; vitality P⫽0.008; mental health P⫽0.014). Patients reported less problems on the EQ-6D after 1 year (usual activities P⬍0.001; pain P⫽0.004) but compared with QOL before ICU, there were still more problems on all dimensions (P⬍0.001; anxiety P⫽0.02). 0.9% patients (N⫽18) were lost to follow-up. Conclusions: Three months after ICU discharge, QOL was significantly worse compared with pre-ICU QOL. Over 1 year however, QOL improved significantly but remained under the baseline level.

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589

EFFECT OF A TELE-ICU (TICU) FACILITATED PROGRAM ON CARE AND DOCUMENTATION OF ICU PATIENTS AND PRESSURE ULCERS (PU)

IMPROVED GLYCEMIC CONTROL RESULTS IN A REDUCTION IN HOSPITAL-ACQUIRED INFECTIONS, BUT DOES NOT IMPROVE IN-HOSPITAL MORTALITY

Kathryn Brown, Jude Gamel, Sheryl Arbogast, Donna Butler, Terri Ross, The Christ Hospital, Janet Spinks, Valencia McCree, Erkan Hassan, Philips VISICU

Holly Sheldon, Boston Medical Center, Joanna Ng, Boston University School of Medicine, Gustavo Bauza, Boston Medical Center, Juan Mella, Boston University School of Medicine, Peter Burke, Suresh Agarwal, Boston Medical Center

Introduction: PUs are expensive, costing up to $8.5 Billion/year. Assessment and intervention on all PUs is necessary but stage III/IV PUs present on admission (POA) must be documented to receive CMS payment. Hypothesis: This initiative was designed to improve 4 areas of PU practice: 1) Collaboration between bedside and remote clinicians in the identification/staging of PU; 2) Detailed wound description in the chart; 3) Documentation of status (improved or not); 4) Physician documentation required for CMS. Methods: Remote/bedside hospital administrators and clinicians developed a PU management program in a 555 bed tertiary care hospital with 3 ICUs (48 beds) and a tICU. Rigorous definitions of roles/responsibilities, pt. assessment, metrics, and education tools were developed. Each patient with a PU (POA/hospital acquired [HA]) or at high risk for a PU was reviewed daily for the presence or absence of the study objectives. Baseline (Phase I) data were collected (10/09 –1/10). Education on the initiative occurred in 2/10. tICU RNs were trained as extended wound care clinicians in the evaluation and staging of PUs. Post data ( Phase II ) were collected over 4 months (3/10 –7/10). Results: In Phase I, 1777 MICU pts had 58 (3.4%: 43 POA/15 HA) PUs. In Phase II, 3182 pts (all ICU’s) had 86 (2.7%: 55 POA/31 HA) PUs. Neither age nor gender was significantly different between groups. Collaboration and wound assessment documentation significantly improved from 62.1% to 96.5% & 24.1% to 60% respectively (P⬍0.05). Wound documentation achieved 95.4% compliance; however, the 75.9% Phase I rate precluded a statistical difference. Physician wound documentation remained low (20.7% vs 23.3%). No difference was found in physician documentation based on the stage of PUs regardless of POA or HA. Conclusions: tICU RNs trained as extended wound care clinicians, in a collaborative PU management program with bedside RNs, are effective and significantly improves initial and ongoing wound assessment. Improved physician documentation should result in higher DRG reimbursement for pts with PU-POA.


Introduction: Despite 10 years of analysis regarding blood sugar control in critical care unit patients, debate continues regarding the benefit of intensive insulin therapy and its impact upon mortality and rate of infection. As such, we sought to evaluate the impact of blood glucose control upon hospital-acquired infections and mortality in a Surgical Intensive Care Unit. Hypothesis: We predict that an improvement in blood glucose control will result in a decrease in hospital-acquired infections with a subsequent improvement in in-hospital mortality. Methods: Retrospective review of prospectively collected data on all patients admitted to the Intensive Care Unit at a large, urban, level 1 trauma center from January 2005 until August 2009. Patient with an Intensive Care Unit stay, hospital admission of at least 48-hours, and a minimum of 8 Point-of-care (POC) glucose readings were included. Data was collected via the Clinical Database Warehouse and Trauma Registry (TRACS). Glucose values were obtained, averaged over the length of stay, and assigned a range (⬍80mg/dL, 81-149mg/dL, 150-180mg/dL, 181-200mg/dL, and ⬎200mg/dL). Hospital-acquired infections (HAI) were assigned by an independent Infection Control Committee. Results: Of the 1,561 patients included, 1039 (66.6%) were admitted with a trauma diagnosis. Overall mean glucose improved significantly from 2005 to 2009 (134.6 ⫹/⫺ 1.5 mg/dL versus 127.6 ⫹/⫺ 1.3 mg/dL, p ⬍ 0.05). The rate of hospital-acquired infections declined from 0.27 infections/patient to 0.03 infections/patient over this same time period. However there was no correlation in the yearly trends between mean glucose and the rate of infections. While HAIs decreased significantly, this did not result in a significant change in in-hospital mortality (0.06 death/admissions versus 0.04 deaths/admission, p⬎0.05). Conclusions: Improving blood glucose control decreases HAI but does not significantly affect in-hospital mortality. Although this suggests that blood glucose may be important to infection control, it also implies that other factors modify inhospital mortality.

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GLASGOW COMA SCALE SCORE IS ASSOCIATED WITH MORTALITY IN ABUSIVE HEAD TRAUMA IN CHILDREN

UTILIZING AN UPDATED THERAPEUTIC INTERVENTION SCORING SYSTEM IN PEDIATRICS (P-TISS) DETERMINES THE PROBABILITY OF UNTOWARD EVENTS IN CRTICALLY ILL PEDIATRIC PATIENTS

Steven Shein, Michael Bell, Children’s Hospital of Pittsburgh, Patrick Kochanek, University of Pittsburgh Medical Center, Elizabeth Tyler-Kabara, Children’s Hospital of Pittsburgh, Stephen Wisniewski, University of Pittsburgh, Ken Feldman, Seattle Children’s Hospital, Kathi Makoroff, Cincinnati Children’s, Philip Scribano, Nationwide Children’s Hospital, Rachel Berger, Children’s Hospital of Pittsburgh Introduction: Abusive head trauma (AHT) is a consequence of child abuse and is associated with high mortality and morbidity, but factors associated with adverse outcome are not well understood in this patient population. Hypothesis: Younger age and higher injury severity are associated with higher risk of mortality in AHT. Methods: A database of children (n ⫽ 459) with child abuse diagnosed by a Child Protection team was developed in 4 children’s hospitals (Cincinnati, Columbus, Pittsburgh and Seattle). Demographics, physical findings and neuroimaging results were collected. Univariate analyses and multivariate models were used to analyze the entire cohort as well as children with severe traumatic brain injury (TBI - GCS ⱕ 8) to determine factors associated with death. Data were reported as OR[95% CI]. Results: Mean age was 9.4 mo ⫾ 11.4 and 15.9% died. Severe TBI was common (n⫽139, 37.0%) and associated with high mortality (45.3%). In univariate analysis, categorized Glasgow Coma Scale (GCS) score, age, retinal hemorrhage and several neuroimaging findings were associated with death. In the multivariate analysis, only GCS was independently associated with death (GCS 3: 100.3 [29.5-340.8]; GCS 4 –5: 42.5 [10.1-179.2]; GCS 6 – 8: 11.9 [2.7–52.4]; p⬍0.001, all vs. GCS ⱖ12). In children with severe TBI, multivariate analysis demonstrated that GCS score (20.1 [5.4-75.2] for GCS 3 vs. GCS 6-8, p⬍0.001), cerebral edema (5.3 [1.4 –19.6], p⫽0.014) and retinal hemorrhage (16.0 [1.7–148.1], p⫽0.014) were independently associated with death. Conclusions: In this large cohort of abused children, decreased GCS score at presentation was the only evaluated factor that was independently associated with death, a unique finding in pediatric TBI. Decreased GCS score was also independently associated with death in the subgroup of abused children with severe TBI. Other independent variables were identified in this subgroup, but some common intracranial injuries (e.g. acute subdural hematoma, epidural hematoma, subarachnoid hemorrhage) did not demonstrate such an association. Studies aimed at limiting mortality from AHT are warranted.

Sandra Vaz, Randi Trope, Mayer Sagy, Cohen Children’s Medical Center Introduction: TISS was originally introduced in 1970 for adult critical care and has never been updated for current pediatric critical care practice. Our study introduces an updated P-TISS that was used to determine the relationship between P-TISS scores and the probability of untoward events. Hypothesis: We hypothesize that patients with untoward incidents will have P-TISS scores that are higher than random PICU patients. Methods: An updated P-TISS was developed based on tertiary level of pediatric critical care practice. The system evaluates 12 clinical categories of therapeutic interventions with assigned scores commensurate with clinical and operational complexity. Thus, recent advanced interventions in the respiratory and cardiac sections include ECMO, high frequency oscillatory ventilation, and inhaled nitric oxide; the neurology section includes induced hypothermia and barbiturate coma and the nephrology section includes continuous renal replacement therapy. P-TISS scores were randomly calculated for patients in the PICU and subsequently compared with P-TISS of patients in whom untoward incidents had occurred. Incidents were defined as type A: those that may have been prevented by uninterrupted bedside human (nursing) surveillance (i.e. self-extubation) and type B: incidents that are unrelated to continuous direct human surveillance (i.e. medication error). Results: One hundred twenty five PICU patients were randomly selected and their mean P-TISS was 14.6 ⫾ 11.8, while other 98 patients with untoward incidents had a mean score of 19.9 ⫾ 11.6 (p⬍0.05). Of the 98 patients, 24 had type A incidents and 74 had type B incidents with mean P-TISS of 24.03 ⫾ 11.36 and 18.6 ⫾ 11.40, respectively (p⬍0.05). Conclusions: We conclude that a high P-TISS is associated with a higher incidence of untoward events. This correlation can be explained by an increase in nursing workload with increasing likelihood of distractions/interruptions in delivering human bedside surveillance to patients. This results in more untoward incidents, particularly incidents that can be preventable, should bedside human surveillance remain uninterrupted.

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A MULTIDISCIPLINARY APPROACH TO CENTRAL LINE PLACEMENT AND CARE CAN REDUCE RATES OF CLABSI

HYPOGLYCEMIA IS ASSOCIATED WITH INCREASED RESOURCE UTILIZATION IN CRITICALLY ILL PATIENTS, INDEPENDENTLY OF SEVERITY OF ILLNESS AND SURVIVOR STATUS

Anita Reddy, Sara Cobb, Tarik Hanane, Sarah Kus, Claire Strauser, Jorge Guzman, Cleveland Clinic Introduction: Approximately 500,000 central line associated bloodstream infections (CLABSI) are diagnosed every year. Bloodstream infections can prolong hospital stay, increase mortality, and increase cost of stay. In addition, the Joint Commission’s National Patient Safety Goals have set forth more guidelines and policies regarding infections related to central lines. Hypothesis: We hypothesized that increased awareness about central line placement, maintenance and duration would help decrease CLABSI. Methods: A quality committee comprised of physicians assigned as quality review officers (QROs), assistant nurse managers (ANMs), respiratory therapist (RT), nurse practitioner, quality manager, infection control practitioner, critical care fellow was assembled to address quality measures in the ICU. The central line initiative to reduce CLABSI included education of housestaff on proper sterile procedure during line placement (full sterile field and appropriate sterile attire for all personnel in the room, chlorhexidine scrub, placing Bio-patch and caps on catheter after line insertion); as well as nursing education on proper hand hygiene during use and maintenance of lines and dressing changes. Checklists were maintained to ensure that proper procedure was followed during line placement. We also implemented twice weekly notification to physicians of central lines that had been in place for greater than five days to assess need for line. Results: Prior to implementation of the central line initiatives, the rates of CLABSI in the ICU were 5.8 CLABSI/1000 central line days (January-May 2010). Since implementation of initiatives, CLABSI rates dropped to 2.1 CLABSI/1000 central line days (p⫽0.0485). The number of line infections per month were significantly reduced (mean 4.4 vs 1.5/month, p⫽0.0228), and the number of line days were also reduced (mean 719 vs 747/month, p⫽0.4156). Conclusions: Education about proper procedure for line placement and line maintenance and vigilance regarding central line removal are key to reducing and preventing central line associated bloodstream infections. A multidisciplinary approach to infection prevention can improve outcomes related to CLABSI in the ICU.

Brent Baboolal, James Krinsley, Stamford Hospital Introduction: While a small body of literature describes the cost savings associated with the implementation of intensive insulin therapy for treatment of hyperglycemia in the critically ill, it is not known whether hypoglycemia (HYPO) during ICU stay has an impact on resource utilization. The purpose of this study is to assess the cost implications of HYPO in a heterogenous population in critically ill adult patients. Hypothesis: HYPO occurring during ICU stay is associated with increased resource utilization. Methods: This is a retrospective analysis of prospectively collected data from 3,263 consecutive patients admitted to the 16 bed mixed medical surgical ICU of a university affiliated hospital between 1/12/07 and 5/31/10. HYPO was defined as blood glucose (BG) level ⬍ 70 mg/dL. All patients were treated with an insulin protocol targeting BG 80-125 mg/dL. Data were prospectively collected and retrospectively analyzed using the comprehensive ICU clinical and financial database. The analysis includes costs associated with ICU length of stay, ventilator days, and laboratory, pharmacy, and radiology services. Charges were converted to cost using appropriate Medicare cost:charge ratios for each department. Results: The cohort included 857 patients with at least one BG ⬍ 70 mg/dL (HYP) and 2,406 without hypoglycemia (NON). For the entire cohort, there were decreases in ICU LOS(3.0 vs 1.2 days, p⬍0.0001); ventilator days (4.0 vs 2.0 days, p⬍0.0001); % ventilated (55.o vs 28.5, p⬍0.0001), and total laboratory, pharmacy and radiology costs comparing HYP and NON. APACHE IV predicted mortality (%) was significantly higher for HYP vs. NON: 30.4 (28.5) vs. 14.2 (20.6) p⬍0.0001 and mortality (%) was higher as well: 29.1 vs. 8.9. Nevertheless, stratifying patients by APACHE IV predicted mortality (0-10%, 10-25%, 25-50% and 50%⫹) as well as survivor status consistently demonstrated higher LOS and other resource utilization parameters for HYP vs. NON. The median difference in cost between HYP and NON was $5,178 per patient. Conclusions: Patients experiencing even a single episode of HYPO (BG ⬍70 mg/dL) in the ICU sustained substantially higher cost of care than did those without any HYPO.


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NATIONWIDE OUTCOMES OF SEVERE SEPSIS IN THE OCTOGENARIANS

CROSS-VALIDATION OF THE SEQUENTIAL ORGAN FAILURE ASSESSMENT (SOFA) SCORE TO PREDICT MORTALITY IN MEDICAL AND SURGICAL PATIENTS WITH CANCER ADMITTED TO THE INTENSIVE CARE UNIT

Jayshil Patel, Gagan Kumar, Amit Taneja, Ankit Sakhuja, Medical College of Wisconsin, Abhishekh Deshmuk, University of Arkansas, Rumi Ahmed Khan, Orlando Regional Medical Center, Sandeep Markan, Rahul Nanchal, Medical College of Wisconsin Introduction: The elderly, with their unique clinical characteristics constitute an increasing proportion of the national population. Aggressive management which is norm for severe sepsis (SS) is often not performed secondary to concerns about age, co-morbidities, survivability and quality of life post survival. The outcomes of SS in octogenarians is not well studied. Hypothesis: The octogenarians with SS experience worse outcomes when compared with younger age groups. Methods: Using the Nationwide Inpatient Sample from 2000 to 2008, patients aged 80 or more, discharged with SS were identified through appropriate ICD-9, clinical modification codes. Outcome variables included all cause in-hospitalmortality, LOS and discharge disposition. Chi-square and t-tests were used to compare categorical and continuous variables between the 2 groups, respectively. A multivariate logistic regression was performed to adjusted for demographics, Elixhauser co-morbidity index and severity of sepsis. Results: Of 5,247,400 estimated hospital admissions with SS during the study period of 2000 to 2008 in the United States, the octogenarians accounted for about 27%. Their numbers has increased in both absolute and relative terms. The mortality in this group has decreased from 46% in 2000 to 32.8% in 2008 (P ⬍ 0.001). The adjusted odds for mortality were significantly higher (OR 2.9; 95% CI 2.8-2.9) in elderly when compared to age 50 or less. The elderly had significantly lower rates of respiratory and hepatic failure and higher renal and cardiac failure than those aged 50 or less.The LOS in elderly who survived was 4 days shorter than those aged 50 or less (numbers). Discharges to long term facilities were also significantly greater in the elderly. (81% vs. 44% p ⬍0.001). Conclusions: The elderly with SS have significantly higher mortality than younger age groups. However mortality in this group has declined over the years and is now comparable to other age groups.Though the LOS in the elderly with SS is less that other age groups, a significantly higher proportion are discharged to long term facilities. The elderly suffer higher rates of cardiac and renal failure than other age groups.


Marylou Cardenas-Turanzas, Kristen Price, Joseph Nates, The University of Texas MD Anderson Cancer Center Introduction: The SOFA score is widely used in the ICU to predict mortality. Hypothesis: We aimed to simulate an external validation of an electronically and automated version of the SOFA score at admission to predict ICU mortality of the medical and surgical patients with cancer admitted to a Comprehensive Cancer Center. Methods: We conducted a retrospective study of ICU discharges between 1/1/2006 and 12/31/2008. We randomly splited admissions (medical or surgical) into training and validation study groups. We used logistic regression (LR) to calculate the probabilities of death in the training samples and applied those probabilities to the validation samples to calculate sensitivity and specificity and constructed receiver operating characteristics (ROC) curves. Results: We included 6645 patients, 60.7% were surgical admissions and 58.2% were men. The mean (median) age was 57.8 (60) years. The mortality rate was 24.8% for the medical admissions and 1.9% for the surgical admissions .The mean admission SOFA score was higher for medical admissions than for surgical ones 7 vs. 4 (p ⱕ .001). The AUC of the ROC curve was 0.79 (95% Confidence Interval [CI], 0.74 – 0.83) for the medical admissions validation group and 0.83 (95% CI 0.70 – 0.96) for the surgical admissions validation group. The accuracy rates of the LR models in validation groups were 75.9% the medical and 98.5% for the surgical, respectively. The goodness-of-fit tests in the validation groups of admissions were Chi2 ⫽ 7.07, df ⫽ 8 and p ⫽ .53 for the medical and Chi2 ⫽ 4.63, df ⫽ 7, p ⫽ .71 for the surgical. Conclusions: Despite the electronically automated adaptation of the SOFA score, in this model the score had good performance indicating it is a good tool to predict ICU mortality in patients with cancer. Indeed we found slightly superior performance in the surgical than in the medical admissions.


597

ASPERGILLOSIS IN INTENSIVE CARE UNIT (ICU) PATIENTS: IMPACT OF ANTIFUNGAL THERAPY ON PATIENT OUTCOMES

HOSPITAL LENGTH OF STAY BENCHMARKS FOR ICU ADMISSIONS

John Baddley, University of Alabama, Birmingham, AL, Xin Gao, Xiang Ji, Jennifer Stephens, Pharmerit North America, LLC, Haran Schlamm, Miriam Tarallo, Pfizer Inc

Hypothesis: The purpose of this study is to present a method for estimating case-mix adjusted benchmarks for hospital length of stay after ICU admission. Methods: To do this we developed and validated a multivariable linear regression model. We retrospectively collected institutional, demographic, clinical, and physiologic data on ICU day 1 for 202,300 patients admitted from 1/1/2002 to 12/31/2008 at 75 ICUs in 25 hospitals with an APACHE system. To avoid the impact of extreme outliers, hospital lengths of stay ⬎ 50 days were truncated down to 50 days. The 156,561 patients from 2002-2006 were randomly assigned to either a 60% sample for training or a 40% sample for internal validation. The 45,544 patients from 2007–2008 were used for external validation. A linear regression model was created that included all predictors. From this model we identified those variables with a p-value ⬎ 0.10, and then re-ran the model without them. Results: The final model used 39 demographic, clinical, and physiologic variables, and 115 binary variables for diagnostic groups. Partitioning the model’s variance into its components, the most important factor was the acute physiology score (60.4%) followed by ICU admission diagnosis (28.1%). For the external validation data set mean observed and mean predicted hospital stay were 9.93 and 9.52 days (p⬍0.01). While statistically significant this difference amounted to only 9.7 hours. Across deciles of increasing hospital length of stay, mean observed values deviated from mean predicted values only for deciles 1 (19.3 hours), 9 (15.3 hours), and 10 (37.7 hours); and for patients with a high (⬎80%) risk of death. Conclusions: We conclude that patient and institutional characteristics can be used to accurately predict hospital stay remaining after ICU admission for ICU patient groups. Comparison of observed and expected hospital stay can be used to benchmark unit and hospital efficiency.

Introduction: There is an increasing interest in aspergillosis in patients with nontraditional risk factors, especially those who are critically ill, as the impact of initial antifungal (AF) on length of stay (LOS) and total hospital costs are not well characterized. Hypothesis: The study purpose was to examine clinical and economic outcomes among ICU patients with aspergillosis. Methods: Using the large Premier US administrative hospital database from 2005-2008, we identified adults with ICU stays who were diagnosed with pneumonia in aspergillosis (ICD-9 117.3x ⫹ 484.6) and received the initial (index) AF in the ICU. Patients with traditional risk factors (cancer, transplant, neutropenia) were excluded. AF treatment and outcomes were examined using univariate and multivariate analyses. Results: From 6,424 aspergillosis patients in the database, 412 ICU patients with pneumonia in aspergillosis were identified. Mean age was 64 yrs, 53% male, and 68% Caucasian. Common underlying conditions included steroids (77%), acute respiratory failure (76%) and acute renal failure (41%). Hospital mortality was 46%. The most frequently used AF was voriconazole (vori) (71% received vori at least once); followed by caspofungin (39%) and ampho B (13%). Delayed Aspergillus-active therapy (index fluconazole) was received by 28%. Average length of AF treatment, LOS, ICU, and mechanical ventilation (MV) days were 15, 27, 16, and 17 days, respectively. Total hospital costs averaged $76,235 per patient. In multivariable analysis, use of index fluconazole (when compared with an Aspergillus-active AF; p⫽0.001), mortality (p⬍0.001), MV (p⬍0.001), renal failure (p⫽0.001) and geographic region were associated with increased LOS. In survivors, greater total costs were associated with initial fluconazole vs. Aspergillus-active AF therapy (⫹14%, p⫽0.013). In addition, delaying therapy with initial fluconazole was associated with an extra 7 days LOS (p⬍0.003) and 42% more costs (p⫽0.017) vs initial vori. Initial AF therapy impacts LOS and hospital costs, but not mortality. Conclusions: Initial use of an Aspergillus-active AF is associated with improved outcomes, underscoring the importance of timely diagnosis and treatment of aspergillosis.

Jack Zimmerman, Andrew Kramer, Cerner Corporation

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DOES ICU READMISSION RATE IMPACT ICU OUTCOMES?

DEVELOPMENT OF A MODEL THAT USES ENHANCED ADMINISTRATIVE DATA TO PREDICT MORTALITY AMONG PATIENTS WITH SEPSIS

Andrew Kramer, Jack Zimmerman, Cerner Corporation Hypothesis: The purpose of this study is to assess the association of ICU readmission rate with case-mix adjusted quality of care measures: mortality before ICU discharge and ICU length of stay. Methods: To do this we retrospectively collected institutional, demographic, clinical, and physiologic data for 212,095 patients admitted from 1/1/2002 to 12/31/2008 at 76 ICUs in 25 hospitals with an APACHE system. We eliminated 10 units that had collected data for ⬍ one year and three other units that had admitted fewer than 500 patients; a total of 4,978 admissions (2.3%). Readmission was defined as any ICU admission other than the first within a hospital encounter. The ICUs were split into three categories according to their readmission rate: low (0%-5.0%; n⫽20 units; 60,945 admissions), medium (5.1%-7.0%; n⫽22; 80,743 admissions), and high (⬎ 7.0%; n⫽21; 65,429 admissions). We used the APACHE IV predictive models for ICU mortality and ICU stay to generate predictions for each patient. The mean observed and predicted values within an ICU were obtained, and compared across ICUs. Results: The ICU mortality rate for low, medium, and high readmission groups was 7.3%, 8.9%, and 8.9% respectively; and the standardized mortality ratio was 0.902, 0.904, and 0.842, respectively. The ICU LOS was 3.49 days for the low readmission group, 4.28 days for the medium readmission group, and 4.30 days for the high readmission group. However when the observed – predicted ICU LOS was calculated, it was 0.07, 0.48, and 0.20 days for the low, medium and high readmission groups, respectively. ICUs with high readmission rates had the highest mean acute physiology scores, percentage of ventilated patients, and percentage of patients requiring life-sustaining therapy on the first ICU day. Conclusions: We conclude that ICU readmission rate does not negatively impact an ICU’s outcomes when case-mix is considered.

Tara Lagu, Peter Lindenauer, Baystate Health, Brian Nathanson, OptiStatim, LLP, Michael Rothberg, Penelope Pekow, Baystate Health, Jay Steingrub, Thomas Higgins, Baystate Medical Center Introduction: Existing models used to assess the severity of illness in critically ill patients rely on the manual collection of physiologic data and other historical information. This burden of data collection limits the ability to conduct largescale observational studies. Moreover, these models were not specifically designed for sepsis patients. Hypothesis: A model to predict mortality among patients with sepsis developed using detailed administrative data will have similar discrimination as existing mortality prediction models such as APACHE, SAPS, and MPM. Methods: We gathered information from the cost accounting systems of 309 hospitals that cared for at least 100 patients with sepsis between 2004-2006. We developed a non-parsimonious multilevel (hierarchical) mixed effect logistic regression model to predict mortality at the patient level while accounting for clustering of patients being treated within the same hospital. The model included information about patient demographics (age, sex, race, insurance type), the site and source of sepsis, the presence of 25 individual comorbidities, whether the patient was admitted to the ICU, and whether they received mechanical ventilation and vasopressors within the first 2 days of hospitalization. Results: The 309 hospitals included in the analysis contributed a total of 166,931 patients, with 103 to 1,932 patients per hospital. Overall, 33,192 patients (19.9%) died in the hospital. Using fixed and random effects at the patient level, the predicted mortality ranged from 0.002 to 0.938 with a mean of 0.199. Our model had good discriminatory ability (AUROC ⫽ 0.78) and had acceptable calibration as evidenced by a calibration plot. Conclusions: A model to predict mortality in sepsis patients that relies only on claims data can be developed with high discrimination. External validation is needed to confirm the model’s performance.


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INFERIOR VENA CAVA FILTERS IN SPINAL CORD INJURY PATIENTS: NECESSARY OR DISCRETIONARY?

RISK FACTORS FOR POSTOPERATIVE CHRONIC CRITICAL ILLNESS AFTER COMMON GENERAL SURGICAL PROCEDURES

Megan Brenner, University of Maryland Medical Center R Adams Cowley Shock Trauma Center, Grant Bochicchio, University of Maryland School of Medicine, Kelly Bochicchio, University of Maryland, Thomas Scalea, University of Maryland Medical Center R Adams Cowley Shock Trauma Center Introduction: Spinal cord injury patients (SCI) are at increased risk for potentially lethal venous thromboembolism (DVT) and pulmonary embolism (PE). Hypothesis: Our objectives were to determine the incidence of DVT and PE in this high risk population and the potential benefit of prophylactic inferior vena cava (IVC) filter placement. Methods: 1424 critically injured patients admitted to our urban trauma were prospectively evaluated over a four year period. Patients admitted with acute spinal cord injury (SCI) were identified and data on demographics, spinal cord injury level and completeness, outcomes, venous thromboembolic events, and presence of IVC filter were recorded and analyzed. Results: A total of 84 SCI patients were identified out of 1424 critically injured trauma patients reviewed for an incidence of 5.9%. Of the 84 SCI patients, 64 (76.2%) had cervical, 17 (20.2%) thoracic, and 3 (3.6%) lumbar spine injuries. The mean age of SCI patients was 39 ⫾ 17 years, and 88.1% of patients were male (n⫽74). The mean ISS was 32.9 ⫾ 16.2, mean hospital length of stay was 22.7 ⫾ 14 days, mean number of ICU days was 17 ⫾ 12, and mean days on the ventilator was 18 ⫾ 14. DVT was identified in 2 patients for an overall incidence rate of 2.4%; both patients had an IVC filter in place at the time of diagnosis. One patient (1.2%) experienced a pulmonary embolism; this patient had neither a DVT nor an IVC filter. In this cohort, 72.6% of all SCI patients underwent insertion of an IVC filter, with placement occurring a mean of 7 ⫾ 4 days after admission. 15.5% of patients had a concomitant pelvic or long bone fracture. Conclusions: The rate of DVT and PE in this high risk population was much lower than expected. The practice of prophylactic IVC filter insertion should be closely re-evaluated.

Zara Cooper, Brigham & Women’s Hospital, Nathanael Hevelone, Brigham and Women’s Hospital, Selwyn Rogers, Louis Nguyen, Brigham & Women’s Hospital Introduction: Chronic critical illness (CCI) affects over 100,000 patients and accounts for over $20 billion per year of healthcare expenditures. CCI consumes 20 - 40% of ICU bed days, and the incidence is rising; in some series mortality approaches 50%. Given recent healthcare reform, addressing the needs of these patients has important implications for cost containment and resource distribution. Relatively little is known about CCI in surgical patients compared to medical patients with chronic conditions. We sought to identify factors associated with postoperative CCI after four common general surgery procedures. Methods: CCI was defined as mechanical ventilation ⬎96 hours with tracheostomy and hospital LOS ⬎21 days. Using multivariate logistic regression, patients undergoing appendectomy, cholecystectomy, colectomy, and small bowel resection in the Nationwide Inpatient Sample from 2003 to 2007 were analyzed to identify factors associated with postoperative CCI. Results: Of 256,822 admissions, 809 (0.32%) met the criteria for CCI. Using appendectomy as the reference group, patients with cholecystectomy (OR 7.86, 95%CI 4.77-12.96), colectomy (OR 16.50,95%CI 10.57-25.77) and small bowel resection (OR 22.07, 95%CI 14.08-34.60) were more likely to have CCI. Large (OR 1.81, 95%CI 1.38-2.39), medium-sized (OR1.77, 95%CI 1.32-2.38), and urban teaching hospitals (OR 1.59, 95%CI 1.37-1.84) were also associated with CCI. Patient and procedure characteristics including age⬎65 (OR 1.33, 95%CI 1.12-1.58), Black race (OR 1.38, 95%CI 1.11-1.71), COPD (OR 1.69, 95%CI 1.42-2.01), preoperative renal failure (OR 2.36, 95%CI 1.85-3.01), preoperative CHF (OR 2.96, 95%CI 2.42-3.62), and emergency surgery (OR 2.68, 95%CI 2.27-3.17) predisposed patients to CCI. Conclusions: We found that age, race, emergent surgery, preoperative CHF and renal failure are associated with CCI, a rare but dire outcome, after these common surgical procedures. Surgeons and intensivists can preoperatively identify patients at greater risk for CCI, thus improving pre-operative risk assessment, resource allocation, and helping patients and families anticipate CCI as a potential outcome.

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RECOGNIZING OPIOID AND BENZODIAZEPINE RELATED ADVERSE DRUG EVENTS IN CHILDREN THROUGH AN AUTOMATED DETECTION SYSTEM

GENDER DIFFERENCES IN SEPSIS OUTCOME IN PRE-PUBERTAL AND POST-PUBERTAL CHILDREN

Kitman Wai, Brian Jacobs, David Stockwell, Children’s National Medical Center Introduction: Excessive sedation and/or respiratory depression associated with the use of opioid or benzodiazepine can cause significant morbidity in children. Identifying correctable patterns can improve care. Adverse drug event (ADE) detection utilizing triggers derived from the electronic health record (EHR) has been shown to be more effective and efficient than voluntary incident reporting. Hypothesis: An EHR-driven automated detection system is effective in identifying opioid and benzodiazepine ADEs utilizing their respective antagonists and can efficiently targets areas for improvement in children. Methods: A retrospective observational study of all automated naloxone/flumazenil triggers generated by an EHR-driven surveillance system was conducted at a large urban children’s hospital over 30 months. All triggers were investigated to determine if an ADE occurred, the degree of patient harm, if the ADE was preventable and to identify populations at risk for ADEs. Results: Sixty naloxone triggers were identified, of which 48 were ADEs (PPV ⫽ 0.8) and 54% were preventable. Three out of 6 flumazenil triggers were determined to be ADEs (PPV⫽ 0.5) and 66% were preventable. Of 51 total ADEs identified via this system, only 2 (3.7%) were also identified via voluntary incident reporting. Seventy percent of ADEs from opioid/benzodiazepine use occurred in the ICUs for procedures, pain control, and following tracheal extubation. Of the preventable ADEs, 25% occurred when the analgesic regimen was escalated concurrent with respiratory distress, 20% from extubation following recent use of sedation infusions, and 12% during in-hospital transfers. Eighty percent of preventable ADEs caused temporary harm while 15% lead to prolonged hospital stays, of which 50% occurred from extubation following recent sedation. Conclusions: Automated antagonist triggers are much more effective in detecting opioid and benzodiazepine ADEs than incident reporting. Our data suggest that most ADEs can be prevented by early recognition of respiratory distress, diligent assessment of pre-extubation sedation, and improve communication during patient hand-offs.


Anoopindar Ghuman, Childrens Hospital Los Angeles, Christopher Newth, Childrens Hospital of Los Angeles, Robinder Khemani, Childrens Hospital Los Angeles Introduction: Studies have suggested hormonal differences in females may lead to better sepsis outcome. Hypothesis: Pre-pubertal males and females will have similar sepsis outcome, but post-pubertal males will have a worse outcome than post-pubertal females. Methods: Retrospective review of the VPS database (74 PICUs) from 2006-2008. Patients had a primary or secondary diagnosis of sepsis or septic shock and were pre-pubertal (2–7 years) or post-pubertal (16 –21 years). Results: Pre-pubertal females (n⫽496, 11.7% mortality) and males (n⫽552, 13.8% mortality) had similar mortality, comorbidities, interventions (dialysis, mechanical ventilation), ICU length of stay (LOS) for survivors, and PIM2 Risk of Mortality (ROM). Pre-pubertal females had a PIM2 Standardized Mortality Ratio (SMR) of 1.84 (1.4, 2.38) compared to 1.69 (1.33, 2.12) for pre-pubertal males. Post-pubertal females (n⫽368, 10.6% mortality) and males (n⫽383, 16.4% mortality) had similar comorbidities. However, males were more frequently mechanically ventilated (44.2% vs. 34.8% p⫽0.03), had longer ICU LOS (3.75 days vs. 2.73 days p⫽0.045), and higher mortality (p⫽0.03). Postpubertal females were more likely to have a primary diagnosis of sepsis or septic shock (p⫽0.03) and have dialysis (p⫽0.01). PIM2 ROM was not significantly different for post-pubertal males and females but in a subgroup of 501 patients with PRISMIII available post-pubertal males had higher PRISMIII Probability of Death (p⫽0.04). Post-pubertal females had a PIM2 SMR of 2.56 (1.82, 3.5) compared to 2.53 (1.95, 3.24) for post-pubertal males. After controlling for severity of illness with PIM2, post-pubertal females had a non-significant trend for lower mortality than males OR 0.6 (0.35, 1.02). Conclusions: Sepsis outcome is not different in pre-pubertal males and females. However, post-pubertal septic males have higher mortality, longer ICU LOS, and higher PRISMIII severity of illness than post-pubertal septic females. Severity adjusted mortality was similar between groups. These post-pubertal gender differences may reflect hormonal influence on the cardiovascular and immune response to sepsis, behavioral differences, or unmeasured comorbidities.

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OUTCOMES OF PATIENTS WITH CANCER AND SEPSIS IN TEXAS: A POPULATION BASED STUDY OF CRITICALLY ILL PATIENTS

POST-OPERATIVE PULMONARY COMPLICATIONS IN US ABDOMINAL SURGERY: ATTRIBUTABLE MORTALITY AND MORBIDITY

Marylou Cardenas-Turanzas, Elenir Avritscher, Imrana Malik, Nisha Rathi, Kristen Price, Joseph Nates, The University of Texas MD Anderson Cancer Center

Walter Linde-Zwirble, Z D Associates, Jonathan Bloom, Covidien, Lee Fleisher, University of Pennsylvania

Introduction: Sepsis is a common and fatal complication of patients with cancer. Hypothesis: We described demographic, medical and resource utilization factors associated with sepsis in adults with cancer who utilized the emergency room (ER) and the intensive care units (ICU) of hospitals in Texas. Methods: By using the Texas Inpatient Data Collection (2005-2006) we selected discharges of patients who had ICD-9-CM codes for cancer, were admitted thru the ER, stayed in the ICU and were ⱖ18 years old. We collected data on sepsis, age, sex, race, ethnicity, type of cancer, mortality, hospital length of stay (LOS) and total hospital charges ($x1000 U.S.). We calculated the Charlson’s comorbid index and the sum of acute organ dysfunctions. We used the Chi2 when analyzing nominal or ordinal variables and the t-test and Mann-Whitney U test for continuous variables. Outcome of study: Sepsis vs. non-sepsis. We considered statistically significant a p-value of ⱕ0.01. Results: A total of 63,869 patients met inclusion criteria and 11.7% had sepsis. Demographic factors significantly associated with sepsis were: old age, male gender, non-white race, and Hispanic ethnicity. Medical factors significantly associated with sepsis were: hematological cancer, Charlson’s comorbid index ⱖ3 and, 1 or more acute organ dysfunctions. Compared with nonsepsis, the mean LOS and mean total hospital charges were significantly higher for patients with sepsis 7.1 vs 11.6 days and 44.6 (median 29.6) vs 84.5 (median 53); respectively. The in-hospital mortality was 33.5% for patients with sepsis compared to 7.9% for patients with non sepsis. The most frequently associated medical conditions in patients with sepsis were pulmonary compromise (38.3%) followed by pneumonia (34.8%), the mean total hospital charges when these conditions were present were $116.9 (median $76.8) and $96.3 (median $61.1) with a mortality of 38.9% and 55%; respectively. Conclusions: We found demographic, medical and resource utilization factors associated with sepsis in patients with cancer that deserve further investigation. The in-hospital mortality rates observed suggest that, patients with cancer must be included in all programs aimed at early detection and treatment of sepsis.

Introduction: Post-operative pulmonary complications (PPC) are associated with poor outcome. However, patients with more comorbidity may cost more in the absence of PPC and develop more PPCs, complicating attributable outcomes. We created a case-mix cost-model in abdominal surgery without PPC to quantify the risk of PPC from patient complexity and calculate attributable costs of PPC. Hypothesis: Patients with greater complexity are more likely to develop PPCs, but the attributable cost of PPC is not strongly associated with complexity. Methods: We selected all abdominal surgeries age 15⫹y from the 2008 Premier database. PPCs (pneumonia, bronchitis, pleural effusion, pulmonary collapse, pneumothorax and respiratory failure) and post-operative cardiac complications (PCCs: PVC, acute CHF, Vfib, AMI, cardiogenic shock, cardiopulmonary arrest) were identified with ICD-9-CM. The cost model was built using those with no PPC & no PCC (Simple) with age and Charlson co-morbidity as predictors. The predicted cost was used as the severity measure, stratified into complexity quartiles. Attributable resource use and outcome in PPC cases without PCC (PPCO) was calculated by complexity in comparison to Simple cases. Results: There were 45,969 cases, 3.6% mortality, 20.9% PPC and 1.9% PCC. The PPC rate increased nearly 3-fold with complexity (Q1-11.4%, Q4- 31.3%). While the cost of Simple cases increased 29% from 15,094 in Q1 to 19,412 in Q4, cost of PPCO cases increased only 9% from 40,063 in Q1 to 43,575 in Q4. The average added cost due to PPC was 26,086 after complexity adjustment. PCC increased with complexity (Q1-0.4%, Q4-3.5%). Attributable PPC cost in the PPCO was 91% of added and 23% of all costs. Attributable PPC deaths in the PPCO was 76% of added and 61% of all deaths. Conclusions: Underlying complexity increased the rate of PPC/PCC and the cost of those without post-operative complications. PPCO is 10 times more common than PCC and is associated with an almost tripling of costs compared to those without complications after correcting for complexity. Better strategies to prevent and manage PPCs could lead to greatly improved outcomes.



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LONG TERM OUTOCOME IN CHILDREN WITH CONGENITAL HEART DISEASE WHO SUFFERED FROM ACUTE KIDNEY INJURY DURING POSTOPERATIVE ICU STAY

RECALIBRATION OF APACHE II IN A RESPIRATORY DISEASE REFERRAL CENTER

Yuichiro Toda, Tatsuo Iwasaki, Kazuyoshi Shimizu, Tomohiko Suemori, Noriko Ishii, Hirokazu KAWASE, Kentaro Sugimoto, Moritoki Egi, Okayama University Hospital, Hiroshi Morimatsu, Okayama University Medical School, Kiyoshi Morita, Okayama University Hospital Introduction: We previously reported that approximately one third of children who underwent cardiac surgery suffered from acute kidney injury (AKI) judged by pediatric RIFLE criteria. However, no study exists where long term outcome is described in survivers from AKI during postoperative Intensive Care Unit (ICU) stay. Hypothesis: Most of survivers from AKI after pediatric cardiac surgery have good long term survival and good renal outcome. Methods: Retrospective chart review. One hundred and twenty patients who underwent cardiac surgery throughout 2007 and was diagnosed AKI by pediatric RIFLE during ICU stay were included in this study. 2 years follow upafter subjected cardiac surgery during 2007 was carried out from electronic medical records. To identify survival, renal outcome, and hospital admission status 2 years after cardiac surgery in patient with AKI during postoperative periods, any cause of deaths, creatinin, height, age, episodes of hospital admission at 2 years after the surgery were collected. And use of diuretics was also investigated. Results: Of total 120 patients with AKI during ICU stay after pediatric cardiac surgery, 89 children had complete medical records including survival. Eighty five patients (95.5%) survived at 2years after discharge from surgical admission. Fifty seven children (64%) had 2nd hospital admission within 2 years and most of them (41 patients, 46.1%) underwent scheduled next surgery at the admission. There were 55 patients who had blood tests at 2 years later and 54 patients had no kidney injury at 2 years later. Sixty three children take oral diuretics medication at 2 years later and only 6 patients were admitted into hospital at 2 years later. 4 deceased children were in AKI category Injury or Failure at the primary surgery. The patients in Failure at surgery take oral diuretics more often than those in Injury or Risk (Failure: Injury: Risk ⫽ 72.2%: 63.3%: 58.1%). Conclusions: Most of pediatric patients who suffered from AKI during ICU stay after cardiac surgery have good survival and normal kidney function at 2 years later from surgery.

Seyed Mohammad Hashemian, National Research Institiute of Tuberculosis & Lung Disease, Hamid Reza Jamaati, Shahid Beheshti University of Medical Sciences, kiarash Noorizadeh, Denever,USA, majid malekmohammad, Mandana Chitsazan, Golnar Radmand, Kowsar Hedayat, Shahid Beheshti University of Medical Sciences, Ali Akbar Velayati, NRITLD Introduction: Several models have been developed to measure the severity of illness of the intensive care unit (ICU) patients, so far. It is confirmed that the models should be recalibrated and customized depending on the characteristics of different population of patients. Hypothesis: This study is aimed to assess and recalibrate the performance of Acute Physiology And Chronic Health Evaluation II (APACHEII) model in an Iranian respiratory diseases referral center. Methods: A total of 730 patients, admitted to the intensive care unit of National Research Institute of Tuberculosis and Lung Diseases (NRITLD) during one year, were randomly divided into two sets (71% training and 29%test). Local APACHEII model was developed and calibrated on the training set. Then, the integrity of the calibrated model was checked and compared to the original APACHE II, on the test set. Logistic regression was used to develop and ROC analysis, F-measure and kappa coefficient were employed to calibrate the model. Results: Both Original and Local APACHE II scores performed acceptable discriminative power (AUC⫽0.908: 95%CI 0.861-0.854; and AUC⫽0.856: 95%CI 0.789-0.923, respectively); the difference was not significant (P⫽0.132). The Local APACHEII showed improved accuracy (87.9% vs. 84.1%) and sensitivity (56.4% vs. 16.3%) compared to the original model. F-measure and Kappa also gave the impression of improvement for the Local APACHE II system. Conclusions: The results demonstrate that developed local APACHEII systems have similar discrimination but better calibration compared to the original model.

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APOLIPOPROTEIN E E4 ALLELE DOES NOT INCREASE THE RISK OF POSTOPERATIVE DELIRIUM AFTER MAJOR SURGERY

MRSA SURVEILLANCE STUDY USING STANDARD NASAL SWAB CULTURE AND MRSA PCR ASSAY AT AN EMERGENCY DEPARTMENT TO AN INTENSIVE CARE UNIT IN JAPAN

Vera Fernandes, Hospital de S. Joaõ, Porto - Portugal, Miguela Botelho, Hospital de Saõ Joaõ Porto - Portugal, Patricia Santos, Hospital de S. Joaõ Porto - Portugal, Alice Santos, Hospital de Saõ Joaõ Porto - Portugal, Fernando Abelha, Hospital de S. Joaõ Porto - Portugal

Haruaki Wakatake, St. Marianna University, Shigeki Fujitani, St Mariannna, Yasuhiko Taira, St. Marianna University Hospital

Introduction: A relashionship between patients who develop postoperative delirium and genetic predisposition has not been yet determined. Hypothesis: The presence of Apoliprotein E 4 (APOE4) allele increases the risk of postoperative delirium after major surgery. Methods: This prospective study was carried out in the Post-Anaesthesia Care Unit (PACU) with 5 intensive care beds. Of 230 patients admitted to PACU among a period of 3 months after non cardiac and non neurological major surgery, 173 were included. Patients’ demographics, perioperative data, PACU and hospital length of stay (LOS) and mortality were collected. Patients were screened for delirium using the Intensive Care Delirium Screening Checklist. DNA was extracted from whole blood samples at admission. The APOE4 genotype was determined using polymerase chain reaction and restriction enzyme digestion. Pearson Chi-square test and logistic binary regression analysis were used. Results: Of the 173 patients studied, 26 (15%) developed delirium after surgery. Twenty-four patients (14%) had at least one APOE4 allele. The presence of APOE4 allele was not associated with an increased risk of early postoperative delirium (4% vs 17%; p⫽ 0.088). Univariate analysis identified age, hyperlipidemia, congestive and ischemic heart disease, ASA physical status, emergency surgery, RCRI score, Troponin I at PACU admission, Lawton score and dependency in Personal Activities of Daily Living as predictors for development of delirium in postoperative period.Multivariate analysis identified age (OR 9.3, 95%CI 2.0-43.0, p⫽0.004 for age ? 65 years), congestive heart disease (OR 6.2, 95%CI 2.0-19.3, p⫽0.002) and emergency surgery (OR 59.7, 95%CI 6.7-530.5, p⬍0.001) as independent predictors for delirium.SAPS II and APACHE II were significantly higher in patients with delirium (p⬍0.001 and 0.008 respectively). Hospital mortality was higher (35% vs 3%, p⬍0,001) and PACU LOS was longer (46 vs 19 hours, p⬍0.001). Conclusions: APOE carrier status was not associated with an increased risk for postoperative delirium. Age, congestive heart failure and emergency surgery were independent risk factors for delirium. Delirium had serious impact in PACU LOS and in mortality.


Introduction: In Japan, few MRSA surveillance studies using nasal swab cultures and rapid MRSA PCR Assay have been reported. MRSA colonization rate in patients hospitalized through ED to ICU in Japan is unknown. Hypothesis: An epidemiology survey to investigate MRSA colonization ratio using standard nasal swab culture and MRSA PCR Assay for high-risk patients hospitalized through ED to ICU. Methods: From November 1, 2009 to August 31, 2010, a prospective epidemiology study was performed at two metropolitan tertiary EDs. High risk of MRSA colonization was determined a priori including 7 factors, and both MRSA surveillance culture and PCR Assay (BD GENEOHMTM MRSA) was examined in each patient with high risks of MRSA colonization hospitalized through EDs to the ICU. Results: Total 156 cases were collected. 28.2% (44/ 156) of cases was positive either from surveillance cultures or PCR Assay. 8.3% (13/156) cases was culture negative with PCR Assay positive, while 1.3% (2/156) cases was culture positive with PCR Assay negative. A case compatible either with following 1-71. Past history of MRSA colonization: 57.1%(4/7)2. Hospitalization from a nursing facility : 27.8%(15 /54)3. ⱖ 30 days hospitalization in the past 3 months : 33.3%(14 /42)4. End-stage kidney diseases on hemodialysis : 22.7%(5 /22)5. Chronic skin diseases : 20.0%(4/20)6. Patients with malignant diseases with ⱖ 1 factors among following 5 factors : 28.0%(7/25) [5 factors were ⱖ 5 hospitalizations in the past 1 year, history of chemotherapy in the past 30 days, history of surgical operation in the past 30 days, history of antibiotics usage in the past 30 days, and continuous Foley catheter placement.]7. ⱖ 2 factors among following 4 factors : 31.6%(30/95)[4 factors were ⱖ 75 years old, history of hospitalization due to acute illness in the past 6 months, history of following antibiotic usage in the past 6 months, and ⱖ10 days hospitalization in the past 3 months]. Conclusions: The prevalence rate of MRSA colonization in cases with high risk MRSA colonization was ⱖ 25%. MRSA PCR Assay shows very low rate of false negative, and about 10% cases would have been missed to detect MRSA colonization without using MRSA PCR Assay.

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KL-6, A HUMAN MUC1 MUCIN, AS A PROGNOSTIC FACTOR FOR DIFFUSE ALVEOLAR HEMORRHAGE SYNDROME

INTERMEDIATE TERM OUTCOMES IN ICU PATIENTS WITH SEIZURES FOLLOWING CARDIAC SURGERY

Yoshiko Kida, Shinichiro Ohshimo, Kohei Ota, Tomoko Tamura, Shoichi Kurosaka, Tadatsugu Otani, Taku Takeda, Yasumasa Iwasaki, Nobuyuki Hirohashi, Koichi Tanigawa, Grad. School of Biomed. Sci., Hiroshima Univ.

Rizwan Manji, Hilary Grocott, Jill Leake, Sadia Khan, Kristen Black, Jacqueline Manji, Alan Menkis, Johann Strumpher, Eric Jacobsohn, University of Manitoba

Introduction: Diffuse alveolar hemorrhage (DAH) syndrome is a group of lifethreatening complication following diverse pathogenesis including infection, excessive anticoagulation and vasculitis. To date, the prognostic factors for DAH have not been well investigated. KL-6, a complex sialo-carbohydrate glycoprotein present in the human MUC1 mucin, is a sensitive serum marker for various interstitial lung diseases (ILD). Previous studies have demonstrated that the serum KL-6 level was associated with the disease activity and the prognosis in ILD. Hypothesis: The purpose of our study was to investigate a utility of KL-6 as a prognosticfactor for DAH. Methods: We retrospectively collected the consecutive patients clinically diagnosed as having DAH who were admitted to the Advanced Emergency and Critical Care Center/ ICU of Hiroshima University Hospital (Hiroshima, Japan) between 2004 and 2010. Correlations between prognosis and age, sex, laboratory findings,radiological findings, ventilatory modes or therapeutic regimens were evaluated. Results: A total of 17 patients were included in this study (male/female, 10/7; mean age,60 (16-83)). The pathogenesis of the enrolled patients was excessive anticoagulation (n⫽7), idiopathic (n⫽6), infection (n⫽3) andMPO-ANCA-associated vasculitis (n⫽1). Six patients survived, while 11 died. Thenon-survivors were significantly older than the survivors(non-survivor/survivor, 72⫾11/55⫾22, p⫽0.02). The length of ICU stay wassignificantly longer in non-survivors than survivors (42⫾21/7⫾7 days, p⫽0.002).No significant difference was found in the initial serum KL-6 levels betweenthe groups; however, the serum KL-6 levels 48 hours after admission and thepeak levels were significantly higher in non-survivors than survivors (1563⫾2246/270⫾131U/ml, p⫽0.02; 2040⫾2522/446⫾223 U/ml, p⫽0.02). In univariate analysis, femalesex and peak serum KL-6 level ⬎1000 U/ml were the poor prognosticfactors (p⫽0.04, p⫽0.02). In multivariate analysis, only peak serum KL-6 level ⬎1000U/ml was the independent poor prognostic factor (p⫽0.03; Hazard ratio, 11.8; 95%CI,1.25-111.1). Conclusions: In conclusion, the peak serum KL-6 level ⬎1000 U/ml may be of clinical use as the poor prognostic factor for DAH.

Introduction: Seizures (SZ) occur in patients following cardiac surgery (CS) in the ICU. There is minimal descriptive data outlining the implications of seizures on overall outcome. Hypothesis: We sought to provide a descriptive analysis of the intermediate outcomes in patients with SZ post CS. Methods: A retrospective chart review was conducted of all patients that had SZ following CS at a single institution from April 2003 to Jan 2010. In addition to recording in-hospital outcomes, patients were followed post discharge via telephone interview. Results: SZ occurred in 56 of 5958 (0.94%) cardiac surgery ICU patients with 35% of the seizing patients being females. Patients were mean (SD) 70.9 (11.6) years old, with an APACHE score of 20.8 (7.1) and had a cardiopulmonary bypass time of 156.5 (79.7) min. Preop neurological disease was present in 29%, preop cardiac arrest in 6%, preop renal dysfunction in 20% and preop peripheral vascular disease in 26%. Seventy-one percent had open heart procedures and 12% had previous cardiac surgery. The time to first SZ was -median (IQR) - 4.5 (2.3 – 9.2) hours after end of surgery with 60% having grand mal SZ; 64% having recurrent sz within 24 hours of first sz, and 49% having recurrent sz during hospital stay. Most seizures lasted minutes however 4 patients (females, mean age 78 years, mean APACHE score 26.5, all having had aortic valve or other aortic surgery) demonstrated nonconvulsive status epilepticus confirmed via EEG. CT head demonstrated old or new stroke in 45% of all patients. ICU LOS was 4.7 (2.0 – 7.8) days with ICU mortality 7%. Hospital LOS was 15.0 (10.0 – 33.0) days with hospital mortality 20%. Follow up was available on 70% of patients with a median follow up of 16 (9 – 29) months. No patient experienced a seizure after discharge from hospital; at the median follow-up period, only 30% continued on anticonvulsant therapy. Stroke after discharge occurred in 5% of patients. Thirtysix percent of patients were unable to drive post op due to restrictions secondary to SZ. Conclusions: SZ following CS are relatively uncommon but when they occur, they are associated with long ICU and hospital LOS, as well as high ICU and in-hospital mortality.

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CRITICALLY ILL CHILDREN IN THE EMERGENCY DEPARTMENT MAY IMPACT ED QUALITY AND EFFICIENCY

ELECTRONIC SIRS ALERT FACILITATING RECOGNITION OF SEPSIS BY HOUSESTAFF

Adam Silverman, Christopher Carroll, Connecticut Children’s Medical Center

Tracy McGrane, Vanderbilt University, Michael Hooper, Vanderbilt Pulmonary Division, Todd Rice, Supriya Srinivasa Gowda, Vanderbilt University, Lisa Weavind, Vanderbilt University Medical Center

Introduction: The care of a critically ill child in a pediatric emergency department (PED) requires an immediate reallocation of resources. In many situations, this could result in the care of other patients being compromised or prolonged. We theorized that when a critically ill child presents to a PED, the efficiency of the care provided is affected, and the length of stay (LOS) for the non-critically ill children in the PED is prolonged. Hypothesis: During periods when a critically ill child is present in the PED, LOS increases for non-critically ill children. Methods: For a study period between 1/1/2009-12/31/2009, demographic data, triage acuity level, and outcome data (disposition and PED LOS) were compared between a study group of non-critically ill children treated in the PED in the same time period as a critically ill child and a control group treated without a critically ill child present in the PED. Groups were matched by time and day of the week, and an exposure period of 270 minutes was used. Critical illness was defined by admission to a pediatric intensive care unit. Results: During the study period, there were 349 critically ill children seen in the PED. While these children were treated, there were 8805 non-critically ill children also seen in the PED. Compared to the control group of 8934 children, there were no significant differences in the LOS associated with the presence of a critically ill child in the PED (155 ⫹ 93 vs. 154 ⫹ 98 minutes; p⫽0.63). Age, admission diagnosis, or triage level also did not affect LOS in the PED. However, for a subset of non-critically ill children who required admission to the hospital (n⫽1550), presence of a critically ill child was associated with a decrease in PED LOS from 270 ⫹ 108 minutes to 241 ⫹ 103 minutes (p⬍0.001). Conclusions: Although critically ill children require a reallocation of resources, their presence in the ED did not increase the LOS for other patients in the PED. In fact, LOS was shortened in some children during those periods when a critically ill child presented to the PED. Further study is needed to determine whether the presence of a critically ill child affects the quality of care provided to the other non-critically patients.

Introduction: Despite advances in critical care practice guidelines and therapies, sepsis mortality rates remain high. Early recognition and treatment of sepsis is associated with improved outcomes. Hypothesis: We hypothesized that in ICU patients with modified SIRS criteria, realtime housestaff evaluation for sepsis would be positively correlated with a retrospective evaluation by critical care physicians. Methods: An electronic surveillance tool was used to identify 327 consecutive patients who met modified SIRS criteria (2 SIRS criteria with at least one being abnormal WBC count or temperature) in the medical and surgical intensive care units at a single center. The tool subsequently provided a text page alert to housestaff who ascertained whether the modified SIRS criteria were due to infection. Results: Patients enrolled were 57% male with a mean age of 56 years, 27% were in shock, and 31% were intubated. The mean WBC count was 14.7x103/mm3, temperature 37.5°C, respiratory rate 30 breaths/min, and heart rate 117 beats/min. Rates of positive blood cultures were low both before (9%) and after (7%) enrollment. The mean ICU LOS was 9 (⫾ 9.7) days and 16% of patients died. Housestaff identified 143 (43.7%) of the patients as septic at enrollment. An ICU fellow or attending retrospectively determined 163 (49.8%) of the SIRS alerts were due to an infectious etiology. Using retrospective analysis as the gold standard, housestaff ascertainment had 75% sensitivity, 74% specificity, 69% positive predictive value and 79% negative predictive value. Conclusions: We conclude that a real time electronic detection and SIRS alert to housestaff can help facilitate sepsis recognition and is positively associated with retrospective evaluation. However, a substantial number of patients were not correctly identified as septic at the time of SIRS alert. Further analysis of septic patients that were not correctly identified at enrollment may help recognize the characteristics of patients at risk for treatment delays.


615 RESOURCE USE 1 YEAR PRIOR TO AND 3 YEARS POST ICU SEVERE SEPSIS Walter Linde-Zwirble, Z D Associates, Hannah Wunsch, Columbia University Medical Center, Sachin Yende, University of Pittsburgh, Carmen Guerra, Columbia University, Derek Angus, University of Pittsburgh Critical Care Medicine CRISMA Laboratory Introduction: ICU severe sepsis (ISS)patients have great resource use during hospitalization and are oftendischarged to skilled care, resulting in ongoing resource use. On the otherhand, they often have multiple chronic co-morbidities and could havesignificant resource use independent of ISS. We examined resource use 1-yearprior and 3 years following hospitalization for Medicare ISS patients andage/race/gender matched hospital (HOS) and general (GEN) controls. Hypothesis: Post-discharge costs arecorrelated with prior year cost of care. Methods: We identified the first ISShospitalization for all Medicare beneficiaries age 66⫹ from a 2.5% fee-for-servicesample in 2003 using Angus methodology. Total Medicare Trust Fund payments for ISS and matched HOS andGEN controls were calculated by quarter and inflated to 2009 using the urbanCPI for the year prior and 3y post index date. Costs were stratified bysurvival status: hospital dead; died by day 180 (EARLY); died day 181-1080(LATER); alive after 1080 (3y SURV). Results: There were 7468 ISS discharges, mean age of 78. Prior year cost was higher in ISS non-survivors $20,614for hospital dead, $22,461 for EARLY, $22,227 for LATER, compared to $12,196for 3y SURV. Prior year costs for 3y SURV control groups was much less, $8,528for HOS and $3,999 for GEN. ISS 3y SURV cost $4,100/qtr compared to $2,636 forHOS and $1,356 for GEN during the 3 years of follow-up. After the first quarter post hospitaldischarge, ISS 3y SURV were less costly than the quarter prior to ISS ($4,100vs. $4,224/qtr), while HOS increased by 46% and GEN by 25% by 3 years. ISS postdischarge non-survivors were 41% more costly ($9,559/qtr) after dischargecompared with the quarter prior to ISS ($6,761). Conclusions: ISS non-survivors are veryexpensive in the year prior to ISS and more costly following discharge for latenon-survivors. ISS 3 year survivors did not have greater quarterly cost afterISS hospitalization in contrast to control groups that became more expensiveover time. ISS hospital survivors are costly following ISS because they costmore before acute illness.



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RISK FACTORS ASSOCIATED WITH CONTRAST-INDUCED NEPHROPATHY IN TRAUMA PATIENTS

THE SIGNIFICANCE OF USING AKIN CRITERIA FOR ASSESSING THE INCIDENCE OF ACUTE RENAL INJURY, OUTCOME AND OTHER PROGNSTIC FACTORS OF CRITICALLY ILL PATIENTS IN ICU

Lauren Jones, J. Bethea, Charleston Area Medical Center Introduction: Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal insufficiency. Limited data exists assessing risk factors associated with CIN in the trauma population. The purpose of this study was to determine the risk factors associated with CIN in trauma patients at Charleston Area Medical Center. Hypothesis: Patients with baseline renal dysfunction, increased age, hypotension at the time of contrast, rhabdomyolysis due to associated injuries, or concomitant nephrotoxic medications are at an increased risk of developing CIN. Methods: This was a retrospective review of trauma patients who developed AKI during hospitalization and received at least one dose of intravenous contrast. Patients were included if they had a baseline and repeat SCr 48-72 hours after contrast. CIN was defined as an increase in SCr ⬎ 0.5mg/dL or ⬎ 25% from baseline within 48-72 hours following contrast. Comparisons between the groups were performed using Chi-square or Fisher’s Exact tests for categorical variables and Mann-Whitney U or t-tests for continuous variables. An alpha level of ⬍ 0.05 was used to determine statistical significance. Results: Fifty patients were included in the study (CIN positive n⫽22, CIN negative n⫽28). Baseline renal insufficiency, increased age, hypotension, and concomitant nephrotoxic medications had no effect on the development of CIN. There was no difference in rhabdomyolysis as evidenced by creatine phosphokinase and urine myoglobin; however, the majority of patients did not have these values measured at baseline. CIN was more common in patients with liver (p⫽0.0124) or pancreatic/gallbladder (p⫽0.0318) injuries. All other injuries including orthopedic, CNS, and renal were not found to significantly impact the development of CIN. Patients were less likely to develop CIN if they received fluid boluses prior to contrast (p⫽0.0498). Prophylaxis with N-acetylcysteine or a bicarbonate infusion did not prevent the development of CIN. Conclusions: Data from this study showed that liver, pancreatic, and gallbladder injuries contributed to the trauma patient’s risk for developing CIN. Hydration with prophylactic fluid boluses prior to contrast decreased the risk of developing CIN.

Da-Wei Wu, Jin-Feng Yue, Chen Li, Deprtment of Intensive Care Medicine, Qilu Hospital, Shandong University, Jinan,China. Introduction: The Acute Kidney Injury Network (AKIN) proposed a new threestage classification for acute kidney injury (AKI) in 2005. Our aim was evaluating clinical significance of AKIN criteria for predicting the prognoses in critically ill patients, and further identifying the risk factors associated with the prognoses of the patients. Hypothesis: The AKIN classification system has directing significance to the early identification and classification of AKI, and can be used for predicting clinical outcomes in critically ill patients. Methods: We retrospectively studied 544 adult patients that had been hospitalized for ⱖ24 h in ICU at Qilu Hospital of Shandong University in the period of January 2008 to December 2009. Based on AKIN criteria, the 544 patients were classified into NAKI (no AKI), AKI I, II, and III respectively. Results: According to the AKIN criteria, AKI occurred in 191 of the 544 cases (35.5%), with 14.8% AKI I, 8.2% AKI II, and 11.9% AKI III respectively. Compared with the overall mortality rate 24.1% in our ICU, AKI, defined by any AKIN category, was associated with a significant increase in mortality (OR 7.48, 95%CI 4.831-11.587, P⬍0.0001). The mortality rate was 37% for AKI I, 51.1% for AKI II, and 60% for AKI III, with an average mortality of 48.2%. In multivariate analysis, each AKIN category was independently associated with ICU mortality (OR: AKI I, 3.532; AKI II, 5.231; AKI III 10.301). The other independent risk factors for ICU mortality included septic shock, pre-existing chronic illnesses, APACHE II score, the number of failed organs, and the need of mechanical ventilation and CRRT. Conclusions: The AKIN category closely related to the prognoses in critically ill patients, even the mild AKI – AKI I is associated with a much higher mortality rate than that of the patients without AKI. We conclude that the AKIN criterion provides a guideline for early identification and classification of AKI, and also can be used for predicting clinical outcomes in critically ill patients.

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OUTCOMES OF SEVERE SEPSIS IN UNINSURED PATIENTS

A PRIMER ON MECHANICAL VENTILATION IN AUSTERE ENVIRONMENTS: INSIGHTS GAINED FROM POST-EARTHQUAKE HAITI

Gagan Kumar, Medical College of Wisconsin, Abhishekh Deshmuk, University of Arkansas, Puneet Sood, Amit Taneja, Jayshil Patel, Thomas Kaleekal, Rahul Nanchal, Medical College of Wisconsin Introduction: According to the United States Census Bureau, in 2007, 15.3% the US population were without health insurance for at least part of the year. Previous work has demonstrated that a lack of health insurance impedes access to health care services and adversely affect outcomes in acute medical events. The aim of our study was to examine the outcomes of uninsured patients hospitalized with severe sepsis. Hypothesis: Uninsured patients will have worse outcomes in severe sepsis as compared to those with health insurance. Methods: Using the Nationwide Inpatient Sample Database (NIS) 2007, patients aged 18 or more who had the discharge diagnosis of severe sepsis were identified through ICD-9 code 995.92. NIS encompasses information on all patients regardless of payer, including Medicare, private insurance and the uninsured. Our primary outcome of interest was all cause in hospital mortality. The secondary outcomes was length of stay (LOS). Chi square test and t tests were used to compare the variables for unadjusted analysis. Multivariate logistic regression was used to obtain odds ratios. The model was adjusted for patient demographics, hospital characteristics and Elixhauser co-morbidity index. ␣ was set at 0.05. Results: In the 2007 NIS database, there were an estimated 338,456 discharges with severe sepsis. Of these, 3.0% of the patients were uninsured. The unadjusted mortality in uninsured patients was 37.9% compared to 31.8% in patients with private insurance. The mortality in Medicare patients was 38.2%, but this group were significantly older and had higher burden of co-morbidities.The multivariate analysis showed that the in hospital mortality in uninsured patients with severe sepsis was significantly higher even when compared to Medicare patients (OR 1.51; 95%CI 1.35-1.70). Uninsured patients had significantly shorted LOS when compared to Medicare patients (1.5 days shorter; 95%CI 0.6-2.5days). Conclusions: This observational study shows that adjusted in-hospital mortality is significantly higher in uninsured patients when compared to private insurance and Medicare patients. The LOS in uninsured is significantly shorter than the insured.

Randeep Jawa, University of Nebraska Medical Center, Tanya Zakrison, St. Michael’s Hospital, Frank Freihaut, Nebraska Medical Center, David Young, Joseph Stothert, David Mercer, University of Nebraska Medical Center Introduction: The earthquake of January 12, 2010 in Haiti created an unprecedented healthcare need in an impoverished country. The limited healthcare resources were placed under further duress. The Project Medishare field hospital was able to provide intensive care because it had oxygen and also functional mechanical ventilators a few weeks after the earthquake. Hypothesis: Mechanical ventilator set-up and maintenance in austere environments is complex, but possible. Methods: We discuss essential elements of ventilator set-up in austere environments, as both a descriptor of our experience and as a guide for aid workers. Results: The first element is a reliable oxygen supply. As the length of time that an oxygen canister lasts varies greatly, depending on patient and equipment needs, the oxygen needs to be continually replenished. These canisters should be secured in place. The second component is a selection of pressure valves (dual-stage vs. single-stage) and oxygen tubing (high pressure vs. low flow), as they vary by ventilator. A third component is ventilator maintenance. As the ventilators will need servicing, establishing service agreements is worthwhile. Air filters need to be cleaned. Ready access to ventilator operation manuals and technical support is important. Some ventilators have lock-down software; access codes are needed. Many ventilators have self-test modes, which should be run prior to their use. A fourth element is having spare circuit parts. We required constant replenishment of ventilator circuits, heat and moisture exchangers, suction catheters, ambu-bags, and PEEP valves. The fifth component is a portable x-ray machine. Sixth, a constant electrical source is vital. Finally the above information needs to be relayed to co-workers. Conclusions: While it is arguable whether mechanical ventilation should be provided in austere environments, it was accomplished and saved lives in post-earthquake Haiti. Our experience at the Project Medishare field ICU suggests an opportunity for betterment of mechanical ventilator training for physicians and nurses, and underscores the role of respiratory care personnel. We hope this work helps provide guidance for aid workers in austere environments.


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IS THERE A RELATIONSHIP BETWEEN SOFA SCORES AND ALBUMIN LEAK RATES AS A MARKER OF ENDOTHELIAL DYSFUNCTION?

ICU TRANSFERS FROM INPATIENT UNITS: HOW MANY RESULT FROM ADVERSE EVENTS AND ARE THEY PREVENTABLE?

Damian DeFrancesch, David Inouye, Brian Nishiguchi, Sho Furuta, Michael Hayashi, Kevin Pei, University of Hawaii , Fedor Lurie, Straub Foundation, Danny Takanishi, University of Hawaii , Mihae Yu, University of Hawaii and the Queen’s Medical Center

Alison Miles, Brian Jacobs, David Stockwell, Children’s National Medical Center

Introduction: Increased capillary permeability is a hallmark of the systemic inflammatory response syndrome (SIRS) or sepsis. An assessment of organ dysfunction may be obtained using the Sequential Organ Failure Assessment (SOFA) score. The albumin leak rate can be measured using I-131 tagged albumin injected into the patient and measuring serial disappearance of the isotope. The albumin leak rate - a surrogate of capillary permeability - may represent the degree of endothelial dysfunction and severity of illness. Hypothesis: There may be a relationship between the SOFA score and albumin leak rate. Methods: Criticallyill surgical patients requiring resuscitation after septic shock, cardiogenic shock and ARDS had blood volume analysis (BVA) performed on day 1 after resuscitation. Plasma volume was measured with the BVA-100 (Daxor, NY, NY) using I-131 labeled albumin (1ml) injected into the patient with 5 sequential blood draws at timed intervals to compensate for albumin leak. As part of the blood volume report, the albumin leak rate is presented as a % per minute, with normal values being 0-0.4% per minute. Albumin leak rate at Day 1 after resuscitation was compared with the SOFA scores obtained on the same day. Results: Of the 46 patients studied, demographics were: age 61 ⫾ 16 years, 15 females: 31 males, 38 septic shock/severe sepsis, 8 cardiogenic shock, 10 ARDS patients, APACHE II score 24 ⫾ 3 with a mortality rate of 8/46 (17%). Average SOFA score for the study patients was 7.17 ⫾ 2.9. The mean albumin leak rate was 0.19 ⫾ 0.1 % per minute. There was no difference in SOFA scores or albumin leak rate measured at 24 hrs after resuscitation between survivors and nonsurvivors. There was no correlation between SOFA scores and albumin leak (both done at 24 hours after resuscitation), r ⫽ 0.073 (p⫽0.628). Conclusions: The SOFA score measures the degree of organ failure and has been related to mortality. This study, however, did not demonstrate a relationship between the SOFA score and albumin leak at 24 hours.

Introduction: Unplanned transfers to an ICU from inpatient units may result from adverse events (AEs). Preventative strategies to mitigate AEs leading to ICU transfer can be implemented once risk factors are identified. Hypothesis: We hypothesized that AEs account for a significant rate of ICU transfers and that some may be preventable. Methods: A retrospective observational study of ICU transfers from inpatient units during a 6 month interval in a tertiary care children’s hospital. Transfers were electronically identified via the electronic health record then investigated to establish if an AE had occurred. The preventability of the AE and associated patient harm were determined. Predefined AEs included ICU transfers in less than (⬍) 12 hours of hospital admission, re-admissions to an ICU in less than (⬍) 24 hours after ICU discharge, and cardiopulmonary arrest events. AEs that did not meet these criteria were examined for causes and trends. Results: 249 ICU transfers occurred and 48 (19.3%) were attributed to AEs. 29 (60.4%) were transfers in ⬍12 hours of admission, 5 (10.4%) were ICU readmissions in ⬍24 hours of ICU discharge, and 8 (16.7%) were cardiopulmonary arrests. The remainder (12.5%) included postoperative complications (3), medication effects (1), electrolyte derangements (1), and hypotension (1). The most common diagnosis associated with AE related transfer was respiratory distress (25, 52.1%) with 18 (72%) transfers in ⬍12 hours of admission. 15 (31.3%) AEs were determined to be preventable. Of these,12 (80%) involved inappropriate triage with 8 ICU transfers in ⬍12 hrs of admission and 4 ICU readmissions in ⬍24 hours. Other preventable AEs included 2 (13.3%) cardiopulmonary arrests, and 1 (6.7%) patient with unresolved hyponatremia. Of all 48 AEs, 42 (87.5%) resulted in prolonged hospitalization and temporary harm, and 6 (12.5%) required treatment/intervention, resulting in temporary harm. Conclusions: Nearly one-fifth of unplanned ICU transfers resulted from AEs and almost a third were preventable. Interventions directed at triage processes are likely to reduce these events as many occurred early in admission. More than half of AE-related ICU transfers were associated with respiratory distress.

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PATTERN OF CERVICAL SPINE INJURY IN BLUNT ASSAULT: IT’S NOT HOW THEY’RE HIT, IT’S HOW THEY FALL

THE CIRCULATING PLATELET MICROPARTICLE INDEX IS ELEVATED IN SEVERE SEPSIS PATIENTS BUT DOES NOT PREDICT OUTCOMES

Narong Kulvatunyou, University of Arizona College of Medicine, Randy Friese, Bellal Joseph, Rifat Latifi, Terrance O’Keefe, Andy Tang, Julie Wynne, Peter Rhee, University of Arizona Introduction: The bio-mechanism of cervical spine injury (CSI) involves: (1) a significant acceleration-deceleration of the patient’s head and neck, resulting in flexion-extension with a distracting pattern of injury i.e., as seen in motor vehicle collisions; (2) a compressive pattern of the patient’s head or face after contacting an immovable object where the principal direction of force (PDOF) is transmitted down the cervical spine. These two components yield imparted energy (IE). Hypothesis: We think IE is low for blunt assault and the incidence of CSI is low. Methods: The trauma registry at our level I urban trauma center was queried for patients admitted with the diagnosis of blunt assault over a 5-year period (2005 through 2009). Patients with CSI were identified by International Classification Diagnosis (ICD) codes of 805, 806, 839, or 952. In order to eliminate those patients without PDOF to the head and face, those with a head or face abbreviated injury score (h-AIS, f-AIS) of 0 were excluded. For eligible patients data were extracted from inpatient charts, including radiographic reports. A single author (NK) reviewed all individual with CSI computerized tomography (CT) scans. Summary and correlation statistics were performed. Results: We identified 1,336 blunt assault patients with PDOF to the head and face. All underwent CT of the head, cervical spine, and face. CSI was diagnosed in 82 patients; however, 65 had negative CT and were diagnosed as having cervical sprain. Of the remaining 17 patients, 6 had incorrect diagnosis, 1 had a herniated disc, 2 had spinal stenosis, and only 8 had a true CSI, yielding an incidence of 0.6%. There was no correlation between CSI and f-AIS severity (r⫽ -0.07). All CSI patterns were unique and involving the level of C5-6 that was associated with fall but not associated with PDOF to the head or face. Two patients had a fall after the assault and suffered significant subluxation that was associated with spinal cord injury. The other 6 patients had injuries that were considered benign and did not require immobilization. Conclusions: The incidence of CSI after blunt assault is very low, and the pattern of injury is related to fall occurring after the assault.


SeungHye Han, Rochester General Hospital, Judith Stewart, Cynthia Mack, University of Rochester Medical Center, Michael Gough, Univ. of Rochester Medical Center, Mary Anne Morgan, Mark Frampton, Strong Memorial Hospital Rochester University, Michael Apostolakos, Strong Memorial Hospital, Denise Darling, Kathleen Doolin, University of Rochester Medical Center, Anthony Pietropaoli, Univ. of Rochester Medical Center Introduction: Circulating platelet microparticles are defined as serum particles with diameter ⬍ 1 micron displaying the cell surface markers of CD42b and CD31. Higher numbers of circulating platelet microparticles have been associated with systemic inflammation and vascular dysfunction in a variety of disease states. Previous studies indicate that lower numbers of platelet microparticles are associated with increased mortality in sepsis, suggesting a counter-intuitive protective effect of platelet microparticles. However, these findings were not adjusted for the thrombocytopenia commonly observed in septic patients. Hypothesis: The platelet microparticle index (ratio of platelet microparticles to platelets) is elevated in sepsis and associated with higher mortality. Methods: Venous platelet and platelet microparticle concentrations were measured using flow cytometry in 113 patients with severe sepsis and 52 healthy control subjects. The Mann-Whitney test was used to compare platelet microparticles and the platelet microparticle index between severe sepsis patients and control subjects, and between sepsis survivors (n⫽80) and non-survivors (n⫽33). Results: The numbers of platelet microparticles were similar between sepsis patients and controls (median ⫾ interquartile range (IQR): 1580 ⫾ 1800/␮L vs. 1760 ⫾ 1700/␮L, p⫽0.9109), but lower in sepsis non-survivors versus survivors (median ⫾ IQR: 1380 ⫾ 1600/␮L vs. 1740 ⫾ 2500/␮L, p⫽0.0339), the latter consistent with prior studies. In contrast, the platelet microparticle index was higher in severe sepsis patients compared to control subjects (median ⫾ IQR: 0.01046 ⫾ 0.0123 vs. 0.00639 ⫾ 0.0059, p⫽0.0001), but similar between sepsis non-survivors and survivors (median ⫾ IQR: 0.00975 ⫾ 0.0120 vs. 0.01061 ⫾ 0.0133, p⫽0.8557). Conclusions: After adjustment for the degree of sepsis-associated thrombocytopenia, platelet microparticle counts were elevated in septic patients but not associated with mortality. The pathological significance of platelet microparticles in sepsis remains unclear. Research support: This study was supported by NIH K23 HL080077, NCRR 1 UL1 RR024160-01, and T32 HL066988.

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DAILY INTERRUPTION OF SEDATION: FEAR AND LOATHING IN THE ICU

THE PIRO CONCEPT: INFECTION-ASSOCIATED CONDITIONS FOR COMMUNITY-ACQUIRED SEVERE SEPSIS AND SEPTIC SHOCK RELATED-MORTALITY (RESULTS FROM THE SACIUCI STUDY)

Melissa Miller, University of Michigan Health System, Emily Bosk, Sarah Krein, University of Michigan, Theodore Iwashyna, University of Michigan Health System Introduction: Despite strong medical evidence and policy initiatives supporting the use of daily interruption of sedation (DIS), compliance remains suboptimal and often refractory to efforts to improve. Hypothesis: Practitioners’ understandings of DIS are influenced by strong emotional responses, including specific fears and concerns which impact decision-making regarding DIS. Methods: Focus groups of physicians, nurses, and respiratory therapists were conducted in an academic medical intensive care unit regarding practice of and attitudes and barriers toward DIS. Transcripts were analyzed to evaluate for practitioner concerns, emotional responses, and subsequent practical outcomes. Results: Practitioners were primarily concerned about three major themes regarding the patient experience of sedation interruption: patient anxiety, patient discomfort, and safety. These concerns resulted in a wide range of strong practitioner emotional responses, including empathy, “If it was me sitting there? I’d want to be out” (physician); terror, “The thought of turning off that sedation scared me to death!” (nurse); and protectiveness, “I think that we all err on the side of over-sedating versus having too light sedation and putting the patient at risk” (physician). These emotional responses resulted in two classes of responses: adaptive or maladaptive. Practitioners with adaptive responses were more likely to view DIS positively and to report performing it more often, whereas practitioners with maladaptive responses were more likely to view DIS negatively. Specific emotional responses were not uniquely linked to either adaptive or maladaptive responses. Conclusions: DIS elicits potent emotional responses in practitioners which strongly influence their described approach to DIS. Appreciating and managing the strong emotional content of work practices in the ICU may be important to improving compliance with evidence-based guidelines. Supported by NIH/NHLBI T32: HL07749-17

Nuno Cortesao, Medical Intensive Care Unit - Hospital Pedro Hispano, Armando Pinto, Faculty of Medicine - University of Oporto, Cristina Granja, Hospital Pedro Hispano; Faculty of Medicine of Porto Introduction: Infection-associated conditions influences sepsis-associated mortality risk. This hypothesis, a part of the PIRO concept, has been addressed in several studies. Hypothesis: To identify infection-associated conditions associated with hospital mortality in ICU patients admitted with community-acquired sepsis. Methods: Severe sepsis and septic shock patients were selected from the Portuguese ICU-admitted community-acquired sepsis prospective cohort study (SACiUCI). Infection-associated variables potentially affecting hospital mortality were described and included in hypothesis tests (Chi-square tests). A multiple logistic regression was used to obtain the best prediction of hospital mortality. Variables with p⬍0.2 in the univariate analysis were candidates for the final model and were kept in the model if p⬍0.1. Interactions were tested with the final group of variables but none was found to contribute significantly. PASW (SPSS) software 18.0 was used for statistical analysis. Results: 808 patients were included. Hospital mortality rate was 40% (321). In univariate analysis, positive hemocultures (47.3% vs. 36.8%; OR ⫽ 1.5; p⫽0.018) and patients with at least one non-bacterial infection (63.2% vs. 39.2%; OR 2.7; p⫽0.042) were more likely to die. No association was found for infection site (Respiratory⫽ref Urological; p⫽0.114 Intra-abdominal; p⫽0.236 Other; p⫽0.999), microbiological identification (yes vs no; p⫽0.132) and single agent infection Gram stain (p⫽0,222). Adjusted ORs computed with both variables in a logistic model were similar to the crude ones (OR ⫽ 1.5, p ⫽ 0.021 and OR ⫽ 2.5, p ⫽ 0.067, respectively). Sensitivity analysis showed an AUC⫽0.54 (CI95%:[0.50; 0.59]). Conclusions: These results derive from a large prospective cohort that included a clinically homogeneous sample of patients with community-acquired sepsis. Our model showed a low discriminatory capability, which might be improved after inclusion of other PIRO dimensions. Hospital mortality instead of 28-day mortality, as outcome, may further enhance our understanding on sepsis-related mortality. Finally, these findings may add to our knowledge concerning infection-associated conditions for sepsis-related mortality.



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HEALTH ECONOMICS OF SUBCUTANEOUS DESIRUDIN (DES) RELATIVE TO ARGATROBAN (ARG) IN PATIENTS WITH HEPARIN-INDUCED THROMBOCYTOPENIA (HIT): THE PREVENT-HIT STUDY

THE DEVELOPMENT OF A CONSORTIUM OF PEDIATRIC ICU CENTERS CAN GREATLY FACILITATE RESEARCH EFFORTS IN PEDIATRIC CRITICAL CARE

James Frame, David Lee Outpatient Cancer Center, Charleston, WV, Belinda Duncan, Canyon Pharmaceuticals, Clyde Spence, Charleston Area Medical Center-Memorial Division

Catherine Preissig, Medical Center of Central Georgia, Kevin Maher, Children’s Healthcare of Atlanta Emory University, Daniel Keaton, Jeryl Huckaby, Emory University, Mark Rigby, Emory University School of Medicine, Children’s Healthcare of Atlanta

Introduction: PREVENT-HIT was a multi-center, randomized comparison of two direct thrombin inhibitors, SC DES v IV ARG in patients (pts) with clinicallysuspected or laboratory-confirmed HIT. The study was designed to randomize 120 pts, but was closed after 16 pts due to slow enrollment. Previously published analyses of pts enrolled showed no difference in thrombotic outcomes (0 DES vs 1 ARG) or major bleeds (0 DES vs 3 ARG). There were no deaths in either group. The purpose of this study was to investigate resource utilization differences and economic outcomes between the treatment groups. Methods: Patients were randomized to receive IV aPTT-adjusted ARG or SC DES as a fixed-dose of 15 mg BID (n⫽7) or 30 mg BID (n⫽1) if thrombosis was present. Patients were enrolled regardless of prior indication for heparin administration. Resource utilization captured included total amount of medication used, laboratory monitoring and length of stay. Medication costs were calculated using 2010 wholesale acquisition costs of $150 per 15 mg vial of DES and $1100 per 250 mg vial of ARG. Results: Sixteen pts were randomized; 8 per group. Eleven pts had serologically confirmed HIT. The mean cost of study medication per course of treatment was $1991 for DES and $10,230 for ARG for a savings of $8239 per patient ($2288-15,325) with DES. DES pts had a shorter total mean duration of treatment (5.9 v 9.3 days) and a shorter mean post-randomization length of stay (LOS) (9.4 v 16 days). The mean duration on DES and ARG, alone and with warfarin overlap (if applicable), was 3.6 and 4.9 days and 4.6 and 5.7 days, respectively. In pts with confirmed HIT transitioning to warfarin therapy, pts on DES (n⫽5) were started on warfarin sooner (3.6 v 6 days) and required an average of 1.8 fewer days of DTI-warfarin overlap compared with ARG (n⫽6) (4.6 v 6.4 days). DES pts transitioned to warfarin (n⫽5) had a mean of 5.0 INR tests compared with 8.7 INR tests with ARG (n⫽7). Conclusions: Based on these limited data, there may be less cost, fewer dose adjustments and INR tests during warfarin transition, and a shorter LOS with the use of DES in pts with suspected or confirmed HIT. These findings require confirmation in a larger cohort of patients.

Introduction: While research efforts in adult critical care have reached great proportions and yeilded optimistic advances in patient care and outcomes, such efforts in pediatric critical care, while exciting, have still lagged behind that of adult care. Pediatric ICU practitioners face limitations specific to this population, including limited number of patients, and limited ability to power studies based on outcomes such as mortality. One area that has received much attention in adult ICUs but remains under-studied in children is glycemic control. Hypothesis: The development of a consortium of pediatric ICUs would facilitate our research efforts to further understand glucose dysregulation and glycemic control in critically ill children. Methods: We previously implemented as standard care a glycemic control protocol in our pediatric ICUs, and conducted single-center evaluations to further understand glucose dysregulation and glycemic control in children. We aimed to further our research by developing a registry of centers desiring to implement glycemic control via our protocol, and study hyperglycemia and glycemic control in this population. We approached centers of varying size, patient make-up, and acuity in order to increase the generalizablity of our findings. We asked groups to adopt our protocol as a tool to study glycemic control, provided protocol training, and created a secure online database accessible for data collection at all centers. Results: We secured seven for participation in this multi-center effort to study hyperglycemia and glycemic control in children. Centers were of varying size, ranging from 12-30⫹ beds, and of varying make-up, including academic and private models. The consortium of centers includes a mix of medical, surgical, and cardiac pediatric ICU patients. Each site has or will enroll approximately 50 patients with hyperglycemia managed via our glycemic control protocol, yeilding ⬎300 patients for analysis within 1-2 years. Conclusions: By developing a group of pediatric ICU centers with a common interest and desire to study hyperglycemia in this children we have been able to facilitate timely research in an area of extreme importance in critical care populations.

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LACK OF STANDARDIZATION FOR CENTRAL VENOUS CATHETER EXCHANGE USING A GUIDEWIRE - A SURVEY STUDY

INTENSIVE CARE UNIT ATTENDING PHYSICIANS’ REPORTS OF ERRORS, FATIGUE, AND WORK-HOURS POSTIMPLEMENTATION OF ACGME DUTY-HOUR LIMITS

Katrina Hawkins, George Washington University, Danielle Davison, George Washington University Medical Center, Lakhmir Chawla, Sunjeet Sidhu, George Washington University, Michael Seneff, Christopher Junker, George Washington U. Medical Center

M. Hossein Tcharmtchi, Baylor College of Medicine-Texas Children’s Hospital, Katri Typpo, University of Arizona College of Medicine, Eric Thomas, University of Texas-Houston Medical School, Leticia Castillo, University of Texas Southwestern Medical Center, P. Adam Kelly, Hardeep Singh, Baylor College of Medicine

Introduction: Medical procedures are performed under strict standards in order to minimize complications and maximize sterility. The exchange of a central venous catheter (CVC) over a guidewire is frequently performed. Despite its common practice, a standardized technique does not exist. This allows for the potential contamination of the site and further catheter-related bloodsteam infection. Hypothesis: Clinicians across the country exchange CVCs over guidewires frequently but do not do so in a uniform fashion. Methods: We performed an online survey using surveymonkey.com about practices involving guidewire exchange of CVCs. Questions addressed how often lines are exchanged as well as the techniques used when performing this procedure. Video links were provided for the 4 most common methods of CVC guidewire exchange (http://www.gwumc.edu/ edu/anes/Research/ICU%20Survey%20videos.html). The survey was distributed via email to intensivists and hospitalists across the US in both academic and private practice. Results: Approximately 1700 clinicians were queried, 144 responded. Twenty-eight percent of physicians reported changing a malfunctioning line over a wire more than 10% of the time; 12% admitted to doing so more than 50% of the time. Greater than 30% of physicians reported changing a CVC over a wire more than 5% of the time in the evaluation of a new onset fever. Of the four techniques provided (Standard CVP Swap, Condom CVP Swap, Cut Down Technique, Double Drape Technique), 57% of physicians reported using the Standard Swap, while 17% and 26% used the Cut Down and Double Drape techniques respectively. Sixty-four percent of physicians stated that there is no uniformity in the technique used by members within their own practice. Conclusions: This is the first national survey looking at clinicians’ practices regarding the exchange of a CVC over a guidewire. Clearly this procedure is common yet the technique is highly variable. The lack of standardization leaves open the opportunity for complications, most notably line infection. Further randomized trials need to be conducted to evaluate these techniques for sterility in order to standardize this procedure to the same degree as the other procedures we frequently perform.


Introduction: The effect of ACGME duty-hour limits implemented in 2003 on safety in the ICU (Intensive care unit) is unclear. Hypothesis: To determine perceptions of ICU attending physicians regarding their own duty hours, fatigue, and error rates in the setting of current duty-hour limits as well as in a possible future setting of additional reductions in duty-hours. Methods: Between 01/ 2010 and 04/2010, we administered an anonymous 26 item web-based survey nationally to 688 attending physicians in Pediatric, Neonatal and Cardiovascular ICUs (PICU, NICU, and CVICU) providing coverage in fellowship programs. Physicians received 2 reminders after the initial email invitation. Results: The overall response rate was 52.3% (N⫽360); 60%, 36% and 14% for NICU, PICU and CVICU respectively). Most reported no improvement or some worsening in resident error rates (94%) and patient safety (85%) with current work hour rules. More than half of respondents (61%) perceived that their own work-hours related to direct patient care increased with current regulations and that they were more fatigued with current regulations (57%). Although majority (85%) perceived no increase in their own error rate in the current duty-hour setting, a substantial number (42.8%) believed that their own error rates would increase with further reduction in resident duty hours. Majority of respondents also perceived that their own duty hours and fatigue would increase (75% and 79% respectively) with further reduction in duty hours and that this would lead to worse patient safety culture in the ICU (54%). Conclusions: Attending physicians in the NICU, PICU, and CVICU perceive that resident duty hour limits have not improved safety and error rates in the ICU setting while their own work-hours and fatigue may have worsened. Many perceived that further reductions in duty hours would have a negative impact on patient safety.

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DEEP VENOUS THROMBOSIS CHALLENGES OF BASELINE DATA AVAILABILITY, MANAGEMENT AND ONGOING TREATMENT OF AT-RISK ICU PATIENTS

ACUTE RESPIRATORY DISTRESS SYNDROME CAUSED BY MILIARY TUBERCULOSIS: A MULTICENTER SURVEY IN SOUTH KOREA

Elizabeth Cowboy, Advanced ICU Care

Kwangha Lee, Pusan National University School of Medicine, Je Hyeong Kim, Korea University Ansan Hospital, Jin Hwa Lee, School of Medicine, Ewha Womans University, Won-Yeon Lee, Yonsei University Wonju College of Medicine, Moo Suk Park, Severance Hospital, Yonsei University College of Medicine, Jae Yeol Kim, Chung-Ang University, College of Medicine, Kyung Chan Kim, College of Medicine, Catholic University of Daegu, Myung-Goo Lee, Chuncheon Sacred Heart Hospital, Hallym University School of Medicine, Ki-Suck Jung, Department of Medicine, Hallym Medical Center, Hallym University School of Medicine, Younsuck Koh, Asan Medican Center,University of Ulsan College of Medicine

Introduction: Multi-center assessment on data availability and tracking of deep venous thrombosis (DVT) prophylaxis in at-risk patients. Hypothesis: The availability and validity of baseline data for DVT prophylaxis is scarce. Computer enabled and interfaced data base with remote intensivists can track data, deliver timely intervention and prevent DVTs. Methods: 24,860 adult patients were admitted to 18 intensive care units (ICU) over 54 month period. The average APACHE score was 49 with a range of 36 to 77. Patients were admitted and co-managed with intensivists via integrated electronic medical system from a central location. All at-risk patients were evaluated by the team every 6 hours. Pharmalogical or mechanical interventions was initiated and co-managed. Results: The ICU populations were studied from January 1, 2006 to June 30, 2010. Baseline data was available from 3 of the ICUs. Only 1 site used the same definition of at-risk being: bed rest ⬎24 hours, certain surgical procedures, age ⬎60, mechanical ventilation, cancers and coagulabilities. The compliance rate was 38%. 2 sites considered only ventilated patients. 15 sites had no baseline data due to inadequate tracking mechanisms, scares financial or human resources to pull concurrent or retrospective data. 13,838 patients of the 24,860 patients 56% in our systems were at-risk, with 12,666 or 92% receiving treatment in ⬍ 24 hours. The most recent 3 month period revealed 2,603 patients admitted with 1,587 meeting criteria for being at-risk with 1,540 or 97% receiving treatment ⬍ 24 hours. Conclusions: A retrospective of 18 ICUs in America found baseline and hospital acquired data unavailable, variable and often inconsistent with national definition. National studies comparatives show average of 19% to 29% of patients received prophylaxis treatment.1-2 Using the best pre-data of 38% would have lead to only 5,258 patients treated or 8,580 untreated patients. Using 33 patients as the number needed to treat to prevent a DVT, the remote Intensivists integrated model prevented 260 DVTs. The program has demonstrated the ability to track the data in multiple ICUs simultaneously and deliver appropriate treatment. 1.Stroke. 2001;32:337. 2.Chest . 2004;126:338s

Introduction: Miliary tuberculosis (TB) is an unusual cause of acute respiratory distress syndrome (ARDS). We evaluated the clinical characteristics and outcomes of patients with ARDS caused by miliary TB who were admitted to the intensive care unit (ICU). Hypothesis: We hypothesized that a multi-center survey would identify a large number of patients with ARDS caused by miliary TB, allowing us to determine distinct clinical and survival data compared with ARDS caused by pulmonary TB. Methods: We assessed the clinical characteristics and outcomes of 67 patients with miliary TB treated at 10 tertiary-care hospitals in South Korea during the period 1999 –2008. Results: Median patient age was 56 years (range 17– 81 years), 19 (28.4%) were aged more than 71, and 38 (56.7%) were male. All-cause mortality in the ICU and hospital were 58.2% and 61.2%, respectively. The median interval from hospital admission to start of anti-TB treatment was 1 day, with 49 (73.1%) starting anti-TB medication within 3 days of hospital admission. In addition, 47 patients (70.1%) were diagnosed with pneumonia with no causative pathogen, and were simultaneously prescribed broad-spectrum antibiotics; these patients had significantly higher Sequential Organ Failure Assessment (SOFA) score (9.6⫾3.5 vs 7.5⫾4.0, p⫽0.048) and mortality rate (70.2% vs 40% p⫽0.029) than patients who received anti-TB treatment alone. Multivariate analysis showed that SOFA score on the day of ARDS diagnosis was a significant predictors of survival (odds ratio 0.831, 95% confidential interval 0.709 – 0.976,p ⫽ 0.024). It was difficult to determine the efficacy of systemic corticosteroid on patients’ survival. Conclusions: ARDS caused by miliary TB was associated with a high in-hospital mortality rate, with SOFA score on the day of ARDS diagnosis being a valuable prognostic indicator.

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PEDIATRIC EXTRACORPOREAL MEMBRANE OXYGENATION: IS ANTIBIOTIC PROPHYLAXIS NECESSARY?

TRENDS IN VENTILATION STRATEGY IN THE OPERATING ROOM: ANALYSIS OF A LARGE DATA SET

Kartheek Nagappala, Raquel Gonzalez, Joseph Lelli, Scott Langenburg, Children’s Hospital of Michigan

Edward Bittner, Massachusetts General Hospital, Haobo MA, Wilhelm Driscoll, MGH, Dean Hess, Massachusetts General Hospital , Ulrich Schmidt, Massachussets General Hospital

Introduction: The use of antibiotic prophylaxis to prevent bloodstream infections in pediatric patients while on extracorporeal membrane oxygenation (ECMO) is not a standard practice. The reported incidence of bloodstream infections in non-cardiac pediatric ECMO patients based on the Extracorporeal Life Support Organization (ELSO) registry is six percent. Hypothesis: Routine use of antibiotic prophylaxis reduces the incidence of bloodstream infection in pediatric ECMO patients. Methods: A retrospective chart review was conducted from 1999-2009 on all non-cardiac pediatric ECMO patients admitted to our institution. All of our patients received prophylactic antibiotics during their entire ECMO course. Patient demographics were obtained, as well as ECMO-related data (indication, mode & duration), and blood culture-related data (number of cultures obtained, positive cultures, organisms isolated, antibiotic use & duration of treatment). Statistical analysis was performed using SPSS. This study was IRB approved (1002008095). Results: A total of 196 patients were analyzed of which 12 had bloodstream infections (6.1%), defined as two or more positive cultures during their ECMO run. Fifty percent of these patients were females; their average age was 45 (SD⫾96) days at initiation of ECMO. The most common indication for ECMO was congenital diaphragmatic hernia (33.3%, p⫽0.28), followed by primary pulmonary hypertension of the newborn (16.7%, p⫽ 0.34). All patients were supported with veno-arterial ECMO. The average duration of ECMO was 354 (SD⫾151) hours, with the majority of cultures becoming positive at 196 (SD⫾170) hours. The organism most commonly isolated was Staphylococcus epidermidis (33.3%). The overall mortality rate for non-infected patients was 33.7%; this increased to 83.3% once infected (p ⫽ 0.0004). Conclusions: In comparison to the ELSO registry, where antibiotic prophylaxis is not routinely used, our institution’s current practice of prophylaxis does not appear to decrease bloodstream infections. Mortality with a bloodstream infection is extremely high. A prospective randomized trial is warranted to better delineate indication and timing of antibiotic therapy.

Introduction: Lung protective ventilation strategies (limitation of tidal volume, airway pressures and use of PEEP) have evolved as standard of care in the intensive care unit (ICU). It is however unknown whether a similar ventilation approach is used in the operating room (OR) Hypothesis: We hypothesized that during the last years applied tidal volumes and peak airway pressures would decrease and applied positive end expiratory pressure would increase. Methods: We examined the records of 104,679 patients undergoing general anesthesia in a tertiary care center from 2004 to 2009. We recorded tidal volumes (VT), peak airway pressures (PIP) and positive end-expiratory pressures (PEEP). We stratified the patients by ASA classification as well as emergent vs. non- emergent cases. Results: During the study period mean VT was under 8cc /kg ideal body weight, Form 2004 to 2009 VT increased from a mean of 7.1 ml/kg (SD ⫽ 2.16 ml/kg) to 7.7 ml/kg (SD ⫽ 1.71 ml/kg) (P ⬍ 0.001 ). PIP increased from a mean of 14.6 cm H2O (SD ⫽ 6.94 cm H2O) to 18.6 cm H2O (SD ⫽ 6.50 cm H2O) (P ⬍ 0.001). The applied PEEP remained constant at 3.4 cm H2O (SD 2.1 cm H2O) over the study period. When stratified for ASA classification VT was higher in ASA IV 7.5 ml, SD ⫽ 2.16 ml compared to ASA I patients 7.3 ml/kg (SD 1.97 ml/kg, P, 0001). In emergent cases mean VT (7.85 ml/kg SD 1.92 ml/kg was higher compared to non-emergent cases (7.66 ml/kg, SD ⫽ 2.02 ml/kg, P ⬍ 0.001). Conclusions: In this large data set of over 100,000 patient ventilated in the OR a lung protective ventilation strategy with VT of less than 8cc/kg and PIP under 20 cmH2O was used. The set PEEP was lower than commonly used in the ICU. Over time VT and PIP increased. Sicker patients and patients undergoing emergent surgery were ventilated with higher VT compared to less severe ill patients.


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ASSOCIATION BETWEEN MARITAL STATUS AND SURVIVAL AMONG PATIENTS WITH SEPSIS TREATED IN THE INTENSIVE CARE UNIT

COMPARISON OF 24/7 SURGICAL ICU (SICU) COVERAGE BY PHYSICIAN ASSISTANTS (PA’S) & PGY-3’S FOLLOWING EVIDENCE-BASED GUIDELINES WITH 24/7 SICU COVERAGE BY SURGICAL INTENSIVISTS AND CARDIAC SURGEONS

Jay Steingrub, Baystate Medical Center, Brian Nathanson, OptiStatim, LLP, Richard Wells, Tara Lagu, Peter Lindenauer, Baystate Medical Center Introduction: A significant relationship has been demonstrated between marital status and mortality. However, analyses of gender based differences in outcomes of patients with sepsis have shown conflicting results. Methods: We conducted a retrospective analysis using data from hospitals that participated in the Perspective database (Premier Healthcare Informatics, NC) between 2004 - 2006. We included adult medical patients with a principal or secondary diagnosis of sepsis who were admitted to an ICU by their second day of hospitalization. Patients were also required to have had a blood culture and three consecutive days of antibiotics. We excluded patients with unknown marital status and transfers to or from an acute care facility. Marital status was dichotomized into Married vs Nonmarried, where Nornmarried was single, divorced, widowed, or other known status. We used multivariate regression and propensity score analyses to assess differences in mortality by marital status. Results: There were 35,336 patients from 170 hospitals who fulfilled inclusion criteria. A propensity matched analysis showed marriage conferred a survival advantage (risk ratio (RR) ⫽ 0.96; 95% CI (0.92, 0.99). This apparent survival advantage varied by age and gender. Married women had a lower risk of death than nonmarried women (RR ⫽ 0.88, 95% CI (0.84, 0.93). This difference was more pronounced among women ⱕ 50 (RR ⫽ 0.81, 95% CI (0.68, 0.98). For patients receiving vasopressors, married women still had a lower risk of death than nonmarried women (RR ⫽ 0.91, 95% CI (0.86, 0.96). Marital status had no association with mortality in males regardless of age or shock status. Conclusions: We observed an association between marital status and lower mortality among female sepsis patients, particularly among the pre-menopausal group. Being married may serve as a proxy for other socioeconomic factors that affect mortality. Hormonal status may also affect mortality in sepsis and needs further evaluation. Researchers should consider adjusting for marital status when conducting randomized clinical trials for sepsis. References: Amer J Epidemiology 2009;170(5):546-555; Inten Care Med 2000; 26(2):167-172; Chest 2010;137(6):1289-1296


Marvin McMillen, Beth Israel Medical Center, David Keith, Montefiore Med Ctr, Nathan Boucher, Asaf Gave, Beth Israel Medical Ctr Introduction: Many critical events occur at night & current societal/regulatory patient safety expectations require expanded nightime ICU coverage by experienced caregivers. With resident work hour limitations, this is a complex & expensive undertaking. Our 3 year’s experience with 24/7 in-house surgical intensivist/cardiac surgeon coverage was compared to the previous 5 year’s rapid consultation & protocolization by Fundamentals of Critical Care Support-certified pa’s/PGY-3’s, covered at night by intensivists from home. Hypothesis: While implementation of national standards & FCCS-certification by experienced pa’s & PGY-3’s improves SICU mortality, 24/7 on-site coverage by attending intensivists & cardiac surgeons may provide no further mortality benefit. Methods: SICU mortality for an 800 bed teaching hospital was reviewed for 8 yrs. In 2002-4, 24/7 rapid & organized consultation by FCCS-certified pa’s/PGY-3’s was initiated using FCCS, SCCM, American Heart, ACCP, SIS & ASPEN guidelines/best practices. Evenings, attending intensivists were contacted at home for consults & emergencies, & came in when necessary. In 2004, a 9 bed stepdown unit (SDU) was created. In 2007, 24/7 in-house surgical intensivists & cardiac surgeon coverage with pa’s & PGY-1’s was implemented. Operative volume, complexity & critical care increased over 8 yrs. as 3 nearby hospitals closed. SICU was consulted on 15% of surgical cases throughout. Results: SICU census grew from 867 (2002) to 1800 in SICU/SDU (2008-09.) Mean APACHE II score remained 22-25 throughout (predicted mortality-7.8%.) SICU 31 day mortality exceeded 4% in 2001, but decreased to 2% in 2002, 1.8% (2003), 2.1% (2004), 1.9% (2005), 1.5% (2006) & 1.5% (2007.). 24/7 attending coverage instituted mid-2007 did not change mortality- 1.5% (2008), & 2% (2009.) Conclusions: Initial improvement in daytime intensivist coverage (10-12 hrs.) & 24/7 rapid consultation & protocolization with pa’s/PGY-3’s improved mortality. Cost/yr. of additional nightime intensivist/cardiac surgeon coverage ($100/hr.) is $613,600, while the same hours covered by pa’s ($38/hr ⫹ 30% ) costs $303,118. 24/7 on-site coverage by SICU attendings & cardiac surgeons provided no further benefit in mortality.


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ACUTE MECHANICAL VENTILATION IN U.S. CHILDREN, 1997-2006

THE PREVALENCE OF VITAMIN D DEFICIENCY IN CHILDREN ADMITTED TO THE PEDIATRIC CRITICAL CARE UNIT

Brian Benneyworth, Matthew Davis, Thomas Shanley, Fola Odetola, University of Michigan Introduction: The use of mechanical ventilation (MV) in children has grown markedly in the last two decades. The mortality rate for children who require acute MV is higher than other hospitalized children. It is not known if the duration of acute MV affects the inpatient mortality rate of children. Hypothesis: To describe the trend in the frequency of hospitalizations associated with acute MV in the non-newborn population, and to evaluate any association of prolonged acute MV (ⱖ 96hrs) with mortality in hospitalized children. Methods: Serial cross-sectional analysis of the 1997 to 2006 Kids’ Inpatient Databases (AHRQ’s HCUP project). Non-newborn children ⱕ18 years were identified after exclusion of ICD-9 diagnosis codes associated with newborn care including prematurity and hospitalization at the time of birth. Acute MV was defined using the ICD-9 procedure codes 96.70-72 (prolonged acute MV 96.72). Chi-square was used for group comparisons and variance-weighted least squares regression was used for trend analysis. Results: The overall number of hospitalizations for nonnewborn children remained stable from 1997 to 2006. Hospitalizations associated with acute MV represented approximately 1.7% of all non-newborn hospitalizations. There was a 17% increase in the rate of discharges associated with acute MV; including a 25% increase in hospitalizations associated with prolonged acute MV. Inpatient mortality occurred in approximately 14% of discharges associated with acute MV with no difference in the frequency of mortality by the duration of MV. Inpatient mortality for all acute MV hospitalizations was stable from 1997 to 2006. Conclusions: In a nationally representative population of hospitalizations for U.S. children ⱕ18 years of age, exclusive of birth hospitalizations, there was an increase in hospitalizations associated with acute MV from 1997 to 2006. Importantly there was no change in their inpatient mortality over time, even among children who required prolonged acute MV. Further work is needed to investigate this upswing in hospitalizations associated with acute MV and to elucidate the associations of chronic illness on the length of acute MV and inpatient mortality. This work is supported by an NIH T-32 Grant.

Marco Ayulo, Todd Sweberg, Chhavi Agarwal, Chhavi Katyal, Children’s Hospital at Montefiore Introduction: Despite the fortification of foods with vitamin D, vitamin D deficiency remains common in children. In adults, low concentrations of vitamin D have been linked to many diseases including osteoporosis, hypertension, ischemic heart disease, type I diabetes, cancer, and poor lung function. Outside of rickets, the morbidity of vitamin D deficiency in children has not been well defined. Recent data in children has demonstrated that low levels of vitamin D are associated with increased asthma severity and cardiovascular risk factors. Vitamin D is a regulator of calcium metabolism and homeostasis, and deficiency can result in hypocalcemia. In critically ill children, hypocalcemia has been associated with increased mortality. The prevalence and clinical significance of vitamin D deficiency in critically ill children has not been documented. Hypothesis: Vitamin D deficiency is prevalent among patients admitted to the Pediatric Critical Care Unit (PCCU), and is associated with increased disease severity. Methods: A prospective observational study was conducted in patients admitted to the PCCU between the ages of 1-21 years, excluding those requiring re-admission with a previous vitamin D level. Serum 25-OH vitamin D levels were drawn on all patients within 24 hours of admission to the PCCU, and the severity of patient illness was assessed with the use of the Pediatric Logistic Organ Dysfunction (PELOD) score on admission. Vitamin D deficiency is defined as serum levels of 25-OH vitamin D ⬍ 15 ng/mL. Vitamin D insufficiency is defined as serum levels 15-30 ng/mL. Results: 216 patients were enrolled. 28% of patients were vitamin D deficient and 47% were vitamin D insufficient. When evaluating for disease severity, no correlation was found between vitamin D level and PELOD score (p⫽0.09). A significant correlation was found between serum vitamin D and serum calcium levels (p⫽0.005), but no correlation was demonstrated between serum vitamin D and ionized calcium levels (p⫽0.62). Conclusions: Vitamin D deficiency is common in children admitted to the PCCU, with only 25% of patients having normal levels. The relationship between serum vitamin D levels and disease severity remains unclear, and warrants further study.

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DIAGNOSIS OF ACUTE AORTIC DISSECTION USING A FIBRINOLYTIC MARKER

INCIDENCE OF VENOUS THROMBOEMBOLISM IN TRAUMA PATIENTS AND ASSOCIATED RISK FACTORS

Akiyoshi Hagiwara, Digo Sakamoto, Ryo Sasaki, Kentaro Kobayashi, Takunori Sato, Akio Kimira, National Center For Global Health and Medicine

M. Curtright, J. Bethea, Charleston Area Medical Center

Introduction: Acute aortic dissection (AAD) is easily misdiagnosed or overlooked because it presents with a variety of symptoms. Although measurement of D-dimer (D-d), an indicator of secondary fibrinolysis, was recently reported to be useful for diagnosis, increases in D-d may not be sufficient for differential diagnosis of the aortic intramural hematoma (AIH) type. Hypothesis: Plasma fibrin and fibrinogen degeneration products (FDP), an indicator of both primary and secondary fibrinolysis, can be used to differentiate AAD from acute myocardial infarction (AMI), angina, brain infarction (BI), and transient ischemic attack (TIA). Methods: Subjects were consecutive patients with AAD who underwent chest contrast-enhanced CT (CECT) between January 2003 and December 2009. Controls were patients admitted during the same period for whom a diagnosis of either AMI, angina, BI, or TIA was confirmed. Results: FDP was measured on admission for 91 of a total of 100 cases of ADD. Of these patients, 43 had classic acute aortic dissection (CAAD) and 48 had the AIH type. FDP was significantly higher in CAAD (221 ug/mL; 80-375) than in AIH (14 ug/mL; 6-48). For patients with AMI (n⫽190), angina (n⫽142), BI (n⫽357), and TIA (n⫽94), FDP was 3.1 (1.0-5.7), 2.2 (0.9-4.3), 2.4 (1.1-5.4), and 1.4 (0.6-3.0), respectively. CAAD and AIH patients had a significantly higher FDP than each of the control subjects (p⬍0.0001). ROC analysis indicated that the cutoff value with the best sensitivity and negative predictive value (NPV) for differentiating CAAD patients from the control subjects was FDP ⱖ12.6 (sensitivity, 100%; NPV, 100%). When control subjects were subdivided according to disease, the best cutoff value for differentiating AIH patients from angina, BI, or TIA patients was ⱖ4.9 (sensitivity, 88%; NPV, 93 to 98%). The best cutoff value for differentiating AMI was ⱖ5.4 (sensitivity, 83%; NPV, 95%). Conclusions: In patients with suspected symptoms of AAD, FDP of ⬍12.6 would suggest that CAAD is not responsible. However, AIH can not be ruled out, and for FDP values of approximately 5 or greater, CECT should be performed even for patients with AMI, angina, BI, or TIA in order to avoid overlooking AIH.

Introduction: Traumatic injury induces a hypercoagulable state increasing risk of venous thromboembolism (VTE) and associated morbidity and mortality. The timing of pharmacologic prophylaxis requires a careful comparison of the risk of bleeding versus the risk of VTE. Data from this study will be used to identify injury types and/or patient characteristics in which current practices for the prevention of VTE at Charleston Area Medical Center (CAMC) may need to be evaluated. Hypothesis: The incidence of VTE will be significantly higher in patients with CNS injuries or BMI greater than or equal to 25 kg/m2 as standards of practice for pharmacologic prophylaxis in these populations remain controversial. Methods: Patients diagnosed with VTE between January 1, 2008 and December 31, 2009 were identified by the trauma registry. An analysis was completed to identify types of injuries and/or patient characteristics associated with VTE. A control group of patients who were not diagnosed with VTE was randomly selected and analyzed to determine the significance of injuries and characteristics. Results: 7.4% of trauma patients developed VTE. The most frequent characteristics associated with a significant increase in VTE risk, when compared to the control group, were traumatic brain injury (42 vs 27, p⫽0.035), lower extremity long bone fracture (32 vs 13, p⫽0.002), pelvic fracture (24 vs 11, p⫽0.024), and age (50 vs 43, 0.007). A correlation between VTE formation and elevated BMI was not found. Mechanical prophylaxis was initiated in 87.6% of VTE patients and 99.0% of control patients (p⬍0.001). Pharmacologic prophylaxis was administered in 40.2% of VTE patients and 42.2% of control patients (p⫽0.884). Conclusions: Patients with traumatic brain injury, pelvic fractures, lower extremity long bone fractures, and increased age are at significantly higher risk of VTE development. A significantly higher number of patients in the control group received mechanical prophylaxis. There was not a difference in the administration of pharmacologic prophylaxis between the two groups. This analysis suggests prophylaxis practices need to be re-evaluated in CAMC’s high-risk patients.


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A TOOL TO TRACK INPATIENT HEALTH CARE DELIVERY: THE PATIENT SAFETY FLIGHT PLAN

11-YEAR LONGITUDINAL STUDY OF 19,169 TRAUMA PATIENTS: PATTERNS OF UTILIZATION WITHIN A SUBURBAN TRAUMA SYSTEM

Rajit Basu, Cincinnati Childrens’s Hospital Medical Center, Derek Wheeler, Cincinnati Children’s Hospital Medical Center Introduction: Checklist based performance evaluations of health care delivery are inapplicable to the dynamic nature of inpatient care. Management plans for children in the intensive care unit (ICU) are heterogeneous, individualized, and constantly changing. Follow-up on these plans and adjustments made throughout the day are performance measures that have not, to date, been adequately measured. Such measures are significant in preventing patient error and improving patient care and satisfaction. Hypothesis: Aviation safety practices are adaptable models for improving patient safety. Thus, we describe the development of a “Patient Daily Flight Plan” and hypothesize that it will highlight specific areas of needed quality improvement in the ICU. Methods: The Patient Daily Flight Plan segments a hospital day into pre-flight (rounds), in-flight (daytime events), and landing (evening rounds) and is a patient specific tracking tool to follow-up performance adequacy on plans. Results: Omitted or mistaken patient events and incorrect information presented on rounds were considered pre-flight errors and occurred in 131/344 (38.1%) individual patients. In-flight errors included: failure to assess patient conditions deemed critical during pre-flight (i.e. ventilation status or hemodynamic status) (41/287, 14.3%), delay in obtaining results from ordered radiology or laboratory tests (22/141, 15.6%), and failure to assess patients upon return from a road-trip from the ICU or after a procedure (25/76, 32.9%). Landing errors included missed consultant recommendations (13/101, 12.9%) and failures in follow-up on issues arising during the day (18/205, 8.9%). Conclusions: In this observational study, the Patient Daily Flight Plan highlighted glaring problem areas in the care delivery in our ICU. Use of this tool offers a two-fold benefit: it will create more clarity and direction for the care team which will likely lead to less medical error and it will offer more transparency for the patient and the family which will likely increase satisfaction with care.

Keneth Hall, Emily Huang, Jane McCormack, Lynn Hydo, Marc Shapiro, Jared Huston, Stony Brook University Medical Center Introduction: To accommodate an aging and growing United States population, trauma systems may have to devote a disproportionate amount of resources to care for the elderly. We reviewed over 19,000 patients treated by a suburban, countywide trauma system in New York State between 1999 and 2009 to examine how outcomes and resource utilization have evolved over time. Hypothesis: We hypothesized that older and sicker patients are treated more at Level 1 trauma centers versus Level 2 and 3 centers. Methods: All patients treated at hospitals in Suffolk County, New York from 1/1999 to 12/2009 with a discharge diagnosis of moderate to severe traumatic injury as described on the state inclusion list were included. Hip fractures, burns, age ⬍ 18, and those who died in the ED were excluded. Data collected include age, gender, trauma center designation (Level 1, 2, 3), injury mechanism, hospital mortality, and Injury Severity Score (ISS). Patients were grouped as Level 1 versus Levels 2 and 3. Statistics: ANOVA, chi-square, linear and binary regression (p ⬍ 0.05). Results: There were 19,169 trauma patients. Patients treated at Level 1 trauma centers were younger (Level 1 age 48.6 ⫾ 0.2 versus Levels 2 and 3 56.8 ⫾ 0.2, p⬍0.01), male (p⬍0.001), and had higher injury severity (Level 1 17.7 ⫾ 0.1 versus Levels 2 and 3 12.7 ⫾ 0.1, p⬍0.0001). Patients involved in motor vehicle collisions received more Level 1 care (p⬍0.001). Hospital mortality was significantly higher at the Level 1 center versus Levels 2 and 3 (7.2% versus 6.2%, p⬍0.008). Using logistic regression, age, gender, ISS, and injury mechanism correlate with level of care (chi-square 1707.6, p⬍0.0001). The predictive accuracy of the model is 67.8%. Conclusions: Level 1 trauma centers are achieving excellent outcomes despite caring for severely injured patients. Older females appear less likely to receive Level 1 trauma care. It is unclear why younger male patients and those involved in motor vehicle collisions are more likely to utilize Level 1 trauma centers. Further studies are needed to determine whether this represents an equitable and appropriate delivery of trauma care, or if unintentional age and gender biases are present.

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DO CRITICALLY ILL PATIENTS WITH SUBARACHNOID HEMORRHAGE HAVE IMPROVED OUTCOMES WITH EXPOSURE TO NATURAL LIGHT?

CRITICALLY-ILL CHILDREN WITH NOVEL H1N1 INFLUENZA A IN A NEW YORK CITY MEDICAL CENTER: FIRST VS SECOND WAVE

Hannah Wunsch, Columbia University, Hayley Gershengorn, Beth Israel Medical Center, Stephan Mayer, Neurological Institute of New York, Jan Claassen, Columbia University

John Baird, Amanda Buet, Thyyar Ravindranath, Columbia University Medical Center, Bruce Greenwald, Sheemon Zackai, Weill Cornell Medical College, Jean-Marie Cannon, Maria Messina, New York Presbyterian Hospital, Philip Graham, Columbia University Medical Center, Patricia DelaMora, Weill Cornell Medical College, Lisa Saiman, Columbia University Medical Center

Introduction: Clinicians and specialty societies often emphasize the potential importance of natural light for quality care of critically ill patients, but few studies exist examining outcomes for patients associated with exposure to natural light. Hypothesis: Receiving care in an intensive care unit (ICU) room with a window improves outcomes for critically ill patients with acute brain injury. Methods: This was a secondary analysis of a prospective cohort study. Seven ICU rooms had windows, and five ICU rooms did not. Admission to a room was based solely on availability. We analyze data from 789 patients with subarachnoid hemorrhage (SAH) admitted to the neurological ICU from August 1997 to April 2006. Patient information was recorded prospectively on admission, and patients were followed up to one year to assess mortality and functional status, stratified by whether or not care was received in an ICU room with a window. Results: Of 789 SAH patients, 455 (57.7%) received care in a window room, and 334 (42.3%) in a non-window room. The two groups were balanced with regard to all patient and clinical characteristics. There was no statistical difference in modified Rankin Scale (mRS) at hospital discharge, three months or one year (44.8% with mRS 0-3 with window versus 47.2% non-window at hospital discharge, P ⫽0.51; 63.8% versus 64.0% at 3 months, P ⫽ 0.97; 73.5% versus 71.9% at one year, P ⫽ 0.63). There were also no differences in any secondary outcomes, including length of mechanical ventilation, time to following commands in the ICU, need for percutaneous gastrostomy tube or tracheotomy, ICU and hospital length of stay, and hospital, three month, and one year mortality. Conclusions: The presence of a window in an ICU room did not improve outcomes for critically ill patients admitted to the ICU with SAH. Further studies are needed to determine whether other groups of critically ill patients, particularly those without acute brain injury, derive benefit from natural light.


Introduction: We previously described the epidemiology and clinical presentations of critically-ill children admitted to our medical center during the first wave of novel H1N1 influenza A. Such children had a broad spectrum of illness severity including upper respiratory tract infection, bronchiolitis, and pneumonia, but a low mortality rate (⬍ 1%). Hypothesis: The second wave will be characterized by increased severity of illness with increased mortality. Methods: We performed an observational study at Morgan Stanley Children’s Hospital (Columbia University Medical Center) and Komansky Center for Children’s Health (Weill-Cornell Medical Center) to assess the demographic and clinical characteristics of patients ⬍18 years old hospitalized from August 2009 - April 2010 (the second wave) with ⬎1 positive test for influenza A. We assessed illness severity in patients admitted to the Pediatric Intensive Care Unit (PICU) using the PRISM III score, the incidence of respiratory failure, peak oxygenation index, lowest PaO2/FiO2, the incidence of bacterial superinfection, and PICU length of stay. We also reviewed any use of high frequency oscillatory ventilation and ECMO. Results: During the second wave 76 children (median age: 4.8 years; p⫽0.65 vs first wave) were admitted with influenza A, and 62 (82%) had confirmed novel H1N1 subtype (PCR); 15 (20%, p⫽0.10 vs first wave) patients were admitted to the PICU (median age: 4.5 years, p⫽0.41 vs first wave). The incidence of underlying conditions, obesity, and lymphopenia were similar between first and second wave PICU patients, and between PICU and non-PICU patients. The clinical presentations and respiratory support required in the first and second wave were similar (Table). During the second wave, two patients had myocarditis, one of whom received 6 days of ECMO support. Conclusions: While fewer children were hospitalized with novel H1N1 influenza A during the second wave, both waves were characterized by a broad spectrum of illness severity in the PICU and a low mortality rate.

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OUTCOMES IN ONE YEAR MORTALITY FOLLOWING TRACHEOSTOMY OF ADULT INTENSIVE CARE PATIENTS

SWEETENING EFFECTS OF THE NICE-SUGAR STUDY IN AMERICAN ICUS

Shannon Kline, Penn State Hershey Medical Center, Colin Huntley, Penn State University College of Medicine, Sandralee Blosser, Penn State Milton Hershey Medical Center, Margaret Wojnar, Penn State University, Kane High, M. S. Hershey Medical Center, Eric Schaefer, David Goldenberg, Penn State Hershey Medical Center

Elizabeth Cowboy, Advanced ICU Care

Introduction: The objectives of this study are to identify correlating patient characteristics with one year mortality following tracheostomy placement in a heterogeneous adult ICU patient population. Hypothesis: We hypothesize that one year mortality following a tracheostomy will be most significantly correlated to increased age. Methods: A retrospective chart review of adult ICU patients having received a tracheostomy was performed. A total of 193 patients were included in a univariate statistical analysis to determine individual significant variables correlating to one year mortality following tracheostomy. Results: Overall mortality at one year following tracheostomy in adult ICU patients was 12.6% (N⫽41). A total of 13 variables were found to have a significant correlation to one year mortality outcome. Several significant variables were specific to the ICU stay including hyperglycemia (p⬍0.0001), acute renal failure (p⫽0.0001), vasopressor infusions (p⫽0.0002), total number of mechanical ventilation days (p⫽0.0002), peak white blood cell count (p⫽0.0157), number of sedation days following tracheostomy (p⫽0.0208), nadir hemoglobin level (p⫽0.0217), and the presence of infection (p⫽0.0230). Other significantly correlating variables include vasopressor infusions during tracheostomy procedure (p⬍0.0001), late ambulation (p⫽0.0001), tracheostomy procedure independent of a head and neck surgery (p⫽0.0019), increased age (p⫽0.0021) and total parenteral nutrition (TPN) (p⫽0.0182). Conclusions: The most significant factors associated with one year mortality following tracheostomy are hyperglycemia and use of vasopressor infusions during the procedure. Although increased age was identified as a correlating factor, it was not the most significant. Other characteristics associated with one year mortality following tracheostomy include acute renal failure, white blood cell count, hemoglobin levels, mechanical ventilation duration, sedation length, infection, late ambulation, TPN, and tracheostomy performed independently of another surgical procedure. The knowledge of these correlating factors with one year mortality following tracheostomy may guide clinical decision making within the adult ICU patients.

Introduction: Multi-center evaluation of the effects of the NICE-SUGAR Study on glucose management among critically ill patients Hypothesis: The NICE SUGAR Study results will raised the average glucose in intensive care units (ICU). Hypoglycemia rates will be low if managed 24 hours per day by intensivists. Methods: 24,860 patients with a critical diagnosis were admitted to 18 ICU with APACHE score of 49 with a range of 36 to 77. These patients were admitted and co-managed with intensivists via integrated electronic medical system from a central location. Glucose values were interfaced with lab samples and glucometers. Patients’ nutrition status, oral glycemic controlling agents and insulin values were reviewed every 6 hours by the team. All ICU practices included intensive glucose control model, with a target blood glucose range of 80 to 110 mg/dl. Values ⬎ 150 mg/dl or ⬍ 80 were intervened following verbal or electronic notification. Following the NICE-SUGAR Study practice patterns changed in coordination with recommendations. Glucose values ⬎ 180 mg/dl or ⬍80 received intervention. Results: The ICU populations were studied from January 1, 2006 to June 30, 2010. The total glucose values were retrieving during the reporting period with an average for each individual patient calculated on a daily basis. The first 24 hours of values were excluded for patients with DKA or HGC. Data was divided into two groups before April 1, 2009 involved 11,178 patients and post 13,682 patients. Comparatives showed an increase in the average blood glucose from 137 to 146 mg/dl. The range of the averages per individual ICUs before was 132-141 mg/dl and after 142-150 mg/dl. Hypoglycemic events with glucose ⬍ 50 were rare 0.5% before and 0.4% post. Conclusions: A retrospective of 18 ICUs in America of 24,860 critically ill patients found an increase in average blood glucose in all units by 10 mg/dl post NICE SUGAR Study. The Intensivist lead team maintained significantly low hypoglycemia rate of ⬍ 0.5%. Reference: 1. N Engl J Med 2009; 360:1283-1297.



648

EARLY MORTALITY IN AN ONCOLOGIC ICU: CHALLENGING AND DISTRESSING

CARDIAC INDEX MEASURED BY THE TRANSPULMONARY THERMAL DILUTION TECHNIQUE WAS CORRELATED WITH DEATH IN TRAUMA PATIENTS WITH HEMORRHAGIC SHOCK

Cristina Gutierrez, Jubran Dakwar, Sanjay Chawla, Stephen Pastores, Kaye Hale, Memorial Sloan-Kettering Cancer Center, Nina Raoof, Memorial Sloan Kettering Cancer Center, Louis Voigt, Neil Halpern, Memorial Sloan-Kettering Cancer Center Introduction: Death within 24 hours of ICU admission is a difficult outcome for the multidisciplinary ICU team. Hypothesis: To analyze the characteristics of early (⬍24hrs) versus all other deaths (⬎24hrs) in an adult medical/surgical oncologic ICU. Methods: Using hospital databases, we retrospectively analyzed all ICU deaths from 1/2005 to 12/2009. We compared the characteristics of patients who died within 24 hours of ICU admission (early deaths) to all other deaths in the ICU (⬎24 hrs). ICU admission data included age, gender, service type (medical or surgical), pre-ICU length of stay (LOS), Mortality Probability Model score (MPM0II), admitting diagnosis, use of mechanical ventilation (MV) or vasopressors (VP), arterial pH, lactate, and pre-ICU cardiac arrest. Data are presented as means (⫾SD), absolute numbers and percentages. P values were calculated by Student’s t-test and chi-square tests. Results: During the study period there were 632 ICU deaths. Of these, 123 (19%) died within 24 hours of ICU admission. The most common ICU admission diagnoses in both groups were septic shock and respiratory failure. There were no significant differences in age, gender or admitting service between the two groups. Compared with all other deaths, early deaths had significantly higher MPM0II scores (73.5 vs. 55.2, p⬍0.0001), lactate (7.5 vs. 3.7, p⬍0.0001), greater use of MV (72.4% vs. 52.8%, p⬍0.0001) and VP (66.7% vs. 34%, p⬍0.0001), lower arterial pH (7.27 vs. 7.32, p⬍0.0001), shorter pre-ICU LOS (7.3 days vs. 12 days, p⫽0.02), and were more likely to have a cardiac arrest (19.5% vs. 3.5%, p⬍0.0001) prior to ICU admission. Conclusions: Approximately 20% of our ICU deaths occurred within 24 hours of ICU admission. Early deaths were more than five times as likely to have suffered a cardiac arrest prior to ICU admission. While there were discernable differences between the two groups, none of these appear to be modifiable as to avert death.

Nobuyuki Saito, Kunihiro Mashiko, Hisashi Matumoto, Chiba Hokusou Hospital,Nippon medical school Introduction: Optimal monitoring of cardiac index (CI) is of importance in the hemodynamic management of trauma patients with hemorrhagic shock (HS).The efficacy and accuracy of the cardiac output evaluation of the pulse contour cardiac output (PiCCO) system (Pulsion, Germany) have been reported in many studies. We employed data measured just after intensive care unit (ICU) admission by the transpulmonary thermal dilution (TTD) techniqueusing the PiCCO system in trauma patients with HS. Hypothesis: Thisstudy was aimed to determine whether hemodynamic parameters can be used to predict death in trauma patients with HS. Methods: A single-institution prospective observational study was conducted from July 2007 to June 2010.Of 1713 trauma patients admitted during the study period, 110 developed hemorrhagic shock requiring blood transfusion and mechanical ventilation.We divided the patients into the survival group and the death group. We compared the following PiCCO data of the patients: CI, stroke volume index (SVI,intrathoracic bood volume index (ITBVI) on ICU admission after hemostatic therapy. The chi-square test and Mann-Whitney U test were used for comparing the two groups and multivariate analysis by the stepwise method was used to identify prognostic factors. Results: Victims of blunt trauma accounted for 91.8%. Median age of the patients was 51.5 [37-70] years, median injury severity score (ISS) was 30 [22-41], and mortality rate was 10.9%. Ninty-eight patients were assigned to the survival group and 26 to the death group. CI, SVI, and ITBVI values were significantly lower in the death group than in the survival group. CI on ICU admission was independent prognostic factors for death (odds ratio 14.4 [p⬍0.01; 95% confidence interval (CI): 2.7-75.1]).The area under the curve of the receiver operating characteristic curve for death in CI was 0.93 (p⬍0.01;95% CI: 0.87-0.99).The cutoff value for CI on ICU admission according to the sensitivity specificity curve in relation to death was 2.5 L/m2. Conclusions: CI on ICU admission measured by the TTD technique was correlated with death in trauma patients with HS.

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RETROSPECTIVE REVIEW OF THE RELATIONSHIP BETWEEN VENTRICULAR ASSIST DEVICE PLACEMENT AND BILIARY TRACT DISEASE

USE OF A PREDICTIVE SCORE AS AN EARLY INDICATOR LEADING TO ICU ADMISSION

Manpreet Chadha, Henry Ford Hospital, Eric Rinker, Wayne State Univ, Subhash Reddy, HFH, Jack Jordan, Henry Ford Hospital, Emily Smeltzer, HFH, Ilan Rubinfeld, Henry Ford Hospital, Hasan Nemeh, H Mathilda Horst, HFH Introduction: Liver function is affected by severe congestive heart failure. Ventricular assist devices (VAD) are used to support patients with Class IV heart failure as either destination therapy or as a bridge to transplantation. There are abnormalities in markers for biliary tract disease, such as alkaline phosphatase, that are observed after VAD placement, but the frequency and significance of this is unclear. To better assess the relationship between VAD placement and alkaline phosphatase levels, we reviewed our data from the past decade. Hypothesis: Alkaline phosphatase levels are increased after the placement of a VAD. Methods: A retrospective review was performed on all patients with VAD placement from 2000-2009. Patient alkaline phosphatase levels were analyzed from 30 days preoperative to 6 months post-operative. Ultrasound and HIDA scan evaluations on these patients were also evaluated. Results: 140 patients had 192 VADs placed from 2000-2009 (158 Left VAD, 14 Right VAD, 20 Bilateral VAD). 9 patients (6.4%) were identified by preoperative imaging as having previous cholecystectomy. 95 patients (67.9%) showed elevated levels of alkaline phosphatase. Half of these patients (n⫽48) showed post-operative elevations only. A total of 103 ultrasound examinations of the gallbladder were performed on 74 patients. 58.1% (n⫽43) undergoing ultrasound had abnormal alkaline phosphatase levels. HIDA scans were completed on 4 patients, with 2 showing low ejection fraction, one with normal findings, and one suggesting common bile duct obstruction (leading to ERCP). A single patient had cholecystectomy, showing elevated alkaline phosphatase and an ultrasound with sludge only. An additional patient had cholecystostomy tube placement, and showed normal alkaline phospatase levels and an inconclusive ultrasound. Conclusions: Elevated alkaline phosphatase levels are seen in the majority of patients receiving a VAD, but half of these patients demonstrate this elevation pre-operatively. Imaging the biliary tree in VAD patients rarely shows significant abnormalities that require intervention, even in conjunction with an elevated alkaline phosphatase level.


Crystal Jenkins, Banner Health System, Erkan Hassan, Elaine Comeau, Philips VISICU, Deb Dahl, Banner Health Introduction: The ability to predict which Med/Surg pts will require transfer to an ICU may target clinical attention, improve outcomes and reduce hospital length of stay. Hypothesis: To determine if pts requiring ICU admission could be identified by an easily determined score while on the floor, within 24 hrs prior to ICU transfer. Methods: Pts transferred to a 12 bed ICU after spending at least 24 hrs on a 79 bed med/surg floor from 4/09 to 7/10, of a 176 bed community hospital were retrospectively evaluated. A predictive score (PS) with weighted values for systolic blood pressure, heart rate, respiratory rate, temperature, oxygen saturation and age was calculated (whole number) for each pt: 24, 12, 6 hrs prior to transfer and at time of ICU admission. Statistical analysis was conducted via 2 way ANOVA. Results: 31 patients (0.8% of the Med Surg pts) required transfer to the ICU. Mean age (SD) 62.5 (16.6) yrs; 45.2% males; reasons for ICU admission (# pts) included: infection (10); respiratory (10); cardiovascular (6); other (5). The mean (SD) days on the floor prior to ICU transfer was 3.9 (3.0). A score could not be calculated for 3 pts at the 6 hr prior to admission time. The mean (SD) PS for the 4 measurements progressively increased indicating higher severity from 24 hrs prior to ICU admission: 24 hrs⫽2.87 (1.97); 12 hrs⫽3.65 (2.12); 6 hrs⫽3.57 (1.91) ICU admission⫽5.00 (2.31). P⫽0.001. Based on range of PS (Low ⫽ 0-2, Medium ⫽ 3-4, High ⫽ ⬎ 5) a gradual worsening of PS occurred over the 24 hrs prior to ICU admission (# patients by time-Low/Medium/High score: 24 hrs -16/7/8; 12 hrs -11/10/10; 6 hrs -10/8/10; admission -4/12/15). Conclusions: An easily calculated PS composed of readily available variables worsened over 24 hrs prior to ICU admission. In this patient group, the PS would have provided a 12 hour warning. There was no difference between the 6 hr and 12 hr PS. A floor patient with a PS ⬎ 2.0 should have ongoing clinical and PS determinations at least every 12 hrs. A patient with a PS ⬎ 3.0 should be closely evaluated for ICU admission before further clinical deterioration occurs. This PS is currently being prospectively evaluated.

651 ONGOING ROUTINE SCREENING FOR SEVERE SEPSIS (SS) IS AN IMPORTANT COMPONENT OF A SS PROGRAM David Simonds, Moses Cone Hospitals, Phyllis Griffin, Moses Cone Health System, Robert Groves, Banner Health Systems, Crystal Jenkins, Banner Health System, Marilyn McCord, Philips VISICU, Erkan Hassan, Philips-VISICU, Omar Badawi, Philips VISICU Introduction: Effective strategies for the management of SS are well defined(1). However, initial and post-ICU admission screening for SS is difficult to accomplish. Hypothesis: Ongoing screening to identify SS in ICU pts after admission might allow for earlier recognition and treatment. Methods: Objectives: 1) quantify the number of pts developing SS ⬎ 24 hr post admission via an ongoing screening process as part of an ICU SS program; 2) determine if an electronic screening prompt (SP) improves early identification of post admission pts with SS.Two tele-ICU’s, managing mixed med/surg ICUs (48 beds total) screened all pts every 2 hrs via a validated SP (sens 90%, spec 80%) throughout the pts ICU stay. Precise definitions of roles and responsibilities for screening, diagnosis and management of SS, metrics, and educational efforts were developed. Data were collected from ICU A 4/09-7/09, ICU B 4/10-7/10. Time to SS diagnosis ⫽ ICU admission time (hrs) to time of diagnosis using surviving sepsis campaign definition, rounded to the nearest day. Pts with SS were classified as diagnosis occurring ⬍ 24 hr or ⬎ 24 hr after ICU admission and if the diagnosis was made bedside (ED or ICU) or via SP. Demographic and clinical characteristics of pts diagnosed with SS ⬍ 24 hr & ⬎ 24 hr were compared using chi squared or t-test. Results: 130 SS pts (90 pts ⬍ 24 hr, 40 pts ⬎ 24 hr) were identified. SS occurred with a mean of 6.7 ICU days (95% CI 4.93-8.42, range 1-24 days) in cases developing ⬎ 24 hrs. 70% of pts developed SS in the first week of ICU stay. The SP identified 20% of SS pts occurring ⬍ 24 hr vs 37.5% ⬎ 24 hr. (P⫽0.058). There was no statistical difference between the ⬍ 24 hr & ⬎ 24 hr groups in any demographic or clinical outcome (age, male/female ratio, APACHE II score, SS bundles compliance, survival). Conclusions: Ongoing screening for SS after admission to the ICU is an important and often overlooked component of a SS program with 31% of identified cases occurring ⬎ 24 hrs after ICU admission. The SP can play an important role in identification of pts in this group. Reference: 1) Surviving Sepsis Campaign:international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36:296-327.

652 BAROREFLEX SENSITIVITY IN SEPTIC PATIENTS Hiroshi Endoh, Seiji Hida, Yusuke Hayashi, Hidenori Kinosita, Tadayuki Honda, Satomi Oohashi, Nigata University Graduate School of Medicine & Dental Science Introduction: Autonomic dysfunction is associated with severity of illness and mortality in patients with sepsis or septic multiple organ dysfunction syndrome (MODS). Impaired heart rate variability (HRV) has been shown to be diagnostic of sepsis, correlating with development of MODS. Baroreflex sensitivity (BRS) measures the ability of the autonomic system to change vagal or sympathetic activity in response to a sudden change in systolic blood pressure (SBP). BRS has not been evaluated in septic patients yet. Hypothesis: In addition to HRV, BRS can also indicate severity of sepsis. Methods: Septic ICU patients with positive blood cultures were enrolled. Continuous 6-hour segments of R-R interval (RRI) and arterial SBP were captured daily at 22:00 to 4:00 hour by using a wave management system (Phillips, Japan) throughout the ICU stay. BRS values were evaluated using a sequence method (linear regression line between at least 3 intervals of more than 1-mmHg SBP and 3-msec RRI changes with correlation coefficient ⱖ 0.8) and a transfer function method (mean value of gain in the range of coherence ⱖ0.5). In addition, HRV related spectral variables (LF power and LF/HF ratio) and non-linear variables [approximate entropy (ApEn), multiscale entropy (MSE), and detrended fluctuation analysis (DFA)] were calculated on the RRI segments. Pearson’s correlation coefficient between APACHE II or SOFA score and the above 7 variables were evaluated. All calculations were performed using Matlab (Mathworks, USA). Results: A total of 121 segments from 21 patients with a mean age of 67 years were evaluated. Three patients were expired during the ICU stay. BRS values were 3.8⫾3.2 (mean ⫾ SD) msec /mmHg by the sequence method (n⫽108) and 5.0 ⫾3.6 msec /mmHg by the transfer function method (n⫽56). Both methods correlated well with each other (r⫽0.71, p⬍0.01), but did not correlate with APACHE II (n⫽21) or SOFA (n⫽ 121) scores. Only LF/HF ratio correlated with APACHE II score(r ⫽ -0.247, p⬍0.05). ApEn and MSE correlated well with SOFA score (r ⫽ -0.395 and -0.480, p⬍0.01). Conclusions: BRS does not appear to be an effective indicator of severity of sepsis, whereas HRV related spectral or non-linear variables are effective indicators.

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MODERATE HYPOGLYCEMIA IS ASSOCIATED WITH INCREASED MORTALITY IN MEDICAL ICU PATIENTS, INDEPENDENT OF SEVERITY OF ILLNESS, DIABETIC STATUS AND GLYCEMIC VARIABILITY

OUTCOMES OF SURGICAL ICU PATIENTS REQUIRING PROLONGED MECHANICAL VENTILATION

Bethany Lussier, James Krinsley, Stamford Hospital

Introduction: A relatively small percentage of patients admitted to intensive care units, those with extended stays, consume a disproportionate percentage of resources. While there is some literature describing the outcomes of prolonged mechanical ventilation (PMV, duration 96⫹ hours) in medical populations, limited information is available about PMV in critcally ill surgical populations. Hypothesis: PMV, as an indicator of severe illness, is associated with high mortality among surgical ICU patients. Methods: This is a retrospective analysis of prospectively collected data. 3630 surgical service patients were admitted to the 16 bed adult ICU of a university affiliated hospital between 1/1/00 and 6/30/10. Information was abstracted from the unit’s comprehensive clinical database. 227 (6.6%) required PMV. APACHE II score modified to delete the age component (APmod), ICU LOS and hospital (H) and ICU mortality (MORT) were calculated for each. Results: Table PMV- PMV⫹ p valueN 3403 227 Age 65 (48-77) 64 (45-78) 0.5058Diabetic (%) 14.7 16.3 0.5634Ventilated 19.3% 100.0%APmod 7 (4-10) 17 (13-22) ⬍0.0001H MORT (%) 6.8 30. ⬍0.0001ICU MORT (%) 3.9 23.8 ⬍0.0001 A lower percentage of patients requiring PMV had full functional status before admission: 81.0% vs. 88.7%, p⫽0.0029.The percentage of patients requiring PMV, grouped by diagnostic group: Trauma 9.0; Vascular 3.9; Respiratory 4.7; GI 9.1; Ortho-Neuro 3.8.75 patients (33.0%) underwent tracheostomy (T). T⫹ and T- patients had similar age and APmod. ICU LOS was 20.1 (14.8-27.0) (T⫹) vs. 11.3 (7.1-14.8) (T-) p⬍0.0001. H MORT (%) was 22.7 (T⫹) and 34.8 (T-) p⫽0.0856. Conclusions: Critically ill surgical patients requiring PMV were less likely to live independently before ICU admission, and had high severity of illness and mortality. Trauma and GI patients had the highest rate of PMV. Patients with PMV undergoing tracheostomy had even higher ICU LOS, but there was a trend towards reduced mortality in this group.

Introduction: Hypoglycemia (HYPO) is independently associated with increased risk of mortality (MORT) in critically ill patients, especially at a threshold of ⬍40-45 mg/dL. The possible deleterious effect of moderate HYPO - BG ⬍ 60 mg/dL, has not been clearly defined. Hypothesis: Moderate HYPO has an adverse effect on risk of MORT in critically ill medical patients, independent of severity of illness, diabetic status and glycemic variability (GV). Methods: This is a retrospective review of prospectively collected data involving 1764 medical service patients admitted to the 16 bed adult ICU of a university affiliated hospital from 10/1/05 to 5/31/10. Information was abstracted from the unit’s comprehensive clinical database. Diabetic (DM) status was defined at the time of ICU admission based on all available clinical information. APACHE IV predicted mortality (APIV pred), DM and CV were used in mulitvariable analysis. Patients were stratified by minimum BG (MIN, mg/dL) during ICU stay. Results: Patients with MIN ⬍ 60 mg/dL (MIN60) (n⫽369, 20.9%) tended to be older, more likely to be diabetic, ventilated, and had a higher APIV pred MORT than did patients in other strata.Multivariable analysis demonstrated that DM (p⫽0.0015) and APIV pred MORT (p⬍0.0001), but not GV (coefficient of variation [CV]), age or ventilation, were independently associated with development of MIN60.MORT (%) stratified by CV (%): MIN60yes MIN60noCV ⬍ 20 22.7 12.5CV 20-30 35.7 18.8CV 30⫹ 39.4 26.1For the entire cohort MORT (%) decreased with each 10 mg/dL change in MIN:⬍40 40-49 50-59 60-69 70-79 80-89 90-99 100-109 110-119 120⫹57.5 36.1 29.8 27.6 16.0 15.6 13.0 15.0 10.0 22.8 Multivariable analysis demonstrated that MIN60 was independently associated with increased risk of MORT: OR (95% CI) 1.57 (1.10-2.24) p⫽0.0124. Conclusions: Moderate hypoglycemia (⬍60 mg/dL) was independently associated with increased risk of mortality in this large cohort of medical ICU patients, idependently of severity of illness, diabetic status and glycemic variability.

Preetha Umamaheswaran, James Krinsley, Elijah Min, Kevin Dwyer, Timothy Hall, Stamford Hospital


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656

A MODIFIED 4TS SCORE TO DIAGNOSE HEPARIN INDUCED THROMBOCYTOPENIA IN CRITICALLY ILL PATIENTS

EVOLUTION OF SERUM LEVELS OF PROCALCITONIN (PCT) AND C-REACTIVE PROTEIN (CRP) IN SEPTIC PATIENTS UNDER ANTIBIOTIC THERAPY

Chee Chan, Christian Woods, Vikramjit Mukherjee, Spyros Kamarinos, Andrew Shorr, Washington Hospital Center

Sandro Oliveira, Albert Schweitzer State Hospital

Introduction: Heparin induced thrombocytopenia (HIT) remains a challenging diagnosis. The 4Ts represents a scoring tool developed to facilitate the diagnosis of HIT. The accuracy of the 4Ts in a medical intensive care unit (MICU) has not been assessed. Hypothesis: We hypothesized that a modified 4Ts would be more accurate in stratifying patients with HIT. Methods: We retrospectively scored the 4Ts (maximum score 8) on consecutive MICU patients undergoing HIT antibody testing (2008). We excluded subjects evaluated for HIT ⬍48 hrs after MICU admission. The final diagnosis of HIT, our primary endpoint, was based on the evaluation of the MICU attending. Raw 4T points were segregated to reflect pre-test probabilities for HIT: low (0-3), intermediate (4-5), and high (6-8). We calculated a modified 4T score (m4T) that excluded the attribution of points based on the potential for an alternative explanation for thrombocytopenia. The results of the m4Ts (maximum score 6) were also converted into pretest probability groups: low (0-1), intermediate (2-3), and high (⬎3). We measured the area under the receiver operating characteristic (AUROC) curves to assess the discriminatory power of these scores for the diagnosis of HIT. Results: We included 59 subjects (Age: 61.1⫹/⫺17.4 yrs; APACHEII: 22.1⫹/⫺6.3) and 11.9% were diagnosed with HIT. The mean 4T score in the entire cohort was 2.3⫹/⫺1.7 and 1.9⫹/⫺1.5 for the m4T. The AUROC for the original raw 4T score was 0.75 (95% CI: 0.58-0.92), and decreased to 0.64 (95% CI: 0.38-0.89) when categorized by pre-test probability. The AUROC for the m4T score was similar (0.73; 95% CI: 0.56-0.90). There was minimal loss in discriminatory power when m4T was segregated by pretest probability (0.72: 95% CI: 0.560.89). The negative predictive value of a 4T score of ⬍4 was 91% vs. 100% for a m4T score of ⬍2 (p⫽0.043). Conclusions: The m4T score is simpler than and as accurate as the complete 4T score. Patients with low m4Ts scores are unlikely to have HIT. Physicians should consider not testing for HIT in MICU patients with m4T score of less than 2.


Introduction: The advent of biomarkers has been solidified as new tools for therapeutic management of sepsis, making it more reliable emprı´rical therapy and suggesting a future point to end of treatment or adjust the same. Hypothesis: The objective was to evaluate the behavior of serum PCT and CRP during and after the treatment of sepsis. Methods: The method included patients hospitalized for more than 24 hours in the Intensive Care Unit (ICU) of the Albert Schweitzer State Hospital (HEAS) with criteria of SIRS and this new focus of infection characterized by chest radiography, ultrasonography, computed tomography or urinalysis / urine culture, no recent use of antibiotics. Central venous sampling being performed to measure PCT (ng / dl) and CRP (mg / dl) at 1, 3, 5, 7, 10, 14 and 21 days of recognition of sepsis. The decision of the antibiotic to be started if done by the intensivist who recognized sepsis, based on history, risk factors and co morbidities of the patient and microbiological profile of the hospital. Results: The result was the inclusion of 490 patients, 270 male, average age 59 ⫾ 18.7 years, higher SOFA score of 07 ⫾ 5, mean duration of antibiotic use in days 11.3 ⫾ 3 2 and in-hospital mortality of 16.3%. There were 67% positive culture results. Mean values of PCT and CRP are respectively on day 1: 15.3 (⫾ 17.9) and 203 (⫾ 113), day 3: 18.8 (⫾ 21.5) and 246 (⫾ 131), 5 days : 6.13 (⫾ 7.1) and 168 (⫾ 100.4), day 7: 2.76 (⫾ 4.15) and 109 (⫾ 71.18), day 10: 1.26 (⫾ 1 61) and 94 (⫾ 70.27), day 14: 0.91 (⫾ 0.74) and 87 (⫾ 68.91) and on day 21: 0.45 (⫾ 0.33) and 49.1 ( ⫾ 27.8). Conclusions: The main finding in the value curve is the similarity in the variation of both biomarkers following treatment mainly because at the peak on day 3 and decreased from the 5th day. Note also the relationship between the reduction of PCT and CRP levels with response to the antibiotic and organic resolution of sepsis, however it can be seen the moment of normalization of values. Thus, the data provided suggest that these biomarkers may be beneficial in observing the efficacy of antibiotic therapy offered.


658

PATIENTS’ PREDICTIONS OF INTENSIVE CARE UNIT READMISSION IN SURGICAL ICU

DECREASED CODES OUTSIDE OF THE INTENSIVE CARE UNIT: EFFECT OF THE RAPID RESPONSE TEAM

Tim Timmers, University Medical Centre of Utrecht

Steven Trottier, Saint John’s Mercy Medical Center, Darshan Patel, St. John’s Mercy

Introduction: Readmission to the ICU within 48 hours is a leading indicator for the quality of ICU care. The aims of this study are to investigate different variables which could be associated with readmission to the surgical ICU (SICU). In this study we quantified and measure the long-term survival and QoL over a period of more than 10 years of patients readmitted to a SICU. Methods: Of all surgical patients admitted to the ICU of the St. Elisabeth hospital between 1995 and 2000, patient characteristics, disease category, severity of illness score (APACHE II and SAPS 3) and survival were prospectively registered. We quantified readmission occurrence during hospital length of stay within 50 days after ICU discharge. We used the EuroQol-5D⫹ questionnaire to measure quality of life. A mean follow up of 8 years after discharge was achieved. Multivariate logistic regression analysis was used to calculate the independent association of expected covariates. Results: One-hundred-fifty-six of 1979 patients (8%) were readmitted to the SICU. The main cause of readmission was respiratory decompensation (48%) followed by sepsis (17%). Patients readmitted to the SICU were older, mostly suffered from a vascular (39%) or gastro-intestinal surgical disease (26%), had a significantly higher initial admission APACHE II and SAPS 3 score (p⬍0.01) and significantly more comorbidities (14% versus 7%, p⫽0.003). We found an independent association with readmission in all different surgical classifications except in the general surgical patient, for the type of admission and for the need for mechanical ventilation. Long-term mortality was higher compared to the total study population (68 versus 53%; p⬍0.001). Readmitted patients had the same mean QoL score compared to non readmitted patients, EQ-us 0.74⫾0.22 versus 0.77⫾0.21. Conclusions: The negative effect of readmission to the SICU on survival appears to be long lasting. Predictors for ICU readmission are scarce. Readmitted patients had worse SAPS 3 scores, higher prevalence of preadmission disease (comorbidity) and their initial admission type was more active treatment (true ICU) dependable.

Introduction: Many hospitals have embraced and supported the rapid response team (RRT) concept. The Institute for Health Improvement recommended the RRT as part of the Saving Lives Campaign. Despite the enthusiasm for the RRT, robust clinical data supporting the RRT is lacking. Hypothesis: The purpose of this study is to determine the effect of an intensive care unit (ICU) based RRT on hospital mortality and cardiac arrest in a large community hospital. Methods: This historical control study compared two years before and after the institution of a RRT regarding hospital mortality and cardiac arrest. The rapid response team consisted of an ICU nurse clinical supervisor, respiratory therapist, physician extender, and the bedside nurse. The activation of the RRT was according to set physiologic criteria. RRT calls were documented in an electronic medical record and recorded in a database. Results: One-thousand nine-hundred and sixty-four rapid response calls were recorded over a two year period. The main reasons for the rapid response calls were: respiratory distress (715, 36%), neurological changes (376, 19%), arrhythmia (280, 14%), hypotension (259, 13%), chest pain (85, 4%) and other (221, 11%). The average time for a rapid response call was 40 minutes. The disposition of patients was: stay in the room (952, 48%), transfer to the ICU (866, 44%), transfer to intermediate care (113, 6%), transfer to telemetry (11, 0.6%), and other (22, 1%). The hospital mortality for the two years prior to and after the institution of the RRT averaged 1.6%, no change. The number of cardiac arrests in the two years prior to the RRT was 412 with 213 (52%) occurring outside of the ICU. The number of cardiac arrests in the two years following the institution of the RRT was 402 with 114 (28%) occurring outside of the ICU. Conclusions: The RRT did not effect the hospital mortality or the actual number of cardiac arrests but did result in more of the cardiac arrests occurring in the ICU. The RRT decreased the codes outside of the ICU by 54% helping to match the patient acuity with the hospital resources. Further evaluation of the RRT appears warranted.

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OUTCOMES OF CONGESTIVE HEART FAILURE REQUIRING MECHANICAL VENTILATION

DIAGNOSTIC UNITLITY OF PLASMA PROCALCITONIN LEVELS IN PULMONARY ASPIRATION

Amit Taneja, Gagan Kumar, Jayshil Patel, Thomas Kaleekal, Medical College of Wisconsin, Rumi Ahmed Khan, Orlando Regional Medical Center, Sandeep Markan, Medical College of Wisconsin, Abhishekh Deshmuk, University of Arkansas, Puneet Sood, Rahul Nanchal, Medical College of Wisconsin

Jahan Porhomayon, Strong Memorial Hospital Rochester University, Hardick Vora, Paul Knight, University at Buffalo, Ali El-Solh, University of Buffalo

Introduction: Reductions in preload and afterload, decrease in the work of breathing, attenuation of the sympathetic drive and reversal of hypoxemia and hypercarbia are some benefits of positive pressure ventilation (PPV) in acute congestive heart failure (ACHF). However, mechanical ventilation (MV) has its own complications and those requiring PPV probably also represent the more severely ill cohort. Several studies have demonstrated the utility of non invasive positive pressure ventilation (NIPPV) in ACHF although a clear mortality benefit has not been shown. Further outcome data of both invasive mechanical ventilation (IMV) and NIPPV from large epidemiological studies are lacking. Hypothesis: Patients with ACHF requiring any form of MV have worse outcomes than those not requiring MV. Methods: Using the Nationwide Inpatient Sample 2008, patients older than 18 years, discharged with a primary diagnosis of acute congestive heart failure (428.21, 428.23, 428.31, 428.33, 428.41, and 428.43) were identified using ICD-9-CM codes. The status of IMV (96.7x) and NIPPV(93.90) was also identified. Outcome variables included frequency, inhospital mortality and length of stay. Chi square test and t tests were used to compare the variables for unadjusted analysis. Multiple logistic regression was used to adjust for age, demographics, co-morbidities and hospital characteristics. Results: There were total of 309,085 adult discharges with primary diagnosis of ACHF in 2008. The frequency of NIPPV was 3.1% and that of IMV was 1.9%. In-hospital mortality of patients admitted on IMV and NIPPV was significantly higher in when compared to those not on MV. The all cause in-hospital mortality was 34.4%, 6.6% and 2% for IMV, NIMV and those not on MV respectively. MV was found to be an independent predictor of mortality in patients with ACHF. (NIPPV: OR 3.5; 95%CI 2.8-4.4 and IMV: OR 30.9; 95%CI 25.8-37.1 ).The length of stay was 16.9 days for patients on IMV, 7.4 days for NIPPV and 5.4 days in those not on MV. Conclusions: About 5% of acute congestive heart failure admissions undergo MV. Mortality and LOS are significantly higher in ventilated patients. MV is an independent predictor of mortality in these patients.

Introduction: Pro-calcitonin level has been introduced in clinical practice to differentiate between aspiration and chemical pneumonitis. Hypothesis: To assess the predictive accuracy of serum procalcitonin in distinguishing chemical aspiration pneumonitis from bacterial aspiration pneumonia Methods: A prospective obsevational study of 65 consecutive patients admitted with pulmonary aspiration and 7 controls intubated for airway protection.Quantitative cultures from bronchoalveolar lavage (BAL) fluid were conducted on all participants. Serial serum procalcitonin levels were measured on day 1 and day 3 using the BRAHMS PCT enzyme-linked fluorescent assay. Results: There were no differences in the median serum concentrations of PCT between patients with positive BAL cultures (n⫽32) and patients with negative BAL cultures (n⫽33) on either day 1 or day 3 post admission. The areas under the ROC curves for were 0.59 (95% CI 0.47-0.72) and 0.63 (95% CI 0.5-0.75), respectively (p⫽0.74). However duration of mechanical ventilation and antibiotic therapy were shorter in those who had a decrease in their procalcitonin levels on day 3 compared to day 1. Hospital mortality was associated with radiographic multilobar disease (adjusted odds ratio (AOR) 1.14; 95% CI 1.01 to 1.31; p⫽0.04) and increasing procalcitonin levels (AOR 5.63; 95% CI 1.56 to 20.29; p⫽ 0.008).positive BAL cultures (n⫽32) and patients with negative BAL cultures (n⫽33) on either day 1 or day 3 post admission. The areas under the ROC curves for were 0.59 (95% CI 0.47-0.72) and 0.63 (95% CI 0.5-0.75), respectively (p⫽0.74). However duration of mechanical ventilation and antibiotic therapy were shorter in those who had a decrease in their procalcitonin levels on day 3 compared to day 1. Hospital mortality was associated with radiographic multilobar disease (adjusted odds ratio (AOR) 1.14; 95% CI 1.01 to 1.31; p⫽0.04) and increasing procalcitonin levels (AOR 5.63; 95% CI 1.56 to 20.29; p⫽ 0.008). Conclusions: Serum procalcitonin had poor diagnostic value in separating bacterial aspiration pneumonia from aspiration pneumonitis.


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663

RISK FACTORS FOR REINTUBATION AFTER UNPLANNED EXTUBATION: AN EXPERIENCE IN A LOCAL SURGICAL INTENSIVE CARE UNIT

SYNCHRONIZED DRAIN BLEACHING: REDUCING INCIDENCE OF MDR AB IN A SURGICAL ICU

Hee-Pyoung Park, Ji-Hyun Lee, Han-Na Lee, Seoul National University Hospital, Young Tae Jeon, Jung-Won Hwang, Seoul National University Bundang hospital Introduction: Unplanned endotracheal extubation (UE) is recognized as the most common airway adverse event in the intensive care unit (ICU). UE can result in life-threatening complications such as arterial hypoxemia and respiratory insufficiency. UE also increased the need for mechnical ventilation (MV) and ICU care. Reintubation often can lead to hemodynamic and airway complications. Furthermore, patients requiring reintubation have been reported as having higher mortality and morbidity rates. Therefore, it is very important to identify which factors predict the need for reintubation. Although previous reports showed that pneumonia and the amount of ventilatory support were significantly associated with reintubation after UE, factors predicting reintubation after UE are not well established. Hypothesis: The aim of this study is to find the predictors for reintubation after UE in mechanically ventilated patients in a tertiary-care surgical intensive care unit (SICU). Methods: Medical charts of patients who admitted to SICU from October 2007 through July 2010 were retrospectively reviewed. Patients with intentional extubation, less than 18 aged, and brain death for organ transplantation were excluded from the data. Post-cardiac surgery patients were also excluded in this study because they were admitted to post-cardiac surgical ICU. Results: 6374 patients admitted to SICU during the study period. A total of 3645 patients received MV. UE occurred in 75 patients (2.1%, 6 patients for accidental extubation and 69 for self-extubation) and the incidence density of UE was 0.51 of 100 ventilated days. Reintubation was needed in 25 patients. Compared to patients without reintubation, patients with reintubation had higher in-hospital mortality (25% vs 2%, p ⬍0.01), longer days on MV (15.4 ⫾ 14.0 vs 1.3 ⫾ 2.6, p ⬍0.01) and ICU stay (20.4 ⫾ 16.2 vs 6.2 ⫾ 10.2, p ⬍0.01). Admission from ward, accidental extubation, MV with full support, low score on Richmond Agitation-Sedation Scale and MV duration more than 24 hours before UE were predictable factors for reintubation after UE. Conclusions: Caution to the increased risk of reintubation after UE is needed in patients that have aforementioned factors.

Ashley DesRrocher, Molly Kane-Carbone, Spectrum Health, Lisa Bishop, Meijer Heart Center Introduction: Several techniques have been proposed to reduce environmental contamination and transmission of multidrug-resistant (MDR) Acinetobacter baumannii (AB). This is a report of our experience with a simple, effective method to control infections from MDR AB. Hypothesis: A novel approach to AB eradication under study at another institution involved pouring a diluted bleach solution into all sink drains. We sought to evaluate an amended strategy to eradicate MDR AB, which was responsible for an identified cluster of infections in our 36-bed surgical/trauma critical care unit. Methods: Six adult patients with MDR AB were identified in June and July 2008. A before-after study was begun in late June 2008 using an AB eradication process of synchronized drain bleaching. A solution of 200 mL of bleach to 5000 mL of tap water mixed in a bath basin was poured down all sink drains in the hospital’s adult ICUs daily at 7:25 am for 2 weeks. Frequency of bleaching was then reduced to once a week for 2 months. At that point, no further AB cases were identified and drain bleaching was stopped. Unfortunately, 4 other cases emerged in October and November 2008. Weekly synchronized drain bleaching was then resumed in December 2008, and it has continued. Results: Incidence of MDR AB (defined as resistant to 3 or more classes of antibiotics) was compared pre and post the bleaching intervention. The 2008 incidence rate was .19/100 patient days. The 2009 incidence rate was .00/100 patient days, a 100% reduction. With the continued implementation of this strategy, no patient has developed an infection from an MDR AB strain for 20 months, since December 2008. In addition, there has not been transmission from any patient admitted with any type of AB infection to any other patient in the ICU. Conclusions: Weekly drain bleaching is a simple, inexpensive, and efficacious intervention to decrease environmental contamination with MDR AB. Hospitals should consider using this valuable, novel tool as an adjunct to other traditional infection control measures to reduce transmission of these deadly infections.

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PROTEIN-C EITHER ALONE OR AS PART OF A NOVEL HEMOSTATIC SCORE COULD REPRESENT A BETTER BIOMARKER THAN PLATELETS TO INDICATE AN HEMATOLOGIC DYSFUNCTION IN PATIENTS WITH SEVERE SEPSIS

AN ANALYSIS OF SCHEDULED FOLLOW-UP COMPUTED TOMOGRAPHY (CT) SCANS IN PEDIATRIC TRAUMA PATIENTS WITH CLOSED HEAD INJURIES

Jean-Francois Mathieu, University of Montreal, Sylvie Boucher, Verdun General Hospital Introduction: Sepsis is the host response to infection. Severe sepsis (SS) is associated with acute organ dysfunction. The inflammatory response leads to an increased production of proinflammatory cytokines. The latter generate a procoagulant state via these mechanisms: Activation of the coagulation system, Downregulation of physiologic anticoagulants, and Inhibition of fibrinolysis. Hypothesis: Hypercoagulability may lead to the formation of microthrombi in the microvasculature, thereby disrupting blood flow to vital organs, and cause a Multiple Organ Dysfunction Syndrome (MODS). Methods: 65 patients hospitalized in the ICU with a diagnosis of Sepsis were included and examined for these variables: All-cause mortality during the hospital stay, Number of Organs showing an acute Dysfunction (NOD), Serial values of Platelets, PT, D-Dimers, Protein-C (PC), and Antithrombin-III (AT), and the calculation of our recently thoroughly described Hemostatic Score (HS) (cf.Dec 2009 CCM suppl.Abstract 755). Results: A HS ⱕ 5 points and a PC ⱖ 0.50 Un/l were suggestive of a mild Sepsis-Associated-Coagulopathy (SAC); while a HS ⱖ 6 points and a PC ⬍ 0.50 Un/l were compatible with an overt SAC and with an Acute Hematologic Dysfunction (AHD). In the first and second groups of patients, All cause mortality were respectively 22% and 59%, the NOD average were 2.8 and 4.8, and the mean PC values were 0.79 Un/l and 0.35Un/l. Conclusions: In Canada, Sepsis with two or more organ failures are required to prescribe Activated Protein-C (APC). Presently, the only criterion of AHD is based on the Platelet count. AHD is diagnosed when Platelets fall below 80 000, or when a 50% decrease is seen over the last 3 days. The latter occurs too late, knowing the earlier the drug is given, the better is the outcome. Limiting AHD to the Platelet count may miss patients with ongoing microvascular thrombosis related to a SAC. Fibrin deposition and clot formation may lead to a reduced blood flow to vital organs, causing hypoxia, cellular distress, and ultimately MODS.To identify patients with SS and AHD, more at risk of developing MODS, a combination of PC values and our new HS may help decide to add APC to the treatment, to protect or reopen the microcirculation.


Susan Duthie, Rady Children’s Hospital- San Diego, Helen Harvey, Ruth Bush, Michael Levy, Mary Hilfiker, Rady Children’s Hospital Introduction: Pediatric head trauma patients undergo head CT scans as part of initial evaluation and it is often practice to repeat the CT within 24 hours of admission. The efficacy of this routine, given risk of transport and radiation exposure, is unclear. Hypothesis: This study is undertaken to determine whether scheduled follow-up CT scans for pediatric trauma patients are needed. Methods: This is an IRB approved retrospective review of patients ⬍ 15 years of age with blunt head injury. Patients were admitted to the Pediatric Intensive or Intermediate Care Units at a Level I trauma center between June 30, 2006 and June 30, 2009. Eligible patients had no significant developmental delay, were on no anti-coagulants,and had a follow-up CT scan within 24 hours of admission. Scheduled CTs were ordered based on the recommendation of the same two attending neurosurgeons. Follow-up CTs were graded as better, worse, unchanged, or expected post-operative change based on the pediatricradiologist’s report. Patients were identified from a search of the hospital trauma registry. Results: 151 patients met inclusion criteria. Eighty four percent (127/151) of the follow-up CTs were scheduled. Of these, 12 were done post-operatively, none leading to treatment change. These patients were excluded from further analysis. Scheduled CT scans were done 577 minutes (SD 322.7 minutes) after the first scan. Thirteen percent (15/115) were worse. 5 patients with worse CTs had a treatment change. The remainder (96%) had no change in treatment. Of the patients who had a change in treatment, two had larger epidural hematomas meeting neurosurgical criteria for evacuation. Two had treatment of coagulopathy when intracerebral contusions were larger. One intubated patient never had purposeful activity, and on repeat CT 315 minutes later, contusion size was larger. An external ventricular drain was placed. Need for treatment change following scheduled CT was associated with low platelet count (Fisher’s Exact Test, p ⫽ 0.03). Conclusions: Despite small numbers, a subset of patients had significant treatment change based on scheduled CT scan results. A repeat CT should be considered for patients whose platelet count is low.

666 NEED FOR ABDOMINAL SURGERY FOLLOWING TRAUMA SIGNIFICANTLY INCREASES THE INCIDENCE OF INFECTIONS Fahim Habib, University of Miami-Jackson Memorial, Fawzi Abukhalil, University of Miami, Carl Schulman, DeWitt Daughtry Family Dept.of Surgery, George Garcia, University of Miami, Mark McKenney, University Miami Jackson Memorial MC, Nicholas Namias, University of Miami/Jackson Memorial Hospital Introduction: Critically ill trauma patients requiring operative intervention are reported to have a greater predilection for the development of infectious complications. These infections add to the morbidity, and increase healthcare resource utilization. Identification of those at greatest risk may allow for more directed application of infection control policies. Hypothesis: Characteristics of operative intervention following traumatic injury determine risk for development of infectious complications. Methods: A retrospective analysis of prospectively collected data over a 12-month period in 2009 was performed at our urban Level I trauma center. Data regarding demographics, operative interventions and development of infectious complications was collected. Statistical analysis was performed using the chi-square test and t-test as appropriate. A p value of ? 0.05 was considered significant. Results: Of 490 critically injured trauma patients admitted to our trauma ICU, 208 (42.4%) developed infections. Pulmonary infections were most common with 263 episodes versus 250 episodes for all other sites. Need for abdominal surgery was significantly associated with increased an incidence of infections. Extra-abdominal surgery and need for emergent surgery did not produce similar increases. Development of infection resulted in a significantly increased ICU stay (p⬍0.0000001) and hospital stay (p⬍0.0000001). It did not however influence survival (p⫽0.05). Intervention Odds Ratio 95%CI p value Any Surgery 1.99 1.34-2.9 0.0003 Abdominal Surgery 2.41 1.67-3.5 0.0000001 Emergency Surgery 0.90 0.67-1.22 0.44 Conclusions: Need for surgery, specifically abdominal surgery following trauma significantly increases the risk of developing infectious complications. The majority of these infections are pulmonary in nature. This should prompt further investigations into the pathophysiologic basis of this finding and target this subgroup for intensive infection control practices.



668

TROPONIN ELEVATIONS AND MORTALITY IN MEDICAL ICU PATIENTS

TROPONIN ELEVATION IS AN INDEPENDENT RISK FACTOR FOR MORTALITY IN SURGICAL ICU PATIENTS

Michael Marchese, Dmitriy Khodorskiy, James Krinsley, Stamford Hospital

Paul Chugay, James Krinsley, Kevin Dwyer, Timothy Hall, Stamford Hospital

Introduction: While cardiac troponins (TR) are sensitive and specific to myocardial injury, elevated TR levels may occur in critically ill patients without acute coronary syndrome (ACS). Emerging literature suggests that medical ICU (MICU) patients without ACS with elevated TR have increased risk of mortality (MORT). The purpose of this study is to evaluate the relationship between TR and MORT in a mixed MICU population. Hypothesis: Increased TR is associated with increased MORT in MICU patients without ACS. Methods: This investigation is a retrospective analysis of prospectively collected data. Information was abstracted from the unit’s clinical database. 2,653 patients were admitted between 10/1/05 - 6/30/10 to the 16 bed adult ICU of this university affiliated hospital; 304 with a primary diagnosis of acute myocardial infarction were excluded. Patients were stratified into groups according to diagnostic category and peak TR (ng/mL) (T0: not measured; T1: 0.00 - 0.10; T2: 0.10-0.75; T3: 0.76⫹). APACHE IV predicted MORT (APIV pred) and Standardized Mortality Ratio (SMR, actual/predicted MORT) were calculated for each patient. Results: Data stratified by peak TR: T0 T1 T2 T3Number 930 637 403 379DM (%) 22.4 26.2 28.3 28.8APIV pred (%) 21.1 24.5 36.5 43.7 MORT (%) 15.6 19.6 31.8 40.1SMR 0.74 0.80 0.87 0.92The OR (95% CI) for MORT associated with T1 ⫽ 0.74 (0.59-0.93), p⫽0.0083; T2 ⫽ 1.68 (1.33-2.12), p⬍0.0001; T3 ⫽ 2.64 (2.10-3.33), p⬍0.0001.MORT (%) stratified by diagnostic group: T0 T1 T2 T3Cardiac 12.2 12.9 24.0 41.0Respiratory 18.4 22.9 29.1 33.8Gastrointestinal 10.9 9.1 28.1 32.6 Neurologic 14.2 15.9 34.9 40.9Septic shock 39.8 50.7 55.4 52.2 Conclusions: Even modest elevation of TR (0.10-0.75 ng/mL) is strongly associated with increased mortality in non-ACS MICU patients.

Introduction: Elevated troponin (T) levels are typically associated with myocardial infarction (MI). However, recent literature has evaluated the significance of elevated T in various ICU populations other than MI. Hypothesis: T elevation in patients (pts) admitted to the surgical ICU may be a possible marker for increased potential for morbidity and mortality. Methods: This study is a retrospective analysis of prospectively collected data from the ICU’s clinical database. The cohort consists of 1,920 SICU pts admitted between 10/1/05 and 6/30/10 to the 16 bed adult ICU of this university affiliated hospital. Data were stratified by diagnostic category (DX), and peak T (ng/dL): T0: not measured; T1: 0.01-0.09; T2: 0.10-0.75; T3: ⬎0.75. APACHE IV predicted MORT (APIV pred) and Standardized Mortality Ratio (SMR, actual/predicted MORT) were calculated for each pt. Results: Data stratified by peak T: T0 T1 T2 T3Number 1321 391 129 79DM (%) 13.6 19.4 22.5 17.7APIV pred (%) 5.7 11.0 19.7 30.7MORT (%) 2.7 6.4 21.7 41.8SMR 0.48 0.58 1.10 1.39Multivariable logistic regression including APIV pred demonstrated that elevated T was independently associated with increased risk of MORT: OR (95% CI) T2 ⫽ 2.67 (1.46-4.81), p⫽0.0014; T3 ⫽ 4.89 (2.51-9.53), p⬍0.0001.MORT stratified by DX: T0 T1 T2 T3VASC 4.0 1.4 35.3 33.3 RESP 1.7 3.2 16.7 0.0GI 6.0 6.3 18.2 38.5 NEURO 0.9 13.5 33.3 50.0Trauma 3.4 8.7 24.3 55.0 Conclusions: Elevated T is independently associated with increased risk of MORT in SICU pts. These pts may benefit from further risk modification to minimize the potential for adverse outcomes.

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FEASIBILITY OF BARTHEL INDEX COLLECTED THROUGH ELECTRONIC MEDICAL RECORD (EMR) AS LONG-TERM ASSESSMENT OF FUNCTIONAL STATUS IN CRITICALLY ILL SURVIVORS

IS THERE AN IDEAL METHOD FOR ACHIEVING GLYCEMIC CONTROL IN THE ICU? A RETROSPECTIVE CHART REVIEW OF INSULIN DRIP PROTOCOL VS. GUIDELINES

Michelle Biehl, Guangxi Li, Martin Reriani, Adil Ahmed, Ramez Smairat, Gregory Wilson, Rahul Kashyap, Ognjen Gajic, Mayo Clinic Introduction: Barthel Index (BI) is a widely used instrument to assess functional status, and it has been employed for long-term assessment of physical performance in critically ill patients. Previous studies have used prospective survey personal to collect BI; however, this is time- and cost-consuming. In this study we aimed at exploring the feasibility of collecting BI from EMR information documented during outpatient visits and hospital readmissions. Hypothesis: It is feasible to collect BI through EMR for long-term assessment of functional status of critical illness survivors. Methods: We performed a study of 48 hospital survivors who were at hospital admission at high risk for acute respiratory distress syndrome based on known risk factors for this syndrome. BI was prospectively collected at baseline and at six months after hospital discharge by phone surveys. Retrospectively, BI was collected through EMR at baseline and when the patients returned to hospital for outpatient visit or readmission. The agreement of changes in BI obtained by two methods was compared using McNemar test. Results: From the 48 hospital survivors, 43 patients survived to six months and could have follow-up of functional status. Survey personal followed-up 34 patients(79%) and EMR captured 33 patients(77%). From the 32 patients where BI was collected through EMR, 42% was through outpatient visits, 26% readmission and 7% both. At baseline and readmission, the missing components of EMR BI were Stairs and Dressing; while at outpatient visit, Grooming, Bladder and Bowel were missing. The difference between the first survey time and first EMR time collection was median 6(IQR 3-9)days; and between the second survey and second EMR time collection was median 38(IQR 14-108)days. When evaluating the trends in BI at 6 months comparing to baseline (improvement or worsening), changes in functional status survey scores correlated well to changes in EMR BI scores (86% agreement, 25 out of 29; mean difference 1.14;p⫽0.76). Conclusions: EMR collection of BI as a measure of long-term assessment of functional status is feasible. Phone surveys and EMR information provide comparable assessment of changes on functional status of critical illness survivors.


Anne Rain Tanner, Inova Fairfax Hospital, Mary Beth Bobek, New Hanover Regional Medical Center, Bruce Canaday, Philadelphia College of Pharmacy Introduction: Intensive glucose control has been shown to improve patient outcomes in the critically ill, but there is little evidence as to the best method to achieve control. New Hanover Regional Medical Center (NHRMC) utilizes two methods for insulin drips: the Cardiac Surgery ICU (CVICU) utilizes clinical judgment/guidelines and the Surgery/Medical ICU’s (STICU/MICU) utilize an insulin drip protocol. Hypothesis: The purpose of this research was to compare two insulin drip methods to determine which method of insulin drip titration more effectively achieved blood glucose (BG) control in the ICU. Methods: Thirty patients admitted from January 2008 to August 2009 to either the CVICU (n⫽15) or the STICU/MICU ((n⫽15) on insulin drips for atleast 24 hours were reviewed retrospectively. Demographic data collected included age, sex, diabetes, and diagnosis. BG results were analyzed over 3 days to compare the time to reach target BG, maintenance of intensive BG control and hypoglycemia. Results: Thirty charts were reviewed. There were more males in the protocol (STICU/ MICU) group (60% vs. 47%), patients were younger (64.1yr vs. 69.9yr), and had higher initial BG values (268 mg/dL vs. 245 mg/dL). More patients in the CVICU group had diabetes (53% vs. 40%). The guidelines (cvicu) method allowed patients to reach target BG range more quickly (7h vs. 10.5h p⫽0.0371). There were no statistically significant differences between guideline and protocol groups respectively for duration of protocol (65.5h vs. 78.7h), average BG (150.93mg/dL vs. 141.6mg/dL), drip stops (1.93 vs. 1.80), time spent below goal (9% vs. 12%), above goal (28% vs. 32%), and at goal (63% vs. 56%). Incidences of hypoglycemia (BG ⬍ 60 mg/dL) were higher in the protocol group versus the guidelines group (7 vs 3). Conclusions: Guidelines titration was more efficient in reaching the target BG range. There was more time spent hyperglycemic and hypoglycemic for the protocol group but it was not statistically significant.

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THE CLINICAL IMPACT OF PACKED RED BLOOD CELL TRANSFUSION IN PEDIATRIC ARDS/ALI PATIENTS

BLOOD MANAGEMENT IN PEDIATRIC SPINAL DEFORMITY SURGERY: REVIEW OF A TWO YEAR EXPERIENCE

Surender Rajasekaran, Dominic Sanfilippo, Allen Shoemaker, Helen Devos Children’s Hospital, Nabil Hassan, DeVos Children’s Hospital

Nabil Hassan, DeVos Children’s Hospital, Dominic Sanfilippo, Matthew Halanski, Diann Reischman, Surender Rajasekaran, Helen DeVos Children’s Hospital

Introduction: Maintaining adequate tissue oxygen delivery in critically ill children with Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) is challenging. Oxygen delivery can be further compromised by the frequent incidence of anemia in pediatric ICU patients. Some clinical reports suggest maintaining a minimal hemoglobin threshold may be beneficial as arterial oxygen content diminishes with deteriorating pulmonary compliance. Hypothesis: Red blood transfusion in children with ARDS/ALI may be associated with adverse unanticipated effects. Methods: Retrospective review of data collected after IRB approval. A Levene’s test was done to assess equality of means prior to t-test. The Pearson product-moment correlation coefficient was used to determine dependence between variables. Results: Data from 227 Pediatric ICU patients who received 478 transfusion was analyzed. 53 patients with ARDS/ALI who received 119 transfusion were separately analyzed. Patients with ARDS/ALI had an elevation in their Mean Airway Pressure (MAP) from 15.2 ⫾ 0.7 to 18.3 ⫾ 0.7 Cm/H2O (16.9 % increase) while in nonARDS patients the elevation was 13.8 ⫾ 0.4 to 16.2 ⫾ 0.4 Cm/H2O (14.8 %). At the same time there was also a significant drop in Absolute Lymphocyte Count ALC by -656 cells/uL (24.4 % decrease) which had a negative correlation with MAP. ARDS/ALI patients with elevated PRISM score ⬎10 had a significant 43.8% drop in their PF ratio compared to 16.4 % in patients with ARDS/ALI and PRISM score ⬍10 .Off Interest, changes in Absolute Neutrophil Count in patients with ARDS/ALI did not reach statistical significance. Also age of blood did not associate with any of the clinical variables. Conclusions: Blood transfusions in with ARDS/ALI are associated with increased MAP in mechanically ventilated patients and a correlated decrease in ALC. This is a hypothesis generating study and is limited by its retrospective design.

Introduction: Pediatric scoliosis surgery is invasive and historically associated with considerable blood loss and RBC transfusions. Blood transfusions independently contribute to morbidity, poor outcomes and cost. Hypothesis: The institution of a blood management program would decrease perioperative blood transfusion rates and ICU utilization. Methods: Data was collected prospectively after initial IRB approval onto a dedicated database. The data was retrospectively analyzed using Mann Whitney and Kruskall Wallis tests and compared using Fisher’s exact or Chi Square tests. Results: Over a 2 year period, 110 scoliosis surgeries were performed with 104 (94%) receiving pre-operative evaluation for blood management. 60 patients were idiopathic (IS), 28 neuromuscular (NMS) and 22 other. 37 patients (34%) required oral Fe and folate and 13 (12%) needed pre-operative erythropoietin to optimize hemoglobin. At initial workup, 12 patients (4 were (NMS), 6 (IS), and 2 in the (O) groups) were diagnosed with mild Von Willebrand disease. Significantly, NMS Patients compared to IS were smaller (46.1g ⫹ 18 vs. 58 kg ⫹ 18, more co-morbidities (96% vs. 30%) longer OR time (348 minutes ⫹ 79 vs. 301 ⫹ 9); had more total blood loss (50 ml/kg ⫹ 45 vs. 20 ⫹ 13); higher transfusion requirements (36% vs. 1.7%)and longer PICU stay (2.3 days ⫹ 1 vs. 1.7 ⫹ .6). Transfused patients had lower preoperative von Willebrand activity (78% ⫹ 34 vs. 95% ⫹ 38). Overall, transfused patients had longer PICU stay (2.8 ⫹ 1.1 vs. 1.8 ⫹ 0.24). Conclusions: Transfusion requirements in scoliosis surgery are dependent on patient characteristics and operative course. An organized blood management approach in our institution resulted in a low transfusion rate of 13 % compared to other reports, with shorter ICU stay.

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LONG-TERM (>6 YEARS) QUALITY OF LIFE AFTER SURGICAL INTENSIVE CARE ADMISSION

INTER-RATER VARIABILITY OF THE 4TS AND CHONG SCORE FOR HEPARIN INDUCED THROMBOCYTOPENIA


Chee Chan, Christian Woods, Washington Hospital Center, Theodore Warkentin, Jo-Ann Sheppard, McMaster University, Andrew Shorr, Washington Hospital Center

Introduction: Aim of this study was to quantify the long-term health-related quality of life (HrQoL, ⬎6 years) of a large cohort of patients admitted to a surgical ICU. In addition, we explore the influence of different surgical-classifications on long-term health status and to make comparisons with general population. Methods: HrQoL was measured in all surviving surgical ICU-patients admitted to a Dutch teaching hospital (1995-2000). Patient-reported data on HrQoL were collected with the EuroQol-6D after a mean follow-up of 8 years. Patient characteristics were prospectively registered. EQ-utility scores (EQ-us) and domain-specific health problems were calculated. The effect of surgicalclassification on EQ-us was assessed by multivariable-generalized-linear-regression analysis. Logistic regression was used to explore the influence of surgicalclassifications on domain-specific health problems. Long-term HrQoL of surgical ICU-patients was compared to an age-and sex-matched general Dutch population using the T-test analysis. Results: 834 patients survived the ICU and were available for follow up. In 575 (69%) patients the HrQoL was measured. For all surgical-classifications combined, after 6-11 years nearly half of all patients still suffered from problems in the dimensions mobility, usual activity, pain and cognition. Compared to the age-and sex-matched general population HRQoL was worse with a difference of 0.11 on the EQ-us (range 0-1). Oncological surgery patient had the best (EQ-us 0.83) and vascular patients the worst (EQ-us 0.72) HrQoL. Conclusions: More than 6 years after surgical ICU-admission, HrQoL of this patient population is largely reduced. Many patients still suffer from a variety of health problems, including decreased cognitive functioning.

Introduction: Accurate diagnosis in suspected Heparin Induced Thrombocytopenia (HIT) is paramount in the management of this syndrome. Two clinical scoring tools, the 4Ts and Chong scores, exist to assess the probability for HIT. The inter-rater variability of these systems has not been evaluated. Hypothesis: We hypothesized that the 4T and Chong scores are reproducible when calculated by different observers. Methods: Two clinicians prospectively evaluated the charts of consecutive patients who had undergone HIT antibody testing for thrombocytopenia. They calculated the 4Ts and Chong scores. Scorers were blinded to: the other rater’s score, the final diagnosis for thrombocytopenia, and patient outcomes. Raw 4T scores and Chong scores were converted into class groups as proposed by the creators of the respective scores: low, intermediate, high (4Ts) and unlikely, possible, probable, definite (Chong). Class groups were further dichotomized into high vs low risk groups: low vs at least intermediate and unlikely vs all else, respectively. We determined the intraclass correlation coefficient to assess inter-rater variability of the raw scores, and calculated the kappa statistic for agreement regarding risk group. Results: The cohort includes 100 subjects (mean age: 64.0 ⫹/⫺ 16.2, male: 53%). The mean 4T score was 2.9 ⫹/⫺ 1.5 for observer 1 and 2.3 ⫹/⫺ 1.4 for observer 2; the mean Chong scores were 1.9 ⫹/⫺ 1.4 and 1.8 ⫹/⫺ 1.5, respectively. The intraclass correlation for the 4Ts was moderate (0.50; p⬍0.0001) and good for the Chong score (0.61, p⬍0.0001). The inter-rater variability was fair for both class and risk group comparisons. The kappa statistic for 4T was 0.34 and 0.38, and 0.35 and 0.40 for Chong, respectively. There was discordance in class group in 25% of 4T cases and in 33% for the Chong score. Conclusions: Inter-rater agreement for the 4Ts and Chong score are fair. There is minimal improvement in overall agreement between raters after further segregating scores into bivariate risk groups. The 4Ts and Chong score are inconsistently reproducible scores for determining the probability of HIT.Funding: This study was funded by GSK.


676 CHANGE IN ANION GAP AND MORTALITY IN CRITICALLY ILL PATIENTS Michael Lipnick, Andrea Braun, Brigham and Women’s Hospital, Heidi Bazick, Massachusetts General Hospital, Domingo Chang, Brigham and Women’s Hospital, Ting-Wai Cheung, Schulich School of Medicine and Dentistry, Fiona Gibbons, Massachusetts General Hospital, Kenneth Christopher, Brigham and Women’s Hospital Introduction: There are significant limitations in interpreting the anion gap especially in critically ill patients. Hypothesis: We hypothesized that the difference between ICU admission anion gap and pre-hospital admission anion gap (⌬AG) is associated with all cause mortality in the critically ill. Methods: We performed a multicenter observational study of 18,985 patients, age ⱖ 18 years, who received critical care between 1997 and 2007. The patients were treated in 209 medical and surgical ICU beds in two hospitals in Boston, Massachusetts. The exposure of interest was ⌬AG and categorized a priori as ⬍0 mEq/L, 0-5 mEq/L, 5-10 mEq/L, and ⬎10 mEq/L. Logistic regression examined death by days 30, 90 and 365 post-ICU admission and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Adjustment included age, gender, race, hematocrit, WBC, creatinine, BUN, Deyo-Charlson Index, transfusions and sepsis. ROC analysis was performed for a subset of patients with lactate drawn (n⫽2,700) with the gold standard being lactate ⬎ 5 mmol/L. Results: ⌬AG was a strong predictor of mortality 30 days following ICU admission with a significant risk gradient across ⌬AG quartiles following multivariable adjustment: ⌬AG ⬍0 mEq/L OR 0.75 (95% CI, 0.67-0.81; P⬍.0001); ⌬AG 5-10 mEq/L OR 1.56 (95% CI, 1.35-1.81; P⬍.0001); ⌬AG ⬎ 10 mEq/L OR 2.18 (95% CI, 1.76-2.71; P⬍.0001); all relative to patients with ⌬AG 0-5 mEq/L. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 post-ICU admission as well as in-hospital mortality. Effect modification is present with urine ketones but is absent with lactic acidosis. Inclusion of albumin correction to pre-admission anion gap and ICU admission anon gap did not materially change the ⌬AG-mortality association. The sensitivity of ⌬AG⬎3 mEq/L for lactate⬎5 mmol/L is 68.2%, with a specificity of 68.1%, a positive predictive value of 27.6%, a negative predictive value of 92.3% and an AUC of 0.682. Conclusions: An increase in anion gap at ICU admission relative to pre-hospital admission anion gap (⌬AG) is a significant predictor of the risk of all cause patient mortality in the critically ill.



678

RESPIRATORY PARAMETERS AND PROGNOSIS OF CHILDREN WITH INTERSTITIAL LUNG DISEASE IN ICU

CORRELATION BETWEEN ANEMIA AND DELAYED CEREBRAL ISCHEMIA (DCI) AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

Kyung Won Kim, Yong Ju Lee, Jiyoung Baek, Myung Hyun Sohn, Kyu-Earn Kim, Severance Children’s Hospital, Yonsei University College of Medicine Introduction: The mortality rate of pediatric interstitial lung disease (ILD) is very high. Hypothesis: We investigated the relation between the prognosis and respiratory parameters of children with ILD in intensive care unit (ICU). Methods: Pediatric ILD patients with ventilator care in ICU were enrolled retrospectively from Jan 2005 to Dec 2009. We reviewed the changes of their respiratory parameters in first 4 days and their prognosis. Results: A total of 31 children with ILD was admitted. Ten patients were admitted in ICU for ventilator care among them. Two children were survived, but 8 patients were dead. The survivors were 2.8 years old and the deads were 2.4 years old. The average of length of stay in ICU was 77 days in survivors and 31 days in deads. There were no differences in PaO2/FiO2, oxygenation index (OI), ventilation index (VI) at the time of start in ventilator care. PaO2/FiO2, OI and VI at the second day did not differ between the groups. Survivors had significant higher levels of PaO2/FiO2 at the third day [median, 239.4; range, 197.1 to 281.7) than deads (108.3; 50.6 to 174; P ⫽ 0.033). Survivors had significant lower levels of OI at the third day (4; 4 to 4) than deads (15.5; 5 to 35; P ⫽ 0.034). Survivors had significant lower levels of peak inspiratory pressure (PIP), FiO2, OI and higher levels of SatO2, PaO2/FiO2 at the fourth day. Conclusions: Our findings suggest that respiratory parameters at the third day might be more important for survival than those at the time of start in ventilator care for children with ILD in ICU.

Muhammad Taqi, Medical College of Wisconsin, John Lynch, The Medical College of Wisconsin, Michel Torbey, Froedtert & Medical College of Wisconsin Introduction: Delayedcerebral ischemia (DCI) is responsible for the morbidity associated withaneurysmal subarchnoid hemorrhage. Higher clinical grades (fisher or WFNS) are associated with occurrence of DCI. Conventional treatmentto prevent DCI consists of hypertension, hypervolemia and hemodilution (HHHtherapy). Changes in hematocritcan potentially affect the brain tissue oxygenation in two ways: higherhematocrit increases oxygen carrying capacity and lower hematocrit decreasesviscosity and hence increase cerebral blood flow. This optimal hematocrit is unknown. Hypothesis: Recent studies have shown that blood transfusion increases cerebral blood flow and decreases O2 extraction ratio in subarachnoid patients. We analyzed relationship of hematocrit with incidence of stroke in our subarachnoid population. Methods: Records of the patients with aneuriymal subarachnoid hemorrhage admitted to our institute were reviewed. 87 patient with aneurysmal subarachnoid hemorrhage wereidentified from July 2009-June 2010. Results: 24 delayed cerebral ischemic events were identified in 24 patients. DCI were diagnosed clinically and were confirmed by either CT head orMRI brain. Patientswere divided among three groups based on their nadir hematocrit during the first 21 days: group A Hematocrit ⬍26 (n⫽15), group B hematocrit 26-30(n⫽12) and group C hematocrit ⬎30 (n⫽60). Incidence of delayed cerebral ischemia in group A⫽12/15(86.7%), group B⫽4/12(33.4%) and group C⫽ 7/60(11.7%). All patients had higherclinical grades (Fisher 2 or more). Conclusions: Although lower hemtocrit decreases blood viscosity andtheoretically should increase cerebral blood flow, it significantly decreasesthe oxygen carrying capacity of blood and therefore could result in ischemia ofbrain tissue. In our cohort ofpatients, the highest incidence of DCI was observed in patients with ahematocrit of ⬍26% while keeping the clinical grade constant. This suggest that anemia (hematocrit of⬍26) predisposes to DCI and should be avoided in patients with aneurysmal SAH.

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LONG-TERM SURVIVAL AFTER SURGICAL INTENSIVE CARE ADMISSION: 50% DIES WITHIN 10 YEARS

INITIATION OF SAFETY SEAT INSPECTION STATIONS AND RESULTANT INJURY REDUCTION IN THE STATE OF DELAWARE

Tim Timmers, University Medical Centre of Utrecht Introduction: Intensive care unit (ICU) treatment of surgical patients comes along with major disadvantages which have to be justified by an acceptable shortand long-term outcome. Short-term effects of ICU treatment have been well documented. The aims of this study were to quantify the long-term survival of more than 10 years follow up of a large cohort of patients admitted to a surgical intensive care unit and to investigate the effects of age, gender and underlying disease on this long-term survival. Methods: Of all surgical patients admitted to the ICU of the St. Elisabeth hospital between 1995 and 2000, patient characteristics, disease category, APACHE II score and survival were prospectively registered. A follow up with a mean of 8 years after discharge was achieved. The independent association of multiple co-variates was done using cox proportional hazard analysis. Results: Of the 1822 patients included, 936 (51%) had died within 11 years. 52 patients were lost to follow up. Overall ICU and in-hospital mortality were 11% and 16% respectively. Age, gender, APACHE II score, the need for dialysis and surgical classification were independently associated with long-term survival. Mortality increased with age of admittance to the ICU (hazard ratio 1.058), whereas female patients had a lower chance to die, HR 0.793. However, the pre-admission disease did not influence long-term outcome. Longterm mortality rates in various surgical classification groups varied between 29% for trauma and 80% for gastro-intestinal patients. In gastro-intestinal, oncological, general surgical and/or high-aged patients a negative effect on mortality persisted beyond 5 years. The mortality ratio was increased two-fold in comparison to the general population (51 vs 27%). Conclusions: Ten years after ICU discharge, survival was only 50%. After ICU treatment survival follows distinct patterns in which age, gender, surgical classification, the need of dialysis and APACHE II score are independent determinants, and long lasting.

Kevin Couloures, Oklahoma University Children’s Hospital, Sean Elwell, AI duPont Hospital for Children Introduction: Proper restraint of children in vehicles is important since motor vehicle deaths are the leading cause of unintentional injury deaths in children ages 1-9 accounting for 976 deaths in 2006. Child safety seats can reduce fatal injury by 71 percent for infants and by 54 percent for toddlers, ages 1-4. Child safety seats can also reduce the need for hospitalization and the risk of minor injury. Proper use of rear seat positioned safety seats can reduce the risk of injury to 1.1% while inappropriately used safety seats only reduce the risk of injury to 1.8%. Hypothesis: Determine if the initiation of safety seat inspection program reduced the number of installation errors and the number of unrestrained fatalities and injuries within the State of Delaware. Methods: Retrospective analysis of 17,610 safety seat inspections performed in the Delaware safety seat inspection program during 2005-2009 and Delaware Trauma Registry data for 573 children ages 0-9 years-old and 2072 children ages 10-19 years-old. Results: Safety seat inspection stations have reduced the number of major installation errors by 200% over the 5-year-period analyzed. In 2008 and 2009, 2526 children were injured and 30 children were killed. In 2008, 61 of the 1257 injured children required hospitalization. The use of restraints in injured children under the age of 4-years-old was greater than 93%. The use of restraints in children killed in motor vehicle accidents during 2008 and 2009 was 50% (5/10) in children ages 0-9 years-old and 40% in children ages 10-19 years-old (8/20). Conclusions: Safety seat inspections are having a positive effect in ensuring that seats are installed correctly and emphasizing the importance of their use. Greater efforts need to be made to ensure that older children are properly restrained.


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MULTIPLE CO-MORBIDITY AND PRIOR YEAR HOSPITALIZATION INCREASE THE RISK OF ICU SEVERE SEPSIS

THE USE OF APACHE II, CHILD-PUGH, CHARLSON, AND MELD INDEXES FOR PREDICTION OF EARLY MORTALITY IN POST-LIVER TRANSPLANTATION

Walter Linde-Zwirble, Z D Associates, Hannah Wunsch, Columbia University Medical Center, Sachin Yende, University of Pittsburgh, Carmen Guerra, Columbia University, Derek Angus, University of Pittsburgh Critical Care Medicine CRISMA Laboratory Introduction: While population basedhospital discharge databases linked to the US census have allowed for estimatesof severe sepsis (SS) prevalence as a factor of age/gender/race, andco-morbidity is known to be common in SS patients, the risk of developing SS asa function of these factors has not been explored. We modeled ICU SS (ISS) incidence in the Medicare population to examine the relationshipbetween demographics, co-morbidity and intensity of health resource use for theprobability of developing ISS. Hypothesis: Health state (co-morbidityand recent institutional care) has greater impact on the risk of ISSthan demographics. Methods: We selected all beneficiaries aged 66⫹y from a 2.5% sample of the fee-for-service population in 2003. All encounters for 2002 were examined toidentify chronic co-morbidity (Charlson-Deyo) and institutional care (acute hospitalization and SNF). ISS in 2003 was identified using the Angus methodology. We built a logistic regression model for the incidence of ISS as afunction of age/race/gender, prior year institutional care and co-morbidity.The effect of a risk factor is expressed by its odds ratio (OR). Results: There were 869,568 beneficiaries in the cohort with an ISS incidence of 0.9% (N⫽7486). Prior year hospitalization was common (15.3%), as was co-morbidity (25% single, 17.7%multiple) and 27.7% were aged 80⫹y. The model fit well with chi-sq dispersion of 1.02, LL r-sq of 54% and ROC⫽0.76 and was well calibrated (H&L C⫽29, 18df, p⫽0.16). Several factors were both common and high risk: pulmonary disease(9.3%, OR 2.42); multiple hospitalizations (5.6%, OR 2.36); chronic renaldisease (5.4%, OR 1.86); and diabetes (17.6%, OR 1.77). Advancing age had alesser impact on ISS incidence (1.16, 1.46, 1.68, 2.02 for 70-74, 75-79, 80-84,85⫹ compared to 66-69). Overall, the predicted risk of ISS ranged from 0.2% to40%. Conclusions: ISS incidence variedgreatly in the Medicare population and was most strongly associated withunderlying health state of the beneficiary both through chronic co-morbidityand poor health state as seen with prior year hospitalization. Better awareness of and care for patients at high risk of developing severe sepsis might allowfor avoidance of ISS.

Anibal Basile-Filho, Edson Antoˆnio Nicolini, Maria Auxiliadora-Martins, Gil Cezar Alkmim-Teixeira, Divisaõ de Terapia Intensiva, HCFMRP, Universidade de Saõ Paulo, Ribeiraõ Preto, SP, Brasil, Olindo Assis Martins-Filho, LBDM, Instituto Rene´ Rachou, Fundaçaõ Oswaldo Cruz, Belo Horizonte, MG, Brasil, Orlando Castro e Silva Jr., Unidade de Transplante Hepa´tico, HCFMRP, Universidade de Saõ Paulo, Ribeiraõ Preto, SP, Brasil Introduction: The survival rate of patients submitted to orthotopic liver transplantation (OLT) does not depend only on the choice of donor, the transplant candidate, or the employed surgical technique. Various studies have been conducted in an attempt to find an ideal prognostic index that employs clinical symptoms or comorbidities and that can accurately predict which patient is more susceptible to developing postoperative complications. Hypothesis: The aim of this study was to determine which prognostic index is the most efficient in predicting early (one-month) mortality of patients submitted to orthotopic liver transplantation (OLT). Methods: This is a retrospective study of sixty-three patients (49 males, 14 females, median age 51.6⫾9.7 years) admitted to the Intensive Care Unit (ICU) of a tertiary hospital. The APACHE II death risk, Child-Pugh, Charlson, and MELD indexes were analyzed by generation of receiver-operator characteristic (ROC) curves as evidenced by the area under the curve (AUC), in order to evaluate predictive factors for each index. The level of significance was set at p⬍0.05. Results: The general posttransplantation mortality of OLT patients within one month was 19% (12 patients). The AUC was 0.81 (CI ⫽ 0.66-0.96; sensitivity ⫽ 72.5; specificity ⫽ 83.3) for APACHE II death risk; 0.70 (CI ⫽ 0.54-0.85; sensitivity ⫽ 64.7; specificity ⫽ 66.7) for ChildPugh; 0.57 (CI ⫽ 0.36-0.78; sensitivity ⫽ 74.5; specificity ⫽ 50.0) for Charlson; and 0.50 (CI ⫽ 0.31-0.67; sensitivity ⫽ 98.0; specificity⫽16.7) for MELD. Conclusions: Among the studied indexes, the APACHE II death risk scoring system was the most effective in predicting early mortality after OLT.

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684

EXTUBATION FAILURE IN PATIENTS WITH PRIMARY BRAIN INJURY

PREDICTORS OF MECHANICAL VENTILATION AFTER BURN INJURY

Navaz Karanjia, Johns Hopkins Hospital, Diana Nordquist, Westchester Medical Center, Robert Stevens, Johns Hopkins University School of Medicine, Paul Nyquist, Johns Hopkins School of Medicine

Arash Pirat, Pinar Zeyneloglu, Aycan Kundakci, Cem Aydogan, Gulnaz Arslan, Mehmet Haberal, Baskent University, Faculty of Medicine

Introduction: Patients with acute brain injury but normal lung function are often intubated for airway protection. Extubation often fails. Currently, no clinical data exist that describe the events leading to extubation failure and reintubation in this population. Hypothesis: Our objective was to identify the clinical characteristics of patients for whom extubation failed whose primary reason for intubation was a primary brain injury independent of mechanical lung injury. We also identified the extubation failure rate, reintubation rate, and clinical characteristics of these patients. Our primary hyopthesis was that causes other than aspiration and or pneumonia would be the main reason for reintubation. Methods: Retrospective review of electronic databases supplemented by chart review from January 2002 to March 2007. Results: Patients admitted to the neurocritical care unit who were intubated because of primary neurological injury of brain, spinal cord, or peripheral nerve numbered 1265. Of these, 25 (2%) died before extubation and 767 (61%) were extubated. The number of patients extubated to comfort care was 292 (23%). Tracheostomies were placed in 181 (14%) patients, of which, 77 (5.9%) were attempted before extubation. A total of 129 (10%) patients were reintubated; 77 (5.9% ) met the clinical definition of extubation failure. Ninety-nine of the patients reintubated had encephalopathy that resulted from primary brain injury. Of these, 12 (12%) had a documented pneumonia, six (6%) aspirated, six (6%) experienced stridor, and 17 (17%) experienced a medical emergency. The most common clinical scenario leading to reintubation was respiratory distress with altered mental status [59 patients (59%)]; these patients usually suffered from atelectasis and decreased minute ventilation, independent of fever, pneumonia, aspiration, and increased work of breathing [39 patients (39%)]. Conclusions: The extubation failure rate in our neurocritical care unit is low. In patients with primary brain injury who were intubated, atelectasis and decreased minute ventilation were the most common causes for reintubation. Aspiration and pneumonia were not the most common reason for reintubation.


Introduction: It is important to predict the need for mechanical ventilation (MV) in burn patients in order to improve their management and also optimize resource ultilization. However, there is scant data on the predictors of MV in burn patients. Hypothesis: The purpose of this study was to determine the predictors of MV during the first three days of hospitalization in our burn patients. Methods: A retrospective chart review was completed for patients admitted to Baskent University Burn Institute, from January 2003 through December 2008. Patients were divided into two groups based on whether they required MV during their first three days of hospitalization or not. After comparing the two groups for the recorded variables, a binary logistic regression model was developed using statistical and clinical significance to identify the predictors of MV. Results: Out of 160 patients, 33 patients (21%) required MV during their first 3 days of hospitalization. Patients who required MV were similar to those who did not in terms of demographic features. Patients who required MV were significantly different from those who did not regarding mean burn percentage (54%⫾23% vs 21%⫾14%, p⬍0.001), mechanism of burn (flame, 70% vs 34%, p⬍0.001), ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) (335.3⫾119.5 vs 432.3⫾68.8, p⬍0.001), and inhalation injury (27% vs 3%, p⬍0.001). Binary logistic regression revealed that inhalation injury (OR, 5.4; 95% CI, 1.1-28.4; p⫽0.049) and burn percentage (OR, 1.1; 95% CI, 1.1-1.2; p⬍0.001) were predictors of MV. Conclusions: Our results demonstrated that inhalational injury and burn percentage were predictors of MV in burn patients. Particularly, patients with inhalational injury were 5 times more likely to require MV during their first three days of hospitalization in our series.

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686

EVALUATION OF THE INCIDENCE AND ASSOCIATED MORBIDITY OF ILEUS IN THE INTENSIVE CARE UNIT

PREDICTORS OF PROLONGED INTENSIVE CARE UNIT STAY AFTER ORTHOTOPIC LIVER TRANSPLANTATION

Salmaan Kanji, Tiffany Nguyen, Rakesh Patel, Avinder Singh, Christel Johanson, Robert MacLean, Allison Simpson, Colleen Golka, Ottawa Hospital, David Williamson, Anne Julie Frenette, Hoˆpital Sacre´-Coeur de Montreál

Aycan Kundakci, Arash Pirat, Ozgur Komurcu, Adnan Torgay, Hamdi Karakayali, Gulnaz Arslan, Baskent University, Faculty of Medicine

Introduction: Although ileus is common in critically ill patients, its definition, epidemiology and associated morbidity are poorly described. In this prospective multicenter observational study, we propose a clinical definition of ileus, describe its incidence, course and risk factors in ICU patients. Methods: Consecutively admitted, mechanically ventilated patients and enterally fed for ⱖ72 hours were prospectively identified over a 3 month period at 3 Canadian ICUs (April 1st 2010-September 1st 2010). Ileus was defined as the absence of a bowel movement for ⱖ 3 days, initiation of constipation treatment, and one of the following: 1) radiographic evidence consistent with ileus, 2) feed intolerance, 3) new abdominal distension or 4) suction/deflation via nasogastric tube. We extracted patient data pertaining to patient demographics, severity of critical illness, incidence of ileus and its associated complications. Results: From 236 eligible patients, 38 (16.1%) were identified as having ileus, the mean duration of which was 6.4 ⫾ 2.6 days. No difference in severity of illness was identified between those with and without ileus (APACHE II: 23.1 ⫹ 9.3 vs 23.0 ⫹ 8.4, respectively, p⫽0.95). The use of pharmacological prophylaxis for constipation was similar in patients with and without ileus (71.4% vs. 62.1%, respectively; p⫽0.4). Patients with ileus received a mean of 1.4⫾1.6 mg/day equivalent hydromorphone before and during their ileus. Comparatively, patients without ileus received a mean of 5.1⫾8.1 mg/day in their first week of admission. Nutritional goals were met in 72% of patients with ileus compared to 88% in the non ileus patients (p⫽0.15). ICU length of stay was significantly longer (19.0 ⫹ 12.3 days) in patients with ileus versus those without (12.8 ⫾ 8.2, p⬍0.004). ICU mortality in patients with ileus was higher but not statistically different (31.6% vs. 22.3%; p⫽0.22). Conclusions: Ileus is common in the ICU and is associated with a potential for nutrition compromise and significantly longer ICU length of stay. Opiate dose was not a predictor of ileus in our population. Future research should focus on recognition of signs and development of therapeutic strategies for prevention and treatment.

Introduction: Intensive care unit (ICU) stay consumes physical and financial resources and may increase the risk of complications and possibly mortality. Hypothesis: The purpose of this study was to evaluate the factors predicting prolonged ICU length of stay (LOS) after orthotopic liver transplantation (OLT). Methods: We reviewed the data of 112 adult patients who underwent OLT between January 2000 and February 2009. The data included the demographic and clinical features, preoperative laboratory values, intraoperative hemodynamic parameters and transfusions, and mortalities. Prolonged ICU LOS was defined as more than 3 days stay in the ICU after OLT. Results: Out of 112 patients 59 (50%) of them required prolonged ICU LOS. Patients who required prolonged ICU LOS compared to those who did not had higher model for end stage liver disease with sodium scores (MELD-Na) (23.3⫾7.0 vs 15.8⫾5.2, p⬍0.001), had longer duration of anesthesia (11.2⫾2.2 hours vs 10.2⫾2.0 hours, p⫽0.010), had more frequent hypotensive periods intraoperatively (1.4⫾1.5 vs 0.7⫾1.1, p⫽0.013), and required more fresh frozen plasma (FFP) intraoperatively (44.2⫾27.1 ml/kg vs 24.5⫾12.8 ml/kg, p⬍0.001). Binary logistic regression revealed higher MELD–Na score (odds ratio: 1.2, CI%95:1.1-1.5, p⫽0.007) and larger amount of intraoperative FFP requirement (odds ratio: 1.0, CI 95%:1.01.1, p⫽0.046) as the risk factors for prolonged ICU LOS. Patients with prolonged ICU LOS had higher mortality rates than their controls (41% vs 9%, p⬍0.001). Conclusions: In conclusion, higher MELD–Na score and larger amount of intraoperative FFP requirement were the predictors of prolonged ICU stay in our patients.

687 MORBIDITY AND MORTALITY CONFERENCE IN THE INTENSIVE CARE UNIT: PROCESS AND OUTCOME ANALYSIS Tarik Hanane, Anita Reddy, Aanchal Kapoor, Sandra Sykes, Jorge Guzman, Cleveland Clinic Introduction: Morbidity and Mortality conferences (M&M) are peer reviews of adverse events and deaths aimed at improving patients’ safety and quality of care. Despite being mandated by the Accreditation Council of Graduate Medical Education for all residency training programs, no specific guidelines for M&M format or content exist. Hypothesis: The present format of the M&M conferences at the Cleveland Clinic medical intensive care unit (MICU) is useful in monitoring the quality of patient care and determining areas for improvement. Methods: M&M conferences are held biweekly and chaired by two designated staff intensivists. The meetings are attended by rotating residents, fellows, physician extenders, and additional ICU staff. The rotating fellows are responsible for presenting cases with fatal outcomes according to a designated template. Preventable factors contributing to death are reviewed and classified as diagnosis or communication failure, or inappropriate treatment or delivery of care. Additionally, all non-fatal adverse events, accidental extubations and unit readmissions are also reviewed. Results: There were 1314 admissions to the MICU between January 1st and June 30th 2010. A total of 237 deaths occurred during the study period. A case review was performed on 99% of deaths, 77% of them being completed within 30 days of death. Eighteen potential preventable factors (7.6%) were documented. System issues were associated with either diagnostic or communication failure or inappropriate treatment plan. Morbidity review identified 240 non-fatal events. The 2 most common were related to skin care and diagnostic testing or specimen handling. Only 8 patients sustained permanent harm or required prolonged hospitalization or interventions to sustain life. Thirty ICU readmissions occurred within 48 hours (2%) and the observed accidental extubation rate was 0.25/100 ventilator days. Conclusions: Timely review of ICU deaths and adverse events is challenging and requires the engagement of all ICU team members. The process is helpful in creating a culture of safety and identifying targets for process improvement that ultimately enhance patient care.



689

THE RELATIONSHIP BETWEEN BODY TEMPERATURE ON PRESENTATION TO THE ICU AND MORTALITY AMONG PATIENTS ADMITTED WITH SEPTIC SHOCK

RISK OF TROPONIN ELEVATION IN ICU PATIENTS WITH NO ACUTE HEART DISEASE

Victor Rivera-Santiago, James Krinsley, Stamford Hospital Introduction: Sepsis (S) is associated with high mortality (M). Abnormalities in temperature (T) regulation - hypothermia and hyperthermia - are frequently seen, but the prognostic impact of T dyregulation occurring early in the course of S has not been well described. The purpose of this study is to describe the relationship of initial T to M in patients admitted to the ICU with S. Hypothesis: Among patients admitted to the ICU with S, hypothermia and hypothermia have different prognostic impact. Methods: This is a retrospective study using prospectively collected data. Between 10/1/05 and 6/3010 4,787 patients were admitted to the 16 bed adult ICU of this university affiliated hospital. 2217 were admitted from the Emergency Department. Of this group, 169 (7.6%) had S, and constitute the study cohort. Data were abstracted from the unit’s comprehensive clinical database. APACHE IV predicted mortality % (APIVPrM) and Standardized Mortality Ratio (SMR, actual/predicted M) were calculated, and compared to initial T as well as maximum (max) and minimum (min) T during the first 24 hours of ICU stay. Results: Median (IQR) age of the cohort was 75 (58-84). 44.4% were ventilated. APIVPrM (%) (mean [SD]) and M (%) were 44.2 (28.7) and 45.6 respectively. # M APIVPrM SMR Initial T ⬍95.0 14 57.1 49.2 1.16⬍97.0 46 52.2 47.1 1.1197.0-100.9 73 49.3 48.1 1.02⬎100.9 50 34.0 36.0 0.94⬎102.9 20 25.0 34.1 0.73 Tmin 24 hr ICU⬍95.0 21 66.7 59.6 1.12⬍97.0 66 56.1 52.1 1.0897.0-100.9 101 38.6 38.5 1.00 Tmax 24 hr ICU97.0-100.9 111 48.6 46.3 1.05⬎100.9 54 37.0 38.0 0.97⬎102.9 14 21.4 40.8 0.52 Conclusions: Hypothermia was associated with higher severity of illness and higher M than was hyperthermia in this cohort of S patients. The lower SMR among patients with hyperthermnia suggests a possible protective role; further investigation including larger cohorts would be needed to confirm this finding and elucidate its mechanism.

Nasrien Ibrahim, University of Cincinnati College of Medicine, Robin Vandivier, Florence Rothenberg, VAMC Introduction: Our study seeks to identify the mortality associated with elevated troponins in critically ill patients with no known coronary artery disease. This data will be used to help determine best clinical practice in management of such patients. Methods: We evaluated patients admitted to the Cincinnati VAMC critical care units from ’05-’08 who had an elevated troponin T or I. We excluded patients admitted for acute coronary syndromes, those admitted following surgical or medical procedures, and women. 560 patients had an elevated troponin T or I; 266 had no known coronary artery disease. The primary endpoints were mortality at 30 days, 6 months and one year. For troponin T, a value ⬍ 0.03 was considered “normal” (value at the 99 percentile of a healthy reference population), 0.03-0.1 “intermediate”, and ⬎0.1 “high”. For troponin I, a value ⬍0.05 was considered “normal”, 0.05-0.78 “intermediate”, and ⬎0.78 “high”. Results: 266 included patients (mean age 68.3), majority had sepsis as the admitting diagnosis. Average troponin I of those alive at one year was significantly lower than patients who died within the first year (0.52 vs. 0.94, p⫽0.03). This was not seen with troponin T (0.51 vs. 0.56, p⫽0.28). 65% of patients with high troponin died within one year as opposed to 48% with intermediate troponin (p⫽0.006). Lower average peak troponin was not associated with improved survival at 30 days (0.71 vs. 1.17 for I, p⫽0.10 ;0.45 vs. 0.57 for T, p⫽0.60) but was at 6 months (0.66 vs. 0.97 for I, p⫽0.03; 0.37 vs. 0.54 for T, p⫽0.64). Patients receiving a beta blocker had improved survival compared to patients not receiving a beta blocker (48% vs. 35%, p⫽0.03). Improved survival was also seen in patients who received a statin (49% vs. 36%, p⫽0.03, Chi-square). The combination of statin and beta-blocker however was not found to be beneficial (48% vs. 39%, p⫽0.14). Conclusions: High cardiac troponin was associated with higher mortality. The use of a beta blocker in this setting is associated with improved mortality as was the use of a statin alone. The combination of a beta blocker and statin however was not found to be beneficial.

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691

MODERATE HYPOGLYCEMIA IS ASSOCIATED WITH INCREASED MORTALITY IN SURGICAL ICU PATIENTS, INDEPENDENT OF SEVERITY OF ILLNESS, DIABETIC STATUS AND GLYCEMIC VARIABILITY

THE UTILITY OF THE SAPS II, SAPS III AND APACHE II FOR PREDICTING SURGICAL OUTCOMES AND ICU OUTCOMES IN PATIENTS > 90 YEARS

Brian Kelly, James Krinsley, Kevin Dwyer, Timothy Hall, Stamford Hospital Introduction: Intensive glycemic management protocols to treat even moderate hyperglycemia have been implemented worldwide in the 9 years since publication of the original surgical ICU study from Leuven, Belgium. Hypoglycemia often results, and this complication has been found to be independently associated with increased risk of mortality (M). The threshold for harm regarding degree of HY has not been clearly identified. Hypothesis: Moderate hypoglycemia, defined as blood glucose (BG, mg/dL) ⬍ 60, is independently associated with increased risk of M in critically ill surgical patients. Methods: This is a retrospective review of prospectively collected data involving 1499 surgical service patients admitted to the 16 bed adult ICU of this university affiliated hospital. Data were abstracted from the unit’s comprehensive clinical database. Coefficient of variation (%) (CV) was used as a measure of glycemic variability. APACHE IV predicted M (APIVPrM), diabetic status and CV were used in multivariable analysis. Patients were stratified by minimum BG (MIN) during ICU stay. Results: Patients with MIN ⬍ 60 (MIN60) were older, with higher APIVPrM and were more likely to be diabetic (DM) and to undergo mechanical ventilation.Multivariable analysis demonstrated that APIVPrM and DM were independently associated with the development of MIN60 (p⬍0.0001 for each).M (%) stratified by CV (%) MIN60yes MIN60noCV ⬍ 25 31.6 3.1 CV 25⫹ 26.4 4.9 For the entire cohort, M (%) decreased with each 10 mg/dL increase in MIN: ⬍40 40-49 50-59 60-69 70-79 80-89 90-99 100-109 110-119 120⫹36.4 31.9 22.7 7.8 8.6 3.2 1.7 2.2 1.3 1.8 Multivariable analysis demonstrated that MIN60, but not CV or DM, was independently associated with increased risk of M: OR (95%CI) 10.08 (5.08-19.23) p⬍0.0001. Conclusions: Moderate hypoglycemia, defined as minimum BG ⬍ 60 mg/dL during ICU stay, was independently associated with markedly increased risk of mortality in this cohort of critically ill surgical patients. Clinical practice should be changed to prevent BG ⬍ 60 mg/dL in this population.


Aftab Haq, Sachin Patil, Alexis Lanteri, Ronald Chamberlain, Saint Barnabas Medical Center Introduction: Individuals ⬎ 65 years old in the United States will reach 20% by 2026. Elderly patients currently represent between 26-50% of all ICU admissions. Specific information on factors influencing ICU survival rates is essential. We evaluated the utility of three previously used intensive care unit (ICU) scoring systems to predict clinical outcomes among 117 patients ⬎ 90 years admitted to surgical ICU (SICU) between 2000 and 2010. Hypothesis: To test the utility of ICU scoring systems in surgical patients ⬎90 years old. Methods: 1189 surgical procedures involving 951 patients ⬎ 90 years (between 2000 and 2010) were analyzed. Age, gender, co-morbidities, procedure type, operative time, LOS, ICU admission and outcome were abstracted. SAPS II, SAPS III and APACHE II were calculated for all patients admitted to SICU. Differences between the patients who died and those who survived were analyzed using the student’s t-test. Results: 117 (9.8%) surgical patients ⬎90 years old were admitted to the SICU. Sufficient information was available for 89 patients. The mean age of these patients was 93.2 years (91-100) with a M: F ratio of 1: 1.02. Surgical procedures performed including general surgery (32.6%), neurosurgery (13.5%), orthopedic (11.2%), vascular surgery (11.2%), cardiac (9%), urologic surgery (9%) and 12.4% of patients had invasive procedures (endoscopy, cystoscopy and biopsy). The mean ASA score was 3.3 ⫾ 0.7, and the mean operative time was 152 ⫾ 112 minutes. The mean ICU and hospital stay was 6 ⫾ 8 days and 16.6 ⫾ 15 days, respectively. The overall mortality in this group was 15.7% (14 of 89) compared to 5.1% (55 of 1077) for those not admitted to the SICU. The mean SAPS II, SAPS III and APACHE II scores (predicted mortality) for patients who died were 57.4⫾20.0 (55.2%⫾29.7%), 74.6 ⫾ 14.2 (60.7%⫾22.1%) and 23.1⫾8.7 (46.4%⫾26.4%) while the scores for those who were discharged were 41.7⫾14.9 (30.5%⫾23.7%), 57.8⫾ 14.5 (32.4%⫾23.6) and 16.0⫾7.0 (26.8⫾19.1), respectively, p ⬍ 0.05. Conclusions: Patients ⬎ 90 years of age represent a poor surgical risk group and there is an increased mortality rate for those who require SICU admission. SAPS III scoring system predicted mortality more accurately in this age group.

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693

ADMISSION SERUM BILIRUBIN LEVELS ARE PREDICTIVE OF OUTCOMES IN SEVERE SEPSIS AND SEPTIC SHOCK

PROGNOSTIC INDICATORS OF MORTALITY OF MECHANICALLY VENTILATED PATIENTS WITH ACUTE LEUKEMIA IN A COMPREHENSIVE CANCER CENTER

Jayshil Patel, Amit Taneja, David Niccum, Dana Soetaert, Muhammad Ali, Shahryar Ahmad, Gagan Kumar, Rahul Nanchal, Medical College of Wisconsin Introduction: Severe sepsis – sepsis associated with organ failure is common and often fatal. Most often, demise from this disease is secondary to multiple organ failure. Severity of disease scoring systems such as the ‘sequential organ failure assessment’ (SOFA) have incorporated the serum bilirubin into a composite score of multiple organ dysfunction to estimate prognosis. Serum bilirubin has been independently evaluated in outcome prediction in patients with the acute respiratory distress syndrome. No prior investigation has systematically evaluated serum bilirubin as a tool to independently predict outcomes in patients with severe sepsis. Hypothesis: Serum bilirubin levels independently predict worse outcomes in patients with severe sepsis Methods: Using retrospective chart review, we evaluated consecutive patients admitted to the medical intensive care unit (MICU) of an academic tertiary care hospital with a diagnosis of severe sepsis from July 1, 2009 through April 30, 2010. We excluded patients with a previous diagnosis of liver disease. The highest serum bilirubin level obtained within 72 hours of admission was used for our analysis. Our primary outcome of interest was all cause in hospital mortality. Secondary outcomes included need and duration of both vasopressor use and mechanical ventilation as well as ICU and hospital length of stay. Chi square and t tests were used for unadjusted analysis and multiple logistic regression was performed to adjust for demographics, Charlson co-morbidity index and severity of illness using APACHE II scores. Results: We identified 52 patients with severe sepsis or septic shock without pre-existing liver disease. On univariate analysis, serum bilirubin levels greater than 1 mg/dL was associated higher mortality (33% vs. 10%, p⫽0.049). On adjusted analysis, the odds of in-hospital mortality is 16.6 times (95% CI 1.4-192) greater for bilirubin level of ⬎ 1 mg/dL. ICU length of stay was 4.4 days longer (95% CI 0.43-8.48) for admission bilirubin ⬎ 1 mg/dL. An elevated bilirubin was not associated with duration of mechanical ventilation and vasopressor use. Conclusions: Serum bilirubin level is an independent risk factor for outcomes in patients with severe sepsis

Kristen Price, Marylou Cardenas-Turanzas, Heather Lin, Linda Roden, The University of Texas MD Anderson Cancer Center, Rupesh Nigam, The University of Texas Health Science Center, Joseph Nates, The University of Texas MD Anderson Cancer Center Introduction: The mortality in patients with acute leukemia and respiratory failure is about 80%. Hypothesis: We aimed to identify prognostic indicators for 30-day hospital mortality of patients with acute leukemia, respiratory failure and who received invasive mechanical ventilation. Methods: We conducted a case control study and retrospectively reviewed the medical records of patients older than 16 year of age with acute leukemia, and respiratory failure admitted the ICU of a Comprehensive Cancer Center between January 2002 and January 2006. All patients had received invasive mechanical ventilation during the stay and excluded were blood and marrow transplantation recipients, those admitted to rule out myocardial infarction and patients following cardiopulmonary arrest. The main outcome measure was 30-day hospital mortality. Results: Median patient age was 61 years, and the most frequent reason for ICU admission was respiratory insufficiency/failure (69%). The 30-day hospital mortality rate was 86%, the in-hospital mortality rate was 83%. Multivariate logistic regression analysis showed the independent predictors of 30-day hospital mortality to be increased sequential organ failure assessment (SOFA) score at intubation (odds ratio [OR] ⫽ 1.44; 95% confidence interval [CI] ⫽ 1.19, 1.76), advanced disease status (OR ⫽ 7.59; 95% CI ⫽ 2.34, 24.70), and tracheal intubation 24 hours after ICU admission (OR ⫽ 3.78; 95% CI ⫽ 1.37, 10.40). The Hosmer and Lemeshow goodness-of-fit test showed a chi-square value of 8.28, degrees of freedom ⫽ 8 and P value ⫽ .41. The model discrimination was .83. Similar results were observed for in-hospital mortality. Conclusions: Advanced disease status, the severity of illness identified by a higher SOFA score, and delayed intubation following ICU admission were strong predictors of increased 30-day and inhospital mortality. These prognostic factors may impact future medical decisions after mechanical ventilation is initiated in this population of critically ill patients.

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695

IMPACT OF MULTIDISCIPLINARY TEAM TRAINING IN A SURGICAL INTENSIVE CARE UNIT

VALIDATION OF SIX MORTALITY PREDICTION SYSTEMS FOR SURGICAL INTENSIVE CARE UNIT PATIENTS

Mira Loh-Trivedi, William Croley, Carmel Goudzwaard, Rush University Medical Center


Introduction: Medical error is a leading cause of adverse events, including death. It is estimated that 44,000 to 98,000 patients die in US hospitals annually due to preventable human error. Poor communication has been readily identified as a contributing factor to medical errors. The purpose of this study is to evaluate the impact of multidisciplinary team training in a Surgical Intensive Care Unit. Hypothesis: Crew Resource Management has been found to improve communication, patient safety and outcomes in specific patient populations. Methods: In an effort to reduce the number of preventable errors, over 200 multidisciplinary members of the Surgical Intensive Care Unit (SICU) staff at Rush University Medical Center (RUMC) were required to attend a 4 hour Crew Resource Management (CRM) class. This class emphasizes empowering each member of the healthcare team to be a patient safety advocate. Team decision-making, assertive statements, identification of red flags and hardwired safety tools are critical components of CRM. Multidisciplinary groups meet monthly to create or refine hardwired safety tools that address red flags for identified areas of risk. The data was prospectively collected and reviewed retrospectively. After development and implementation of these communication tools, we collected data on the following items: device utilization (central lines, arterial lines, urinary catheters and drains) and associated infection rates, compliance with mechanical ventilation bundles, medication reconciliation and the SICU culture survey. Results: To date, endpoints that have resulted from the CRM training include: decreased device utilization (foley device utilization decreased from above the 50% percentile(FY10Q3) to less than the 25th percentile (FY10Q4), decreased urinary catheter associated infection rates, increased medication reconciliation and improved mechanical ventilation bundle compliance. Conclusions: CRM training and execution has resulted in improved engagement in the SICU from multidisciplinary healthcare providers.

Introduction: This study investigates the prognostic quality of six prediction models (APACHE II Score, SAPS II, SAPS II(Expanded), SAPS 3, MPM II0 and MPM III) for the assessment in an adult surgical intensive care unit in the Netherlands. Secondly, we tested the capability of the APACHE II model to identify patients at risk of dying the first five years after ICU discharge. Methods: Of all single admissions to the surgical ICU of the St. Elisabeth hospital between 1995 and 2000, data to calculate the results of six prediction models were prospectively documented. To evaluate discrimination and calibration, receiver operating characteristic (ROC) curves, area under the characteristic (AUC) curve and the Hosmer-Lemeshow goodness-of-fit test were performed. Results: The data of 1821 patients were applied to all six models. Accurate overall mortality prediction was found for the APACHE II, SAPS II, SAPS 3 and MPM models. Discrimination was best for the SAPS 3 and MPM III models and worst for the APACHE II model with AUC of 0.81, 0.77 and 0.77, respectively. Calibration was poor for the six prediction systems, varying between 23 (SAPS 3) to 233 (SAPS II(Expanded)). There was a significant improvement in calibration for the APACHE II, SAPS II, SAPS II(Exp) and MPM II models after adjusting the baseline risks (intercepts) for each model. The SAPS 3 and MPM III system did not so much show improved calibration, as the former was already good in the lower probability groups Conclusions: The newer SAPS 3 prediction mortality model is the best validated model for a surgical ICU population of six models tested. The other general prognostic models underestimate the risk of dying. The APACHE II model could also be helpful to identify patients at risk of dying during the five years after ICU discharge.


696

697

BAROTRAUMA IN PATIENTS WITH H1N1-INDUCED ALI/ ARDS; VENTILATOR SETTINGS OR DISEASE SEVERITY?

PRESSURE ULCER REDUCTION IN MEDICAL INTENSIVE CARE UNIT: SUCCESS OF MICU SKIN BREAKDOWN PREVENTION PROTOCOL

Gustavo Cumbo-Nacheli, Cleveland Clinic, Satish Chandrasekaran, Mayo Clinic, John Komara, Tarik Hanane, Jorge Guzman, Cleveland Clinic Introduction: Critical illness due to 2009 H1N1 influenza has been characterized by a high incidence of respiratory symptoms and increased need for mechanical ventilation (MV). Barotrauma is a complication of MV associated with increased morbidity and mortality. Variations in the reported incidence of ventilator-associated barotrauma may relate to differences in patients underlying disease. Hypothesis: It is unknown whether H1N1 infection predisposes to higher incidence of barotrauma. This study was performed to evaluate risk factors for barotrauma development and in mechanically ventilated H1N1 positive patients. Methods: All mechanically ventilated patients admitted to the MICU who tested positive for H1N1 infection between October 1st and December 31st 2009 were included in the study and divided in two groups according to the presence (Group I) or absence of barotrauma (Group II). Results: Twenty patients were included in the study (G I n ⫽ 8; G II n ⫽ 12). Mean overall age and APACHE II scores were 44.5 ⫾ 12.5 years and 24.0 ⫾ 8.8, respectively. Mean mechanical ventilation time before barotrauma was 8.1 ⫾ 8.3 days (range⫽0-21 days). Patients in Group I were more hypoxic; PaO2/FiO2 90.9⫾ 26, 97.5 ⫾ 53, and 95.1 ⫾ 46, vs. 192.5 ⫾ 137, 228.3 ⫾ 100 and 194.2 ⫾ 80 for patients in Group II for days 0, 3, and 7, respectively (P ⬍ 0.05). Patients in Group I received higher PEEP (cm H2O): 17 ⫾ 7, 16 ⫾ 7 and 17 ⫾ 7, vs. 12 ⫾ 7, 13 ⫾ 9 and 10 ⫾ 6 for patients in Group II for days 0, 3, and 7, respectively. Group I patients received higher Plateau Pressure (cm H2O) for days 0, 3, and 7: 35 ⫾ 9, 37 ⫾ 7 and 37 ⫾ 11, vs. 34 ⫾ 9, 34 ⫾ 6 and 27 ⫾ 7 for Group 2. There was a statistically significant difference for PEEP and Plateau Pressure between groups at day 7 (P ⬍ 0.05). There was no difference in indexed tidal volumes.Patients with barotrauma required more alternative modes of ventilation and rescue therapies. Overall 28-day mortality was 30% and was higher for patients with barotrauma (63% vs. 8%, P ⫽ 0.01). Conclusions: The development of barotrauma is associated with adverse outcomes among H1N1 infected patients with ALI/ ARDS. It is unclear whether ventilator settings, disease severity, or both are contributing factors.


Carolyn Holder, Emory University Hospital Introduction: Pressure Ulcer Reduction : Success of MICU Skin Breakdown Prevention Protocol The MICU Practice Council reviewed unit specific data from the National Data for Nursing Quality Indicators and identified that reduction of pressure ulcers needed to be a priority. Hypothesis: A goal for pressure ulcers to reduce Hospital Acquired Pressure Ulcers to the the 50th percentile of Magnet organizations which is 2.10%. The MICU specific target is below 8.02%. By implementing a Skin Prevention Protocol a target of unit acquired preessure ulcers would be reduced to 8.02%. Methods: Unit Practice Council members to identified problems and potential solutions. with an interdisciplinary team to develop a plan. In February , the group agreed upon a Skin Breakdown Prevention Protocol which includes evidence based and best practice strategies. One component of the protocol is a bed decision tree that increases use of low air-loss surfaces based on integumentary assessment and Braden scoring. This decision was based on review of unit data, and supported by Braden recommendations. The protocol includes a recommendation that pressure relief boots and sequential compression devices be removed every 12 hours for 30 minutes. Results: Weekly ‘Skin Rounds‘ were conducted by the Skin Champions, Clinical Nurse Specialist, and bedside nurses in March 2010. During rounds, NDNQI information was monitored it was an opportunity to validate documentation, and educate staff. Weekly data analysis revealed 45% of unit acquired pressure ulcers occur on non-traditional areas such as around tracheostomy sites. Targeting patients with a Braden score less than 14 on who were likely to develop a pressure ulcer were placed on low air-loss surfaces. Since March 2010, the MICU pressure ulcer rate has dropped from 18.8% in January 2010 to 0% on the July 2010 NDNQI quarterly survey. Conclusions: Conclusion: Implementation of a MICU Pressure Ulcer Prevention Protocol provided a standard process for skin assessment, identification of pressure ulcers on admission, identification of patients at high risk for pressure ulcers and preventive strategies. The MICU was successful in acieving the goal.


699

BRONCHOALVEOLAR LAVAGE AS A SCREENING TOOL FOR PULMONARY INFECTIONS IN BURN PATIENTS

2-YEAR EXPERIENCE OF PIGTAIL CATHETER IN THE MANAGEMENT OF TRAUMATIC PNEUMOTHORAX: A CHANGING TREND

Daniel Fisher, Grace Thorne, Mary-Liz Bilodeau, Shawn Fagan, Massachusetts General Hospital Introduction: Ventilator associated pneumonia (VAP) has been attributed with an increase in both morbidity and mortality of the ICU patient. When VAP is coupled with burn injury, the incidence of mortality can increase as much as 40% when compared with the burn injury alone. There are many factors that contribute to the development of VAP and the presence of inhalation injury may complicate diagnosis. Hypothesis: We hypothesize that blind bronchoalveolar lavage can be safely used as a screening tool for patients at risk for VAP in a burn center including those with inhalation injury. Methods: All patients requiring invasive mechanical ventilation who were admitted to an adult burn center from January 21, 2009 through June 4, 2010 underwent a mini-BAL within 6 hours of admission to the unit. The mini-BAL was performed by a respiratory therapist who was trained in the procedure. Sputum cultures were followed for 7 days after the procedure.The fluid returned was then sent for micobiological testing. Samples were considered satisfactory if there a ring of bubbles were present when shaken, and there were leukocytes noted in the microbiology report. All airway instrumentation such as flexible bronchoscopy was postponed until the sample was obtained. Results: 54 mechanically ventilated patients underwent BAL (36 male, 18 female; mean ages 47.7 years male, and 46.5 years female). 40 (74.1%) of the samples contained leukocytes. 14 (25.9%) of these patients developed pneumonia. From this group, 6 (42.8%) had an inhalation injury. 7 (50%) had a positive BAL culture. 1 patient developed pneumonia who had no growth reported. 14 (25.9%) of the 54 patients did not have leukocytes present, and did not have growth, 3 of these patients developed pneumonia. Conclusions: VAP has numerous contributing factors. Using BAL as a screen to identify those patients at increased risk has been shown to be an effective tool. The results of the following culture can then direct the medical team. By early recognition of pneumonia, patients can be spared prolonged ICU stay. Reported rates of nosocomial pneumonia for burn patients may be reflective of these patients being innoculated prior to admission. Further study is required.

700 EMERGENCY DEPARTMENT LENGTH OF STAY DOES NOT CORRELATE WITH PEDIATRIC INTENSIVE CARE UNIT LENGTH OF STAY IN CRITICALLY ILL CHILDREN Adam Silverman, Christopher Carroll, Connecticut Children’s Medical Center Introduction: Long stays in the Pediatric Intensive Care Unit (PICU) result in significant costs and utilization of resources. Adult studies have found associations between prolonged ICU length of stay (LOS) and medical, social, psychological and institutional factors. Few pediatric studies exist looking at factors that influence PICU LOS. Infections, fever and renal dysfunction have all been found to be independently associated with longer PICU LOS. A significant number of PICU admissions start in emergency departments (ED). There is little data looking at the way in which care provided in the ED influences the outcome of critically ill children. ED LOS may be influence PICU LOS. Hypothesis: ED LOS may be associated with PICU LOS in critically ill children. Methods: Children admitted to the PICU from the ED of a tertiary children’s hospital between 1/1/2009 through 12/31/2009, for which there was complete data, were retrospectively analyzed. The ED had approximately 52,000 visits during this time period. The ED LOS was determined using an EMR used for all ED visits. The PICU LOS was determined using a spreadsheet into which data for all PICU admissions is prospectively entered. There were 349 children admitted from the ED to the PICU during this time period. Complete data was available for 300 patients. There were approximately 1000 PICU admissions during this time period. Results: For critically ill children admitted from the ED to the PICU, the average ED LOS was 3.3 hrs ⫾1.6 hrs. The mean PICU LOS for these children was 83.0 hrs ⫾ 123.5 hrs. No correlation was found between ED LOS and PICU LOS (P⫽0.67). We further looked at various categories of disease to see if there was this influenced correlation. In admissions classified as being for asthma, diabetic ketoacidosis and shock, the relations ship approached a negative correlation (ie. longer ED LOS resulted in shorter PICU LOS). Conclusions: Overall ED LOS does not correlate with PICU LOS. Specific categories of critical illness in which require ED interventions, which increase the ED LOS, may result in an overall decrease in PICU LOS. Further analysis may lead to identifying what interventions are most effective at decreasing PICU LOS.

Narong Kulvatunyou, University of Arizona College of Medicine, Aparna Vijayasekaran, Randy Friese, Bellal Joseph, Rifat Latifi, Terrance O’Keefe, Julie Wynne, Peter Rhee, University of Arizona Introduction: Conventional treatment of traumatic hemo-pneumothorax (HPTX) is chest tube thoracostomy (CT). CT however is large in size, can cause pain, and worsen outcome. The pigtail catheter (PC) is smaller, less invasive, and has worked well in patients with a non-traumatic pneumothorax (PTX). Hypothesis: This study is to review our early experiences of using PC in traumatic PTX. Methods: We retrospectively reviewed the chart of trauma patients over our last 2-year period (2008-2009) at a Level 1 trauma center that required CT or PC placement for HPTX. The PCs were 14F Cook catheters placed over a guide-wire with an introducer and were placed by the trauma team. We excluded CT/PC that was placed during an emergency resusci-tation or after thoracotomy. Subgroup analysis is performed for CT/PC placed for PTX. Results: Of 9,624 trauma patients evaluated, 97 were treated with PC and 369 with CT. Our PC placement has increased over time (graph). Eighty percent of PC was placed for PTX, comparing to 39% for CT. The failure rate, defined as an additional tube placement is comparable between CT and PC (12% vs. 16%, p⫽.27). Similarly, PC has a higher insertion- related complication rate than CT but it is not statistically significant (4%vs. 2%, p⫽.12). Subgroup analysis for PC/CT placed for PTX has a similar outcome (table). PC-PTX (79) CT-PTX(190) P-value Age 43⫹21 40⫹18 0.18 Sex (M:F) 1.9:1 3.4:1 0.046 Blunt (%) 82 84 0.74 ISS 17 ⫹ 11 21 ⫹ 13 0.14 Tube, (d) 4(3,5) 4 (3,6) 0.09 Vent day 0(0,4) 0 (0,3) 0.37 ICU day 1(0,5) 1(0,6) 0.59 Mortality (%) 10 9 0.75 Conclusions: We report our increased use of PC in the acute trauma setting. PC placed for PTX works equally well and has a similar outcome to CT.

701 MHA KEYSTONE: ONE ICU’S SUCCESS Linda Schofield, Michele Adaline, Northern Michigan Hospital Introduction: The MHA Keystone Center was created by Michigan hospitals in March 2003 and brings together hospitals, state, and national patient safety experts to improve patient safety and reduce costs by enhancing the quality of care delivered. Since MHA Keystone’s inception, Michigan hospitals that have partnered with the center have achieved significant, measurable patient safety improvements — saving lives and reducing healthcare costs. Northern Michigan Regional Hospital has been a leader in MHA Keystone: ICU collaborative since its inception as a means to evaluate existing practice based on evidence. Hypothesis: The purpose of this collaborative is a focus on improving organizational culture using change principles and behavioral science resulting in the evaluation and improvement of existing practice based on evidence. Methods: A multidisciplinary team was brought together to develop bundles based on evidence-based practice for ventilator associated pneumonias, central line-associated bloodstream infections urinary track infections. Beginning in 2004 data was tracked using a baseline data before the initiation of the ICU Keystone bundles. Graphs representing data collected from 2004 through 2nd quarter 2010 will be presented. Results: Northern Michigan Regional Hospital was able to create a culture change, decreasing the rate of ventilator-associated pneumonia from 6.5 to 0 infections per 1000 device day by year. ICU central line associated blood stream infections were reduced from 1.8 to 0 per 1000 Device Days. Blood stream infections have remained at 0 since 2008. They were also able to decrease ICU indwelling catheter-associated urinary track infections from 5.0 to o.5 per 1000 Device Days. Conclusions: Northern Michigan Regional Hospital’s ICU has been able to sustain improvements and make advancements in the prevention of hospital acquired infections. We continue to participate in MHA Keystone’s new programs to improve patient safety. Led by a team of critical care nurses, physicians, performance improvement staff and nursing researcher, efforts currently under way include implementing and data collection on sepsis, glycemic control, sedation, wake-up, and early mobility evidence-based bundles.


702

703

PREDICTORS OF INTENSIVE CARE UNIT ADMISSION FOLLOWING SURGERY FOR ADVANCED OVERIAN CARCINOMA

EFFECT OF THE IMPLEMENTATION OF AN INTENSIVIST PROGRAM AND VENTILATOR BUNDLE IN AN ADULT MEDICAL/SURGICAL ICU ON RATE OF VENTILATOR ASSOCIATED PNEUMONIA

Cafer Kaplan, Selim Candan, Arash Pirat, Pinar Zeyneloglu, Ali Ayhan, Gulnaz Arslan, Baskent University, Faculty of Medicine Introduction: A substantive percentage of patients with stage III-IV overian carcinoma are transferred to intensive care unit (ICU) after cytoreductive surgery. Since ICU beds are scarce and costly, it is important to identify individuals who will require ICU admission after cytoreductive surgery. Hypothesis: Pre- and intraoperative data can be used to identify which stage III-IV overian cancer patients undergoing cytoreductive surgery will require postoperative ICU admission. Methods: The charts of all patients with overian carcinoma who underwent cytoreductive surgery from January 2007 to December 2009 were reviewed. The data recorded were demographic features, co-existing disease, preoperative laboratory findings, intraoperative data, and admission/no admission to ICU postoperatively. Results: Out of 122 patients who underwent cytoreductive surgery for advanced overian carcinoma during the study period, 58 patients (48%) required ICU admission postoperatively. Compared with the group not admitted to ICU, the patients with ICU admission were significantly different regarding the frequency of chronic obstructive pulmonary disease, occurrence of intraoperative hypotension and sinus tachycardia, need for blood products transfusion. The patients who required ICU admission were older, had a higher mean body mass index (BMI) value, had lower preoperative oxygen saturation, and required more intraoperative fluids than those who were not admitted to the ICU. Binary logistic regression revealed that age (OR, 1.078; 95% CI, 1.012-1.148; p⫽0.020), BMI (OR, 1.106; 95% CI, 1.000-1.224; p⫽0.050), occurrence of intraoperative sinus tachycardia (OR, 11.111; 95% CI, 1.869-66.667; p⫽0.008), and need for intraoperative transfusions (OR, 6.452; 95% CI, 1.23234.483; p⫽0.027) were the predictors of ICU admission in these patients. Conclusions: The results suggest that older patients with a higher BMI who develop intraoperative sinus tachycardia and require intraoperative transfusions carry a higher risk of transfer to ICU after cytoreductive surgery for overian carcinoma.

Kristine Willett, Massachusetts College Of Pharmacy, Margaret Lambert, Catholic Medical Center, Cheryl Durand, Massachusetts College of Pharmacy & Health Sciences, Mary Sanford, Catholic Medical Center Introduction: Up to 15% of patients who are mechanically ventilated will develop ventilator-associated pneumonia (VAP). Patients with VAP experience higher mortality rates, longer duration of mechanical ventilation, and greater length of stay. According to data from the CDC, the cost per VAP diagnosis is estimated to be $28,508. The Institute of Healthcare Improvement recommends the implementation of a ventilator bundle to decrease the rate of VAP. Hypothesis: Implementation of an intensivist program and ventilator bundle will decrease the rate of VAP in an adult medical/surgical ICU. Methods: An intensivist program and ventilator bundle was implemented in a 20 bed adult medical/surgical ICU in a community hospital in October of 2008. Components of the bundle included elevation of the head of bed by 30 degrees, daily interruption of sedation, peptic ulcer disease prophylaxis, deep vein thrombosis prophylaxis, and daily oral care using chlorhexidine rinse. Usage of a Hi-Lo® Evac endotracheal tube was also adopted. Additionally, continuous innovative methods for staff education were employed, which included staff participation in the development of an educational video. Results: Baseline annual rates of VAP in 2006 and 2007 were 4.90 and 6.21 per 1000 ventilator days, respectively. Following the implementation of interventions in October 2008, VAP rates from the last quarter 2008 had a mean of 2.27. Since that time, rates continue to decline and were found to be 2.19 in 2009 and 1.68 in 2010. Continuous staff education was provided throughout the implementation process. Conclusions: Implementation of an intensivist program and a VAP bundle can dramatically reduce the rate of VAP in an adult medical/ surgical ICU. Prior to concerted efforts to reduce VAP, there were 26 cases found in 2007. This was reduced to 2 cases in 2009 following the implementation of interventions. Based upon cost data provided by the CDC, that reflects a cost savings of greater than $684,192 over a two year period. Although bundle implementation was a critical component to reduction in VAP rates, the importance of staff education cannot be underestimated. Innovative education methods were employed to emphasize the importance of VAP prevention.

704

705

TIME FROM HOSPITAL ARRIVAL TO ADMINISTRATION OF ANTIBIOTICS: EFFECT ON MORTALITY IN SEPTIC PATIENTS

ASSESSMENT AND MANAGEMENT OF DELIRIUM IN THE CARDIAC SURGERY PATIENT

Amy Leib, John Showalter, Robert Cherry, Penn State Milton S. Hershey Medical Center

Introduction: Delirium or acute confusion state is a transient global disorder of cognition. The condition is a medical emergency associated with increased morbidity and mortality rates. Despite improved outcomes after cardiac surgery, post-operative delirium remains a common complications adversely affecting mortality and morbidity. The incidence of delirium has been reported to range from 3%-47% of the cardiac surgery population. The mortality rate of delirium has been as high as 76%. Patients who are elderly and patients in the postoperative period, delirium may result in a prolonged hospital stay, increased complications, increased cost, and long-term disability. Taken together, the cardiac surgery patient is at high risk for delirium and delirium has a high morbidity and mortality rate Hypothesis: Daily interventions by nurses can decrease the incidence of delirium. Methods: We assessed delirium in the cardiac surgery population. We have been collecting pre-intervention data using the CAM-ICU to determine the incidence of delirium in the CTICU. Of the143 post-cardiac surgery patients; all of the patients were not CAM-ICU positive before surgery, nor were they diagnosed with dementia. Of the 143 patients, 6 (4%) have developed delirium with the first 24 hours; 17 (12%) at 48 hours. Subsequent to the pre-data collection, we institutied a sedation vacation (RASS goal of -2 to ⫹2) and functional mobility (range of motion, getting the patient up to the chair, walking in the hall) in 166 post-intervention patients. Results: There were similar diagnoses in the pre- and post-intervention post-cardiac surgery patients. The post intervention incidence of delirium was significantly lower after the intervention: 5% at 24 hours and 7% at 48 hours (P⫽0.03). Conclusions: We conclude that a sedation vacation and increased functional mobility decreased the incidence of delirium in the post-cardiac surgery patient population.

Introduction: The timing of appropriate antibiotics has recently been shown to affect mortality of patients with severe sepsis/septic shock and the purpose of this study was to determine if the benefits of antibiotic timing on mortality persist in patients identified with any degree of sepsis when adjusted for severity of illness. Hypothesis: We predicted that early administration of antibiotics to septic patients would decrease mortality regardless of their modified APACHE II score on admission and regardless of their degree of sepsis on admission. Methods: A retrospective chart review was performed on all patients (18 years or older) who presented to our emergency department or who were directly admitted to our hospital by their physician and had a primary billing diagnosis of sepsis (based on ICD-9 codes 38.0-38.9) between July 1, 2007 and June 30, 2010. The review includes 845 charts, 780 of which were used because they contained complete data and met sepsis criteria. Data was collected on severity of sepsis on presentation, timing of first antibiotic, timing of first fluid bolus, and modified APACHE II criteria. A logistic regression analysis controlling for the above covariates was performed. Results: Administering a fluid bolus after 3 hours of arrival versus ⬍3 hours had an odds ratio for mortality of 1.45 (95% CI 0.90-2.35; p value 0.13). Administering the first IV antibiotic within 2-6 hours of arrival versus ⬍2 hours had an odds ratio for mortality of 1.27 (95% CI 0.73-2.20; p value 0.39), and administration of IV antibiotics after 6 hours of arrival versus ⬍2 hours had an odds ratio for mortality of 1.88 (95% CI 1.04-3.38; p value 0.04). Appropriateness of antibiotics was not assessed. Conclusions: Early administration of antibiotics to patients with all levels of sepsis improves mortality even after adjusting for severity of illness.


Tennille Echard, Elizabeth Perron, Northwestern Memorial Hospital

706

707

IMPLEMENTING THE MINNESOTA DETOXIFICATION SCALE (MINDS) PROTOCOL RESULTS IN REDUCED ICU LENGTH OF STAY AND BENZODIAZEPINE USE

SUICIDE AND SELF INFLICTED INJURIES AMONG KIDS IN UNITED STATES

Alexa Calfee, Richard Rutherford, Ventura County Medical Center Introduction: Alcohol withdrawal syndrome (AWS) accounts for over 500,000 inpatient hospital stays annually in the United States. Protocol based treatment studies show significantly reduced hospital based morbidity, cost and length of stay (LOS). The Clinical Institute Withdrawal Assessment for Alcohol (CIWA) is a symptom based scoring system validated for assessing the severity of mild to moderate AWS but is heavily reliant on patients’ ability to communicate and therefore is less applicable to critically ill individuals with delirium tremens (DT). Hypothesis: We hypothesize that use of a physiology based alcohol withdrawal protocol to care for critically ill patients with delirium trements will decrease ICU length of stay and benzodiazepine use among those patients. Ventura County Medical Center (VCMC) implemented the Minnesota Detoxification Scale (MINDS) protocol developed at the Minneapolis Veterans Affairs Medical Center to treat DTs in critical care settings. MINDS uses physiologic signs to score the severity of AWS. Prior to implementing this protocol, patients received benzodiazepines at the discretion of the attending physician with large variance in the medication used, method of delivery (intermittent or continuous infusion) and total quantity of medications given. Methods: Data was collected using ICUTracker®, an analysis tool that transfers patient data to a web based software program from which analyses were conducted. VCMC implemented ICUTracker® to monitor adherence to patient safety standards and evaluate efficacy of performance improvement projects. In this study, 37 patients were evaluated prior to protocol implementation and 16 patients were evaluated after protocol implementation. Results: Implementing the MINDS protocol trended toward a reduced LOS 4.93 ⫾ 5.74 versus 3.63 ⫾ 0.69 days (p⫽0.056) and total benzodiazepine use per patient 1430 ⫾ 2144 versus 251 ⫾ 170 mg (p⫽0.056). Conclusions: The analysis was limited by a small sample size. Nonetheless, findings approached statistical significance, and our expectation is that statistical significance will be reached when more critically ill patients with AWS have been evaluated.

Veerajalandhar Allareddy, Rainbow Babies and Children’s Hospital, Sankeerth Rampa, Cleveland State University, Veerasathpurush Allareddy, Harvard University Introduction: Suicide is a major public health problem for children and adolescents in United States and is the fourth leading cause of death among all children. Hypothesis: The objective of this study is to obtain estimates of children that are HOSPITALIZED for “Suicide and Self Inflicted Injuries” in the United States. Methods: The Kids Inpatient Database of the Healthcare Cost and Utilization Project for the year 2006 was used for this study. All hospitalizations with ICD9-Codes for suicide and self inflicted injuries (E950 through E959) were selected for analysis. Hospitalization characteristics including age, gender, and insurance status were examined. Results: A total of 21,961 hospitalizations among kids were attributed to “suicides and self inflicted injuries” in the United States during the year 2006. Close to 72% of all hospitalization occurred among the females. Kids aged between 15 and 17 years accounted for 72.9% of all hospitalizations while those aged between 10 and 14 years accounted for 25.9% of all hospitalizations. Private insurance plans (52.06%) were the major payors for hospitalizations followed by Medicaid (35.2% of all hospitalizations). Conclusions: Female children and those aged between 15 and 17 years appear to constitute a major proportion of all children hospitalized for “suicides and self inflicted injuries”.

708 CLINICAL FEATURES AND PROGNOSIS OF PATIENTS ADMITTED TO A SURGICAL ICU IMMEDIATELY AFTER ABDOMINAL SURGERY Yon Ju Ryu, You Ri Jo, Ji Hye Kim, Jin Hwa Lee, Eun-mi Chun, Jung Hyun Chang, Ewha Womans University, School of Medicine, Mokdong Hospital Introduction: Postoperative admission to an intensive care unit (ICU) is not uncommon, but few reports have addressed the outcome of patients admitted to a postoperative ICU. Hypothesis: The aim of this study was to describe the clinical features and outcomes and to assess the predictive factors for mortality in patients admitted to the ICU after abdominal surgery. Methods: We enrolled 168 patients admitted to the ICU on the day after abdominal surgery from January 2008 to December 2008, and retrospectively reviewed the records of patients. Results: The median age was 72 years (range, 18 –90), and the number of males was 94 (56%). The median body mass index (BMI) was 23.0 kg/m2 (range, 15.6 –32.9), and the majority of the patients were in American Society of Anesthesiologists class 2 (66%). An emergency operation occurred in 60 cases (36%), laparascopic operation in 21 (13%) and a cancer-related operation in 93 (55%). The SOFA score was 2 (range, 0 –15), and the SAPS II score was 21 (range, 3–71) on the day of ICU admission immediately after surgery. The overall mortality rate was 8.9% (15 of 168), and seven factors were associated with mortality in a uivariate analysis (p ⬍ 0.05): two preoperative factors (BMI ⬍ 18.5 kg/m2, p ⬍ 0.0001, and a serum albumin ⱕ 3.0 g/dL, p ⫽ 0.002), two operative factors (requirement for transfusions, p ⫽ 0.015, and the use of a vasopressor, p ⫽ 0.028, during surgery), and three postoperative variables at ICU admission (acute respiratory failure requiring mechanical ventilation immediately following surgery, p ⬍ 0.0001, SOFA score, p ⬍ 0.0001, and SAPS II score, p ⬍ 0.0001). After adjusting for age and gender, these seven factors were introduced into a Cox regression hazard model, which revealed that a serum albumin ⱕ 3.0 g/dL (hazard ratio [HR], 6.7; p ⫽ 0.041), BMI ⱕ 18.5 kg/m2 (HR, 45.8; p ⫽ 0.001), and transfusion during the operation (HR, 17.3; p ⫽ 0.016) were independent predictive factors of mortality. Conclusions: Preoperative measurement of serum albumin, BMI, and a transfusion during surgery may identify patients at a high risk for mortality in those admitted to the ICU immediately after abdominal surgery.



710

CORRELATION BETWEEN GLASGOW COMA SCALE ON ADMITION AND OUTCOME IN ICU PATIENTS

PREVALENCE OF ACTIVE CYTOMEGALOVIRUS INFECTION IN A CARDIOVASCULAR INTENSIVE CARE UNIT

Aristeidis Vakalos, Anastasia Amanatidou, Maria Patkopoulou, Xanthi General Hospital

Haruhiko Ishioka, Yusuke Tsutsumi, Jichi Medical University Saitama Medical Center, Masamitsu Sanui, Jikei University School of Medicine

Introduction: Glasgow Coma Scale (GCS) on admition affects the APACHE II (Acute Physiology and Chronic Health Evaluation) scoring system. APACHE II score was developed to provide an objective assessment of severity of illness in the ICU. Low GCS values in critical ill patients, especially in patients with severe head injury reflects limitation in cerebral activity and may have impact to the outcome. Hypothesis: The aim of our study was to test the correlation between GCS values on admition and outcome in ICU patients. Methods: During November 2005 and July 2010, 253 patients admitted to our adult both medical and surgical ICU and included retrospectively in our study. Mean age: 61.9 years, mean APACHE II score: 18.5, mean length of stay (LOS): 13.1 days, with predicted and actual mortality: 31.6 % and 23.71 % respectively, normalized mortality ratio (NMR): 0.75. The patients separated in two groups. Group A involved 193 patients who survived and discharged ICU and group B 60 patients who died into the ICU. We looked for statistical significant difference (p value two tailed) between the medians GCS values of group A and group B, using the unpaired Mann - Whithney test (nonparametric) or the unpaired t test Welch corrected (parametric), according to the normality test. Results: Values did not pass normality test, so we used nonparametric test.Group A: Mean: 11.2, S.d: 4.73, Lower 95 % C.L: 10.34, Upper 95 % C/L: 11.87, min: 3, max: 15, median: 15.Group B: Mean: 9.78, S.d: 5.29, Lower 95 % C.L: 8.41, Upper 95 % C/L: 11.15, min: 3, max: 15, median: 11.5The two-tailed p value was 0.083, considered that there was no statistical significant difference between the two groups. Conclusions: According to our data, patients who died into the ICU did not appear to have statistical significant higher GCS values on admition. The absence of statistical significant correlation recorded between GCS on admition and outcome may be due to early and effective support of patients with limited cerebral function, while suggests that low GCS alone may not be used as an exclusive ICU admition criterion.

Introduction: Active cytomegalovirus (CMV) infection, diagnosed by a positive CMV antigenemia, is not as uncommon in critically ill non-immunosuppressed patients, as previously thought. Also, recent studies have shown that CMV infection may play a role in progression of chronic cardiovascular diseases. However, its association with active cardiovascular conditions has never been studied. A preliminary observational cohort study was conducted to determine the prevalence of active CMV infection in cardiovascular surgical patients. Hypothesis: Active CMV infection is common in a cardiovascular surgical ICU. Methods: Ninety patients admitted to our intensive care unit (ICU) following cardiovascular surgery between January 2010 and May 2010 were enrolled. Serum pp65 antigens for CMV at ICU admission, day 7, and day 14 were evaluated. CMV serology (IgG) tests were also performed on admission. Results: Two of 90 patients (2.2%) were positive for serum pp65 antigens. One of these patients had a history of rheumatic arthritis on long-term corticosteroids, who underwent elective aortic valve replacement. The other had a diagnosis of severe endocarditis, and underwent emergency aortic valve replacement. Acute Physiology and Chronic Health Evaluation (APACHE) II scores for those two patients on admission were 20 and 6 respectively, compared to the average of 16 in the remaining patients. CMV positive serology (IgG) was found in 88 patients (97.8%) including those two patients. Conclusions: According to these preliminary results, few patients in a cardiovascular surgical ICU have active CMV infection despite of high prevalence of CMV IgG antibody. Active cardiac diseases and their operative procedures may not be significant risk factors for active CMV infection unless systemic derangements, denoted by high APACHE II scores, are also present.

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CORRELATION BETWEEN BLOOD GLUCOSE AND OUTCOME IN ICU PATIENTS

MULTI-CENTER REVIEW OF RAPID STRESS ULCER ASSESSMENT AND TREATMENT OF AT-RISK PATIENTS IN 18 AMERICAN ICUS

Aristeidis Vakalos, Anastasia Amanatidou, Maria Patkopoulou, Xanthi General Hospital Introduction: Blood glucose affects the APACHE II (Acute Physiology and Chronic Health Evaluation) scoring system. APACHE II score was developed to provide an objective assessment of severity of illness in the ICU. Hyperglycemia is common in critical ill patients while the impact to the outcome is still debated. Hypothesis: The aim of our study was to test the correlation between blood glucose values (Glu) on admition and outcome in ICU patients. Methods: During November 2005 and July 2010, 253 patients admitted to our both medical and surgical ICU and included retrospectively in our study. Mean age: 61.9 years, mean APACHE II score: 18.5, mean length of stay (LOS): 13.1 days, with predicted and actual mortality: 31.6 % and 23.71 % respectively, normalized mortality ratio (NMR): 0.75. The patients separated in two groups. Group A involved 193 patients who survived and discharged ICU and group B 60 patients who died into the ICU. We looked for statistical significant difference (p value two tailed) between the medians blood glucose values (mg/dL) on admition of group A and group B, using the unpaired Mann - Whithney test (nonparametric) or the unpaired t test Welch corrected (parametric), according to the normality test. Glucose measurements were obtained using the arterial blood gas analyzer Radiometer Copenhagen ABL 800 Flex device. Results: Values did not pass normality test, so we used nonparametric test.Group A: Mean: 175.45, S.d: 89.34, Lower 95 % C.L: 162.85, Upper 95 % C.L: 188.06, min: 11, max: 624, median: 159 Group B: Mean: 175.73, S.d: 98.96, Lower 95 % C.L: 150.18, Upper 95 % C.L: 201.28, min: 41, max: 477, median: 154The two-tailed p value was 0.71, considered that there was no statistical significant difference between the two groups. Conclusions: According to our data, patients who died into the ICU did not appear to have statistical significant higher blood glucose values on admition. The absence of statistical significant correlation recorded between the blood glucose values on admition and the outcome, may be due to early and effective management of intravascular volume disturbances, as well as to early management of septic shock


Elizabeth Cowboy, Advanced ICU Care Introduction: Current stress ulcer treatment is comprised of multiple loose-knit protocols with rare assessments of true at-risk patients. A rapid initiation of therapy when indicated and discontinuation when not indicated is key to patient safety and pharmacoeconomics. Hypothesis: Dedicated intensivist lead team with searchable databases can collect valid data, assess and treat at-risk patients within 1 hour of admission and on an ongoing basis, giving proper therapy when indicated and preventing unnecessary therapy among critically ill patients. Methods: 24,860 patients with a critical diagnosis were admitted to 18 intensive care units (ICUs). The average APACHE score was 49 with a range of 36 to 77. Prior to the initiation of the co-management program, none of the 18 ICUs had reliable tracking mechanisms. Subsequently, patients were admitted and co-managed with intensivists via integrated electronic medical system from a central location. All patients were evaluated for risk of stress ulcer as defined by ventilated for ⬎ 24 hours, head injury, serious burns, and coagulopathies.1-2 Patient assessments were ⬍ 1 hour of admission every 6 hours by the intensivist-led team with use of integrated computer algorithms with treatment initiated and discontinued . Treatments varied and included H2 antagonists, proton pump inhibitors, or sucralfate. Results: The ICU populations were studied from January 1, 2006 to June 30, 2010 included 24,860 patients. Over a 54 month period, 9,729 at-risk patients were identified as at-risk with 8,359, or 86% treated. The most recent 3 months, 2,603 patients were admitted with 987 patients at-risk identified and 921 patients or 93% received therapy. Recent studies in post cardiac stent patients was the main reason cited for ⬍ 100% compliance.3 Conclusions: A retrospective of 18 ICUs in America found co-managed with intensivists via integrated electronic medical system from a central location were able to assess and treat at-risk patients within 1 hour of admission. Re-assessment and discontinuation were reviewed every 6 hours around the clock, achieving increased compliance. References: 1 Pharmacotherapy 2008;28(8):968 –976. 2 Am J Gastroenterol 2006;101(10):2200 –2205. 3 JAMA. 2009;301(9):937-944.

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IMPROVING GLYCEMIC CONTROL IN ALL INTENSIVE CARE UNITS

THE EPIDEMIOLOGY OF ACUTE RESPIRATORY FAILURE IN OLMSTED COUNTY, MINNESOTA

Krista Garner, Emory University Hospital, Elaine Chang, Zachary Milner, Emory Healthcare, Timothy Buchman, Emory University Hospital, Jason Stein, Emory Healthcare, Owen Samuels, The Emory Clinic

Guangxi Li, Rodrigo Cartin-ceba, Rahul Kashyap, Matthew Pieper, Vitaly Herasevich, Ognjen Gajic, Mayo Clinic

Introduction: Hyperglycemia is extremely common in patients with critical illness. Strict control of elevated blood sugar with intensive insulin therapy has been shown to decrease hospital morbidity and mortality, inpatient stays and hospital costs. Insulin treatment guidelines developed and implemented by multidisciplinary teams allow for rapid, effective and consistent control of hyperglycemia. Hypothesis: To improve glycemic control across ICUs in a single health system, workflow and protocol adherence strategies adopted from a higher performing ICU should be replicated. Methods: We compared performance for glycemic control across multiple ICUs in our system. The correlation between average blood glucose and the number of daily blood glucose determinations per patient was calculated using the Pearson correlation coefficient. For the highest and lowest performing ICUs we conducted a phone interview with the providers to determine: 1)open vs.closed ICU 2) presence of a glycemic control protocol and 3) presence of criteria and types of mechanisms to trigger the protocol. Results: The regression of all ICUs using the number of determinations to predict the average glucose per patient resulted in a Pearson correlation coefficient of -0.38 and an R2 equal to 0.14. One ICU was identified as a positive deviant, demonstrating lower average blood glucose despite a lower number of blood glucose determinations. After removing the outlier, a second regression analysis consisting of the remaining 6 ICUs resulted in a strong negative slope correlation (R2⫽0.8) between the average glucose per patient and the number of blood glucose determinations per patient per day with a Pearson correlation coefficient of -0.89. A phone interview between NP/PAs from the highest and lowest performing units revealed key differences in workflow and practice patterns. The higher performing ICU compared with the others used an insulin drip protocol routinely, clear trigger process for protocol implementation and a primary team rounding process. Conclusions: Analyzing and sharing comparative performance across ICUs in our health system identified key success factors to optimize glycemic control in critically ill patients.

Introduction: Acute respiratory failure (ARF) remained the most common reason of ICU admission. No population-based clinical study has adequately addressed the incidence and outcome of ARF from different etiologies. Olmsted County is an ideal setting for population-based epidemiology studies where all residents who require mechanical ventilation for ARF are treated a single medical center with ready access to critical care service. Hypothesis: The purpose of this study was to determine the incidence of acute respiratory failure and mechanical ventilation use in the community of Olmsted County during 2006. Methods: Retrospective cohort study was done of adult (ⱖ18 years) Olmsted county residents admitted to any Mayo Clinic ICU during 2006. Olmsted county residents were identified based on the Rochester Epidemiology Project (REP) database. Acute respiratory failure was defined as any mechanical ventilation support for more than 1 hour excluding patients ventilated less than 12 hours after surgical procedure and those who chronically use mechanical ventilation. Only the first ARF episode during the study period was included in the analysis. Results: A Total of 371 patients developed ARF in 2006 yielding a cumulative incidence of 383 ARF per 100,000 person-years at risk. Mean age was 65 (⫾19); 163 (44%) were female, median APACHE IV scores were 44 (IQR, 31 to 59). The main etiology for ARF were postoperative 99 (27%), acute exacerbation of chronic obstructive lung disease 44 (12%), heart failure 37(10%), severe sepsis 28 (8%) and acute lung injury (ALI) 18 (5%). Two hundred seventy five patients (74%) received invasive mechanical ventilation with a median of 40 (IQR, 17-96) hours and 96 (26%) patients only received non-invasive mechanical ventilation. The median length of stay in intensive care unit was 4.3 (1.9-8.8) days. The overall hospital mortality was 23% (from 8% in postoperative to 28% in ALI). Conclusions: The incidence of community patients who developed acute respiratory failure requiring mechanical ventilation was higher than previous reports. The cause for the increasing burden is not known but may in part reflect aging demographics and increased use of invasive surgical procedures.

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EMERGENCY DEPARTMENT VISITS FOR SKULL AND FACIAL FRACTURES IN UNITED STATES

CORRELATION BETWEEN AGE AND OUTCOME IN ICU PATIENTS

Veerajalandhar Allareddy, Rainbow Babies and Children’s Hospital, Sankeerth Rampa, Cleveland State University, Veerasathpurush Allareddy, Harvard University

Aristeidis Vakalos, Anastasia Amanatidou, Maria Patkopoulou, Xanthi General Hospital

Introduction: Skull and facial fractures account for significant number of Emergency department(ED) visits in both children and adults. In adults, the incidence of skull fractures in head injury patients who visit ED is relatively unknown. Skull and facial fractures can lead to significant morbidity and mortality in all age groups. Hypothesis: This study examines the epidemiology of hospital based emergency department visits for skull and facial fractures in the United States during the year 2007. Methods: The nationwide emergency department sample (year 2007), a component of the Healthcare Cost and Utilization Project family of datasets was used for the current study. All hospital based emergency department visits with a primary diagnosis code for skull and facial fractures (based on ICD-9-CM and Clinical Classification Software codes) were selected for analysis. Characteristics of patients including age, gender, insurance status, and discharge status were examined. Results: A total of 301,893 hospital based emergency department visits had a primary diagnosis code for skull and facial fractures. Males accounted for the majority of visits (68.5%). Children aged less than 18 years accounted for 22% of all visits while those aged between 18 and 44 years accounted for close to 51% of all emergency department visits. Medicare, Medicaid, Private insurance plans, and other governmental supported plans were the primary payors for 12.8%, 14.2%, 38.8%, and 7.3% of all emergency department visits. Close to 26.3% of all visits occurred among the uninsured. About 16% of all emergency department visits necessitated inpatient admission into the same hospital while 165 patients died in the emergency department. Among those admitted into the same hospital for further care, 294 patients died during their hospitalization. Conclusions: This study highlights the burden associated with skull and facial fractures in the United States and identifies cohorts that comprise a significant proportion of subjects visiting hospital based emergency departments.

Introduction: Age affects the APACHE II (Acute Physiology and Chronic Health Evaluation) scoring system. APACHE II score was developed to provide an objective assessment of severity of illness in the ICU. Advanced age in critical ill patients reflects limitation in systemic functions and may have impact to the outcome. Hypothesis: The aim of our study was to test the correlation between age on admition and outcome in ICU patients. Methods: During November 2005 and July 2010, 253 patients admitted to our adult both medical and surgical ICU and included retrospectively in our study. Mean age: 61.9 years, mean APACHE II score: 18.5, mean length of stay (LOS): 13.1 days, with predicted and actual mortality: 31.6 % and 23.71 % respectively, normalized mortality ratio (NMR): 0.75. The patients separated in two groups. Group A involved 193 patients who survived and discharged ICU and group B 60 patients who died into the ICU. We looked for statistical significant difference (p value two tailed) between the medians age values (years) of group A and group B, using the unpaired Mann - Whithney test (nonparametric) or the unpaired t test Welch corrected (parametric), according to the normality test. Results: Values did not pass normality test, so we used nonparametric test.Group A: Mean: 60.78, S.d: 19.75, Lower 95 % C.L: 57.99, Upper 95 % C/L: 63.56, min: 16, max: 96, median: 67Group B: Mean: 66.09, S.d: 15.60, Lower 95 % C.L: 62.05, Upper 95 % C/L: 70.11, min: 23, max: 98, median: 71The two-tailed p value was 0.11, considered that there was no statistical significant difference between the two groups. Conclusions: According to our data, patients who died into the ICU did not appear to have statistical significant higher age. The absence of statistical significant correlation recorded between age and outcome may be due to early and effective support of older patients, while suggests that advanced age alone may not be used as an exclusive ICU admition criterion.


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POSTOPERATIVE INTRAABDOMINAL PRESSURE AS A SURROGATE MARKER OF SEVERITY OF PATIENT’S CONDITION AND AS A PREDICTOR OF UNFAVORABLE OUTCOME IN PATIENTS WITH SELLAR REGION TUMORS

THE PRESENCE OF BACTEREMIA RELATES TO THE SEVERITY AND THE MORTALITY OF SEPTIC SHOCK PATIENTS IN INTENSIVE CARE UNIT

Konstantin Popugaev, Neurosurgical Institute Named N.N.Burdenko, Ivan Savin, Alexander Goriachev, Alexander Polupan, Andrew Oshorov, Temur Abramov, Neurosurgical Research Institute named NN Burdenko

Introduction: It is still controversial whether bacteremia itself affects the severity and the mortality of septic patients. Recent diagnostic criteria of septic shock do not include the presence of bacteremia, because rapid diagnosis and immediate treatment are necessary to improve the survival of septic shock. Furthermore, blood culture will take several hours or days to get the results and the use of antibiotics may affect the results of blood culture. However, the presence of bacteremia seems to relate to the severity and mortality of septic shock patients in intensive care unit. Hypothesis: The presence of bacteremia significantly affects to the severity and the mortality of septic shock patients in intensive care unit. Methods: The patients clinically suspected sepsis were tested serum procalcitonin level using procalcitonin kit (BRAHMUS PCT kit). One-hundred twenty five times of PCT test were performed in 99 patients. Among them 24 patients showed high PCT level (⬎10ng/ml). Twelve of 24 (50%) patients showed the bacteremia. The hemodynamic parameter, APACHE II score, SOFA score, catecholamine dose, serum lactate, some other laboratory data and mortality rate were compared between the patients with bacteremia and those without bacteremia. Statistical analyses were performed by chi-square test and Mann-Whitney U-test. Results: There is no significant difference in APACHE II score between the bacteremic and non-bacteremic patients. However, the bacteremic patients showed significant higher SOFA score, doses of catecholamine, serum lactate concentration and lower white blood cell counts. The mortality rate of the bacteremic patients was significantly higher than that of non-bacteremic patients (50% vs. 8%). Conclusions: The presence of bacteremia relates to the severity and the mortality of septic shock patients in intensive care unit.

Introduction: Sellar region tumors (SRT) constitute 14% of all brain tumors in adults. In our hospital 10-12% of these patients have complicated postoperative period and require ICU treatment. The main cause of the complicated postoperative period is diencephalic dysfunction (DD). DD leads to the failure of endocrine and autonomic nervous regulation of gastrointestinal tract. Intraabdominal hypertension (IAH) (intraabdominal pressure (IAP) ⱖ 12 mmHg) is a sign of gastrointestinal dysfunction. Hypothesis: IAH reflects the severity of postoperative condition, because it could be considered as a specific sign of DD. IAH can be a predictor of outcome. Methods: Study includes 33 (17 females) patients: 18 pituitary adenomas, 7 craniopharyngiomas, 6 suprasellar meningiomas, 2 astrocytomas of third ventricle. Age ranged from 19 to 61 years old. All patients had critical illness. They postoperatively had delirium (n⫽14), coma (n⫽8) water-electrolytes disturbances (n⫽5), dynamic ileus (n⫽28), arterial hypotension with the need of vasopressors (n⫽21), prolonged mechanical ventilation (n⫽26). IAP was measured in urinary bladder four times daily during all period of ICU stay. The combination of 2 or more signs as: delirium, waterelectrolytes disorders, arterial hypotension, and dynamic ileus was considered as DD. Outcome was assessed on discharge from the hospital using modified Rankin scale: death, moderate disability – unfavorable outcome and slight disability, no significant disability – favorable outcome. Main statistical method was calculation of odds ratio (OR). Results: DD was revealed in 28 pts and IAH in 19 pts. 18 pts with IAH had DD and 1 sepsis. In 19 IAH pts favorable outcome was in 8 pts, unfavorable – in 11 pts. IAP was normal in 14 pts and 10 of them had DD: favorable outcome was in 12 pts, unfavorable outcome – in 2 pts. IAH significantly increased risk of unfavorable (OR⫽8.25). DD significantly increased risk of development of postoperative IAH (OR⫽7.2). Conclusions: In patients after SRT removal postoperative IAH can be used as a surrogate marker of DD and consequently as a marker of severity of patient’s conduction. IAH is a significant predictor of unfavorable outcome.

719 PREVALENCE OF HEPARIN INDUCED THROMBOCYTOPENIA IN THE MEDICAL INTENSIVE CARE UNIT Chee Chan, Christian Woods, Vikramjit Mukherjee, Spyros Kamarinos, Andrew Shorr, Washington Hospital Center Introduction: Thrombocytopenia is common in critically ill patients. Because of the frequent use of heparin in this setting there may be concern for heparin induced thrombocytopenia (HIT). Although selected surgical patients (eg cardiac surgery, orthopedics) are considered high risk for HIT, controversy exists regarding the prevalence of HIT in the medical intensive care unit (MICU). Hypothesis: We hypothesized that the true prevalence of HIT is low in the MICU. Methods: We retrospectively reviewed the charts of all patients in the MICU undergoing HIT antibody testing (Jan-Dec 2008). Our definition of HIT required a clinical diagnosis by the ICU attending along with a concomitant positive ELISA HIT antibody (OD ⱖ 0.4). The prevalence of HIT served as our primary endpoint. Mortality in HIT served as a secondary endpoint. We also assessed the discriminatory power of certain variables (eg, severity of illness, extent of platelet drop, development of thrombosis) at predicting mortality in this cohort based on receiver operating curves (ROC). Results: The cohort included 59 subjects (mean age: 61.1 ⫹/⫺ 17.4; male: 44.1%; mean APACHE: 22.1 ⫹/⫺ 6.3) drawn from nearly 1400 MICU admissions. Approximately 14% of subjects had positive HIT antibodies while 8.5% met our definition for HIT. One individual developed thrombosis due to HIT. Approximately 60% of the 59 subjects died. The platelet count drop was greater in those who died than those who survived (60.3% vs 43.6%, p⫽0.026). The strongest predictor of mortality among these patients was the % drop in platelet count from admission to when the HIT antibody was sent [area under ROC (AUROC): 0.674; 95% CI: 0.530.82], which is poor. This was minimally better as a predictor of mortality than whether the subject had HIT (based on our definition) [AUROC: 0.536; 95% CI: 0.39-0.69]. Conclusions: Few patients develop HIT in the MICU. Even in those with clinical thrombocytopenia, true HIT is rare. Mortality is high in critically ill patients with thrombocytopenia. Despite the high mortality rate, predictors of death were not readily evident. HIT is an extremely rare diagnosis in medically critically ill patients. Thrombocytopenia confers high mortality.


Masayuki Kamochi, University Hospital of UOEH

Poster: Ethics and End of Life-1 720

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USING A CHECKLIST IMPROVES PEDIATRIC BRAIN DEATH DOCUMENTATION

PALLIATIVE CARE SERVICES IN THE ADULT INTENSIVE CARE UNIT: EFFECT ON LENGTH OF STAY

Mudit Mathur, Loma Linda University Children’s Hospital, Almas Syed, Loma Linda University, Stephen Ashwal, Loma Linda University School of Medicine

Herbert Patrick, ARIA Health - Frankford Campus, Sara Abbruzzi, Susan Holland, Vitas Palliative Care Solutions, Barbara Salapata, ARIA Health - Frankford Campus

Introduction: Clinical guidelines for determining brain death (BD) in children were widely disseminated in1987 by the American Academy of Pediatrics but great variability persists in BD determination and documentation. (Mejia et al, JAMA 1995, 274: 550-553 and Mathur et al, Pediatrics 2008; 121(5):988993)Hypothesis: Codifying existing guidelines into a checklist could improve the consistency of clinical practice during BD determination in children. Methods: A one-page checklist based on the 1987 BD guidelines was made available for use in our PICU in January 2008. Either the checklist or a free-text note was acceptable for BD documentation based on the examining attending physician’s preference. We evaluated checklist use and effectiveness over the subsequent 30-month period (from January 2008 through June 2010) in this retrospective chart review. Medical records were scrutinized for physician documentation of 14 specific neurologic examination elements and apnea testing. The completeness of documentation with and without the use of the checklist was compared using chi square test with alpha at 0.05. Results: Twenty-nine children between 2 months and 17 years of age had a total of 59 BD examinations during the study period. Twenty were done by neurology, 10 by neurosurgery and 29 by PICU physicians. Inter-examination intervals were age appropriate in all. Checklist use for documentation increased from 13/23 examinations in 2008 to 33/36 in 2009-10 (p⬍0.01). Documentation of examination elements was complete in all but one case when the checklist was used (absence of spontaneous respiratory effort not documented). A median of 4 elements was missed in every handwritten note (range 1-9 missed elements, p⬍0.05). PCO2 rise and final pCO2 during apnea testing were appropriate in all. However, six patients had only one apnea test documented, 3 with and 3 without checklist use. Conclusions: Adoption of a checklist was gradual, but has significantly improved documented adherence to brain death guidelines at our hospital. Education regarding the need for performing an apnea test with each examination is needed to further improve the consistency of BD determination.

Introduction: A large proportion of deaths occur in the intensive care unit (ICU) or after a stay in the ICU. Palliative care services in the United States consist of medical care or treatment by a team that concentrates on reducing the severity of disease symptoms, rather than striving to halt, delay, or reverse progression of the disease or provide a cure. Two popular services of palliative care are pain management and/or plan of care discussions. Hypothesis: Palliative care services will reduce ICU length of stay by improving interdisciplinary care, discussions and family communication. Methods: This study was a performance improvement project. A retrospective nonequivalent pre- post- control group design was used. Palliative care was introduced in one adult medical ICU (twelve beds) with two other ICUs (twenty-four beds and ten beds) as controls. Number of palliative care consultations and length of stay were reviewed monthly for a fiscal year prior to palliative care services (2008-09) and for the first year of services (2009-10). The primary outcome measure was percentage change in patient annual average length of stay in each ICU over the two year period. Results: For the ICU with palliative care services, there were 97 palliative care consultations performed in 2009-2010. The annual average length of stay between 2008-09 and 2009-10 was reduced by 23.8%. For the two control ICUs without palliative care services the annual average length of stay was reduced by 8.2% and 8.3%. The ICU using palliative care services had a significantly reduced annual average length of stay compared to the control ICUs. Conclusions: Palliative care services were associated with a reduced annual average ICU length of stay. Analyses of other factors such as differences in mortality rates or discharge disposition are needed before attributing these findings to palliative care services alone.

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CLINICIAN PERSPECTIVES ON THE DO NOT RESUSCITATE ORDER AT A CHILDREN’S HOSPITAL

REVERSIBLE BRAIN DEATH FOLLOWING CARDIOPULMONARY ARREST

Amy Durall, Children’s Hospital, Boston, Joanne Wolfe, Dana-Farber Cancer Institute and Children’s Hospital, Boston

Adam Webb, Emory University, Owen Samuels, The Emory Clinic

Introduction: Studies have shown variability in the interpretation of the Do Not Resuscitate (DNR) order but little pediatric data exist. We sought to identify clinician attitudes regarding the meaning, timing and implication of the DNR order for pediatric patients. Hypothesis: We hypothesize that there is a large amount of variability in the interpretation of the DNR order. Methods: Critical care and oncology physicians and nurses were surveyed regarding resuscitation status discussions and the DNR order. Results: 266 providers responded (54% response rate). Fifty-three percent were critical care clinicians, 20% were cardiac critical care providers and 27% specialized in oncology. Nurses comprised 60% and 40% were physicians. Forty-three percent of clinicians had practiced less than 10 years, 30% 10-19 years and 27% 20 years or more. There was substantial variability in the interpretation of the DNR order. Sixty-five percent believed that a DNR order indicates limitation of resuscitation only upon cardiopulmonary arrest, whereas 35% considered a DNR order to be the threshold for the limitation of treatments not specifically related to resuscitation. Nearly three quarters of respondents reported that, ideally, resuscitation status discussions should first be initiated either upon diagnosis (41%) or during a period of stability (32%) rather than during an acute illness (16%) or when death is clearly imminent (3%). However, in actuality a majority of clinicians reported that the discussions take place during an acute illness (33%) or when death is clearly imminent (54%). Concerning the implications of a DNR order, 69% of clinicians reported that the care of a patient changes once a DNR order is written. Nonetheless, many (62%) believed that patients with a DNR order receive the same amount of attention as patients without a DNR order. Conclusions: Many physicians and nurses use the DNR order not only to guide therapeutic decisions during a cardiopulmonary arrest but also as a surrogate for broader treatment directives. Future studies should focus on the impact of differing clinician perspectives regarding DNR status on the experience of children with life-threatening illness and their families.

Case Report: A 55 y.o. man presented with respiratory failure followed by cardiac arrest with pulseless electrical activity. After successful resuscitation therapeutic hypothermia was initiated for neural protection. A temperature of 33°C was maintained for 24 hours. After rewarming to 36.5°C, exam showed no eye opening or response to pain, spontaneous myoclonic movements, sluggish pupils, absent corneals, and intact gag and spontaneous respiration. Over the next 24 hours, sedation was held and the exam progressed to brain death. EEG, apnea test and repeat clinical exam confirmed brain death. Testing was performed in accordance with American Academy of Neurology (AAN) guidelines for the determination of brain death. The family consented to organ donation. 24 hours later, on arrival to the OR for organ procurement, the patient had regained corneal and cough reflexes and spontaneous respiration. The care team faced the challenge of un-declaring death and offering an explanation to the patient’s family and others involved. Repeat EEG showed no electrical activity and brain MRI revealed severe hypoxic-ischemic injury. The patient ultimately lost all brain stem function. Tc-99 blood flow study confirmed brain death. This is the first report of reversal of diagnosis of brain death in an adult patient made in full adherence to AAN guidelines with 2 clinical examinations performed by neurologists 6 hours apart with a positive apnea test. While the reversal was transient and did not impact the patient’s overall prognosis, it impacted his eligibility for organ donation and cast doubt on our ability to determine irreversibility of brain death. We postulate that treatment with therapeutic hypothermia may have impacted the progression to brain death. A recent update to the AAN guidelines acknowledged insufficient evidence for a minimum accepted interval between examinations to insure that the loss of brain function is permanent. We strongly recommend caution in the determination of brain death following cardiac arrest when hypothermia is employed. A minimum observation period following rewarming before brain death testing ensues should be established.


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PROVIDER PERCEPTIONS OF END OF LIFE (EOL) DISCUSSION IN THE INTENSIVE CARE UNIT (ICU): IMPACT OF EOL BUNDLE

FROM SIMULATION TO DCD: IMPLEMENTING A PEDIATRIC DCD PROGRAM

Mithil Gajera, Ankur Kalra, Ian Butler, Cooper University Hospital, snehal gandhi, cooper hospital, Umashanger Thayasivam, Rowan University, Janette McFetridge, cooper hospital, Jean Minder, Nduka Okorie, Sri-Sujanthy Rajaram, Cooper University Hospital Introduction: There have been significant advances in medicine and inevitable death is regarded as a medical failure. Health care providers therefore have become uncomfortable in addressing EOL care. A quality initiative in the form of an EOL bundle was introduced in ICU. Hypothesis: Significant improvement in provider satisfaction of EOL discussion and communication with family occur after the introduction of EOL bundle. Methods: EOL bundle was implemented as an “ICU communication and collaboration bundle” by the ICU Physicians. This bundle included providing information regarding EOL issues (brochure), addressing the advanced directive, pain control, identifying a health care proxy and scheduling a family meeting within 24 hours of admission to the ICU followed by documentation of the goals of treatment and a family meeting within the next 36 hours.An ICU staff survey was conducted prior to implementation of the bundle and two years after it. ICU attending, fellows, residents and nurses participated in the study. The questions assessed the staff satisfaction in dealing with EOL discussion in a timely fashion, their knowledge and comfort level in implementing comfort care measures in ICU. They were asked to use a scale of 1-5, ranging from poor quality for 1 and excellent for 5. We used the t-test for independent sample analysis with the pool variance. Results: Total of 107 providers (87 nurses & 20 physicians) participated in the initial survey. After the implementation of the bundle 67 providers (56 nurses & 13 physicians) completed the survey. Average nursing satisfaction score was initially 3.40 improved to 3.44 after the bundle, (p ⫽ 0.34 not significant). For Physicians the pre-bundle score 3.60, improved to 3.92 post-bundle, is statistically significant (p ⫽ 0.03). Physicians perception of time of EOL discussion decreased from 3.05 to 2.69 days, as opposed to nurses perception increased from 3.65 to 3.95 days. Conclusions: Introduction of ICU communication and collaboration bundle improved communication between physicians and family regarding goals of treatment and staff satisfaction with EOL discussion. Lack of improvement in nursing staff satisfaction might be due to non involvement in the bundle initiative.

726 IDENTIFYING OPPORTUNITIES TO INCREASE ORGAN DONATION THROUGH A SYSTEMATIC ANALYSIS OF STATEWIDE INPATIENT DEATHS Devashish Anjaria, UMDNJ - New Jersey Medical School, William Reitsma, Fred Goerlitz, New Jersey Organ and Tissue Sharing Network, Alicia Mohr, Ziad Sifri, Robert Lavery, David Livingston, UMDNJ - New Jersey Medical School Introduction: Despite the nationwide push to increase organ donation and procurement, the gap between the number of people waiting for an available organs and the number of organs recovered and transplanted continues to grow. Hypothesis: A systematic evaluation of a statewide organ procurement organization (OPO) registry can identify opportunities to increase organ donation. Methods: A statewide review of deaths referred to the OPO between July 1, 2009 and June 30, 2010 was performed to define the population of potential organ donors, both Brain Dead (BD) and Donation after Cardiac Death (DCD) Results: In the study period, a total of 24,526 inpatient deaths were reported to the OPO of which 3946 met standard clinical triggers as potential organ donors. 264 of these patients progressed to BD; 203 (77%) of these were consented for donation; 135 of these were successful donors, while 68 were medically ruled out as unsuitable. 3682 patients did not progress to brain dead, of these, 3528 patients were ruled out as potential donors. Of the 154 patients suitable for DCD, 85 patients (55%) were consented for DCD, 63 did not consent, and 6 were not referred prior to withdrawal of support (WOS). Of the 85 consented patients, 37 were subsequently medically ruled out for donation; 48 patients underwent attempted DCD with 40 patients successfully donating. Of the 63 no consents, approximately half declined consent due to the delay in withdrawal of support an attempted DCD would require, after the decision to withdrawal support was finalized. Conclusions: Only 1.7% of all inpatient deaths are potential organ donors. The total potential donor pool is 63% BD and 37% DCD; revealing a marked variance from the national goal that 10% of total donors should be DCD. As concerted efforts have increased BD consent rates up to 77%, diminishing opportunity exists to further increase BD donors. DCD consent rate at 55%, however, provide the largest potential to capture lost donors. Studies examining system changes to result in earlier OPO referral of potential WOS; provider education to consider DCD in every WOS, and process improvement to decrease time from consent to WOS could result in substantial increases in DCD rates.


Beth Wathen, The Childrens Hospital, Joseph Albietz, Amanda Rosengren, Shannon Buckvold, Diane Redmond, Clayton Dobronyi, The Children’s Hospital, Diane Bacino, Donor Alliance, Faith Beazer, Linda Young, Emily Dobyns, The Children’s Hospital Introduction: Prior to implementing our donation after circulatory death (DCD) program, a core team of ICU and OR staff met to discuss potential logistical challenges a DCD program may present. ICU and OR staff were unclear what their roles would be and how withdrawal of life support would proceed in the OR. Hypothesis: In order to work through questions that arose, the team decided to simulate a DCD event. It was believed that simulation would provide valuable insight into this new practice. Methods: An infant DCD simulation scenario was developed. Staff members were identified for the roles of the parents and bedside caregivers. 23 participants from respiratory therapy, social work, nursing, physicians, patient safety and quality, OR staff and our Organ Procurement Organization participated. The simulation began in the PICU with the family consent process and preparation of patient for transport to the OR. The simulation than proceeded with transport to the OR, surgical preparation and draping of the patient, positioning of monitors and staff members and than withdrawal of life support with the ‘mother’ present. The entire simulation process from preparation in the PICU to declaration of death in the OR was videotaped. Results: Following the enactment of the simulation scenario, the group reconvened to debrief and review the videotape in detail. ICU and OR workflows were reviewed and formatted into a checklist. This DCD checklist is now integral to our DCD policy. The DCD checklist is separated into ICU management, ICU Preparation for OR, Transport to OR and Surgical Preparation, Withdrawal of Treatment, and Documentation. Conclusions: Using simulation to assist in implementing a DCD program represents a novel use of simulation technology. The simulation allowed us to operationalize a complicated new policy with the development of a DCD Checklist. Two weeks after the simulated DCD, the DCD Checklist was utilized successfully for the first DCD at our organization. In each subsequent DCD, we have reviewed and updated the checklist to further enhance its utility.

Poster: Ethics and End of Life-2 727

728

THE PROCESS AND PURPOSE OF PROGNOSTICATION: OPINIONS AND EXPERIENCE OF PEDIATRIC SPECIALISTS

PEDIATRIC INTENSIVISTS’ VIEWS OF UNILATERAL DECISION MAKING IN DIFFICULT CASES

Sabrina Derrington, Cheryl Lew, Jeffrey Gold, Theodora Stavroudis, Robert Bart, Childrens Hospital Los Angeles

Mindy Dickerman, Saint Christopher’s Hospital For Children, Kavita Morparia, Sarah Hoehn, St. Christopher’s Hospital for Children

Introduction: Physicians must develop and communicate prognoses to direct care and assist patients and families in decision-making, yet receive minimal training. Little is known about the process of prognostication. Hypothesis: The role and process of prognostication in pediatrics were explored. Methods: Semistructured interviews of 20 pediatric specialists were conducted. Interviews were transcribed and analyzed using modified grounded theory by a multidisciplinary team. Results: After achieving adequate saturation, three themes emerged: development, delivery, and difficulty.Pediatric specialists believe prognosis involves an estimate of short (survival) and long-term (quality of life) outcomes, both at initial diagnosis and at critical points during disease course. They develop a gestalt based on relevant medical literature, experience, colleagues and consultants, and the patient’s history and clinical status. Observing a patient’s response to therapy further refines prognosis and increases certainty over time. Long-term prognosis is affected by the patient and family’s resilience, socioeconomic status, and education.Pediatric specialists adjust delivery of prognoses by assessing parents’ understanding, emotional state, and decision-making style. These physicians admit a tendency to ‘sugar coat‘ bad prognoses, but most believe parents need to know ‘as much as we do‘ to have realistic expectations and make good decisions. Physicians struggle to balance hope and realism in themselves and when communicating to families.Those who have experienced prognostic error believe ultimate outcomes are ‘out of their control‘ and prefer to be vague when talking to families. Prognostication is difficult due to patient and situational variability, making it impossible to apply population-based statistics to individuals. Experience with patients who ‘beat the odds‘ fuels optimism that physicians share with families. Conclusions: Pediatric specialists view prognosis within the context of patient, family, and disease variability. They rely on published data and clinical experience to develop prognoses, but believe their ability to predict exact outcomes is limited. More data is needed to develop methods for teaching prognostication.

Introduction: Many hospitals have established medical futility policies allowing a physician to withdraw or withhold treatment considered futile against families’ wishes. Although navigating conflicts over life-sustaining therapy is the primary responsibility of the pediatric critical care attending, little is known about how pediatric intensivists view this process. The goal of our study was to elucidate the perspective of pediatric critical care physicians on futility. Methods: Using survey monkey to ensure anonymous results, we sent a survey to all active members of the American Academy of Pediatrics Section of Critical Care. The survey included four clinical vignettes where families insisted on futile care. In each scenario, participants were asked if they would go against the families’ wishes and how they would resolve the conflict. Results: 263/618 (43%) physicians completed the survey. For an infant with severe hypoxic ischemic injury and intestinal failure, the majority of physicians (83.7%) would not enact a unilateral Do Not Attempt Resuscitation (DNAR) order. For an oncology patient with multi-organ system failure and encephalopathy, the majority (90.4%) would not enact a unilateral DNAR. In the case where a child was declared brain dead, 54.3% of physicians would support unilateral DNAR, yet a third (33.1%) would continue mechanical ventilation. In the case of cardiac surgery for a patient with Trisomy 13, the majority (67.1%) would not advocate for surgery. In most scenarios intensivists cited consultation from the ethics committee (53.8%-76.6%), followed by support from palliative care teams, risk management, and critical care colleagues, as the most appropriate way to resolve the conflict. Qualitative data revealed intensivists would prefer to honor families’ wishes and utilize time with support from a multidisciplinary team rather than unilateral DNAR to resolve these conflicts. Conclusions: The majority of pediatric intensivists are not in support of unilateral DNAR or withholding care against families’wishes. Therefore, we should focus our energies on supporting families struggling with difficult decisions rather than imposing our will on them.

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CLINICAL OUTCOMES AND MORTALITY IN ADULT NONTRAUMA JEHOVAH’S WITNESS PATIENTS WITH ACUTE ANEMIA

SYMPTOM EXPERIENCES OF FAMILY MEMBERS OF HIGH RISK OF DYING ICU PATIENTS THREE MONTHS AFTER THE ICU EXPERIENCE

Abhijit Duggal, Sunnybrook Health Care Sciences, Kanwaljit Waraich, Western reserve Care System/ NEOUCOM

Jennifer McAdam, Samuel Merritt University, Dorrie Fontaine, University of Virginia School of Nursing, Douglas White, University of Pittsburgh Medical Center, Kathleen Dracup, Kathleen Puntillo, University of California San Francisco

Introduction: Jehovah’s Witnesses have a religious objection to blood donation and transfusion. Hypothesis: To evaluate adult non-trauma Jehovah’s Witness patients identified by treating physicians as needing transfusion of any blood products. To see what percentage of patients change their mind despite their religious conviction. To study the clinical characteristics and outcomes of NonTrauma Jehovah’s Witness patients who received the blood products as compared to patients who continued to refuse any blood products Methods: We retrospectively analyzed charts from 410 admissions of 280 Jehovah’s Witness patients Results: After implementing our exclusion criteria 36 (12.8%) patients were recognized as needing blood products.12(4.28%) patients agreed to transfusion of blood products in contradiction to their religious beliefs. From the patients who received blood products,9(75%) patients signed the consent for blood products themselves, 7(58.3%) had acute blood loss, the mean time period to blood transfusion after recognition of need was 2.25⫾3.13 days. There was no difference in the age(72.42⫾17.32 vs 70.48⫾22.08 p 0.79), sex, lowest hemoglobin (7.91⫾0.93,p0.77), rates of transfer to ICU (58.3% vs 54.16% p0.55) and the LOS in ICU (5.42⫾6.07 vs 6.38⫾6.40 p0.66) of patients who received blood products as compared to patients who refused blood despite a documentation of need. There was no statistical difference in overall mortality (25% vs 16.6% p 0.66) and discharge to home (50% vs 41.6% p 0.72) in the two groups. Rates of renal failure were higher in patients refusing blood (0vs25% p0.07), and rates of pulmonary edema/ CHF(33.3%vs8.3% p0.14) were higher in patients receiving blood products. But they were statistically not significant. Conclusions: Almost 1/3rd of Jehovah’s Witness patients recognized as having a need for blood transfusion agreed to it despite their religious convictions. In majority of the cases the decision was made by the patient themselves within 1-2 days of the documented need. There is no difference in clinical outcomes and overall mortality in NonTrauma Jehovahs witness patients who receive blood transfusions as compared to patients who refuse blood products due to their religious convictions

Hypothesis: To describe levels of traumatic stress, anxiety and depression in family members (FMs) of patients at high risk of dying in the ICU 3 months after patient discharge or death (Time 2); to compare those levels to when patients were in the ICU (Time 1); to determine if differences between Time 1 and Time 2 were related to the patient’s final disposition (i.e., death or discharge). Methods: A longitudinal descriptive study of 41 FMs in 3 tertiary care ICUs. Measures: Impact of Event Scale-Revised (IES-R) and Hospital Anxiety and Depression Scale (HADS). Repeated measures ANOVA was used to analyze symptom changes over time and to compare differences according to the patient’s final disposition. Results: One-third (32%) of the patients died in the ICU or hospital. Mean (SD) scores for FMs’ levels of traumatic stress at Time 2 were significantly lower than at Time 1 [1.27 (0.86) versus 1.61 (0.81), respectively; p ⫽ 0.013]. There were no significant differences in traumatic stress scores of FMs of patients who died (n ⫽ 13) versus those who did not die (n ⫽ 28) (p ⫽ 0.108). Yet, 31.7% of FMs of patients who died in ICU (n ⫽ 13) and 41.5% of the total sample (n ⫽ 41) had IES-R scores of 1.5 or greater, indicating a significant risk of PTSD symptoms 3 months post ICU. Overall levels of FMs’ anxiety and depression at Time 2 were significantly lower than at Time 1 (anxiety: 11.5 (4.88) versus 7.35 (3.91) (p ⬍ 0.001); depression: 9.51 (4.31) versus 5.63 (4.58) (p ⬍0.001). There were no significant differences in anxiety and depression scores of FMs of patients who died compared to those who did not die. Yet, 44% of FMs had significant anxiety and 26.8% were depressed.. Conclusions: FMs’ symptoms of traumatic stress, anxiety and depression significantly decreased 3 months after the ICU experience. Symptoms were not different between FMs of patients who died or survived. Many FMs still had a significant risk of PTSD and borderline anxiety 3 months after ICU. More support and understanding of FMs’ symptom experiences are needed in order to improve family centered care in the ICU.


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PREDICTORS OF SURROGATES’ PERCEIVED ABILITY TO MAKE DECISIONS FOR INCAPACITATED ICU PATIENTS

UNDERSTANDING BASELINE ATTITUDES TOWARDS GENE-VARIATION RESEARCH IN CRITICALLY ILL PATIENTS: IMPLICATIONS FOR CONDUCTING SOCIAL SCIENCES INVESTIGATION IN THE ICU SETTING

Alyssa Majesko, University of Pittsburgh Medical Center, Seo Yeon Hong, Lisa Weissfeld, University of Pittsburgh Graduate School of Public Health, Douglas White, University of Pittsburgh Medical Center Introduction: Although many family members of ICU patients seem to struggle in the role of surrogate decision maker, little is known about predictors of family members’ perceived ability to function as a surrogate. Hypothesis: To quantify family members’ perceived ability to function as surrogates and to determine predictors of lower confidence to carry out this role. Methods: We conducted a prospective study of 230 surrogate decision-makers for incapacitated, mechanically ventilated patients at high risk of death in 4 ICUs at UCSF Medical Center from 2005 to 2008. Surrogates completed a survey about their role in decisionmaking that included a question addressing their perceived ability to make decisions that reflected the patient’s values and preferences. We used clustered multivariate logistic regression to identify predictors of low levels of perceived ability as a surrogate. Results: Most surrogates reported a high degree of confidence in their ability to make decisions in accord with the patient’s values (mean 8.21, SD 2.3, on a 1-10 scale), however 27% rated their ability as 7 or lower. In the clustered multivariate regression model, significant predictors of lower confidence were poor quality of communication with the ICU physician (p ⬍0.001), no prior experience as a surrogate (p⫽ 0.04) and no discussion with the patient (p ⬍0.001). Conclusions: Family members with no prior experience as a surrogate and those who have not had prior conversations with the patient about treatment preferences are more likely to feel ill-prepared to act as a surrogate decision maker. High quality communication from the clinical team is associated with higher perceived ability among family members to act as a surrogate.

Ellen Iverson, Chlidrens Hospital Los Angeles, Erica Shehane, Aaron Celious, Childrens Hospital Los Angeles, Carie Kennedy, Washington University School of Medicine, Alex Eastman, Mandy Oerke, University of Texas Southwestern Medical Center, Victoria Warren, University of Texas Southwestern School of Medicine, Bradley Freeman, Washington Univ. School of Medicine Introduction: Conducting clinical ICU studies is ethically challenging because consent is often granted by surrogate decision makers (SDM’s). Collection of genetic data is increasingly common in such investigations, adding complexity (Pharmacogenomics J;10:77-85;2010). This study is part of a multicenter effort to enhance understanding of attitudes of SDM’s regarding gene-variation research. Methods: To establish baseline characteristics and knowledge prior to participating in a qualitative study involving focus groups/interviews, SDM’s for ICU patients meeting inclusion criteria (sedated/ventilated for ⬎48 h, expectation of ⬎24 h of additional support) and cared for in 2 tertiary care centers (St. Louis, MO; Dallas, TX) were invited to complete a 27-item questionnaire designed to assess demographics and perceptions of genetics. Results: We screened 224 eligible patients to identify 53 SDM’s (24%) who agreed to survey participation. The most common barriers to SDM recruitment included inability to locate the SDM (corresponding to 40% of eligible patients), lack of availability (12%), and refusal (11%). SDM’s (mean (⫾SD) age 48.0 (⫾14.5) yrs, 72.6% female) were ethnically diverse (42.5% C, 34.2% AA, 20.5% L) and related to the patient most commonly as a child (27.5%), spouse (23.2%), or parent (18.8%) with duration of the relationship long-lived (33.6 (⫾13.1) yrs). Most had completed high school (12.4 (⫾3.7) yrs of formal education) with minorities reporting prior experience working in healthcare (37.7%) or participating in some form of research (14.5%). While 84.5% of respondents described themselves as having limited knowledge of genetics, 65.5% described genetic technology as ‘more good than harm’ and 72.3% would permit enrollment in hypothetical genetics research. Conclusions: We were successful in interviewing a minority of eligible SDM’s. Characteristics and attitudes of our sample may not accurately reflect those of the broader SDM population limiting impact of interventions derived from these types of investigation. Willingness of SDM’s to permit genetic specimen collection despite limited knowledge raises questions as to whether these individuals are sufficiently informed to provide consent.

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KNOWLEDGE, ATTITUDE AND PERCEPTIONS OF PROVIDERS ABOUT GENETIC TESTING IN THE PEDIATRIC CRITICAL CARE ENVIRONMENT

CURRENT STATUS OF END-OF-LIFE TREATMENT IN KOREA

Ellen Iverson, Rita Burke, Adriana Armenta, Childrens Hospital Los Angeles, Erica Shehane, Childerns Hospital Los Angeles, Maryann Nyc, University of California, Los Angeles, Jeffrey Upperman, Childrens Hospital Los Angeles, Rick Harrison, University of California Los Angeles Medical Center

Introduction: Korea is one of the few industrialized countries that have yet to come to a consensus on end-of–life (EOL) treatments. Interest in this issue has grown following the Supreme Court’s decision to respect the presumed wishes of a persistent vegetative state patient and allow the removal of the mechanical ventilator. Hypothesis: We attempted to evaluate the current status of EOL treatments in Korea with claims data of Health Insurance Review & Assessment Service (HIRA), the single payer in health insurance in Korea. Methods: Data was extracted from the database of medical care fee claim submitted by medical institutes in Korea to HIRA in 2007. The source population was defined as individuals who died in 2007. Newborn death and deaths with no history of receiving medical services within the previous year were excluded. Individuals with a history of medical service utilization in the last 30 days before death with the disease codes related to EOL treatment were selected analyzed. Results: The average days of hospital visit was 17.1 days in the last month of life with an average cost per visit of US$ 141. The average length of hospital stay in the last month of life was 10.3 days. One quarter of Koreans received ICU care, 17.6% received CPR, and 16.5% received mechanical ventilation in their last month. Only 56.5% received pain killers whereas 16.3% and 34.8% received antibiotics and transfusion in their last month. Conclusions: Despite the high costs associated with life sustaining EOL treatment, greater societal consensus is required in order to develop a national guideline/regulation regarding EOL treatment decisions.

Introduction: We examined the medical, social and ethical implications of genetic testing in the pediatric critical care setting. Hypothesis: We hypothesize that critical care providers will support the advancement of genetic testing in the critical care setting. Methods: After IRB approval, a sample of critical care providers from two large urban hospitals in Los Angeles County was recruited to elicit their knowledge and opinions about “personalized medicine”, the emerging application of genetic testing to guide treatment decisions. We conducted qualitative analysis with nurses, intensivists, social workers, genetic counselors, and genetic counseling students. Themes discussed during the focus groups included knowledge about genetic testing, knowledge of personalized medicine, and concerns about testing. The qualitative analysis was based on Thematic Analysis approach. Results: Themes that were examined included perceptions of how genetic testing differed from other clinical tests, role of informed consent in genetic testing, whether genetic testing should become the standard of care, importance of a medical team in interpreting the results, and differences between pediatric and adult genetic testing. Intensivists, nurses and genetic counselors were more inclined to view genetic tests as they would other clinical tests used to direct treatment, but most acknowledged that genetic data had the potential to reveal far more that could impact care, communication, insurance coverage and a patient’s future. Though there was enthusiasm for the use of personalized medicine in the PICU, there were many concerns, including denial of care, equity, stigma and challenges to interpretation of genetic test results. Providers were also concerned about parents’ ability to synthesize the information presented to them to make a decision about their child’s care as well as their own ability to keep up with the field. Conclusions: The central issue with genetic testing in the acute setting is that the genetic information obtained may not only have an impact on current care decisions but also on future care. Therefore medical, social and ethical implications should be considered as society embarks on the new era of personalized medicine.


Ho Geol Ryu, Boramae Medical Center, Seoul National University, Jong-Myon Bae, National Evidence-based Healthcare Collaborating Agency

Poster: Patient and Family Support 735

736

IMPACT OF FAMILY PRESENCE DURING ROUNDS ON PHYSICIAN COMFORT AND PERCEPTION OF TEACHING AND EFFICIENCY

EXPLORATION OF THE EXPERIENCES OF PARENTS REGARDING THE DEATH OF THEIR CHILD IN A PEDIATRIC INTENSIVE CARE UNIT

Treva Ingram, Pradip Kamat, Craig Coopersmith, Atul Vats, Emory University School of Medicine

Gerald Williams, Loma Linda University

Introduction: The Institute of Medicine recommended that healthcare systems become more patient-centered in 2001, and the American College of Critical Care Medicine Task Force 2004 -2005 endorsed family presence on rounds in order to improve communication between families and the healthcare team. Hypothesis: Intensivist participation in Family Centered Rounds (FCR, family presence at physician led rounds) leads to increased comfort with FCR and decreases concern that teaching and efficiency are compromised. Methods: Surveys were sent to Pediatric and Adult Intensivists at Emory University. Responses of physicians that do participate in FCR were compared to those that do not. Survey questions were developed using a 5-point Likert scale (1⫽negative impact, 3⫽no impact, 5⫽positive impact). The survey questions were generated and responses tabulated using Zoomerang.com. Data were exported from Zoomerang and analyzed using Excel. Results: 30/46 (65%) intensivists responded. 15 (50%) stated that they have participated in FCR, 14 (47%) had not, and 1 did not provide a response to the question. Comfort with the practice of FCR was statistically significant between the two groups (4.33⫹SD for those who participated vs 2.60⫹SD for those who have not, p⬍0.05). Open-ended comments from 4/15 participants in FCR relayed hesitation that resolved with participation. There is also a significant difference in the perception of the impact of FCR on staff’s involvement during rounds (3.53⫹SD vs 2.27⫹SD, p⬍0.05). Alternately, perceptions on teaching (2.87⫹0.83 vs 2.53⫹1.41, p ⫽ 0.44) and efficiency (2.34⫹0.74 vs 2.07⫹1.28, p ⫽ 0.50) amongst participants and nonparticipants in FCR were not statistically different. Conclusions: Participation in FCR is associated with increased comfort with family presence on rounds, and a perception of positive impacts on staff involvement. It does not, however, change perceived impacts on teaching and efficiency. As experience with FCR appears to improve comfort and acknowledgment of its benefits, concerns of FCR may also be alleviated with trials after further investigation is undergone to develop methods to ensure that teaching and efficiency do not suffer..

Introduction: Families experiencing the death of their child in the Pediatric Intensive Care Unit (PICU) face challenges different from families experiencing the death of an older relative. Hypothesis: This study aimed to determine the experiences of families experiencing the death of a child and the recommendations they have for Intensive Care physicians and other providers. Methods: This study interviewed parents of children who had died in the PICU between six months and a year prior to the interview. After telephone consent was obtained, parents were asked 10 open-ended questions regarding their experiences during the end of their child’s life and what they would recommend to physicians and other health care professionals taking care of dying children. Results: 13 interviews were conducted with respondents from five different hospitals throughout the United States. Seven (54%) respondents reported being upset by the lack of empathy shown by staff while three (23%) reported being comforted by the staff’s empathy. Six (46%) responders felt that they had inadequate or inconsistent communication with their child’s providers while four (31%) felt they were provided adequate and consistent information on their child. Four (31%) of those interviewed considered it helpful to have monitors turned off and invasive equipment removed at the time of death, while one respondent wished staff had removed invasive equipment. Five (38%) respondents reported being comforted in the belief that everything possible was done to help their child. No respondents reported concerns regarding the quality of care their child received in the PICU. Conclusions: This study suggests that PICU staff can support families dealing with the death of their children by providing them with clear and consistent communication and empathy. Removing invasive medical equipment and turning off monitors may also help families at that time.

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QUALITY AND QUANTITY OF SLEEP IN MULTIPLE VERSUS SINGLE PATIENT ROOM INTENSIVE CARE UNITS

PARENTAL DECISION MAKING PREFERENCES IN THE PEDIATRIC INTENSIVE CARE UNIT

Maarten Van Eijk, University Medical Center Utrecht, Renilde van den Bossche, Sein Zwolle, Marinus Nouwen, Univeristy Medical Center Utrecht, Frans Leijten, University Medical Center Utrecht, Al de Weerd, SEIN Zwolle, Margriet Schneider, Jozef Kesecioglu, Arjen Slooter, University Medical Center Utrecht

Vanessa Madrigal, Karen Carroll, Kari Hexem, Children’s Hospital of Philadelphia, Wynne Morrison, The Children’s Hospital of Philadelphia, Chris Feudtner, Children’s Hospital of Philadelphia

Introduction: Sleep fragmentation and deprivation is common in Intensive Care Unit (ICU) patients and may increase the risk of delirium. It is generally assumed that the ICU environment, including over-exposure to sound and light in the night-time, is an important cause for disturbed sleep. In the University Medical Centre, Utrecht, the Netherlands, a new ICU was built with quiet, single-patient rooms with much daylight. Hypothesis: This created an unique opportunity to study the effects of nursing environment on sleep quality and quantity in ICU patients. Methods: We included 20 post-cardiothoracic surgery (either CABG or valve replacement) patients: ten subjects were admitted to the old, ward-like ICU, and ten patients to the new, single-room ICU. We exclude patients with an underlying sleep disorder. A 15-lead polysomnography recorded sleep patterns from 07:00 p.m. to 07:00 a.m. 24 hours before and 48 hours after the registration, subjects were asked to fill in a questionnaire concerning the subjective quality of sleep. Results: Polysomnography recordings showed that the total sleep time in both situations was equal, but in the new, single-room ICU, subjects showed significantly less superficial sleep and more N2 sleep, as compared to the old ICU. No significant differences between the subject’s sleep experiences were found. Conclusions: This study shows that quality of sleep can be influenced by ICU design. We used a homogenous group to improve comparison. The number of patients is too small to study the association with delirium; the relation of nursing environment with delirium is currently being studied in a larger population. ICU design aimed at decreased light and sound exposure leads to less superficial sleep.

Introduction: To assess parental decision-making preferences in the high stress environment of the Pediatric Intensive Care Unit (PICU) and test whether preferences vary with the chronicity of disease, prior admissions to the PICU and parental affect. Hypothesis: Parents prefer shared decision-making even when making extraordinary decisions on behalf of their child in the PICU setting. Parents’ preferences are affected by chronicity of disease, exposure to the PICU and parental affect. Methods: IRB approved, prospective cohort study conducted between December 2009 and April 2010 of English-speaking parents whose children were less than 18 years of age (or cognitively incapable of making their own decisions) and were hospitalized in the PICU at the Children’s Hospital of Philadelphia for greater than 72 hours. Parents were interviewed in person. Topics included exposure to the PICU, chronicity of disease and standardized instruments assessing decision-making preferences and parental affect. Results: 87 parents of 75 index patients enrolled in the study. With respect to preferred role in decision-making, 3 (2.8%) prefer to leave all decisions to the physician, 74 (86%) prefer some degree of shared decision- making and 10 (11%) prefer to make treatment decisions alone. Trends in decision-making suggest that parents with high degree of negative affect and depression move away from shared decision-making in a bimodal distribution, as do parents with palliative care team involvement. Parental preference does not appear to be influenced by either chronicity of disease, or prior admissions to the PICU. Conclusions: Our study suggests that in the high stress environment of the PICU, most parents prefer shared decision-making with their children’s physician. The data also suggest that when parents are experiencing more negative affect and depression, they may prefer either making treatment decisions alone, or leaving all decisions to their physician. Preferences do not appear to be influenced by chronicity of disease or prior admissions to the PICU.


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ATTITUDES OF PHYSICIANS AND NURSES TO A CHANGE IN ICU VISITING HOURS

SOCIAL WORK IN ADULT CRITICAL CARE: A NATIONAL SURVEY

Hina Chaudhry, William Owens, Martin Durkin, Nakita Barnes, Juan Morales, Husam Najjar, Franklin McGuire, University of South Carolina

Katherine Shea, Anne Hahn, Joanne Kraus, Joyce Maygers, Johns Hopkins Bayview Medical Center, Jonathan Sevransky, The John Hopkins Bayview Medical Center, Grace Cordts, Johns Hopkins Bayview Medical Center

Introduction: The Medical ICU at our hospital recently extended visiting hours from a total of 2.5 hours/day to 8.5 hours/day. Hypothesis: The attitudes of ICU nurses and physicians regarding extended visiting hours differ; and, the attitudes of both physicians and nurses toward extended visiting hours will become more favorable over time. Methods: A voluntary and anonymous ten question survey was sent 3 and 10 months after the policy change to 45 MICU nurses and 14 critical care physicians. For five questions, a “Strongly Agree” or “Agree” response indicated the change was favorable. These concerned improvement in the overall effect of the change, communication, patient care, patient/family satisfaction and discussion of end-of-life issues. For the other five questions, a “Strongly Agree” or “Agree” response indicated that the change was unfavorable (limitations in patient care, increased infections, family interference with treatment, compromised confidentiality, and prolonged nursing shifts). The major outcome was the number of responses that strongly agreed or agreed with favorable questions, or strongly disagreed or disagreed with unfavorable questions. P-values were computed using the Chi-squared test. Results: 9 physicians and 31 nurses responded to the first survey; 14 physicians and 31 nurses answered the second survey. On the first survey, physicians viewed the change as a “good idea” more frequently than nurses (OR⫽0.09, p⫽.03); for the other nine questions, there was no significant difference in attitudes between the two groups. In general, physicians tended to have a more favorable view of extended visitation compared with nurses (OR 0.35, p⬍.001). On the second survey, physicians still held a favorable view of extended visitation, while nurses still held an unfavorable view (OR 0.5, p⬍.001). Neither group had a significant change in attitudes between the first and second survey. Conclusions: Physicians tend to have a favorable view of extended visitation in the MICU, while nurses tend to view this unfavorably. Attitudes toward this policy did not change over a seven month period.

Introduction: There is limited information in the literature about the role of the social worker in the critical care unit. Critical care social workers may assist with understanding of family dynamics, team functioning, crisis response and end of life care. Hypothesis: The most frequent activity of social workers in critical care units is assessment of the patient and family’s coping srategies. Methods: We surveyed attendees at the Society for Social Work Leadership in Health Care (SSWLHC) at the 2009 national conference. Study questions were derived from a previous literature review and from clinical experience of two critical care social workers, and were field tested by three practicing critical care social workers. Survey questions were grouped according to four categories determined by the research social workers: Team Intervention, Social Work Intervention, Patient/ Family Assessment and Patient/Family Assistance. Responses were graded on a five point Likert scale. Results: A total of 86 completed surveys were received from 204 (42%). Social Workers rated activities in the category of Patient/Family Assessment with the highest frequency with 6 items having ratings ⬎80% of “all of the time” or “most of the time”. The highest frequency items in this category were assessment of social supports (97.6%), assessment of abuse and neglect (91.6 %), assessment of the social context of the illness (85.7%) and assessment of the family’s understanding of the critical illness (84.7%). Additional high frequency activities included provision of community resources (89.4%), financial assistance (84.7%), facilitation of communication between the patient or family and the medical team (84.7%), support with medical decision making (78.6%), arrangement of family meetings to discuss discharge planning (76.8%) or goals of care (72.8%) and end of life interventions (75.9 %). Conclusions: Assessment of family needs, communication interventions, end of life care and facilitation of referrals are frequent activities of the critical care social worker. Our data suggests that social work training programs need to incorporate these topics for those students who will practice in critical care units.

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STANDARDIZED INTERDISCIPLINARY FAMILY MEETINGS FOR LONG-STAY SURGICAL INTENSIVE CARE UNIT PATIENTS – RESULTS OF A FEASIBILITY PILOT

EVALUATION OF MEDICAL NECESSITY OF TRAUMA AIR MEDICAL TRANSPORT IN A PREDOMINANTLY RURAL STATE

Rebecca Aslakson, The Johns Hopkins University School of Medicine, Maureen Coyle, The Johns Hopkins Hospital, Rhonda Wyskiel, The John Hopkins Hospital, Christina Copley, Kathryn Young, The Johns Hopkins Hospital, Nita Ahuja, The Johns Hopkins University School of Medicine, Peter Pronovost, The John Hopkins University School of Medicine

Gina Berg, University of Kansas School Of Medicine, Mike Simmons, EagleMed, Dan Clark, Denise Spaeth, Wesley Medical Center, Scott Pauly, Lucas Thompson, Robin Crowe, KU School of Medicine - Wichita, Paul Harrison, Kansas Surgical Consultants

Introduction: For intensive care unit (ICU) patients and their families, proactive communication decreases use of ineffective ICU treatments, reduces ICU length of stay (LOS), and promotes earlier consensus around goals of care. However, particularly in surgical ICUs (SICUs) operating under ‘semi-open‘ plans, these meetings are difficult to enact and few subsequently occur. Identifying a subset of SICU patients likely to most benefit from meetings and ensuring that meetings occur for these patients, would enable more effective and efficacious utilization of resources. Hypothesis: (1) We can identify a duration of SICU stay that predicts high mortality, long stay SICU patients. (2) An interdisciplinary team can champion a quality improvement initiative to facilitate meetings. Methods: We convened meetings with senior division members and general practitioners to agree upon identification criteria for patients and completed a pilot study. Patients identified for meetings were tracked throughout their hospitalization and demographics recorded. Results: Leaders in the divisions of surgical nursing, social work, pastoral care, surgery, the hospital ethics committee, anesthesia, and surgical critical care agreed on the identification criteria of approximately seven days SICU admission. During the six month pilot study in the 16-bed Weinberg surgical ICU at The Johns Hopkins Hospital, twenty-five patients with an overall in-house mortality of 44%, were identified for meetings. Median (mean) hospital LOS was 44 (54.1) days and 37 (50.8) days and median ICU LOS was 32 (37.4) days and 34 (46.5) days for survivors and non-survivors, respectively. Approximately 60% of patients received interdisciplinary meetings with patient death or transfer out of the SICU being the most common reasons for a meeting not to occur. Conclusions: The criteria of seven days admission to a SICU identifies a subset of high mortality, long stay SICU patients likely to benefit from proactive interdisciplinary meetings. An interdisciplinary steering committee can facilitate the occurrence of these meetings.


Introduction: Air transport is recognized for speed and efficiency in emergencies. Moreover, it benefits rural communities unable to sacrifice their EMS ground vehicles for long-distance travel. Hypothesis: Evaluate the reasons for air medical transport of trauma patients in a rural state. Methods: A retrospective crosssectional registry review of trauma patients transported by an air medical transport service to a level 1 trauma center between 1/1/07 and 12/31/08. Patients were stratified into an exclusive hierarchical taxonomy based on level of consciousness, vital sign data, anatomy of injury, age risk (⬍5 or ⬎55), need for ALS services when only BLS available, and need for specialist. Travel time, patient loaded miles and ED dismissal were also evaluated. Results: Registry identified 483 trauma patients: 409 adults and 74 pediatric. Patients were mostly white (87%), male (63%), mean adult age was 45 and mean pediatric age was 10. Registry records were missing incoming vital sign data for 200 patients thus were excluded from hierarchical stratification leaving 246 adults and 37 pediatric patients.Adult hierarchical stratification included: GCS/vital sign (58%), anatomy of injury (6%), age risk (9%), need for ALS service (16%), and specialist need (11%).Pediatric hierarchical stratification included: GCS/vital sign (62%), anatomy of injury (8%), age risk (3%), need for ALS service (19%), and specialist need (8%).Mean travel time was 42 minutes and 118 patient loaded miles.There were 12 ED dismissals; 4 required ALS transport, 3 were high risk due to age, and 1 had an injury requiring level 1 services. Conclusions: Most of the identified trauma patients required air transport based on ACS criteria, however the lack of ALS services required patients to travel by air as ground transport personnel were not ALS certified. Need for specialist care may not necessitate the speed of air travel, however, ground travel would require EMS services to be unavailable for long periods of time. Patients who require immobilization on rigid spine boards for long transport times are at increased risk for pressure ulcer development. The necessity for air transport in a rural state is complex and requires further research.

Poster: Therapeutics-Drugs and Pharmacokinetics-1 749

750

MULTICENTER RANDOMIZED CONTROLLED TRIAL TRA204 TO EVALUATE THE SAFETY AND EFFICACY OF MP4OX IN LACTATE CLEARANCE FOLLOWING TRAUMA HEMORRHAGE

COMPARISON OF INTRAVENOUS COLISTIN WITH AND WITHOUT INHALED COLISTIN FOR MULTI-DRUG RESISTANT GRAM-NEGATIVE PNEUMONIA IN CRITICALLY ILL PATIENTS

Karim Brohi, Royal London Hospital, Frank Plani, Chris Hani Baragwanath Hospital, Maeyane Moeng, Charlotte Maxeke Johannesburg, Bruno Riou, Hopital Pitie Salpetriere, Jaques Goosen, Netcare Union Hospital, Jan Pretorious, Steve Biko Academic Hospital, Yun Hardiman, Howard Levy, Sangart

Neha Doshi, Kari Mount, The Ohio State University Medical Center, Erin Frazee, Heather Personett, Mayo Clinic-Saint Mary’s Hospital, Garrett Schramm, Mayo Clinic, Claire Murphy, The Ohio State University Medical Center

Introduction: Prolonged ischemia complicates trauma haemorrhage and is associated with worse outcomes in terms of mortality, organ dysfunction, sepsis and hospital stays. Hypothesis: This was a Phase IIa international multicenter randomized controlled trial of the oxygen therapeutic agent MP4OX to investigate its safety and efficacy in terms of improved lactate clearance and clinical outcomes. Methods: 51 adult trauma patients in hemorrhagic shock with lactic acidosis (lactate ⱖ5 mmol/L) were enrolled within 2 hrs of arrival and 4 hrs of trauma at 11 centers in 4 countries. Patients received: Control (CON): 500 mL Ringer’s lactate (RL) [18 pts]; MP4OX250: 250 mL MP4OX ⫹ 250mL RL [18 pts]; or MP4OX-500: 500 mL MP4OX [15 pts], in addition to standard care. Results: Groups were well matched for age, sex, weight, mechanism or severity of injury, total fluids (colloids or crystalloids) and red blood cell (RBC) administration. MP4OX was effectively absent from the circulation after an additional 6 unit RBC transfusion.There was no significant difference in overall serious adverse events, cardiac events or mortality. There was no difference in AST, ALT, amylase, lipase, troponin I and creatinine to 28 days.Baseline lactates were similar - MP4OX: 6.6mmol/L and CON: 7.0mmol/L. There was immediate lactate decrease seen by the end of infusion (MP4OX: 5.3mmol/L vs. CON: 8.5mmol/L, p⫽0.004) and this was sustained to Hour 2. More MP40X patients had a ⬎10% lactate clearance between baseline and Hour 2 (86% vs. 56%; p⫽0.035). There was no difference in lactate clearance between MP4OX-250 and MP4OX-500 groups.Overall there was a trend towards improved outcomes with reduction in median total hospital days (MP4OX vs. CON: median 13 vs. 28 days; p⫽0.089) and the proportion discharged from hospital by Day 28 (MP4OX vs. CON: 48% vs. 28%; p⫽0.234). Conclusions: MP4OX has a satisfactory safety profile and was associated with an immediate and sustained lactate clearance. There is sufficient evidence of trends in better outcomes to advance to pivotal studies. The TRA-204 study was funded by Sangart Inc., San Diego, CA.

Introduction: Throughout the last decade, the rise of multi-drug resistant (MDR) gram-negative organisms has resulted in an increased use of colistin. Inhaled colistin as an adjunct to intravenous (IV) therapy is currently being used in practice to treat pneumonia caused by these organisms; however the data supporting this practice is limited. The objective of this study is to evaluate the efficacy of adjunct inhaled colistin for MDR gram-negative pneumonia in critically ill patients. Hypothesis: Inhaled colistin increases the rate of clinical cure when used in combination with IV colistin compared to IV colistin monotherapy. Methods: This retrospective evaluation conducted at two large academic medical centers included critically ill patients with MDR gram-negative pneumonia between July 1, 2007 and July 31, 2009 who received IV colistin for at least 48 hours. Patients who received inhaled colistin were compared to those who did not. The primary outcome was clinical cure defined by resolution of symptoms associated with their infection. Secondary endpoints included mortality, duration of mechanical ventilation and length of stay. Continuous variables were analyzed using Student’s t-test or Mann-Whitney U-test. The Chi-square or Fisher’s exact tests were used to compare categorical variables. Results: Seventy-eight patients were enrolled; 31 (40%) patients received inhaled colistin and 47 (60%) received only IV colistin. Baseline characteristics were similar between groups. There was no difference in clinical cure between patients who received inhaled colistin and those that did not (61.3% vs. 57.4%, p⫽0.816). More patients in the IV monotherapy group received an additional IV antibiotic for the same MDR organism (63.8% vs. 38.7%, p⫽0.029). There was no difference in mean hospital or ICU length of stay or duration of mechanical ventilation. Mortality was 55% in the IV monotherapy group and 39% in the adjunct inhaled colistin group (P⫽0.151). Conclusions: This study failed to show a benefit of adjunct inhaled colistin with regards to clinical cure; however, a trend toward improved mortality was appreciated. Larger, prospective studies are warranted to further explore the role of inhaled colistin.

751 SAFETY AND EFFICACY OF LUCINACTANT, A PEPTIDECONTAINING, SYNTHETIC SURFACTANT, IN INFANTS WITH ACUTE HYPOXEMIC RESPIRATORY FAILURE: A MULTICENTER PHASE 2 STUDY Neal Thomas, Penn State Children’s Hospital, Carlos Guardia, Discovery Laboratories, Fernando Moya, Coastal Carolina Neonatology, Ira Cheifetz, Duke University Medical Center, Barry Markovitz, Childrens Hospital Los Angeles, Robert Segal, Phillip Simmons, Discovery Laboratories, Adrienne Randolph, Children’s Hospital Boston, for the PALISI, Network Introduction: Acute hypoxemic respiratory failure (AHRF) in infants and young children is associated with surfactant dysfunction. Intratracheal (IT) administration of endogenous surfactants to mechanically ventilated (MV) infants may improve oxygenation and shorten duration of MV. Hypothesis: Treatment with IT lucinactant, a peptide-containing, synthetic surfactant is safe and improves clinical outcomes. Methods: Multi-center, phase 2, double-blind, placebo-controlled study in infants ⬍2 yrs old with AHRF. Infants requiring MV with hypoxemia meeting acute lung injury criteria were randomized to receive IT lucinactant (175 mg/kg) or air placebo. One re-treatment was allowed 12-24 hrs after initial dosing if hypoxemia persisted. Results: 165 infants (84 lucinactant; 81 placebo) were enrolled at 24 U.S. and Chilean sites. There were no significant differences in demographics or baseline characteristics. There was a non-significant reduction (⬃10%) of duration on MV with lucinactant vs. placebo (geometric mean: 3.8 vs. 4.1 days, respectively; p⫽0.25). Oxygenation improved in infants randomized to lucinactant, thus they required fewer second treatments (67% vs. 81%, p⫽0.03). A trend toward improvement in P/F ratio at 48 hrs post-dose with lucinactant was observed in patients where measured (p⫽0.06). As in prior surfactant studies, the incidence of transient peri-dosing bradycardia and desaturation were significantly higher in the treatment group, but peri-dosing adverse events were not associated with unfavorable clinical outcomes. A single episode of severe bradycardia requiring brief resuscitation did not reoccur following retraining at that site. There were no statistical differences between groups for other adverse events or mortality. Conclusions: In ventilated infants with AHRF, treatment with IT lucinactant appeared to be safe despite the expected transient peri-dosing events. An improvement in oxygenation, even with a non-significant decrease in the duration of MV, suggests that lucinactant might improve the pathophysiology of AHRF. Other dosing regimens, including earlier or prolonged treatment or administration by non-invasive means (aerosolized), may merit further study.



753

PSEUDOMONAS AERUGINOSA (PSA): NOT JUST IN THE ICU ANYMORE; IMPLICATIONS FOR EMPIRICAL THERAPY

ERYTHROPOIETIN PLUS METHYLPREDNISOLONE OR METHYLPREDNISOLONE IN THE TREATMENT OF ACUTE SPINAL CORD INJURY: A PRELIMINARY REPORT

Kathryn Eagye, Mary Banevicius, David Nicolau, Center for Anti-Infective Research & Development, Hartford Hospital Introduction: PSA causes substantial hospital morbidity/mortality and is frequently considered in ICU patients. Surveillance of susceptibility (%S) by unit type (ICU vs. Non-ICU) has been advocated to improve empiric therapy choice. Hypothesis: Utilization of pharmacodynamic profiling may assist with antibacterial optimization. Methods: We tested n⫽614 non-duplicate, non-urine PSA collected at 11 US hospitals from Q1 2009 –Q2 2010 by broth microdilution for MIC to 10 agents (3 carbapenems— doripenem [DOR], imipenem [IMP] and meropenem [MEM]— plus 3 other beta-lactams, 2 fluoroquinolones and 2 aminoglycosides). Non-susceptible (NS) by class⫽NS to ⬎⫽ 1 drug; multi-drug resistance (MDR)⫽NS to ⬎⫽1 drug in each of all 4 classes. Wilcoxon rank sums compared agent MIC distributions by unit type. Cumulative fraction of response (%CFR) predicted likelihood of pharmacodynamic target attainment of varying dosing regimens vs. observed MIC distributions. Results: Of n⫽614 PSA, 65% were obtained outside the ICU. Percent MDR were (ICU, Non-ICU, p): (12, 5, p⬍.01). By class, %NS were (ICU, NonICU, p): fluoroquinolones (37, 36, p⫽.87); aminoglycosides (18, 13, p⫽.09); betalactams (84, 88, p⫽.15); and carbapenems (35, 27, p⫽.03). MIC profile in ICUs was (carbapenem, MIC50, MIC90, %S): DOR, 1, 8, 69; IMP, 2, 16, 67; and MEM, 1, 32, 70. In Non-ICUs: DOR, 0.5, 8, 78; IMP, 1, 16, 75; and MEM, 1, 16, 82. MIC distributions differed by unit type for IMP (p⬍.01) but not for MEM (p⫽.09), or DOR (p⫽.30). Other agents were not different. Standard carbapenem regimens resulted in %CFR (regimen, ICU, Non-ICU): DOR 500mg q8h 1h infusion (inf), 73, 79; IMP 500mg q6h 0.5h inf, 62, 69; MEM 500mg q6h 0.5h inf, 67, 76. More aggressive doses and prolonged infusion improved %CFR: DOR 1000mg q8h 4h inf, 92, 97; IMP 1000mg q8h 3h inf, 77, 83; MEM 2000mg q8h 3h inf, 87, 94. Conclusions: While MDR and NS carbapenem phenotypes were more common in the ICU, a high prevalence (65%) of initial PSA cultures of systemic isolates were taken outside the ICU. Our data suggest that unit-specific antibiograms may provide information of use in empiric therapy decisions; consideration of the carbapenem, dose and infusion time may further enhance outcomes for PSA infection.

Ehsanali Alibai, Shiraz University of Medical Sciences, Farid Zand, Shiraz Anesthesiology and Critical Care Research Center, Aziz Rahimi, Jahrom University of Medical Sciences Introduction: Recent studies in animal models indicate that recombinant human erythropoietin (rhEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). Hypothesis: We aimed to evaluate the effect of rhEPO plus methyl prednisolone sodium succinate (MPSS) compared to MPSS alone to improve neurological function of patients after SCI in a randomized clinical trial. Methods: During a 15-month period 30 patients presenting to emergency departments of two university affiliated hospitals within less than 6 hours after acute SCI were randomized to two groups. Both groups received MPSS 30mg/kg initially and 5.4 mg/kg every hour till 23 hours if admitted within 3 hours and till 47 hours if recruited within 3-6 hours after injury. Group EPO also received 500unit/kg rhEPO on admission and another 500 unit/kg 24 hours later instead of placebo in group MPSS. Neurologic evaluation was performed on admission, 24, 48, 72 hours and one and 6 months later. Results: Ranges of patients’ age were 18-65 years. There was a significant improvement in neurologic exam of the patients in both groups after one and 6 months, however the improvement in American Spinal Injury Associated (ASIA) scale in group rhEPO was significantly more profound than group MPSS after one and six months (p value⬍0.003 and ⬍ 0.006, respectively). There was no significant difference between groups regarding sphincter function and sexual dysfunction during the follow-up period. Conclusions: MPSS plus rhEPO started within 6 hours after acute spinal injury is more effective than MPSS plus placebo in improvement of neurologic dysfunction.

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EFFECTS OF A PERIPHERAL CHOLINESTERASE INHIBITOR ON CYTOKINE PRODUCTION AND AUTONOMIC NERVOUS ACTIVITY IN A RAT MODEL OF SEPSIS

A PILOT STUDY OF QUETIAPINE THERAPY IN PATIENTS WITH ACUTE TRAUMATIC BRAIN INJURIES

Daisuke Setoguchi, Shigeto Oda, Tomohito Sadahiro, Masataka Nakamura, Yoh Hirayama, Eizo Watanabe, Yoshihisa Tateishi, Henry Yatsuki, Hiroyuki Hirasawa, Department of Emergency and Critical Care Medicine,Chiba University Graduate School of Medicine Introduction: Recently, the cholinergic anti-inflammatory pathway has been proposed as a new strategy to control cytokine production in sepsis. Experimental monitoring of autonomic nervous activity by heart rate variability (HRV) analysis has been attempted, involving measurement and analysis of the R-R intervals in electrocardiograms. Hypothesis: HRV could evaluate changes in autonomic nervous activity in sepsis, and hypercytokinemia could be controlled by a therapeutic approach via the cholinergic anti-inflammatory pathway in a model of sepsis. Methods: Sepsis was induced by cecal ligation and puncture (CLP). Distigmine bromide, a peripheral, non-selective cholinesterase inhibitor (0.01 mg/kg), was administered subcutaneously 90 min after surgery. Continuous electrocardiograms were recorded for 5 mins before and after surgery (at intervals of 5 hrs) in CLP and sham-operated animals for HRV analysis. Blood samples were collected 20 hrs after surgery for serum cytokine and catecholamine assay. Results: When HRV at a particular time point after surgery were compared between the CLP animals with and without distigmine administration, distigmine significantly inhibited reduction of total power(TP) in the CLP animals 15 hrs after surgery and later. In addition, It was found that distigmine significantly inhibited reduction of high-frequency (HF) component 15 hrs after surgery and later. Distigmine significantly inhibited induction of cytokines (IL-6: 6892.7⫾6628.2 (CLP) vs. 697.2⫾688.3 (CLP⫹distigmine) pg/ml, p⬍0.05 and IL-10: 84.3⫾42.9 vs. 35.6⫾12.2pg/ml, p⬍0.01, respectively) as well as increase in serum levels of catecholamines (noradrenaline: 2394.9⫾498.9 vs. 1469.0⫾720.0pg/ml, p⬍0.01 and dopamine: 1292.2⫾817.2 vs. 576.8⫾439.6 pg/ml, p⬍0.05, respectively). Conclusions: The cholinesterase inhibitor, distigmine, inhibited induction of inflammatory cytokines and catecholamines as well as HRV suppressionin a rat CLP model. These findings suggest that sepsis can be treated via the cholinergic anti-inflammatory pathway. It is also suggested that HRV analysis has the potential to serve as a method for objective assessment of therapeutic effects of this approach to treating sepsis.


Jason Clark, Xi Liu-DeRyke, Jeremy Johnson, Marissa Weber, Kara Birrer, Michael Cheatham, Orlando Regional Medical Center Introduction: Atypical antipsychotics such as quetiapine have been studied for treatment of agitation and delirium in critically ill patients. However, there is a paucity of data evaluating the role of quetiapine in patients with acute traumatic brain injury (TBI). Hypothesis: Quetiapine is an effective adjunctive therapy to benzodiazepine for agitation in patients with acute TBI. Methods: We retrospectively identified all patients admitted between 01/2008 to 12/2009 with acute TBI who were ⱖ18 years of age, had an admission GCSⱕ12, and received quetiapine. Demographic data were collected including age, gender, and type of injury. Quetiapine usage and concomitant medications including sedatives, analgesics, and haloperidol were collected. All benzodiazepine doses were converted to midazolam equivalents and all opioid analgesics were converted to fentanyl equivalents. Clinical outcomes including mechanical ventilation (MV) free days, ICU and hospital LOS were assessed. Student t-test was used for data analysis and data were reported in mean⫾SD. Results: Twenty TBI patients were included in the preliminary analysis. The mean age was 38⫾20 with 90% of patients being male. The majority of patients suffered subdural hemorrhage (60%) followed by subarachnoid hemorrhage (40%) and intracerebral hemorrhage (40%). The mean daily quetiapine dose was 118⫾69 mg given for 11⫾9 days. The initial dose of quetiapine was 48⫾27 mg and was rapidly titrated to 119⫾114 mg by day 5 (p⫽0.01). There was a significant decrease in the benzodiazepine (28⫾37 vs 8.2⫾19 mg, p⬍0.05) and opioid analgesic requirements (485⫾482 vs 225⫾224 mcg; p⫽0.04) between day 1 and day 5 of quetiapine therapy. There was no difference in the level of sedation as evaluated by the Riker sedation and agitation scale on the day of quetiapine initiation and day 5 of therapy (p⫽0.29). No serious adverse events were recorded during quetiapine therapy. The MV free days were 14⫾8 days; ICU and hospital LOS were 9⫾4 and 22⫾11 days, respectively. Conclusions: Quetiapine reduces the benzodiazepine and analgesic requirements and was well tolerated in patients with acute TBI. This may potentially reduce over sedation and the need for MV. Further study is needed for validation.

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INTRAVENOUS HEPARIN VERSUS SUBCUTANEOUS HEPARIN IN SURGICAL INTENSIVE CARE UNIT PATIENTS

TALACTOFERRIN MAY CONFER INCREASED SURVIVAL IN PATIENTS WITH SEPTIC SHOCK AND SYSTOLIC CARDIAC DYSFUNCTION

Sara Cheng, University of Colorado Denver, Christine Hamiel, University of Colorado Health Science Ctr., Angela Baer, David Matero, Kirsten Nordenholz, University of Colorado Denver, Nathan Pearlman, University of Colorado, Paul Wischmeyer, University of Colorado At Denver School of Medicine Introduction: The current standard ofcare in thromboembolism (VTE)prophylaxis for critically ill patients is subcutaneously administered heparin. Hypothesis: This may not be optimalsecondary to decreased absorption of subcutaneously administered drug in thesepatients. Methods: We randomized 50 intensivecare unit patients who just had major abdominal surgery to receive 1 of 2 VTEprophylaxis regimens: subcutaneous heparin 5000 units TID (standard of care) oran intravenous heparin infusion, titrated to a target aPTT range of 40-45 seconds. We obtained daily blood heparin activity levels, daily whole blood coagulationparameters, and screening lower extremity ultrasounds for up to 10 days aftersurgery. Results: Patients were well-matchedwith regards to clinical characteristics including age, Apache II score, BMI,and VTE risk factors. Over 80% of patients had cancer. Patients receivingsubcutaneous heparin (SQH) had no detectable heparin peak activity (anti-Xaassay) for 5 days after surgery. Patients receiving intravenous heparin (IVH)showed statistically significant increases anti-Xa activity when compared toSQH patients on day 3 (0.04 vs. 0.00 units/ml; p⫽0.01) and day 4 (0.05 vs 0.00units/ml; p⫽0.03). We used the Sonoclot analyzer to measure the activatedclotting time (ACT) and clot rate (CR). SQH patients were hypercoagulable for 5days after surgery as evidenced by shortened ACT and higher CR. IVH was associated with normalizationof ACT when compared (p⫽0.001) andCR (p⫽0.045) when compared to SQH. No lower extremity deep venous thrombosis was found on lower extremityscreening ultrasounds on days 0, 5, and 10 in either group. There were no episodes of majorbleeding or heparin-induced thrombocytopenia in both groups. Conclusions: This data demonstrates that absorption of SQH is inadequate in major abdominal surgery patients. IVH results in detectable blood levels that lead to normalization of the postoperative hypercoagulable response. A larger phase III study is needed to assess the efficacy of IVH for the prevention of postoperative VTE in surgical intensive care unit patients.Supported by a grant from the Foundation for Anesthesia Education and Research

Michael Lanspa, University of Utah Medical Center, Samuel Brown, Colin Grissom, Intermountain Medical Center, Peter Morris, Wake Forest University School of Medicine, Rajesh Malik, Agennix, Inc, Joel Pittman, University of Utah Medical Center, Nathan Dean, Intermountain Medical Center Introduction: In a recent phase-2 randomized, placebo-controlled trial, talactoferrin was associated with decreased 28-day mortality in patients with severe sepsis and septic shock. (Guntupalli ATS 2009) The benefit was greatest among patients with severe sepsis. Patients with septic shock, defined as hypotension unresponsive to a ⬎20 ml/kg fluid bolus, had less benefit from talactoferrin. Hypothesis: Echocardiographic assessment of cardiac function among patients with septic shock will identify a subgroup with greater benefit from talactoferrin. Methods: We reviewed echocardiograms obtained within 24 hours of randomization from patients in the talactoferrin clinical trial at Intermountain Medical Center and Wake Forest University Baptist Medical Center. Reviewers were blinded to all other clinical data. We defined left ventricular systolic dysfunction as ejection fraction ⬍ 45%. We defined right ventricular systolic dysfunction as a fractional area change ⬍ 35% or tricuspid annular plane systolic excursion ⬍ 16mm. Results: Of 49 patients enrolled and followed for 28 days, 30 had an interpretable echocardiogram within 24 hours preceding or following randomization; 19 of those 30 had septic shock; 12 of the 19 with septic shock had systolic dysfunction of either or both ventricles. Of those 12 patients, 1 of 5 survived in the placebo group, while all 7 of 7 survived in the talactoferrin group. Of the 7 patients with septic shock and normal systolic function, 3 of 4 in the placebo and 1 of 3 in the talactoferrin group survived. Exploratory logistic regression demonstrated a significant interaction between systolic dysfunction and talactoferrin in predicting survival; Fisher exact test suggested that among patients with systolic dysfunction, assignment to talactoferrin was strongly associated with increased survival (p ⫽ 0.01). Conclusions: In patients with septic shock and abnormal systolic function, talactoferrin therapy may be associated with improved survival. This could be due to an effect of talactoferrin on septic cardiomyopathy. While these findings are limited by the small size of this post hoc subgroup analysis, they warrant further study.

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HEPARIN OR 0.9% SODIUM CHLORIDE FLUSH TO MAINTAIN CENTRAL VENOUS CATHETER PATENCY: A RANDOMIZED TRIAL

HIGH DOSE DEXMEDETOMIDINE DOES NOT RESULT IN ENHANCED SEDATION IN CRITICALLY ILL PATIENTS

Marilyn Schallom, Barnes- Jewish Hosptial, Donna Prentice, Barnes-Jewish Hosptial, Carrie Sona, Barnes Jewish Hospital, Scott Micek, Barnes-Jewish Hosptial, Lee Skrupky, Barnes-Jewish Hospital Introduction: The superiority of heparin (H) flush for prevention of central venous catheter (CVC) thrombosis is unproven. Hypothesis: There will be no difference in CVC lumen major occlusion (MO) rates in patients randomized to H (3 ml, 10 units/ml) or 0.9% sodium chloride (0.9% NaCl, 10 ml) flush. Methods: Patients in the MICU or SICU with a new centrally placed triple or quad lumen CVC were consented and randomized within 12 hours of insertion. Flush and withdrawal assessments were performed every 8 hours in lumens without continuous or pressurized infusions during the entire CVC dwell time in the ICU and the morning after transfer from the ICU. MO was defined as the inability to infuse or manually flush the lumen plus the inability to withdraw blood after position change and needleless access device change. A sample size of 684 lumens was estimated to detect a 5% difference in MO, assuming a 10% rate in the 0.9%NaCl group and a 2-sided alpha error of 0.05 at a power of 80%. Secondary outcomes included time to MO, as well as the rate and time to minor occlusion. Minor occlusion was defined as the ability to infuse or flush but not withdraw blood from the lumen. The use of alteplase to restore lumen functionality, heparin-induced thrombocytopenia (HIT), and catheter-related bloodstream infection (CR-BSI) were documented. Patients with at least 1 lumen with a minimum of 2 flushes were included in the analysis. Results: After applying exclusion criteria, 295 patients remained for analysis. Among these patients, 326 CVCs were studied yielding 709 lumens for analysis. The MO rate was 3.8% in the H group (n⫽314) and 6.3% in the 0.9%NaCl group (n⫽395) (RR 1.66, 95%CI 0.86-3.22, p ⫽ 0.136). The Kaplan-Meier analysis for time to first MO was not significantly different (p⫽0.321) between groups. The minor occlusion rate was similar between the H and 0.9%NaCl groups (22.3% v. 27.8%, p ⫽ 0.091). Alteplase was used in all 0.9%NaCl lumens and in 75% of H lumens with MO; all had restored patency. Two cases of HIT and 4 cases of CR-BSI were observed, all in the 0.9%NaCl group. Conclusions: In conclusion, 0.9%NaCl to flush CVCs is a safe practice eliminating the need for H flush and patient exposure to heparin.

G. Morgan Jones, Claire Murphy, Anthony Gerlach, Erin Goodman, Lindsay Pell, The Ohio State University Medical Center Introduction: Dexmedetomidine (DEX) is an ␣2-receptor agonist used for sedation in the intensive care unit (ICU). Although DEX is labeled for dosing up 0.7 mcg/kg/hr for ICU sedation, many recent studies have used more liberal dosing regimens. Based upon these studies, our academic medical center increased the maximum dose from 0.7 to 1.4 mcg/kg/hr. Hypothesis: We hypothesized that increasing the maximum dose of DEX would lead to a larger percentage of RASS scores at goal (⫺1 to⫹1) while maintaining a similar adverse effect profile to the standard dosing regimen. Methods: This retrospective study included patients who received DEX in medical, surgical, mixed medical/surgical, and cardiothoracic ICUs. A sample of patients treated prior to and all patients treated in the first five months after the change were included. Patients were included in the low dose (LD) group if their maximum dose was ⬍0.7 mcg/kg/hr, and in the high dose (HD) group if dosed ⬎0.7 mcg/kg/hr. Efficacy was determined by the percentage of RASS scores for each patient that were maintained at goal and safety was determined by the incidence of hypotension (MAP ⬍ 60 mmHg) and bradycardia (HR ⬍ 50 beats/minute). Results: Forty-three of the 133 included patients received high dose DEX. Patients in the LD group had a significantly higher percentage of RASS scores at goal (60.0% vs 48.6%; p⫽0.03), while patients in the HD group experienced a higher percentage of RASS scores classified as undersedated (RASS ⬎ ⫹1) than those in the LD group (4.9% vs 19.2%; p⬍0.05). Hypotension was the most common adverse effect (37.6%) among all patients; however, there was no difference in the incidence of hypotension or bradycardia between groups. Conclusions: Patients treated with higher doses of DEX had fewer RASS scores at goal. Our data suggests that increasing the dose of DEX does not lead to enhanced efficacy nor does it increase the incidence of adverse effects. Thus, patients who have not achieved goal sedation at doses ⬍0.7 mcg/kg/hr may not respond if the dose is increased.


760 EARLY VASOPRESSIN APPLICATION IN SHOCK ( EVAS ) Sandro Oliveira, Albert Schweitzer State Hospital Introduction: During the last decade, the use of vasopressin in shock, especially septic, became more frequent when relying on clinical evidence. Hypothesis: This study is looking into the hypothesis of vasopressin compared with norepinephrine would decrease the severity of septic status and mortality among patients with septic shock. Methods: In this randomized, double-blind study, we assigned patients who needs vasopressors and separeted to receive norepinephrine (0,05 to 2,0 ␮g /kg/min) or vasopressin ( 0.01 to 0.03 U/min) with low-doses of norepinephrine. Both groups had the vasoactive drugs infusions titrated and tapered to maintain a target blood pressure. Results: A total of 218 patients underwent randomization but 193 patients were included in this study ( 99 patients received vasopressin, and 94 received norepinephrine only ). The total time of vasopressors was 37 hours and 68 hours in the vasopressin and norepinephrine groupswith P⫽0,02. Referring to single organ dysfunction and multiple organ dysfunction using vasopressin and norepinephrine respectively(27,3% vs 54,3%, P⫽0,03 ; 13,1% vs 27,7%; P⫽0,02 ). The length of stay in ICU was 13 and 19 days ( P⫽ 0,03 ) and time of hospitalization was 21 and 34 days ( P⫽0,11 ) respectively. There was a significant difference between the vasopressin and norepinephrine groups in the mortality rate of 14 and 28 days ( 25,3% vs 34%, P ⫽ 0.005; 29,3% and 43,6%, P⫽0,02) however in 07-day mortality there were no significant differences in the overall rates (21,2% vs 23,4%, respectively; P ⫽ 1,0 ). Conclusions: Early application of vasopressin reduced time of vasopessors use, progression to multiple organ dysfunction, length of stay in ICU, mortality rates in 14 and 28 days as compared with norepinephrine only. This observed difference can be attributed to early restoration of tissue perfusion in the control group making the state of septic shock shorter and reducing the potential for multiple organ dysfunction that directly influenced patient survival.



762

THERAPEUTIC ANTICOAGULATION WITH ENOXAPARIN IN OBESE PATIENTS

EVALUATION OF THE IMPACT OF A CHANGE IN TARGET BLOOD GLUCOSE RANGE IN CRITICALLY ILL PATIENTS RECEIVING INTRAVENOUS INSULIN AT A LARGE ACADEMIC MEDICAL CENTER

Stephanie Edwin, St. John Hospital and Medical Center, Jace Nielson, Ann Arbor Pharmacometrics Group, Varsha Mehta, Michael Dorsch, Cesar Alaniz, University of Michigan Introduction: Patients with extreme body weight measurements are often excluded from clinical trials, yet have been noted to experience higher rates of bleeding in post-marketing studies. The goal of this study is to evaluate peak anti-factor Xa levels in obese and non-obese patients receiving therapeutic anticoagulation with enoxaparin. Hypothesis: Supratherapeutic anti-factor Xa levels will be more prevalent in obese patients compared to patients with a lower total body weight. Methods: This retrospective, cohort study approved by the institutional review board at the University of Michigan was designed to further evaluate the pharmacodynamic properties of enoxaparin in obese and non-obese patients. All anti-factor Xa levels drawn during an inpatient hospital admission from January 1, 2006 – October 31, 2009 were evaluated. Patients who were pregnant or receiving renal replacement therapy were excluded. All remaining anti-factor Xa levels drawn 3 to 5 hours following an enoxaparin dose were deemed appropriate for study inclusion (n⫽89). Anti-factor Xa levels ⬎ 1.0 unit/mL were designated as supratherapeutic. Results: The mean weight of patients who had serum antifactor Xa levels ⬎ 1.0 was significantly greater than those with levels ⬍ 1.0 (102.1 ⫹ 31.8 kg vs. 83.3 ⫹ 33.3 kg, respectively, p ⫽ 0.021). Other variables associated with supratherapeutic anti-Xa levels included advanced age (56.1 ⫹ 12.2 years vs. 46.7 ⫹ 19.0 years, p ⫽ 0.009) and time to peak level from previous dose (3.9 ⫹ 0.6 hours vs 4.1 ⫹ 0.5 hours, p ⫽ 0.023). There was no significant difference between groups with respect to serum creatinine (0.93 ⫹ 0.3 mg/dL vs. 0.87 ⫹ 0.3 mg/dL, p ⫽ 0.46) or the enoxaparin weight-based dose (1.0 ⫹ 0.2 mg/kg vs 1.0 ⫹ 0.2, p ⫽ 0.58). Lastly, evaluation of all anti-factor Xa levels within the therapeutic range, stratified by patient weight, showed those ⬎ 90 kg had a significantly lower weight-based dose (0.89 ⫹ 0.21 mg/kg) compared to those ⬍ 90 kg (1.0 ⫹ 0.12 mg/kg), p ⫽ 0.022. Conclusions: Dosing of enoxaparin for therapeutic anticoagulation should not be based on actual body weight in obese patients.

John Allen, Maresa Glass, Earnest Alexander, Tampa General Hospital Introduction: In light of previously published studies evaluating the impact of tight blood glucose (BG) control in critically ill patients and the ongoing debate over the ideal blood glucose range, institutional adjustments were made to the target blood glucose range in patients receiving intravenous (IV) insulin in the intensive care unit. The target BG was modified from 80-120 mg/dL to 90-150 mg/dL. Hypothesis: We sought to assess the impact of a change in target BG range expecting a reduced incidence of low BG post-intervention in patients receiving continuous infusion IV insulin at a large academic medical center. Methods: This study was designed as a retrospective cohort study involving chart review and data obtained from a computer database, over a 60 day period pre and post-intervention. The primary outcome is mean BG compared pre and post-intervention. Secondary outcomes include number of point-of-care (POC) readings within target range, incidence of hypoglycemia (POC ⬍60 mg/dL), incidence of hyperglycemia (POC ⬎200 mg/dL), number of patients requiring IV dextrose to alleviate hypoglycemia and time to goal glucose range and number of POC measurements per patient. Results: Our study included a total of 286 patients (n⫽155, pre-intervention, n⫽131, post-intervention). The primary outcome, mean BG,was similar in the pre and post-intervention groups (132.3 mg/dL vs 140.2 mg/dL). Additional findings included a higher percentage of readings within target range (54.3% vs 74.1%), a lower percentage of hypoglycemic POC (0.73 % vs 0.26%), and fewer patients with at least one hypoglycemic reading (20.7% vs 9.9%) in the post-intervention group. Hyperglycemic POC readings were similar between groups (5.8% vs 7.2%). The percent of patients requiring IV dextrose to manage hypoglycemia was lower in the post-intervention group (20% vs 9.1%). Time to goal and number of POC measurements were also similar amongst the groups. Conclusions: Our findings describe the efficacy and safety associated with widening a tight BG target range that is more consistent with the NICE-SUGAR study. Patients in the post-intervention group achieved similar mean BG values and had lower incidence of hypoglycemia compared to pre-intervention patients.

763

764

EARLY USE OF VASOPRESSIN IN THE TREATMENT OF SEPTIC SHOCK AND FACTORS PREDICTING PROLONGED VASOPRESSIN DEPENDENCY

PKPD MODELS FOR BIVALIRUDIN INFUSION IN POSTCARDIAC SURGICAL PATIENTS: COMPARISON OF LINEAR, NON-LINEAR, AND ADAPTIVE MODELS

Heather Personett, Joanna Stollings, Lance Oyen, Mayo Clinic

Thomas Edrich, James Rawn, Gyorgy Frendl, Brigham and Women’s Hospital/ Harvard Medical School

Introduction: Prolonged vasopressor use has been linked with poor clinical outcomes, including higher mortality. Hypothesis: The objective was to identify characteristics that may be predictive of prolonged vasopressin (AVP) use for seven or more days in patients treated for septic shock. Methods: This was a retrospective nested cohort analysis of adult patients receiving AVP as initial hemodynamic support, either alone or in combination with norepinephrine (NE), at Mayo Clinic (Rochester, Minnesota) between October 1, 2008 and March 30, 2010. One-hundred sixty-eight patients were included, 23 of whom required AVP for 7 or more days. Results: Mean AVP days were 1.8 in the short therapy group and 9.1 in the extended therapy group (p ⬍0.001). The extended therapy group also required NE for a longer time period (4.8 vs. 1.4 days, p ⬍0.001). Nested patients had significantly higher acuity of illness scores, including a mean APACHE II of 26.9 vs. 22.7 (p⫽ 0.004). Groups were comparable with regard to fluid-resuscitation, adherence to early goal directed therapy, timely and appropriate antibiotics, corticosteroid and drotrecogin alfa use. Statistical analysis included the student t-test, chi-squared and Fisher’s exact test. Univariate risk factors predictive of patients requiring extended AVP support were peripheral vascular disease (PVD) (48% vs. 18%, p⫽ 0.001), congestive heart failure (30% vs. 12%, p⫽ 0.024) and acute kidney injury (AKI) (83% vs. 49%, p⫽ 0.003) on admission to the intensive care unit (ICU). They more frequently experienced a new ICU arrhythmia on AVP therapy (39% vs. 7%, p ⬍0.001) and had higher 28-day mortality (74% vs. 20%, p ⬍0.001). Multivariate logistic regression revealed the strongest independent predictors of prolonged AVP dependence were new ICU arrhythmia (OR 5.3, CI 1.6-17.8), PVD (OR 4.3, CI 1.4-13.1) and AKI (OR 3.9, CI 1.1-14.5). Conclusions: Patients with pre-existing PVD and AKI, as well as those experiencing a new ICU arrhythmia on AVP may be more likely to remain on AVP for seven or more days.

Introduction: Bivalirudin is a direct thrombin inhibitor that is known to decrease thrombo-embolic complications due to heparin-induced thrombocytopenia. It requires dose reduction for renal dysfunction. Although it is FDA-approved for catheter interventions only, it is increasingly used for prolonged anticoagulation. Hypothesis: Response of the patient to bivalirudin infusion over several days can be predicted more accurately using a non-linear PKPD model that takes changing renal function into account, than with a linear PKPD model. Also, an adaptive component that slowly adjusts for previous errors will improve model performance. Methods: In a retrospective chart review of 149 post-cardiac surgical ICU patients, the coagulation parameters, PTT and INR, the estimated GFR (eGFR), blood product use, and the continuous infusion rate of bivalirudin was collected. After randomly assigning subjects to a derivation and a validation cohort, four PKPD models (linear, adaptive linear, non-linear, and adaptive non-linear) were fitted to the derivation data resulting in coefficients which were averaged. The non-linear PKPD models incorporate variable eGFR while the linear models do not. The optimized models were then tested in the validation cohort. Results: In the derivation and validation cohorts of 74 and 75 patients, respectively, the average duration of bivalirudin infusion was similar at 15.8 and 14.4 days and was weight-based. For PTT, the root-mean-square errors and Pearson’s correlation coefficients (in brackets) between the actual and model results were 22.0 (0.57), 13.0 (0.58), 21.4 (0.55), and 13.3 (0.54) seconds for the linear, adaptive linear, non-linear, and adaptive non-linear models, respectively. The correlation coefficients for the INR models ranged from 0.27 to 0.34. Conclusions: The prediction of PTT response to bivalirudin is greatly improved when the model includes an adaptive component which reflects inter-individual variability and also compensates for changing intra-individual sensitivity during prolonged infusion. The addition of a non-linear component accounting for changing eGFR did not improve accuracy. The INR response to bivalirudin was difficult to predict with these models.


765 TREATMENT OF INTRAOPERATIVE WITH INTRAVENOUS EXENATIDE

766 HYPERGLYCEMIA

VANCOMYCIN PHARMACOKINETICS (PK) AND DOSING REQUIREMENTS IN NEUROLOGICALLY INJURED PATIENTS

Benjamin Kohl, Mary Hammond, University of Pennsylvania, Stanley Schwartz, Presbyterian Medical Center, Andrew Ochroch, University of Pennsylvania

Christine Lesch, NewYork-Presbyterian Hospital, Raymond Gachette, New York University Hospital, Christine Kubin, Kelly O’Neil, NewYork-Presbyterian Hospital, Neeraj Badjatia, Columbia University Medical Center

Introduction: Intraoperative hyperglycemia has been associated with long-term morbidity and mortality. The current investigation evaluated the efficacy of an incretin-based strategy in the perioperative setting. Hypothesis: Treatment with intravenous Exenatide would maintain intraoperative euglycemia (60 - 125 mg/ dL) in subjects with initial blood glucose ⬍ 126 mg/dL and would establish intraoperative euglycemia in subjects with initial blood glucose ⱖ 126 mg/dL by 150 minutes. Methods: Randomized, double-blind, placebo-controlled. After IRB approval, non-insulin dependent diabetic and non-diabetic subjects undergoing carotid endarterectomy, AAA, esophagectomy, nephrectomy, or cardiac surgery were randomized to receive placebo, low-dose (0.27 ng/kg/min), or highdose (0.41 ng/kg/min) Exenatide. Blood glucose was determined pre-infusion, and every 30 minutes after. The infusion was discontinued upon placement of bandages. Planned enrollment was 100 patients with an a priori unblinding and analysis after completion of 30 patients. Results: 30 patients were included for analysis (10 placebo, 11 low-dose, 9 high-dose). In the cardiac surgery population (n⫽12), the median glucose at 150 minutes was 182 mg/dL (placebo), 167 mg/dL (low-dose), 131 mg/dL (high-dose); p⫽NS. For non-cardiac surgical patients (n⫽18), the median glucose at 150 minutes was 192 mg/dL (placebo), 122 mg/dL (low-dose), 152 mg/dL (high-dose); p⫽NS. For all surgical patients with a pre-infusion glucose ⬍ 126 mg/dL, the median glucose at 150 minutes was 192 mg/dL (placebo), 142.5 mg/dL (low-dose), 137 mg/dL (high-dose); p⫽NS. For those with a pre-infusion glucose ⱖ 126 mg/dL, the median glucose at 150 minutes was 186 mg/dL (placebo), 109 mg/dL (low-dose), 166 mg/dL (highdose); p⫽NS. There were no episodes of hypoglycemia (ⱕ 60 mg/dL) and no adverse events in any group. Conclusions: There was a trend toward improved glycemic control in both Exenatide groups. As there were no adverse events, this appears to be a safe and potentially efficacious therapy for intraoperative glycemic control. These data were reviewed by the data safety monitoring board and it was recommended that the trial continue.Source of Funding: Amylin Pharmaceuticals

Introduction: There exists a lack of data in the treatment of critically ill patients to recommend optimal vancomycin dosing. Several studies suggest higher than standard doses (30 mg/kg/day) in neurologically injured patients to achieve adequate levels. Hypothesis: Patients with acute neurological injury may require higher than standard doses of vancomycin to achieve target trough concentrations. Methods: A retrospective, single center, observational study was conducted from August 2009 to March 2010 in adult patients admitted to the NYPH Neuro-ICU. Inclusion criteria included receipt of at least 4 doses of vancomycin and availability of vancomycin trough and post dose levels. Exclusion criteria included pregnant females, as well as those with unstable renal function, renal failure (CrCl ⬍ 30 ml/min) or receiving renal replacement therapy. Results: Eighteen patients were evaluated. Forty four percent of patients were male with a median age of 59 years (25-83 years). The median APACHE II score was 21 (11-38), median glascow coma score was 5 (3-15), 50% had external ventricular drains, and 94% had CrCl ⬎ 50 ml/min. Initial vancomycin dose was a median of 27.5 mg/kg/day (11-37.7) of actual body weight. Median PK parameters were ke⫽0.136 hr-1 (0.041¬-0.35), t1/2⫽5 (2-17), Vd⫽0.75 L/kg (0.29-1.48) compared to population estimates of ke⫽0.081 (0.049-0.178), t1/2⫽7 (6-8), Vd⫽0.7 L/kg (0.5-1). Twelve patients attained their goal trough, doing so with a median dose of 36.6 mg/kg/day (20.7-88.2). In patients with CrCl ⬎ 100, 50-99, and 30-49 ml/min, the median dose requirement was 47.4 (31.2-88.2), 30.7 (22.4-68.9), and 29.9 mg/kg/day, respectively Patients with CrCl ⬎ 100 ml/min and a diagnosis of subarachnoid hemorrhage(n⫽2) required a median dose of 59.7 (31.2-88.2) mg/kg/day to achieve their desired trough. Conclusions: Evaluation of current practice in neurologically-injured patients indicates potential subtherapeutic initial dosing. The higher end of the NYPH recommended dose range (15 mg/kg q 8 hours) may be more appropriate to achieve goal trough levels in this population when the CrCl ⬎ 100 ml/min.

767

768

AMIKACIN PHARMACOKINETICS DURING CONTINUOUS VENO-VENOUS HEMODIALYSIS

EVALUATION OF A POST-OPERATIVE WEIGHT-BASED HEPARIN DOSING PROTOCOL FOR VENTRICULAR ASSIST DEVICE AND ARTIFICIAL HEART VALVE RECIPIENTS

Simon Lam, Seth Bauer, Cleveland Clinic Introduction: Critically ill septic patients are frequently treated with broad spectrum antibiotics including amikacin. Patients with septic shock and renal failure may also require continuous renal replacement therapy (CRRT). A thorough search of the literature revealed less than 10 cases of reported amikacin pharmacokinetic (PK) parameters during CRRT. Hypothesis: We hypothesized that patients receiving continuous veno-venous hemodialysis (CVVHD) have unique amikacin PK which may have significant therapeutic implications. Methods: This prospective observational study included patients admitted to a medical intensive care unit of a tertiary care academic medical center who received amikacin therapy while on CVVHD. Patients with at least two amikacin serum sample concentrations measured after a dose of amikacin were included in the study. First order pharmacokinetic was assumed and estimations of the peak concentration (Cmax), volume of distribution(Vd), elimination constant (Kel), clearance (Cl), and terminal half-life (t1/2) were performed. Patient characteristics and CVVHD parameters including machine, filter, effluent, and dialysate flow rates were recorded. Results: Fifteen patients were included in the analysis. The median (range) dose of amikacin and dialysate flow rate, based on actual body weight, were 11.4mg/kg (6.7-17.1) and 23.4 mL/kg/hr (12.8-31.2), respectively. This corresponded with a median Cmax of 28.5 mcg/mL (17.4-89.5). The Vd, Cl, and t1/2 were 0.39 L/kg (0.18-0.63), 2.2 L/hr (0.75-5.7), and 12.7 hr (5.1-20.6), respectively. Correlation analyses did not find any significant relationship between any PK parameters and dialytic dose. Similar analyses also did not find any relationship between PK parameters andtype of CVVHD hemofilter. Conclusions: A wide range of amikacin PK parameters were observed during CVVHD therapy. This would suggest that amikacin dose and interval should be individualized for each patient based on first dose pharmacokinetics. A median amikacin dose of 11.4 mg/kg of actual body weight generated a projected Cmax below usual targeted peak amikacin concentrations.


Ann Marie Prazak, Amanda Walker, Robert Pendleton, Craig Selzman, Joseph Stehlik, Erin Davis, Cathyyen Dang, University of Utah Hospitals and Clinics Introduction: No standard for anticoagulation following implantation of ventricular assist devices (VAD) or artificial heart valves currently exists, resulting in center-specific anticoagulation protocols. Hypothesis: We hypothesized that a weight-based heparin dosing protocol (initiation rate: 6 units/kg/hr) targeting an aPTT goal of 40 to 60 seconds would decrease bleeding events and prevent thromboembolic complications post-operatively. Methods: We developed and implemented a continuous infusion unfractionated heparin protocol (Cardiothoracic Surgery Heparin Protocol). In this descriptive case series, data collection occurred one year prior to protocol implementation to establish an historical evaluation of heparin use and one year after to evaluate efficacy and safety of the protocol. Results: Fifty adult patients (pre-protocol, n⫽23) who were recipients of either a ventricular assist device (n⫽25) or artificial heart valve and initiated on a continuous infusion heparin drip from July 1, 2008 to July 31, 2010 were included in the study (age: 26-84, 66% male, mean BMI: 29.7). Median time to achieve goal aPTT, defined as two consecutive aPTT values within target range, was 16 hours for the pre-protocol group and 6 hours for the post-protocol group. Prior to the protocol, 58% of aPTT values were within target range compared to 69% of aPTT values following the protocol. There were 5 minor bleeding events, 17 major bleeding events, and 3 thromboembolic events prior to the protocol compared to 1 minor bleeding event, 6 major bleeding events, and 1 thromboembolic event after protocol implementation. Conclusions: Heparin initiated at an infusion rate of 6 units/kg/hr and adjusted to an aPTT level of 40 to 60 seconds decreased time to achieve target aPTT and provided a greater percentage of aPTT values in goal. Fewer bleeding and thromboembolic events were observed following implementation of the Cardiothoracic Surgery Heparin Protocol.

769 COMPARISON OF NEW VANCOMYCIN DOSING REGIMEN VS TRADITIONAL IN A TERTIARY PEDIATRIC HOSPITAL INTENSIVE CARE UNIT Kelli Crowley, University of Pittsburgh Medical Center Introduction: Evaluation of new vancomycin dosing regimen derived from 2009 Infectious Diseases Society of America, American Society of Health-Systems Pharmacists and Society of Infectious Diseases Pharmacists consensus recommendations initiated at Childrens Hospital of Pgh of UPMC and compare to traditional dosing for achievement of therapeutic trough levels, efficacy and toxicity in the Pediatric Intensive Care Unit (PICU) population. Hypothesis: New dosing regimen will achieve therapeutic levels and improve outcomes without increasing toxicity. Methods: Retrospective analysis of dosing strategy, trough values, clinical improvement and toxicity for all initial courses of vancomycin in the PICU over 6 week period. Charts reviewed for age, weight, serum creatinine (SCr)/calculated creatinine clearance (CrCl)/urine output days 1 and 3, dosing regimen, steady state trough level, culture results, concurrent nephrotoxic agents and treatment outcomes. Conclusions based on achievement of trough range 8-15mcg/ml, nephrotoxicity (SCr increase of 50% or urine output decrease to ⬍1 ml/kg/hr) and improved clinical status/sterile cultures. Results: 80 patients were ordered vancomycin in the PICU. 45 received the new regimen:60mg/kg/ day (45mg/kg/day if renal dysfunction/other nephrotoxic agent) for ages 1 month-12 years and 40-45mg/kg/day if ⬎12years; 20 persons received traditional(40mg/kg/day); 15 had alternative dosing/renal dosing/no levels. In the new dosing cohort 16(35.6%) achieved therapeutic level while 27(60%) were below and 2 were beyond. Further stratification by age yielded similar percentages. In the traditional dosing group 40% had values in the target range, 40% were suboptimal and 4 were above. 5 persons with suboptimal values in the traditional cohort were escalated to the new regimen with 3 achieving therapeutic levels. There were no detectable treatment failures or differences in adverse events between cohorts. Conclusions: There appears to be no difference between new and traditional regimens. Both resulted in similar rates of attaining therapeutic levels with no difference in outcomes or adverse events. Further dosing escalation will be essential to achieve therapeutic levels in the PICU population.



771

HYPERTONIC SALINE AND MANNITOL ARE EFFECTIVE IN LOWERING ELEVATED INTRACRANIAL PRESSURE IN PEDIATRIC PATIENTS WITH TRAUMATIC BRAIN INJURY

CONTINUOUS INFUSION VANCOMYCIN IN NEONATES ON EXTRACORPOREAL MEMBRANE OXYGENATION

Carolyn Ragsdale, Leah Hatfield, Children’s Healthcare of Atlanta, Traci Leong, Emory School of Public Health, Atul Vats, Emory University School of Medicine and Children’s Healthcare of Atlanta

Introduction: Current literature advocates vancomycin trough levels of 15 – 20 mcg/mL for certain therapeutic situations which is not consistently achieved with current intermittent neonatal vacomycin dosing recommendations. There is limited information regarding continuous infusion doses for vancomycin in neonatal patients on extracorporeal membrane oxygenation (ECMO) support. Hypothesis: The objective of this study was to determine a vancomycin continuous infusion (VCI) dose that will result in a plateau level of 15-20 mcg/mL for neonates on ECMO. Methods: This was retrospective chart review from November 1, 2001 through July 30, 2010. Neonates that were ⱖ 38 weeks gestational age (GA) and received intermittent vancomycin for ⱖ 48 hours while on ECMO with at least 2 serum vancomycin concentrations were eligible for inclusion. Vancomycin serum concentrations were plotted against time, and individual pharmacokinetic (PK) parameters were determined by a one-compartmental analysis and used to estimate population PK parameters. Results: There were a total of 16 ECMO patients that met the inclusion criteria. The median post-natal age was 8.5 days (range 2 -31 days). The mean vancomycin elimination rate constant was 0.130 ⫾ 0.04 hrs-1. The mean vancomycin volume of distribution was 2.08 ⫾ 0.65 L/kg. A starting dose of 12 mg/kg/dose IV q6h or 18 mg/kg/dose IV q8h would achieve vancomycin serum trough concentrations between 15-20 mcg/mL. Dose (mg/ kg/hour) Vancomycin Plateau Level (mcg/mL) 4.5 16.5 5 18.4 5.5 20.2 6 22.1 6.5 23.9 7 25.7 Conclusions: Neonatal PK data suggests a VCI dose between 4.5-5.5 mg/kg/hr would obtain a vancomycin plateau level between 15-20 mcg/mL for term neonates on ECMO. This dose needs to be validated in a prospective study.

Introduction: Hypertonic saline (HS) and mannitol (MAN) are both considered effective pharmacologic treatment options for reducing elevated intracranial pressure (ICP) in traumatic brain injury (TBI). No studies have provided evidence to prove one therapy as more effective. The purpose of this study is to retrospectively compare the effectiveness of HS and MAN when used in pediatric TBI. Hypothesis: HS and MAN have beneficial effects on ICP and CPP. Methods: This is an IRB approved retrospective review utilizing the electronic medical record (EMR) at Children’s Healthcare of Atlanta. Patients were included if admitted to the pediatric intensive care unit (PICU) between 9/1/2008 and 12/31/2009 with TBI, had documented administrations of HS or MAN bolus doses, and had an invasive ICP monitor. Patients that received both HS and MAN were not included. When documented in the EMR, ICP and CPP were recorded prior to the administration of each dose of HS or MAN and then each hour thereafter for up to six hours or until a subsequent dose of HS or MAN was given. The time of the additional dose was noted. Results: 32 patients met inclusion criteria. Patients were categorized based on their treatment: HS or MAN. 21 patients received HS for a total of 131 doses. Five patients received MAN for a total of 13 doses. For the HS group, the changes in ICP and CPP were statistically significant at hours 1 through 6 (p⬍0.05). For the MAN group, the change in ICP was statistically significant at hours 2, 3, and 5 (p⬍0.05), with no significant change in CPP. 58% of HS doses required an additional dose at an average of 2.3 hours. 21% of MAN doses required an additional dose at an average of 4.7 hours. Conclusions: HS demonstrated significant and sustained beneficial effects on ICP and CPP. MAN demonstrated significant and sustained beneficial effects on ICP. Patients that received MAN required a subsequent dose less often, and later than patients that received HS.

Jeffrey Cies, St. Christopher’s Hospital For Children

772

773

NEONATAL VANCOMYCIN DOSING ON EXTRACORPOREAL MEMBRANE OXYGENATION

COMPARISON OF METHODS FOR ESTIMATING VANCOMYCIN ELIMINATION RATE CONSTANT IN CRITICALLY ILL ADULTS

Jeffrey Cies, St. Christopher’s Hospital For Children Introduction: Pharmacokinetic (PK) parameters such as the volume of distribution (Vd) and clearance can be significantly altered for individuals on extracorporeal membrane oxygenation (ECMO). Current literature advocates vancomycin trough levels of 15-20 mcg/mL for certain therapeutic situations, which is not consistently achieved with current neonatal dosing recommendations. There is limited information regarding intermittent dosing to achieve vancomycin serum trough concentrations (Vt) of 15-20 mcg/ml in neonatal patients on ECMO. Hypothesis: The objective of this study was to determine an intermittent vancomycin dose to achieve Vts between 15-20 mcg/mL. Methods: This was retrospective chart review from November 1, 2001 through July 30, 2010. Neonates that were ⱖ 38 weeks gestational age and received intermittent vancomycin for ⱖ 48 hours while on ECMO with at least 2 Vts were eligible for inclusion. Individual PK parameters were determined by a one-compartmental analysis and used to estimate population PK parameters. Results: There were 16 ECMO patients that met the inclusion criteria. The median post-natal age was 8.5 days (range 2 -31 days). The mean elimination rate constant was 0.130 ⫾ 0.04 hrs-1. The mean Vd was 2.08 ⫾ 0.65 L/kg. A starting dose of 12 mg/kg/dose IV q6h or 18 mg/kg/dose IV q8h would achieve Vts between 15-20 mcg/mL. Different intermittent vancomycin doses are displayed in table 1 with the resulting troughs; Dose Interval Trough(mg/kg) (hrs) (mcg/mL)11 6 15.712 6 17.213 6 18.714 6 19.917 8 15.618 8 16.519 8 17.420 8 18.3 Conclusions: Neonatal population PK data suggests an intermittent vancomycin dose of 12 mg/kg/dose IV q6h or 18 mg/ kg/dose IV q8h would obtain a Vts between 15-20 mcg/mL for term neonates on ECMO. These doses need to be validated in a prospective study.


Christopher Burke, James McMillen, Anthony Rowe, University of Tennessee Medical Center Introduction: At our institution pharmacists use both peak (Cpk) and trough (Ctr) vancomycin concentrations to individualize therapy by calculating twopoint patient specific pharmacokinetic (PK) parameters. Hypothesis: In a critically ill adult population, elimination rate constant (Ke) calculated using Cpk and Ctr will differ from Ke calculated using only Ctr and a population volume of distribution (Vd). Methods: An IRB approved, retrospective study of adults ⱖ18 years old who received IV vancomycin while admitted to the ICU. Patients were included if at least one Cpk and one Ctr were available. Patients were excluded if their SCr changed ⬎50% during therapy, or for the presence of renal insufficiency at vancomycin initiation. Ke was calculated two ways: (1) using two-point PK, requiring Cpk and Ctr to calculate Vd, and (2) using iterative PK, requiring Ctr and a population Vd⫽0.7L/kg. Ke calculated by methods (1) and (2) was compared using an independent samples t-test. Using an anticipated effect size of 0.69, 70 patients total were required to detect a significant difference in Ke, to satisfy 80% power with a two-sided ␣⫽0.05. Results: Overall, 134 patients were included, with 68 from the medical ICU and 66 from the trauma/surgical ICU. Mean SCr was 0.80⫾0.3mg/dL, with a mean CrCl of 93⫾25mL/min. Actual (88.4⫾26.7kg) and ideal body weight (66.1⫾11.3kg) were similar overall (p⫽0.11). Mean total daily dose was 2661⫾973mg, producing a mean Cpk⫽34.4⫾11.1mg/L and mean Ctr⫽10.9⫾5.4mg/L. There were significant differences in Ke calculated by methods (1) and (2) in the entire population (Ke1⫽0.118⫾0.05/hr vs. Ke2⫽0.095⫾0.04/hr, p⬍0.0001), in the medical group (Ke1⫽0.106⫾0.05/hr vs. Ke2⫽0.087⫾0.03/hr, p⫽0.007), and in the trauma/surgical group (Ke1⫽0.131⫾0.06/hr vs. Ke2⫽0.104⫾0.04/hr, p⫽0.002). Conclusions: Values for Ke were significantly higher when estimated using patient specific PK as compared to population PK. Reliance on population PK in adult critically ill patients could underestimate vancomycin Ke, potentially leading to underdosing. Monitoring of Cpk should be considered in this population. Future research should evaluate the impact of methods of Ke calculation on subsequent Ctr attainment and patient outcomes.

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EFFECT OF THERAPEUTIC HYPOTHERMIA ON THE PHARMACOKINETICS OF MIDAZOLAM IN CARDIAC ARREST SURVIVORS

EFFICACY OF SEMIQUANTITATIVELY MEASURED SERUM PROCALCITONIN AS A MEASUREMENT TO GUIDE CESSATION OF ANTIBIOTIC THERAPY

David Seder, Richard Riker, Laurel Libby, Maine Medical Center, Samuel Poloyak, University of Pittsburgh, Tracy Robbins, Maine Medical Center, Thomas Nolin, University of Pittsburgh

Tomoki Wada, Akiyoshi Hagiwara, Takunori Sato, Aki Inaka, Akio Kimura, National Center for Global Health and Medicine

Introduction: Several preclinical and clinical studies demonstrate that drug metabolism is impaired during therapeutic hypothermia (TH). Midazolam (MDZ) is commonly used in cardiac arrest patients and requires hepatic metabolism by cytochrome P450 3A. In order to determine if the metabolism of MDZ is altered we assessed the pharmacokinetics of MDZ administered orally (PO) and intravenously (IV) during TH and after rewarming in cardiac arrest survivors. Hypothesis: We hypothesized that TH in the post-arrest state would decrease MDZ elimination. Methods: Six patients participated in this open-label study after receiving informed consent from the medical power of attorney. Eight hours after achieving the goal temperature of 32-34°C, MDZ 2 mg was administered via orogastric tube, followed 4 hours later by MDZ 1mg IV. Serial blood samples for PK analysis were collected after both oral and IV doses. After 18 hours of cooling, subjects were rewarmed over 6 hrs to ⬎36°C. The MDZ dosing and sampling regimens were repeated 24 hrs after rewarming. Plasma MDZ and metabolite levels were determined by LC-MS/MS, and PK parameters were calculated by noncompartmental methods. Results: One subject died after completing the initial PK assessment. No statistically significant differences in PK parameters were observed in this preliminary analysis. However, we observed a trend toward delayed absorption with a ⬃3 fold greater median time to maximum concentration in the hypothermic (97 ⫾ 64 min) versus normothermic (31 ⫾ 21 min) period. Furthermore, a trend towards decreased 1-OH-MDZ area under the plasma concentration time curves was observed in the hypothermic versus normothermic periods after both PO (44% decrease) and IV (36% decrease) routes of administration. Conclusions: These preliminary findings suggest that enterally administered drugs may have delayed absorption during TH. These results also suggest that the formation of the 1-OH-MDZ metabolite may be decreased during TH after cardiac arrest. Future studies in a larger cohort of subjects are needed to confirm these observations.

Introduction: The recommended period of antibiotic therapy is from 7 to 10 days in the “Surviving Sepsis Campaign Guidelines 2008”. However, there are no definitive measurements to guide cessation of antibiotic therapy. Hypothesis: We examined whether semiquantitatively measured serum procalcitonin (PCT) help determine when to stop antibiotic therapy. Methods: Subjects were consecutive septic patients comprising: 1) those who admitted to our ICU, 2) those who were administered antibiotics for at least 4 days, and 3) those who stopped the antibiotics during their ICU stays.Patients were treated from July 2009 to April 2010 with reference to their serum PCT (PCT group). On the other hand, patients prior to June 2009 were treated without the PCT measurement (control group). In the PCT group, when PCT was below 0.5 ng /ml, we examined whether to stop antibiotic therapy. We compared the durations of antibiotic therapy and the values of WBC and CRP when the antibiotic therapy ended. Results: Both PCT and control groups had 38 patients. At baseline, both groups were similar regarding age, male / female, APACHE II scores, the ratio severe sepsis / septic shock, the ratio of non survivor and the focus of infection. Antibiotic therapy was significantly shorter in the PCT group than in the control group (7 (6 - 9) d versus 8 (7 - 17) d , p ⫽ 0.037). At the end of the antibiotic therapy, both groups were similar regarding WBC values (7060 (6100 – 9450) x103 /␮l versus 7810 (5980 – 9940) x103 /␮l , p ⫽ 0.427). On the other hand, CRP values were significantly higher in PCT group than in control group (7.1 (2.4 – 9.2) mg/dl versus 2.7 (1.6 – 6.8) mg/dl , p ⫽ 0.011). Readministraiton cases seemed to be higher in PCT group than in control group ( 4 vs 1 ).However, about two of four patients in PCT group, the focus of the second infection was different from the primary infection. Conclusions: Semiquantitative PCT measurements safely shorten the periods of antibiotic therapy for septic patients. PCT values were more appropriate to stop the antibiotic therapy.

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PHARMACOKINETIC AND CLINICAL EFFECTS OF D50W IN PATIENTS PRESENTING WITH HYPOGLYCEMIA

INTRAVENOUS ZANAMIVIR FOR CRITICAL ILLNESS DUE TO PANDEMIC H1N1 INFLUENZA

Evelyn Luo, Antonia Alafris, Bishoy Luka, Maricelle Monteagudo-Chu, Henry Cohen, Shakir Adewale, Mark Russell, Phillip Hew, Kingsbrook Jewish Medical Center

Judy Pham, Chris Rudd, Cameron Wolfe, Ira Cheifetz, David Turner, Duke University Medical Center

Introduction: In one study, the administration of 50 mL of D50W led to elevated blood glucose (BG) ranging from 37 to 379 mg/dL at 5 minutes post-dose. Another study showed that plasma glucose levels peaked at 5 minutes and returned to baseline at 30 minutes post-dose of 50 mL of D50W. The objectives of our study are to determine the clinical effects of D50W, the BG level increase from baseline post IV bolus of D50W at 5 and 30 minutes, and whether BG levels will be sustained at ⬎ 90 mg/dL at 30 minutes. Hypothesis: Different degrees of hypoglycemia (BG ⬍ 70 mg/dL) are inadequately managed with the standard treatment of 50 mL of IV D50W. Methods: From April to June 2010 all inpatients and emergency department patients with episodes of hypoglycemia were administered D50W 50 mL IV push over 3 to 5 minutes. A second and third set of BG levels were determined at 5 and 30 minutes post-infusion using the fingerstick method. Results: Twenty-one patients (mean age, 73 y/o) with 25 hypoglycemic episodes received 50 mL of D50W. The majority of patients were black females with diabetes mellitus and on insulin. The mean baseline hypoglycemic BG was 54 ⫾ 8.9 mg/dL (mean ⫾ SD). The mean post-D50W BG levels were 193 ⫾ 59 mg/dL at 5 minutes and 144 ⫾ 43.3 mg/dL at 30 minutes. Baseline BG levels were stratified into three groups: ⱕ 49 mg/dL (group 1), 50 –59 mg/dL (group 2), and 60 – 69 mg/dL (group 3). The amount of BG increase in group 1 (n ⫽ 8) was 131 ⫾ 80.3 mg/dL (5 min), 89 ⫾ 57.4 mg/dL (30 min); group 2 (n ⫽ 9) was 141 ⫾ 60.3 mg/dL (5 min), 84 ⫾ 41.3 mg/dL (30 min); and group 3 (n ⫽ 8) was 141 ⫾ 43 mg/dL (5 min) and 101 ⫾ 22.9 mg/dL (30 min). In 5 cases, BG dropped as low as 66 mg/dL after 30 min and two of these cases required additional doses of 50 mL of D50W. Conclusions: The mean total amount of BG increase after 50 mL of D50W were 138 ⫾ 58.2 mg/dL at 5 minutes and 91 ⫾ 41.7 mg/dL at 30 minutes. All hypoglycemic episodes normalized numerically and symptomatically within 5 minutes after one dose of 50 mL D50W. Although 80% of patients had sustained BG levels ⬎ 90 mg/dL at 30 minutes, frequent BG determinations are needed to prevent recurrence of hypoglycemia.

Introduction: Limited therapeutic options exist for the treatment of critically ill patients with influenza, including the pandemic H1N1 (pH1N1) subtype. Hypothesis: Intravenous (IV) zanamivir may offer a safe and effective alternative for critically ill children and adults who fail or are unable to tolerate oral oseltamivir therapy. Methods: Investigational IV zanamivir was administered on a compassionate use basis to patients who could not tolerate or failed oral oseltamivir therapy. World Heath Organization guidelines were used to define failure of oral oseltamivir in those patients who continued to have positive viral cultures and/or positive polymerase chain reaction for pH1N1 in the setting of worsening respiratory status. Results: Between October, 2009 – January, 2010, 5 patients were treated with IV zanamivir, 3 of whom required intensive care unit (ICU) admission. The ICU patients, aged 7, 33, and 39 years, had underlying co-morbidities which included obesity, hypoplastic left heart syndrome, and multiple myeloma. All 3 ICU patients required mechanical ventilation with a mean duration of 34 days (range 22-50d). Due to the severity of illness, 2 of these patients required Extracorporeal Membrane Oxygenation (ECMO) for durations of 308 and 662 hrs. One of the ECMO patients also required concomitant continuous renal replacement therapy (CRRT). Treatment with IV zanamivir ranged from 4-10 days and was at the discretion of the treating clinical team after failing at least 5 days of oral oseltamivir therapy. Of the 5 patients treated with IV zanamivir, there were no adverse events or changes in renal or hepatic function attributed to IV zanamivir. Each patient survived to hospital discharge. Conclusions: Five patients with severe pH1N1 influenza, including 3 critically ill patients requiring mechanical ventilation, CRRT, and ECMO, were successfully treated with IV zanamivir without complication. While limited, this experience supports the notion that IV zanamivir may be a safe and effective therapy for severe influenza infection. Investigation is warranted to further evaluate zanamivir and other IV antiviral agents as potential therapeutic options for severe influenza infection.


778 PROPRANOLOL AS A THERAPEUTIC OPTION OF INFANTILE LARYNGO-TRACHEAL HAEMANGIOMA: A TERTIARY PAEDIATRIC CENTRE’S INDEX EXPERIENCE OF THREE CASES Joel Meng Fai Chan, Melissa Anu, Henry Tan , Jan Hau Lee, Annette Ang, KK Women’s and Children’s Hospital Case Reports: Since the first reported observation of haemangioma regression in infants treated with propranolol in June 2008, several paediatric centres have reported the effective treatment of infantile haemangiomas with systemic propranolol. Current treatment options include steroids, interferon, vincristine, LASER and open surgery. All these are associated with significant adverse reactions and morbidity. Propranolol however, is proving to be an efficacious option with less severe adverse reactions.We describe our experience with the use of systemic propranolol in the treatment of 3 infants with symptomatic laryngo-tracheal haemangiomas. Their clinical progress was monitored from the time of admission to the time of discharge.All three children presented with significant airway obstruction requiring eventual intubation. They were between 1 and 3 months of age at presentation. 2 of the infants had concomitant mediastinal haemangioma, and 1 had cutaneous haemangioma. 1 of the children did not respond to previous treatment with systemic steroids and interferon at the referring hospital. They were treated with oral propranolol at an eventual dose of 2mg/kg/day. All 3 demonstrated significant improvement in the extent of their laryngeal haemangioma with propranolol (on serial microlaryngobronchoscopy). The cutaneous and mediastinal components of the haemangioma regressed as well. The infants were closely monitored in the ICU, with no significant side effects namely bradycardia, hypotension and hypoglycaemia.This study corroborates the efficacy of systemic propranolol in the treatment of infantile laryngeal haemangiomas. The ICU provided an optimum set-up for the management of infants with laryngeal haemangiomas with signifiicant airway obstruction, as well as the monitoring of potential adverse reactions to propranolol. References: C. Leaute-Labreze, E Dumas de la Roque et al: Propranolol for severe hemangiomas of infancy. New England Journal of Medicine 358 (June 24 2008) 2649-2651



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PHARMACIST MANAGED AMINOGLYCOSIDE MONITORING IN A PEDIATRIC INTENSIVE CARE UNIT LEADS TO IMPROVED TARGET LEVELS

PERIOPERATIVE AND PERIPROCEDURAL BRIDGING WITH EPTIFIBATIDE AFTER CLOPIDOGREL DISCONTINUATION

Jeffrey Cies, St. Christopher’S Hospital For Children, Venkat Shankar, Children’s National Medical Center

James Hollands, Barnes - Jewish Hospital, Eli Deal, Lee Skrupky, Barnes-Jewish Hospital, Richard Reichley, BJC

Introduction: Suboptimal treatment of infections among patients requiring intensive care unit (ICU) admission appears to be an important determinant of hospital mortality. Efforts must be made to optimize both the choice and dosing of currently available antibimicrobials (AM) to decrease morbidity and mortality. An optimal dosing strategy for an AM requires analysis of pharmacokinetic and pharmacodynamic (PK/PD) characteristics. With aminoglycosides (AG), the PK/PD parameter associated with efficacy is the peak to MIC ratio (peak:MIC). Early achievement of therapeutic serum AG concentrations is shown to improve clinical outcomes in gram-negative infections. This study evaluated whether there was an improved achievement of desired AG PK/PD parameters when a pharmacist was actively managing the therapeutic drug monitoring (TDM) and dosing in Pediatric ICU (PICU) patients. Hypothesis: AG PK/PD targets are achieved earlier and more frequently in children in PICU when a clinical pharmacist manages the TDM than with the conventional approach. Methods: Children in PICU who received an AG for at least 48 hours and had at least two serum AG levels obtained between January 2007 and August 2009 were eligible for inclusion. A 25% difference with an ␣ ⫽0.05 and a power of 80% could be detected with 40 treatment courses in each group. Chi-square and student’s t-test test was used to analyze nominal/ordinal and continuous variables, respectively. Results: There were 29 patients (65.5 % male) in the pharmacist (P) group and 35 patients (48.5% male) in the non-pharmacist (NP) group. The median age was 2 years and 1 year in the P and NP groups, respectively. The median weight was 13 kg and 9 kg in the P and NP groups, respectively. Twenty-nine of 29(100%) patients in the P group reached the AG PK/PD target compared with 11 of 35 (31%) in the NP group (␹2 ⫽ 31.8, p ⬍ 0.0001). Conclusions: Pharmacist managed TDM resulted in significantly improved achievement of PK/PD targets in children in PICU. Furthermore, patients attained AG PK/PD targets earlier than controls, which could improve clinical outcomes and reduce costs related to dosage adjustments and drug wastage.

Introduction: Withholding clopidogrel prior to a procedure or surgery after recent percutaneous coronary intervention (PCI) can place a patient at risk for developing stent thrombosis. Hypothesis: The purpose was to describe our experience with the use of eptifibatide infusion for antiplatelet activity in patients whose clopidogrel was held prior to a procedure/surgery . Methods: Inpatients at a large academic medical center from 2005-2008 with recent PCI who received eptifibatide as a bridge to diagnostic or surgical procedure after clopidogrel discontinuation were retrospectively analyzed. Patients were assessed for complications including evidence of myocardial ischemia (EKG changes, troponin elevations, anginal symptoms) and major bleeding (requiring ⱖ2 units of blood for transfusion for ⱖ2gm/dL drop in hemoglobin, or confirmed intracranial or retroperitoneal bleeds) occurring within 12 hours of discontinuing eptifibatide therapy. Results: Seventeen patients were included: 14 patients (82%) recently received drug-eluting stents, 3 had bare metal stents. Median time from PCI to clopidogrel discontinuation was 57 days (range, 2-210) and patients remained off clopidogrel for a median of 5 days (range 3-18). Six patients (35%) also had their aspirin discontinued. All patients received eptifibatide infusion at 2mcg/kg/min (adjusted for renal dysfunction) and 10 (59%) received bolus prior to infusion; median duration of infusion was 104 hrs (range 12-408). Most common procedures were CABG (n⫽4), tracheostomy (n⫽3), and invasive biopsy (n⫽2). None developed myocardial ischemia during eptifibatide infusion though 2 (12%) had mild isolated postoperative troponin elevations. No cases of stent thrombosis were observed. One patient (6%) had a bleeding event during the infusion requiring infusion cessation; an additional 4 patients (24%) were transfused 2 units of blood after surgery and within 12 hours of eptifibatide discontinuation. Conclusions: Eptifibatide bridging when clopidogrel discontinuation is required prior to a surgical or diagnostic procedure appears to be effective option for platelet inhibition. Following surgical intervention, patients should be monitored closely for signs of bleeding and myocardial ischemia.

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INTERMITTENT DOSING TO ACHIEVE HIGHER VANCOMYCIN TROUGH CONCENTRATIONS IN NEONATES

COMPARISON OF CREATININE CLEARANCE ESTIMATES IN CRITICALLY ILL SURGICAL PATIENTS

Jeffrey Cies, St. Christopher’s Hospital For Children

Anthony Gerlach, Ohio State University Medical Center, Claire Murphy, The Ohio State University Medical Center, Stanislaw Stawicki, Ohio State University Medical Center, Charles Cook, Ohio State University Hospitals

Introduction: Current literature advocates vancomycin trough levels of 15 – 20 mcg/mL for certain therapeutic situations. Standard neonatal vancomycin dosing regimens are not intended to obtain serum vancomycin trough concentration of 15-20 mcg/mL. Vancomycin is a time-dependent, bactericidal antibiotic, which correlates with the duration of bacterial exposure to the antibiotic. Hypothesis: The objective of this study was to determine an intermittent vancomycin dosing regimen that will result in serum vancomycin trough concentration of 15-20 mcg/mL. Methods: This was retrospective chart review from of January 1, 2007 through July 30, 2010. Patients admitted to the neonatal intensive care unit (NICU) that received intermittent vancomycin for ⱖ 48 hours with at least 2 serum vancomycin concentrations were eligible for inclusion. Patients were stratified into groups based on gestational age (GA) age; ⬎ 27 weeks GA (Y group), 28-32 weeks GA (M group), and ⬎ 32 weeks GA (O group). Vancomycin serum concentrations were plotted against time, and individual pharmacokinetic (PK) parameters were determined by a one-compartmental analysis. Individual PK data was used to estimate population PK parameters. Results: Thirty-eight patients met the inclusion criteria. There were 15, 12, and 11patients in the Y, M, and O groups, respectively. The median GA was 28.5 weeks (range 23 -41 weeks). The median post-natal age was 16 days (range 1-82 days). The mean elimination rate constant was 0.147 ⫾ 0.07 hrs-1, 0.19 ⫾ 0.13 hrs-1, and 0.18 ⫾ 0.07 hrs-1 in the Y, M, and O groups, respectively. The mean volume of distribution was 0.64 ⫾ 0.4 L/kg, 0.71 ⫾ 0.37 L/kg, and 1.6 ⫾ 0.6 L/kg in the Y, M, and O groups, respectively. Conclusions: Neonatal population PK data suggests an intermittent vancomycin dose of 10 mg/kg/dose IV q6h and 12-13 mg/kg/dose IV q6h would obtain serum vancomycin trough concentrations between 15-20 mcg/mL for neonates with a GA ⬍ 28 weeks and 28-32 weeks, respectively. For neonates ⬎ 32 weeks GA, a regimen of 15 mg/kg/dose IV q6-8h or 20 mg/kg/ dose IV q8h would obtain serum vancomycin trough concentrations between 15-20 mcg/mL. These doses need to be validated in a prospective study.

Introduction: Assessment of renal function and adjustment of renally eliminated drugs are fundamental tasks of critical care practitioners, especially pharmacists. Although serum creatinine (SCr) remains the primary biomarker, standard formulae for estimating clearance should not be used when SCr is not at steady state or in patients with oliguria or anuria. Previous studies have suggested that aminoglycoside pharmacokinetics may accurate predictors of renal function in critically ill but the optimal estimate is unknown. We therefore compared standard formulae and 24-hr urine creatinine collection to aminoglycoside estimates of creatinine clearance (CrCl) in surgical ICU (SICU) patients. Hypothesis: Estimated CrCl vary by formulae. Methods: Patients admitted between July 2004 and June 2008 to the SICU who received aminoglycosides and 24-hour urine collections were retrospectively evaluated. Patients were excluded if they were pregnant, received concurrent dialysis, did not have an albumin within seven days of aminoglycoside concentrations, did not have 24-urine collection within 48 hours of aminoglycoside concentrations, had changing SCr, oliguria or anuria. Statistical analyses were performed by ANOVA. Results: Fifty four patients were included for analysis (36 males). They had mean ⫹ standard deviation of age 57.8 (⫹15) years, weight 82.3 (⫹25.1) kg, body surface area 1.95 (⫹0.26) m2, SCr 0.85 (⫹0.43) mg/dl, and albumin 1.6 (⫹0.4) g/dl. The mean estimated CrCls (⫹SD ml/min/1.73 m2) were: aminoglycoside 46.6⫹24.5, Crockroft-Gault 125.3⫹65.6, modified Crockroft-Gault 102.3⫹57.9, Jeliffe 86.7⫹28.5, Modified Diet in Renal Disease 4-variable 121.2⫹63.4, Modified Diet in Renal Disease 6-variable 85.3⫹53.3, and 24-hr urine 108.9⫹68.8, p⬍0.001. Conclusions: In critically ill surgical patients, there is a wide variation in estimation of CrCl various formulae or 24-hour urine collection. Further studies are needed to define the optimal formula for estimation of renal function.


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LEVOSIMENDAN IN SEVERE REFRACTORY RIGHT HEART FAILURE IN INFANTS

CYSTATIN C AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: RESULTS FROM NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES 1999-2002)

Joe Brierley, Great Ormond St, London Introduction: a) To describe the effects of levosimendan in refractory right heart failure in infants. Hypothesis: Levosimendan can improve severe RV failure in infants in extremis from hypoxic respiratory failure and heart failure. Methods: Prospective study of 3 infants in tertiary PICU undergoing innovative therapy protocolized trial of levosimendan for severe right heart failure – 2 severe chronic lung disease of prematurity, 1 right sided cardiomyopathy due to metabolic disease. All were on maximal conventional Rt heart support: with nitric oxide (20ppm), sildanefil, multiple inotropes & inodilators (all on epinephrine, norepinephrine, 2 on milrinone and 1 on nor-adrenaline with dobutamine) with extensive hemodynamic optimization. HFOV used in all as conventional ventilation failed. Despite FiO2 of 1.0 & optimized settings there was refractory hypoxia and low cardiac output state at commencement of levosimendan No other therapy available as ECMO contraindicated. Hemodynamics assessed by ultrasonic cardiac output monitor (USCOM) with CI & SVCO2 measured sequentially together with BNP - a sensitive measure of heart failure- (iStat Abbott) before and at set intervals after levosimendan 6mcg/kg loaded over 10 mins, followed by 0.2mcg/kg/min infusion. No changes in vasoactive medication occurred in first 60 mins, some weaning occurred thereafter. Results: All infants tolerated infusion. CI (L/min/m2) improved rapidly 0.8, 1.1, 1.8 to 1.1, 1.5, 2.5 at 15 mins to 1.5, 2.5, 2.8 at 30 minutes and 1.9, 3.5, 3.4 at 60 minutes. SVCO2 (%) changed from 38, 24, 40 to 54, 51, 59 at 60 minutes. BNP (pg/ml) improved ⬎ 5000, 3547, 1867 to 800, 500, 986 at 60 minutes and ⬍200, 804 and 543 at 4 hours. All patients survived this episode, the child with cardiomyopathy died of sepsis before discharge, one child discharged home on long-term ventilation, the other died at the local from end stage lung disease and effects of prematurity. Conclusions: Levosimenden lead to a rapid improvement of hemodynamic status, and fall in BNP levels presumably indicating improved RV status. It should be considered for infants in severe right heart failure, and it role in less severe infant right heart failure states such as PPHN should be investigated

Haala Rokadia, Shikhar Agarwal, Cleveland Clinic Introduction: Evidence about a direct association between serum cystatin c (CysC) and chronic obstructive pulmonary disease (COPD) is scarce. CysC is a potent inhibitor of cysteine proteases. Hypothesis: Increased inhibition of cysteine proteases is hypothesized to contribute to elastolysis in the lung. We aimed to examine association between CysC and COPD in large representative smaple of noninstitutionalized US population. Methods: Pooled data from NHANES 1999-2002 were used. The outcome COPD was determined using a questionnaire asking about emphysema, active bronchitis or past history of bronchitis. Active smoking was defined as self reported current smoking or serum cotinine ⬎10ng/mL. Survey statistics used to analyze complex semi-random survey designs were employed. Data obtained from the website were pooled using standard methods, and subsequently, 4 year combined weights were calculated. Results: revalence (95% CI) of emphysema, active bronchitis, or past history of bronchitis was 1.5% (1.0-2.1), 3.3% (2.2-4.3), and 3.1 (2.0-4.1) respectively. Mean (SE) CysC levels in these categories were 1.14 (0.01) mg/L, 0.91 (0.01) mg/L, and 0.89 (0.01) mg/L respectively. In comparison to the mean (SE) CysC level of 0.89 (0.01) mg/L in the non-COPD population, only emphysema group had significantly higher CysC levels (p⬍0.001). Using multivariate regression analysis adjusting for demographic and clinical variables including C-reactive protein, the CysC levels in the emphysema group were significantly higher than the control group (p⫽0.02). Stratifying the emphysema group by smoking status, the activesmokers had 0.11 (0.01-0.2) mg/L higher CysC levels than non-COPD group (p⫽0.03). The difference in adjusted CysC levels between past-smokers and never-smokers compared to non-COPD group were not significant. Conclusions: Emphysema was found to be associated with elevated CysC levels. Stratifying the emphysema group by smoking status, the active-smoker subgroup had significantly higher CysC levels. The persistence of association after adjustment for glomerular filtration rate and C reactive protein suggests that mechanisms other than impaired renal function and inflammation may be involved in the pathogenesis of emphysema.

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VASOPRESSIN IS NON-INFERIOR TO NOREPINEPHRINE AS AN INITIAL VASOACTIVE AGENT FOR EARLY GOAL-DIRECTED THERAPY

IMPACT OF LOVENOX PROPHYLAXIS ON THE DEVELOPMENT OF DEEP VENOUS THROMBOSIS IN CHILDREN WITH A CENTRAL VENOUS CATHETER

Mitchell Daley, Ishaq Lat, Katherine Mieure, Sharmeen Younus, Heath Jennings, Jesse Hall, John Kress, University of Chicago Medical Center

Charlene Davenport, Emory University, Michael Briones, Jana Stockwell, Children’s Healthcare of Atlanta/Emory University

Introduction: To determine if vasopressin is non-inferior to norepinephrine for the achievement of a mean arterial pressure (MAP) goal greater than or equal to 65 mm Hg within the first 6 hours of onset septic shock.. Methods: This retrospective cohort evaluated 130 adult patients, 65 in each treatment arm, who received either norepinephrine (0.03-0.3 mcg/kg/min) or vasopressin (0.02-0.04 units/min) as initial vasoactive therapy for the management of septic shock. Non-inferiority was defined as a less than 25% difference in proportions of goal MAP attainment at 6 hours. Patients were excluded in reverse chronological order if treatment arm initiation was not monotherapy, admitted to a cardiology or cardiothoracic surgery service, or lacked a subsequent comparator group based on severity of illness, as defined by Acute Physiology and Chronic Health Evaluation II (APACHE II) ranges. Results: Demographic variables and severity of illness were similar between groups. No significant difference was identified between vasopressin and norepinephrine for goal MAP attainment (63% and 67.7%, respectively; p⫽0.58; 95% CI 0.51-0.75 and 0.56-0.76), final MAP achieved (76 ⫾ 8.2 mm Hg and 75.0 ⫾ 9.6, respectively; p⫽0.6) or the total change from baseline MAP to goal (14.1 ⫾ 8.4 mm Hg and 15.1 ⫾ 9.1 mm Hg, respectively; p⫽0.6). Conclusions: Vasopressin was non-inferior to norepinephrine for the achievement of a MAP goal within the first 6 hours of onset septic shock. Prospective studies are needed to account for the inherent limitations in a retrospective design.

Introduction: In children, use of central venous catheters (CVC) is known to increase the risk of development of deep venous thrombosis (DVT). However, there are no evidence based recommendations regarding the best way to prevent DVTs in this setting. At Children’s Healthcare of Atlanta, our Pediatric Intensive Care Unit (PICU) instituted a protocol for DVT prophylaxis in February, 2006 utilizing either lovenox or sequential compression devices (SCD), for ventilated and sedated or otherwise poorly mobile children ⬎ 6 months of age, who had any form of CVC. Hypothesis: Use of lovenox at a prophylactic dose will reduce the incidence of DVT’s in children who are ventilated and sedated with CVC’s. Methods: We undertook a retrospective analysis of our daily quality checklist of PICU patients 0-18 years of age during the year 2009. Patients were included if they were ventilated and had a CVC (permanent and/or percutaneous (including PICC lines). The use of lovenox prophylaxis per our protocol (lovenox 0.5mg/kg SubQ Q12 if ⬎5 kg) versus non-usage per physician discretion was recorded. Clinically significant DVT occurrence was defined using radiology reports, pharmacy records of therapeutic lovenox use, and/or hematology records of clinical follow-up. Patients excluded due to coagulopathy, thrombocytopenia or recent surgery were not removed from analysis. Data were analyzed using Fisher’s Exact test. Results: 278 patients met criteria for DVT prophylaxis. Of the 175 1-18 year olds, 63 (36%) were on lovenox and the overall incidence of DVT was 6.9%; yet there was no difference in DVT incidence or relative risk if patients were on lovenox or no lovenox prophylaxis (p⫽0.67, RR⫽ .98). For patients ⬍ 1 year, the incidence of developing a DVT was 13/103 (12.6%, RR ⫽ 1.19, p⫽ 0.07) Twenty (19.4%) received lovenox prophylaxis None of the ⬍1 year olds who developed a DVT received lovenox prophylaxis, though this did not reach statistical significance. Conclusions: In this pilot study, lovenox prophylaxis does not seem to reduce the risk of DVT in 1-18 year olds. Children ⬍ 1 year of age have an increased risk of DVT development. The impact of lovenox on this population requires further study.


787 REVIEW OF A MEDICAL-SURGICAL POTASSIUM REPLACEMENT PROTOCOL USED AT AN 840 BED COMMUNITY TEACHING HOSPITAL – HIDDEN FAILURE? Angela Straughn, Amy Truckor, David Penny, Miami Valley Hospital, Harry Anderson, III, Wright State University Boonshoft School Of Medicine Introduction: Protocols meant to correct potassium abnormalities are thought to facilitate the maintenance of normal serum potassium levels in patients, which may provide a benefit of reduction in clinically significant arrhythmias, particularly in cardiac or postoperative cardiac surgery patients. Hypothesis: Potassium replacement protocols are by design complex, result in excess blood sampling and wastage, and are typically not followed correctly. Methods: This study was a retrospective chart review of 124 patients over a 4 day period that were placed on the hospital’s potassium replacement protocol. The study evaluated the number of laboratory draws performed, the measured potassium levels of the patients, and whether the protocol was followed correctly. The protocol required administration of potassium chloride to patients who required supplementation, and rechecking serum potassium levels four hours after supplementation. Results: A total of 267 potassium levels were drawn (range 1-4/patient/day). Sixty nine percent of the initial potassium levels were 3.6 or greater (hospital laboratory normal range 3.4 to 5.3 mEq/L). Only 5% of the serum potassium levels were moderate to severely low at 2.5-2.9 mEq/L. Twenty nine percent of the patients had at least one repeat lab draw driven by the protocol to recheck serum potassium levels after supplementation. Overall, the potassium replacement protocol was followed correctly only 48% of the time. The most common reason for protocol failure was no potassium supplement being given when supplementation was required per the protocol, with other reasons including no follow-up lab draws after supplementation, lab draws done at the incorrect time interval, and incorrect dose of potassium administered. Conclusions: The potassium replacement protocol is prescribed frequently at our hospital, but it is not followed correctly the majority of the time. While the protocol is thought to automate potassium replacement, it drives additional blood draws. The potassium replacement protocol is designed to automate supplementation and correction of serum potassium, but occult protocol failure may provide a false sense of security to the clinician, and may be injurious to patients.



789

USE OF ACTIVATED RECOMBINANT FACTOR VII FOR REFRACTORY BLEEDING CONTROL IN THE ICU, 4 YEARS OF EXPERIENCE IN A VENEZUELAN HOSPITAL

NEPHROTOXICITY ASSOCIATED WITH INTRAVENOUS COLISTIN IN CRITICALLY ILL PATIENTS

Pablo Perez, Sunnybrook Health Sciences Centre, Stevens Salva , Fernando Perez, Gabriel d’Empaire, Hospital de Clinicas Caracas Introduction: Activated recombinant factor VII (rFVIIa) has been studied for refractory bleeding control in non-hemophilic patients and it has shown controversial results. Hypothesis: The use of rFVIIa is effective to control refractory bleeding in non-hemophilic ICU patients. Methods: Retrospective analysis including all the non-hemophilic patients who received rFVIIa for refractory bleeding control in the Hospital de Clinicas Caracas ICU from January of 2006 and 2010. Blood products requirements and laboratory test results before the rFVIIa administration were recorded. Outcomes evaluated were bleeding control within the first thirty minutes of the rFVIIa administration and hospital survival. Results: 26 non-hemophilic patients received rFVIIa for hemorrhage control in our ICU during the study time. Age was 56.73 (⫾19.36), 10 (38.46%) were male. All of patients were in shock with vasopressor support at the time of rFVIIa administration and all anatomic causes of bleeding had been solved previous to the rFVIIa administration. Causes of bleeding were 7(26,92%) patients from cardiac surgery, 6(23,07%) from major abdominal surgery, 5 (19,23%) from perforating trauma, 4(15,38%) from upper gastrointestinal bleeding, 3(11,53%) from blunt trauma and 1(3,84%) from obstetrical bleeding. All the 26 patients were coagulopathic according to laboratory test results. Blood products requirements were 5.69 (range 4-12) units of PRBC, 9.38 (6-34) FFP, 5.73 (2-16) of platelets and 1.65 (0-8) cryoprecipitate before the rFVIIa administration. The rFVIIa dose was 90 mcg/kg for all the patients and 9 (34.61%) patients received two doses. Bleeding was controlled in 21 (80.76%) of the patients within the 30 minutes of the rFVIIa administration. Hospital survival after bleeding control was 80.95%, the rest of the patient died from other causes different than hemorrhage and no thrombotic events were detected during the hospital stay. Conclusions: rFVIIa administration was effective and safe for bleeding control in non-hemophilic patients who were refractory to the conventional treatment in our ICU. This is the only rFVIIa study in our country, however being a small single center retrospective study has limitations for definitive conclusions

Neha Doshi, Kari Mount, Claire Murphy, The Ohio State University Medical Center Introduction: The use of intravenous (IV) colistin is associated with developing acute renal failure (ARF), especially in critically ill patients; however given the lack of a standardized definition, the true incidence is unknown. This study aims to determine the incidence and risk factors for ARF observed with IV colistin in critically ill patients using the RIFLE criteria. Hypothesis: Baseline comorbidities and concomitant nephrotoxic agents will increase the risk of nephrotoxicity with IV colistin. Methods: This retrospective study included critically ill patients who received IV colistin for greater than 48 hours. Patients receiving renal replacement therapy at baseline were excluded. ARF was defined using the validated Risk, Injury, Failure, Loss and End-stage renal disease (ESRD) (RIFLE) criteria based on change in serum creatinine or glomerular filtration rate from baseline. Risk, Injury and Failure are considered reversible whereas Loss and End-stage renal disease are irreversible. Risk factors for nephrotoxicity were also collected. Results: Forty-nine patients were included with 30% meeting RIFLE criteria for ARF. Of the patients with ARF, only 2 had irreversible kidney damage. Eight patients with ARF were unable to be categorized due to lack of serum creatinine at four weeks due to discharge or death. Patients with ARF were more likely to have a history of hypertension (86.7 vs. 55.9%, p⫽0.05) or chronic renal insufficiency (CRI) (40 vs. 2.9%, p⫽0.002). In the group that developed ARF, 50% of patients received an aminoglycoside compared to 13.5% of patients that did not (p⫽0.069). In addition, more patients with ARF received IV contrast (33.3 vs. 0%, p⫽0.001).The risk of developing ARF was 6.50 times higher if the subject had been given at least two nephrotoxic agents compared to none (p⫽0.034). Conclusions: Critically ill patients receiving IV colistin had an incidence of ARF of 30%. Since the majority of injury was reversible, the risk of nephrotoxicity may not be as severe as previously believed. Risk factors for nephrotoxicity include hypertension, CRI, IV contrast, aminoglycosides and multiple nephrotoxic agents. IV colistin should be used cautiously in these patients.

790

791

DEVELOPMENT, IMPLEMENTATION, AND EVALUATION OF A PROTOCOL FOR ADULTS WITH DIABETIC KETOACIDOSIS AND HYPERGLYCEMIC HYPEROSMOLAR STATE IN THE ICU

EVALUATION OF GLYCEMIC OUTCOMES IN CRITICALLY ILL ONCOLOGY PATIENTS TRANSITIONED OFF CONTINUOUS IV INSULIN INFUSION

Said Sultan, Carolinas Medical Center, Stacy Campbell-Bright, UNC Hospitals

Sharla Tajchman, University of Texas MD Anderson Cancer Center, Brent Anderegg, UT MD Anderson Cancer Center

Introduction: Multiple studies have shown that protocols in the intensive care unit can decrease morbidity, mortality, length of stay, errors, and costs. DKA and HHS are disease states that have shown the benefit of protocols. Hypothesis: Treatment of DKA/HHS with a protocol will lead to quicker resolution of acidosis, decrease time in the ICU and hospital, and decreased hospital complications and costs. Methods: Medical records were reviewed for adult patients admitted to the hospital from Jan. 1, 2009 to Dec. 31, 2009 diagnosed with DKA or HHS. The following data was collected: time to correct acidosis and close anion gap, insulin management , length of stay in emergency department, ICU, and hospital, and incidence of hypoglycemia. During this time the DKA/HHS protocol was developed by pharmacists, nurses, and physicians and built into the CPOE system so that there is access in a central electronic location. The MICU team was educated about the use of the protocol. The implementation of the DKA/HHS protocol in the Medicine ICU took place on Jan. 1, 2010. Observational data was collected on patients treated with the new protocol until June 15, 2010. Results: A total of 48 patients met the inclusion criteria for the preprotocol group. After the protocol was implemented a total of 16 patients were enrolled. The DKA/HHS patients in the pre-protocol and post-protocol were similar between both groups. The results were separated per disease state to observe the effects of the protocol. It was noted that the mean time to close the anion gap post-protocol was 12.5 hours compared to 14.2 hours in the preprotocol group, which is showing a trend to better outcomes with the protocol. The length of ICU time and hospital stay in both the pre- and post-protocol was very similar with a difference 1.6 hours and 0.2 hour between both groups, respectively. The incidence if hypoglycemia was 15% in the post-protocol group and 8% in the pre-protocol group. For patients treated with HHS protocol, it was noted that the time to correct osmolality is lower. Conclusions: Our data suggests that the DKA/HHS protocol is as effective as treatment of the disease states without a protocol, however more data is needed to evaluate the protocol.

Introduction: Despite recommendations from the American Association of Endocrinologists and The American Endocrinology Association, the use of standardized protocols to transition patients from continuous insulin infusion therapy (CIIT) to an alternative regimen for the maintenance of euglycemia is not widely practiced. Oncology patients with variable baseline characteristics and pharmacological therapies present an added challenge to glycemic control. Hypothesis: Transitioning oncology patients from CIIT to various insulin regimens without the use of a standardized protocol may result in poor glycemic control. Methods: Critically ill oncology patients ⱖ 18 years of age on CIIT were eligible for evaluation. Serum and capillary glucose measurements were collected for 72 hours following discontinuation of CIIT. The primary endpoint was mean morning serum glucose level. Secondary endpoints included mean capillary glucose level and the percentage of morning serum glucose levels and capillary glucose levels within target range (70 to 180 mg/dL) and the incidence of hypoglycemia. Results: 117 patients were categorized according to post-CIIT insulin regimen: supplemental insulin only (SI), supplemental plus long-acting insulin (SI plus LA) and insulin-containing parenteral nutrition (TPN). Differences at baseline included a history of diabetes, hypertension, prior use of long-acting insulin, need for mechanical ventilation, steroid use, average grams of carbohydrates administered per day and the presence of an endocrinology consult. There were no differences in mean morning serum glucose among the three groups (SI 137 mg/dL, SI plus LA 151 mg/dL and TPN 143 mg/dL). Differences in mean capillary glucose levels were also not statistically significant. The incidence of hypoglycemia did not differ among the three groups. Outcomes remained statistically insignificant when adjusted for baselines differences. Conclusions: Despite the complex comorbidities, medical and pharmacological therapies in critically ill oncology patients, maintenance of glycemic control can be accomplished after discontinuation of CIIT using careful clinical assessment of patient risk factors for hyperglycemia in lieu of a standardized protocol.


792

793

EVALUATION OF INTRAVENOUS ANTIHYPERTENSIVE INFUSIONS FOR BLOOD PRESSURE MANAGEMENT IN THE NEUROSCIENCES INTENSIVE CARE UNIT

THE IMPACT OF SEVERE DELIRIUM TREMENS (DT) ON POSTOPERATIVE/TRAUMATIC RECOVERY WITH THE APPLICATION OF THE CIWA-AR

Shazia Raheem, St. Vincent’s Medical Center, Janine Douglas, Cleveland Clinic, Christine Lesch, NewYork-Presbyterian, Columbia University Medical Center, Neeraj Badjatia, Columbia University Medical Center

Stacie Kahan, Katherine Petersen, James Krinsley, Timothy Hall, Stamford Hospital

Introduction: Blood pressure (BP) management in the neurosciences intensive care unit (NICU) is an integral component of care in patients with neurological injuries. To achieve rapid and adequate BP control, continuous infusion antihypertensive agents (most commonly nicardipine and labetalol) are often utilized. There are, however, no studies comparing these agents as continuous infusions in neurologically injured patients. Hypothesis: The purpose of this study was to determine the safety and efficacy of continuous infusion antihypertensives for BP control. Methods: An IRB approved, prospective observational study was conducted from November 2009 to March 2010 in all patients admitted to the NICU initiated on continuous infusion nicardipine (NIC) or labetalol (LAB) within 24 hours of admission and had an arterial line placed. Individual patient BP goals were defined by the primary team and BP was measured every minute for 30 minutes then hourly up to 24 hours. Results: In the 5 month study period, twenty seven patients were included in the study: NIC n⫽19, LAB n⫽5, combination nicardipine and labetalol (NIC/LAB) n⫽3. Fifty one percent of patients were male with a median age of 60 years (22-93 years), median APACHE II score of 12 (3-33) and median GCS score of 15 (4-15). Fifty six percent (n⫽15) of patients required continuous infusion antihypertensives for post operative hypertension, 30% (n⫽8) for hemorrhagic stroke, 11% (n⫽3) for ischemic stroke and four percent (n⫽1) for hypertensive encephalopathy. At initiation of NIC, LAB, and NIC/LAB the median SBP was 156 mmHg (142-186 mmHg), 152 mmHg (146-220 mmHg), and 214 mmHg (184-228 mmHg), respectively. Within 9 min (1-240 min), 5 min (1-120 min), and 120 min (28-180) the NIC, LAB, NIC/LAB group, respectively, attained BP goal. Once at BP goal, patients in the NIC, LAB, and NIC/LAB groups remained at BP goal 67%, 90% and 33% of the total duration of the infusion, respectively. Bradycardia (HR ⬍ 60 bpm) occurred in 20% of patients in the NIC and LAB monotherapy group and in all patients in the NIC/LAB group. Conclusions: NIC and LAB continuous infusions were effective in attaining BP goal in neurologically injured patients.

Introduction: The standard of care to treat acute alcohol withdrawal syndrome (AWS) is the application of the Clinical Institute Withdrawal Assessment (CIWA) protocol, however it was never designed for post surgical or trauma patients. Alcohol dependence was established based on previous admissions, documentation of withdrawal symptoms and elevated admission blood alcohol levels. Hypothesis: This study evaluated the effectiveness of CIWA-ar in treating severe Delirium Tremens following inpatient surgery or a trauma related admission. Methods: All patients with severe DTs admitted to the surgical ICU were studied over a two year period (2008-2009). Data for patient demographics, medications, and clinical outcomes for length of stay (LOS), complications and mortality (MORT) were collected prospectively. The CIWA-ar protocol was applied as described by The American Society of Addiction Medicine and assessed for additional doses of benzodiazepams or other medications for DT. Results: 58 cases were identified with a confirmed diagnosis of alcohol dependency; 27 patients developed severe DT. The mean age was 57.4⫹14.1 years and 85% were male. The admitting service designation was general surgery/trauma 55%, Orthopedic19%, thoracic surgery 15%, urology 7% and neurosurgery 3% of patients. The average ICU LOS was 5.9⫹6.5 days and an overall LOS of 17.5⫹13.1 days. The APACHE 2 and 3 scores were 14.1⫹66 and 46.4⫹18.8 respectively. Ventilatory support was required in 52% for an average of 7.6 days. The predicted and actual mortalities were 16.1% and 10.7%, A/P ratio of 66.5%. The discharge status was: 42% to home, 29% to rehabilitation, 17% to a skilled nursing facility and 12% with home health care services. Additional medications to control the physiological effects of DTs were required in a majority of these patients. Conclusions: The application of CIWA- ar has limited control of the physiological effects of severe DT as assessed by APACHE scoring and a limited impact on the need for ventilatory support, ICU LOS and mortality. When a patient exhibiting AWS progresses to DT, it is imperative for the physician to consider protocol application of CIWA-ar with additional medications and frequent re-assessments.

794

795

COMPARISON OF HEPARIN DOSING BASED ON ACTUAL BODY WEIGHT IN NON-OBESE, OBESE AND MORBIDLY OBESE CRITICALLY ILL PATIENTS

CORRELATION OF APTT TO ANTI-XA ASSAYS IN A MIXED SURGICAL/TRAUMA POPULATION FOR THE MONITORING OF IV ANTICOAGULATION WITH HEPARIN

Anthony Gerlach, Ohio State University Medical Center, Jerilynn Folino, Riverside Methodist Hospital, Ben Morris, Wake Forest University Baptist Medical Center, Claire Murphy, The Ohio State University Medical Center, Stanislaw Stawicki, Ohio State University Medical Center, Charles Cook, Ohio State University Hospitals

Prasad Abraham, Grady Health Systems, Brian Williams, University of Texas Southwestern Medical Center - Parkland Memorial Hospital, Andrew Young, Jeffrey Nicholas, Grady Health System

Introduction: Evaluation of heparin dosing based on actual body weight in non-obese (NO, BMI 20-29.9) obese (OB, BMI 30-39.9) and morbidly obese (MO, BMI ⬎ 40) critically ill patients to determine if admission body weight or ideal body weight should be used for the dosing nomogram. Methods: Retrospective review of obese patients admitted to the Intensive Care Unit between July and December 2007 that received heparin for ⬎24 hours. Prisoners, pregnant women and those ⬍18 or ⬎89 years were excluded. Patient charts were reviewed for demographics, heparin dosage/therapy duration, laboratory values, and bleeding. Steady state (SS) heparin dosage was defined as three consecutive PTT levels within target range. Major bleeding was defined as a documented cerebrovascular, gastrointestinal or retroperitoneal bleed. Minor bleeding was defined as ecchymosis, epistaxis, hematoma, hematuria hemoptysis, petechiae, or oozing. Statistical analysis was performed by Fisher’s exact test for nominal data and Student’s t- test for continuous data. Results: Sixty-two patients were analyzed including 20 NO (mean BMI 23.5⫹3.4); 22 OB (mean BMI 34⫹3), and 20 MO (mean BMI 55.3⫹13.7). Patient groups had otherwise similar characteristics. Only 55% of patients reached SS (55% NO, 50% OB and 60% MO). Six patients developed minor bleeding with no major bleeds reported. Mean weight-based heparin dosage (units/kg/hr) was similar (12.2⫹3.3 NO, 10⫹4 OB and 11⫹1.4 MB) but the total heparin dosage (units/h) was statistically higher in the morbidly obese (818⫹369 NO, 1000⫹420 OB, 1850⫹620 MO, p⬍0.001). The corresponding dose (units/kg/hr) at SS based on ideal body weight was statistically higher in the MO (30⫹11.4) compared to NO (12.9⫹4.5, p⬍0.001) and OB (16.6⫹6.6 units/kg/h, p⫽0.002). Conclusions: Dosing of heparin based on admission body weight in morbidly obese ICU patients was associated with similar outcomes compared to obese and non-obese patients, although about half reached SS. Targets for improvement have been identified.

Introduction: Monitoring of IV heparin therapy with aPTT’s if fraught with limitations. Our institution recently switched to anti-Xa assays for the monitoring of IV heparin therapy. While anti-Xa assays appear to be better, correlation of aPTT to anti-Xa assays in a surgical/trauma population has not been demonstrated. Because aPTT is a global marker of anticoagulation while anti-Xa assays are limited to factor Xa, concerns of bleeding due to this more specific test arose. Hypothesis: Anti-Xa assays are a reasonable test for the monitoring of IV heparin therapy in a general surgery/trauma population. Methods: Surgical patients initiated on IV heparin therapy were identified via a pharmacy report. Once identified, both anti-Xa assays and aPTT’s were monitored simultaneously while on heparin. Patients could be initiated on the following protocols: 1. Low intensity (goal anti-Xa range of 0.3-0.5), 2. High intensity (goal anti-Xa range 0.5-0.7), 3. MD managed protocol (goal range aPTT of 60-90 sec). Patients were monitored for bleeding during the therapy. Correlations of anti-Xa assays to aPTT were evaluated once data collection complete. Results: Over a 6 month period 23 patients were identified. Mean age was 47 years and mean weight was 88.5 kg. Forty eight percent were trauma patients and 52% of them were located in the ICU. Bleeding occurred in 6 patients (1 severe, 5 moderate). Of the patients with anti-Xa assays and aPTTs around the time of bleeding, 2 had supratherapeutic heparin levels based on anti-Xa assays but not aPTTs, 2 had therapeutic heparin levels based on anti-Xa assays and aPTTs and 1 had a supratherapeutic anti-Xa assay and aPTT. Anti-Xa assays and aPTT’s were in reasonable agreement (r⫽0.55). Conclusions: Anti-Xa assays appear to be a reasonable tool in the monitoring of IV heparin therapy in general surgery/trauma patients.


796

797

A PHASE IV, OPEN-LABEL, MULTICENTER PILOT STUDY WITH DROTRECOGIN ALFA (ACTIVATED) IN THE TREATMENT OF BURN PATIENTS WITH SEVERE SEPSIS

USE OF ANTIFUNGAL THERAPY IN A MEDICAL AND SURGICAL INTENSIVE CARE UNIT (ICU) IN A UNIVERSITY HOSPITAL

Bruce Friedman, Joseph Shaver, Doctors Hospital of Augusta, Robert Mullins, Zaheed Hassan, Claus Brandigi, Joseph M. Still Burn Centers, Inc.

Jerusha Taylor, Oregon Health and Sciences University

Introduction: This pilot study (F1K-US-X004) was the first prospective study to evaluate the safety profile of drotrecogin alfa (activated) (DrotAA) exclusively in burn patients with severe sepsis. Hypothesis: Burn patients with severe sepsis and treated with drotrecogin alfa (DrotAA) will exhibit an acceptable safety profile as it relates to bleeding tendencies. Methods: Patients with severe sepsis were defined as having three or more modified SIRS criteria, at least one organ failure, and suspected or proven infection. The primary objective was to demonstrate an acceptable safety profile for Drott AA with reference to increased blood transfusion requirements. Secondary objectives included evaluation of DrotAA effects on organ dysfunction using Sepsis-related Organ Failure Assessment (SOFA) methodology, and examination of mortality data. Results: A total of 15 patients in 3 burn centers (8, 5, and 2 patients per respective center) were exposed to treatment in the trial. No treatment failures occurred with regard to transfusion requirements or uncontrolled blood loss. A total of four patients discontinued the infusion period due to adverse experiences which may or may not have been drug related. Three of them died; two during the infusion because of multi-system organ failure (MSOF) and one a few days after discontinuation of the drug. Conclusions: In this study where burn patients with active or recent bleeding, and those with serious risk of bleeding, were screened and excluded, no serious bleeding was encountered with DrotAA treatment.


Introduction: Invasive fungal infections are an important cause of mortality in the ICU. Many ICU patients are started empirically on antifungal (AF) therapy when a fungal infection is suspected. Risk factors for fungal infections include the use of broad spectrum antibiotics, use of central venous catheters (CVC), total parenteral nutrition (TPN), renal replacement therapy (RRT), and receipt of immunosuppressive agents. Many patients without these risk factors are started on empiric AF therapy without evidence of a fungal infection. Hypothesis: There is an over-use of AF therapy in our medical and surgical ICUs. Methods: We performed a retrospective chart review comparing two similar time periods; fluconazole and micafungin use in 2008 vs. 2009. Data collected included patient demographics; AF used, dose, duration , frequency; use of broad specturm antimicrobials; diagnosis; use of CVC, RRT, CCS, ISA, TPN, use of pressors; Charlson comorbidity score(CIS); reason for AF (i.e. empiric, treatment, colonization); ICU and hospital LOS; and survival. We performed statistical analysis comparing these two time periods using Fisher’s exact test. Results: We compared 20 patients in 2008 and 39 patients in 2009. There was no difference in age, comorbidities, CIS, and risk factors between years. AF were started empirically in 66% of the patients in both years, but more patients in the ‘08 group received AF for colonization (p⫽0.05) There was more use of ⬎ 1 Gram negative antibiotic (p⫽ 0.001) and more AF days (p⫽ 0.04) in ‘08. More patients in ‘08 had Candidemia and there was 1 case of C glabrata. There was no difference in mortality between the groups (p⫽0.3). In both groups, use of RRT, pressors, and Charlson ⬎ 3 were predictors of mortality regardless of AF use. Conclusions: AF use continued to be used for empiric and colonization of candida despite guideline implementation and there was no impact on survival. Decreased use of AF between ’08 and ’09 can be attributed to implementation of antimicrobial management team and publication of guidelines. AF was mostly used when severity of illness was high and resulted in non-adherence to guidelines but did not impact patient outcomes, LOS and resulted in C. glabrata

Poster: Therapeutics-Other-1 798

805

CORRELATION BETWEEN PCO2 (ARTERIAL- ENDTIDAL) GRADIENT AND POSITIVE END EXPIRATORY PRESSURE TITRATION IN MECHANICALLY VENTILATED PATIENTS WITH ACUTE LUNG INJURY OR ACUTE RESPIRATORY DISTRESS SYNDROME

GLUCOSE MEASUREMENT ACCURACY OF A NOVEL INLINE WHOLE BLOOD GLUCOSE MONITORING SYSTEM

Hassan Abu-Khabar, Alexandria Faculty of Medicine, Amr Elsayed, Mohammad Ahmad, Alexandria University Introduction: PEEP is the cornerstone of hypoxemia treatment in patients with ALI/ ARDS, but there is still some controversy over the optimum level to be used and how this should be determined. To reach to optimal PEEP, several studies on applied PEEP titration were performed over the last years according to physiologic measures which included esophageal pressure, pressure volume curves, oxygenation. Hypothesis: Our aim was to determine whether arterial minus end-tidal carbon dioxide (PaCO2-PetCO2) can be used for titration to find optimal PEEP in correlation with dead space fraction (Vd/Vt) in patients with ALI/ARDS. Methods: The present study included 20 adult ALI /ARDS patients of both sexes who were heavily sedated and mechanically ventilated with lung protective strategy. During this study PEEP was titrated from baseline (5 cmH2O) by increments of 2 cmH2O for 30 min till reaching the value of optimal PEEP that corresponded to the least (PaCO2-PetCO2) gradient, least Vd/Vt and best shunt fraction and PaO2. The PaCO2-PetCO2 gradient and Vd/Vt decrease with each PEEP level till they started to increase and this point was taken as the highest PEEP and the value preceding this by 2 cmH2O was taken as the optimal PEEP. The value obtained before the optimal PEEP by 2 cmH2O was taken as the pre-optimal PEEP. Results: The mean value of PaCO2-PetCO2 gradient was 17.95⫾3.47 mmHg at baseline PEEP, and decreased to 13.45⫾2.52 mmHg with pre optimal PEEP (12.3⫾3.06 cmH2O), further decreased to 11.7⫾2.83 mmHg with optimal PEEP (14.3⫾3.06 cmH2O) and increased to 15.3⫾2.47 mmHg at highest PEEP (16.3⫾3.06 cmH2O) significantly. Vd/Vt follows the same course as the PaCO2-PetCO2 gradient, so the two variables were closely related. Highest and optimal PEEP significantly reduced shunt fraction in comparison to baseline and pre-optimal. PaCO2-PetCO2 gradient was minimal when PaO2 was maximal. Conclusions: In patients with ALI/ARDS, the PaCO2-PetCO2 gradient is a good indicator of the efficiency of ventilation and is directly proportional to the degree of alveolar dead space. So, PEEP titration using the PaCO2-PetCO2 gradient is a useful and easily available bedside parameter to find the optimal PEEP in patients with ALI/ARDS.

Shonn Hendee, Stephen Vanslyke, Joelle Faught, Mike Borrello, Jim Macemon, Rick Thompson, Annie Truong, Christopher Wang, Luminous Medical Introduction: Accurate and timely assessment of blood glucose is required for managing glycemic control protocols in critically ill patients. Current hand-held monitors have limited accuracy, and clinical laboratory equipment is labor-intensive and inconvenient for frequent blood glucose sampling. Luminous Medical is developing an in-line, patient-attached system to address these issues. The GLine™ Glucose Monitoring System integrates with a patient’s existing arterial line and uses standard arterial blood sampling methodology to draw blood into the in-line sensor for glucose measurement. Hypothesis: The G-Line system provides accurate glucose measurements when compared to a gold standard clinical reference method. Methods: Whole blood samples were prepared using blood collected from 14 healthy human donors under informed consent. Samples were spiked with glucose to achieve target levels ranging from 30-700mg/dL. Measurement procedures modeled arterial blood sampling methods used in standard nursing practices. Blood samples were drawn directly from a sample container into the in-line sensor using a 5 mL blood-conserving device (VAMP™, Edwards Life Sciences™, Irvine CA). Following each measurement, blood was returned to the container using the BCD and the sensor was flushed with saline from an IV bag. On average, 33 samples were measured on each of the 23 G-Line sensors evaluated in this study, with 768 total samples reported. G-Line results were compared with YSI 2700 (YSI Inc., Yellow Springs, OH) plasma glucose reference measurements. Results: G-Line measurements showed excellent agreement with YSI reference measurements (over 95% of measurements within ⫾10 mg/dL or ⫾10% target limits). Results were linear (R2⫽0.99) for individual sensors and for multiple sensors over multiple study days. Conclusions: The G-Line Glucose Monitoring System provides highly accurate glucose measurements relative to a gold standard reference method. The technology shows promise as a solution for managing glycemic control protocols in critical care settings.

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LIMITING PERIOPERATIVE NORMAL SALINE IS BENEFICIAL TO CARDIAC SURGICAL PATIENTS

IMPACT OF AGE OF BLOOD ON NOSOCOMIAL INFECTIONS IN CRITICALLY ILL PATIENTS

Jeffrey Brown, Robert Kramer, Robert Groom, Sally Whitten, Steven McGrath, Barbara Heyl, Joseph Dalton, Maine Medical Center

Mariam Abboud, Cooper University Hospital, Raquel Nahra, Sparks Health System, Patricia Henry, Krystal Hunter, Barry Milcarek, Cooper University Hospital, Christa Schorr, Jean-Sebastien Rachoin, Cooper Hospital University Med Ctr, David Gerber, Cooper Hospital/UMC

Introduction: Metabolic acidosis is a common occurrence in postoperative cardiac surgery patients, imparting risk to patients and imposing additional use of resources. We sought to improve quality by implementing guidelines for its prevention. Hypothesis: We hypothesized that reducing chloride levels would result in less acidosis, fewer arterial blood gas (ABG) determinations and less administration of sodium bicarbonate. Methods: A multidisciplinary group was convened to study post-operative acidosis in cardiac surgery. Laboratory data from 150 consecutive patients over a two month time period was collected and analyzed. Hyperchloremia appeared to be the most common cause of metabolic acidosis. At that time, normal saline was the crystalloid of choice in the operating room and in the postoperative setting. In the operating room, a balanced crystalloid solution (Normosol-R, Hospira) was substituted for 0.9% normal saline solution, and its use was encouraged as the crystalloid of choice in the cardiothoracic intensive care unit (CTICU). Educational sessions on the subject of acidosis were held and an acidosis treatment algorithm was developed. Subsequently, data was collected on an additional 135 consecutive patients over a two month time period and then analyzed using the Mann- Whitney test and Student’s T- test (2 tailed). Results: Mean postoperative chloride concentrations dropped from 111.99 mEq/l to 107.15 mEq/l. (p⬍0.01) Mean serum bicarbonate concentration (p⬍0.01) and nadir bicarbonate concentration (p⬍0.01) increased. The mean number of ABGs sampled dropped from 3.69 to 3.51 (p⬍0.1). Additionally mean monthly sodium bicarbonate usage decreased from 96 50 mEq/l doses to 40 doses (p⬍0.01). Conclusions: Iatrogenic hyperchloremic acidosis was recognized in many of our postoperative open heart surgical patients. It led to frequent ABGs and unnecessary sodium bicarbonate administration, as well as being potentially deleterious to the patient and distracting to clinicians. Changing from normal saline to a balanced crystalloid solution, coupled with increased staff education and an evidence based acidosis treatment algorithm resulted in less metabolic acidosis, fewer phlebotomies and less sodium bicarbonate use.

Introduction: It has been shown that older Packed Red Blood Cells (PRBC) are associated with worse clinical outcomes when transfused in cardiac surgical patients. We studied the impact of the age of PRBC on the incidence of nosocomial infections in a general medical-surgical ICU population. Hypothesis: “Older” PRBC are associated with higher incidence of nosocomial infections in critically ill patients. Methods: We performed a retrospective study of all transfused patients admitted to an ICU from July 2003 to July 2009 and entered in the Project IMPACT database. We examined the association between the age of PRBC (date of collection to date of transfusion) and the development of nosocomial infections (line related, pneumonia, UTI, sepsis, shock, endocarditis). In case of repeated admissions, only the first was analyzed. Results: 667 patients were included for analysis. Median patient age was 65y, ICU length of stay (LOS) 4.14d, Hospital LOS 11d, APACHEII score 19. Bracketed ranges represent inter-quartile ranges. The median of average age of blood was 26d [20-32]. 89 patients developed a nosocomial infection; in 57 it occurred after PRBC transfusion (considered as a true event -TE). Analysis was performed on: age of the first unit of blood (FI), age of the “oldest” unit of blood (OL), the average age of all units of blood transfused and the outcome -TE. Patients with TE had higher OL (36d [31-41] vs 28d [21-36] p⬍0.001) and there was a positive correlation between higher OL and ICU LOS (p⬍0.001). To further evaluate the relationship between OL and infection, we divided the oldest units received by weeks of storage time: less than or equal to 3, 4, 5, and more than 5 weeks. We found that as OL week increased the risk of TE increased (3.6%,8.4%, 13.3% and 25% respectively). The association became significant at week 4 (22 days or more), p⬍0.001. Conclusions: Our study found an association between duration of blood storage (age of oldest unit of blood given) and incidence of nosocomial infection, as well as ICU length of stay. While transfusing “younger” blood may be preferable, it may not be feasible. These results may lend additional support to a clinical approach including a more restrictive transfusion strategy.


808 NON-ISCHEMIC MITOCHONDRIAL DYSFUNCTION IS THE MOST COMMON METABOLIC ABNORMALITY AFTER TBI Maria Filippou, Jeffry Alger, David McArthur, UCLA, Paul Vespa, UCLA Health Sciences Center Introduction: Traumatic brain injury (TBI) results in widespread but heterogeneous mitochondrial dysfunction. It is unclear whether ischemia is the main cause of this metabolic disturbance. Hypothesis: We hypothesize that mitochondrial dysfunction is commonly present in normal appearing brain tissue in absence of brain ischemia. Methods: We prospectively studied 10 severe TBI patients with the combination MRI techniques of Multivoxel Spectroscopy (MRS) and MRI Apparent Diffusion Coefficient (ADC) and cerebral microdialysis during the initial 7 days post injury. MRS and ADC valued were co-registered to the location of cerebral microdialysis placed in normal appearing frontal lobe white matter. The incidence and duration of metabolic crisis, as indicated by an elevation of microdialysis lactate/pyruvate ratio (LPR) to ADC and MRS metabolites were made. Comparison of pericontusional tissue with normal appearing white matter was done. Results: One thousand MRI/MRS voxels were studied. N-acetyl aspartate/creatine(NAA/Cr) ratios were reduced below 40% of normal in all 10 patients, with a frontal-to-occipital gradient noted in all cases. NAA/Cr were universally low, with a gradient ranging from lowest near contusions (p ⬍ 0.01), followed by normal frontal lobe, and highest in posterior frontal areas. Five subjects had metabolic crisis by LPR, but the NAA/Cr was non-significantly lower as compared with those without metabolic crisis (1.03 vs 1.5, p ⬍ 0.21). ADC was ⬎ 700 in all subjects, in all voxels, indicating no ischemia. Conclusions: Mitochondrial dysfunction is universally present to varying degrees in normal appearing, non-ischemic tissue after TBI, and may be worsened by metabolic crisis. Treatments to reverse metabolic crisis but not ischemia may improve mitochondrial function.



811

CHARACTERIZATION OF GLUCOSE BEHAVIOR AND EFFECT OF EXOGENOUS INSULIN ADMINISTRATION DURING THERAPEUTIC HYPOTHERMIA AND REWARMING

DOES PRBC TRANSFUSION AFFECT OUTCOMES IN THE ELDERLY CRITICAL CARE PATIENT?

Jenna Bernabei, Henry Ford Hospital, Dustin Spencer, Timothy Ellender, Michelle Deckard, Clarian Health/Methodist Hospital Introduction: Therapeutic hypothermia (TH) and controlled rewarming is utilized to preserve neurologic function in patients resuscitated from cardiac arrest. The impact of glycemic control has not been well studied in patients treated with TH. The purpose of this study is to characterize glucose behavior and the effect of exogenous insulin administration. Hypothesis: Exogenous insulin administration increases the incidence of hypoglycemia during rewarming. Methods: A retrospective, observational analysis of post-cardiac arrest patients treated with TH from September 2008 to August 2009 was performed. Patient demographics, documented sepsis, use of vasopressors or corticosteroids, glucose values, temperatures, and the amount of insulin administered were collected and analyzed. Results: 112 consecutive patients were evaluated for the study; 76 had complete data available for analysis. At baseline, 25 patients (33%) had documented diabetes and 63 patients (82%) received exogenous insulin during the study period. During cooling, hypoglycemia (glucose ⬍70 mg/dL) occurred in 17% of blood glucoses in patients receiving insulin vs. 12% in patients that did not (p⫽0.677) and 21% vs. 17% (p⫽1.0) during rewarming. Incidence of hyperglycemia (glucose ⬎180 mg/dL) was highest (63% of glucoses) during the first 6 hours of cooling (mean temp 33.2°C) and lowest (3.9%) during the first 6 hours of rewarming (mean temp 33.6°C). Incidence of hypoglycemia was highest (11%) during the first 6 hours of rewarming and lowest (1.3%) during the first 6 hours of cooling. Diabetes was associated with an increased incidence of hyperglycemia during cooling (p⫽0.02). Documented sepsis, vasopressor use, and corticosteroid administration did not affect the incidence of hyperglycemia during TH. Conclusions: Exogenous insulin administration was not associated with an increased incidence of hypoglycemia during rewarming. Results suggest that patients with a history of diabetes have an increased risk of hyperglycemia during cooling. However, no other contributing factors were identified. Further study in this area is warranted to determine if other contributing factors affect glycemic control during therapeutic hypothermia.

Karen Vito, Priyank Desai, Thomas Rishling, Krystal Hunter, Barry Milcarek, Cooper University Hospital, David Gerber, Cooper Hospital/UMC Introduction: Packed red blood cell transfusion (PRBC) is commonly used in ICU patients, but may not be as beneficial as previously assumed for all patients. Little data exists on the use of PRBC transfusion in the elderly ICU population, its effect on outcomes, and comparison of use and outcomes with younger patients. Hypothesis: We hypothesized that PRBC transfusion in critically ill elderly patients increases ICU LOS, Hospital LOS (HLOS) and mortality compared to non-elderly critically ill patients. Methods: This is a retrospective study using our hospital’s Project Impact database. We identified 1,363 non-surgical patients admitted to the ICU from the Emergency Department between 1/2005 and 12/2009. Patients were divided into 4 groups: Group 1 (⬎79 years receiving PRBC [T]), Group 2 (⬎79 years not receiving PRBC [NT]), Group 3 (50-70 years receiving PRBC [T]) and Group 4 (50-70 years not receiving PRBC [NT]) during their ICU stay. Continuous variables were compared using the MannWhitney U test or t-test as appropriate; categorical variables were compared using the X2 test. Results: Transfusion was slightly but not significantly more common in elderly patients (29% vs 22%, p⫽0.08). HLOS & ICU LOS (p⬍0.0001) and duration of mechanical ventilation (MV) (p⬎0.002) were significantly higher for the elderly T group compared to the elderly NT group. Mortality was higher for the elderly T group (32.0%) compared to the elderly NT group (23.0%) but was not statistically significant. Elderly T patients have significantly worse functional outcomes than younger T patients (p⫽0.001). APACHE II was similar between elderly T and elderly NT as well as elderly T and younger T patients (p⬎0.05). Conclusions: Results indicate that elderly transfused patients have longer ICU LOS, HLOS and duration of MV than elderly patients who are not transfused, although elderly patients are not transfused significantly more than middle-aged patients. There was no overall difference in mortality between the elderly transfused group and the middle aged transfused group. Despite the adverse effects associated with PRBC, the additional negative consequences this intervention confers upon elderly patients compared to younger patients seem to be modest.

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BLEEDING RISK FACTORS ASSOCIATED WITH ARGATROBAN THERAPY IN THE CRITICALLY ILL

IMPROVEMENT OF CARDIAC ELECTROPHYSIOLOGICAL STABILITY IN RATS WITH MYOCARDIAL INFARCTION TREATED WITH CARDIAC STEM CELLS

Bruce Doepker, Anthony Gerlach, Kari Mount, Lindsay Pell, Claire Murphy, Crystal Tubbs, Gary Phillips, The Ohio State University Medical Center Introduction: Argatroban is a direct thrombin inhibitor used to treat patients with suspected or confirmed heparin-induced thrombocytopenia or intolerance to unfractionated heparin or low molecular weight heparins. Bleeding is the most serious adverse event associated with argatroban therapy. Major bleeding rates are reported between 2-11% and may be higher in certain high risk populations such as the critically ill. Hypothesis: To determine risk factors for bleeding in critically ill patients receiving argatroban. Methods: A retrospective cohort study was performed at an academic tertiary care center. The study included critically ill patients from our medical, cardiothoracic, and surgery intensive care units who received argatroban from July 2007-June 2008. Major and minor bleeding rates were assessed. Major bleeding was defined as a hemoglobin (Hgb) reduction of ⱖ 2g/dL plus a transfusion of at least two units of blood in a 24hr period or retroperitoneal, intracranial, or other life-threatening bleed. Minor bleeding was any bleed reported that did not fit the major bleeding definition. Univariate analysis of categorical data was performed using ␹2 test or Fisher’s exact. Continuous data were compared using Student’s t-test or Mann-Whitney U for non-parametric data. Univariate logistic-regression was used to evaluate independent risk factors for bleeding. Results: 73 patients were included with a total of 16 (21.9%) bleeds [major n⫽7 (9.6%); minor n⫽9 (12.3%)]. Six patients had a decrease in Hgb ⱖ 2g/dl and transfusion of ⱖ 2 units of blood and one developed an intracranial bleed. Four risk factors were identified by univariate analysis for bleeding in the critically ill: major surgery prior to or during argatroban therapy (OR ⫽8.4, 95% CI: 2.3-30.1, p⫽0.001), dosing weight ⱖ 90kg (OR ⫽ 4.8 95% CI 1.4-15.8, p⫽0.01), total bilirubin ⱖ3mg/dL (OR ⫽6.6, 95% CI: 1.8-24.3, p⫽0.004), and baseline platelets ⱕ 70K/␮L (OR ⫽4.2, 95% CI: 1.1-16.3, p⫽0.039). Conclusions: Risk factors for bleeding in the critically ill include major surgery prior to or during argatroban therapy, dosing weight ⱖ 90kg, total bilirubin ⱖ 3mg/dL, and baseline platelets ⱕ 70K/␮L.

Tong Wang, Shaoxin Zheng, The Second Affiliatied Hospital of Sun Yat-sen University, Changqing Zhou, Yinlun Weng, Hui Huang, The Second Affiliated Hospital of Sun Yat-sen University, Wei Wu, The Second Affiliatied Hospital of Sun Yat-sen University, Shijie Sun, Institute of Critical Care Medicine, Jingfeng Wang, The Second Affiliatied Hospital of Sun Yat-sen University, Wanchun Tang, Institute of Critical Care Medicine Introduction: Arrhythmia is of concern after cardiac stem cells (CSCs) transplantation in repairing infarcted myocardium. However, whether severe malignant ventricular arrhythmia is induced after CSCs transplantation in the myocardial infarction model are still unclear. Hypothesis: Cardiac electrophysiological stability would be significant improved in myocardial infarction rats treated with CSCs compared with PBS. Methods: Myocardial infarction was induced by ligation of the left anterior descending artery in 20 rats. Two weeks later, animals were randomized to receive 5⫻106 CSCs labeled with PKH26 or phosphate buffer solution (PBS) alone as a placebo injection into the infarction zone in the anterior ventricular free wall. 6 weeks after CSCs or PBS injection, activation recovery time (ART) dispersions and induction of malignant ventricular arrhythmias were measured. Labeled CSCs were observed in 5 ␮m cryostat sections from each harvested heart. Results: There were no significant differences in Unipolar electrograms ART on the infarct area between the CSCs group and PBS group(91.5⫾11.6ms vs 112.8⫾37.0ms, p⫽0.0991). However, in CSCs group, the ART was significantly shorter in the infarct marginal zone(94.5⫾10.9ms vs 118.1⫾24.8ms p⫽0.0129)and the non-infarct zone(94.0⫾11.5ms vs 120.1⫾26.0ms p⫽0.0094). While the ART dispersion was shorter in the CSCs group compared with that in the PBS group(15.5⫾4.4ms vs 38.6⫾14.9ms p⫽0.000177). The malignant ventricular arrhythmias were significantly less inducible in the CSCs group (1 of 10) than the PBS group (9 of 10), (p⫽0.001). Labeled CSCs were identified in the infarct zone and infarct marginal zone and expressed Connexin-43, von Willebrand factor, ␣-smooth muscle actin and ␣-sarcomeric actin. Conclusions: CSCs can improve cardiac electrophysiological stability in rats with myocardial infarction treated with allogenic CSCs.


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815

TRENDS IN BEST PRACTICE ADHERENCE IN A LARGE COHORT OF ICUS: 2005 – 2010

IMPROVING VANCOMYCIN INITIAL DOSING IN CRITICALLY ILL PATIENTS

Omar Badawi, Michael Breslow, Philips VISICU, Haani Jaber, North Florida Regional Medical Center, Erkan Hassan, Philips VISICU

Janice Li, National University Hospital, Andrew Udy, Royal Brisbane and Women’s Hospital, Carl Kirkpatrick, The University of Queensland, Jason Roberts, Royal Brisbane and Women’s Hospital

Introduction: Despite identification of multiple clinical practices known to improve ICU outcomes, little is known about the use of these therapies in routine practice. The uniform data structure in the ⬎1M patient eICU® Program database allows for standardized reporting of adherence rates providing insight into use of these therapies in a large ICU cohort. Hypothesis: There is inconsistent use of ICU best practices, but increased prioritization has had a beneficial effect on usage over time. Methods: Retrospective, multi-center analysis of existing data in the eICU Program database. Explicit criteria were developed using evidencebased medicine (EBM) standards for the following metrics: % of patients (pts) at risk for VTE treated within (w/n) 24 hrs of admission; % of ventilated pts given stress ulcer prophylaxis (SUP) w/n 24 hrs; % of PRBC transfusions with a hgb ⬍ 7 g/dL in eligible pts; % of ABGs with a TV ⬍ 6.5 mL/kg (LTVV) in pts with ARDS or ALI. Each pt discharged between 2005 and 2010 was evaluated and adherence to each metric was reported at quarterly intervals to each eICU program and benchmarked against the entire eICU population. Negative binomial regression was used to assess trends in quarterly adherence. Results: 1,060,663 patients from 321 ICUs (195 hospitals) were analyzed. Annual patient counts were 57,251; 134,410; 194,819; 247,194; 273,978; 153,011 between 2005 and Q2 2010 respectively. Overall, 81.9% of 648,575 pts at risk for VTE were treated w/n 24 hrs with adherence increasing from 60.4% in 2005 to 91.7% in 2010 (p⬍0.001). 95.7% of 131,096 of at risk pts received SUP w/n 24 hrs, increasing from 92.5% to 96.5% (p⫽0.01). 9.9% of 153,683 PRBCs transfused were associated with a hgb ⬍ 7g/dL, increasing from 3.5% to 13.0% (p⬍.001). 23.9% of 3,791 ABGs indicated LTTV, increasing from 21.3% to 26.3% (p⫽0.051) between 2006 and 2010 (2005 data N/A). Conclusions: This large ICU cohort demonstrates adherence to EBM has improved over time yet remains suboptimal for LTTV and restrictive transfusion strategies. Baseline adoption rates of EBM, presence of a tele-ICU, and/or quarterly measurement and reporting of compliance with internal and external benchmarking to peers may have contributed to this trend.

Introduction: Clinical outcomes of infections in critically ill patients caused by resistant Gram-positive bacteria are poor. Vancomycin remains the preferred antibiotic for this indication, however dosing that is not individualised to patient requirements may contribute to sub-therapeutic exposures leading to poor outcomes and resistance. Weight-based loading doses are recommended in critically ill patients to rapidly achieve therapeutic concentrations. Hypothesis: A dosing protocol would help to improve the initial dosing of vancomycin in critically ill patients and subsequent target achievement in the first 24 hours of therapy. Methods: A retrospective evaluation was conducted in an intensive care unit preand post-implementation of a vancomycin dosing protocol advocating weightbased initial dosing (25-30 mg/kg). Vancomycin exposures (AUC) and trough concentrations in the first 24 hours were obtained using serum concentrations and the Bayesian Software, TCIWorks (www.tciworks.info). AUC/MIC ratios were calculated with MICs of 1mg/L assumed for all cases given local susceptibility patterns. Initial vancomycin doses, exposures and trough concentrations were compared between the 2 groups using Chi-square tests and Mann-Whitney tests. Results: A total of 111 vancomycin orders were analysed in the pre- (n⫽80) and post- (n⫽31) implementation groups. The post-implementation group had significantly higher weight-based initial doses (20.0 mg/kg vs 12.5mg/kg; p⬍0.01) compared to the pre-implementation group. This corresponded to significantly higher vancomycin exposures (363.0 mg.h/L vs 260.0 mg.h/L; p⫽0.01) and trough concentrations (10.1 mg/L vs 6.8 mg/L; p⫽0.01) in the post-implementation group. Despite higher weight-based initial doses, approximately 50% of patients in the post-implementation group had not achieved optimal vancomycin exposures (AUC/MIC ⬎350) in the first 24 hours of therapy. Conclusions: A vancomycin dosing protocol improved the initial dosing of vancomycin and the proportion of patients that rapidly achieved optimal vancomycin exposures. However, sub-therapeutic exposures within the first 24 hours of therapy were still prevalent and may warrant more aggressive approaches to dosing in this population.

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IMPACT OF A TWO-HOUR TIME TARGET TO ACHIEVEMENT OF THERAPEUTIC HYPOTHERMIA POST-CARDIAC ARREST

POSTOPERATIVE DELIRIUM RISK FACTORS AND OUTCOMES IN A CARDIOVASCULAR INTENSIVE CARE UNIT

Giulia Vicari, Cleveland Clinic, Dustin Spencer, Timothy Ellender, Michelle Deckard, Methodist Hospital/Clarian Health Introduction: Therapeutic hypothermia (TH) for post-cardiac arrest patients with return of spontaneous circulation (ROSC) has been proven to reduce mortality and improve neurologic outcomes. While the benefits of TH have been proven, the optimal time from initiation of hypothermia to achievement of target temperature has not been established. Hypothesis: Achieving target temperature within two hours from initiation of TH improves survival to hospital discharge. Methods: We conducted a single center, retrospective cohort study of postcardiac arrest patients treated with TH during 2009. Subjects were divided into two cohorts for comparison; those who reached target temperature (33 °C) in ⱕ two hours (cohort A) and those who reached the target in ⬎ two hours (cohort B). Patient demographics, initial temperature, site of arrest, time from ROSC and TH initiation to target temperature, initial rhythm, Glasgow Coma Scale (GCS) and Cerebral Performance Category (CPC) at discharge, and cooling methods were collected and analyzed using Chi-Square and Mann-Whitney U tests. Results: 123 patients completed the TH protocol and were included for analysis; 44 patients in cohort A and 79 in cohort B. Patients in cohort A had a significantly lower average initial temperature (35.4 vs. 36.4 °C, p⬍0.001) and body mass index (25.2 vs. 31.8 k/m2, p⫽0.008) compared to patients in cohort B. 20 patients (45.5%) in cohort A survived to hospital discharge compared to 34 patients (43%) in cohort B (p⫽0.37). There were more patients in cohort A discharged with minor neurologic injury (GCS ⱖ 13), (36.4 vs. 32.9, p⫽0.75) and a favorable neurologic outcome (CPC ⱕ 2), (31.8 vs. 30.4%, p⫽0.87) compared to patients in cohort B. Conclusions: More patients who achieved target temperature in ⱕ 2 hours survived to hospital discharge and with a higher level of cerebral functioning although these results did not achieve statistical significance. Though we were unable to show a difference between survival and functional outcomes for those who achieved earlier cooling, our data suggests earlier cooling might offer added metabolic protection. Further study is needed to fully assess the impact of achieving target temperature within a specified time period.


Jaime Foushee, Presbyterian College School of Pharmacy, Sarah Bush, Douglas Furmanek, Emily Ohanuka, Christopher Wright, John Kudlak, Anna Cass, Greenville Hospital System University Medical Center Introduction: Delirium is a postoperative complication that occurs frequently in older adults undergoing cardiac surgery. Increased patient morbidity and mortality are associated with postoperative delirium. Hypothesis: This study was designed to identify patient factors associated with postoperative delirium, as well as examine outcomes based on delirium development and treatments received. Methods: Adult patients admitted postoperatively to the cardiovascular intensive care unit (CVICU) between November 2009 and March 2010 were included in this prospective, cohort study. Delirium assessments were conducted as part of routine care throughout the CVICU admission. Pre-, intra-, and post-operative patient factors were collected and analyzed for associations with delirium. Patients with delirium were divided into nested cohorts based on pharmacologic treatments received. Outcomes assessed for both the overall and nested cohorts included CVICU and hospital length of stay, in-hospital mortality, need for reintubation, and discharge to a long term care (LTC) facility. Results: Delirium occurred at an incidence of 14.75% during the study period. A significant association existed between peripheral vascular disease (PVD), aortic cross clamp time (CCT) of ⬎ 90 minutes, postoperative benzodiazepine receipt, or age ⬎ 65 and the development of delirium in a logistic regression analysis. The log-rank test identified PVD, postoperative benzodiazepine receipt, dementia, and aortic CCT ⬎ 90 minutes as risk factors for the time to delirium development. Delirium was associated with increased hospital (p⬍0.01) and CVICU (p⬍0.01) length of stay, as well as discharge to LTC facilities (p⬍0.01). No differences in the aforementioned outcomes were observed between patients who received delirium treatment and those that did not, or when comparing typical and atypical antipsychotics. Delirium resolution variables also did not differ. Conclusions: Delirium was associated with significant patient morbidity in this study. While PVD, postoperative benzodiazepine receipt, and aortic CCT were consistently correlated with the development of postoperative delirium, the use of pharmacologic agents as treatment did not affect overall outcomes.

818 THE NOVEL METHOD FOR BEDSIDE POSTPYLORIC FEEDING TUBE PLACEMENT USING NASAL ENDOSCOPY Atsunori Hashimoto, Joji Kotani, Taihei Yamada, Takahiro Ueda, Sachikou Fuse, Tomoko Inoue, Mitsunori Kawai, Keisuke Kohama, Takaaki Osako, Atsushi Miyawaki, Hyogo College of Medicine Introduction: Postpyloricfeeding may facilitate tolerance to enteral nutrition (EN) in the criticallyill patients (pts). However, the techniques using conventional oral endoscopyis difficult and radiological method requires transfer of pts to radiology suites,which may delaythe commencement of EN. Hypothesis: The new method ofbedside nasojejunal (NJ) tube placement using a newly developed nasal endoscopyas thin as 5.5 mm in diameter can be performed successfully. Methods: Thetubes were inserted by Seldinger’s technique-like method, i.e., the nasalendoscope was inserted through a nasal foramen into the descending part orhorizontal part of duodenum, and the thick guidewire for ileus tube wasinserted through the endoscope channel as far as possible under directobservation. Then, the endoscope was pulled out leaving the guidewire, thefeeding tube was inserted along the guidewire, and then the gudewire was pulledout. The 100 ml of contrast medium was injected into the tube, followed by theabdominal X-ray immediately and 24 hours later to estimate the location of thetube tip, regurgitation of the contrast medium into the stomach and intestinalmotility. Results: Consecutive40 pts requiring EN were enrolled in the study. The tubes were successfullyplaced postpylorically in 36 pts (90%), i.e., beyond the ligament of Treitz in18 pts (45%), at thehorizontal part in 5 pts (12.5%), at the descending part in 11 pts (27.5 %),and at the bulb in 2 pts (5%). There was no regurgitation of the contrast medium into the stomach in these ptsexcept the last group. The mean time for tube insertion was 13(7-18) minutes. The tubes placed at the horizontal part moved beyond theligament of Treitz in 4 pts (4/5⫽80%) whereas the tubes placed at thedescending part moved to the horizontal part in 4 pts (4/11⫽36.4%) and beyondthe ligament of Treitz in 2 pts (2/11⫽18.2%) in 24 hours. Conclusions: Bedsidepostpyloric feeding tube placement using nasal endoscopy is possible in 90% ofpts in short time. Once placed postpylorically, the tubes tend to move ahead in24 hrs. This may overcome delays in the commencement of EN resulting from other methods of postpyloric tubeplacement.



820

SECRETION OF GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE IS DEPENDENT ON THE RATE OF GASTRIC EMPTYING AND A DETERMINANT OF THE PLASMA INSULIN RESPONSE IN THE CRITICALLY ILL

INTRA-ABDOMINAL HYPERTENSION IN THE CRITICALLY ILL CHILD: LOCAL EXPERIENCE AND A RESEARCH DATABASE

Adam Deane, Antony Zaknic, Royal Adelaide Hospital, Michael Horowitz, University of Adelaide, Matthew Summers, Marianne Chapman, Royal Adelaide Hospital Introduction: In health, the incretin effect which accounts for ⬃70% of the insulin response to an enteral glucose load is mediated primarily by glucose-dependent insulinotropic polypeptide (GIP) which is secreted from the proximal small intestine. However, in type 2 diabetes the incretin effect is attenuated, principally because the insulinotropic effect of GIP is markedly reduced and this has stimulated the use of the other incretin hormone, glucagon-like peptide-1, in the management of glycaemia in this group. Hypothesis: Secretion of GIP is maintained in the critically ill, and there are relationships between gastric emptying, plasma GIP and insulin concentrations. Methods: 23 critically ill nondiabetic patients were studied (age 53(65) yrs;18M;APACHE II score 21 (27)). A test ‘meal’ of 100 ml of nutrient liquid 1 kcal/ml, mixed with 100 ␮l 13C-octanoic acid and 3 g of 3-O-methylglucose (3-OMG) (an index of glucose absorption), was administered intragastrically over 5 min. Breath samples were collected between t⫽0-330min and analysed for 13CO2 used to calculate the gastric emptying coefficient (GEC)-a global index of gastric emptying; with the greater the GEC value, the more rapid emptying, and a GEC ⬍2.64 defined delayed gastric emptying. Arterial blood was sampled at t ⫽ 0,30,60 and 330 min for measurement of plasma GIP, serum insulin and 3-OMG, and blood glucose. Data are median(range) and comparisons were made using Mann-Whitney U tests. Correlations were measured within subject and evaluated adjusted for repeated measures. Results: 9 patients had delayed gastric emptying. 30 min after the meal patients with normal gastric had greater plasma GIP concentrations, when compared to delayed gastric emptying (normal: 290(2552) pg/mL vs. delayed: 95(227) pg/mL;P⬍0.01) Plasma GIP rose after the meal with the magnitude of the initial increase related to both gastric emptying (GEC and GIP at t⫽30:r⫽0.41;P⫽0.05) and glucose absorption (3-OMG and GIP:r⫽0.53;P⬍0.01). Serum insulin concentrations were strongly associated with plasma GIP (r⫽0.58;P⬍0.01). Conclusions: In the critically ill the secretion of GIP is dependent on the rate of gastric emptying and a determinant of the plasma insulin response.

Kristene Nagy, Akron Children’s Hospital, Gabriel Mancini, Loyola University Chicago, John Crow, Akron Children’s Hospital, Michael Forbes, Children’s Hospital Medical Center of Akron, Michael Bigham, Akron Children’s Hospital Introduction: The spectrum of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) is an area of growing clinical interest but lacking informative pediatric data regarding intra-abdominal pressure (IAP) thresholds and staged therapies. The purpose of this study is to review our 1-year experience with IAP monitoring and IAH/ACS treatment while trialing an experimental database. Hypothesis: We proposed that a review of IAH/ACS in the PICU can serve to test the capabilities of a newly constructed pediatric-specific relational database. Methods: This IRB approved study evaluated retrospectively all patients in the med/surg PICU who had IAP monitoring over a 12 month period (7/09 –7/10). Patients were evaluated/managed according to a locally developed IAH/ACS algorithm. A relational database for these data was developed using FileMaker Pro 11 Advanced. Numerous calculations, integrity checks, and visual alerts helped guarantee integrity of data. Data were exported to Excel and analyzed using SPSS v17.0. Statistical testing was twosided and all inferences were based on a type I error rate of 5%. Results: 21 patients had IAP measurements during the study period with a mean age of 5.0⫾6.4yrs representing a local IAH incidence of 1.5% with an ACS incidence of 0.5%. The average admission PRISM score was 9.7⫾9.3 with a cohort mortality of 23.8%. There were no deaths in cohort patients without IAH, but death rates exceeded PRISM-predicted mortality in 3 of 4 IAH Grades. A trend was noted between increasing IAH Grades and duration of mechanical ventilation (p⫽0.107), PICU LOS (p⫽0.116), and Hospital LOS (p⫽0.051). Increasing IAH Grades (I-IV) were associated with a coincident decrease in weight-adjusted hourly urine output (p ⬍ 0.001). All patients had NG decompression and experienced the following therapies: 1 paracentesis, 2 peritoneal drainage catheters, 2 CRRT, and 1 decompressive laporotomy. Conclusions: IAH/ACS remain relatively low frequency occurrences in the PICU but are associated with high mortality rates. The representative cohort reported here have permitted the development/testing of a robust relational database that can support data collection necessary for large-scale prospective studies.

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RELIABILITY OF 3 DIFFERENT CULTURE DIAGNOSTICS FOR IDENTIFICATION OF THE MICROBIAL ETIOLOGY OF PEDIATRIC VAP

HAND HYGIENE COMPLIANCE AND MULTI-DRUG RESISTANT ORGANISM INFECTION IN THE INTENSIVE CARE UNIT

Ramya Srinivasan, UCSF, Jeanine Wiener-Kronish, Massachusetts General Hospital, Heidi Flori, Children’s Hospital Oakland

Dorothy Bird, Boston University Medical Center, Carol Sulis, Dale Ford, George Barth, Peter Burke, Suresh Agarwal, Boston Medical Center

Introduction: Appropriate management of VAP relies upon accurate microbial diagnosis. During a prospective study of pediatric patients suspected of VAP, we ascertained the sensitivity, specificity, and reliability between endotracheal [ET], bronchoscopic BAL [bBAL], and blind mini-BAL [mBAL] cultures. Methods: From 4/2006 to 5/2007, all PICU patients mechanically ventilated ⬎48 hours with a positive ET gram stain were eligible. VAP was defined by both CDC/ NNIS criteria and clinician diagnosis. Patients had ET samples sent and subsequently had either a bBAL or mBAL sample of lower respiratory tract secretions sent for culture. All cultures were qualitative except mBAL which was quantitative. Results: The first suspected episode of VAP was analyzed in a total of 33 patients enrolled. All 16 patients with VAP had antibiotics prior to cultures while 70% of 17 patients diagnosed with airway colonization had antibiotic exposure. A bacterial index [BI] of 10 4 cfu/mL did not distinguish between VAP and colonization {30% vs. 22%, p⫽1.0). The median time from ET to BAL culture was also significantly different (bBAL 4335 vs mBAL 1440 min, p⬍0.01). The sensitivity and specificity for diagnosis of VAP by cultures were for ET 87.5% & 17.7%, mBAL 70.0% & 22.2%, and 66.7% and 50.0% for bBAL. The concordance rate, expected agreement, and Kappa score [95% CI] of intertest reliability between ET and mBAL for those with VAP vs. colonization were: 60.0%, 16.0%, 0.52 [0.23,0.88] vs. 33.3%, 7.41%, 0.28 [0.03,0.60], respectively. The concordance rate, expected agreement, and Kappa score [95% CI] of intertest reliability between ET and bBAL for those with VAP vs. colonization were: 66.7%, 13.9%, 0.61 [0.29,1.0] vs. 37.5%, 15.6%, 0.26 [0.07,0.64], respectively. Conclusions: In the setting of antibiotic use within the previous 72 hours of culture, mBAL or bBAL compared to ET has moderate intertest reliability for a diagnosis of VAP and fair intertest reliability for the diagnosis of colonization. BI of 10 4 cfu/mL is unreliable for diagnosis of VAP with prior antibiotic use. The ideal culture sample for diagnosis of VAP in this setting is unclear and needs further investigation. Funding: SCCOR HL 74005 & 69809, RR01271

Introduction: Multi-drug resistant organism (MDRO) infection is an important problem in the intensive care unit (ICU), and the impact of hand hygiene on its reduction has not been assessed. Hypothesis: We believed that reduction in MDRO infection would follow improved hand hygiene compliance. Methods: Prospectively-collected data were examined retrospectively from our infection control databases during a 33-month hand hygiene task force. Rates of methicillin-resistant S. aureus (MRSA), C. difficile (CD), and vancomycin-resistant enterococcus (VRE) were calculated based on infections per 1000 patient days in one surgical intensive care unit (SICU) and 2 medical intensive care units (MICUs). Hand hygiene was estimated by measuring product consumption. Infection rates are expressed as infection per 1000 patient days. Our institution is an urban academic level 1 trauma center. Results: Hand sanitizer use increased significantly during the study period, while hand soap use did not change. At the same time, overall MDRO infection decreased significantly from 5.22 in the MICUs and 4.72 in the SICU to 2.46 and 2.27 , respectively. MRSA decreased from 3.48 in the MICUs and 4.44 in the SICU to 1.64 and 0.95, respectively. VRE decreased in the MICUs from 1.24 to 0.23 and remained very low in the SICU (0.00-0.85). Incidence of CD did not change in the MICUs or the SICU during the study period. Conclusions: Improvement in hand sanitizer use was associated with decreased incidence of MRSA and VRE in the MICUs and decreased incidence of MRSA in the SICU. Incidence of CD did not change during the study period, likely because hand soap use did not change significantly. Hand hygiene likely has an important role in the reduction of MDRO in the ICU.


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EFFECT OF ANTIPSYCHOTICS FOR THE TREATMENT OF ACUTE DELIRIUM DETECTED BY THE CAM-ICU ON VENTILATOR FREE DAYS IN THE CRITICALLY ILL

UNIDIRECTIONAL BREATHING PATTERN IMPROVES THE BREATHING EFFICIENCY IN COPD PATIENTS

Bruce Doepker, Gary Phillips, The Ohio State University Medical Center Introduction: Delirium is a common condition diagnosed in ICU. Incidence of delirium ranges from 60-80% in mechanically ventilated (MV) ICU patients. Delirium is associated with prolonged MV, long term cognitive dysfunction, increased hospital length of stay (LOS), and mortality. Limited data exists evaluating the use of antipsychotics (A) for the treatment of delirium. Hypothesis: Medical ICU (MICU) patients treated with A for delirium will have increased number of MV-free days (day 1-28) than patients that did not receive antipsychotics (NA). Methods: Retrospective single center cohort study performed at an academic tertiary care center. The study included MICU patients admitted between April 2008-May 2009 with a LOS ⬎ 5 days, spent ⬎ 48hrs on the MV who developed delirium according to the CAM-ICU. Treatment was defined as receiving at least 1 dose of haloperidol, seroquel, or risperidone every 12 hrs for at least 48hr. Demographic data and outcome measures were collected. Univariate analysis of categorical data was performed using ␹2 test or Fisher’s exact. Continuous data was compared using Student’s t-test or Mann-Whitney U for nonparametric data. Multivariate linear-regression was used to evaluate independent risk factors for MV-free days. Results: A total of 103 patients were identified (A n⫽53, NA n⫽50). There were no statistically significant differences in the use of BZ drips [A-38 (72%) NA-34 (68%), p⫽0.68)], total midazolam equivalents [median, A-41.5(0-177) NA-56.4 (0-214), p⫽0.58], or continuous sedation days (median, A-5.3 (0-18) NA-4.9 (0-12), p⫽0.99) in our study population. Upon univariate analysis delirium days were found to be statistically different between the groups [median, A-9 (2-32) NA-7 (2-31), p⫽0.004]. There was not a statistically significant difference in MV-free days (median, A-17 (0-25) NA19.5 (0-24), p⫽0.28). Conclusions: Antipsychotic use in delirious MICU patients did not impact the number of MV-free days. However, this was a retrospective evaluation and future studies with well defined endpoints should prospectively evaluate the impact of A on MV days.

Demet Sulemanji, Fangping Bao, Yandong Jiang, Robert Kacmarek, Massachusetts General Hospital Introduction: Pursed-lip breathing (PLB), nose in and mouth out breathing (NMB), is thought to create positive end expiratory pressure, stabilize small airways and facilitate exhalation in patients with expiratory obstructive disorders. However, the exact mechanism remains unknown. Hypothesis: The benefits of PLB, are achieved mainly through reduction of upper airway dead space. Methods: Four breathing patterns were performed in random order in 8 spontaneously breathing patients with severe COPD. The study mask had nasal and mouth pieces. Each piece had a removable one-way valve. The nose in and nose out (NNB) and mouth in and mouth out (MMB) breathings were achieved without the use of one-way valves and the mouth in nose out breathing (MNB) and NMB were achieved with the one-way valves in place each facing opposite directions. Each breathing pattern lasted for 5 min followed by a rest period. Breathing effort, tidal volume and breathing frequency were controlled by the patient. A flow and infrared CO2 sensor was placed in the exhalation mask limb to continuously monitor respiratory parameters. The anatomic dead space and expired tidal volume were determined. The mechanical dead space of the masks during MMB and NNB was subtracted and the true natural airway dead space during MMB and NNB was calculated and used for data analysis. Breathing efficiency was calculated as alveolar tidal volume divided by expired volume. Results: There was no significant difference in breathing efficiency between the two unidirectional breathing patterns, NMB (73.8⫾6.5%) and MNB (73.5⫾4.6%), however there was between the two bi-directional breathing patterns, MMB (58.6⫾9.4%) and NNB (63.8⫾6.4%) (p⬍0.01). The breathing efficiency achieved with bidirectional breathing was significantly lower than that of unidirectional breathing (p⬍0.01). Anatomic dead spaces (ml) for each pattern were: NMB: 186.4⫾31.2, MNB: 205.2⫾35.2, MMB: 231.8⫾22.7, NNB: 200.4⫾20.2. The most favored breathing pattern was NMB. Conclusions: Unidirectional breathing results in a higher breathing efficiency than bi-directional breathing. The benefits of PLB in COPD patients may be achieved mainly by reduction of anatomic dead space and improvement of breathing efficiency.

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VANCOMYCIN TROUGH LEVELS >10.0 MCG/ML – INCREASING THE RISK OF NEPHROTOXICITY?

PREVENTION OF ACUTE KIDNEY INJURY WITH LARGE VOLUME OF URINE OUTPUT IN TRAUMATIC RHABDOMYOLYSIS

Leslie Cihak, Richard McKnight, Joan Newbolt, Jessica Wolfe, West Virginia University Hospital Introduction: A recently published study evaluated the incidence of nephrotoxicity in all hospitalized patients receiving intravenous (IV) vancomycin, with a reported incidence of 22.5%. In this study, residence in the intensive care unit (ICU), initial vancomycin trough level (VTL) of ⬎9.9mcg/mL and actual body weight ⱖ101kg were found to be independent predictors for the development of nephrotoxicity. Based on the current guideline recommendations to target a VTL of 10-20mcg/mL, this incidence of nephrotoxicity is concerning. As a result, we evaluated the incidence of nephrotoxicity in critically ill adult patients receiving IV vancomycin at our institution. Methods: A retrospective analysis was performed for patients admitted to the ICU between January 2008 and March 2010. This study was designed to have identical inclusion and exclusion criteria to the study mentioned above. The primary objectives was to determine the incidence of nephrotoxicity, which was evaluated using SCr (increase of 0.5mg/dL or 50% on two consecutive days), urine output and the RIFLE criteria. To reach an 80% power to detect a 10% difference in the incidence of nephrotoxicity, a sample size of 60 patients was required. Results: Of the sixty patients identified, 7 patients (11.7%) developed nephrotoxicity (defined by increases in SCr alone). Only 3 of these 7 patients also had concomitant decreases in urine output, suggesting that only 5% of patients truly developed nephrotoxicity by these standards. Therefore the incidence of nephrotoxicity was significantly different between these two studies (11.7% [or 5%] vs. 22.5%). The Z-test revealed that if the real rate of nephrotoxicity is 22.5%, the chances of having 7 or less patients develop nephrotoxicity was 2.5%. Additionally, when utilizing the CART analysis, a VTL ⬎18.1mcg/mL was associated with more nephrotoxicity (24.0% vs. 2.9%). Conclusions: Although controversial, vancomycin is considered a risk factor in the development of nephrotoxicity. Our analysis found a lower percentage of patients who developed nephrotoxicity compared to a previously published study, suggesting that the risk may not be as high as perceived, even in critically ill patients.

Ryoko Warabi, Kunihiko Maekawa, Naofumi Bunnya, Kazuhisa Mori, Yasufumi Asai, Sapporo Medical University Introduction: Large volume urination of 3ml/kg/hr (approximately 200 ml/hr) has been recommended to prevent acute kidneyinjury (AKI) in patients with traumatic rhabdomyolysis despitethe absence of sufficient evidence validating its use. Hypothesis: Large volume of urine output mightbe effective for preventing AKI in traumatic rhabdomyolysis. The objectiveof this study was to evaluate the efficacy of large volume urineoutput for preventing AKI in traumatic rhabdomyolysis. Methods: Weconducted a retrospective cohort study on trauma patients with rhabdomyolysis defined as a creatine kinase (CK) levels greater than 2000 U/L,referred to a single tertiarycare ICU over 4 years(2006-2009). Hourly urine output,serum creatine, CK, demographicdata, trauma scores, and need for renal replacement therapy (RRT) were collected and were stratifiedaccording to Acute Kidney Injury Network criteria. Patients with urine output of greaterthan 3 ml/kg/hr were assigned to largevolume of urine output (LVUOP) group. Patientsreceived the LVUOP strategy onthe basis of the intesivist’s discretion. Results: A total of 72 patients werestudied. Of those, 22 patients were enrolled in LVUOP group and 50patients were enrolled in non-LVUOP group. There were no significantgroup differences in age, gender, Injury Severity Score (ISS), Revised TraumaScore (RTS), peak CK level except for median volume of urine output (LVUOPgroup 4.0 ml/kg/hr vs. non-LVUOP group 1.9 ml/kg/ hr,P⬍0.0001). Compared with non-LVUOP group, LVUOP group had a significantdecrease in the incidence of AKI (LVUOP group 4.5% vs. non-LVUOPgroup 22.0%; adjusted odds ratio, 0.036; 95% confidenceinterval, 0.002-0.596; p⫽0.02). There was no significant difference in theneed of RRT (LVUOP group 0% vs. non-LVUOP group 6%; p⫽0.98). Conclusions: Large volume of urine output may be effective for preventing AKI intraumatic rhabdomyolysis. Further studies are warranted to establish the efficacyfor avoidance of RRT.


828 DURATION OF RED BLOOD CELL STORAGE AND DEVELOPMENT OF POSTOPERATIVE INFECTIOUS COMPLICATIONS: A RETROSPECTIVE COHORT STUDY Arun Subramanian, Liang Hui Tan, Daryl Kor, Mayo Clinic Introduction: RBC storage age has been recognized as a risk factor for postoperative complications. Hypothesis: We hypothesized that a longer duration of RBC storage would be associated with an increased rate of postoperative infections. Methods: After IRB approval, data was retrospectively collected on all patients who had esophagectomy from 2005 to 2009 (n⫽465). From this cohort, we identified all patients who received RBC transfusion either before the development of a postoperative infection or during a similar exposure interval in those without infection. The age and volume of each RBC unit were determined. The primary endpoint was postoperative infection, defined as a composite of postoperative pneumonia, surgical site infection (SSI) and/or blood stream infection (BSI). Using univariate and multivariate logistic regression, the association between RBC age and postoperative infection was assessed while controlling for preoperative hemoglobin, diabetes, smoking, duration of surgery, median intraoperative temperature, and total number of RBC units administered. Results: 146 patients received RBC transfusion either before the development of a postoperative infection or during a similar exposure interval. In univariate analysis, the median age of the oldest RBC unit transfused was significantly higher in patients who developed an infection (32.5 days vs 22.5 days, P⬍0.01). Multivariate analysis demonstrated that RBC storage duration (OR ⫽ 1.10 per additional storage day, 95% CI 1.04-1.16; p ⬍ 0.01), intraoperative temperature (OR ⫽ 0.51 per °C increase, 95% CI 0.29-0.83; p ⫽ 0.01), and duration of surgery (OR ⫽ 1.10 per each additional 30 minutes, 95% CI 1.0-1.22; p ⫽ 0.05) were predictive for the development of a postoperative infection. However, when controlling for the number of RBC units administered, the association between RBC storage age and the development of postoperative infection was no longer significant (OR ⫽0.99 per additional storage day, 95% CI 0.93 - 1.06; p ⫽ 0.77). Conclusions: Although our initial results indicated an association between RBC storage age and postoperative infection, this association was lost when appropriately controlling for the total number of RBC units transfused.



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THE BALLOON DILATATIONAL TRACHEOSTOMY PROCEDURE NOT COMPROMISES THE BLOOD GAS VALUES

HOUSESTAFF DIFFICULT AIRWAY PERFORMANCE IMPROVEMENT PROGRAM REDUCES AIRWAY COMPLICATIONS IN THE ICU

Maria Jose´ Sucre, Aniello De Nicola, San Leonardo Hospital - Castellammare di Stabia, Italy Introduction: All traditional techniques for percutaneous dilatation tracheostomy (PDT) have analogous procedural complications. Some of the major complications are unrecognized hypoxia, hypercarbia and respiratory acidosis. The Ciaglia Blue Dolphin (CBD) is the device for PDT that uses the radial balloon dilatation that have the advantage of a short operating time and a good safety profile. Hypothesis: To evaluate whether the CBD procedure has a negative impact on blood gas values when it is video-guided through the laryngeal mask airway (LMA). Methods: An observational, clinical study was conducted in adult coma patients. We report our clinical practice of 40 video-guided PDT performed using CBD technique (Cook Inc., Bloomington, USA) in consecutive patients undergoing elective tracheostomy for failure to wean and continued mechanical ventilation. Informed consent was obtained from family member. All tracheostomies were carried out under general anesthesia using a LMA. We performed the technique inflating the balloon during 25 seconds to create a tracheostoma. Blood samples for arterial blood gas measurements were taken before the procedure (first value) and just after the insertion of tracheostomy tube (second value). Results: Bedside PDT with CBD technique was successfully performed in the ICU for all 40 patients. The procedures were completed in mean time of 5.5⫾1.3 minutes and with negligible blood loss in all patients. There was no significant difference in pH, PaO2, or PaCO2 between the first and second arterial blood gas values. The oxygenation did not deteriorate even in patients with gravely impaired gas exchange with a PaO2/FiO2 averaging 130⫾42 mmHg (range 45-192 mmHg) at a PEEP of 17⫾4 mbar. The procedural drawbacks were limited to three patients requiring the repetition of balloon inflation to create an adequate tracheostoma and that was completed without respiratory interferences. Conclusions: In all patients fiberoptic-assisted CBD, performed using a LMA, did not compromise the blood gas values during and after the procedure. CBD has been shown to be a minimally invasive alternative to the conventional techniques which may have a tendency to produce acid-base disorders.

Andrew Levinson, Rhode Island Hospital, Kevin Dushay, Brown/Rhode Island Hospital Introduction: Patients requiring endotracheal intubation in the intensive care unit are at high risk of complications. [1,2]. Practitioners face major challenges in caring for patients with difficult airways. These challenges are heightened when the practitioners are physicians in training with limited airway experience. The use of difficult airway algorithms and difficult airway equipment by skilled clinicians has been demonstrated to reduce the complication rates of emergent intubations in the ICU [3,4]. As part of a performance improvement program, housestaff rotating at a 20 bed closed academic medical intensive care unit (MICU) received training in the use of difficult airway algorithms and alternative airway devices. Devices, including bougies, laryngeal mask airways, and a video laryngoscope were then made available. Hypothesis: Our hypothesis is that training of MICU housestaff and attendings in the use of difficult airway algorithms, combine with the immediate accessibility of difficult airway devices, would result in reduced airway complications. Methods: Data from 54 consecutive intubations were analyzed following the implementation of an intensive performance improvement program. Institutional review board approval was obtained prior to data collection. Number of attempts, regurgitation, aspiration, subsequent cardiac arrest, hypoxemia, and Cormack Lehane view were recorded. Data was compared to 55 consecutive intubations from a retrospective chart review of intubations in the seven months prior to the initiation of the project. Results: There was a reduction in complications, including hypoxemia (p.04) and multiple intubation attempts (p.03), after implementing the performance improvement project. Conclusions: The implementation of difficult airway algorithms and access to difficult airway devices may improve the care of patients with difficult airways while waiting for the arrival to the ICU of more experienced personnel. References: 1. Schwartz, D.E. Anesthesiology, 1995. 82(2): p. 367-76.2. Jaber, S. Crit Care Med, 2006. 34(9): p. 2355-61.3. Mort, T.C. J Clin Anesth, 2004. 16(7): p. 508-16.4.Jaber, S. Intensive Care Med, 2010. 36(2): p. 248-55. This study was funded by a Lifespan risk management grant.

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ED OVERCROWDING AND ACCURACY OF SCREENING FOR PULMONARY EMBOLUS IN THE ED: POOR PREDICTIONS AND BAD OUTCOMES

ADAPTIVE SUPPORT VENTILATION WITH AND WITHOUT END-TIDAL CO2 CLOSED LOOP CONTROL VS. CONVENTIONAL VENTILATION

David Milzman, Georgetown University, dana kindermann, pam hu, brian weiss, veronika sudekem, connor king, georgetown University/Washington Hospital Center

Demet Sulemanji, Andrew Marchese, Massachusetts General Hospital, Marc Wysocki, Hamilton Medical AG, Robert Kacmarek, Massachusetts General Hospital Introduction: Adaptive Support Ventilation (ASV) is a new mode of ventilation.

Introduction: Despite many new evidence-based screening tools, Pulmonary Embolus detection remains difficult and mortality rates are not improving. This study examines recent ED screening success and evaluates outcomes of early ED intervention. Hypothesis: PE can not be described with HR and Pulse ox alone and delays in treatment have no effect on outcome in hemodynamically stable patients. Methods: A retrospective analysis of prospectively collected data using Electronic Medical Record (Amalga, Microsoft; Redmond, WA) and patient data was performed in a 951 bed urban teaching hospital. The study utilized information from the ED, Radiology and in-patient records to determine number of PE studies ordered, accurate results and timing of medical intervention as well as survival and hospital and ICU length of stays. Results: 7,100 consecutive patients underwent either Chest CT with angio or V/Q scan to rule out PE on presentation to the ED of the study hospital during 2year study period. 387 patients were found with acute PE (Accuracy: 5.5%)78% by CTA and remainder by V/Q. The mean age of ED pts was 61.3 (95%CI:56.2-65.9), 61.7% female, 86.6% Black 10.3% White and 285 with pre-existing disease (PED; in order: COPD,AKI,HIV,CHF,CA and Obesity). Standard vital sign cut0ffs for HR⬎100, p ox ⬍95% as cutoffs: positive predictive values of 45% and 22%, respectively. Age ⬎50 alone was 55% sensitive. Overall mortality was 6.0%. The time to intervention in the ED to initiate anti-thrombus rx was delayed compared with a co-hort of in-pts. 18% of pts had anti-thrombus RX initiated prior to radiologic evaluation. There was a difference in hospital LOS and mortality for those that received early heparin (LMW or unfractionated) VS. those that were treated after radiologic reading. This mean wait or delay was 3.6 hours. (95% CI: 2.2-6.4). Conclusions: Conclusion: ED dectection of PE is both poorly predictive and standard vital sign cutoffs used in PERC and Well’s criteria are poorly discriminatory for the majority of PE. Delays in initiating treatment based on wait to radiologic study and final reading lead to longer LOS and increased mortality in ED patients newly diagnosed with a PE.

Hypothesis: ASV with and without closed loop control by end tidal CO2 (ETCO2) (ASVCO2) would perform equivalent or better when compared to pressure control (PC) and volume control ventilation (VC) during simulated scenarios (normal lung (N), COPD, ARDS and brain injury (BI)). Methods: During VC and PC tidal volume (VT) was 6 ml/kg. The Michigan Instruments test lung with CO2 titrated into one chamber was used for all comparisons. CO2 productions of 3 ml/kg PBW/min (70 kg) or 210 ml/min, 280 ml/min, 350 ml/min and 140 ml/min were established. After stabilization at each CO2 level data was collected. Compliance and resistance of the lung model was varied in each test scenario. Results: In N and BI settings, VT (ml/kg) in ASV (7.2⫾0.4 N and BI) and ASVCO2 (N:7.3⫾0.7, BI:7.5⫾0.7) were higher than in VC (6.4⫾0.1 N and BI) and PC (6.3⫾0.3 N and BI) (p⬍0.001). ETCO2 levels (mmHg) were similar for all modes but ETCO2 ranges were narrower in ASVCO2 in N (37.3⫾1.3) and BI (38.8⫾1.7). Plateau pressures (PP, cmH2O) and respiratory rates (RR) were similar for all modes. In COPD, VT in ASV (7.6⫾0.5) and ASVCO2 (7.4⫾0.6) were higher than VC (6.2⫾0.1) and PC (6.6⫾0.3) (p⬍0.001). ETCO2 in ASVCO2 tended to be higher with a narrower range, then in other modes. PP were similar for all modes. RR in ASVCO2 were lower than in VC and PC. In ARDS settings, ETCO2 level in ASVCO2 (45.3⫾6.8) was higher than in other modes (ASV 35.6⫾13.5, VC 29.4⫾9.5, PC 31.7⫾9.7) (p⬍0.001). VT in ASVCO2 (5.3⫾1.7) was lower than in VC (6.3⫾0.2) (p⫽0.033). Overall, PP in ASV (29⫾1.9) and ASVCO2 (28.6⫾2) were lower than in VC (33.8⫾8.2) (p⫽0.001). When PP was ⱖ28 cmH2O, PP ASV [30 (29-31)] and ASVCO2 [30 (28-30)] were lower than in VC [39.5 (28-44)] and PC [37 (28-41)] (p⫽0.024). Conclusions: Disease specific CO2 management algorithms in ASVCO2 yield different patterns under different simulated conditions. Tighter CO2 control is prominent in all scenarios. The CO2 algorithm had the greatest impact during ARDS; ASVCO2 allows ETCO2 to gradually increase, resulting in greater hypercapnia than ASV, VC or PC and lower VT than VC or PC. In ARDS ASVCO2 and ASV maintained lower PP than VC or PC.


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CVP DOES NOT CORRELATE WITH ICP IN PATIENTS WITH TBI

EFFICACY OF HIGH-FLOW NASAL CANNULA VERSUS NONINVASIVE VENTILATION FOR HYPOXEMIC RESPIRATORY FAILURES: A HISTORICAL COMPARISON

John McNelis, Devan Lenhart, Jonas DeMuro, Winthrop University Hospital, Adel Hanna, Withrop University Hospital Introduction: Some intensivists have advocated the use of central venous pressure (CVP) as a bedside approximation of intra cranial pressure (ICP) in cases where an ICP monitor could not be established. Several authors advocate the use of CVP to calculate Cerebral Perfusion Pressure (CPP) when the CVP is grater than the ICP (CPP⫽MAP-CVP).The authors seek to investigate whether a clear correlation exists between ICP and CVP in patients with Traumatic Brain Injury (TBI) and whether CVP readings can be used to estimate ICP. Hypothesis: CVP corresponds with ICP in patients with TBI. Methods: The medical records of 22 patients admitted to a level one regional trauma center with TBI were reviewed retrospectively. All patients studied had both CVP pressure monitor devices applied as well as ICP monitors. Data acquired included Demographic data, age, sex, CVP, ICP, PEEP, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) on admission. Statistical Analysis was by chi squared and student t-test. Results: Twenty two medical records were examined. Twenty patients were male. All patients sustained blunt force trauma. The average age was 33.2 ⫾ 22.3 years old. The average SBP on admission was 126 ⫾ 30.8 mm H2O, the mean DBP was 64.3 ⫾ 13.2 mm H2O and the average MAP was 83.7 ⫾ 17.5 mm H20. Those patients intubated (n⫽18) did not require significant levels of PEEP: 5.1 ⫾ 1.7 mm H2O. The mean ICP of the group was 13.7 ⫾ 9.4, while the mean CVP was 7.7⫾ 3.9. This difference was statistically different, p⬍.01. Conclusions: Based on our data, our hypothesis stating that CVP can be utilized to approximate ICP is rejected. CVP pressures are not only unreliable predictors of ICP; they differ significantly from ICP readings in our cohort of patients. Such a difference may be a reflection of inaccuracies inherent within CVP monitoring (hemodynamic lability, variability in patient position, transducer and reader error, malposition of CVP catheter) as well as the limitations of the CVP to adequately estimate the varied intracranial pressures incurred within different areas of the cerebrum. CVP measurements should not, therefore, be utilized to estimate or measure ICP pressure.

Ara Synn, ASAN Medical Center, Jin Won Huh, Sang-Bum Hong, Younsuck Koh, Chae-Man Lim, Department of Pulmonary and Critical Care Medicine, Ulsan University College of Medicine Introduction: Avoiding the need of endotracheal intubation in the setting of respiratory failure is of prime interest to both clinicians and patients. In this regard, noninvasive ventilation using a mask (NIV) is established an effective modality in patients with hypercapnic respiratory failures. However, for hypoxemic respiratory failures, NIV is not only ineffective but even carries an unacceptably high mortality if failed. Recently, a new apparatus called high-flow nasal cannula (HFNC) has been introduced in the treatment of hypoxemic respiratory failures. Owing to the capability of providing with higher oxygen concentration, adequate humidity, and a small amount of nasal CPAP via a nasal prong, HFNC theoretically offers a few advantages over existing modalities including NIV. This study was aimed at comparing HFNC and NIV with regard to the efficacy of avoiding intubation in hypoxemic respiratory failure and mortality. Hypothesis: We hypothesized that HFNC would result in higher success rate and lower mortality than NIV. Methods: We reviewed medical record of patients with hypoxemic respiratory failure who were cared with NIV (n⫽77, from January 2003 to August 2004) and with HFNC (n⫽57, from April 2009 to July 2010) in an adult ICU. Hypoxemic respiratory failure was defined as PaO2/FiO2 (PF) ⬍300 mmHg, pH ⬎7.35 with symptoms/signs of respiratory failure despite standard oxygen therapy (nasal cannula, Venturi mask, reservoir bag). Success of NIV or HFNC was defined as the state of having avoided the need of intubation, and absence of entry criteria for more than 24 hours after weaning of NIV or HFNC. Results: There were no differences in baseline characteristics between the two groups including age, underlying medical conditions, precipitating cause of acute respiratory failure and PF ratio. The success rate of NIV was 22% (17/66) and that of HFNC 72% (41/57) (p ⬍0.001). Mortality rate was 61% (47/77) and 18% (10/57), respectively (p ⬍0.001). Conclusions: In our historical comparison, in patients with hypoxemic respiratory failure, HFNC was far more effective than NIV in terms of avoiding intubation and mortality.

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EVALUATING THE EFFECT OF RED BLOOD CELL TRANSFUSION ON TISSUE OXYGENATION IN SEPTIC PATIENTS USING NEAR-INFRARED SPECTROSCOPY

A LOW COST ALTERNATIVE FOR MECHANICAL VENTILATION IN LARGE SCALE DISASTERS

Farid Sadaka, RaviKumar AgguSher, Katie Krause, Jacklyn O’Brien, Robert Taylor, Saint John’s Mercy Medical Center/St. Louis University Introduction: Microvascular alterations and Tissue Oxygen consumption play a role in the development of multiple organ failure in sepsis. Hypothesis: The aim of this study is to evaluate the effect of red blood cell(RBC) transfusion on muscle tissue oxygenation, oxygen consumption and microvascular reactivity in septic patients using near-infrared spectroscopy(NIRS). Methods: This prospective,observational study included 21 septic patients requiring RBC transfusion for hemoglobin ⬍7, or between 7 and 9 with either lactic acidosis or central venous oxygen saturation ⬍70%. All RBC units used were non-leukoreduced. Thenar tissue oxygen saturation (StO2) and muscle tissue hemoglobin index (THI) were measured using a tissue spectrometer (InSpectra™ Model 650; Hutchinson Technology). A vaso-occlusive test was performed before and 1 hour after transfusion by rapid inflation of a pneumatic cuff around the upper arm for 3 min. The following variables were recorded: THI, the StO2 desaturation slope during the occlusion (%/minute) and the StO2 upslope of the reperfusion phase following the ischemic period (%/second). Muscle oxygen consumption (NIRVO2) was calculated as the product of the inverse StO2 desaturation slope and the mean THI over the first minute of arterial occlusion. Results: Blood transfusion resulted in increase in hemoglobin(7.2 (6 to 9) to 8.7 (7.1 to 10.5) g/dl; P ⬍0.001). RBC transfusion did not globally affect NIRS-derived variables. However, Percent Change in NIRVO2([After Transfusion NIRVO2-Baseline NIRVO2]/ Baseline NIRVO2) was negatively correlated with Baseline NIRVO2(R2⫽0.46, p⫽0.001). There was no statistically significant correlation between Percent Change in the StO2 upslope([After Transfusion StO2 upslope -Baseline StO2 upslope]/Baseline StO2 upslope) and Baseline StO2 upslope(p⫽0.275). There was a positive correlation between Percent Change in NIRVO2 and Percent Change in the StO2 upslope(0.442,p⬍0.05). Conclusions: Muscle tissue oxygenation, oxygen consumption and microvascular reactivity were globally unaltered by RBC transfusion in septic patients. However, muscle oxygen consumption improved in patients with low baseline and deteriorated in patients with preserved baseline.


Matthew Callaghan, Stanford Unversity, Dhruv Boddupalli, Stanford University, Paul Yock, Stanford University School of Medicine, Thomas Krummel, Stanford University School of Medical, Stephen Ruoss, Stanford University School of Medicine Introduction: Catastrophic disasters, particularly aninfluenza pandemic, force difficult allocation decisions for mechanicalventilation due to the high cost of these devices. Pandemic modeling suggests750,000 additional ventilators may be required to meet demand in the US. Thisstudy compared a novel low-cost device with current ventilators using in-vivoand simulated ARDS models. Hypothesis: We hypothesized that a low-cost solution based on a novel air delivery platform could provide mechanical ventilation with the same accuracy as currently available devices. Methods: A low-cost ventilator was constructed arounda unique microprocessor and solenoid assembly to support adults and children inaccordance with the ARDSnet protocol. An Oceanic/Magellan was used forcomparison. ARDS was induced in swine with oleic acid injection (0.3mg/kg) anddefined as PaO2/FiO2 ⬍200. Ventilation targets were a PaO2 ⬎60mmHg and tidal volume ⬃15cc/kg. In simulation studies (Ingmar 4000 Servo Lung), ARDS wasdefined by 30ml/cmH2O compliance and 10cmH2O/l/s airway resistance. A DragerEvita was used for comparison. Results: In swine studies, there was nosignificant difference in performance between ventilators. Both maintained tidalvolumes of 15cc/kg delivering inspiratory pressures to 50cmH2O with PEEP of15cmH2O. Above 35cmH2O, the error in displayed pressure was 10%⫹/⫺2 on the Oceanic/Magellanand ⬍1% on the experimental device. In simulation studies, there was nosignificant difference in performance or display accuracy (⬍1%) betweenventilators. Trigger sensitivity and response times (⫹/⫺ 0.5cmH2O and⬍0.3sec) were similar in A/C modes. Conclusions: Here we describe a novel design for alow-cost ventilator. In-vivo and simulator performance in ARDS was comparable to existing devices. At approximately 1/10 the cost of current ventilators, thistechnology represents an alternative solution for pandemic stockpiling andemergency use.

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EFFECT OF OPEN-LUNG APPROACH AND PLATEAU PRESSURE ON RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH ACUTE LUNG INJURY/ACUTE RESPIRATORY DISTRESS SYNDROME

HALOPERIDOL USE IN PATIENTS WITH ACUTE TRAUMATIC BRAIN INJURY: A SAFETY ANALYSIS

Byung Hoon Park, Young Sam Kim, Moo Suk Park, Joon Chang, Se Kyu Kim, Young Ae Kang, Severance Hospital, Yonsei University College of Medicine

Introduction: Haloperidol (Hal) is recommended to treat agitation and delirium in critically ill patients. The use of Hal in acute TBI patients is complicated by its side effect profile. Additional data is needed concerning the safety of Hal in acute TBI patients. Hypothesis: Haloperidol is safe for short term treatment of agitation and delirium in patients with acute TBI. Methods: We retrospectively identified 101 TBI patients ⱖ18 years of age admitted to the ICU from 01/2007 to 10/2009 with an admission GCS ⱕ12. Demographics and concomitant medications including sedatives/analgesics were collected. Hal usage was recorded throughout the hospital stay. The development of complications including seizures (SZ), neuroleptic malignant syndrome (NMS), QTc prolongation, extrapyramidal symptoms (EPS), and hematologic disturbances (HEM) was assessed. Clinical outcomes were compared between patients who received Hal and those who did not receive haloperidol (NHal). Data were reported in mean⫾SD or median (range). Results: Baseline demographics including TBI type and systemic injuries were similar between the Hal (N⫽45) and NHal (N⫽56) groups, except for patients in the Hal group were younger [32(18-82) vs 47(18-93); p⬍0.01] and had a lower APACHE II (21⫾6 vs. 23⫾5; p⫽0.04). The mean daily Hal dose was 9(2-52) mg and given for 4(1-35) days. Twenty patients developed complications: 8(18%) in the Hal group and 12(21%) in the NHal group (p⫽0.80). SZ occurred in 3 patients (Hal⫽2; NHal⫽1). QTc prolongation occurred in 17 patients (Hal⫽6, NHal⫽11), 1 patient (NHal) required intervention. There were no reports of NMS, EPS or HEM. Patients with complications had a higher daily Hal dose than those without complications [14(5-52) vs. 7(2-26) mg; p⫽0.01]. The Hal group received a higher daily benzodiazepine dose (p⫽0.03) and longer duration of therapy (p⬍0.01). Hospital LOS was shorter in the NHal group [11(4-66) vs 22(6-69) days; p⬍0.01]. There was no difference in ICU LOS or length of mechanical ventilation. Conclusions: There were few complications documented with short term Hal use. Administration of Hal appears to be safe following acute TBI. The clinical impact of Hal in this population needs to be further investigated.

Introduction: To evaluate the change of right ventricular overload before and after open-lung approach (OLA) in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Hypothesis: RV afterload positively correlates with plateau pressure despite the use of OLA combined with protective ventilator strategies. Methods: Eight patients with early ALI/ARDS underwent OLA that consisted of 2-minute steps of tidal ventilation with a fixed 20-cm H2O pressure control and progressive positive end-expiratory pressure (PEEP) levels up to 30 cm H2O, followed by stepwise decrement of PEEP level by 2 cm H2O from 20 cm H2O every 2 minutes. Hemodynamic/respiratory parameters, including right ventricular stroke work index (RVSWI) and right-over-left ventricular stroke work ratio (RVSW/LVSW), were measured at baseline, immediately postOLA, 2 hours post-OLA, and 6 hours post-OLA. Results: Whereas PaO2/FiO2, peak pressure, plateau pressure, and PEEP all increased significantly from baseline values in survivors and nonsurvivors (p ⬍ 0.05 for all measures), RVSWI decreased only in survivors (p ⫽ 0.014). Moreover, RVSW/LVSW decreased in survivors but increased in nonsurvivors over time (p ⬍ 0.001). Despite plateau pressure limitation, RVSW/LVSW and PVRI decreased in correlation with the decrease of plateau pressure immediately post-OLA (r ⫽ 0.75 and r ⫽ 0.85, respectively) and 2 hours post-OLA (r ⫽ 0.87 and r ⫽ 0.80, respectively). Conclusions: OLA combined with protective ventilation strategies does not guarantee RV protection. Despite plateau pressure limitation following OLA, RV afterload decreased in correlation with the reduction in plateau pressure. Further studies concerning the role of RV monitoring with regard to individualized OLA and safe upper limit of plateau pressure are necessary.

Rebecca Anderson, Kara Birrer, Michael Cheatham, Jason Clark, Xi Liu-DeRyke, Orlando Regional Medical Center



840

EFFECTS OF HISTAMINE RECEPTOR ANTAGONISTS ON INFECTION RATES IN CRITICALLY ILL TRAUMA PATIENTS

FEASIBILITY OF REAL-TIME ULTRASOUND-GUIDED PERCUTANEOUS TRACHEOSTOMY

Stephen Phillips, Ehsan Esmaeili, Kristine Lombardozzi, Charles Morrow, Phillip Humphrey, Heather Bendyk, Devonne Barrineau, Derek Brenda, Spartanburg Regional Medical Center

Venkatakrishna Rajajee, Jeffrey Fletcher, Lauryn Rochlen, Teresa Jacobs, University of Michigan

Introduction: Infectious complications (IC) are a significant obstacle in the management of critically-ill trauma patients (pts) and impart a significant financial impact on the healthcare system. Recent data suggest a possible link between histamine receptor antagonist use and increased susceptibility to post operative infection in children. H2RA or proton pump inhibitors (PPI) have traditionally been used for prophylaxis against stress gastritis. H1RA are commonly used for itching, insomnia and as pre-treatment for blood product transfusion. Hypothesis: We proposed that any exposure to an H2RA or H1RA (HRA) would increase the incidence of IC in critically ill adult trauma pts. Methods: A level 1 trauma center’s admissions from January 2003 to December 2009 were retrospectively reviewed. Inclusion criteria consisted of pts admitted to an ICU, ⬎ 18 years old and intubated ⬎48 hours. IC s (pneumonia, urinary tract infections (infxn), bacteremia, intra-abdominal infxn, intra-thoracic infxn, central venous catheter infxn, and surgical site infxn) as well as ICU length of stay (ICULOS), hospital LOS (HLOS) and the number of ventilated days (VD) were compared among pts with any HRA exposure vs. no HRA exposure. Results: A total of 308 pts (71% male) met inclusion criteria with an average age of 46 and Injury Severity Score of 24. Of the study population, 251 (81%) had HRA exposure. Pts with HRA exposure had an increased incidence of IC (76% vs 39%, p⫽0.0232), longer ICU LOS (15.7 vs 12.0 d, p⫽.0109), longer HLOS (30.6 vs 17.9 d, p⬍.001) and more VD (12.4 vs 9.3 d, p⫽.0105). There were no statistically significant differences among specific types of IC. Conclusions: In critically ill adult trauma pts who required mechanical ventilation ⬎48 hours, our data showed an increased incidence of IC as well as prolonged HLOS, ICULOS and VD in pts who received an HRA during their hospitalization. The routine use of HRAs in trauma pts should be reconsidered.

841 GLUCOSE CONTROL IN CRITICAL CARE ONCOLOGY Timothy Cooksley, Thomas McAvoy, Philip Haji-Michael, The Christie Hospital Introduction: The optimal strategy for glucose control in Critical Care patients remains controversial and may vary dependent on the diagnostic group. Hypothesis: Tight glucose control in Critically Ill Oncology patients will improve outcome with regards to mortality, requirements for organ support and length of Critical Care stay. Methods: This retrospective study examines the experience of a Specialist Oncology Critical Care Unit (CCU) in England between January 2009 and May 2010. Serial blood glucose levels were measured. Intravenous insulin therapy was instituted when blood glucose levels exceeded 10mmol/L (180mg/dL) aiming for a target of below 10mmol/L. Results: 565 patients were admitted to the CCU of which 181(32%) were medical and 384(68%) surgical. The mean blood glucose was 7.8mmol/L (140mg/dL). Mortality rates relative to mean glucose followed a U-shaped curve. There was a statistically significant increase in mortality among patients who spent longer periods with blood glucose levels ⬍6 mmol/L and ⬎10 mmol/L as compared to those maintained between 6-10mmol/L (20% vs 7.3%; p⫽⬍0.001). Mean glucose levels did not significantly affect the length of stay on CCU or the requirement for respiratory or cardiovascular support. Higher fluctuations in blood glucose levels resulted in a significant increase in mortality – e.g - patients with a mean glucose of 6-10mmol/L who had a ⬎25% coefficient of variation compared to those ⫽ ⬍0.001). Higher coefficients of variation were also associated with an increased length of CCU stay and readmission rates to CCU. Conclusions: In Critically Ill Oncology patients optimal blood glucose control appears to be between 6-10mmol/L with significantly increased mortality observed outside of this range. Variability in glucose levels may be the main driver behind this relationship and warrants further study.


Introduction: Percutaneous Tracheostomy (PT) is commonly performed with bronchoscopic guidance to ensure proper placement of the tracheal tube. Disadvantages of bronchoscopy include the need for specialized equipment and personnel, expense and the risk of airway occlusion and respiratory acidosis. Bedside ultrasound (US) guidance minimizes hypoventilation and can be performed using equipment widely used to assist with central line placement. US performed prior to PT has been shown to be useful in avoiding vascular structures during the procedure and also in avoiding high placement of the tube. Real-time US guided tracheostomy with bronchoscopic verification has not been described. Hypothesis: It is feasible to perform PT entirely under real-time US guidance. Bronchoscopic examination will confirm accuracy in the level and site of tracheal puncture and cannulation performed under ultrasound guidance. Methods: Mechanically ventilated patients requiring tracheostomy underwent US guided PT using the Ciaglia Blue Rhino® and a Sonosite bedside US machine. The orotracheal tube was withdrawn using direct laryngoscopy. The trachea was punctured under real-time US guidance (with visualization of needle path) inferior to the thyroid isthmus. The acoustic shadows of the cricoid and the tracheal rings were also used to determine the level of puncture. After guidewire passage the site and level of entry were verified using the bronchoscope, which was then withdrawn. Following dilatation and tube placement, placement in the airway was confirmed using auscultation and the “lung sliding” sign on US. Bronchoscopy and chest X-ray were then performed to identify any complications. Results: Twelve patients underwent US guided PT. In all 12 cases bronchoscopy confirmed that guidewire entry was- a) through midline anterior wall and b) between the 2nd and 5th tracheal rings. There was no case of tube misplacement, pneumothorax, posterior wall injury, significant bleeding or other complication. Conclusions: Real-time ultrasound guided percutaneous tracheostomy is feasible and appears accurate and safe in this preliminary study. Larger studies are required to further define the safety and relative benefits of this technique.

842 REPLACEMENT USING AN ELECTROLYTE PROTOCOL IN AN ADULT SURGICAL INTENSIVE CARE UNIT: A RETROSPECTIVE EVALUATION (REPLACE) Jackie Sharpe, Shands Jacksonville Medical Center, Donald Johnson, Shands Jacksonville, Gerald Schmidt, Christine Small, Shands Jacksonville Medical Center Introduction: Electrolyte abnormalities are a common complication among intensive care unit patients. The intensive care unit is a dynamic environment and variations in patient care may occur. Studies have shown that protocol implementation to standardize care produces better patient outcomes. The purpose of this study is to retrospectively evaluate the efficacy, timeliness and safety of electrolyte replacement before and after implementation of a nurse-driven replacement protocol. Hypothesis: A nurse-driven electrolyte protocol will increase electrolyte replacement, the effectiveness of those replaced and time to replacement. Methods: REPLACE is a retrospective cohort evaluation of patients admitted to the surgical intensive care unit. Patients will be included if one or more of the following occur: potassium ⬍ 4 mEq/L, phosphate ⱕ 2.5 mg/dL, magnesium ⱕ 1.8 mg/dL. Data was collected for four months pre-protocol and post-protocol.Primary endpoints include: percent of sub-therapeutic electrolyte values replaced, efficacy of electrolyte replacement for each electrolyte replaed and time to replacement. Secondary endpoints include: occurrence of post-replacement supra-therapeutic electrolyte values, electrolyte replacement requirements in patients with a serum creatinine ⱖ 2 mg/dL and evaluation of the dose-weight relationship with phosphate replacement. Results: After implementation of the electrolyte protocol the percent replaced increased for potassium from 70.6% to 83.1% (p ⬍0.001), phosphorus 73.7% to 85.9% (p⬍0.001), and magnesium from 78.3% to 82.7% (p ⫽ 0.61). The percent at goal also increased in the post-protocol group: potassium 34.1% to 45.9% (p⬍0.001), phosphorus 51.5% to 59.8% (p⫽0.03), magnesium 85.3% to 91.4% (p⫽0.01). Time to replacement of electrolytes decreased for the post-protocol group from a mean of 5.3 to 3.9 hours. The frequency of supra-therapeutic levels was not greater post-protocol versus pre-protocol. Conclusions: The implementation of a nurse-driven electrolyte replacement protocol improved the percent of electrolytes replaced and efficacy of the electrolytes replaced, while maintaining safety. Nurse-driven replacement also decreased time to electrolyte replacement.

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ASSESSING THE VALIDITY AND USE OF A DVT RISK ASSESSMENT PROFILE IN A TRAUMA POPULATION

SAFETY OF FLEXIBLE BRONCHOSCOPY IN CHILDREN WITH SEVERE STATUS ASTHMATICUS AND RESPIRATORY FAILURE

Gina Berg, University of Kansas School Of Medicine, David Acuna, Wesley Medical Center, Bridget Harrison, Trenton Wray, Cyndi Sook, KU School of Medicine - Wichita, Diane Dorsch, Wesley Medical Center SICU Introduction: Patients suffering from trauma are at increased risk, up to 58% without prophylaxis, for the development of veneous thromboembolism (VTE). VTE impacts mortality as well as length and cost of hospital stay. Hypothesis: The study aims were: (1) investigate VTE development in a trauma population deemed low risk by Greenfield’s Risk Assessment Profile (RAP), (2) identify factors associated with VTE development, and (3) evaluate if the daily risk score changes over time. Methods: Retrospective case (confirmed VTE) - control (no confirmed VTE) chart review of trauma patients, admitted from January 2001 through December 2005. Evaluation of initial and continuous risk assessment profiles scores over the course of hospitalization, and risk factors associated with VTE development. Results: In the study time period, 31 patients were identified as confirmed VTE and 79 patients in the same time period were used as controls. VTE occurred in 3 of 26 patients with a RAP score ⬍ 5; one resulting in death. Risk factors significantly associated with VTE development were femoral venous line insertion (5.8 [1.9-17.8] p ⫽ 0.001), operation ⬎ 2 hours (2.3 [1-5.5] p ⫽ 0.047), head abbreviated injury score (AIS) ⬎ 2 (3.1 [1.3-7.7] p ⫽ 0.008), and Glasgow Coma Scale ⬍ 8 (7.3 [2.7-19.6] p ⬍ 0.001).Half (50.9%) RAP scores remained constant over hospitalization. RAP score fluctuations in the remaining 50.1% were due to: increases (39.1%) were due to known iatrogenic effects and decreases (10%) were due to physiologic improvements such as GCS. Conclusions: Study conclusions were: 1) trauma teams should not completely rely on 5 as the threshold in a trauma population, 2) all trauma patients should be treated prophylacticly through the hospital stay, except when contraindicated, and 3) trauma teams should re-evaluate the need for daily RAP scoring. This study did not validate Greenfield’s RAP model. Results support the American College of Chest Physicians’ recommendations that all major trauma patients receive routine thrombo-prophylaxis, if possible (and unless contraindicated). Moreover, routine thrombo-prophylaxis is proposed even in low risk patients, essential in a pay-forperformance environment.

J. Carlos Maggi, Christopher Babbitt, Glenn Levine, Flavio E Maggi, Eliezer Nussbaum, Miller Children’s Hospital Introduction: Status asthmaticus leading to respiratory failure causes thickened secretions needing aggressive pulmonary clearance. Hypothesis: Bronchoscopy is a safe procedure in pediatric mechanically ventilated asthmatic patients. Methods: A retrospective chart review was performed on all patients admitted to the PICU with asthma and respiratory failure over a 12 year period and 44 patients were identified. Patients were managed based on our guidelines for intubated asthmatics. Therapies included glucocorticoids, bronchodilators, aminophylline or terbutaline infusions, ketamine infusions, and heliox. The ventilatory management prioritized spontaneous breathing with pressure support after arrival in the PICU. Patients were extubated when spontaneous tidal volumes were 5-7cc/kg on minimal pressure support. While on ventilatory support, patients were suctioned and lavaged with saline as needed. Additionally, 29 patients underwent bronchoscopy as an adjunctive therapy. Indications for bronchoscopy included: pulmonary infiltrates, atelectasis, mucus plugs producing severe air trapping, suspected aspiration and poor response to standard therapy. Results: Bronchial lavage was accomplished in 29 patients with an age range of 1-18 years. The airways were found to have thick mucus plugs, secretions, and bronchial casts.The large airways were lavaged clean with normal saline. All of the patients tolerated the procedure without any complications or desaturation during or after the bronchoscopy. None of the patients required increased ventilatory support after the procedure and most demonstrated an immediate improvement in pulmonary compliance. The median time of extubation for the 29 patients who underwent bronchoscopy was 10 hrs compared with 20.5 hrs for the 15 patients that did not undergo bronchoscopy (P⬍0.19). The mean PICU LOS was 3.06 days, median 2 days for the bronchoscopy group and mean of 3.40, median 3 days for the non-bronchoscopy group (p ⬍0.61). All 44 patients survived and there were no complications. Conclusions: Flexible bronchoscopy with bronchial lavage is a safe adjunctive therapy in pediatric asthma patients with respiratory failure and may shorten mechanical ventilation time and PICU length of stay.

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COMPLIANCE WITH THE EAST GUIDELINES FOR PROPHYLACTIC ANTIBIOTICS AFTER OPEN EXTREMITY FRACTURE

USE OF HIGH FLOW NASAL CANNULA (HFNC) O2 THERAPY FOR FAILED EXTUBATION POST CARDIAC SURGERY

Cassie Barton, Wesley McMillian, Fletcher Allen Health Care, Turner Osler, University of Vermont, Bruce Crookes, Craig Bartlett, Fletcher Allen Health Care Introduction: Antibiotic prophylaxis, paired with wound care and surgical intervention, is considered the standard of care for all patients with open fracture. Guidelines from the Eastern Association for the Surgery of Trauma (EAST) recommend specific prophylactic antimicrobial therapy based on the type of open fracture. We quantified adherence to EAST guideline recommendations and documented the incidence of infection in patients with open fractures. Hypothesis: Non-compliance with guideline recommended prophylactic antibiotics after open extremity fracture may result in infectious complications. Methods: This study was a retrospective review of all adult patients admitted to our institution with a diagnosis of open fracture between January 2004 and December 2008. Results: Antibiotic prophylaxis was compliant with the EAST guideline recommendations in 28.5% of patients. Compliance ranged from 52.7% in type 1 fractures to 10.0% type 3b fractures. The most common reason for non-compliance was use of guideline recommended coverage that exceeded the suggested duration (71.2%). Patients who received non-compliant therapy had longer hospital length of stay (10.0 vs. 6.9 days, p⫽0.0001) and intensive care unit (2.6 vs. 2.2 days, p⫽0.0202) length of stay, increased number of packed red blood cell units transfused (2.9 vs. 1.9 units, p⫽0.02), and number of surgeries performed on the open fracture (1.6 vs. 1.4, p⫽0.05). The overall incidence of infection was similar regardless of guideline compliance (17.0% versus 11.5%, p⫽0.313). Conclusions: Antibiotic prophylaxis for open fractures frequently exceeded EAST guideline recommendations in duration and spectrum of coverage, especially in more severe fracture types. Non-compliance with EAST recommendations was associated with increased in-hospital morbidity.

Daniel Herr, University of Maryland, Robin Smith, University of Maryland Medical Center Introduction: Unexpected repiratory failure after meeting appropriate extubation parameters, is not common after CABG and often results in reintubation. BiPAP is often attempted in these pts but is not well tolerated and hard to manage. High flow nasal cannula (HFNC) therapy (Vapotherm) is a new method of delivering high flow (40 l/min) O2 with high levels of humidification and proper warmth. HFNC have been used in the neo-natal & pediatric population but there are few reports of HFNC use in adults. Therapeutic properties of HFNC; decres dead space in the nasopharyngeal cavity, decre resistive work of breathing, adequate gas humidification & decre metabolic cost of breathing, acquisition of pharyngeal distending pressure. Hypothesis: Because of these properties, HFNC has been used in our institution to avoid intubation 2nd to failed extubation in the immediate post-op. We conducted a retrospective review of the use of HFNC tx in this post cardiac surgery population. Methods: HFNC was provided for any pt who did not require emergent intubation after failed, appropriate extubation (patient met standard extubation criteria). BiPAP was not available. Provider recorded therapy they would have used if HFNC was not available; re-intubation, BiPAP, or increased O2 tx. Outcome of the pt was then recorded. 10 month retrospective review was then done looking at respiratory outcome as to avoidance of intubation. Results: 39 pts had HFNC therapy, of the 19 pts expected to be reintubated 5 required reintubated; of the 12 pt thought to require BiPAP 2 (17%) required re-intubation and of the 8 pt thought to require more O2, 2 required re-intubation. Of the 39 pts failing original extubation, 30 (77%) pts treated HFNC weaned off therapy and did not require re-intubation. Conclusions: This is the 1st report of successful use of HFNC O2 therapy in adult post-op CABG pop. HFNC oxygen therapy appears to be a new technology for respiratory support in the CABG post-op population that may avoid the need for reintubation for immediate post-op respiratory insufficiency. HFNC was well tolerated in patients and did not require discontinuation 2nd patient discomfort.


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EFFECTS OF THE COMBINATION THERAPY OF ENDOTOXIN ADSORPTION AND CONTINUOUS HEMODIAFILTRATION IN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS TOXIC SHOCK SYNDROME

A RANDOMISED COMPARISON OF THE SAFETY OF FOUR CHEST DRAIN INSERTION TECHNIQUES

Takumi Taniguchi, Masaki Okajima, Kanazawa University Hospital

Introduction: A National Patient Safety Agency (UK) alert reported 12 deaths (due to puncture of the heart, lungs and liver) and 15 cases of serious harm related to chest drain insertion (2005-8) [1]. However, this is an underestimate as a recent survey reported major chest drain insertion complications in 68% of UK hospitals in 5 years [2]. This study aimed to objectively compare the safety of four chest drain insertion techniques, one blunt dissection, two Seldinger techniques and one new “combination” or hybrid technique. The hybrid technique uses novel blunt dissection forceps with an integral wire channel to allow the Seldinger technique to be performed avoiding a sharp needle introduction. Hypothesis: We hypothesised that the Seldinger techniques cause more underlying lung perforation than the blunt techniques and the new hybrid technique would cause a smaller stoma than the blunt technique. Methods: Participants performed each technique in random order on a sheep’s thorax, which had a model lung underlying it. Lung puncture was recorded. Statistical analysis was by multiple ChiSquared tests with a Bonferoni correction. Results: N⫽32. Lung puncture occurred in all techniques: Hybrid (16%), Blunt (9%), Cook Seldinger (94%) Rocket Seldinger (69%). The two blunt dissection techniques were equally safe, but significantly safer than the Seldinger techniques (p ⫽ ⬍0.0001). The stoma size was smaller for the Hybrid and Seldinger than the Blunt dissection technique. All lung perforations using the Seldinger technique were due to the needle, and all perforations using the blunt and hybrid technique were due to too deep scalpel penetration. Conclusions: In this model, lung trauma is significantly more likely using Seldinger than the blunt techniques to insert a chest drain. The hybrid technique offered smaller insertion stoma, in combination with improved safety. Our sheep thorax had little adipose tissue and the scalpel lung injuries with the blunt techniques may not realistically reflect clinical practice. Further work is required in a clinical setting. Refs: [1] http://www.nrls.npsa.nhs.uk/resources[2] Harris A et al. Postgrad Med J. 2010;86:68-72.

Introduction: Toxic shock syndrome (TSS), which can be life threatening, is defined by clinical and laboratory evidence of high fever, skin rash, desquamation, hypotension, and multiple organ failure caused by Staphylococcus aureus enterotoxin. Therapy of TSS includes removal of potentially infected wounds, intravenous administration of an antistaphylococcal agent and aggressive management of hypotension, ARDS, myocardial dysfunction and DIC. However, several cases reported that this conventional therapy was not effective in severe TSS patients. The present study evaluated the effects of the combination therapy of endotoxin adsorption (PMX) and continuous hemodiafiltration (CVVHDF) in critical patients with methicillin-resistant Staphylococcus aureus TSS (MRSA-TSS), who did not improve with conventional therapy. Hypothesis: We hypothesis that the combination therapy has beneficial effects for critical MRSA-TSS patients. Methods: Five patients (M/F 3/2, mean age 40 years) with MRSA-TSS, who did not improve conventional therapy, underwent the combination therapy of PMX and CVVHDF in addition to conventional therapy. The combination therapy was undergone as long as possible. Primary outcome was change in systolic arterial pressure (SAP) and vasopressor requirement after the combination therapy, and secondary outcomes were change in laboratory data and SOFA scores at 24 hours after the combination therapy. Results: The combination therapy underwent for mean 10 hours (4-20 hours). SAP increased (84 to 124 mmHg; p⬍0.05) and vasopressor requirement decreased (12 to 4; p⬍0.05) after the combination therapy. WBC counts decreased (16966 to 10392 /uL; p⬍0.05), C-reactive protein decreased (26.1 to 15.6 mg/dL; p⬍0.05) and SOFA scores decreased (14.8 to 10.8; p⬍0.05) at 24 hours after the combination therapy. All patients recovered and discharged in ICU. Conclusions: In the present study, the combination therapy of PMX and CVVHDF significant improved hemodynamics and organ dysfunctions in critical patients with MRSA-TSS.


Thomas White, Alex Doyle, Karen McGuire, Parvez Moondi, Peter Young, Queen Elizabeth Hospital


850

NORMAL SALINE VERSUS HALF NORMAL SALINE IN THE MANAGEMENT OF DIABETIC KETOACIDOSIS

ABDOMINAL COMPLICATIONS AFTER MECHANICAL SUPPORT FOR HEART FAILURE

Preethi Venepalli, Janak Koirala, Jennifer Andoh, Gurpreet Mander, Sangita Basnet, Southern Illinois University School of Medicine

Alyssa Chapital, Linda Staley, Daniel Johnson, Christopher Pierce, Joel Larson, Francisco Arabia, Mayo Clinic

Introduction: Isotonic fluid is recommended for maintenance fluid and correction of fluid deficit when treating patients with diabetic ketoacidosis (DKA). It has been hypothesized that corrected sodium should remain the same or increased throughout the management period in order to avoid rapid decrease in effective serum osmolality to prevent cerebral edema. Hypothesis: There is a difference in the change in corrected serum sodium between normal saline (NS) versus half normal saline (1⁄2 NS) when used as maintenance fluid during management of DKA. Methods: A retrospective chart review of children admitted to the pediatric intensive care unit (PICU) with the diagnosis of DKA from 2005 to 2009 was done. All patients under 18 years with initial serum pH ⬍7.3 and serum bicarbonate ⬍15 meq/L with hyperglycemia and ketonuria were included in the study. Statistical analyses were done to compare NS and 1⁄2 NS groups by Student’s T-Test, ANOVA table and Mantel-Haenzel common odds ratio (OR) estimates. Results: NS was used in 48 and 1⁄2 NS in 40 patients. Corrected serum sodium decreased in the 1⁄2 NS group while it increased in the NS group (mean changes -2.5 mEq/L vs. 1.7 mEq/L, OR⫽5.4, p⫽⬍0.001). Although total fluid received was similar (mean 3.8 ⫾1.3 cc/kg/hr in both groups, p⫽0.95), total sodium received by the NS group was much higher than the 1⁄2 NS group (mean 13.9⫾4.7 vs. 6.9⫾ 2.3 mEq/kg/day, p⬍0.01). Another group of 16 patients was initially placed on NS which was subsequently changed to 1⁄2 NS after a certain period because of hyperchloremia (mean 116.5 ⫾ 4.9 mEq/L). Although maximum serum chloride was similar in the first 2 groups, i.e., NS and 1⁄2 NS groups (means 111.3 ⫾ 6.2 mEq/L and 108.8⫾ 6.4mEq/L, respectively, p⫽0.11), it was significantly higher in the group that was changed from NS to 1⁄2 NS as compared to the patients receiving only 1⁄2 NS (p⬍0.01). Conclusions: Corrected serum sodium may not decrease when NS is used as maintenance fluid in the management of DKA, however, hyperchloremia may occur requiring a change to 1⁄2 NS after a certain period.

Introduction: Mechanical circulatory support has become common for refractory cardiogenic shock. While survival has improved, morbidity of device placement is a common occurrence. Hypothesis: The goal of this evaluation was to evaluate the abdominal complications (AC) of device patients and define the consequences of these issues. Methods: A retrospective review of all patients who underwent mechanical circulatory support device placement for heart failure at a tertiary care center. Complications were defined as events that were attributable to device placement. Patients were stratified using Intermacs (IM) classification. Results: Between Sept 2005 and April 2010, 134 patients underwent placement for 174 devices at our institution for cardiogenic shock. 42 (31%) were placed as a bridge to recovery, 64 (48%) as a bridge to transplantation and 28 (21%) as destination therapy. 62 were placed for IM-1, 30 for IM-2, 41 for IM-3 and 1 for IM-4. Median days with device were 24. There were more non-pulsatile devices placed (71%). 29 (45%) of patients received a transplantation after device. 75 (56%) of patients are currently alive. There were 66 ACs in 42 patients. Complications were group into these categories: biliary tract (6), intestinal (18), gastrointestinal bleeding (30), abdominal wall (9), and misc (3). Only 13 (20%) required operative intervention. 28 (42%) were treated with less invasive techniques. The remaining were treated with antibiotics and observation. Patients with an AC were on a device for a longer period of time (p ⬍ 0.003). However, there was no difference found in survival. Interestingly, there were statistically significant fewer complications in the IM-1 group (p ⬍ 0.006). There were more complications found in the destination therapy patients and bridge to recovery patients (p ⬍ 0.001). Conclusions: The management of patients in refractory shock continues to evolve. While literature may suggest a reduced survival with ACs after device placement, our data does not concur. Even so, the discussion should be included in the consent process. Optimal management has yet to be elucidated but perhaps aggressive medical and non-operative intervention explains our improved survival.

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THROMBOPROPHYLAXIS IN THE CRITICALLY ILL: UNDERUTILIZATION DESPITE A 50% ABSOLUTE RISK REDUCTION IN VENOUS THROMBOEMBOLISM (VTE)

COMPARISON OF DYNAMIC VERSUS STATIC VARIABLES IN A POST CARDIOPULMONARY (CP) ARREST PEDIATRIC ANIMAL MODEL

Melissa McLenon, The University of Texas M.D. Anderson Cancer Center, Joseph Nates, The University of Texas M.D. Anderson Cancer Center/University of Texas

Carsten Bandt, Jai Udassi, Hunter Schrank, Alessio Vigani, Shrini Badugu, Melissa Lamb, Stacy Porvasnik, Geary Kaliki-Venkata, University of Florida, Renata Shih, UF, Andre Shih, University of Florida

Introduction: VTE is the 3rd leading cause of cardiovascular death in the United States, with 2 million cases of VTE per year, costing $1.5 billion. The incidence of VTE among critically ill patients varies from 22-80%, yet few studies have addressed thromboprophylaxis in this population. The lack of evidence on the effectiveness of thromboprophylaxis in the critically ill adult lead to a systematic review of the literature. Hypothesis: The purpose of this study was to investigate whether the use of thromboprophylaxis, compared to no prophylaxis, decreased the incidence of VTE in the hospitalized critically ill adult. Methods: A systematic search for relevant articles was performed using The Cochrane Library, PubMed, CINAHL Plus, Science Citation Index, SCOPUS, and Ovid. Only randomized control trials (RCTs), retrospective, and prospective studies published in English, between 1980 and 2010, were utilized. Studies consisting in subsets of patients were excluded. Each study was critiqued using the Critical Appraisal Skills Programme tool. Results: Among the 17 studies identified, only 13 met criteria. Two were double blinded RCTs, 9 were prospective, and 2 were retrospective studies. Both RCTs showed a 50% absolute risk reduction, and a 28.6% and 27.6% relative risk reduction in incidence of VTEs among patients who received pharmacological thromboprophylaxis, as compared to a placebo. In the observational studies, the overall incidence of VTE was 9.2% (range 5.4% -33%). Of the 169 VTE cases reported, 28.4% did not receive any type of thromboprophylaxis. The retrospective studies did not show a significant difference in the incidence of VTE between patients who did or did not receive thromboprophylaxis. However, the use of thromboprophylaxis was high in these studies, 87.6% and 75%. Conclusions: Pharmacological thromboprophylaxis in the critically ill significantly reduces VTE incidence. The Agency for Healthcare Research and Quality calls thromboprophylaxis against VTE the number one patient safety practice. However, there is still evidence of inadequate use of VTE prophylaxis in the ICU setting. These findings support the need for performance improvement programs, as well as additional research on VTE in this setting.

Introduction: Knowledge of cardiac output (CO) and preload isparamount for treatment of patients surviving CP arrest. Clinical cardiovascularmonitors often lacks those determinations due to invasiveness and complexity ofmost methods. COstatus offers a minimally invasive easy way to determine CO, totalend diastolic volume (TEDV) and central blood volume (CBV). Hypothesis: We hypothesized thatCOstatus values would have good agreement compared to intracardiac Millar Pressure Volume Catheter (MPVS) in a post arrest pediatric animal model. Methods: Prospective animal studyusing 8 anesthetized(⬃2 months old, 12 kg) piglets. After 4 minutes of untreated ventricularfibrillation (VF) animals underwent standard CP resuscitation (S-CPR) until return of spontaneous circulation (ROSC)was achieved. Animals were maintained inROSC for 120 minutes (lowCO state). CO, TEDV and CBV were determined by ultrasounddilution COstatus and compared to MPVS placed in left ventricle. Measurements weretaken at baseline (before arrest) and at lowCO state. Data (mean⫾SD) was analyzed with Blant Altman and A-nova, p ⱕ 0.05 was significant. Results: 6/8 animalssurvived to the end of lowCO state, 96 comparisons were made. Post arrest altered CO, MAP and CBV but not TEDV. CO andTEDV maintained good agreement to MPVS CO and end diastolic volume (EDV) throughoutthe study with bias and limits of agreement (LOA): 0.1(LOA: 1.5, -1.3 L/min) and67.2 (165, -31.5 mls) respectively. Conclusions: Conclusion: Hypothesis wasvalidated. With COstatus being a viable clinical alternative to measure cardiacparameters when compared to intra-cardiac pressure volume catheter in pediatriccritical care.


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RETROSPECTIVE COMPARISON OF PHENYTOIN VS. LEVETIRACETAM VS. NO MEDICATION IN THE PREVENTION OF SEIZURES IN SUBARACHNOID HEMORRHAGE

BACTEREMIAS IN CRITICALLY ILL BURN PATIENTS: DO INITIAL APPROPRIATE ANTIBIOTICS MATTER?

Gregory Peitz, The Nebraska Medical Center, Keith Olsen, University of Nebraska Medical Center, Tammy Winterboer, The Nebraska Medical Center, Donald Klepser, UNMC, William Thorell, The Nebraska Medical Center Introduction: Phenytoin has traditionally been the standard of care for seizure prophylaxis following traumatic or spontaneous subarachnoid hemorrhage (SAH), but levetiracetam utilization has increased in this population. However, data with its use are limited. Hypothesis: Levetiracetam provides similar seizure prophylaxis compared to phenytoin following SAH and that seizure prophylaxis greater than seven days with either antiepileptic provides no additional benefit. Methods: Retrospective cohort study of 473 patients identified via ICD-9 codes for SAH given phenytoin, levetiracetam, or no medication for seizure prophylaxis. Data collected included demographics, severity of illness as measured by APACHE II scores, head bleed characteristics, intracranial procedures, febrile episodes, and seizure data within each cohort. Fisher’s Exact and Kruskal-Wallis statistical tests were used to compare categorical and continuous data, respectively. Results: We observed 178 patients on phenytoin, 28 patients on levetiracetam, and 267 patients on no seizure prophylaxis. The cohorts were similar in regards to race, alcohol and drug abuse while patients receiving phenytoin had higher admission APACHE II scores. Fifteen patients experienced seizures prior to hospital admission. Of the patients observed without a pre-admission seizure, 10 patients developed a seizure after hospitalization. Of these, 5 (1.8%) did not receive seizure prophylaxis and 5 (1.1%) received phenytoin with the mean time to seizure events being 2.6 and 6.2 days respectively. Zero patients on levetiracetam monotherapy exhibited a seizure. The anti-epileptic cohorts had an average of 9.5 prophylaxis days. The hospital length of stay was shorter for those patients who received no seizure prophylaxis vs. either phenytoin or levetiracetam (7.55 vs. 10.44 days, p-value ⬍0.001). No difference in mortality was observed among the cohorts. Conclusions: More seizure events following SAH occurred in the period preceding hospitalization. No difference in seizure rate was seen among the cohorts studied while hospitalized. Randomized controlled trials evaluating phenytoin vs. levetiracetam in this setting are warranted.

Katri Abraham, Janie Faris, Lisa Hall Zimmerman, David Edelman, Michael White, Detroit Receiving Hospital Introduction: Nosocomial blood stream infections in critically ill patients are associated with a mortality as high as 80% and a prolonged hospital stay. Currently, limited data exists in the burn literature regarding the importance of appropriate initial antibiotic therapy in critically ill patients with positive blood cultures. Hypothesis: Critically ill burn patients with bacteremia have poor outcomes with initial inappropriate antibiotic therapy. Methods: This study evaluated 50 consecutive adult burn intensive care patients with bacteremia from Jan 06 –Jun 09. Bacteremia was defined as identification of a recognized pathogen from one or more blood cultures. Empiric antibiotics were appropriate if the pathogen isolated was susceptible based on MIC data. Patients were divided into two groups: initial appropriate (AAT) vs inappropriate (IAT) antibiotic therapy. Time to AAT was defined as time from initial antibiotics prescribed to administration of appropriate antibiotics. Results: Of the 50 patients, 78 episodes occurred with 58 (74%) receiving AAT and 22 (28%) receiving IAT with an overall bacteremia rate of 13%. Patients were 49⫾18 years of age with an APACHE II of 17⫾7. Time for appropriate antibiotics to begin was longer for IAT vs AAT, [3.1⫾1.2vs1.5⫾1.4 days, p⫽0.004]. IAT was more commonly seen in the gram negative bacteremias [82%vs37%, p⫽0.001], specifically Acinetobacter spp. [63%vs18%, p⫽0.00008] and also with Enterococcus faecalis (27%vs8%, p⫽0.04). If 2 or more bacteremic episodes occurred, Acinetobacter spp. was more likely, p⫽0.07. The top 2 isolates in late onset bacteremias (⬎21 days) were Pseudomonas spp. and Enterococcus faecalis. In the surviving patients (n⫽49) comparing IAT vs AAT, overall hospital length of stay (LOS) was longer, [101⫾56vs72⫾53 days, p⫽0.10], and ICU LOS tended to be longer (96⫾53vs70⫾53 days, p⫽0.13) with no difference for in-hospital mortality [41%vs35%, p⫽0.43]. Conclusions: Bacteremias in critically ill burn patients complicates the clinical course with increased morbidity and mortality. Incorrect choice of initial antibiotic therapy was found to magnify LOS. Acinetobacter spp. is a particular problem in this population, and initial appropriate antibiotics is important.

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CLINICAL SIGNIFICANCE OF INTRA-ABDOMINAL HYPERTENSION IN SURGICAL PATIENTS WITH SEVERE SEPSIS

IMPLEMENTATION OF CRITICAL CARE BEST PRACTICES THROUGH THE USE OF A DAILY CHECKLIST

KyuHyouck Kyoung, Ulsan University college of Medicine, Asan Medical Center, Suk-Kyung Hong, University of Ulsan College of medicine, Asan Medical Center

Hira Shafeeq, The University of Chicago Medical Center, William Vincent, Evangelia Davanos, The Brooklyn Hospital Center

Introduction: Intra-abdominal hypertension (IAH) is known as to be associated with morbidity and mortality in critically ill patients. We tried to analyze the clinical significance of IAH in surgical critically ill patients. Hypothesis: We expect IAH will cause morbidity and mortality in severe sepsis patients. Methods: The study was performed prospectively in severe sepsis patients admitted to surgical intensive care unit (ICU). Intra-abdominal pressure (IAP) was measured 3 times a day via urinary catheter filled with 50mL of normal saline. IAH is defined above 12mmHg and peak IAP was considered as IAP the day. Results: 46 patients were enrolled and 42 patients developed IAH during ICU care. Causes of sepsis were divided into peritonitis (n⫽25) and non-peritonitis (n⫽21). 38 patients underwent laparotomy. Incidence of mechanical ventilation (MV) (P⫽0.009), duration of MV (P⫽0.012), enteral feeding (EF) starting day (P⫽0.023), ICU stay (P⫽0.006), hospital stay (P⫽0.006) and acute physiology and chronic health evaluation II score (APACHE II) (P⫽0.009) showed significant differences between IAH group and non-IAH group. However, the mortality between two groups showed no difference. Considering duration of IAH, EF interruption (P⫽0.014), duration of vasoactive drugs use (P⫽0.014), total transfusion of red blood cell (P⫽0.008) and the prothrombin time (P⫽0.038) were aggravated in patient who were persistent IAH more than 2 days (n⫽38). Especially, the patient with IAH more than 5 days group (n⫽28), 60 day mortality was increased significantly (P⫽0.038). Initial APACHE II score (P⫽0.021), peritonitis as a cause of sepsis (P⫽0.010) and duration of IAH(P⫽0.006) showed significant differences analysis between survivors and non-survivors on univariate analysis. However, in multivariate regression analysis, the duration of IAH was an only significant predictor of 60 day mortality (P⫽0.014). Conclusions: IAH delayed or even failed to proceed EF and weaning from MV. Persistant IAH rather than initial level affect on the organ failure development and mortality. We suggest that control of IAP should be considered as a one of the goal of resuscitation during critical care.


Introduction: Critically ill patients require a daily assessment of clinical best practices to achieve better outcomes. Simple checklists may improve adherence to best practices. Hypothesis: In this study we aimed to assess the improvement in adherence to clinical best practices through the use of a daily pharmacist-driven checklist. Methods: This was an IRB approved, prospective study including 38 mechanically ventilated patients admitted to the intensive care units (ICUs) of The Brooklyn Hospital Center (TBHC) from January to March 2010. A standardized checklist was developed by a pharmacy resident, the ICU clinical pharmacist and the ICU attending physicians based on published literature. The checklist was designed to assess the baseline adherence to the best practices and outline the recommendations needed to be made for those that were not implemented. Best practice categories included were analgesia, sedation, venous thromboembolism (VTE) prophylaxis, head of bed (HOB) elevation, stress ulcer prophylaxis (SUP), glycemic control and eligibility for a spontaneous breathing trial. The checklist was used daily on rounds by the clinical pharmacist or the pharmacy residents and verbal recommendations were made for any best practices not already implemented. The primary outcome was the improvement in adherence to best practices and the secondary outcome was the acceptance and implementation of verbal recommendations during rounds. Results: Overall adherence to best practices increased from 82% to 87% (p ⬍ 0.002). Adherence to best practices significantly improved pre vs. post-rounds for the categories of analgesia (74% vs. 80%, p ⫽ 0.006), sedation (67% vs. 75%, p ⫽ 0.002) and HOB elevation (54% vs. 64%, p ⫽ 0.001). The percentage of accepted recommendations implemented was significantly different for the category of VTE prophylaxis (50% accepted vs. 13% implemented, p ⬍ 0.001). Conclusions: Utilization of a pharmacist-driven checklist in the ICUs of TBHC was associated with an overall improvement in adherence to the outlined best practices. The checklist may serve as a bedside tool for pharmacists to evaluate the need for interventions that will assist in direct implementation of critical care best practices.

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THE EFFECTS OF ATORVASTATIN ON CARDIOPULMONARY BYPASS INDUCED INFLAMMATORY RESPONSE AND INTENSIVE CARE UNIT LENGTH OF STAY AFTER CORONARY ARTERY BYPASS SURGERY

BEDSIDE ULTRASOUND CAN ACCURATELY PREDICT THE VOLUME OF PLEURAL EFFUSION IN PEDIATRIC PATIENTS

Coskun Araz, Arash Pirat, Adnan Torgay, Muammer Yucel, Gulnaz Arslan, Baskent University, Faculty of Medicine Introduction: Statins may decrease inflammatory response that is associated with cardiopulmonary bypass (CPB) and may improve patient outcome after coronary artery bypass surgery (CABG). Hypothesis: We hypothesized that pre-CABG statin use decreases CPB induced inflammatory response and may improve patient outcome. Methods: After obtaining Institutional Ethics Committee approval and patients’ written informed consent, 20 patients who were atorvastatin users (for ⬎3 months) and 20 matched controls were included in this prospective observational cohort study. All patients underwent CABG with CPB using standard anesthetic and surgical techniques. Blood samples were collected for measurement of serum interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNFalpha), p-selectin, and c-reactive protein (CRP) levels. Results: The two groups were comparable regarding demographic features; preoperative characteristics; duration of CPB, aortic cross clamping, and anesthesia; intra- and postoperative hemodynamic parameters; inotrope and vasopressor needs; blood products and fluid requirements; and extubation times (p⬎0.05 for all). Compared to baseline values, in both groups serum IL-1, IL-6, TNF-alpha, p-selectin, and CRP levels increased significantly at the termination of CPB and 6 hours after surgery (p⬍0.05 for all). However, there were no significant differences between the two groups at any measurement time point in terms of CPB induced inflammatory response (p⬎0.05 for all). Patients in atorvastatin group had a significantly shorter intensive care unit (ICU) length of stay than the control group (56.7⫾19.5 hours vs 72.5⫾26.6 hours, P⫽0.008). Conclusions: In conclusion, pretreatment with atorvastatin did not decrease CPB induced inflammatory response in our CABG patients. The shorter length of ICU stay in our atorvastatin users needs to be further evaluated.

Mark Weber, Duke University, Satid Thammasitboon, West Virginia University, Scott Schulman, David Spielberg, Duke University, Robert Gustafson, West Virginia University Introduction: Pleural effusions are a significant problem in the pediatric postoperative cardiothoracic surgery patient. Although chest radiography (CXR) remains the mainstay in the diagnosis of pleural effusions, its accuracy in quantifying the volume of effusions is very limited. Hypothesis: Bedside ultrasound can be used to both confirm the presence and quantify the volume of pleural effusions. Methods: We conducted a prospective study of children with pleural effusion diagnosed by CXR requiring pleural chest tube placement in the university-based pediatric intensive care unit. Patient demographics and clinical variables were collected. The designated investigator performed a chest ultrasound in 16 subjects prior to chest tube placement. The patients were placed in supine position while the ultrasound probe was placed in a longitudinal axis along the midaxillary line. The width of the effusion was measured at its largest point. The effusion width was correlated with the volume of the chest tube drainage in the first hour. We used a multivariate linear regression model to determine the independent contribution of each predictor variable to the volume of chest tube drainage. Results: The effusion width was correlated with the 1-hr chest tube drainage (0.59, p⫽0.016). Multivariate regression showed that patient weight and effusion width were strongly predictive of the drainage volume (r2⫽0.89, p ⬍ 0.0001). Volume⫽ -13.89⫹4.41(kg weight) ⫹76.84(cm width). The predictive capacity was enhanced by accounting for positive pressure ventilation (r2⫽0.94, p ⬍0.0001). Conclusions: Bedside ultrasound can confirm and accurately predict the volume of pleural effusions in pediatric patients.



860

HUMIDIFICATION PERFORMANCE OF HEAT AND MOISTURE EXCHANGER FOR PEDIATRIC USE

EXTRACORPOREAL LIVER SUPPORT - EXPERIENCE OF AN INTENSIVE CARE UNIT

Yusuke Chikata, Tokushima University Graduate School

Susana Ferreira, Teresa Pinto Pais, Helena Pessegueiro, Jorge Daniel, Fernando Rua, Anibal Marinho, Centro Hospitalar do Porto

Introduction: Heat and moisture exchangers (HME) are popular in ICU as humidifying device for adults, and their performance reportedly varies. Humidification performance of HME has not been fully reported for pediatric use with leak around a tracheal tube. The aim of this bench study was to assess the humidification performance of pediatric HME in the presence of leak. Hypothesis: Humidification performance of HME is affected significantly with leak around a tracheal tube. Methods: We assessed 10 pediatric HMEs by using a lung model similar to Lellouche’s report (Chest 2009;135:276) except we used an infant lung bellows of a pediatric lung model (Vent Aid Training Test Lung; Michigan Instruments). The lung model (compliance of 10 ml/cmH2O) was mechanically ventilated at settings of inspiratory time of 0.8 sec, respiratory rate of 20 and 30 breaths/min, and pressure control of 10, 15 and 20 cmH2O. The expiratory gas passed through a heated humidifier (MR730; Fisher-Paykel) to obtain 37 degree of Celsius at the end of circuit. By inserting a connector with a calibrated-sized hole, two levels of leak were created: 3.2 L/min (small) and 5.1 L/min (large) under pressure of 10 cmH2O. After waiting for 10 min for stabilization, we measured absolute humidity (AH), relative humidity and temperature of the inspiratory gas for 5 min by using a rapid response hygrometer (Moiscope, Skynet). Results: When there was no leak, AH varied among the examined HMEs (28.4 to 32.4 mg/L). Eight of 10 HMEs showed AH values larger than 30 mg/L. Average leak was 22% of the inspiratory tidal volume under a small leak and 44% under a large leak. Under small leak, all HMEs showed AH below 30 mg/L (26.6 to 29.5 mg/L). Under large leak, AH decreased further (19.7 to 27.3 mg/L). As respiratory rate increased, AH increased in all HMEs. The level of pressure control did not affect AH. Conclusions: Eight out of investigated 10 HMEFs showed adequate humidification performance under no leak. However, humidification was not adequate in the presence of leak. We should be careful to use HMEs for pediatric patients in ICU.

Introduction: Artificial liver support system can remove the toxic substances by way of plasma exchange, hemodialysis, hemo-infiltration and absorption, in order to substitute the hepatic function of detoxication and as a bridge to cross over to liver transplantation. Hypothesis: Experience of our intensive care unit in the use of liver support technique (Prometheus®) in the treatment of liver failure. Methods: Retrospective analysis of the patients undergoing treatment with Prometheus®, before and after conducting this treatment, as well as major complications in the period between January 2006 and August 2010. Results: We evaluated seven patients treated with Prometheus®: three for acute liver failure and four for ‘acute on chronic liver failure‘ (sepsis -3 and transplant rejection with refractory pruritus -1) a total of 10 treatment sessions. The average duration of each session was 5hours. Three of the patients (57%) were women. Median characteristic of these patients: 60 years old (26-67), hepatic encephalopathy (HE) grade II, mean arterial pressure (MAP) of 85 mmHg, platelet count 62 000, total bilirubin 23.95 mg/dL and direct 18,97 mg/dL, creatinine 0.6 mg/dL, scores Child-Pugh 12, MELD 19,5 and SOFA 16. Complications occurred in 5 sessions (50%), being the clotting of the circuit the most common (three sessions), and transient hypotension (1). After treatment there was an improvement of HE in four patients (57%), a decrease of MAP ⬎ 20mmHg in three (43%), reduction of platelet count ⬎ 25,000 in four (57%), analytical improvement in total bilirubin ⬎ 8 mg/dL in 5 (71.4%) and a tendency to improve the MELD score. Three patients (43%) were transplanted within a few days, two (28.5%) died within five days and, particularly for refractory pruritus, there was subjective improvement of complaints immediately after the session. Conclusions: The Prometheus® is a safe technique with no reports of serious adverse effects, as it occurred in our study. The drop in MAP is probably a consequence of albumin distribution by the patient’s own secondary circuit. This study does not conclude on the effect on mortality.

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862

THE EFFECT OF NEAR INFRARED SPECTROSCOPY MONITORING ON THE TREATMENT OF PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT IN SHOCK

HEMOPERFUSION FOR THE TREATMENT OF SEVERE PROPAFENONE INTOXICATION: A CASE REPORT

James Miner, Rebecca Nelson, Lisa Hayden, Hennepin County Medical Center Introduction: Near Infrared Spectroscopy (StO2) represents a measure of perfusion. It has been shown to correlate with a patient’s lactate and acid/base status. It is not known if using information from this monitor to guide resuscitation will result in improved patient outcomes. Hypothesis: The goal of this study was to compare the resuscitation of patients in shock when the StO2 monitor is or is not used to guide resuscitation. Methods: This was a prospective observational study of patients undergoing resuscitation in the Emergency Department for shock from any cause. Adult patients (age⬎17) with a shock index (SI) of ⬎0.9 (SI⫽heart rate/systolic blood pressure) or a blood pressure ⬍80 systolic who underwent resuscitation were enrolled. Patients were monitored for oxygen saturation, blood pressure, and heart rate. Patients also had an StO2 monitor placed on the thenar eminence of their least injured hand. Data from the StO2 monitor was recorded continuously and noted every minute along with blood pressure, heart rate, and oxygen saturation. During the first phase of the study, physicians were blinded to the data from the monitor. During the second phase of the study, physicians were able to see the information from the StO2 monitor. All treatments were recorded. Patient’s charts were reviewed to determine the diagnosis, ICU length of stay (LOS), inpatient LOS, and 28 day mortality. Data were compared using descriptive statistics, Wilcoxon rank sum and chi square tests. Results: Two hundred and twenty-two patients were enrolled, 102 in phase 1 and 120 in phase 2. The median presenting shock index was 1.12(range 0.4 to 1.95) for phase 1 and 1.11 (0.39 – 2.1) for phase 2 (p⫽0.84). The median initial StO2 was 76 (range 54-91) for phase 1 and 75 (range 35-95) for phase 2 (p⫽0.44). The median hospital LOS was 11.4 days (range 0-44) for phase 1, and 8.9 days (range 0-81) in phase 2(p⫽0.04). The 28 day mortality was 19% for phase 1 and 22% for phase 2 (p⫽0.61). Conclusions: Patients who underwent resuscitation guided by data from the StO2 monitor demonstrated a shorter hospital LOS. This indicates data from the StO2 monitor may improve resuscitation outcomes.


Ming-Li Sun, Xiao-Liang Liu, Ya-Xin Yu, Hai-Feng Li, Yuan Yuan, Yan Tan, First Affiliated Hospital of Jilin University , Gui-Lan Ye, Qiqihar Medical University Case Report: Propafenone is a commonly used class IC antiarrhythmicmedication. Its intoxication is rare but the clinical outcome can be severe. Here we report a successfully treatment with homoperfusion in a case ofself-poisoning with 10 gram of propafenone tablets. The patient, 35 years old male, presented with coma, recurrent seizures, hypotension, and ventricular fibrillation to the Intensive Care Department of Jilin University 13 hours afterthe suicidal attempt. Although he had previously received a general care andan anti-arrhythmia treatment in a local clinic at four hours after poisoning, thegastric lavage was interrupted by occurring generalized seizure. Upon transferred over, the patient was given intravenous hypertonic saline,hypertonic glucose, lidocaine, and standard support. The patient regainedconsciousness and sinus tachycardia about 20 minutes after the treatment. Due to patient’s continuous abnormal electrocardiogram, hemoperfusion wasperformed at three and 17 hours after admission in a length of 2 hours pertreatment, which completely stabilized patient’s condition. The patient was discharged in full recovery three days later and followed up at seven and 30 days after discharge without any sequelae. The use of hemoperfusionappeared to be very helpful in this particular case, suggesting a critical therapeutic tool in the treatment of propafenone overdose. It is known that propafenone is a drug with higher bioavailability under larger dose and complete absorption taken orally. At a therapeutic dose, its half life is fromtwo to 12 hours, while under overdose its blood concentration can peak at nine to ten hours post-dosing. Thus the time window for performing hemoperfusion needs to be considered. This report also presented a survival case from the highest dose, to the best of our knowledge, of propafenone poisoning up to date found in the literature or rarely documented.

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AN EVALUATION OF INTRA-OPERATIVE EXTRACORPOREAL RENAL SUPPORT DURING LIVER TRANSPLANTATION: A RETROSPECTIVE CASE-CONTROL STUDY

CHALLENGES IN THE RANDOMIZATION OF CANCER PATIENTS INTO THE PROPHYLAXIS FOR THROMBOEMBOLISM IN CRITICAL CARE TRIAL (PROTECT)

Ambica Parmar, David Bigam, Glenda Meeberg, Derek Townsend, University of Alberta, Sean Bagshaw, University Of Alberta Hospital Division of Critical Care Medicine

Joseph Nates, Sajid Haque, Rose Joan Erfe, M. Cardenas-Turanzas, D. Mooring, The University of Texas at M D Anderson Cancer Center, N. Zytaruk, Deborah Cook, McMaster University for the Canadian Critical Care Trials Group

Introduction: Continuous renal replacement therapy (CRRT) is commonly applied intra-operatively during liver transplantation (LT); despite a relative paucity of data. Hypothesis: We hypothesized intra-operative CRRT during LT would be associated with reduced post-operative complications. Methods: This was a retrospective case-control study. Cases were defined as adult (age ⱖ 18 yrs) patients undergoing LT and receiving intra-operative CRRT between August 1, 2006 and July 31, 2009. Controls were matched (1:1) for age, sex and preoperative Model for End-Stage Liver Disease (MELD) score. Data were extracted on demographics, physiology, clinical course and outcomes. Results: In total, 72 patients were included. Mean (SD) age was 47.7 (11.5) years, 44.4% were female, and Charlson index score was 3.4 (0.8). Despite attempts to match by MELD, cases had higher pre-operative scores (35.4 [9.1] vs. 29.9 [9.2], p⫽0.01) compared with controls. Pre-operatively, cases were more likely to be receiving vasopressors (52.8 vs. 19.4%, p⫽0.006), to have acute kidney injury (AKI) (97.2 vs. 55.6%, p⬍0.0001) and to be receiving RRT (94.4 vs. 25.7%, p⬍0.0001) compared with controls. There was no difference in post-operative complications, including bleeding, sepsis, need for re-operation, reintubation or ICU readmission rate (58.3 vs. 44.4%, p⫽0.35; 19.4 vs. 33.3%, p⫽0.29, respectively). Postoperatively, cases had longer stays in both ICU (13.5 d [7-26.5] vs. 6 d [3-12.5], p⫽0.005), and hospital (69 d [48-104] vs. 37 d [17-64], p⫽0.0002). Case were also more likely to require RRT post-operatively (94.4 vs. 25.7%, p⬍0.0001), post-ICU (41.7 vs. 0%, p⬍0.0001) and upon hospital discharge (6 vs. 0%, p⫽0.03). There was no observed difference in hospital mortality (2.8 vs. 8.3%, p⫽0.61). Conclusions: LT patients selected for intra-operative CRRT more commonly have hemodynamic instability and pre-operative AKI requiring RRT. Despite greater pre-operative illness severity and treatment intensity for cases, there were no differences in the rate of post-operative complications or mortality; however, cases required longer stays in hospital and were more likely to remain dialysis dependent.

Introduction: The Frontline study reported a very low rate of venous thromboembolism (VTE) prophylaxis among cancer patients worldwide (1). This population is frequently excluded from randomized clinical trials (RCTs) and little evidence is available to guide VTE prophylaxis recommendations. Hypothesis: To narrow this knowledge gap, we described the characteristics of patients with cancer admitted to the Intensive Care Unit (ICU) of a comprehensive cancer center screened for randomization in the PROTECT; a prospective, stratified, concealed, blinded multicenter RCT testing 2 regimens for VTE prevention (PROTECT, the PROphylaxis for ThromboEmbolism in Critical Care Trial). Methods: In this longitudinal study of consecutive critically ill patients, we screened all admissions from 06/05/2009 to 11/30/2009 for trial eligibility, analyzing patients who met the inclusion criteria and one or more of the exclusion criteria. Results: A total of 999 patients were screened, 4 were enrolled, 2 declined and 690 met inclusion criteria (age ⬎17 y, weight ⬎ 44 kg, and expected ICU stay ⬎72 hrs) but had conditions for exclusion. The mean age was 56 years, the majority was men (61%), most patients (59%) were admitted for medical reasons; 76% had non-hematological cancers. The mean LOS before ICU admission and ICU LOS were 4.3 and 5.2 days, respectively. The commonest reasons for exclusion were thrombocytopenia (33%), brain or spinal surgery (23%), already anticoagulated for VTE (13%), limitations to life support with life expectancy less than 7 days (11%), bleeding complications (11%), and enzymatic coagulopathy (10%). Conclusions: In this analysis of a RCT screening log in our large cancer center, we identified a remarkably high RCT exclusion rate. The low enrollment indicates that researchers interested in including patients with cancer in RCTs of prophylaxis for VTE, should anticipate a prolonged accrual period. Our findings also suggest that previous reports of poor thromboprophylaxis rates in cancer patients are most probably secondary to contraindications rather than lack of physician compliance. Reference: Kakkar AJ et al. The Oncologist 2003; 8(4):381-388.

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MAGNESIUM SLIDING SCALE FOR SUB ARACHNOID HEMORRHAGE

FEVER AND ANTIPYRETIC THERAPY IN CRITICALLY ILL PATIENTS: A SYSTEMATIC REVIEW

Muhammad Taqi, Medical College of Wisconsin, John Lynch, The Medical College of Wisconsin, Michel Torbey, Froedtert & Medical College of Wisconsin

Moritoki Egi, Kiyoshi Morita, Okayama University Hospital

Introduction: Magnesium sulfate has been studied to prevent vasospasm anddelayed cerebral ischemia (DCI) in subarachnoid hemorrhage(SAH) with mixed results. MASH and IMASH trials failed to showany benefit in outcome at three months. Recently Westermaier et al. showed reduce incidence of vasospasm by highdose IV magnesium therapy. Hypothesis: To replicate the effects of above study. Test safety and feasibility of highdose magnesium therapy. Methods: All patients with SAH admitted to NICU from June 2010 werestarted on 4gms magnesium sulfate IV bolus followed by 2 gms IV/hr for 10 daysto keep serum magnesium levels 4-5 mg/dl. Serum levels were checked 3 horus post bouls and then 8 hoursthereafter. Adjustment were made accordingto following scale. Serum level Adjustments ⬍4 Increase rate by 0.5gm/hr4.1-5 No change 5.1-6 Decrease rate by 0.5 gms/hr ⬎6 Hold infusion until next serum level, if ⬍5 restart at half the previous dose. Results: All patients achieved target serum concentration with in 8 hours of bolus dose.None of the patients had infusion relatedhemodynamic instability. Only onepatient lost deep tendon reflexes (DTR’s) at target serum magnesium level. None of the patients had any sideeffects or complications from high dose magnesium sulfate.When CSF was available, CSF magnesium levelswere also monitored and correlated with serum levels linearly. Although outcome measures were not assessedat this point, only two patients developed mild vasospasm. No patient developed DCI. Conclusions: High dose magnesium therapy is safeand feasible. Above sliding scale toachieve target serum concentration is efficient and reliable.

Introduction: Fever is common in critically ill patients. Antipyretic therapy for fever is similarly. Hypothesis: There is insufficient information on how body temperature should be controlled in non-neurological critically ill patients. Methods: We performed a systematic literature search (January 1978 – June 2010) to identify publications which assessed the impact of fever and antipyretic therapy on mortality in critically ill patients without neurological injury. The literature search was performed using the electronic databases and the following key words: hyperthermia, fever, temperature, intensive care, critically ill, ICU, death and mortality. Results: We identified 1329 articles, and selected 113 articles for full text review. Of these, 31 assessed the impact of fever and antipyretic therapy on mortality in critically ill patients without neurological injury. Three studies were randomized controlled trials, 20 studies were prospective cohort studies and 8 studies were retrospective cohort studies. There is no multicenter prospective study.A) The definition of fever; All 31 studies reported a definition of fever. We found the definition to be highly variable ranging from 37.5°C to 38.5°C, with a mean of 38.1⫾0.3°C. B) The association of fever with mortality; Eight studies assessed the association of fever with mortality. Meta analysis of these seven studies showed that fever was associated with a 30% increase in mortality (p⬍0.001). C) The effect of antipyretic therpies on mortality; We found three RCTs investigated the effect of antipyretic therapy on mortality. Meta analysis of them shows that aggressive antipyretic therapy, administered for a body temperature ⬎ 38.3 or 38.5°C carried a non-significant 2.5-fold increased risk of death (p⫽0.15). Conclusions: There is little evidence to support any specific management strategy for fever in non-neurological ICU patients. The limited quality evidence available, however, suggests that routine antipyretic therapy in febrile patients without neurological injury may be injurious. Better randomized controlled trials are needed to define the role of antipyretic therapy and the appropriate trigger temperature for intervention.


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EVALUATION OF GLUCOSE MANAGEMENT DURING INDUCED HYPOTHERMIA AT A TERTIARY ACADEMIC MEDICAL CENTER

POST-OPERATIVE CRITICAL CARE MANAGEMENT OF PATIENTS UNDERGOING CYTOREDUCTIVE SURGERY (CRS) AND HEATED INTRAPERITONEAL CHEMOTHERAPY (HIPEC)

Allison Forni, Megan Chesnick, Paul Szumita, Kevin Anger, Kathleen Avery, Benjamin Scirica, Brigham and Women’s Hospital Introduction: Alterations in metabolic function during induced hypothermia (IH) decrease responsiveness to insulin therapy and increase the risk of hyperglycemia. Glycemic control is associated with improved outcomes in select patients, however, management strategies during IH are not defined. Hypothesis: Evaluate the effects of IH on glycemic metrics in critically ill patients during cooling and rewarming. Methods: Adult patients undergoing IH for at least 6 hours following cardiac arrest from January 2007 to January 2010 were retrospectively evaluated. Data included APACHE II score, diagnosis of diabetes, and admission blood glucose. Outcomes evaluated included patients receiving IV insulin, rates of hyperglycemia (⬎200 mg/dL) and hypoglycemia (⬍72 mg/dL), insulin requirements, and mean blood glucose during cooling and rewarming. Results: Thirty-seven patients were included with a mean APACHE II score of 22.9⫾4.8, mean admission glucose of 225.5⫾101 mg/dL, and 14 (37.8%) patients had diabetes. Mean blood glucose was 164.9 ⫾57.9mg/dL and 117.7 ⫾44.1mg/dL; p⬍0.01 during cooling and rewarming, respectively. Twelve (32.4%) patients experienced at least one hypoglycemic event. Nineteen (51.4%) patients experienced at least one hyperglycemic event and 15 (40.5%) patients received IV insulin therapy. Patients on IV insulin had a higher incidence of diabetes (9 vs. 5; p⬍0.05), higher admission blood glucose (250.1⫾110.3 vs. 198.55⫾83.65; p ⫽0.11), and a higher incidence of hyperglycemia (14 vs. 2; p⬍0.01) and hypoglycemia (8 vs. 4; p⬍0.05). Of the patients on IV insulin, mean insulin requirements during cooling and rewarming were 15.2⫾16.1 vs. 7⫾12.5 units/hr, respectively. Conclusions: IH is commonly associated with hyperglycemia, hypoglycemia, and the use of IV insulin therapy at our institution. Further research is needed to determine optimal glycemic management strategies.


Timothy Cooksley, Philip Haji-Michael, The Christie Hospital Introduction: Pseudomyxoma peritonei is a rare epithelial neoplasm, characterized by progressive accumulation of peritoneal mucinous tumour deposition. Treatment of this condition with combined CRS and HIPEC has been shown to improve both patient survival and quality of life. Hypothesis: This procedure results in a number of physiological changes with effects on the cardiovascular system, oxygen consumption and coagulation and post-operative Critical Care interventions required by this cohort of patients may be high. Methods: This retrospective audit examines the experience of a Specialist Unit in England over an 18 month period (Jan 2009 – June 2010) during which 69 patients underwent CRS and HIPEC. All patients were extubated in the operating theatre and transferred to the Critical Care Unit (CCU) for initial post-operative management. Total parenteral nutrition, patient controlled epidural analgesia, IV proton pump inhibitor prophylaxis, nasogastric suction and low molecular weight heparin for prevention of venous thrombosis were given to all patients. Results: The average age of the patients in this study was 53.3 years with an APACHE II score of 13.6. The mean length of surgery was 8.75 hours. Patients needed to remain on the CCU for 2.4 days and mean length of hospital stay was 13 days. There were no 30 day mortalities. 70.1% of patients did not require post-operative organ support. 2 patients who developed pneumonia post-operatively required respiratory support. 18 (26.1%) patients required vasopressor support with norepinephrine. The mean duration of vasopressor requirement was 13.94 hours with a mean dose of 0.04mcg/kg/min. No patient developed renal failure. Post-operative coagulopathy peaked at 24 hours. 15 patients required transfusion with Red Blood Cells in the post-operative period. There was a significant drop observed in serum albumin. There were no surgical complications that necessitated re-operation. Conclusions: The degree of organ support required post-operatively is minimal. Early extubation is efficacious with the aid of epidural analgesia. Critical Care monitoring for 48 hours is desirable in view of the challenges of fluid management, low albumin state, coagulopathy and potential complications.


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THE EFFECT OF PRESSURE-VOLUME CURVE ON THE OUTCOMES OF ACUTE RESPIRATORY DISTRESS SYNDROME: A SYSTEMATIC REVIEW

A DOOR COMMUNICATION TOOL DID NOT IMPROVE THE ALIGNMENT OF A MULTIDISCIPLINARY TEAM’S GOALS FOR INTENSIVE CARE UNIT PATIENTS

Kei Togashi, University of Washington, Linda Hodges, Hannibal Clinic, Paul Tessmann, University of Florida College of Medicine, Christopher Faust, University of Iowa Hospitals and Clinics, Avinash B. Kumar, University of Iowa Hospitals & Clinics, J. Steven Hata, Universtiy of Iowa Hospitals and Clinics

Jeremy Pamplin, BAMC, David Allen, USAISR, John Linfoot, BAMC, Craig Ainsworth, DDEAMC, Kevin Chung, USAISR

Introduction: The pressure-volume curve (PVC) is a bedside diagnostic test that has been used to prescribe PEEP in ARDS. Its role, however, in the management of ARDS remains controversial. This systematic review compared the effect of exposure to PVC-guided ventilator management to standard care on survival in patients with ARDS. Hypothesis: We hypothesized that PVC-guided ventilator management would improve survival in patients with ARDS. Methods: This prospectively designed meta-analysis identified studies with the following inclusion criteria: (1) randomized, controlled design (2) adult patients (3) standard definitions for ARDS, and (4) PEEP support directed by the PVC. We performed a computer search on PubMed from January 1,1960 to January 1, 2010 and the Cochrane Central Register of Controlled Trials (CENTRAL). Results: Three randomized, controlled trials were identified with a total of 185 patients, 97 with PVC-guided treatment and 88 within the control group. Exposure to PVCguided PEEP was associated with an increased probability of survival (OR 2.71, 95% CI 1.48, 4.93) using the random effects model. The cumulative risk reduction in mortality associated with the use of the PVC to guide the ventilator prescription was -0.245 (95% CI -0.384, -0.106). I2 failed to show significant heterogeneity (p ⫽ 0.748). Secondary outcomes showed that PVC-exposed patients received increased levels of PEEP (standardized mean difference (SMD) 5.7 cm H2O, 95% CI 2.4, 9.0), lower plateau pressures (SMD -1.2 cm H20, 95% CI -2.2, -0.2), with higher levels of pCO2 (SMD 8 mm Hg, 95% CI 2, 14). These analyses, however, were associated with significant heterogeneity. Finally, PVC guided, weight-based tidal volumes were reduced as compared with the control groups (SMD -2.65 ml/kg, 95% CI -3.32, -1.98). Conclusions: The results of this systematic review support a hypothesis that use of the PVC-guided ventilator management appears to be associated with improved survival in patients with ARDS.

Introduction: Communication errors remain a major patient safety issue. Intensive care units (ICU) are high-risk environments where medical errors occur frequently. Establishing well understood daily patient care goals should improve multidisciplinary healthcare team (MDHCT) communication and may reduce errors in this environment. Hypothesis: Implementation of a daily goals “Door Communication Card” (DCC) will improve goal alignment between members of the MDHCT. Methods: This project was conducted in a 20-bed transitional model surgical ICU in a 450-bed academic military medical center. To establish a baseline frequency of goal alignment, we asked MDHCT members to “list your top four major goals” for a patient on a given day. Team members queried were the ICU attending, the bedside nurse, the on-call ICU resident, and the primary surgical chief resident. After initial data collection, DCC’s were placed on patients’ doors. Anyone was allowed to write on the card, but the “official” daily goals were recorded during multidisciplinary rounds (MDR). Goal discrepancies noted during MDR were reconciled with phone calls. One month after introduction of the DCC, MDHCT members were re-queried about their goals. Three reviewers (a nurse, an ICU attending, and a resident) independently assessed goal alignment. Results: We collected goals over a 4 month period and selected 5 random days before and after intervention for assessment. The goal alignment between MDHCT members was low before and did not improve after intervention (Attending-to-nurse 36% vs. 29.6%, p⫽0.0267; Attending-to-Resident 36.6% vs. 34.3%, p⫽0.554; Attending-to-Primary 26.1% vs. 24%, p⫽0.7971; Nurse-to-Attending 33.3% vs. 27.6%, p⫽0.0373; Nurse-to-Resident 35% vs. 32.3%, p⫽0.1307; Nurse-to-Primary 26.5% vs. 23.2%, p⫽0.3558; Resident-toAttending 38.4% vs. 35.5%, p⫽0.3079; Resident-to-Nurse 35.5% vs. 29.4%, p⫽0.0558; Resident-to-Primary 25.1% vs. 18.4%, p⫽0.0516; Primary-to-Attending 25.7% vs. 28.4%, p⫽0.5272; Primary-to-Nurse 27.5% vs. 30.5%, p⫽0.7856; Primary-to-Resident 23% vs. 24.1%, p⫽0.6255). Conclusions: Alignment of daily patient care goals between MDHCT members is low overall and did not improve after implementing a DCC available to all team members.

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IMPACT OF HYPOGLYCEMIC EVENTS ON PATIENT OUTCOMES IN A NEUROLOGICAL INTENSIVE CARE UNIT

SUCCESSFUL DIAGNOSIS AND TREATMENT OF THREE CASES OF CEREBRAL SALT WASTING SYNDROME

Lyn Clarito, Brian Smith, Umass Memorial Medical Center, Jeffrey Fong, Massachusetts College of Pharmacy and Health Sciences, Umass Memorial Medical Center

Xiao-Liang Liu, Ming-Li Sun, Yuan Yuan, Hai-Feng Li, Yan Tan, First Affiliated Hospital of Jilin University , Gui-Lan Ye, Qiqihar Medical University

Introduction: Intensive insulin therapy (IIT) is a widely utilized intervention in critically ill patients, however it is associated with greater development of hypoglycemia. Hypoglycemia (HG) can be detrimental in patients with impaired cerebral flow such as those with significant brain injury. There is paucity of data demonstrating impact of HG on neurological outcomes in this vulnerable population. Hypothesis: To determine the impact of HG on patient outcomes admitted to the neurological intensive care unit on insulin therapy. Methods: This is a retrospective database review where patients were included if they met the following criteria: 18 years of age or older and diagnosis of subarachnoid hemorrhage, intracranial hemorrhage, stroke or transient ischemia attack, or traumatic brain injury and receipt of IIT targeting 80-140 mg/dL. Patients were excluded if diabetic ketoacidosis or hyperosmolar state was present. Results: We included 125 patients with the following baseline characteristics: male gender (66%) and mean age of 68 years. HG events occurred in 44 patients where 8 patients had an episode of severe HG (blood glucose ⬍ 40mg/dL) and 36 had an episode of moderate HG (blood glucose 40-70mg/dL). There were 22 (50%) patients in the HG group that experienced neurological outcomes (eg. confusion, somnolence) vs. 3 (3.7%) patients in the non-hypoglycemic group (p ⬍0.0001). The HG group experienced greater mean hospital length of stay 17 days vs. 8 days, (p⬍0.0001). In the HG group, we analyzed glucose variability (standard deviation of mean glucose levels). There was no difference between glucose variability and Glasgow Outcome Score, (p⫽ 0.14). Of the 44 patients that experienced hypoglycemia, 4 (9.1 %) did not survive. Conclusions: We observed an association between hypoglycemia and worsening of neurological, as well as clinical outcomes.

Case Reports: Cerebral salt wasting (CSWS) is a syndrome of hypovolemichyponatremia resulting from renal loss of sodium (Na) in association withintracranial diseases. Currently there is no standardized clinical care practicein the management of CSWS. Here we report a successful treatment of threecases of CSWS. The subjects, admitted to the Intensive Care Departmentdue to difficulty breathing for the first two cases and unconsciousness for thethird at their 10 ⬃ 25 days recovery from original but well controlled headinjury, acute cerebral infarction, or intracranial tumor, were diagnosed withCSWS based on their noticeably reduced skin turgor and low serum Na (104- 122 mmol/L) but high urinary 24 hour Na (304 - 599 mmol/L). Besidesgeneral management, the subjects were specifically treated with acombination of 1) Na supplement 015-0.25g/kg/day (depending on serum Naloss) by oral intake of 10% NaCl in addition to diet Na and intravenousinjection (i.v.) of 3% NaCl 200 ml following balanced fluids i.v. and 2)hydrocortisone 200, 100, and 50mg/day i.v. for the first, second, and thirdthree days respectively. Patient’s serum Na and urinary 24 hour Na weremonitored daily. The symptoms of all subjects were improved gradually bythe treatment, starting serum Na level recovery at day four. The subjectswere discharged at day 10 - 15 of hospitalization with serum Na level of 127 -133 mmol/L. Our diagnosis was made based on patients’ history of recentintracranial diseases, altered serum and urinary Na, and especially poor skinturgor to distinguish CSWS from the syndrome of inappropriate antidiutetichormone secretion. Synthetic steroids have been recommended, there is,however, no standard protocol to date to the management of CSWS. The useof moderate dose of hydrocortisone in supplement to the volume and Narepletion reported here demonstrated an effective algorithm for managementof CSWS patients.


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APPROPRIATE ANTIBIOTICS IN CRITICALLY ILL SURGICAL PATIENTS WITH BACTEREMIA

THERAPEUTIC HYPOTHERMIA FOR COMATOSE NEARHANGING SURVIVORS WITH CARDIAC ARREST

Katri Abraham, Janie Faris, Lisa Hall Zimmerman, David Edelman, George Delgado, Robert Wilson, Detroit Receiving Hospital

Toru Hifumi, Junichi Inoue, Takashi Kanemura, Hiroshi Kato, Yuichi Koido, National Disaster Medical Center

Introduction: Nosocomial blood stream infections in critically ill patients are associated with a mortality as high as 80% and a prolonged hospital stay. Currently, limited data exists in the surgical literature regarding the importance of appropriate initial antibiotic therapy in critically ill patients with positive blood cultures. Hypothesis: Appropriate antibiotic therapy in critically ill surgical patients with bacteremia impacts outcomes. Methods: This is a retrospective study of 55 consecutive adult surgical intensive care patients with bacteremia from 1/06 – 6/09. Nosocomial bacteremia was defined as the presence of a recognized pathogen from one or more blood cultures. Empiric antibiotics were appropriate if the pathogen isolated was susceptible based on MIC data. Patients were divided into two groups: initial appropriate (AAT) vs inappropriate (IAT) antibiotic therapy. Time to AAT was defined as time from initial antibiotics prescribed to administration of appropriate antibiotics. Results: There were 55 patients admitted to the surgical ICU with 72 episodes of bacteremia with an overall bacteremia rate of 14% (55/382) primarily due to a central venous catheter (86%). Patients were 54⫾17 years of age with an APACHE II of 17⫾8, with 57 receiving AAT and 15 receiving IAT. IAT tended to have a higher mortality rate vs AAT, 33% (5/15) vs 16% (9/57), p⫽0.12. Time for appropriate antibiotics to begin was longer for IAT vs AAT, [2.6⫾4.7 vs 0.6⫾0.8 days, p⫽0.003]. IAT was seen primarily with Acinetobacter spp. (p⫽0.01) and Enterococcus faecium (p⫽0.03) isolates. If 2 or more bacteremic episodes occurred, Acinetobacter spp. was more likely, p⫽0.001. In surviving patients (n⫽44), overall hospital length of stay (LOS), [86⫾55 vs 47⫾43, p⫽0.03] was longer and ICU LOS (61⫾54 vs 37⫾40, p⫽0.17) tended to be longer with initial IAT vs AAT. In-hospital death occurred when acidosis was present (36% vs 2%, p⫽0.0004) and when Acinetobacter spp. on culture (35% vs 8%, p⫽0.02). Conclusions: Bacteremias in critically ill surgical patients are an important problem. Use of AAT decreases mortality and LOS. Acinetobacter spp. has significant impact on outcomes in this population and should be anticipated in prolonged stay.

Introduction: Therapeutic hypothermia (TH) has been shown to clearly benefit comatose survivors of cardiac arrest (CA). However, the literature is limited in the use of TH specifically for the comatose survivors of near-hanging, especially with CA. Hypothesis: TH demonstrates good outcome even in comatose survivors of CA after near-hanging. Methods: We retrospectively reviewed the records of comatose survivors suffered CA after near-hanging between January 1, 2008 and July 31, 2010 for whom TH was used.Only patients who had received cardiopulmonary resuscitation by medical personnel were defined as having had CA.TH was initiated as early as possible, and the target temperature was set at 33⫾1 degrees Celsius for 24h; the treatment was performed according to an existing protocol for CA patients.The primary outcome measure was the neurological function at discharge as determined by the 5-level cerebral performance category (CPC) scale. A good outcome was represented by a CPC scale score of 1 or 2, and a poor outcome by a CPC scale score of 3-5.Comparison between the good neurological outcome group and bad neurological outcome group was performed in relation to the age, gender, Glasgow Coma Scale (GCS), serum lactate level, arterial blood pH, and base deficit (BD) on admission. Results: A total of 8 patients were analyzed. Seven were male, and the median age was 53 years (range, 35-67 years). All the hangings were unwitnessed. The median serum lactate level was 6.85 (range, 2.6-10.6 mmol/l), the arterial blood pH was 7.344 (range, 6.815-7.597), and the BD was 9.0 (range, 1.0-19.7 mmol/l)Four patients had a good neurological outcome at discharge (50%), and four patients had a poor outcome, one of whom died in hospital and two remained in a vegetative state. Between the two groups, there were no significant differences in the age, gender, GCS, arterial blood pH, BD, or serum lactate level. Conclusions: TH for comatose near-hanging survivors of CA was demonstrated to yield good neurological recovery.

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PROGNOSTIC VALUE OF ENDOTOXIN ACTIVITY ASSAY IN PATIENTS WITH SEPSIS

IN-HOSPITAL MORTALITY AND SEVERITY OF ILLNESS OF ADULT SEPTIC SHOCK PATIENTS TREATED WITH EGDT IN A REGIONAL, NON-TEACHING US HOSPITAL

Takeyuki Kiguchi, Satoshi Fujimi, Critical Care & Trauma Center, Osaka General Medical Center, Japan Introduction: It is known that several serum markers are useful as a prognostic factor in patients with sepsis. Endotoxin Activity Assay (EAA) is a first reported as a method for detecting endotoxin based on the ability of antigen-antibody complex to prime neutrophils and augmented respiratory burst response. Endotoxin assay (EA) levels were expressed in relative units derived from the integral of the basal (no antibody) and stimulated (4600 pg/ml LPS) camiluminescent response. Several reports have shown that EA levels were significantly increased in patients with sepsis. However the usefulness as a prognostic factor is uncertain. Hypothesis: EAA may be an appropriate method for predicting the prognosis in septic patients. Methods: We performed, IRB approved, prospective study of 72 consecutive patients with sepsis who admitted to our ICU from Sep. 2009 to Aug. 2010. Comprehensive clinical and laboratory data were collected on the day of ICU admission. Blood was sampled at that time to measure the EA levels. Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were also calculated using the data at the same time. We examined the correlation of EA levels with APACHE II, SOFA score and the outcome. In addition, we analyzed chemiluminescent intensities after stimulation of 4600 pg/ml LPS that usually did not take a notice for detecting EA levels. Results: 64 patients were alive and 8 were died. Mean EA levels in all patients was 0.50 ⫾ 0.03. EA levels slightly correlated to APACHE II score and SOFA score (r⫽ 0.44; p ⬍0.01 and r⫽ 0.41;p ⬍0.01). However, EA levels were scattered in non survivors. The reason is why the chemiluminescent intensities after stimulation of 4600 pg/ml LPS were significant decreased in non survivors compared to survivors (18371⫾ 14861 RLU/sec vs 171955⫾ 23273 RLU/sec: p⬍0.05). Conclusions: EAA might become an appropriate method for predicting the prognosis in patients with sepsis under the detailed analysis of both EA levels and chemiluminescent intensities.


Dean Sandifer, The Watson Clinic, LLP, Erin Kuecker, Carrie Ogilvie, Troy Batterton, Lakeland Regional Medical Center Introduction: In 2006, we established Early Goal Directed Therapy (EGDT) for adult septic shock (SS) pts. We report the in-hospital mortality our first 244 SS pts. treated with EGDT as well as their APACHE II severity of illness scores. Hypothesis: The utilization of EGDT for septic shock in a regional hospital and can lead to mortality comparable to Rivers’ original publication (CCM 2001). Methods: We retrospectively collected data from 244 adult SS pts treated with EGDT. The severe sepsis diagnosis was made using standard criteria and shock was defined as the need for vasopressors to maintain a MAP ⬎ 65mmHg after at least a 20mL/kg IV crystalloid fluid challenge. The exclusion criteria were pts ⬍18 yrs old and pts with severe sepsis who did not develop shock within 24 hrs. All other SS pts regardless of DNR status or co-morbidities were included. The severity of illness is based on the APACHE II scoring system. The subgroup who developed SS in the Emergency Dept. is designated as EDSS. Results: Of the 244 pts (125 male, 99 female), the mean age was 67.1 yrs, 203 pts required mechanical ventilation, and only 5 received Activated Protein C. Table 1 Pt Group no. of pts no. of deaths prior mean APACHE II no. met 6-hr to hospital d/c (%) ScvO2goal (%)Total 244 114 (46.7) 26.8 142 (58.2)EDSS 153 66 (43.1) 28.0 92 (60.1). Conclusions: Rivers reported a 42.3% in-hospital mortality for his SS subgroup all treated with EGDT in the ED. His standard therapy SS subgroup’s mortality was 56.8%. He excluded DNR pts and pts with 13 other listed co-morbidities. None of his pts developed SS as in-patients. Our overall SS mortality was 46.7% despite including pts with DNR status, significant co-morbidities (see APACHE II data) and pts who developed SS as in-pts ⬎24 hours after admission. Our EDSS subgroup’s mortality was 43.1%. The utilization of EGDT for septic shock in a regional hospital and can lead to mortality comparable to Rivers’ original publication.

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CHARACTERISTICS OF BILATERAL VERSUS UNILATERAL RIB FRACTURES IN A SICU

A STUDY TO IDENTIFY THE POST-OPERATIVE FLUID REQUIREMENTS OF PATIENTS UNDERGOING CYTOREDUCTIVE SURGERY WITH HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY

Jonas DeMuro, Devan Lenhart, John McNelis, Judy Jax, Susan Simmons, William Reed, Winthrop University Hospital Introduction: Patients with Bilateral Rib fractures are assumed to have a greater incidence of associated injuries, higher SICU and Hospital Lengths of stay (SICU LOS, HOSP LOS) as well as a higher mortality than patients presenting with unilateral fractures. In our study, we seek to contrast a series of patients with bilateral rib fractures with a matched cohort of patients with unilateral rib fractures. Hypothesis: Patients with Bilateral Rib Fractures have higher morbidity, mortality as well as higher SICU and Hospital lengths of stay than a similar controlled group of patients with unilateral rib fractures. Methods: The medical records of 39 patients with rib fractures were reviewed retrospectively. Patients were grouped into patients with unilateral (Ufx) and bilateral rib fractures (Bfx). Groups were matched as closely as possibly with regard to age and associated injuries. Data acquired included Demographic data, age, sex, mechanism of injury, SICU LOS, HOSP LOS, Ventilator Days (VENT), ISS, Associated Injuries, co morbidities, location , number of rib fractures, hemothorax, pneumothorax, pneumonia and mortality. Statistical Analysis was by chi squared and student t-test. Results: See table below: ICULOS HOSPLOS VENT ISS Ribfx Ufx 4.6⫾11.2 10.8⫾13.9 2.72⫾9.2 12.4⫾10.2 4.8 Bfx 17.2⫾24.7 23.1⫾23.6 10.9⫾19.2 21.1⫾11.4 10.8 p p⬍.05 p⬍.05 NS p⬍.02 NS Ufx and Bfx did not differ in age (60.9⫾19.7 vs 59.0⫾19.1).Sixty four percent of bilateral fractures resulted from MVAs while 52% of unilateral fractures followed falls. The groups did not differ in incidence of hemothorax, pneumothorax pneumonia or mortality. Conclusions: Based on our data, our hypothesis stating that bilateral rib fractures are associated with higher complications is partially correct. Patients with bilateral rib fractures have higher HOSPLOS and SICULOS and a higher ISS than their corresponding cohort, however, they do not have a higher mortality, incidence of pulmonary complications or mortality. Our data is preliminary and ongoing data collection is being undertaken.

Lewis Somberg, David Milia, Jasmeet Paul, Sam Pappas, Medical College of Wisconsin Introduction: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in combination with Cytodreductive Surgery (CRS) is being employed with increasing frequency for the treatment of peritoneal carcinomatosis associated with various gastrointestinal malignancies. The post-operative management of these patients can be complex, often requiring large volume fluid resuscitation in an intensive care unit. No study to date has examined the post-operative volume requirements. Hypothesis: The post-operative volume requirements of patients undergoing HIPEC therapy can be predicted based on identifiable pre- and peri-operative variables. Methods: IRB approved single institution retrospective chart review of all patients undergoing HIPEC/CRS from 2005-2010. Patients were divided into groups according to post-operative fluid requirements. Standard and large volume of resuscitation (SVR and LVR) were designated as ⱕ3 and ⬎3cc/kg/h for the initial 24h. Intra-operative variables including OR time, estimated blood loss (EBL), base excess, peritoneal cancer index scores, crystalloid, colloid, and total OR volumes were studied. Post-operative variables including hemoglobin (Hgb), base excess (BE), urine output (UOP) and serum creatinine were also analyzed. Results: A total of 14 patients were identified as having undergone HIPEC/CRS. Based on UOP and SCr all patients were resuscitated within 24 hours. 6 patients received LVR . OR time, EBL, base excess, and peritoneal cancer index were not significantly different. Average total intra-operative fluid volume was 17cc/kg/ h ⫾ 6cc for SVR and 27cc/kg/hr ⫾ 10cc for the LVR group (p⫽0.035). Conclusions: Patients requiring larger intra-operative fluid volumes during HIPEC/CRS will continue to require large volume resuscitations during their ICU course. Lower intra-operative fluid requirements predict decreased fluid requirement in the post-operative period. A larger study is necessary to determine other significant differences between the two groups.


Poster: Therapeutics-Sedation-1 879

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PLASMA CONCENTRATIONS OF LORAZEPAM VS DEXMEDETOMIDINE AS RISK FACTORS FOR DELIRIUM DURING MECHANICAL VENTILATION

IMPACT OF QUETIAPINE ON RESOLUTION OF INDIVIDUAL DELIRIUM SYMPTOMS IN CRITICALLY ILL PATIENTS WITH DELIRIUM: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PILOT STUDY

Timothy Girard, Vanderbilt School of Medicine, Jessica Meeks, Lipscomb University College of Pharmacy, Brett English, Vanderbilt University, Jennifer Thompson, Ayumi Shintani, E Wesley Ely, Pratik Pandharipande, Vanderbilt School of Medicine Introduction: High doses of benzodiazepines (e.g., lorazepam), which are frequently used to sedate mechanically ventilated ICU patients, are important risk factors for delirium. The alpha2 agonist, dexmedetomidine, is an alternative sedative that has been shown in recent trials to reduce the prevalence and duration of delirium during mechanical ventilation, compared with benzodiazepines. The importance of plasma sedative concentrations to the development of delirium in these trials has not been previously examined. Hypothesis: Increasing plasma concentrations of lorazepam are associated with more delirium, whereas increasing plasma concentrations of dexmedetomidine are associated with less delirium. Methods: During the MENDS randomized trial comparing lorazepam with dexmedetomidine for sedation in the ICU, we collected blood twice daily until study drug was stopped and measured plasma concentrations of lorazepam using RP-HPLC and of dexmedetomidine using RPHPLC-MS/MS. Delirium was diagnosed daily using the Confusion Assessment Method-ICU. To examine the independent relationships between plasma concentrations of these sedatives and probability of delirium, we used logistic regression and adjusted for the previous day’s mental status and fentanyl dose. Results: Of 106 patients enrolled in MENDS, 103 had ⱖ1 plasma sample collected and were therefore included in this ancillary study. Excluding days in coma (which prevents delirium assessment), 152 observations were analyzed. Higher lorazepam concentrations were associated with increased probability of delirium (OR 13.2, 95% CI 1.4-120.1, p⫽.02), whereas changes in dexmedetomidine concentration were not associated with probability of delirium (OR 1.1, 95% CI 0.9-1.3, p⫽.45). Conclusions: Higher plasma concentrations of lorazepam increased the probability of delirium, but varying dexmedetomidine concentrations did not alter risk of delirium. Future studies are needed to determine if dexmedetomidine’s effect on delirium is related primarily to facilitating avoidance of deliriogenic drugs, such as benzodiazepines, or to a direct treatment affect.

John Devlin, Northeastern Univ, Yoanna Skrobik, Hospital Maisonneuve Rosemont, Eric Hinderleider, Northeastern Univ, Russ Roberts, Tufts Medical Center, Jeffrey Fong, Mass College of Pharm, Richard Riker, Maine Medical Center, Robin Ruthazer, Nicholas Hill, Erik Garpestad, Tufts Medical Center Introduction: Resolution of individual delirium symptoms in ICU patients with delirium administered antipsychotic therapy is unclear. We calculated both resolution over time and time spent with each of the 9 delirium symptoms measured by the Intensive Care Delirium Screening Checklist (ICDSC) for patients enrolled in a double-blind, randomized, placebo (P)-controlled study evaluating quetiapine (Q) for ICU delirium (Crit Care Med 2010;38;419-27). Hypothesis: Individual delirium symptoms respond to Q differently. Methods: ICDSC symptom data was available for 29/36 patients randomized [Q (n⫽15);P (n⫽14)]. Time to resolution of each ICDSC symptom (from randomization to study drug discontinuation) was compared between the Q and P groups (if symptom present at baseline) using a Kaplan-Meier analysis. For this post-hoc analysis, p⬍0.10 was considered significant and data was presented as a median (interquartile range). Results: At baseline, neither the ICDSC score [5(4-6) (Q) vs 5(4-6)] nor % with each ICDSC symptom: inattention [93(Q) vs 100], disorientation (93 vs 85), symptom fluctuation (92 vs 87), inappropriate mood (77 vs 43), sleep-wake disturbance (68 vs 71), hypoactivity (64 vs 60), altered level of consciousness (43 vs 40), agitation (36 vs 40) or hallucinations (25 vs 25) differed (all p⬎0.10). Use of Q led to a shorter time (hrs) to resolution of symptom fluctuation [4(Q) vs 14, p⫽0.004], inattention (3 vs 8, p⫽0.10) and disorientation (2 vs 10, p⫽0.10) and a longer time to resolution of agitation (5 vs 1, p⫽0.04). Q-treated patients spent less % time in study with inattention [47(0-67) vs 78(43-100), p⫽0.025], hallucinations [0(017) vs 28(0-43), p⫽0.10) and symptom fluctuation [47(19-67) vs 89 (33-100), p⫽0.04]. Conclusions: Q resolves many of the common ICU delirium symptoms faster than placebo and results in less time spent with hallucinations, inattention and symptom fluctuation. However, psychomotor agitation, which may be a marker for lower mortality among delirious patients but is predictive of worse outcome among patients not delirious, does not resolve more quickly with Q. Future studies evaluating antipsychotics in ICU patients with delirium should measure the resolution of individual delirium symptoms.

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EVALUATION OF PROPOFOL VERSUS DEXMEDETOMIDINE IN PATIENTS WHO HAVE UNDERGONE A ROBOTIC ASSISTED CARDIOTHORACIC PROCEDURE

HEMODYNAMIC AND METABOLIC RESPONSES TO KETAMINE AND ETOMIDATE SEDATIONS DURING ENDOTRACHEAL INTUBATION IN CRITICALLY ILL PATIENTS

Heather Torbic, Brigham and Women’s Hospital, Stella Papadopoulos, Boston Medical Center

Ozlem Cinar, Arash Pirat, Pinar Zeyneloglu, Nilufer Bayraktar, Gulnaz Arslan, Baskent University, Faculty of Medicine

Introduction: Robotic assisted coronary artery bypass grafts (CABG) allow patients the opportunity to undergo a less invasive procedure, creating the opportunity for decreased hospital length of stay (LOS) and complication rates. Due to their pharmacokinetic profiles, dexmedetomidine (DEX) and propofol would be ideal sedatives following robotic CABG. There are few studies comparing these agents in this population. Hypothesis: There is no difference in outcomes when DEX or propofol is used for sedation after a robotic CABG. Methods: This retrospective cohort evaluated patients who underwent a robotic CABG between March 2008 and April 2010 and were post-operatively sedated with DEX or propofol. The primary outcome was duration of mechanical ventilation (MV). Secondary outcomes included intensive care unit (ICU) LOS, hospital LOS, amount of adjunctive sedatives and analgesics used and incidence of adverse effects. Results: A total of 126 patients met inclusion criteria: 73 patients received propofol and 53 patients received DEX. The groups were similar, except propofol patients were older and had a higher incidence of diabetes and heart failure. The mean duration of mechanical ventilation was significantly lower in the DEX group (7.44⫾0.54 vs 18.24⫾1.16 hours, p⫽0.009). DEX patients had a decreased mean ICU (1.66⫾1.42 vs 4.22⫾7.64 days, p⫽0.018) and hospital (6.62⫾4.34 vs 10.96⫾8.30 days, p⫽0.0007) LOS. There was no difference in the amount of adjunct sedatives and analgesics used. Hypotension (11.6 vs 0%, p⫽0.02) and tachycardia (8.6 vs 0%, p⫽0.04) occurred more frequently in patients who received propofol compared to DEX. Conclusions: Patients who underwent a robotic CABG and received DEX had a shorter duration of MV compared to patients who received propofol. DEX also decreased ICU and hospital LOS compared to propofol. There was no difference in the amount of adjunct sedatives and analgesics used and DEX appears to be associated with fewer adverse events. Based on this study, DEX produces more favorable outcomes than propofol in patients who have undergone a robotic CABG. Further studies are needed to determine if DEX is superior to other agents in this setting.

Introduction: It has shown that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in intensive care unit (ICU) patients. However, the effects of these drugs on immediate metabolic response to endotracheal intubation in ICU patients is unknown. Hypothesis: The aim of this study was to compare the effects of etomidate and ketamine on hemodynamic and metabolic responses to intubation in ICU patients. Methods: After Clinical Research and Ethics Committee approval, 22 ICU patients who required intubation during their ICU stay were enrolled in this prospective, randomized, double-blinded study. Patients in group E (n⫽12) received etomidate 0.3 mg/kg IV and those randomized to group K (n⫽10) received ketamine 2 mg/kg IV for sedation during endotracheal intubation. We evaluated intubation conditions and hemodynamic response to intubation by using laryngoscopy grading scale and recording arterial blood pressure and heart rates for 60 minutes after the intubation, respectively. Total serum cortisol and 11␤-deoxycortisol concentrations were measured immediately before and 5 minutes after intubation in order to measure metabolic response to intubation. Patients’ APACHE II and SOFA scores, duration of mechanical ventilation and length of ICU stay were also recorded. Results: The demographic features, reasons for intubation and causes of ICU admission were similar between the groups (p⬎0.05). Mean heart rate and arterial blood pressure values were not significantly different between the two groups at the baseline and after intubation (p⬎0.05). Groups’ mean serum cortisol and 11␤-deoxycortisol concentrations were similar before and 5 minutes after intubation (p⬎0.05). The groups were not significantly different with regards to intubation conditions, length of ICU stay, duration of mechanical ventilation, and mortality (p⬎0.05). Mean SOFA scores during the first 9 days after intubation were also similar in both groups (p⬎0.05). Conclusions: In conclusion, our results demonstrated that when used for sedation during endotracheal intubation of ICU patients, ketamine and etomidate are comparable in terms of hemodynamic and metabolic responses, intubation condition, and mean SOFA scores.


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A PRE-SEDATION FLUID BOLUS DOES NOT DECREASE THE INCIDENCE OF PROPOFOL-INDUCED HYPOTENSION IN PEDIATRIC PATIENTS

EVALUATION OF THE INCIDENCE OF HYPERTRIGLYCERIDEMIA DURING CONCOMITANT USE OF PROPOFOL AND SIROLIMUS AT A TERTIARY ACADEMIC MEDICAL CENTER

Matthew Jager, Jean Aldag, Girish Deshpande, University of Illinois College of Medicine at Peoria

Kevin Anger, Megan Chesnick, Brigham and Women’s Hospital, Po-Shun Lee, Brigham & Women’s Hospital, Paul Szumita, Brigham and Women’s Hospital

Introduction: The purpose of our study was to determine the effect of a preinduction isotonic fluid bolus on the incidence of propofol-induced hypotension in pediatric patients undergoing procedural sedation, assess for clinical signs of hypoperfusion during the induced hypotension, and evaluate age-related propofol dosing differences. Hypothesis: A 20 ml/kg isotonic fluid bolus prior to induction will decrease the incidence of propofol-induced hypotension. Methods: This prospective, randomized, controlled study was performed at Children’s Hospital of Illinois and was approved by the Institutional Review Board. We enrolled 126 subjects after parental consent, with ages ranging from 6 to 60 months undergoing sedation for magnetic resonance imaging or auditory brain stem-evoked response. The treatment group (n⫽52) was randomly assigned to receive a 20 ml/kg isotonic saline bolus prior to induction with propofol. Patients were monitored per guidelines via continuous cardio-respiratory monitor including pulse oximetry and end-tidal carbon dioxide levels. Blood pressure (BP) was measured at baseline and every 5 minutes after induction until recovery. Systolic and diastolic BP, clinical signs of hypoperfusion, and propofol dosing were compared between groups. The Pediatric Advance Life Support definition was used for hypotension. SPSS 17.0 was used for statistical analysis. Results: There were no demographic differences between groups. Hypotension occurred in 26 subjects, 23.1% (12/52) in the treatment group and 18.9% (14/74) in the control group (p⫽0.66). There was no significant difference between groups in lowest systolic BP (treatment: 81.4 ⫾ 9.8 mm Hg, control: 81.4 ⫾ 8.4 mm Hg; p⫽0.98) or lowest diastolic BP (treatment: 36.6 ⫾ 7.9 mm Hg, control: 38.1 ⫾ 8.3 mm Hg; p⫽0.30). No subject had clinical signs of hypoperfusion. Subjects aged 12 months or younger required significantly (p⬍0.01) more propofol (11.29 ⫾ 5.6mg/kg) than older subjects (6.8 ⫾ 3.4mg/kg). Conclusions: A pre-sedation 20 ml/kg fluid bolus does not decrease the incidence of propofolinduced hypotension. Clinical hypoperfusion did not occur using propofol. Infants ⱕ12 months of age required significantly more propofol for sedation.

Introduction: Sirolimus and propofol are both independently associated with the development of hypertriglyceridemia during therapy. To date, there are no published reports describing synergistic or additive drug interaction resulting in hypertriglyceridemia with concomitant use of these medications. Hypothesis: The risk of hypertriglyceridemia is exaggerated in patients receiving concomitant sirolimus and propofol therapy. Methods: Adult patients receiving sirolimus and a continuous propofol infusion for at least 12 hours from January 2005 to August 2009 were retrospectively evaluated. Data included APACHE II score, weight, length of propofol therapy, and baseline TG concentrations. Outcomes evaluated included hypertriglyceridemia (TG ⬎500 mg/dL), change in triglyceride concentration from therapy initiation, and manifestations of propofol-related infusion syndrome (PRIS). Results: Sixteen patients were included with the following mean values: APACHE II score 20.2⫾5.3, weight 76.3⫾21.2 kg, and baseline TG concentrations 181.3⫾89.7 mg/dL. Indications for sirolimus therapy included hematopoietic stem cell transplant (n⫽15) and heart transplant (n⫽1). Mean length of propofol infusion was 99.8⫾88.5 hours. The mean TG concentration was 515.6⫾468.1 mg/dL, with 8 patients (50%) developing hypertriglyceridemia during therapy. Fourteen (87.5%) patients had an increase of at least 100 mg/dL, 12 (75%) patients had an increase of at least 200 mg/dL, and 6 (37.5%) patients had an increase of at least 300 mg/dL in TG concentrations during therapy. One patient had more than two new onset PRIS manifestations during propofol therapy. Conclusions: Co-administration of propofol and sirolimus resulted in an exceedingly high incidence of hypertriglyceridemia, warranting close monitoring of TG concentrations. Further analysis is needed to examine the mechanism and clinical impact of this interaction.

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DECREASED SEDATION REQUIRED IN PICU PATIENTS VENTILATED IN NEURALLY ADJUSTED VENTILATORY ASSIST(NAVA)

AN EVALUATION OF CONTINUOUS INFUSION REMIFENTANIL IN CRITICALLY ILL PATIENTS

Cynthia White, Brandy Seger, Carrie Morgan, Riad Lutfi, Lesley Doughty, Cincinnati Children’s Hospital Medical Center Introduction: To maintain safety and patient comfort, large amounts of sedation are often necessary in ventilated PICU patients. NAVA is an FDA-approved mode of spontaneous mechanical ventilation. Breath assist is triggered by detection of electrical impulses from the phrenic nerve to the diaphragm and support continues until this impulse ends. Sensors in an NG tube detect impulse and communicate it to the ventilator in contrast to conventional support which is triggered by flow or pressure changes in the circuit. Less time between trigger and response and coupling of ventilatory support with phrenic nerve stimulation of the diaphragm has been shown to improve patient-ventilator breath-cycle synchrony. Hypothesis: Patients ventilated in NAVA will require less sedation to maintain safety and comfort. Methods: Retrospective chart review was performed for 19 PICU patients ventilated in NAVA from 10/09 to 7/10. Age range: 3 wks to 15 y/o. We developed a sedation score to represent the diverse combinations and doses of continuous sedative infusions. We also compared the number of prn doses of sedation each patient received in the 24 hr period Pre and the first 24 hours Post NAVA initiation. Results: Two patients did not to tolerate NAVA. Their sedation decreased respiratory drive or they required repeated doses of neuromuscular blockade (NMB). In the other 17 patients, our continuous sedation score varied greatly between patients (range 1-29 Pre vs 2-30 Post NAVA), however the Pre and Post NAVA score for each patient did not change (p⫽ .85, paired t test). Fewer prn sedative doses were required Post NAVA (17⫹/⫺9) vs Pre NAVA, (p⫽.01, paired t test). Pre NAVA, 12 of 17 patients required 1 to 12 doses of NMB whereas only 2 of 17 patients required a dose of NMB necessitating a brief interruption in NAVA (p⫽.001, Fisher’s Exact). Conclusions: Many of our patients required high doses of continuous sedation and numerous prn doses when in an SIMV mode. In the NAVA mode, without changes in their continuous sedation dosing, fewer prn doses were required for comfort/safety. Further research is needed to assess the impact of NAVA on the morbidity of high dose sedation typically needed in ventilated PICU patients.

Crystal Christensen, Anthony Gerlach, Claire Murphy, The Ohio State University Medical Center Introduction: Remifentanil is a short-acting opioid with both analgesic and sedative effects. Beneficial properties of remifentanil include rapid onset/offset, lack of accumulation, and widespread extravascular metabolism. Additional clinical benefits include shorter extubation times, comparable efficacy to other agents, and faster and more predictable awakening time for neurological assessment. In May 2009, continuous intravenous (CIV) remifentanil was implemented at The Ohio State University Medical Center as a sedation option for patients requiring frequent neurological assessment in the intensive care unit (ICU). This retrospective review aims to evaluate the efficacy of remifentanil CIV for sedation of critically ill patients. Hypothesis: Initiation of CIV remifentanil will reduce the dosing requirements of other opioids and sedatives used for ongoing sedation. Methods: Patients admitted to the medical or surgical ICU between ages 18-89 who received CIV remifentanil between May 1, 2009 and January 31, 2010 were included in this retrospective cohort analysis. Patients were excluded if they were incarcerated or pregnant. Dosing requirements for sedatives and opioids were compared before and after initiation to evaluate efficacy of CIV remifentanil. All comparisons were made using the paired student’s t-test. Results: Fourteen patients met criteria for inclusion including 7 trauma patients, 3 neurosurgery patients, and 4 patients on other services. The mean starting dose for remifentanil was 0.09 ⫹ 0.05 mcg/kg/min with a mean maximum dose of 0.18 ⫹ 0.08 mcg/kg/min and mean duration of 7.6 ⫹ 5.6 days. Total oral morphine equivalents decreased during the 24 hours after initiation of remifentanil (228.9⫹426.8 vs. 13.5⫹23.02 mg, p⫽0.084). In the 9 patients on propofol CIV, the addition of remifentanil significantly reduced the mean propofol rates (25.3 ⫹ 17.7 vs. 10.2 ⫹ 14.1mcg/kg/min, p⫽0.02) and in 4 patients propofol was discontinued. Conclusions: Remifentanil is an efficacious option for sedation and analgesia in critically ill patients with significant reductions in opioid and propofol requirements after initiation. In addition, remifentanil monotherapy for sedation and analgesia may be an option in some patients.


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SAFETY AND TOLERABILITY OF FOSPROPOFOL FOR PATIENTS REQUIRING INTUBATION AND MECHANICAL VENTILATION IN THE ICU: RANDOMIZED, OPEN-LABEL STUDY VS PROPOFOL

CHANGE IN AGITATION PHARMACOTHERAPY AFTER ALPRAZOLAM REINITIATION IN CRITICALLY ILL PATIENTS: THE AMAZE STUDY

Keith Candiotti, University of Miami, Tong Gan, Christopher Young, Duke University Medical Center, Alex Bekker, New York University School of Medicine, S.T. Sum-Ping, University of Texas Southwestern Medical Center and VA North Texas Health Care System, Richard Kahn, Central Maine Pulmonary Associates, Philip Lebowitz, Albert Einstein College of Medicine and Montefiore Medical Center, Jeffrey Littman, Cooper University Hospital Introduction: Patients who are intubated and ventilated in ICU settings often experience agitation and demonstrate excessive stress responses. Hypothesis: We hypothesized that fospropofol, a prodrug of propofol, can be administered safely with minimal adverse eventswhenusedtoinducesedationinthesepatients.Methods:Thesafetyandtolerability of intravenous (IV) infusions of fospropofol compared with IV propofol were evaluated in this randomized, open-label study in adult patients requiring short-term sedation in an ICU. Patients with ASA status P1 to P4 who were expected to require 2 to 12 hours of mechanical ventilation while under sedation in an ICU were randomized to 1 of 3 treatments designed to maintain a Ramsay Sedation Score (RSS) of 2 to 5: (1) continuous IV fospropofol infusion (25 ␮g/kg 䡠 min-1) with a bolus and increased infusion rate for agitation events (infusion/bolus group); (2) IV fospropofol infusion (25␮g/kg䡠 min-1) with an increased infusion rate for agitation events (infusion-only group); and (3) IV propofol infusion (25 ␮g/kg 䡠 min-1) with an increased infusion rate for agitation events (propofol group). Results: Of the 60 enrollees, 18, 20, and 22 were randomized to each treatment group, respectively. Mean infusion rates were 52.0 to 76.2 ␮g/kg 䡠 min-1 for the fospropofol infusion/bolus group, 42.1 to 54.6 ␮g/kg 䡠 min-1 for the fospropofol infusiononly group, and 18.9 to 31.6 ␮g/kg 䡠 min-1 for the propofol group. The most frequently occurring adverse events in the 2 fospropofol groups combined compared with the propofol group, respectively, were procedural pain (21.1% vs 9.1%), hyperglycemia (5.3% vs 13.6%), and nausea (13.2% vs 4.5%), and the largest mean decreases in systolic blood pressure were -13.1 and -14.2 mm Hg, respectively. Two patients (1 each in the fospropofol infusion/bolus group and the propofol group) experienced hypotension during the study. Mean plasma formate levels were not significantly different between groups. On average, RSS scores for each test group were within 2 to 5 for ⬎90% of the time the patients were sedated. Conclusions: Fospropofol is tolerable when used for short-term induction and maintenance of sedation in mechanically ventilated ICU patients.


Chris Droege, Neil Ernst, Eric Mueller, The University Hospital; University of Cincinnati Introduction: Severe withdrawal symptoms are well documented after abrupt benzodiazepine discontinuation. Alprazolam (ALP) may uniquely interact with the GABAA receptor complex precluding pharmacologic substitution and complicating management of agitation in critically ill patients. Hypothesis: ALP reinitiation is associated with a significant decrease in agitation pharmacotherapy requirements in mechanically ventilated patients with apparent preadmission ALP use. Methods: This retrospective study included adult critically ill patients receiving ALP ⬎24 hours while mechanically ventilated at an academic medical center between 5/05-7/09. Preadmission ALP use was categorized as confirmed, likely, or unknown on med reconciliation/progress note review. Primary outcome was intrapatient change in analgesia, sedation, and delirium pharmacotherapy requirements 48 hours before vs. 48 hours after ALP reinitiation. Patients were further subgrouped by % change in pharmacotherapy quartiles to better describe responders (⬎50th percentile). Results: 34 patients were included. Mean ALP daily dose was 1.5⫾1.2mg started 7.4⫾4.7 days from admission. Preadmission ALP use was confirmed 17 (50%), likely 8 (24%), and unknown 9 (26%) patients, respectively. Median % change in pharmacotherapy post-ALP was -24%. 17 (50%) patients had ⬎25% decrease and 13 (38%) ⬎50% decrease. Median (range) % change was -62% (-33 to -100%) in responders vs. 25% (1300 to -24%) in non-responders. In responders, daily pharmacotherapy requirements pre and post-ALP were fentanyl 2367mcg vs. 1304mcg (p⫽0.001); propofol 1824 mcg vs. 305 mcg (p⫽0.003); and lorazepam 56.1mg vs. 10.4mg (p⬍0.001). There was a trend towards reduced delirium (CAM-ICU) post-ALP initiation in responders (62.5% vs. 28.6%, p ⫽ 0.081). There were no pre vs. post-ALP differences in daily acute physiology score, max RASS scores, ICU length of stay, or vent duration among responders. Conclusions: ALP reinitiation significantly, and perhaps disproportionately, decreased agitation pharmacotherapy in ⬎50% of mechanically ventilated patients with possible preadmission use. ALP discontinuation-related agitation should be assessed in patients with preadmisson use.


890

TIMELY ADMINISTRATION OF SEDATION AFTER INTUBATION WITH ETOMIDATE IN THE EMERGENCY DEPARTMENT

UTILIZATION OF A STEPWISE THERAPEUTIC STRATEGY TO OPTIMIZE SEDATION MANAGEMENT IN THE ICU

Daniel Frank, Breena Taira, Anna Domingo, Henry Thode, Adam Singer, Stony Brook University Medical Center Introduction: Etomidate is often used for intubation in the Emergency Department (ED). With a duration of 4-14 minutes, a second sedative should be given within 14 minutes to ensure continuous sedation, especially in chemically paralyzed patients. Hypothesis: We hypothesized that less than half of ED patients intubated with etomidate receive timely administration of a second dose of sedative. Methods: CPT codes were used to identify all patients intubated in the ED of an academic medical center from 5/09 to 5/10. Chart review was performed of those who received etomidate for sedation prior to intubation. Patients were excluded if they were ⬍18 yrs or received a different sedative. Demographics, illness characteristics, vital signs, paralytic agents, sedatives, and times of drug administration were abstracted. Descriptive statistics were used to characterize rates. ␹2 and student’s t tests were used to compare patients who did and did not receive timely administration of a second sedative. Results: 117 patients met inclusion criteria. 42 % were female, 78% were White, and mean age was 60 years (SD⫽21). The most common chief complaints were dyspnea (27/117, 23%), stroke/ICH (24/117, 20.5%), and blunt trauma (23/117, 19.7%). 69/117 (59%) had decreased mental status prior to intubation. 104/117 (89%, 95% CI 0.820.93) received a second dose of sedative, however only 38/104 (36.5%, 95% CI 0.28-0.47) received it within 14 minutes. Midazolam (38%), lorazepam (30%), and propofol (21%) were most common. 107/117 (91.5%) received a paralytic agent for intubation; succinylcholine was used in 100/107 (93.5%). 59/107 (55%) received a paralytic after intubation, of which 56/59 (95%) got rocuronium. Gender, age, race, chief complaint, level of consciousness, blood pressure, and heart rate were examined for association with timely administration of a second dose of sedative and none were significant. Conclusions: Less than half of patients intubated with etomidate in our ED received timely administration of a second sedative. Additionally, a second dose of paralytic was frequently administered, suggesting that patients are at risk of paralysis and mechanical ventilation without sedation.

Natalie O’Gorman, Erie County Medical Center, Kimberly Zammit, Lisa Voigt, Patricia Holtz, Buffalo General Hospital Introduction: Optimal management of sedation of mechanically ventilated patients in the ICU is associated with fewer mechanical ventilation days, shorter ICU length of stay, reduction in healthcare costs, and lower incidence of delirium. Hypothesis: The purpose of this study was to revise our sedation protocol and evaluate the impact of these interventions on patient outcomes and amount of sedatives and analgesics administered. Methods: The revised sedation protocol includes a stepwise approach to manage the sedation of mechanically ventilated patients in the critical care setting. The first step involves setting a goal for sedation using the Richmond Agitation Sedation Scale (RASS) and bolus dosing of analgesic and sedative medications with standing ‘as needed’ orders for further bolus doses. Step two provides a continuous infusion of fentanyl and scheduled doses of a benzodiazepine. Step three includes the addition of a continuous infusion of a benzodiazepine or propofol. The impact of the protocol revision was assessed by comparing baseline data with data following the intervention, including mechanical ventilation days, amount of drug used, and ICU and hospital length of stay. This study was exempt from review by the Institutional Review Board. Results: Twenty-five patients were included in each group. A statistically significant reduction in benzodiazepine administered was observed by days 3, 5, and 7 of mechanical ventilation. The cumulative dose of benzodiazepine was reduced from 527.2 ⫹ 553.3 mg midazolam equivalents at baseline to 109.9 ⫹ 370.3 mg post-implementation (p⫽0.003). The mean daily dose of midazolam equivalents was reduced from 76.6 mg at baseline to 16.1 mg post-implementation. The cumulative amount of opiate administered was similar between the two groups. There was no significant difference in mechanical ventilation days or length of stay. Conclusions: The revised sedation protocol resulted in a statistically significant reduction in mechanically ventilated patients’ exposure to benzodiazepines. Whether this “bolus first strategy” reduces duration of mechanical ventilation, ICU and hospital length of stay, or ICU mortality needs to be evaluated in a larger group of patients.

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892

ASSESSMENT OF CARDIAC OUTPUT AND STROKE VOLUME DURING DEXMEDETOMIDINE SEDATION IN CHILDREN

IMPACT OF A NATIONAL PROPOFOL SHORTAGE ON DURATION OF MECHANICAL VENTILATION AT AN ACADEMIC MEDICAL CENTER

Jackson Wong, Garry Steil, Michelle Curtis, Alexandra Papas, Julie Caplow, Keria Mason, Children’s Hospital Boston Introduction: Dexmedetomidine (DEX) can elicit fluctuations in heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), stroke index (SI) and systemic vascular resistance index (SVRi) in adults. The hemodynamic effects of DEX in children are unknown. Hypothesis: Sedation with DEX produces hemodynamic changes in children are similar to those observed in adults. Methods: Hemodynamic variables were measured continuously by non-invasive cardiac output monitor (ICON, Cardiotronic Inc. La Jolla CA) in a double-blinded study in children sedated with DEX during radiological procedures. All subjects received either: a single dose (DEX-single: 2 mcg/kg over 10 minute) or multiple/ extended doses of DEX (DEX-extended) to complete the procedure. We compared the changes in hemodynamic variables using two-way repeated measures ANOVA with changes from baseline assessed with post hoc analysis. Results: Data is reported as mean ⫾ SEM. In both DEX-single (N⫽8) and DEX-extended (N⫽9) there was an initial decreased in CI (3.8 ⫾ 0.3 to 3.2 ⫾ 0.2; 4.0 ⫾ 0.1 to 3.0 ⫾ 0.2 Liters/m2; respectively, p⬍0.05). In the DEX-single, only HR was decreased at recovery (109 ⫾ 7 to 99 ⫾ 7 beats/min; p⬍0.05). In contrast, in the DEX-extended, all hemodynamic variable were decreased at recovery; HR (118 ⫾ 5 to 94 ⫾ 4 beats/min.; p⬍0.001; CI (4.0 ⫾ 0.1 to 2.5 ⫾ 0.3 Liter/m2; p⬍0.001) and SI (34.6 ⫾ 1.3 to 26.6 ⫾ 2.9 ml/m2; p⬍0.01). MAP tended to decrease while SVRi was significantly increased (1300 ⫾ 35 to 2262 ⫾ 350 dynes/sec/cm5; p⬍0.01). Only 2 of 8 subjects in DEX-single and 4 of 9 subjects in the DEX-extended required additional fluid administration for hypotension (p⫽NS; chi –square test). Conclusions: In this population, DEX produced up to a 38% and 23% change in cardiac and stroke index respectively. Despite these observed hemodynamic changes, no children required pharmacologic resuscitation or therapy nor was there an adverse outcome.

Russ Roberts, Tufts Medical Center, Amy Chi, Tufts Medical Center Pulmonary, Aarti Grover, Tufts Medical Center, Matthew Newman, Northeastern Univ, Shubha Bhat, Notheastern Univ, Stacey Benotti, Erik Garpestad, Stanley Nasraway, Tufts Medical Center, John Devlin, Northeastern Univ Introduction: Propofol is the most used ICU sedative in the U.S. and and is associated with a reduced duration of mechanical ventilation (MV) vs. benzodiazepines. A manufacturer shortage of propofol has lead to a decrease in propofol use at our 360-bed academic institution. Hypothesis: A shortage of propofol in 3 adult, noncardiac surgery, ICUs (n⫽30 beds) will increase the duration of MV. Methods: Data was retrospectively collected for consecutive pts admitted to these 3 ICUs who received MV ⱖ48hrs, were administered a sedative continuous infusion(CI) ⱖ24hrs and were successfully extubated, and then compared between two periods: 1) Before propofol shortage (BPS) (12/1/08 to 5/31/09) 2) After propofol shortage (APS) (12/1/09 to 5/31/10). Results: Compared to the BPS group (n⫽153), the median(IQR) duration of MV was longer in the APS group (n⫽ 128) [6.7(9.8) vs. 9.6(9.5) d, p⫽0.02]. Fewer APS group pts received ⱖ24hrs of CI propofol (94 vs. 15%, p⬍0.0001) and more received ⱖ24hrs of CI lorazepam (7 vs. 15%, p⫽0.037), midazolam (30 vs. 81%, p⬍0.001), dexmedetomidine (9 vs. 30%, p⬍0.0001) and a CI neuromuscular blocker (5 vs. 12%, p⫽0.03). APS-group pts received fewer total midazolam equivalents [1118(524) vs. 450 (813) mg, p⬍0.001], a shorter total duration of all sedation CI administered [6(5) vs. 5(3) d, p⫽0.026)] and a lower average midazolam equivalent infusion rate [(8(3) vs. 4(2) mg/hr, p⬍0.0001]. The APS group included fewer medical pts (78 vs. 64%, p⫽0.01), more neurosurgical pts (5 vs. 15%, p⫽0.006) and was younger [64(13) vs. 56(11), p⫽0.01). Neither admission APACHE-2 [18(4) vs. 19(5), p⫽0.38], % male (65 vs. 63, p⫽0.72), use of pressure controlled (21 vs. 18%, p⫽0.60) or high frequency oscillating (3 vs. 2%, p⫽0.69) MV ⱖ24hrs, worse PaO2/FiO2 ratio (1st 24hrs) [271(86) vs. 240(87), p⫽0.76), admit creatinine [1.1(0.6) vs. 1.1(5), p⫽0.33) or % with acute alcohol withdrawal (5 vs. 9, p⫽0.11) were different between the BPS and APS groups. Conclusions: Despite implementation of a spontaneous awakening/breathing protocol in all 3 ICUs in 2/2010, a shortage of propofol was associated with an increased duration of MV that does not appear to be related to other factors that can influence the duration of MV.


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894

COMPARISON OF SEDATIVES, ANALGESICS AND NEUROMUSCULAR BLOCKER REQUIREMENTS DURING PRESSURE CONTROL AND AIRWAY PRESSURE RELEASE VENTILATION

CLINICAL EVALUATION OF PROPOFOL VERSES DEXMEDETOMIDINE FOR SEDATION MANAGEMENT IN CRITICALLY ILL MECHANICALLY VENTILATED PATIENTS

Michael Cawley, Quinn Czosnowski, Lindsay Palkovic, Philadelphia College of Pharmacy Introduction: Critically ill patients requiring pressure control ventilation (PCV) or airway pressure release ventilation (APRV) are managed with a variety of pharmacological strategies including sedatives, opioid analgesics and neuromuscular blocking agents (NMBAs). Limited data suggests that patients on PCV require more sedatives, NMBAs, and opioid analgesics than patients on APRV. Hypothesis: Patients on PCV will require higher cumulative doses of intravenous sedative, opioid analgesics and NMBAs than patients on APRV. Methods: This retrospective, randomized, case-control pilot study was IRB approved and conducted in a suburban teaching hospital. Consecutive patients in the trauma, medical, surgical and burn intensive care units switched to PCV or APRV from assist control (A/C) ventilation were included. Total midazolam equivalents, fentanyl equivalents, and vecuronium equivalents were collected for all patients for 72 hours on A/C ventilation and 72 hours after switching to PCV or APRV. Demographic and baseline data were compared using Fischer’s exact test, and continuous data were compared using student’s t-test and Mann Whitney U test as appropriate. A p value ⬍ 0.05 was considered significant. Results: 32 patients were included in the study (23 APRV, 9 PCV). Age, gender, baseline APACHE II, and Lung Injury Scores were similar between groups. Total sedative (3.1 vs 5.6 mg/kg, p ⫽0.018) and analgesic (40 vs 75 mcg/kg, p⫽0.016) requirements increased in patients switched from A/C to APRV. Total analgesic (32 vs 54 mcg/kg, p⫽0.034) requirements increased in patients switched from A/C to PCV. Patients on PCV required more neuromuscular blockade (5 vs 0.01 mcg/ kg, P ⬍0.001) than APRV patients, but patients on APRV required more sedation (5.6 vs 2.8 mg/kg, p⫽0.053) than patients on PCV. Median MAAS (2 vs 1, p ⫽ 0.05) and GCS (6 vs. 3, p⫽0.035) were higher on APRV than on PCV. Conclusions: Patients receiving PCV require more neuromuscular blockade to enable adequate ventilation than patients receiving APRV. Larger studies are necessary to investigate the impact of ventilation mode on sedative and analgesic requirements.

Angela Harding, Sarah Day, Riverside Methodist Hospital of OHioHealth, Drew Bockenfeld, Alex Heine, David Prospal, Riverside Methodist Hospital Introduction: Literature comparing dexmedetomidine (D) to benzodiazepine (BZ) therapy suggest improved outcomes with D. In the MENDS trial, delirium/ coma free days was lower in pts who received D v lorazepam (p⬍0.05). The SEDCOM trial (D v midazolam) found delirium to be lower (54% v 76% p ⬍0.05), and mechanical ventilation (MV) 1.9 days less (p⫽0.01). Researchers suggest D (␣2 agonist/GABA receptor sparing) may exhibit favorable outcomes over other GABA agonists. Literature comparing propofol (P), a short acting GABA agonist, to D is limited. This data would be valuable as the pharmacokinetic (PK) profile of D and P are similar, and previous trials comparing D to BZ had lengthy exclusion criteria making the results difficult to extrapolate. Hypothesis: There is no difference in delirium free days between P an D based regimens. Delirium incidence, coma free days, hospital/ICU LOS, MV days and mortality were also evaluated. Methods: ICU pts from 1/1-1/28/10 (P group) was retrospectively compared to pts 2/1-2/28/10 (D group). Study dates were selected based on depleted P supply. Extensive nursing sedation education was done prior to study. Pts on MV and in the ICU⬎24 hrs were included; pts were excluded if ICU stays overlapped study dates. Results: 88 pts were included (n⫽49 P, n⫽39 D). Pts were comparable in APII score (25.5 v 25.9, p⫽0.8), and gender (37% v 44% M, p⫽0.6). Pts were younger in the P group (59 v 66, p⫽0.03). No difference in delirium free days (67% P v 55% D group, p⫽0.41), or coma free days (77% v 55%, p⫽0.052) existed. The incidence of delirium was 63% v 77% in favor of P group (p⫽0.049). Hosp LOS was 13.4d v 11.6d (p⫽0.45), ICU LOS was 5.3d v 7.7d (p⫽0.008), and MV days were 4.2d v 6.5d (p⫽0.03) for P and D group respectively. There was no difference in mortality (24.4% v 33.3%, p⫽0.49). 64% of pts in the P group received P; 33% of pts in the D group received D (p⬍0.05). Antipsychotic use was comparable between groups (29% v 38%, p⫽0.23). Conclusions: No difference exists between P and D in delirium or coma free days. ICU LOS, MV days and delirium incidence, however, was lower in the P group. Further research exploring short acting GABA therapy compared to ␣2 agonist therapy is warranted.

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896

EVALUATION OF SEDATIVE AND NEUROMUSCULAR BLOCKER PRACTICES DURING INDUCED HYPOTHERMIA FOLLOWING CARDIAC ARREST AT A TERTIARY ACADEMIC MEDICAL CENTER

CURRENT CRITICAL CARE PHARMACISTS’ PERCEPTIONS AND PRACTICES SURROUNDING THE RECOGNITION OF DELIRIUM IN THE ICU

Allison Forni, Megan Chesnick, Paul Szumita, Kevin Anger, Kathleen Avery, Benjamin Scirica, Brigham and Women’s Hospital

John Devlin, Northeastern Univ, Shubha Bhat, Notheastern Univ, Christopher Burke, U of Knoxville Medical Center, Russ Roberts, Tufts Medical Center, Yoanna Skrobik, Hospital Maisonneuve Rosemont

Introduction: Medication administration is common for the maintenance of a comatose state and to control shivering associated with induced hypothermia (IH). Optimal pharmacotherapeutic strategies have not been well described and vary significantly among institutions. Hypothesis: Describe sedative, analgesic, and neuromuscular blocking (NMB) practices in critically ill patients undergoing IH. Methods: Adult patients who were cooled for at least 6 hours following cardiac arrest from January 2007 to January 2010 were retrospectively evaluated. Data included APACHE II score, medication selection and dose as well as Bispectral index (BIS) monitoring during cooling and rewarming. Outcomes evaluated include shivering and inpatient mortality. Results: Thirty-seven patients were included with a mean age of 59.3⫾17 years, APACHE II score of 22.2⫾4.8 and GCS of 3.5⫾1.2. Thirty-two patients (86.5%) received fentanyl at a mean dose of 70.2⫾39.9 mcg/hr during cooling and 72.3⫾39.7 mcg/hr during rewarming. Fifteen patients (40.5%) received midazolam-based sedation and 22 patients (59.5%) received sedation with propofol only. The mean doses of midazolam and propofol were 4.8⫾3 mg/hr and 2.6⫾1.1 mg/kg/hr during cooling and 5.1⫾3.9 mg/hr and 2.7⫾0.8 mg/kg/hr during rewarming, respectively. Additionally, 97.3% of patients received cisatracurium for a mean duration of 25.7⫾7.6 hours, at a mean infusion rate of 0.6⫾0.2 mcg/kg/min. In hospital mortality was 62.2% and was significantly lower in patients who received sedation with propofol only as compared with midazolam-based sedation (45.5% vs 86.9%; p⬍0.05). Twenty-five of 37 patients received BIS monitoring with a mean of 31 assessments per patient and mean of 44.5⫾17.8 vs 56.1⫾15.2; p⬍0.05 during cooling and rewarming, respectively. Eight patients (21.6%) had at least one reported event of shivering. Conclusions: While the majority of patients received fentanyl for pain and cisatracurium for shivering, sedative medication strategies were split between propofol only and midazolam-based sedation. Mortality was higher in patients treated with midazolam-based sedation. Further research is needed to determine optimal pharmacotherapeutic strategies for sedative, analgesic, and NMB.

Introduction: While pharmacists are a key member of the ICU team, little data exists regarding their perceptions and practices surrounding delirium recognition. Hypothesis: Current perceptions and practices of ICU pharmacists regarding delirium recognition are unknown. Methods: A validated, self-administered survey was distributed via either paper or the web to pharmacists residing in 7 states who are members of SCCM or ACCP and practice in a clinical role in the ICU ⱖ 25% of the time. Results: Of 457 pharmacists surveyed, 250 (55%) responded. Most had practiced ⱕ 10yrs (61%), had completed a practice (70%) or critical care specialty (32%) residency, worked at a major medical center (55%) in either a medical (33%) or mixed medical-surgical (37%) ICU that had ⱖ 11 beds (71%). While 56% completed ⱖ 20 hrs of CE in 2009, 43% obtained no CE regarding ICU delirium. Agitation (49%), disorganized thinking (17%) and fluctuating symptoms (11%) were more associated with delirium than inattention (8%), hallucinations (8%) or a decreased consciousness (6%). Among the 50% of ICUs where delirium status was frequently or always discussed on rounds, it was screened using a validated tool ⱖ 50% of the time in only 18% of patients. Availability of a screening protocol (43%) was not associated with more patients screened (34 vs 39%, p⫽0.56). Among the 32% who had ever screened ⱖ 1 ICU patient for delirium, most (64%) screen for delirium in ⱕ 10% of their patients. Stated screening barriers were lack of time (34%) and that it is was a RN role (24%). Medications frequently or always associated with delirium included lorazepam (89%), midazolam (85%), high-dose methylprednisolone (70%), fentanyl (37%), propofol (20%), haloperidol (10%) and dexmedetomidine (3%). Conclusions: Current critical care pharmacists’ practices and perceptions surrounding the recognition of delirium in the ICU are heterogeneous. While pharmacists are ideally suited to become more involved in delirium recognition efforts in the ICU, future research is required to establish the impact of these efforts on patient outcome and to identify the ideal educational strategy that should be used to boost pharmacists’ efforts in this area.


897

898

CURRENT CRITICAL CARE PHARMACISTS’ PERCEPTIONS AND PRACTICES SURROUNDING THE TREATMENT OF DELIRIUM IN THE INTENSIVE CARE UNIT (ICU)

EVALUATION OF DEXMEDETOMIDINE: SAFETY AND CLINICAL OUTCOMES IN CRITICALLY ILL TRAUMA PATIENTS

John Devlin, Northeastern Univ, Shubha Bhat, Notheastern Univ, Christopher Burke, U of Knoxville Medical Center, Russ Roberts, Tufts Medical Center, Yoanna Skrobik, Hospital Maisonneuve Rosemont

Sandeep Devabhakthuni, University of Pittsburgh Medical Center, Mehrnaz Pajoumand, Carla Williams, University Of Maryland Medical Center, Kristin Watson, University Of Maryland School of Pharmacy, Joseph Kufera, R. Adams Shock Trauma Center, Deborah Stein, University of Maryland School of Medicine

Introduction: While pharmacists are a key member of the ICU team,little data exists regarding their perceptions and practices surrounding delirium treatment. Hypothesis: Current perceptions and practices of ICU pharmacists regarding delirium treatment are unknown. Methods: A validated, self-administered survey was distributed via either paper or the web to pharmacists residing in 7 states who are members of SCCM or ACCP and practice in a clinical role in the ICU ⱖ25% of the time. Results: Of 457 pharmacists surveyed, 250 (55%) responded. Most had practiced ⱕ10 yrs (61%), worked at a major medical center(55%), in a medical (33%) or mixed medical-surgical (37%) ICU that had ⱖ11 beds (71%). Most (85%) stated that delirium should be frequently or always managed with medication. First-choice delirium treatment options were haloperidol (76%), an atypical antipsychotic (14%), a benzodiazepine (10%) or dexmedetomidine (0.5%). Treatment strategies that were frequently or always used in a patient with agitated delirium included haloperidol (87%), quetiapine (59%), lorazepam (47%), midazolam (37%), fentanyl (32%), olanzapine (26%), dexmedetomidine (25%). Many thought RCTs demonstrating benefit with haloperidol exist (42%) and that it is labeled by the FDA for this indication (34%). The frequency of different haloperidol routes of administration and dosing schedules that were always or frequently used included: IV (93%), oral (23%), ‘as needed’ (93%), scheduled intermittent (61%) and continuous IV infusion (0%). Usual haloperidol daily doses always or frequently used to treat delirium included:ⱕ4mg(47%), 5-10mg(56%), 11-20mg(38%), and ⱖ21mg(9%). A history of preexisting dementia was investigated frequently or always in only 35% of patients ⱖ65yrs. The QTc interval was frequently or always measured ⱖonce/shift via an ECG strip by 64% and ⱖonce daily via a 12-lead ECG by 44%. The QTc(msec) criteria warranting haloperidol discontinuation varied: ⱖ500(36%), ⱖ550(28%) or ⱖ600(32%). Conclusions: Current pharmacists’ practices and perceptions surrounding ICU delirium treatment are heterogeneous and frequently not evidenced-based. Further research and educational strategies are needed to guide the treatment of delirium in the ICU.

Introduction: The effect of prolonged infusions of either standard or higher than recommended doses of dexmedetomidine in critically ill trauma patients is unknown. Hypothesis: To compare the safety and clinical outcomes of prolonged infusions with standard doses (ⱕ 0.7 mcg/kg/hr) or high doses (⬎ 0.7 mcg/kg/hr) of dexmedetomidine to propofol, a current standard of care in critically ill trauma patients. Methods: This was a retrospective review of 127 adult mechanically ventilated trauma patients between 2008 and 2009, who received propofol (50 patients) or standard-dose (35) or high-dose dexmedetomidine (42) for ⬎ 24 hours. The primary outcomes were significant changes in blood pressure or heart rate. Secondary outcomes included hospital and intensive care unit (ICU) length of stay (LOS), time on ventilator, and any concomitant analgesic, sedative, and antipsychotic use. Sedation and delirium assessment scores were not collected due to inconsistent documentation. Chi Square or Fisher exact tests were used to compare proportions, and KruskalWallis and Wilcoxon Rank-Sum tests were used to compare continuous data. Results: Patients in high-dose dexmedetomidine group had a higher rate of hypotension compared to those in the propofol group (98% vs. 78%, p ⫽ 0.02). These patients had a median longer hospital LOS (25 days vs. 12 days, p ⬍ 0.001), ICU LOS (20 days vs. 12 days, p ⫽ 0.004), and longer time on ventilator (14 days vs. 7 days, p ⫽ 0.008). They also had increased requirements for oxycodone (74% vs. 40%, p ⫽ 0.003), midazolam (36% vs. 8%, p ⫽ 0.004), and haloperidol (50% vs. 24%, p ⫽ 0.02). Patients in standard-dose dexmedetomidine group had many similar outcomes to propofol group, except longer hospital LOS (21 days vs. 13 days, p ⬍ 0.001). Many confounding factors such as admission hemodynamics, baseline injury severity score, and age were similar among the groups. Conclusions: More patients in high-dose dexmedetomidine group received midazolam therapy, possibly increasing need for haloperidol due to deliriogenic nature of benzodiazepines, leading to longer ventilator time and LOS. Higher doses may result in higher incidence of hypotension, which should be confirmed by more well-designed studies in trauma patients.



900

SEDATION AND NEUROMUSCULAR BLOCKADE REQUIREMENTS DURING HIGH FREQUENCY OSCILLATORY VENTILATION (HFOV)

ADVERSE EVENTS RELATIVE TO DEXMEDETOMIDINE AND MIDAZOLAM DOSE IN THE SEDCOM TRIAL

Lindsay Pell, Bruce Doepker, Anthony Gerlach, Kari Mount, The Ohio State University Medical Center, Jennifer Severing, University Hospital East - OSUMC, Roy Brower, Johns Hopkins Hospital, James O’Brien, The Ohio State University Medical Center Introduction: High Frequency Oscillatory Ventilation (HFOV) has been promoted as a useful mode of mechanical ventilation (MV) in patients with Acute Respiratory Distress Syndrome (ARDS). Due to differences between HFOV and traditional modes of MV, patients on HFOV may require more sedation and neuromuscular blockade (NMB). To date, there is no published literature characterizing sedation and NMB requirements in patients on HFOV. Hypothesis: Continuous infusions (CI) of sedatives, analgesics, and NMB are used frequently in patients who receive HFOV. Methods: We retrospectively reviewed all patients who received HFOV between August 2007 and March 2010 in the medical and surgical intensive care units (MICU and SICU) at a university medical center. All intermittent doses and CI of benzodiazepines (BZD) and opioids were converted to midazolam equivalents (ME) and fentanyl equivalents (FE) respectively. Time on CI NMB was also recorded. RASS scores were recorded only while patients were not receiving CI NMB. Data was collected during time on HFOV for each patient. Results: We evaluated 87 patients (49% male, 85% MICU). Mean age was 48 ⫾ 14years, mean admission weight 97 ⫾ 36kg, and mean APACHE II on 1st day of HFOV 31 ⫾ 7. Mean HFOV duration was 3.1 ⫾ 2.8 days and ICU survival was 46%. Sepsis or pneumonia was the cause of ARDS in 81.6%. 85% of patients received CI sedation and/or analgesia for the entire duration of HFOV. Among all patients, the mean percent of HFOV time spent on CI sedation and/or analgesia was 96.7%. One patient received no CI sedation or analgesia at any time during HFOV. CI NMB was administered to 33.3% of patients during HFOV; among these patients, the mean percent of HFOV time spent on CI NMB was 74.5%. Mean opioid dose in FE was 84 ⫾ 72mcg per hour of HFOV and mean BZD dose in ME was 5.1 ⫾ 4.1 mg per hour of HFOV. Mean percent of RASS scores that were -4 or -5 was 64.6%. Conclusions: Most patients received CI sedation/analgesia for the majority of time on HFOV while 1/3 of patients received CI NMB. The regimens utilized resulted in deep sedation a majority of the time. More studies are needed to compare sedation and NMB in patients receiving HFOV to those treated with other modes of MV for ARDS.

Richard Riker, Maine Medical Center, Yahya Shehabi, The Prince of Wales Hospital & University NSW, Wayne Wisemandle, Hospira Inc, Robert Bilkovski, Hospira Inc. Introduction: Sedative doses may affect the rate of adverse drug events (AE). This has not been well studied for dexmedetomidine (DEX). Methods: Data from the SEDCOM trial were analysed for AE incidence relative to mean study drug infusion rate (MSD) for DEX and midazolam (MID). A Cochran-Armitage (CA) test assessed trend between AE incidence and MSD quartile. AEs were identified by CA p-value ⬍0.10 for DEX and MID and through DEX regulatory review. Unexpected AEs and those with greater clinical impact are reported in greater detail. Results: 244 subjects received DEX, 122 received MID. The median (IQR) MSD was 0.84 (0.54-1.15) mcg/kg/h for DEX and 0.06 (0.03-0.08) mg/kg/h for MID. CA-identified AEs for DEX included abdominal distension, decreased urine output, hypomagnesemia, agitation, acute respiratory distress syndrome (ARDS), pleural effusion, respiratory failure, decubitus ulcer, and systolic hypertension. CA-identified AEs for MID included bradycardia, tachycardia, hypertension, decreased urine output, hypophosphatemia, pleural effusion, and rash. AEs identified by DEX regulatory review included atrial fibrillation, constipation, peripheral edema, and anxiety. ARDS incidence by DEX quartile was 0%, 0%, 4.9%(3/61), and 4.9%(3/61), and for MID 0%, 0%, 0%, and 3.3%(1/30); none were drug-related. Baseline PaO2/FiO2 ⬍200 or SpO2/FiO2 ⬍235 was present for all 7 pts. Reintubations in SEDCOM were considered serious adverse events and coded as “respiratory failure”. Excluding these, respiratory failure incidence by DEX quartile was 0%, 1.6%(1/61), 1.6%(1/61), and 4.9%(3/61) and for MID 0%, 0%, 3.2%(1/31), and 3.3%(1/30). Atrial fibrillation incidence by DEX quartile was 1.6%(1/61), 0%, 1.6%(1/61), and 4.9%(3/61) and for MID 0%, 0%, 9.7%(3/31), and 3.3%(1/30). Agitation incidence for DEX was 4.9%(3/61), 3.3%(2/61), 8.2%(5/61), and 11.5%(10/61) and for MID 3.2%(1/31), 10%(3/30), 0%, and 10%(3/30). Conclusions: Patients requiring higher sedative doses have a higher incidence of AEs, which differ between DEX and MID. The relationship between sedative dose and AE is complex and potentially confounded by comorbidities, underlying disease, and severity of illness. This relationship warrants further analysis.

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902

THE IMPACT OF DEXMEDETOMIDINE AND MIDAZOLAM DURATION GREATER THAN 24 HOURS ON ADVERSE EVENT INCIDENCE IN THE SEDCOM TRIAL

THE IMPACT OF PAIN AND PAIN MANAGEMENT ON SLEEP IN MECHANICALLY VENTILATED, CRITICALLY ILL CHILDREN

Richard Riker, Maine Medical Center, Yahya Shehabi, Prince of Wales Hospital and University NSW, Wayne Wisemandle, Hospira Inc, Robert Bilkovski, Hospira Inc.

Sapna Kudchadkar, Nicole Shilkofski, Allan Gottschalk, Audrey Hamer, Laura Sterni, Johns Hopkins University, Blaine Easley, Baylor College of Medicine, Myron Yaster, Johns Hopkins University

Introduction: Medication duration may affect the onset of adverse drug events (AE), but this has not been reported in large studies for dexmedetomidine (DEX). Methods: Data from the SEDCOM trial was re-evaluated for AE onset relative to study drug duration for 244 patients receiving DEX and 122 receiving midazolam (MID). AEs occurring ⬎2% were segregated by onset ⱕ or ⬎ 24 hours after start of drug. AE incidence was compared within drug group to identify a difference ⱖ3% between onset ⬍ 24 vs ⱖ 24 hrs. Next, AE incidence between DEX and MID was compared for onset ⱖ 24 hrs. SEDCOM was not designed for this analysis; to avoid type II errors in this safety study, we selected the ⬎3% difference rather than statistical significance threshold. Results: Within drug group, AEs 3-6% more common ⬎24 (vs ⱕ24 hrs) for DEX included constipation, hypoglycemia, pyrexia, tachycardia, and hypokalemia. For MID, AEs 3-6% more common ⬎24 included hypomagnesemia, decubitus ulcer, fluid overload, hypertension, vomiting, peripheral edema, pneumonia, hypoglycemia, urinary tract infection, constipation, and diarrhea. Bradycardia was 17.7% more common ⬎24 hrs after starting MID. AEs more common ⱕ24 hrs included diastolic hypertension for MID, and diastolic/systolic hypertension and bradycardia for DEX. When comparing DEX vs MID for onset ⱕ24 hrs, bradycardia (25.8%), hyperglycemia and hypotension (both 3-6% greater) were more common for DEX. Tachycardia (12.7%) and diastolic hypertension (4.1%) were greater for MID. ⬎24 hrs, pyrexia was 3.3% greater in DEX, while systolic hypertension and tachycardia occurred 6-12% more often for MID. Similarly, hypomagnesia, decubitus ulcer, vomiting, pneumonia, urinary tract infection, hypotension, and fluid overload occurred 3-6% more often ⬎24 hrs for MID compared to DEX. Conclusions: The pattern and incidence of adverse events vary when duration of sedative infusion is considered, with different patterns for DEX and MID that are often unexpected. When administered ⬎ 24 hrs, MID is associated with hypertension, hypotension, tachycardia, pneumonia, urinary tract infection, fluid overload, and decubitus ulcers more often than DEX, while pyrexia is more common with DEX.

Introduction: Adult studies have demonstrated the negative impact of the intensive care unit on the quality and duration of sleep. Though mechanical ventilation reduces sleep, common ICU treatments, such as analgesic/sedative medications, can eliminate restorative sleep. Sleep quality and structure in hospitalized children has not been well studied. We present preliminary data from polysomnography and actigraphy in 2 mechanically ventilated, critically ill children in our pediatric intensive care unit. Hypothesis: We hypothesize that current pain and sedation management in mechanically ventilated children reduces their restorative sleep. Methods: This is a prospective, observational cohort study of intubated children aged 2 to 18 requiring both mechanical ventilation and pain/sedative medications. After a validated screening sleep questionnaire, polysomnography (PSG) and actigraphy are initiated. The primary outcome variables used are total sleep time (TST) and percent-time spent in restorative sleep within the cohort compared with age-matched normative PSG data. The secondary outcome variables of analgesic/sedative medication dosing characteristics will be correlated with each subject’s time-stamped, PSG architecture. Results: Patient #1 was studied with PSG for 36 hours and actigraphy for 7 days, and Patient # 2 was studied with actigraphy for 11 days. Patient #1 demonstrated a severe reduction in restorative sleep as evidenced by a total REM sleep of 1.1% of total sleep time (normative for age 20%) and significant fragmentation and disruption of sleep as evidenced by actigraphy. Patient #2 demonstrated fragmented and disrupted sleep that improved dramatically and correlated with extubation, weaning of sedative medications and transfer out of the PICU. Conclusions: Mechanically ventilated children suffer a severe disruption of restorative sleep. This data will provide us the first hypothesis driven evaluation of sleep in critically ill children and a quantifiable metric that to use in developing strategies to improve sleep and pain/sedation management in mechanically ventilated children in the future. Support: Foundation for Anesthesia Education and Research (FAER) Research Fellowship Grant


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904

MUSIC THERAPY TO DECREASE DEXMEDETOMIDINE REQUIREMENTS IN MECHANICALLY VENTILATED TRAUMA AND GENERAL SURGICAL PATIENTS: A PILOT STUDY

EVALUATION OF A NEWLY IMPLEMENTED SEDATION PROTOCOL IN A MEDICAL INTENSIVE CARE UNIT

Daniel Yeh, San Francisco General Hospital, Julin Tang, University of California San Francisco General Hospital Case Reports: Music has been studied as a sedation and analgesia adjunctive therapy in outpatient settings with mixed results. Some report beneficial effects while others report no benefit. This has not been extensively studied in the ICU population.The purpose of this study was to evaluate the feasibility of implementing music therapy in the ICU for trauma and general surgical patients. Our hypothesis is that use of music therapy is associated with decreased sedation requirements in injured and general surgical intensive care unit (ICU) patients.Inclusion criteria were: trauma and general surgery ICU patients between ages 18 – 70 requiring intubation and mechanical ventilation; requiring sedation with dexmedetomidine, benzodiazepines and/or analgesia with narcotics. Exclusion criteria were: hearing loss, psychiatric illness, hemodynamic instability, traumatic brain injury or coma, and expected extubation within 12 hours. For one hour prior to music intervention, baseline vitals (heart rate, systolic blood pressure, mean arterial pressure, respiratory rate, Richmond Agitation-Sedation Score, nursing Evidence of Pain) and pain/sedation requirements were recorded. A playlist of Western Classical music was played for two hours at a comfortable, reasonable volume through occlusive headphones via Ipod. After the intervention was completed, data capture continued for an additional hour.Five patients were enrolled in this case series. During the two hour intervention, there was no discernable change in vital signs, narcotics and benzodiazepines requirements, and nursing assessments of pain and agitation. The infusion rate of dexmedetomidine was successfully weaned down by an average of 33%. This effect persisted for at least one hour after the music therapy intervention concluded.Passive listening music therapy may be a useful adjunctive to narcotics, benzodiazepines and dexmedetomidine in mechanically intubated injured patients. This modality is inexpensive, easy to administer, safe and deserves further evaluation of efficacy and cost efficiency. Future studies should be randomized, blinded, and placebocontrolled.

905 DAILY SEDATION INTERRUPTON Christy Rooks, RPh, CNSC, Serena Laird, RRT, Ashley Brock, RN, BSN, Stormont-Vail Health Care, Katie Myers, Pharm D Candidate 2011, University of Kansas Introduction: Clinical practice guidelines have shown that multidisciplinary development and implementation of sedation guidelines will reduce direct drug costs, ventilator time and lengths of ICU stay without changing mortality. The use of sedation guidelines, an algorithm or a protocol is recommended. Our institution developed a daily sedation interruption protocol to guide clinicians to obtain these desired endpoints. Hypothesis: With the initiation of a daily sedation interruption protocol, each patient in the ICU meeting criteria will be given the opportunity for sedation interruption, in conjunction with a spontaneous breathing trial (SBT) and delirium screening. This daily interruption will improve patient outcome measures by decreasing ventilator days and ICU length of stay. Methods: Every ICU patient on continuous sedation medications was reviewed for inclusion in the trial. Exclusion criteria included: trauma, alcohol withdrawal, FiO2 of 100%, physician order not to interrupt, ⬍ 24 vent hours, or age ⬍15. Descriptive statistics were used to determine patient outcomes from continuous sedation medication interruptions. Results: A total of 30 patients were identified for this study. Results from the trial included sedation interruption compliance (54.5%), delirium screening compliance (38.2%), and SBT screening opportunities coordinated with sedation interruption (30.9%). Other outcome measures identified included the following: hours on interruptible sedation (15.2), days on the ventilator (4.5), length of stay in the ICU (6.9 days), and length of stay in the hospital (16 days). Conclusions: We identified that our compliance for sedation interruption in ICU is inadequate. This led to extensive education regarding sedation interruption and delirium screening to increase compliance. We also identified the need to improve our rates for coordination with respiratory therapy of SBT with sedation interruption. We forecast that as our sedation interruption compliance increases, our outcome measures will also improve proportionately.

Jeanmarie Salonia, Haley Goodwin, Shilta Subhas, Annette Rowden, The Johns Hopkins Hospital Introduction: Minimization of ICU sedation through use of a goal directed protocol decreases mechanical ventilation time and facilitates patient participation in rehabilitation activities. Caregiver adherence to protocols that minimize sedation may be met with resistance and concerns for patient safety. Hypothesis: The purpose of this study is to evaluate the adherence to an updated sedation protocol. Methods: The sedation protocol was implemented in the JHH MICU on 7/1/09. The protocol requires initial use of intermittent sedation with continuous infusions used only in patients failing intermittent sedation or meeting predetermined criteria. Mechanically ventilated patients 18 years of age or older receiving sedation with fentanyl and midazolam ordered using the protocol from 8/1/09 –12/31/09 were included. Outcome data were collected through retrospective review of the electronic medical record. Results: 78 randomly selected patients were evaluated. 44% of patients received continuous infusion only; 13% of patients received continuous infusions first and then were transitioned to intermittent sedation; 28% of patients received intermittent sedation only; 15% of patients were started on intermittent sedation and then transitioned to continuous infusion. Of patients initiated on intermittent sedation 35% were transitioned to continuous infusion, with 1 meeting transition criteria. Of patients initially prescribed continuous infusions, 27% met criteria. 85% of patients receiving intermittent sedation were administered per protocol boluses to meet RASS goal. 50% of patients receiving continuous infusions were administered per protocol boluses prior to increasing the infusion. RASS scores were documented per protocol in 30% of cases. There were no documented self-extubations. Conclusions: Implementing a protocol does not ensure adherence to the new standard. Data collection of practice after implementation is necessary to determine if additional education or protocol adjustments are needed to improve adherence. Our study findings provided information to modify our protocols and address provider concerns.

906 CONTINUOUS INFUSION OF LORAZEPAM PROVIDES MORE CONSISTENT SEDATION THAN MIDAZOLAM IN MECHANICALLY VENTILATED PEDIATRIC PATIENTS Emily Martin, Children’s Healthcare of Atlanta@Egleston/Emory University, Atul Vats, Children’s Health of Atlanta at Egleston/Emory University School of Medicine, Jana Stockwell, Children’s Healthcare of Atlanta at Egleston/Emory University Introduction: Benzodiazepine (BZD) infusions are often used in conjunction with narcotic infusions to maintain sedation and analgesia in ventilated patients. Lorazepam (LOR) is the preferred agent in adults as it has been shown to provide more consistent sedation and awakening time than midazolam (MID), however this has not been validated in pediatric patients. In our PICU, ventilated patients are placed on a nurse-driven sedation protocol, which includes a fentanyl (FEN) infusion and a BZD infusion (either LOR or MID per physician discretion). When patients reach the maximum defined doses of FEN or BZD, alterations in the protocol are permitted (switching FEN to morphine or changing BZD) or a third agent can be added. Hypothesis: Infusion of LOR provides more consistent sedation than infusion of MID, as evidenced by fewer protocol changes. Methods: Retrospective chart review. Our PICU Quality Daily Checklist Database was reviewed to identify patients ⬎1 year old who were ventilated for ⬎7 days between December 2008 and March 2009. Data collection included narcotic and BZD infusion rates on day 1 and day 7, whether patients were changed from FEN to morphine, had BZD changed, or had a third agent added during the 7 days. Results: 16 patients were identified. 11 were initially on MID, and 5 were on LOR. 6/11 patients on MID (54%) required a change in sedation protocol (either changing narcotic, or switching to LOR), whereas 0/5 on LOR required changes (p ⫽ 0.06). 4/11 (36%) on MID required a third sedative agent, versus 4/5 (80%) of the LOR group (p⫽ 0.14). The mean hourly FEN dose on day 7 for the MID group was 2.68 ␮g/kg/hr, versus 1.54 for the LOR group (p⫽0.08). Conclusions: In ventilated pediatric patients ⬎ 1 year old, lorazepam provides more consistent sedation than midazolam, with fewer patients requiring a change in narcotic or benzodiazepine. The mean fentanyl dose at day 7 was also lower in the lorazepam group, although further study is warranted to determine whether this would be statistically significant with larger numbers.


907 THE CLINICAL USE OF DEXMEDETOMIDINE FOR THE PEDIATRIC PATIENTS WITH CONGENITAL HEART DISEASE Hirokazu KAWASE, Okayama University Hospital, Yuichiro Toda, Dept of Anesthesiology and intensive care Okayama University Medical School, Tatsuo Iwasaki, Kazuyoshi Shimizu, Tomohiko Suemori, Kiyoshi Morita, Okayama University Hospital Introduction: Dexmedetomidine (DEX) is one of major sedative medications in Operating suite and intensive care unit. It is widely used because of its favorable effects. However, a few data are available in which DEX is given children with congenital heart disease. Severe bradycardia and hypotension may be a consequence of DEX administration and their occurrence is quite important in pediatric patients with congenital heart disease. We investigated whether DEX can cause any cardiovascular derangement in patients with congenital heart disease. Methods: We compared retrospectively the clinical data of patients who received DEX (GD) with those of patients who did not receive DEX (GN) for 24 hours from Cardiac Care Unit (CCU) admission. The clinical data was collected from medical records. Student’s t test was used for statistical analyses. A p value of less than 0.05 was considered as significant. Results: We enrolled 278 patients except neonates, and we found 159 patients who received continuous administration of DEX (57.2%). Highest systolic BP (GD;118⫾16 mmHg vs. GN;113⫾20 mmHg: p⫽0.03), highest diastolic BP (GD;66⫾9 mmHg vs. GN;61⫾11 mmHg: p⬍0.01), lowest diastolic BP (GD;42⫾7 mmHg vs. GN;39⫾10 mmHg: p⫽0.03) in GD were higher than those of ND significantly. Lowest HR in GD was significantly lower than in ND (GD;99⫾18 beat per minute vs. GN;105⫾21 beat per minute: p⫽0.01). And lowest RR was lower in GD than in ND significantly (GD;18⫾4 /min vs. GN;20⫾6 /min: p⬍0.01), but highest concentration of carbon dioxide in arterial blood gas analysis is similar in the two groups (GD;48⫾9 mmHg vs. GN;48⫾17 mmHg: p⫽0.83). Duration of mechanical ventilation in GD is significantly shorter than in ND (GD;55⫾133 hours vs. GN;180⫾579 hours: p⫽0.04). Survival rate in CCU and incidence of adverse events were similar in the two groups. Conclusions: Highest systolic BP, highest diastolic BP, lowest diastolic BP in GD were higher than those of ND significantly, and lowest HR in GD was significantly lower than in ND. The incidence of critical adverse events was similar in the two groups.


Poster: Case Reports 909

910

SUCCESSFUL USE OF THE LUCAS-II AUTOMATED CHEST COMPRESSION DEVICE TO PROVIDE PROLONGED HIGH QUALITY CPR IN A PATIENT WITH PRESUMED PE AND MINIMAL CIRCULATION

CASE SERIES: REPORT OF PATIENTS AT OUR INTSTITUTION VENTILATED IN NEURALLY ADJUSTED VENTILATORY ASSIST (NAVA) WITH SEVERE OBSTRUCTIVE PHYSIOLOGY

Martin Stechert, Jan Hirsch, Richard Fidler, Christopher Choukalas, Wilson Cui, UCSF

Brandy Seger, Lesley Doughty, Carrie Morgan, Alicia West, Cynthia White, Cincinnati Children’s Hospital Medical Center

Introduction: Studies have shown that clinician-performed chest compressions during cardiac arrest are slower and shallower than recommended by current ACLS guidelines. LUCAS-2 is an electronic piston-driven device designed to automate chest compressions with the premise to improve overall quality of CPR. Case Report: An 84 year old patient with CAD was admitted to the ICU for A-Fib with RVR and developed PEA arrest. He was intubated; ACLS resuscitation resulted in stabilization and manual chest compressions could be interrupted. However, despite substantial pharmacologic support, his hemodynamic status declined. LUCAS-2 was attached to the patient and automated compressions were initiated when arterial pressure fell to 45/20 mmHg. With mechanical CPR blood pressure stabilized around 140s/50s mmHg. Automated CPR was continued with short interruptions for rhythm checks. CVP line and TEE probe could be placed safely during automated CPR. The TEE exam confirmed effective CPR with rhythmic compression/decompression of the RV⬎LV. Mechanical CPR was held intermittently to allow for a focused TEE exam which was consistent with acute right heart failure due to either PE or acute MI (ST changes were not present). Treatment included full dose TPA and support of the right ventricle by milrinone infusion. Over the next 2 hours, the status of the patient continued to stabilize. CVP decreased from 40 mmHg to 15mmHg, venous saturation rose from 26% to 65%, and sequential TEE exams demonstrated decreased RV/ RA volumes, and significant improvement of the prior most severe TR. Automated compressions were discontinued after a total of 125 minutes, and the patient remained hemodynamically stable on milrinone and norepinephrine infusions. Over 48 hours, pressors could be weaned and the patient successfully extubated; he could be transferred on ICU day 7. Comment: In this case of presumed PE, LUKAS II was used successfully to augment a non-perfusing hemodynamic status for a prolonged duration. Besides consistency of high quality CPR for 125 minutes, other perceived benefits included improved access to the patient compared to manual CPR.

Case Reports: NAVA is an FDA approved mode of ventialtion in which support for spontaneous breathing is triggered by detection of electrical diaphragmatic impulses (edi) and the support continues until the edi signal decreases by 70%. NG tube sensors detect edi and communicate with the vent to initiate a breath in contrast to conventional modes triggered by flow/pressure changes. Increased trigger response and the coupling of ventilatory support with diaphragmatic stimulation is thought to improve patient ventilator synchrony. There are no reports of NAVA use in the pediatrics with severe obstructive disease (OD) or acute respiratory failure (ARF). We report a series of 3 patients with ARF and a significant OD physiology resulting in prolonged exhalation and hypercarbia that were ventilated in NAVA. All 3 patients had a history of asthma, exhibited significant wheezing throughout their ventilatory course and received continuous bronchodilator therapy and steroids. Pt 1 (3 yr) had status asthmaticus and initially was ventilated in SIMV/PS with neuromuscular blockade to avoid patient ventilator dysynchrony. On day 3 NAVA was used until extubation on day 5. Pt 2 (1.5 yr) had pneumonia and pulmonary hypertension complicating her OD exacerbation and ARF. For the first 9 days she required NO with SIMV/PS or HFOV for poor oxygenation. As these issues were improving, wheezing continued complicating synchrony in an SIMV/PS mode. Vent days 15 -19 NAVA was used until extubation. Pt 3 (6 yr) had status asthmaticus complicated by a pulmonary hemorrhage. SIMV/PS or HFOV with NO was required to maintain adequate oxygenation for days 1-14, then NAVA was used until extubation on day 16. In each case, despite wheezing, NAVA was utilized and patients were able to self regulate their I:E ratio, maintain adequate VT’s, C02, and oxygenation. Discussion: In our small cohort NAVA was used successfully in the setting of significant wheezing, OD and complicated respiratory failure. Coupling of ventilatory support to the onset and duration of neurally derived stimulation of the diaphragm may provide another ventilator strategy for ARF complicated by wheezing.

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POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES) AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

COMBINED CONTINUOUS HAEMODYALISIS WITH A SINGLE PASS HIGH CUT OFF ALBUMIN DIALYSIS IN SEVERE CHOLESTATIC JAUNDICE ASSOCIATED TO LIVER FAILURE: A CASE REPORT

Yanjun Zhao, Mayo Clinic Rochetser, Yan Topilsky, Soon Park, Mayo Clinic Rochester Case Report: A 53-year-old male with severe coronary artery disease and end stage ischemic cardiomyopathy (ICM) initially received a Duraheart® LVAD implantation as bridging to transplant then exchanged to HeartMate II® 14 days later due to an inflow cannula obstruction. During his immediate post-op course, he had persistently high cardiac output with significant pulsatility which was most probably related to his improved native left ventricular contractility. In addition, he had been suffering from continuous high grade fevers that were unresponsive to the appropriate antibiotic and antifungal treatments. He also experienced intermittent confusion. In order to rule out the central cause of the fever, a CT scan of the brain was obtained that revealed a possible post circulation stroke involving the right occipital lobe and left side dorsal surface of the pons. Upon neurology evaluation based on the neuroimaging results, the findings were decided to be most consistent with PRES, which can develop as a result of fluctuating blood pressure that exceeds the autoregulatory capability of the brain vasculature and causes hyperperfusion injury. Anti-hypertensives were initiated to maintain constant pressure with minimal drop or rise in systolic blood pressure. The LVAD pump speed was decreased and forced diuresis was initiated in an effort to reduce the high cardiac output. Stable mean blood pressure of 75-80 was achieved with the initiation and up-titration of antihypertensives, forced diuresis, and a decrease to the lowest possible LVAD pump speed needed to maintain proper pump function but avoid hyperperfusion injury. Patient’s confusion was gradually resolved. Resolution of neuroimaging findings occurred within 2 weeks. This case illustrates that patients with ICM status post LVAD implantation are at risk for PRES due to increased cardiac output and the resultant hyperperfusion injury, especially during the immediate post-op phase if patients experience significant hemodynamic instabilities with fluctuating blood pressure. Prompt recognition and treatment is important in preventing the permanent damage that can occur in this otherwise typically reversible condition.

Diego Atzeni, Hospital Marino Cagliari Italy, Patrizia caravetta, S.Camillo Hospital Rome Italy, Paolo Castaldi, Hospital Marino Cagliari Italy, Andrea Farris, Hospital Marino, Pinella Loria, Salvatore Murru, Hospital Marino Cagliari Italy Case Reports: Severe hyperbilirubinemia associated to liver dysfunction has an extreme poor outcome. The use of an extracorporeal liver support system can bridge patients to a resolutive procedure ( ercp ). Combined continuous veno venous haemodialsysis with single pass albumin high cut off hemodyalisis employing the novel membrane septex®gambro is a life saving procedure in such a situation. We report the case of a 60 yo man who has been admitted after a massive hepatic trauma affecting mostly the main biliary tract. He was hemodynamically unstable due to multiple fractures and spleen rupture and showed severe hepatic dysfunction associated to cholestatic jaundice.combined continuous cvvhd-spad was then started and maintained for 72 hours with the purpose of removing bilirubin and reduce organ toxicity. cvvhd was performed for 3 days using the novel high flux-high cut off membrane septex®and an albumin cleansed dyalisate as follows: 250 cc albumin 20 % mixed in 5 liter bag (dyalisate). Blood flow rate was set at 120 cc/min dyalisate flow was set at 66 cc/ min. cvvhd-spad resulted in a significant reduction in bilirubinemia (reduction rate about 0,3 mg per hour). Conjugated bilirubina levels ranged from 35 mg/dl to about 14 mg/dl after 72 hours treatment. Conjugated bilirubina clearance was calculated: 50 ml min. Lactate dehydrogenase dropped from 1700 to 750 ui/l, ast and alt dropped as well from 250ui/l to 80 ui/l .We observed an improvement in ammonia serum levels that returned normal after the completion of the treatment. After cessation of the spad, once hemodynamic status improved, the patient underwent ercp .We conclude that spad employing the novel membrane septex gambro is an effective and life saving procedure in jaundice associated to liver dysfunction when hyperbilirubinemia rises above 20 mg/dl serum level.


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914

THE USE OF RECOMBINANT FACTOR VIIA USE IN A PATIENT WITH GLANZMANN’S THROMBASTHENIA AND DIFFUSE ALVEOLAR HEMORRHAGE

EARLY EFFECTIVE USE OF VENOVENOUS ECMO IN THE TREATMENT OF ACUTE RESPIRATORY FAILURE DUE TO PLASTIC BRONCHITIS

Linda Browning, Detroit Receiving Hospital, Sanjay Dogra, Julie Bourbonnais, Wayne State University School of Medicine

Shaylyn Bennett, University of Toledo, College of Medicine, Girish Deshpande, University of Illinois College of Medicine-Peoria, Randall Fortuna, University of Illinois College of Medicine at Peoria, Alberto Torres, University of Illinois College of Medicine

Case Report: A 30-year-old African American woman with GT who presented to the emergency department with three days of epistaxis, hemoglobin level of 6.1 g/dL, platelet count 145⫻103/mm3 and normal coagulation profile. She was transfused 2 units of packed red blood cells and 5 units of platelets and discharged home after nasal packing was performed. The following day, she presented with recurrent epistaxis after self-removal of her nasal packing. Laboratory data revealed a hemoglobin level of 7.7 g/dL and platelet count 156 ⫻ 103/mm3. The patient was hospitalized and started on oral aminocaproic acid but was noncompliant with nasal packing instructions. She was transferred to the intensive care unit after nasal endoscopy was performed with nasal packing were she remained intubated and hemodynamically stable. Laboratory findings were significant for a platelet count of 43 ⫻ 103/mm3 and HLA immunization. She continued to require multiple transfusions and attempts were made to acquire single-donor matched-HLA platelets. Transcatheter embolization of the right internal maxillary, greater palatine and sphenopalatine arteries was later performed. The patient began to display severe hematuria, melena, vaginal, oropharyngeal and conjunctival hemorrhage. Due to evidence of diffuse alveolar hemorrhage on bronchoscopy, the decision was made to administer rFVIIa. She was given three 90 mcg/kg doses of rFVIIa. Evidence of bleeding rapidly decreased; however, the patient was found to be in asystole the following day and attempts to resuscitate her failed. Autopsy results revealed thrombi in the right atrium and ventricle and within the pulmonary vessels. Discussion: Thromboembolic events associated with the use of rFVIIa in hemophilic patients with inhibitors are rare. In Europe, rFVIIa is indicated for the prevention and treatment of bleeding episodes in patients with GT and antibodies to GP IIb/IIIa and/or HLA with refractoriness to platelet transfusions. The incidence thromboembolism among patients with GT is unknown. To our knowledge, this is the first case report describing fatal venous thromboembolism after the administration of rFVIIa in a patient with GT.

Case Report: A previously healthy 4-year-old boy was admitted to the pediatric ward with left lower lobe pneumonia for worsening of distress, a non-productive cough, and low grade fever. Due to rapid deterioration in condition he was transferred to the PICU, where he was promptly intubated and provided with positive pressure ventilation. Chest x-ray revealed complete atelectasis of the left lung and hyperinflation of the right lung and pneumothorax. Emergency rigid bronchoscopy performed for suspicion of foreign body revealed completely obstructed left mainstem bronchus by a mucous plug, which could only be removed partially. Despite high ventilator pressures and 100% inspired oxygen, the patient continued to have poor oxygenation prompting the decision to initiate VVECMO. The right internal jugular and left femoral veins were cannulated percutaneously and ECMO was initiated within 6 hours of admission to PICU. Oxygen saturations were maintained in low 90s. Ventilator settings were reduced to PEEP of 8, rate of 15 bpm and tidal volume of 6-ml/kg. Fiberoptic bronchoscopy performed after initiation of ECMO showed thick bronchial mucus casts consistent with plastic bronchitis. All infectious disease and cystic fibrosis workup were negative. Mycoplasma IgG was high IgM was negative. The patient remained on VV-ECMO for 6 days and underwent 7 bronchoscopies with removal of casts. The patient was extubated 4 days post-ECMO and discharged home on 18th day, without supplemental oxygen. At 15 months follow up, the patient is being treated for asthma, and has not been hospitalized. Discussion: The pathophysiology of the mucous hypersecretion and cast formation in plastic bronchitis is not well understood. Although many treatment modalities have been attempted none have proven to significantly lower mortality. In our patient, left lung atelectasis from complete obstruction of left mainstem bronchus resulted in hyperinflation of right lung and air-leaks. Early institution of venovenous-ECMO allowed for adequate gas exchange while avoiding ventilator induced lung injury. It also allowed more aggressive pulmonary toilet with daily bronchoscopy to recruit the atelectatic lung.

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916

RARE ORGANISM,RARE PRESENTATION-NECROTIZING FASCIITES

THE NEW GREAT IMITATOR: ISOLATED HEPATIC TUBERCULOMA MASQUERADING AS HEPATOCELLULAR CARCINOMA

Asma Siddiqui, Joseph Smith, Geisinger Medical Center Background: Necrotizing Fasciitis is a life threatening, rapidly progressive soft tissue infection that is commonly caused by group A Streptococcus, Staph Areus, Vibrio Vulnificus, Clostridium Perfringes and Bacteroides Fragilis. Infection caused by Klebsiella Pneumoniae is only reported in a few cases. Klebsiella Pneumoniae is a gram negative bacterium is a common cause of gram negative Bacteremias, but necrotizing fasciitis caused by it is rare, with only 11 to 14 cases documented outside US. Most cases occurred in Asia, with 9 cases being reported from Singapore and Taiwan, and 1 case occurring in Turkey. We report a case of 66 year old female with Necrotizing Fasciitis of abdominal wall, secondary to infected Intra-abdominal drainage with tissue and abdominal fluid cultures growing Klebsiella Pneumoniae. Case Presentation: This is a 66 yr old female caucasian with morbid obesity, HTN, DM, and hypothyroidism, under went elective laproscopic RYGB. Post op, developed sepsis from Necrotizing Fasciitis and shock, taken to the OR for repeated debridements and washouts. Her abdominal wall tissue culture grew Klebsiella Pneumoniae .Patient was treated with Cefepime, Vancomycin and Flagyl.To our knowledge this is the first case of NF associated with post op intra-abdominal drainage after an elective RYGB procedure,growing Klebsiella Pneumoniae.Discussion: The clinical features of necrotizing fasciitis caused by klebsiella, i.e, severe sepsis, a propensity for multiorgan failure and high mortality are unique. Extensive subcutaneous tissue and skin necrosis have been noted intraoperatively. NF due to klebsiella spp is associated with multiple septic foci.( eyes,liver) and is strongly associated with underlying conditions such as, DM, liver diseases,and malignancy. Conclusion: This infection in the western hemisphere is noted to be due to aggressive and virulent K1-type of Klebsiella Pneumoniae. DM and Klebsiella of K1 pheno type were the common factors in most of these cases. It is therefore prudent for the physicians to recognize NF as a potential complication of abdominal surgery and look for other infectious foci when Klebsiella Pneumoniae is the organism.


Leigh Hunter, Omid Nikrouz, Methodist Hospitals of Dallas Case Report: Focal hepatic lesions may be caused by malignancies, adenomas, infections, cysts, and hemangiomas. History and epidemiology are crucial in differentiating cause and guiding evaluation. In addition, these lesions may be complicated by hemorrhage or rupture resulting in acute or catastrophic presentations. We present a case of a previously healthy immunocompetent woman with an expanding hepatic mass. Six mos PTA she presented with intractable abdominal pain and underwent TAH/BSO, but experienced worsening pain and fever post-operatively. Presumed SSI was diagnosed, antimicrobials were prescribed, but symptoms persisted accompanied by nausea, vomiting, night sweats and anorexia. Abdominal CT demonstrated a large hepatic mass presumed to be malignant. She was transferred to our facility for hepatobiliary surgical consultation. Physical examination was significant for decreased BS right base and severe RUQ pain with peritoneal signs. CXR and lab data were normal. Repeat CT of abdomen showed further enlargement of the hepatic lesion so she was taken to the OR emergently for exploration. Histology revealed multiple caseating granulomas, calcifications, and rare AFB. Antituberculous therapy was initiated with complete resolution of symptoms. Tuberculosis with solitary hepatic localization is very rare with fewer than 100 cases reported in the literature. Our case is especially unusual in that the patient was immunocompetent with no evidence of pulmonary or miliary tuberculosis. The clinical presentation, epidemiology, associated laboratory abnormalities, diagnostic strategies, radiologic and histologic characteristics, treatment regimens, and outcomes of localized hepatic tuberculomas will be presented. Classification schemes, pathophysiology, and world literature to date will also be discussed. Since clinical features of this disease mimic neoplastic and other infective hepatic disorders, the diagnosis requires a high index of suspicion and frequently requires laparotomy. In addition, patients may present with acute abdomen, therefore it is essential that critical care physicians and surgeons be aware of this unusual manifestation of a relatively common disease.

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918

DEXMEDETOMIDINE FOR INTRACTABLE PAIN IN A NONINTUBATED MEDICAL INTENSIVE CARE UNIT PATIENT

RARE CASE OF MEDIASTINAL ABSCESS (AND FURTHER UTILIZATION OF INTENSIVIST GUIDED ULTRASOUND)

Christina Candeloro, Virginia Commonwealth University Health System, Keliana O’Mara, St. Mary’s Hospital, AA Fowler, Katie Muzevich, Virginia Commonwealth University Health System

Francis Maguire, Patrick Walsh, Matthew Facktor, Geisinger Medical Center

Case Report: A 39-year-old female was transferred from an outside health system with fever of unknown origin and desquamating rash after oseltamivir use resulting in extensive sacral and lower extremity decubitus wounds. Combination analgesia to cover both opioid-mediated and neuropathic pain pathways was mostly ineffective. While reasonable pain control was obtained with a bupivicane epidural, opiate PCA, and daily nortriptyline, intolerable side effects such as hallucinations, tremor, and difficulty word finding prevented long-term use. Despite revising her regimen, the patient had progressive altered mental status and developed respiratory distress requiring intubation and transfer to the intensive care unit. The epidural was removed and nortriptyline held due to concerns of drug toxicity. While intubated, analgesia was provided with continuous infusion hydromorphone (doses ⬎8 mg/hr) and as needed bolus doses. The patient continued to experience extreme pain and apnea during wound care despite the high dose opioid therapy, which led to consideration of tracheostomy placement. After 10 days of mechanical ventilation she was extubated without a definitive plan for pain management. Transition to a hydromorphone PCA was attempted but pain was so poorly controlled that wound care was not performed. Dexmedetomidine was initiated to facilitate wound care until a second epidural PCA could be inserted despite the potential toxicity with the previous one. The second epidural was never placed because the patient’s pain dramatically improved, hydromorphone requirements decreased, and aggressive wound care was carried out. After five days on dexmedetomidine (mean dose 0.4 mcg/kg/hr) the patient was transitioned to clonidine 0.1 mg by mouth every 8 hours. Clonidine was titrated to 0.2 mg every 8 hours, the patient continued to tolerate wound care and did not receive a tracheostomy.

Case Report: An immunosuppresed 53 year old male presented with presumed urosepsis. Sepsis bundle was initiated; however, the patient’s condition deteriorated necessitating transfer to the intensive care unit. On the right anterior thorax, a palpable soft tissue mass with minimal fluctuation was noted. Computerized tomography scanning revealed a large ill-defined heterogeneous mass within the anterior mediastinum extending from the level of the main pulmonary artery cephlad into the subcutaneous tissue near the clavicle. The intensivist performed a bedside ultrasound guided fine needle aspiration of the mass. Stat gram stain revealed gram-positive cocci in clusters. Thoracic surgery completed an open thoracotomy revealing a large thin walled mediastinal abscess with spontaneous rupture of frank pus. A deeper, thick walled abscess was visualized with spontaneous hemorrhage. Tamponade pressure was applied, but imminent exsanguination was apparent due to the friability of the abscess wall. There was no obvious direct communication with the superior vena cava, azygous vein, or aorta, and direct abscess invasion of an alternative mediastinal vascular structure was presumed. Intraoperative findings were immediately reviewed with family and due to his multi-organ failure he was allowed to expire. All cultures were positive for methicillin-sensitive staphylococcus aureus. A mediastinal abscess is a rare finding, often with subtle presentation, but carries a grave prognosis if not recognize early. Mediastinal abscess’ are most often reported following trauma or postoperatively via complication of sternotomy, esophageal perforation, or more recently, recognized following endoscopic ultrasound biopsies. Most case reports recognize an inciting incident or concomitant oral pharyngeal infection which can lead to devastating necrotizing mediastinitis, but mediastinal abscess without instigation are even less common. Our patient did not present with any of these features which is why intensivist directed bedside ultrasound with FNA was imperative to expedite care. We believe this is just another example of ultrasonography utilization and versatility among critical care professionals.

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920

EXTRACORPOREAL MEMBRANE OXYGENATION: A LIFESAVING PROCEDURE TO TREAT A LARGE POST-OPERATIVE PULMONARY EMBOLISM

A UNIQUE PRESENTATION OF MASSIVE QUETIAPINE OVERDOSE: PROLONGED ANTICHOLINERGIC DELIRIUM AND ACUTE REVERSAL WITH PHYSOSTIGMINE

Anil Paturi, Mayo Clinic, James Onigkeit, Juan Pulido, Mayo Clinic Department of Anesthesiology, Jayanth Vedre, Mayo Foundation For Medical Education and Research, Kevin Greason, Mayo clinic, Mark Keegan, Mayo Clinic Department of Anesthesiology

Sinoj John, Dartmouth-Hitchcock Medical Center, Randy Loftus, William Dewhirst, Stephen Surgenor, Dartmouth Hitchcock Medical Center, Matthew Koff, Dartmouth-Hitchcock Medical Center

Case Report: A 63 year-old man was admitted to the intensive care unit (ICU), still intubated and ventilated, after a left radical nephrectomy and inferior vena cava (IVC) tumor thrombectomy for renal cell carcinoma. Past medical history was significant for morbid obesity (165 kg), type 2 diabetes mellitus, and hypertension. A pre-operative CT scan had demonstrated emboli in the right middle and bilateral lower lobe segmental pulmonary arteries and an IVC filter had been placed.Intraoperatively, the patient developed transient hypotension and hypoxemia. In the ICU, however, he required vasopressin and an increasing dose of epinephrine to maintain mean arterial pressure ⬎60 mmHg. Arterial blood gas analyses demonstrated hypoxemia and progressive metabolic and respiratory acidoses, despite a minute ventilation of 22 L. ECG demonstrated new RBBB. Transthoracic echocardiogram revealed a hyperdynamic left ventricle with moderate right ventricular enlargement, severe right ventricular systolic dysfunction, atrial septal bowing and a D-shaped left ventricle. New pulmonary embolism (tumor and/or clot) with extracardiac obstructive shock was diagnosed although thrombus was not visualized on echocardiography. Inhaled nitric oxide was initiated to improve right ventricular function and oxygenation.Systemic thrombolysis was deemed contraindicated in the immediate perioperative period and pulmonary thromboembolectomy was considered inappropriate in the absence of visualized central thrombi. Accordingly, the patient was returned to the OR for initiation of veno-arterial extracorporeal membrane oxygenation (VA ECMO) to offload the right ventricle and improve cardiorespiratory status. Transesophageal echocardiogram in the OR confirmed the absence of central pulmonary embolism. ECMO flow of 2L/min was achieved via cannulae in the right femoral artery and vein. The patient was weaned from ECMO after 13 days. He was discharged from the ICU with intact neurologic function on hospital day 36. Conclusion: VA ECMO should be considered for pulmonary embolism-induced shock in the postoperative period when other therapeutic interventions such as thrombolysis or embolectomy may be inadvisable.

Case Report: Quetiapine is an atypical antipsychotic indicated for bipolar disorders and schizophrenia and can be used to treat ICU delirium. The maximum dose is 800 mg/day. Overdose is manifested by tachycardia, hypotension, coma, seizures and rhabdomyolysis. Death can occur following ingestion ⬎10gm. Anticholinergic delirium is a difficult to recognize, life-threatening complication. We report a massive quetiapine overdose with prolonged central anticholinergic syndrome immediately reversed by physostigmine.A 22-year-old male with depression and marijuana abuse was found unresponsive at home with empty bottles of alcohol and quetiapine. Estimated ingestion was 21gm of quetiapine (seventy tablets of 300mg each). CT head was negative, drug screen was positive for tetrahydrocannabinol and ethanol level was 120mg/dl. The patient was intubated and after gastric lavage and activated charcoal, admitted to the intensive care unit. He was successfully extubated on ICU day 3; however became increasingly agitated, tachycardic, and febrile with discontinuation of propofol. Delirium tremens was diagnosed, but the patient failed to respond to benzodiazepines. Further history ruled out chronic alcohol abuse. Persistent anticholinergic delirium was considered and physostigmine 2mg intravenously was administered over five minutes followed by a repeat dose. There was rapid, dramatic reversal of delirium and the patient became fully oriented, confirming the diagnosis. He was transferred to the psychiatry ward on ICU day 4 and later discharged home.Anticholinergic delirium is a serious adverse effect of quetiapine overdose and can be a challenge to diagnose. Differential diagnosis includes alcohol/opiate withdrawal, ICU delirium, serotonin syndrome and neuroleptic malignant syndrome. When uncertain, reversal of delirium by physostigmine can confirm the diagnosis. This case is unique that despite a potentially lethal, 21gm overdose of quetiapine; there were no permanent sequelae. The delirium persisted for days and complete reversal by physostigmine supports a central anticholinergic mechanism and to our knowledge, this is the first case to report these findings in quetiapine overdose.


921 DELAYED ONSET SEIZURE AND CARDIAC ARREST FOLLOWING AMITRIPTYLINE OVERDOSE, TREATED WITH INTRAVENOUS LIPID EMULSION THERAPY Aimee Franken, Phoenix Children’S Hospital, Robert Graham, Phoenix Childrens Hospital, Michael Levine, Daniel Brooks, Banner Good Samaritan Medical Center and Phoenix Childrens Hospital Case Report: Toxicity from tricyclic antidepressants (TCA) typically occurs in the first hours post ingestion. Sodium bicarbonate (NaHCO3) is the traditional “antidote;” newer data supports lipid emulsion (LE) therapy. We present a case of delayed seizure and cardiac arrest in a patient treated with NaHCO3 and LE.A 13 year old girl found unresponsive after ingesting amitriptyline. She had an initial respiratory rate of 6 with “shaking of her arms” that resolved spontaneously. Initial EKG revealed a QRS of 76; 5 hours later a QRS of 94 msec and the patient remained comatose. A bicarbonate drip was initiated and midazolam was given. Drug testing revealed amitriptyline, nortriptyline and diprivan. Total tricyclic level (TTL) 14 hours post ingestion 2718 (toxic ⬎300) ng/mL. 20 hours post ingestion intermittent seizure activity occurred, lasting 1 hour. 10 minutes into the seizure, a wide-complex tachycardia developed, followed by torsade de pointes and asystole. The resuscitation included, cardioversion, 350 mEq of NaHCO3, 2 boluses of 1.5 mg/kg of LE, benzodiazepines, barbiturates, magnesium, and levetiracetam. Post arrest, she received vasopressors, NaHCO3 and LE infusion. A repeat TTL, 1 hour post LE, was 4946 ng/mL. Blood gas testing was nonanalyzable due to lipemia. She developed pancreatitis and thrombophlebitis. She was extubated on day 6, yet had residual anticholinergic toxicity. An MRI was normal. She made a full recovery. Seizures and ventricular dysrhythmias are common manifestations of TCA toxicity but typically develop early. Despite early toxicity, further seizures and dysrhythmias didn’t develop until 20 hours post ingestion. The patient’s TTL increased substantially after LE. While it is possible the increased TTL was the result of on-going absorption, more likely, it represents redistribution of the lipophilic drug into the vascular compartment. LE likely develops a “lipid sink” in which lipophilic drugs are removed from target tissue and drawn into the vascular compartment. To our knowledge, this is the first case of LE being used to treat a TCA toxic pediatric patient who developed delayed toxicity.

922 PROBIOTICS IN THE ICU: ARE THEY DANGEROUS? Varsha Gharpure, Advocate Lutheran General Hospital, Deborah Goldberg, Chicago Medical School, Sarah Wieczorkiewicz , Advocate Lutheran General Hospital Introduction: Probiotic Saccharomyces boulardii (Sb) (Florastor®), is frequently used for antibiotic associated diarrhea (AAD).1 Sb has been studied for modification of gut microflora in preterm infants2 as well as in critically ill tube fed patients.3 Though considered a natural product, its use has been associated rarely with invasive infections with Sb or a genetically identical species Saccharomyces cerevisiae (Sc).4 Case Report: A 5-month-old, infant born at 28 weeks of gestation, with multiple co-morbidities was admitted to the pediatric intensive care unit for worsening of chronic lung disease (CLD). She was on Sb supplement for AAD. She received piperacillin/tazobactam for aspiration pneumonia. A femoral central venous line (CVL) was placed. After initial clinical improvement, an ulceration was noted at the CVL site necessitating its removal. She later developed recurrence of fever, worsening respiratory status, hemodynamic instability and leckocytosis. Culture from both the catheter site and the blood were positive for yeast identified initially as Sc. She responded to removal of all CVLs, discontinuation of Sb, and amphotericin B. The fungal isolate was subsequently identified to be S. boulardii and was matched with the strain from Florastor® capsules at Texas Fungal Testing Laboratory by DNA microsatellite typing.5 Conclusion: Probiotic Sb is marketed in the United States as a natural product and there is no control by the Food and Drug Administration. The exact incidence of fungemia with its use is not known. Its use in the ICUs could be especially concerning due to the risk of contamination of central lines and the potential for nosocomial spread.6 The risks and benefits of using Sb in ICUs must be carefully considered. Strict protocols must be followed for its proper handling and administration. References: 1. Szajewska H, et al. J Pediatr 2006;149:367-72. 2.Costalos C, et al. Early Human Development 2003;74:89-96. 3. Bleichner G, et al. Intensive Care Med 1997;23:517-523. 4. Munoz P, et al. Clin Infect Dis 2005;40:1625-34. 5. Malgoire JY, et al. J Clin Microbiol 2005;43:1133-1137. 6. Cassone M, et al. J Clin Microbiol. 2003;41:5340-3.

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PHYSICAL THERAPY AND ACTIVE REHABILITATION WHILE ON EXTRACORPOREAL MEMBRANE OXYGENATION AWAITING LUNG TRANSPLANTATION

DISTAL IVC FILTER MIGRATION WITH QUAD COUGHING

David Turner, David Zaas, Shu Lin, Kyle Rehder, Walter Williford, Michelle Peters, Ira Cheifetz, Duane Davis, Duke University Medical Center Case Report: Transplant of critically ill patients from mechanical ventilation or extracorporeal membrane oxygenation (ECMO) is generally complicated by an inability to participate in physical therapy (PT), development of severe myopathy, prolonged hospitalization, and overall poor outcomes. We describe an adolescent who successfully underwent re-conditioning and PT while on ECMO as a bridge to lung transplantation. The patient is a 16 yr old with cystic fibrosis who was transferred to the Pediatric Intensive Care Unit in our institution for evaluation and emergent listing for transplantation following presentation with a febrile respiratory illness necessitating intubation and ventilation. Her respiratory status deteriorated despite maximal conventional and then high frequency ventilation. After 4 days, lack of clinical improvement and risk of continued de-conditioning led to cannulation for venovenous ECMO via the right internal jugular vein using a 19-Fr double lumen cannula (Avalon). Following cannulation and aggressive ventilator weaning, the patient underwent tracheostomy tube placement within 24 hrs. She then was quickly transitioned to room air via tracheostomy collar, and sedation was discontinued to allow active participation in rehabilitation. During 8 days on ECMO pre-transplant, she participated in a rigorous PT regimen and was ambulatory with assistance. Following bilateral sequential lung transplantation, she was quickly weaned from the ventilator, ambulatory within 24 hrs, discharged from the ICU on post-op day five, and, ultimately, discharged home in good condition. PT and active rehabilitation can be successfully and safely implemented while on ECMO awaiting lung transplantation. Experience with this patient led to the development of an ECMO PT program that has been utilized for a second patient awaiting transplantation. Active rehabilitation on ECMO may lead to a shorter duration of ventilation, ICU stay, and hospital length of stay following transplantation. With further experience, programs of this nature may become the preferred method for bridging critically ill patients to lung transplantation.


Petra Warner, Wright State University, Harry Anderson, Wright State University School Of Medicine, Peter Knoll, Wright State University, Shannon Kauffman, Miami Valley Hospital Case Report: Objective: Inferior vena cava (IVC) filters are utilized to prevent pulmonary embolism in patients with contraindications to anticoagulation, recurrent pulmonary emboli, and long-term immobility. We report a patient who developed distal migration of the IVC filter with perforation through the inferior vena cava as a consequence of quad coughing. Design: Individual case report and literature review. Setting: Surgical Intensive Care Unit. Patient: A 19 year male sustained a C4 fracture with resultant lower extremity paraplegia and partial paralysis of the upper extremities. Due to presence of a spinal epidural, prophylactic anticoagulation was felt to be contraindicated and an IVC filter was placed. Concurrently, due to difficulties clearing respiratory secretions, quad coughing was initiated. This process of allowing the patient to cough involves forceful upward thrusts initiated to the upper abdomen by a caretaker. Given the forces produced with quad coughing, an abdominal xray was obtained to document filter position. The xray demonstrated distal migration of the filter to the iliac bifurcation with lateral rotation concerning for potential perforation. Intervention: The patient underwent extraction of the IVC filter by Interventional Radiology. Angiographic CT reconstruction demonstrated perforation of four struts through the IVC . The filter was extracted utilizing two access routes: the right femoral vein; to allow a balloon Fogarty catheter to reposition the filter; and the right internal jugular; to extract the filter. Post extraction venography demonstrated absence of vascular extravasation. Conclusion: Quad coughing can create abdominal forces that can distally displace an IVC filter and may require innovative filter retraction techniques due to malpositioning or strut perforation.

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926

IT IS NOT ALL ABOUT SEPSIS!: SEVERE LACTIC ACIDOSIS AND SHOCK CAUSED BY THIAMINE DEFICIENCY

A FATAL CASE OF PROLONGED HYPOTENSION FOLLOWING AMLODIPINE AND LISINOPRIL OVERDOSE

Sandeep Tripathi, The Children’s Hospital At Montefiore, Jacqueline Weingarten-Arams, Children’s Hospital At Montefiore

Pashna Munshi, Nitin Puri, Cooper University Hospital, Rachel Haroz, Cooper Health Systems, David Gerber, Cooper Hospital/UMC, Sri-Sujanthy Rajaram, Cooper University Hospital

Case Report: Thiamine is an essential co-factor in oxidative metabolism. Its deficiency, though rare, can present as severe lactic acidosis and shock. Recognition and treatment can be life saving. Case presentation: 20 year old male with a history of intestinal obstruction leading to shock and cardiac arrest 5 years ago . He required resection of 2 feet of intestine including the ileum and his condition resulted in diffuse HIE. For the past 1 year, he was at home, receiving no medical supervision with diet consisting primarily of juice and potato chips. Presently, he had gradual worsening of his mental status, decrease in oral intake, and off and on but progressively worsening diarrhea. In ED he was found to be dehydrated, but with stable vitals. He was admitted to the Pediatric floor for IV hydration and electrolyte correction. On D5 of admission he worsened with change in mental status and hyperpneic respirations. ABG showed severe metabolic acidosis and lactate of 17. Bicarbonate and fluids stabilized his pH but his lactate did not change. Despite adequate fluid hydration with normal blood pressure, CVP and urine output, his lactate showed no improvement. He was evaluated for persistent lactate acidosis despite euvolemia. He was found to be deficient in most mineral and vitamins notably Vitamin B1 62 nmol/lt (N 87-280). Replacements of his minerals and vitamins including thiamine were started and he made a steady improvement with lactate falling to normal levels within 3 days with normal blood gases. Discussion: Lactate is a metabolic end product that accumulates in the setting of impaired oxidative metabolism consequent to tissue dysoxia. Lactate increases when production of pyruvate exceeds its utilization by the mitochondria. Hypoxia or inhibition of oxygen transport in mitochondria will lead to increased pyruvate. The enzyme pyruvate dehydrogenase complex catalyzes this reaction. Thiamine is an important cofactor in this reaction. Thiamine deficiency due to malnutrition leading to severe lactic acidosis and shock is exceedingly rare, although its suspicion and treatment can lead to rapid improvement in clinical state as demonstrated by our case.

Purpose: To understand the prolonged and lethal effects of coingestion of angiotensin converting enzyme inhibitors (ACE-I) and calcium channel blockers. Introduction: Dihydropyridine calcium channel blockers (DCCBs) cause peripheral vasodilatation and block insulin release from the pancreas decreasing the free fatty acid use by the myocardium. This causes hyperglycemia, lactic acidosis and depressed myocardial contractility. Amlodipine’s particular prolonged duration of effect of 72 hours is concerning. DCCB overdose combined with ACE-I can be lethal as ACE-I blunt the body’s normal sympathetic compensatory responses to hypotension. We report a case of severe toxicity with a fatal outcome following co-ingestion of amlodipine and lisinopril. Case: A 19 year old male was brought to the emergency department 12 hours after ingestion of 70 tablets of amlodipine (10mg) and 30 tablets of unknown dose of lisinopril. He was hemodynamically unstable, received calcium chloride and activated charcoal along with glucagon and norepinephrine infusion. Hypotension was refractory to calcium gluconate, vasopressin, norepinephrine, dopamine, epinephrine and 25 liters of crystalloids and colloids. Hyperinsulinemic Euglycemia (HIE) therapy along with a bolus of 20% intralipids and sodium bicarbonate was given. He became pulseless, was resuscitated for 20 minutes and pronounced dead approximately 48 hours post his suicide attempt. Discussion: Co-ingestion of CCB and ACE-I cause a profound toxicity. A few case reports of survival exist with early institution of HIE therapy specifically in amlodipine toxicity at doses of 0.1-1unit/kg/hour. Possible mechanism of action is improved lactate clearance, increased glucose utilization and decreased dobutamine requirement. HIE being standard therapy for CCB toxicity failed to work in our patient likely secondary to coingestion with ACE-I. 20% intralipid was used as salvage therapy. Conclusion: Early institution of HIE therapy is shown to have survival benefit in amlodipine toxicity however lack of randomized controlled trials makes it challenging to treat CCB and ACE-I overdose largely due to delayed effects on blood pressure.

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PRONE POSITION DURING EXTRACORPOREAL LIFE SUPPORT FOR H1N1 PNEUMONIA

CASE OF ANTISYNTHETASE SYNDROME WITH RENAL FAILURE

Pim Van Pommeren, Luuk Otterspoor, Diederik Van Dijk, Jozef Kesecioglu, University Medical Centre Utrecht

Haala Rokadia, Rudy Tedja, Shikhar Agarwal, Diego Conci, Chaim Moeller, George Thomas, Carol Farver, Jonathan Myles, Madhu Sasidhar, Cleveland Clinic

Introduction: Extra Corporeal Life Support (ECLS) is increasingly being used for patients with severe respiratory collapse. Patients on ECLS are virtually always treated in supine position. We report a patient who was treated with ECLS in the prone position. Objective:To evaluate the risks and benefits of prone positioning during ECLS treatment. Case: A 51-year-old male was admitted to our intensive care unit with severe acute respiratory distress syndrome (ARDS) due to Influenza type A (H1N1). After 7 days, veno-venous ECLS was initiated to provide lung rest. Blood flow of the ECLS was set at 3 L/min and fresh gas flow at 6 L/min, while the ventilator settings were PEEP 20 cmH2O; ⌬P 10 cmH2O. With these settings, gas exchange gradually deteriorated. Because a computed tomography (CT) scan of the lungs showed dorsal atelectases, the patient was placed in prone position. Gas exchange immediately improved and prone and supine position were alternated for three days. In prone position sputum drainage was markedly increased and a new CT scan showed reduced dorsal atelectases. The patient was successfully weaned from ECLS after 45 days and later discharged to a rehabilitation center. Discussion: During conventional mechanical ventilation for ARDS, prone positioning is widely used and now considered a simple and safe strategy to reduce atelectasis and improve oxygenation. This case suggests that the same applies to ARDS patients placed on veno-venous ECLS. Turning the patient appeared to be a fairly straightforward and safe procedure. Accidental cannula dislocation did not occur and is in our opinion survivable in case of venovenous ECLS. A literature search in Pubmed yielded one other report of uneventful ECLS in prone position.1 We conclude that putting a patient in prone position while on veno-venous ECLS can be carried out safely and may improve sputum drainage and reduce atelectasis. Reference: 1. Mc Cunn, M et al; Extracorporeal support in an adult with severe carbon monoxide poisoning and shock following smoke inhalation; Perfusion 2000;15:169.

Case Report: 64 year old female, previously healthy, presented with acute onset dyspnea. Patient was treated for community-acquired pneumonia with some improvement. Over the next 4 months, patient had multiple recurrences of multifocal pneumonia requiring hospital admissions. Bronchoscopic biopsy was inconclusive. Open lung biopsy showed patchy interstitial pneumonia with areas of widespread organizing acute lung injury. Sputum cultures grew Pseudomonas riticci and Burkholderia spp. Patient was treated with tailored antibiotic regimens and steroids. During this course, patient had new onset polyarticular arthralgias, hair loss, and generalized skin tightness. Eight months following initial respiratory symptoms, patient presented with fevers and hypoxic respiratory failure requiring mechanical ventilation. Computed tomography of the chest showed progressive multifocal ground glass opacities with associated airway thickening and airway corrugation. Despite treatment with broad-spectrum antibiotics, her clinical status worsened. Infectious workup was significant for negative fungal serologies and bacterial cultures. Rheumatologic workup demonstrated positive anti-Jo1 antibody and anti-nuclear antibody. C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anti-Ro antibody were elevated with low titers of anti-Scl-70 antibody. Patient was treated for anti-synthetase syndrome based on nonspecific interstitial pneumonia by lung biopsy, positive anti-Jo1 and antinuclear antibody, history of joint pain and skin tightness, and high grade fevers.Hospital course was significant for acute renal failure requiring intermittent hemodialysis. Urine studies were consistent with acute tubular necrosis without obvious renal insult. Due to lack of description of acute renal failure in anti-synthetase syndrome, renal biopsy was performed. It demonstrated interstitial fibrosis and interstitial inflammation with lymphocytic predominance. Patient was treated with high dose steroids and mycophenolate mofetil resulting in stabilization of clinical status. To the best of our knowledge, concomitant renal involvement in anti-synthetase syndrome has not been previously described.


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HYPERLEUKOCYTOSIS AND RASBURICASE-INDUCED METHEMOGLOBINEMIA: THERAPEUTIC CHALLENGES

TREATMENT OF HEMORRHAGIC SHOCK SECONDARY TO LONG ACTING ANTICOAGULANT(DIFENACOUM) TOXICITY WITH HIGH DOSE VITAMIN K

Azadeh Fayazi, Virginia Commonwealth University Health System, Sue Sreedhar, Medical College of Virginia, Mark Marinello, Medical College of Virginia Hospital, Shamsur Chowdhury, Virginia Commonwealth University Health System Case Report: Hyperleukocytosis and tumor lysis syndrome are medical emergencies. We report a case of rasburicase-induced methemoglobinemia and hemolytic anemia in a teenager with leukostasis who had no known risk factors for G6PD deficiency.A 15 year-old Caucasian male presented with a white blood cell (WBC) count of 82,200/mm3 (62% blasts). Rasburicase was administered. Four hours later his oxygen saturation decreased and he developed cyanosis unresponsive to oxygen supplementation. His arterial PO2 was 242 and methemoglobin (MetHb) level was ⬎10%. Methylene blue was administered with no improvement. During the next 4 days, he developed hemolytic anemia and his WBC peaked at 240,000/mm3; he received chemotherapy after diagnosis of T-cell ALL was established. On hospital day 5, he was intubated for persistent decline in oxygen saturations and worsening lactic acidosis, both of which improved over the next 24 hours. After hospital discharge, he was diagnosed with G6PD deficiency.The combination of methemoglobinemia and hyperleukocytosis created multiple challenges in the diagnosis and management of our patient’s symptoms. True oxygenation status was difficult to assess; pulse oximetry was inaccurate and blood sample turbidity made arterial blood gas results unreliable. Blood turbidity also interfered with the MetHb assay. Dramatic improvement in oxygenation and tissue perfusion with intubation indicated that leukostasis was the more predominant pathologic process. Chemotherapy is the mainstay of treatment for leukostasis and there was no definitive indication for leukopheresis. However, given the need for intubation, leukopheresis may have improved his oxygenation status and allowed for more accurate lab results. Though G6PD deficiency is rare among Caucasians, it should not be overlooked in the presence of hemolytic anemia and methemoglobinemia after rasburicase administration. Lack of quick resolution of methemoglobinemia with methylene blue should raise suspicion for other pathological processes. More rapid leukoreduction may help assessment and management of patients with hyperleukocytosis.

Gerald Tarirah, State University of New York Downstate Medical Center Case Report: 41 year old male with a past medical history of ESRD on HD was admitted for hypotension, abdominal pain, hematochiezia and hematemesis. An emergent esophagogastroduodenoscopy showed active bleeding in the posterior oropharynx, stomach and duodenum. Impression of severe coagulopathy was made, in the absence of other causes of bleeding (hepatic failure, DIC and Vitamin K deficiency) the elevations in PT and PTT suggested toxicity with an anticoagulant. He was started on high dose intravenous vitamin K . He required 150mg of intravenous Vitamin K per day for 8 days. His bleeding stopped with the correction of the coagulopathy.According to the American Association of Poison Control Center report there were 1,221 of cases of long acting anticoagulant poisoning in 2005. Bleeding is the usual clinical presentation. Difenacoum and related compounds are available commercially as rodent bait under various trade names. These compounds are similar in structure and mechanism of action to warfarin, but are more potent and longer acting . Because of these properties, these compounds are described collectively as “superwarfarins” or “long acting anticoagulants” because of long elimination half-lives. Difenacoum is readily absorbed through the skin, through the respiratory tract after inhalation, and from the gastrointestinal tract after ingestion. Difenacoum’s mechanism of action is inhibition of Vitamin K1-2, 3 epoxide reductase which prevents the regeneration of the active form of vitamin K in the liver. This leads to a state of multiple vitamin K-dependent coagulation factor deficiencies. Depending on the degree of toxicity, the clinical presentation can be simple bruising and mild elevations in the prothrombin time (PT) and activated partial thromboplastin time (PTT), or life threatening hemorrhage in the setting of profound coagulopathy. High dose vitamin K is the antidote for long acting anticoagulant poisoning. Difenacoum induced coagulopathy maybe included in the differential diagnosis for hemorrhagic shock. References: (1) Saquia A.: Severe coagulopathy as a consequence of smoking crack cocaine laced with rodenticide, NEJM,(2001)345,

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SEPTIC SHOCK SECONDARY TO CAPNOCYTOPHAGA SPECIES 24 HOURS AFTER AN ESOPHAGECTOMY AND SPLENECTOMY

USING BRONCHOALVEOLAR LAVAGE TO DIAGNOSE AN UNUSUAL CAUSE OF ACUTE RESPIRATORY DISTRESS SYNDROME

Doyle Ashburn, Emily Larson, Geisinger Medical Center, Omar Rahman, Geisinger Health System

Allen Blaivas, VA New Jersey Health Care System

Introduction: The genus Capnocytophaga is a group of fusiform, Gram-negative bacilli that are considered commensal bacteria in the oral flora of humans and animals. Certain species have been known to cause severe infections in immunocompromised individuals. We present a case in which a relatively immunocompetent patient develops septic shock secondary to Capnocytophaga species after an elective surgical procedure. Case Report: A 55 year old female was found to have adenocarcinoma of the esophagus in September. She underwent adjuvant chemotherapy which was completed in early December; she tolerated this well without significant neutropenia.In late January she underwent a transhiatal blunt esophagectomy and required a splenectomy secondary to intra-operative hemorrhage. 24 hours postoperatively she had continued hypotension requiring the addition of norepinephrine and remained critically ill and dependent on mechanical ventilation. Sepsis was diagnosed when she developed a fever of 39° C and a leukocytosis of 11.5 with 18% band forms. Blood cultures were positive for Capnocytophaga species. She was treated with piperacillin/tazobactam and had gradual improvement. Ultimately she improved to her baseline at discharge from the hospital. Discussion: Five species within the Capnocytophaga genus have been isolated from the oral cavity in humans; these have previously been categorized as Centers for Disease Control group Dysgonic Fermenter-1 (DF-1). Our organism was identified to be within this group. Reports of severe systemic infections by these species typically occur in patients on chemotherapy with neutropenia and mucositis. Our patient was not neutropenic during her hospital stay and had not had chemotherapy for about two months. Overwhelming postsplenectomy infection (OPSI) is an uncommon complication of splenectomy and is most prevalent in the first few years after surgery. Case series studying OPSI have excluded patients with sepsis within two weeks of surgery to avoid preexisting infections. Her recent splenectomy may have been a contributing factor in this case. This illustrates a unique presentation of a classically opportunistic infection.


Case Report: Fat embolism syndrome (FES) is a condition characterized by hypoxia, pulmonary infiltrates, and mental status change that occurs in the presence of long-bone trauma. An 87-year-old male with a femoral fracture following a fall that occurred one day prior to presentation was admitted. He was in mild respiratory distress, and was lethargic. Chest exam revealed bilateral crackles and the left lower extremity was externally rotated and tender to palpation. Petechial rash was absent. Chest x-ray showed bilateral diffuse infiltrates. Orthopedic repair was deferred, as it was felt he had active pneumonia. Respiratory distress progressed, requiring intubation and ARDS was noted on chest x-ray. Cultures were subsequently negative. Pulmonary capillary wedge pressure was 16. Bronchoscopy with bronchoalveolar lavage (BAL) was performed and stained with oilred-O, which demonstrated 70% lipid-laden macrophages, supporting a diagnosis of fat embolism syndrome.Fat embolism indicates the presence of fat globules in the peripheral circulation and lung parenchyma that occurs in almost all patients who sustain a long bone or pelvic fracture. FES is a serious manifestation of fat embolism characterized clinically by a classic triad of respiratory changes, neurological features, and a petechial rash. Symptoms typically occur within 24-72 hours after initial injury. Respiratory symptoms vary, but may progress to respiratory failure and ARDS. Neurologic features result from cerebral embolism, occur after the development of respiratory distress, and range from mild confusion to seizures. The characteristic petechial rash is usually the last to develop and is due to embolization of small dermal capillaries. Oil-red-O staining of lavage fluid is helpful in the diagnosis but fat globules may be seen in up to 50% of asymptomatic patients following fracture. A recent study suggests that fat globules in BAL may be the cause of unexplained hypoxemia in some patients following long bone trauma with no radiographic findings.Although fat embolism syndrome is uncommon, clinicians should be vigilant in considering fat embolism syndrome as a cause of dyspnea and ARDS.

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ACUTE HYPERAMMONEMIC ENCEPHALOPATHY IN ASSOCIATION WITH HIGH DOSE CORTICOSTEROID USE IN A PATIENT WITH BI-URETERO-COLONIC ANASTOMOSES

HIGH FREQUENCY PERCUSSIVE VENTILATION PROFOUNDLY IMPROVES OXYGENATION AND VENTILATION IN A PATIENT WITH H1N1

Mark Hepokoski, Brown Internal Medicine Residency, Adam Vasconcellos, Brown University, Jeffrey Mazer, The Miriam Hospital At Brown University

Felix Khusid, New York Methodist Hospital, Emma Fisher, New-York Methodist Hospital, Sagar Naik, Suhail Raoof, Esan Adebayo, Liziamma George, New York Methodist Hospital, Igor Lebedin, New-York Methodist Hospital

Case Report: Acute hyperammonemia is associated with life threatening complications including coma, cerebral edema, and brain herniation. Whereas the diagnosis of acute hyperammonemia in liver failure is straightforward, non-hepatic hyperammonemia is a diagnostic challenge. We present a case of acute hyperammonemic encephalopathy in association with high dose corticosteroid therapy in a patient thirty years status post bi-uretero-colonic anastomoses. The patient is an 83 year-old male with COPD who presented with wheezing, shortness of breath, and cough. He was diagnosed with a COPD exacerbation and started on IV azithromycin, IV methylprednisolone, and bronchodilators. He improved until hospital day #4, when he became acutely unresponsive requiring intubation. The patient was afebrile with a negative infectious workup. His chemistry panel showed an ammonia level of 364, but his liver enzymes were unremarkable. His INR was 1.0 and serum albumen 3.3. Brain MRI revealed symmetric areas of restricted diffusion in the cingulate gyrus, insular cortex, hippocampus, posterior temporal lobes and thalami, confirming a diagnosis of acute hyperammonemic encephalopathy. He was monitored in the ICU, and treated with lactulose. His mental status slowly improved, and at the time of discharge he was back to his baseline. Urinary diversions, such as bi-uretero-colonic anastomoses, enable additional ammonia reabsorption via gut metabolism of urinary nitrogenous compounds. Typically, cases of hyperammonemic encephalopathy secondary to urinary diversions present shortly after the procedure, but few reports have described acute hyperammonemic encephalopathy in patients with a remote history of urinary diversion. Corticosteroids have been shown to promote renal ammoniagenesis. Our patient, who showed no signs of encephalopathy on admission, developed coma from hyperammonemia within four days of first receiving high dose IV steroids. Therefore, we propose this intervention as the main contributing factor to our patient’s hyperammonemic encephalopathy, by increasing renal ammoniagenesis and subsequent increased gut reabsorption of ammonia.

Introduction: High Frequency Percussive Ventilation is delivered by a Volumetric Diffusive Respirator (VDR)The VDR is a pneumatically powered, pressurelimited, time-cycled flow interrupter that creates biphasic oscillations, which help to generate auto-cephalad flow of gas that helps in removal of secretions. Case Description: A 49 year old male on immunosuppressive therapy following renal transplantation 3 years ago, and with history of type 2 diabetes, asthma and hypertensive chronic kidney disease, presented with a fever, general weakness and shortness of breath. He was diagnosed with H1N1 influenza by PCR of respiratory secretions.In response to profound respiratory acidosis, hypoxia, and shortness of breath, the patient was orally intubated and placed on mechanical ventilation. A chest X-Ray revealed bilateral patchy opacities and inhomogeneous airspace consolidation consistent with ARDS. The ARDSnet protocol of lowvolume (6ml/Kg IBW), low-stretch ventilatory strategy was instituted Within 48 hours, the ventilator settings had been altered to the following: VT-420 ml, A/C rate-30, FiO2-100%, PEEP⫹24 cm. On these settings, the end-inspiratory plateau pressure was 36 cm H20 and the ABG was: pH 7.12, PaCO2-63, PaO2-38, HCO3-20, O2 Sat-53%. The patient was switched to High Frequency Percussive Ventilation (HFPV), with the following settings: Percussive Rate-6oo/min, Convective Rate-14, Percussive I:E Ratio 1:1, Convective I:E Ratio 1:1, PIP-30cm, Fi02-100%. Within 2 hours of placing the patient on HFPV, an ABG was obtained: Ph-7.31, PaCO2-37, PaO2-269.The patient remained on HFPV for 5 days prior to placement on conventional ventilation. A tracheostomy was subsequently performed and weaned off mechanical ventilation. He was discharged to a rehabilitation facility on the 37th day of hospitalization. Conclusion: HFPV effectively improved oxygenation and ventilation in a patient with ARDS secondary to H1N1 influenza. We believe that when the conventional ARDSnet strategy fails in the early stages of severe hypoxemic respiratory failure, the utilization of HFPV presents itself as an attractive option.

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A CASE OF SEVERE DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) SYNDROME COMPLICATING AIRWAY MANAGEMENT

TEE-GUIDED RAPID WEANING FROM PRESSORS IN A POST CARDIAC SURGERY PATIENT WITH AN ISCHEMIC GUT

Asheesh Kumar, Massachussetts General Hospital, Jeremy Goldfarb, Edward Bittner, Massachusetts General Hospital Case Report: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a severe reaction with fever, rash, eosinophilia, and internal organ involvement, occurring weeks after exposure to inciting medications. Severe cases can progress to multi-organ system failure and death. Treatment is largely supportive, with removal of the offending agent.A 65 year-old cirrhotic male was admitted with an esophageal perforation 3 weeks after esophageal variceal banding. He was managed with an empiric course of vancomycin and levofloxacin. Two weeks following, he developed daily fevers to 103° F and a diffuse, pruritic, morbilliform rash. This progressed to near erythrodermatic, with confluent erythema, purpura, and violaceous macules. No oral or mucosal lesions were present. His infectious workup was repeatedly negative. He developed a profound inflammatory response and was transferred to the ICU for hemodynamic instability and intubation. With adequate sedation, three operators were unable to obtain a laryngoscopic view. Fiberoptic examination revealed severe supraglottic edema and grossly distorted glottic structures. The cuff of a difficultly-placed 6.0 endotracheal tube herniated above the vocal cords, unable to be advanced due to tracheal edema. Ultimately, the patient required a 5.0 tube with no cuff leak noted. Over the following 12 hours, the patient rapidly developed multi-organ system failure and severe acidosis refractory to conventional therapy. Despite a leukocytosis of 55x109/L with 10% eosinophils and 21% lymphocytes, antibiotics continued to be held and steroids were initiated. The patient made an equally rapid recovery. Vasopressors were tapered within 24 hours. His rash receded to a mild peripheral exfoliative dermatitis. Laboratory data showed normalization of his acidosis, white blood cell count including the eosinophilia, and liver function tests. He was uneventfully extubated shortly after. We present severe DRESS Syndrome occurring after exposure to antibiotics. While multi-organ system dysfunction is associated with the rash, there have been no previously described cases of DRESS resulting in severe tracheo-laryngeal mucosal involvement.

Jiri Horak, Hospital of the University of Pennsylvania, Frans van Wegenberg, University of Pennsylvia School of Medicine, Scott Roth, Harold Hastings, ImaCor Inc Case Report: A 37-year-old man with a history of hypertension initially presented with a ruptured type A dissection. He underwent aortic valve resuspension, total arch replacement, and replacement of the ascending aorta. Echo on postop day 5 showed normal biventricular function. The patient did well but complained of severe abdominal pain and increasing distress on day 7. Lab work revealed new onset coagulopathy, acute renal failure, hyperkalemia, increased white blood cell count and rising lactate levels. The patient became progressively hypotensive requiring phenylephrine support at 150mg/min and ICU admission. Bedside transthoracic echo (TTE) showed normal biventricular function. CT angiography revealed a flap compromising the superior mesenteric artery (SMA) and celiac artery origins. Emergent thoracic endovascular aortic repair and exploratory laparotomy were performed. The patient required CPR following cardiac arrest in the OR. Exploratory laparotomy revealed only dusky gall bladder and gut. The patient was left open. The patient was hemodynamically unstable at high levels of pressor support. A ClariTEE probe (ImaCor Inc, Uniondale, NY) revealed adequate systolic function, leading the physician to conclude that diastolic dysfunction was the cause of hemodynamic instability. (Cardiac dysfunction after intestinal reperfusion has been described in rats [1].) Pressors were rapidly weaned and fluid administered under TEE monitoring. We were able to confidently wean down pressors because TEE monitoring revealed satisfactory systolic function throughout the process. This was particularly important as excessive pressors in this patient could have caused further gut ischemia, inflammatory mediator release, and further diastolic dysfunction. TEE monitoring in the ICU with a miniaturized probe is a valuable addition for assessing cardiac function. Further studies to evaluate its impact on efficacy and clinical outcomes are warranted. Reference: 1. Horton JW, White DJ, Amer J Physiol 1991; 261:H1164-1170.


937 ROUGHING THE PASSER–SPONTANEOUS ARTERY DISSECTION IN A FOOTBALL PLAYER

938 CAROTID

ACTINOMYCES NEUII-THE UNUSUAL CORYNEFORM THAT CAN BREAK YOUR HEART

Leigh Hunter, Methodist Hospitals of Dallas, Jeff Hirschberg, Maui Memorial Medical Center

Mazen Kreidy, University of Oklahoma Health Sciences Center, Gary Kinasewitz, Oklahoma University Health Sciences Center, Jijo John, University of Oklahoma HSC Pulmonary & Critical Care

Case Report: Although stroke syndromes are relatively common in elderly populations, ischemic stroke in young adults is rare with devastating neurologic consequences. Not only is incidence different between age groups, risk factors and etiologies are also. We present a case of a 20 year old man who suffered an acute ischemic stroke while playing football. Although no obvious head trauma occurred, he became ataxic and collapsed. Upon arrival to the ED, the stroke team was activated, the patient became less responsive, was intubated and transferred to the Critical Care Unit. Physical examination was remarkable for HTN, RLE motor weakness and aphasia. CT of the head did not reveal hemorrhage and MRI demonstrated extensive acute infarction. tPA was administered and CT angiography identified left internal carotid artery dissection with middle cerebral artery thrombus. Anticoagulation was initiated and neurologic deficits resolved prior to discharge. Six months later, repeat imaging showed complete resolution of the carotid dissection and middle cerebral arterial thrombus. Inherited or acquired abnormalities of cerebral vasculature predispose to acute ischemic stroke in the young adult. These may be divided into inflammatory and noninflammatory etiologies with arterial dissection being the most common vascular abnormality in most young adult patient series. Although trauma may be a precipitating event, spontaneous dissection also occurs. Clinical presentation may be non-specific with local symptoms such as headache, neck pain, facial pain, or specific with appropriate neurologic deficits as in our case. We will review pathophysiology, etiologies, risk factors, methods of diagnosis, treatment, complications and outcomes of carotid artery dissection. A review of current literature addressing controversies in treatment will also be presented. Our case demonstrates the importance of immediate activation of the stroke team, consideration of unusual causes for stroke syndromes, and rapid institution of appropriate treatment. It is imperative that critical care physicians be aware of this entity in order that appropriate evaluation is undertaken and therapy is administered.

Case Report: Cardiac troponin I(cTnI) is a protein present in the myocardium, initially studied as a diagnostic and prognostic marker in patients with myocardial infarction(MI).Subsequent studies have shown that elevated cTnI is a prognostic marker for the critically ill.We present a case of severe sepsis secondary to Actinomyces neuii(A.neuii) masquerading as MI.A 50 y old male was admitted with altered mental status.He was hypotensive,tachypneic with cool and mottled extremities.He was intubated, resuscitated and started on pressors.His wbc was 8.6, lactic acid 9.5, and had liver and renal failure.His cTnI was 4.95 initially and 22 four hours later,the EKG showed ST depression in anterolateral leads,the CXR was unremarkable and on TTE his EF was 40% with no wall motion abnormalities.Cardiogenic shock was considered but heart catheterization was deferred as he was on multiple pressors and in multiorgan failure.Medical therapy for a nstemi and broad spectrum antibiotics for possible septic shock were initiated.Shortly after, he developped ventricular tachycardia which was successfully cardioverted, but he clinically deteriorated and died four hours later.The following day his blood grew A. neuii. Elevated cTnI is common in the critically ill and present a diagnostic and therapeutic dilemma.In studies of patients with sepsis, it has been shown that elevated cTnI may be associated with EKG changes suggestive of ischemia in the absence of occlusive coronary artery disease.In 1994, Funke assigned the CDC group 1 coryneform organisms to a new species: A. neuii. It is a facultative anaerobe that can grow rapidly and well under aerobic condition,but can be missed easily if the specie is not identified when a coryneform grows.Unlike Actinomyces israelii ,it does not branch in filaments and doesn’t form sulfur granules.It is isolated as the sole organism more frequently than with a mixed flora, and usually in the settings of a skin abscess,prostatitis,endocarditis,infected atheroma or joint prosthesis. To our knowledge this is the second fatality due to A. neuii. The prognosis is usually favorable as this organism responds well to antimicrobials used for other Gram positive rods.

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TOTAL ABDOMINAL COLECTOMY PERFORMED IN THE INTENSIVE CARE UNIT

AN UNUSUAL CASE OF SEVERE RESPIRATORY FAILURE IN A PREVIOUSLY HEALTHY YOUNG MAN

Lindsay Fairfax, Kent Kercher, Carolinas Medical Center, A. Christmas, FH Sammy Ross Trauma Center, Ronald Sing, Carolinas Medical Center

Oluwole Onadeko, Afshin Sam, University Medical Center, John Bloom, Az Resp Center, Ken Knox, Southern Arizona V.A. Healthcare System

Case Report: A 51 year old male had undergone a laparoscopic nissen fundoplication complicated by an intraoperative perforation of the distal esophagus which was identified the first post-operative day. He was transferred to our hospital in fulminant sepsis with multi-system organ dysfunction: hemodynamics requiring vasopressor support, oliguria, and ARDS (p/f ratio 120). On arrival the patient was taken to the operating room for repair and wide drainage and placed on a broad spectrum antibiotic (pipercillin/tazobactam). Drotrecogin alpha was initiated post-operatively and the patient clinically responded within 24 hours. The patient then developed severe watery diarrhea secondary to Clostridium difficile and intravenous metronidazole was started. Over the next 48 hours the patient clinically deteriorated developing abdominal compartment syndrome (worsening ARDS, oliguria, hypotension, and acidosis) with an abdominal compartment pressure of 28 mmHg. Due to the patient’s hemodynamic instability and extreme mechanical ventilator settings (high frequency oscillation with 100% FiO2) it was felt the patient was too critical to tolerate transport to the operating room. The operating room staff mobilized a laparotomy team (scrub nurse and circulating nurse), equipment, and anesthesiology to the ICU. Rapid abdominal decompression was performed which demonstrated a dilated and inflamed colon consistent with toxic megacolon. The decompression made little improvement in the patient’s clinical status and it was felt the ongoing septic physiology was due to the toxic megacolon. Therefore, a total abdominal colectomy was performed with intestinal staplers. The hemodynamics, oliguria, and ARDS all showed improvement within four hours of surgery. The patient was left in discontinuity as part of the damage control operation and underwent reanastamosis 48 hours later in the operating room once stabilized. This case demonstrates the ability to mobilize hospital resources to perform emergent surgeries in the ICU in patients otherwise too unstable for transport to the operating room.

Introduction: Diffuse alveolar hemorrhage (DAH) can often present diagnostic challenges. We describe a case of pauci-immune pulmonary capillaritis leading to acute respiratory failure in a previously healthy young man. Case Presentation: A 20 year old male presented with 3 weeks of URI symptoms, cough, blood-tinged sputum and severe dyspnea despite antibiotics. He denied any medication use and had no occupational or environmental exposures. He denied family history of connective tissue disease. He was in hypoxemic respiratory failure and required intubation. Chest examination revealed diffuse coarse crackles. Lab data revealed normal wbc and differential, anemia and thrombocytopenia. Renal function was normal. UA showed trace protein without casts. C-rp was markedly elevated. Complements were normal. Broad spectrum anti-microbial, anti-fungal and antiviral therapy was empirically started without improvement. Bronchoscopy revealed normal airway mucosa without active bronchial bleeding, however bronchoalveolar lavage had grossly bloody fluid return in the initial aliquot. Cytology showed acute inflammation and cultures were negative for infectious pathogens. Extensive rheumatologic work up was negative. HIV testing was nonreactive. Surgical lung biopsy showed evidence of acute capillaritis with blood-filled alveolar spaces. High dose corticosteroid therapy was initiated and shortly afterwards, he began to improve. He was eventually discharged to a rehabilitation facility. Discussion: Pulmonary capillaritis is the most common underlying histologic cause of DAH and is usually seen in association with collagen vascular diseases. Isolated pauci-immune pulmonary capillaritis may occur as a small vessel vasculitis limited to the lung. Treatment includes high dose corticosteroids, immunosuppressants and occasionally plasmapharesis. Overall prognosis is more favorable compared with those that have antibody-associated alveolar hemorrhage. Conclusion: Isolated pauci-immune pulmonary capillaritis must remain high on the list of diagnoses causing DAH and severe acute respiratory failure. Prompt recognition and treatment will hasten recovery.


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EXTRA CORPOREAL MEMBRANE OXYGENATION IN THE MANAGEMENT OF TRAUMA PATIENTS WITH SEVERE ARDS

USE OF CONTINUOUS VENO-VENOUS HEMOFILTRATION (CVVHF) TO TREAT REFRACTORY HYPOTENSION IN SEVERE SEPSIS

Abiodun Orija, Louisiana State University Health Sciences Center, Veena Nandwani, Louisiana State University, Laurie Grier, LSU Health Science Center, Keith Scott, Louisiana State University Health Sciences Center, Steven Conrad, Louisiana State University Health Sciences

Introduction: Hypotension is a common presentation and reason for admission to the Intensive Care Unit. The etiology is varied and hence, the severity can range from mild to severe, requiring agents for vasopressor support. Here, we present a case of acute refractory septic shock which necessitated uncommon measures. Case Presentation: A 51-yr old gentleman was brought to our hospital with complaints of altered mental status and shortness of breath for 2 days. After arrival he rapidly decompensated requiring ventilatory support. He was diagnosed to be in severe sepsis and resultant hypotension due to bilateral lower extremity cellulitis and pneumonia and was treated with aggressive fluid resuscitation, intravenous antibiotics and correction of electrolyte imbalances and moderate acidosis. Without any response after these measures, he was started on Phenylephrine infusion which needed titration quickly to the maximum dose due to a lack of response. Second and third agents were added sequentially without any discernible effect. In spite of this, the hypotension was refractory. We then decided to attempt Continuous veno-venous Hemofiltration (CVVHF) to try to remove any possible unidentified toxin or drug that could be contributory. Surprisingly, within a few hours, the blood pressure improved to an extent where we could start weaning down the epinephrine infusion. Within the next day, he was hemodynamically stable to be weaned off all pressor support and was continued on only CVVHF for acute kidney injury. His subsequent recovery was uneventful and he was extubated and was discharged in good disposition. Discussion: This case demonstrates the utility of CVVHF in refractory hypotension unresponsive to pharmacological therapy. CVVHF has been reported before as being useful to remove inflammatory cytokines and other mediators in severe sepsis and improve cardiovascular hemodynamics. Conclusions: CVVHF is potentially a powerful tool in the management of hypotension due to severe sepsis.

Case Reports: Trauma patients with ARDS offer unique challenges. Those that fail conventional & unconventional ventilation have limited additional options. Proning may be impossible due to patient injuries. The use of ECMO has been limited by unidentified brain injuries and anticoagulation. We describe the use of venovenous Extra Corporeal Membranous Oxygenation (vv ECMO) in the management of trauma patients with severe ARDS with head injury successfully treated with a fixed anticoagulation regime. Pt 1: 29 y/o fell suffering occipitoparietal hemorrhage, rib fractures and pulmonary contusions. Day 2 there was clinical deterioration with APACHE II score of 27 and Murray score of 4. Pt failed all interventions and started on vvECMO. After initiation a head CT showed no interval change. Sedation was minimal with dexmedetomidine, ziprasidone & diprivan. He was on ECMO for 10 days and made a full neurologic recovery. Pt 2: 20 y/o thrown from a motor vehicle suffered a liver laceration, pulmonary contusions, pelvic and bilateral femoral fractures. Day 2 there was clinical deterioration due to fat emboli. APACHE II and Murray scores were 35 & 4. He was placed on vvECMO. Sedation was minimal using dexmedetomidine & diprivan. He remained on ECMO for 11 days and had neurological improvement at the time of decannulation. Both patients received heparin boluses of 2,500 units immediately after ECMO cannulation and the ECMO circuit was polypeptide/heparin coated (BIOLINE, Maquet, USA). Heparin was maintained at a dose of 500 units/hr with an activated clotting time between 150-180 sec. Platelets were maintained ⬎100,000/uL. Sedation interruptions were performed every 4 hours for neuro assessment. Neither patient had episodes of bleeding, hemolysis or thrombocytopenia during the ECMO treatment. Both cases illustrate that vvECMO can be successfully performed in the poly trauma patient with head injury using heparin coated circuits & lower anticoagulation regimes. Thus traumatic brain injury or poly-trauma should no longer be considered contraindications to ECMO.

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SADDLE PULMONARY EMBOLISM INDUCED TRANSIENT CARDIAC BALLOONING: THE FIRST CASE

POST-TRANSFUSION PURPURA: A UNIQUE CASE OF THROMBOCYTOPENIA IN THE CRITICALLY ILL SURGICAL PATIENT

Saif Farooq, University of Oklahoma Health Sciences Center, Rahgav Gupta, University of Oklahoma Health Sciences Center., Eva Sawheny, University of Oklahoma Health Sciences Center, Jijo John, University of Oklahoma HSC Pulmonary & Critical Care, Pedro Lozano, University of Oklahoma Health Sciences Center., Gary Kinasewitz, Oklahoma University Health Sciences Center Case Report: We report the first case of massive PE which induced Transient Cardiac Ballooning Syndrome(TCBS).64 yom admitted with dyspnea and presyncope. His BP was 158/118mmHg, pulse126, RR24 and SpO2 89%. Exam showed bilateral wheeze and LE edema.Labs: elevated Trop I-0.31ng/ml,normal CPK 59 U/L and elevated MB 6.9 ng/ml. BNP was 1074;ABGs RA: pH 7.49,PCO2 20.2 mmHg,PO2 53 mmHg and SaO2-91%. ECG showed sinus tachycardia.CXR was clear.IV Heparin was started for ACS but TTE showed normal LV functions,D shaped IVS,RV dilatation/dysfunction with hypercontractile RV apex (McConnell’s sign) suggesting PE.Chest CT angiogram confirmed large saddle embolus.Bilateral LE Doppler ultrasound showed left sided mobile thrombus.Unfortunately he developed recurrent PE with acute SOB. He was taken to MICU for hemodynamic instability and acute hypoxemia. BP-95/65 mmHg;RR 33;pulse 130;SpO2 93% on 50% FiO2.ABGs on 50% FiO2-pH 7.54mmHg;PCO2 18.5 mmHg;PO2 57 mmHg;SaO2 94%. Patient’s exam was remarkable for central&peripheral cyanosis and cold extremities. He was given 100mg of rtPA and his hemodynamics and gas exchange improved. Repeat TTE revealed improved RV dysfunctions but depressed LV functions with EF-30%, mild hypokinesis of mid anteroseptal,anterior,inferior & inferoseptal myocardium with akinesis and hence apparent ballooning of the periapical and apical myocardium.He was taken to Cath lab for IVC filter and left heart catheterization (LHC). On LHC non-obstructive nature of the coronaries was confirmed with apical ballooning pattern of LVgram & 25% EF. Repeat followup TTE after 01 month showed normalization of LV dysfunction and EF with the diagnosis of transient cardiac ballooning syndrome.TCBS can involve any part of heart but mainly LV.Stress has been known to produce TCBS. To our knowledge, this is the first case report of the syndrome associated with massive PE. Based on literature reviewed massive PE and TCBS has many common pathophysiologies,therefore, theoretically,TCBS can be one of the extreme spectrums of cardiac dysfunction due to massive PE. While this is intuitive,it is speculative,and further research in understanding the precise mechanism of the syndrome is ongoing.

Sree Satyapriya, Shiva Birdi, Cleveland Clinic Foundation Introduction: Post-transfusion purpura (PTP) is a rare but potentially misdiagnosed complication in the post-operative course of a critically ill surgical patient. This condition is characterized by an acute, severe immune thrombocytopenia that usually follows transfusion of blood products by approximately week. The incidence is between 1/50,000-100,000 transfusions. 90% of cases occur in female patients with a history of pregnancy or transfusion noted to likely be the source primary immunization, or sensitization. PTP occurs due to allo-immunization against specific glycoproteins located on the platelet surface, most commonly human protein antigens (HPA), which exist in numerous polymorphisms. This leads to the development of platelet-specific alloantibodies following transfusion and for reasons still unclear destruction of autologous platelets. Case Report: A 66 year-old female with a history of multiple abdominal surgeries and resulting infected enterocutaneous fistula underwent an excision of infected mesh and drainage of sub-fascial abscess with segmental enterectomy and primary entero-enterostomy with temporary closure. She required blood as well as platelet transfusions intra-operatively and required post-operative care in the ICU. On post-operative day 6 she developed severe thrombocytopenia with a platelet count of zero without evidence of active bleeding. A series of blood samples revealed an absence of platelet antigen HPA-1a and HPA-2a, both quite rare in the general population, making the diagnosis of PTP likely. No further platelet transfusions were given to the patient. The platelet count gradually improved towards normal range within 4 weeks without further intervention. The patient did not suffer any bleeding complications related to this episode. Conclusion: There is a large differential diagnosis for thrombocytopenia in a critically ill surgical patient, making the diagnose of PTP a difficult task. As demonstrated by this case report, clinical suspicion and prompt diagnosis of PTP followed by restriction of further platelet transfusions can allow for an expeditious recovery for the critically ill surgical patient.


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TRANSAMINITIS DUE TO TRANSIENT HYPERTHYROIDISM OF HYPEREMESIS GRAVIDARUM

SEVERE DIGOXIN CARDIOTOXICITY TREATED WITH DIGOXIN IMMUNE FAB AND PLASMA EXCHANGE

Gilda Diaz-Fuentes, Muhammad Anwer, Archana Sinha, Sindhaghatta Venkatram, Bronx Lebanon Hospital Center

Veena Nandwani, Abiodun Orija, LSU Health Sciences Center, Muralidhar Kondapaneni, University of Louisville, Paul McCarthy, Laurie Grier, L. Keith Scott, LSU Health Sciences Center

Case Report: Transient hyperthyroidism of hyperemesis gravidarum (THHG) occurs in 0.1-0.2% of pregnancies and presents similarly to pathologic hyperthyroidism.We present a rare case of severe transaminitis associated with THHG.20 y/o female,9-weeks pregnant presented with nausea,vomiting and weight loss of 3-weeks duration.No PMH,no heat intolerance,gastrointestinal or constitutional symptoms.Patient was afebrile, BP 104/68mmHg,HR 130 bpm,RR 17/min. She had dry oral mucosa, rest of exam normal with no exopthalamus,lid lag/stare, thyromegaly.Laboratory: potassium 3.1 mEq/L, ALT 1203U/l, AST 361U/l,alkaline phosphatase 177mg/dl,bilirubin 4.8/2.8mg/dl,TSH⬍0.07,T4 24,T3 444,free T4 3.9.Urine,serum toxicology,hepatitis panel and autoimmune work up for liver and thyroid were normal. Abdomino-pelvic ultrasound revealed cholelithiasis and normal pregnancy.Thyroid ultrasound was normal. Diagnosis of THHG was established and her symptoms resolved with fluids,steroids and Bblocker.LFT and TFT normalized. Discussion: In normal pregnancy,thyroidbinding globulins are elevated because of estrogen stimulated synthesis.T3-T4 are elevated,free T3 and T4 are within upper normal limits.Increased free T3 and T4 and decreased TSH is found in pathologic hyperthyroidism and THHG. Distinguishing features of THHG are temporal association with hyperemesis gravidarum(HG),no pre-pregnancy thyroid disease,negative antibody titer,no clinical signs of hyperthyroidism.Mild transaminitis occur in approximately 50% of hospitalized patients with HG.Usually liver tests are in the low hundreds with ALT⬎AST and mild hyperbilirubinemia. The degree of abnormality correlates with the vomiting. Severe transaminitis have been reported with pathological hyperthyroidism.Unique feature of our patient is the association between THHG with very low TSH and high transaminitis.Both the thyroid abnormalities and hyperemesis are related to elevated human chorionic gonadotropin levels.THHG resolves by 18 weeks of pregnancy without sequelae. No treatment is required. Diagnosis and awareness of THHG related abnormal liver and thyroid abnormalities can prevent unnecessary treatment and testing in these patients.

Case Report: We report the use of digoxin immune Fab and plasma exchange to treat a 53 y/o with severe digoxin cardiotoxicity. The patient presented with 2 days of cough, chest pain, exertional dyspnea, abdominal pain, and nausea. She was admitted for COPD exacerbation and atypical chest pain. Initial cardiac enzymes were normal; ECG had nonspecific ST depression in anterior leads. On telemetry, bradycardia, junctional rhythm, SVT, and short runs of v-tach were observed, which prompted serum digoxin level and electrolytes to be checked. Digoxin was 36ng/ml and potassium was 6.4mmol/L. On transfer to ICU, i.v. magnesium, and 26 vials of digoxin immune Fab were administered. Dysrhythmias resolved and the patient remained hemodynamically stable. Subsequent troponin levels were elevated and left heart catheterization (LHC) was scheduled, but 32 hrs after treatment with digoxin immune Fab the patient developed VFIB cardiac arrest. ACLS was administered for 25 minutes until circulatory stability was restored. LHC revealed 30% mid LAD lesion and normal EF but the patient continued to have arrhythmias. Repeat digoxin level 37 hrs after digoxin immune Fab was 20ng/ml. Free digoxin levels are unavailable at our facility. No additional digoxin immune Fab was readily available. Plasma exchange (PE) was performed at 35ml/kg with 5% albumin. Blood flow was 125ml/min and replacement rate was 1100ml/hr with a filtration fraction of 24%. Repeat serum digoxin level 1hr after PE was 10.4ng/ml and the ultrafiltrate level was 13.8. Once available, 5 vials of digoxin immune Fab were given. Rifampicin 600mg was given daily for 4 days to induce cytochromes P450 CYP3A4 and P-glycoprotein, the major proteins involved in the metabolism of digoxin. The patient was extubated and discharged home after a short hospital stay. She suffered no neurologic sequelae or further arrhythmias. Plasma exchange successfully lowers serum digoxin levels as demonstrated by the high filtrate levels. This therapy can be used as adjuvant treatment with digoxin immune Fab in life-threatening digoxin intoxication.

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TOXIC SHOCK SYNDROME DUE TO CA-MRSA IN A HEALTHY PEDIATRIC PATIENT WITHOUT MRSA COLONIZATION IN THE NARES

“MITOCHONDRIAL” THERAPY FOR VALPROATE-INDUCED HYPERAMMONEMIC ENCEPHALOPATHY

Seema Nair, Ronda Oram, Michael Tsifansky, Samantha Rahrig, Advocate Lutheran General Children’s Hospital Case Report: We highlight the importance of maintaining a high index of suspicion for community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) in U.S. children with toxic shock syndrome (TSS), even if their results for nasal carriage are negative.A previously-healthy six-year-old girl presented with a two day history of fever, nausea, and an associated rash after developing a pustule at the site of an insect bite. On examination she was afebrile, hypotensive (88/58), and tachycardic (155), with diffuse erythroderma, non-purulent conjunctivitis, and a skin abscess near her left knee. Her laboratory workup showed elevated transaminase, blood urea nitrogen and creatinine, a mildly prolonged prothrombin time, and a normal white blood cell (WBC) count. Her nasal screen for MRSA via PCR was negative and the gram stain from her debrided pustule showed WBC’s and Gram positive cocci. She required aggressive fluid resuscitation (100 ml/kg) and inotropes (Dopamine up to 10 mcg/kg/min, Dobutamine up to 5 mcg/kg/min). Treatment with clindamycin, vancomycin, and ceftriaxone was initiated while cultures and sensitivities were pending. MRSA was identified from her wound, sensitive to clindamycin and vancomycin, prompting coverage with clindamycin alone on hospital day #3. Inotropes were discontinued by hospital day #2, and she never needed assisted ventilation, renal replacement therapy, or any other support. Her blood cultures remained sterile and she was ultimately discharged home on oral clindamycin on hospital day #4. MRSA has been reported to cause TSS in adults (previously healthy and otherwise) in the U.S. and abroad, and in children outside the U.S., most of whom were not healthy. This, to our knowledge, is the first report of CA-MRSA as a cause of TSS in a previously healthy child in the U.S., and it is especially intriguing with a negative nasal carriage screen for MRSA. With the prevalence of CA-MRSA infections in children on the rise, it is imperative to consider it as a cause of toxic shock syndrome across the U.S., despite a negative screen for nasal carriage, and thereby provide appropriate antibiotic coverage from the time of presentation.


Ashish Arora, Geetika Sachdeva, Jaime Hernandez-Montfort, Baystate Medical Center Case Report: 40 year old gentleman with history of chronic alcoholism and bipolar disorder presented to our emergency department with a 48 hr history of “unwellness and confusion’’ per caregiver. His chronic home medications were haloperidol (2 mg/d), benztropine (1mg/d), valproic acid (VPA) (2 gr/d) and quetiapine (800 mg/d). Vital signs showed: 99 F, HR 150, RR 30, 190/100 mm Hg and GCS of 10 prompted rapid sequence intubation and sedation with propofol. No liver disease stigmata, pupillary abnormalties or focal neurological deficits were noticed on exam. CT scan of the head and urine toxicology were unremarkable. Serum ethanol was undetectable. Laboratory studies were relevant for a VPA level of 117, serum ammonia levels of 187 and a lactate of 10.5 with a high anion gap of 20. Complete blood count, hepatic liver enzymes, bilirrubin, INR and albumin were normal. Renal function was preserved. VPA was held as the patient was started on L-cartinine infusion (100 mg/kg IV in 24 hrs) resulting in successful extubation without further neuralgic deficits, normalization of ammonia and lactate within 24 hours of admission to our ICU. Hyperammonemia in the ICU is not uncommon, however valproate-induced hyperammonemic encephalopathy (VHE) is a rare and potentially life-threatening disease that results from underlying mechanisms independent from hepatic dysfunction in the setting of acute/chronic overdose or chronic therapy. VHE has been mainly related to preexisting or VPA related carnitine and/or urea cycle enzyme deficiencies leading to hyperammonemia. Other factors contributing to VHE not related to hyperammonemia per se include VPA metabolites and hyperlactemia. Administration of exogenous cartinine decreases plasma ammonia levels by enhancing the mitochondrial B-oxidation process and production of acetyl-CoA with subsequent decrease in the inhibition of urea synthesis, and although the clinical benefits in VHE have been reported and shared in our patient, further research needs to define an standarized therapeutic approach.

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REFRACTORY SHOCK SECONDARY TO SEVERE LACTIC ACIDOSIS IN A PATIENT WITH VON GIERKE DISEASE

ACUTE POST OPERATIVE RESPIRATORY FAILURE SECONDARY TO OCCULT PULMONARY ARTERIO-VENOUS MALFORMATION

Luis Diaz, Geisinger Health Care Systems, Svetolik Djurkovic, INOVA Fairfax Case Report: Refractory shock secondary to severe lactic acidosis in a patient with Von Gierke disease. We describe here an adult patient with Von Gierke Disease (VGD) with non-hypoxic severe lactic acidosis who developed refractory shock. A 24 years old female with VGD and morbid obesity was admitted to the ICU for respiratory distress, nausea, vomiting and altered mental status. Her physical exam was unrevealing. Laboratory values showed leukocytosis (WBC 25.9 K/uL), hypokalemia (3.0 meq/uL), hyperuricemia (15.6 mg/dl), severe anion gap metabolic acidosis (pH 6.92, pCO2 10, bicarbonate 2.1, O2 sat 92%, anion gap 48), and lactic acidosis (30.5 mmol/L). She was resuscitated with fluids, glucose, potassium, bicarbonate, and covered with broad-spectrum antibiotics. CT scan of chest, abdomen and pelvis ruled out fluid collections or bowel ischemia. The infectious work up was negative and echocardiogram was normal. Despite aggressive fluid resuscitation, 48 hours after admission developed shock. Vasopressin, norepinephrine, and neosynephrine at maximal doses were added to maintain adequate blood pressure, and required orotracheal intubation. On day 7, lactic acid drop to 10 mmol/L, pressors were gradually weaned and was successfully extubated. Noncompliance with the diet regimen resulted in profound metabolic acidosis. Sepsis, hypoxemia, ischemia, cardiac, liver or renal failure, anemia, or drugs were ruled out as etiology of her clinical presentation. Despite aggressive resuscitation and antibiotic coverage since admitted, the patient developed refractory shock requiring multiple pressors titrated to maximal dose. This could be explained in part by low perivascular pH in metabolic acidosis that decreases the responsiveness to vasoconstrictors, resulting in hypotension. Low pH reduces Ca⫹⫹ influx, inhibits myofilament contractility, and alters receptors on the cell surface, accounting for the attenuation of vasoconstrictor responses. To our knowledge, this is the first report of an adult with VGD presenting with severe lactic acidosis leading to refractory shock. We postulate lactic acidemia subtype B3 as the most likely cause of the refractory shock of this patient.

Joshua Marks, Robert Adamo, Jeffrey McCann, Niels Martin, Thomas Jefferson University Introduction: Pulmonary arterio-venous malformations (AVM) can cause significant right-to-left shunting resulting in uncorrectable hypoxemia. Herein, we present a case of an occult pulmonary AVM causing ventilator dependent respiratory failure in a post-operative patient. After AVM embolization, the patient was weaned from the ventilator. Case Report: A 48 year-old morbidly obese male with no other documented medical history presented with severe abdominal pain out of proportion to physical examination. An abdominal CT angiogram demonstrated a superior mesenteric artery (SMA) embolism. An emergent open SMA thrombectomy was performed. The ischemic intestine was edematous and abdominal wall closure was delayed. On subsequent exploration, a segment of necrotic jejunum was resected. No hypercoagulable condition was identified; however, systemic anticoagulation was initiated post thrombectomy.The patient remained ventilator dependent and required tracheostomy. He was treated for pneumonia and pulmonary hypertension. Periods of significant hypoxic decompensation were treated with non-conventional modes of ventilation and epoprostenol therapy. A CT of the thorax demonstrated a large right lower lobe pulmonary AVM. Pulmonary angiography confirmed a massive right lower lobe AVM with a right-to-left shunt, and the AVM was embolized successfully using a 20mm Amplatzer II vascular plug. Within 24 hours, the patient was weaned from the ventilator.Conclusion:In addition to life-threatening paradoxical embolization, pulmonary AVMs can cause significant right-to-left shunting and resultant severe hypoxemia. Uncorrectable hypoxemia in a ventilated patient should prompt further investigation to exclude pulmonary AVM as an underlying etiology. Embolization should be performed when there is significant hypoxia as well as high risk of paradoxical embolization.

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THROMBOTIC THROMBOCYTOPENIC PURPURA WITH ATYPICAL NEUROIMAGING

USE OF FIBRIN GLUE ADMINISTERED DURING BRONCHOSCOPY TO SEAL A PERSISTENT BRONCHOPLEURAL FISTULA: A CASE REPORT

Satish Chandrashekeran, Mayo Clinic Rochester, Francis Lytle, Mayo Clinic Department of Anesthesiology Introduction: TTP consists of the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurological involvement, renal abnormalities and fever. Etiology is unclear but appears to be related to endothelial cell damage in the microcirculation with resultant platelet-thrombi formation. We present a case of 50 year old woman with traditional clinical features of TTP but previously undescribed MRI findings. Case: A 50 year old woman presented to the ED with bloody diarrhea. A history of ingestion of undercooked hamburger was elicited. She was prescribed ciprofloxacin and metronidazole. She returned 4 days later and was found to be hypotensive, thrombocytopenic (platelet count-55X109/L), anemic (hemoglobin-10.9 gm/dl) and in acute renal failure (creatinine-6.0 mg/ dl). Peripheral smear showed schistocytes. LDH was 2211 U/L. TTP was diagnosed. Neurologically, she had brief tonic clonic seizure activity. She was unresponsive to commands, though she moved all extremities and had normal reflexes. CT was negative and EEG showed only slowing. MRI showed symmetric diffusion signal abnormalities within the thalami, dorsal midbrain and dorsal pons. There was corresponding T2 signal within these locations on the FLAIR study. Plasma exchange and steroids were initiated early. Two weeks later, MRI brain showed substantial resolution. Diffusion weighted imaging was negative. Platelet count improved to 125X109/L. Patient had significant improvement in encephalopathy. Discussion: Neurological features at presentation of TTP include headache, visual disturbances, ataxia, paresis, stroke, aphasia, confusion, seizures, parathesias and coma. Encephalopathy has been reported. In these patients, MRI brain showed features of reversible posterior leukoencephalopathy syndrome (RPLS). RLPS is characterized by neuroimaging findings of reversible vasogenic subcortical edema without infarction, patchy symmetrical bilateral involvement with preferential involvement of the occipital regions.Our patient had symmetric diffusion signal abnormalities within the thalami, dorsal midbrain and dorsal pons. These MRI findings have not been described earlier.

Andrew Faust, Methodist University Hospital, Dept. of Pharmacy, Robert Aguillard, Mid South Pulmonary Specialist, Christopher Finch, Methodist University Hospital Purpose: To report a case of fibrin glue administered during bronchoscopy to treat a persistent pneumothorax with bronchopleural fistula. Summary: A 60year old African American female was admitted for worsening shortness of breath and left sided chest pain. Her past medical history included bullous lung disease of unknown etiology and three prior admissions for pneumothoraces requiring chest tube placement. In the past year and a half, she twice underwent videoassisted thoracoscopic surgey (VATS) with pleurodesis and lobectomies. On this admission, the patient underwent a third VATS with left lung decortication and pleurodesis. During the procedure, a large brochopleural fistula (BPF) was located and closure was attempted with an intercostal muscle flap. Over the next 16 days, the patient’s chest tube was placed on suction without resolution of the air leak. On hospital day 21, a bronchoscopy was performed. A Swan-Ganz catheter was passed through the lumen of the bronchoscope and the site of the BPF was located by serially entering bronchi with an inflated balloon until bubbling ceased in her chest drainage system. Ten milliliters of fibrin glue was administered to the superior segment of the left lower lobe via the Swan-Ganz catheter. Over the next three hospital days, the patient’s air leak lessened; however, was not completely resolved. On hospital day 25, the patient underwent another bronchoscopy and another 10 milliliters of fibrin glue was applied to the site of the BPF, distal to the previous application. On hospital day 28, the patient was transferred to an extended care hospital, her chest tube on waterseal with an intermittent air leak. Her air leak was completely resolved by hospital day 37 and her chest tube was removed on hospital day 39. The patient was discharged home after a 43 day hospitalization. Conclusion: Fibrin glue administered via a Swan-Ganz catheter during bronchoscopy was safe and effective in the treatment of a persistent BPF. Despite the persistence of the pneumothorax after administration of the fibrin glue, this procedure likely reduced length of stay and need for further intervention.


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STRESS-INDUCED CARDIOMYOPATHY SECONDARY TO PHENCYCLIDINE OVERDOSE

NONTRAUMATIC EPIDURAL HEMATOMA RESULTING IN PARAPLEGIA IN A TEENAGE BOY WITH CHOLESTASIS

Kishan Ramachandran, Prashant Gundre, Robbert Crusio, Kavan Ramachandran, Yizhak Kupfer, Chanaka Seneviratne, Sidney Tessler, Maimonides Medical Center

Sule Doymaz, Mayer Sagy, James Schneider, Cohen’s Children Medical Center, North Shore LIJ MC, New Hyde Park, NY

Introduction: Phencyclidine (PCP) intoxication leads to adrenergic and hallucinogenic toxidrome with severe sympathetic stimulation. We report a case of stress induced cardiomyopathy (SIC)due to a PCP overdose. Case Report: A 25 year old male with no medical history was brought to the ED after being found unresponsive at a friend’s house. Physical examination showed a confused, diaphoretic, male with a blood pressure of 80/60 mmHg, a pulse 120 bpm and labored breathing. System exam was normal except for generalized rales in both lung fields. The EKG upon arrival showed ST segment elevation in leads V1-V3 and AVL. Urine toxicology showed evidence of phencyclidine and methadone ingestion. The patient required mechanical ventilation for 3 days due to acute pulmonary edema. Admission troponin I was greater than 50 ng/mL. IV lorazepam was titrated to abolish patient agitation and sympathetic stimulation. STEMI was managed conservatively with ␤-blockade, statins, and aspirin. Echocardiogram performed on day 1 revealed apical and septal hypokinesis with an ejection fraction of 35%. The EKG changes resolved within 24 hours after the initiation of mechanical ventilation. He refused cardiac catheterization. Repeat echocardiogram in 1 month revealed normal wall motions and improved ejection fraction of 55%. Discussion: SIC is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle. To our knowledge, this is the first reported case of PCP induced SIC. The etiology of STEMI and the corresponding EKG changes were likely secondary to PCP intoxication and resultant sympathetic surge that resolved completely. The evolution of the echocardiogram from an EF of 35% to near normal supports the diagnosis of SIC. Treatment for SIC is largely supportive. In our patient benzodiazepine administration was crucial for control of agitation and prevention of further sympathetic discharge. Conclusion: PCP can cause SIC. SIC should be considered as one of the potential complications caused by sympathetic stimulation.

Case Report: We present a case of epidural hematoma in a teenage boy with hyperbilirubinemia due to cholestasis and associated coagulopathy.This is a 15 yr old male with history of cholestasis due to an unknown cause who presented to ER with acute onset of severe neck pain and inability to move his upper and lower extremities without any history of trauma. The subject also had progressive back pain, treated with ibuprofen 400 mg tablets twice. One day prior, he had epistaxis lasting for 10 hours. In the ER, physical examination showed: scleral icterus bilaterally, marked jaundice throughout his body, palpable liver 2 cm below right costal margin , intact cranial nerves, absent deep tendon reflexes bilaterally at lower extremities, absent rectal tone, decrease sensation of upper and lower extremities bilaterally. Initial laboratory results revealed: hemoglobin: 5.5g/dL, hematocrit: 17.5, prothrombin time: 125 seconds, INR: 9.2, activated partial thromboplastin time: 126 seconds, fibrinogen: 396 mg/dL, total bilirubin : 11.2, direct bilirubin: 8.05md/dL, alkaline phosphatase: 276u/L, aspartate aminotransferase: 34u/L, alanine aminotransferase: 16u/L. MRI of the cervical and thoracic spine showed spinal cord compression from C1 to T2 secondary to an epidural fluid collection with abnormal signal involving the spinal cord consistent with spinal cord edema or infarct. Patient received packed red blood cell and fresh frozen plasma transfusions. Neurosurgery was consulted and the patient was immediately transferred to the operating room for cervical laminectomy and evacuation of the fluid collection, which was identified as an epidural hematoma. Post-operatively, the patient remained paraplegic requiring long term rehabilitation.To our knowledge, this is the first case reported in the literature of epidural hematoma culminating in paraplegia where coagulopathy was induced by cholestasis. Though, many other factors are cited as the causes of coagulopathy and epidural hematoma, no report presented in association with cholestasis. Thus, one should consider cholestasis associated coagulopathy among the factors which might cause important hemorrhages in occult locations.

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PR3-ANCA-ASSOCIATED MICROSCOPIC POLYANGITIS IN A PATIENT WITH SEPSIS

THIAMINE DEFICIENCY AS AN ISOLATED CAUSE OF SEVERE LACTIC ACIDOSIS

Takeshi Wada, Nippon Medical School, Mineji Hayakawa, Hokkaido University Graduate School of Medicine, Satoshi Gando, Hokkaido University Hospital

Kristoffer Neu, Deborah Light, Hung Nguyen, Albany Medical Center

Case Report: A 68-year-old male associated with sepsis caused by otitis media developed both acute respiratory failure and acute kidney disease. He initially received treatments with a ventilator and renal replacement therapy at our intensive care unit. We immediately performed atticoantrotomy and started to administer Teicoplanin and Voliconazole due to the identification of methicillin-resistant Staphylococcus aureus, Candida albicans and Candida parapsirosis based on a culture of pus from the auris media. He gradually developed symptoms of bloody sputum and hematuria. The systemic inflammatory responses thereafter become prolonged, and his general condition deteriorated in spite of administering appropriate treatments with antibiotics and a source control for the infectious focus. An enhanced CT scan which was performed in order to identify any new infectious foci showed the presence of a renal pseudo aneurysm. In addition, we also identified an alveolar hemorrhage by a bronchoscopic examination. Based on the CT scan findings and the bronchoscopic examination, as well as due to the high level of PR3-ANCA and his clinical features, we finally made a diagnosis of PR3-ANCA-associated polyangitis. Combined treatment with steroid pulse therapy and plasma exchange eventually improved his general condition. It is well known that microscopic polyangitis sometimes occurs in patients with sepsis. The diagnosis of this disease was both difficult and delayed because the normal signs and symptoms of the disease had been modified due to the presence of sepsis. Microscopic polyangitis with an alveolar hemorrhage is associated with a significant mortality rate, namely as high as 30%. However, a prompt diagnosis and appropriate therapy, for example steroid pulse therapy and plasma exchange (PE), can make it possible for some cases to obtain a good outcome. Recently, some reports have described the effectiveness of PE for the ANCA-associated polyangitis with alveolar hemorrhage. All intensivists, who often treat cases presenting with respiratory failure and renal failure, should therefore pay particular attention to the clinical features of ANCA-associated polyangitis.


Introduction: Thiamine deficiency is known to cause neurological disturbances, beri-beri, and rarely, lactic acidosis. We present a case of severe lactic acidosis secondary to thiamine deficiency in a patient with no other contributing comorbidities. Case: A 54 year old female with a history of alcohol abuse, Wernicke’s encephalopathy, and type II diabetes, presented with confusion and poor p.o. intake for several days. Laboratory studies revealed a glucose of 629, sodium 133, potassium 2.8, bicarbonate 8, an anion gap of 30, and normal liver function. ABG on admission showed a pH of 7.48, pCO2 16, and pO2 151, consistent with a mixed acid-base disturbance of respiratory alkalosis and metabolic acidosis. The patient was never noted to be hypotensive. Salicylates and toxicology results were negative, as well as DKA work up. Serum lactate was found to be significantly elevated at 17.1 mmol/L. CT of the chest, abdomen and pelvis was negative for any evidence of ischemic bowel or malignancy. Her lactic acidosis was thought to be secondary to thiamine deficiency. She was treated with IV thiamine and within 3 hours, the serum lactate was down to 7.8 mmol/L; and within 20 hours it was back to 2.0 mmol/L. Discussion: Wernicke’s encephalopathy has a distinctive acid-base pattern which has been previously reported and was present in our patient. Thiamine is a precursor to thiamine-pyrophosphate, a cofactor in the pyruvate dehydrogenase complex. This enzyme complex is essential in the conversion of pyruvate to acetyl Co-A and subsequent entry into the Krebs cycle. In thiamine deficiency, it has been suggested that there is an accumulation of pyruvate which is converted to lactate. Lactic Acidosis has been reported in patients on TPN without thiamine supplementation and patients with underlying malignancy. Our case is unique, in that it demonstrates a rapidly reversible lactic acidosis after thiamine administration in the absence of other potential causes. Conclusion: Thiamine deficiency is well known to be a causative factor in Wernicke’s encephalopathy. This case illustrates the importance of considering thiamine deficiency as a potential cause of lactic acidosis.

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IDIOPATHIC ACUTE SEVERE HYPERCALCEMIA ASSOCIATED WITH PANCREATITIS AND INTRA-UTERINE FETAL DEMISE IN LATE PREGNANCY

USE OF COMBINED TOPICAL APPLICATION AND INTRAVENOUS INFUSION OF AMINOCAPROIC ACID TO STOP SEVERE REFRACTORY BLEEDING IN A PATIENT WITH END STAGE LIVER DISEASE

Asma Siddiqui, Geisinger Medical Center, Omar Rahman, Geisinger Health System, Mitchell Craft, Mary Reed, Geisinger Medical Center Case Report: Acute pancreatitis is unusual in pregnancy and is associated with cholelithiasis & hypertriglyceridemia. Hypercalcemia from primary hyperparathyroidism causing pancreatitis is rare. Milk Alkali & Vit D toxicity syndromes can cause hypercalcemia in pregnancy.We present a case of a pregnant patient with acute idiopathic hypercalcemia associated with severe pancreatitis. Presentation: 38 y/o 32 week pregnant patient with gestational diabetes presented with vomiting, abdominal pain, hyperglycemia and ketoacidosis. She was placed on mechanical ventilation. Fetal heart tones were intact prior to transfer to our institution. On arrival she had elevated serum lipase and amylase. Fetal evaluation now showed fetal demise. She had markedly elevated total (11 to 14.5 m/dl) & ionized calcium (iCa2) levels (1.85 to 2.45 mmol/L). CT scan showed edematous and inflamed pancreas. PTH level was low at 5 pg/ml (normal 15-65 pg/ml). PTH-related protein (PTHrp) and 25 hydroxy vitamin D levels were normal.She received aggressive intravenous fluid hydration but iCa2 levels continued to rise. Ketoacidosis resolved with treatment. She was treated with IV calcitonin and palmidronate with iCa2 levels returning to normal in 72 hours. Fetus was also evacuated by induction with oxytocin. Clinical improvement corresponded to normalizing calcium levels and she was discharged home on day 9. Fetal autopsy demonstrated recent death without any bone destruction. Discussion: Pancreatitis and ketoacidosis probably led to fetal death. Etiology of hypercalcemia remained obscure. She had no findings to suggest a cause for hypercalcemia that probably led to pancreatitis. PTHrp elevation (placenta or mammary source) has been demonstrated without malignancy in pregnancy but was absent in this case. Primary hyperparathyroidism was absent. Fetal demise causing maternal hypercalcemia due to impaired PTH, calcitonin and calcium homeostasis or bone resorption is not described in humans. In this case, fetal death was acute and hypercalcemia seemed to precede that event. To our knowledge this is the first case of severe idiopathic hypercalcemia manifesting in association with pancreatitis in pregnancy.

Thomas Johnson, Avera Mckennan Hospital Pharmacy Dept, Rina Awan, Avera McKennan Hospital, R. Auvenshine, Avera McKennan Transplant Institute Case Reports: Aminocaproic acid has been reported as a topical solution to minimize bleeding with tooth extraction in patients on warfarin. We report the combined use of topical and IV aminocaproic acid (ACA) in a patient with multiple teeth extraction and refractory bleeding due to end stage liver disease (ESLD).A 39 year old male, Ht 72 inches, Wt 63 kg, with ESLD was accepted for liver transplant and was admitted for complete teeth extraction due to extremely poor dentition and associated risks with liver transplant. On the day of surgery, his INR was 2.3 and platelets 48 K/uL. He was transfused with several units of FFP and platelets after which his INR was 1.7 and plts 64 K/uL. On postoperative day #1, he developed significant bleeding from the gums associated with a marked decrease in his hemoglobin to 6.2 mg/dL. He received 6 units of packed red blood cells (PRBCs), 9 units FFP, 10 mg IV Vitamin K despite which he continued to ooze from the gums. He was intubated for airway protection and sterile packings were used in his mouth. On post-operative day #2, his INR remained elevated at 1.7, he continued to receive FFP, PLTs and PRBCs and also received DDAVP 25 mcg IV x1 and rFVIIa 1 mg x2 (30 minutes apart) to an INR of 0.9 with no hemostasis and hemodynamic instability. Previous packing was removed and sterile gauze soaked in ACA 5 gm in 100 ml of normal saline was then used to pack the patient’s mouth. The patient was concurrently initiated on ACA 5 gm IV over one hour followed by 1 gram per hour IV infusion for the next 20 hours. Bleeding slowed then stopped soon after initiation of the packing and IV infusion. The patient required 1 additional unit of PRBCs. His hemoglobin stabilized at 8.9 mg/dL and he was safely transferred to his assigned liver transplant center where the packing was removed and he had no further significant bleeding from his gums.While the use of ACA for stabilization of clots and tooth extraction is well described with warfarin therapy, the use of combined topical and IV use in ESLD for gum bleeding is not well described to our knowledge. In this case, use of ACA resulted in hemostasis after other hemostatic agents failed.

959

960

IMPACT OF DEXMEDETOMIDINE ON THE DURATION OF MECHANICAL VENTILATION, LENGTH OF HOSPITAL STAY, AND DURATION OF ICU STAY IN ETHANOL POSITIVE TRAUMA PATIENTS

LINEZOLID TREATMENT FAILURE IN A MORBIDLY OBESE PATIENT WITH METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS PNEUMONIA

Theologia Ternas, Long Island University , Audis Bethea, Charleston Area Medical Center Case Reports: Traditionally, the management of ethanol related adverse effects requires high doses of benzodiazepines.Administration of benzodiazepines (BZD) may cause accumulation, over sedation, and unpredictable awakening in intubated patients. Dexmedetomidine (DEX) has sedative and analgesic properties and has been shown to facilitate the withdrawal of mechanical ventilation when compared to BZD. To date, this is the first case series to report data in trauma patients with DEX administration and previous ethanol exposure. This is a retrospective series of surgical/trauma intensive care patients with positive blood alcohol levels who were placed on DEX at Charleston Area Medical Center from January 1, 2007 to August 15, 2009. Patients who were intubated for at least 24 hours, failed a previous attempt at weaning sedation and analgesia, and received DEX for ⬎24 hours during the designated time period were included in the series. The following data were collected before and after the initiation of DEX: duration of mechanical ventilation (MV), narcotic and BZD exposure. Ten patients met criteria for inclusion in the analysis. Included patients were mechanically ventilated for a mean of 6.02 (1.74 – 12.60, SD 3.73) and 6.61 (2.04 – 17, SD 5.13) days prior to and after the initiation of DEX (p⫽0.79). Patients required more hydromorphone (2.48mg/d vs 6.75mg/d, p⫽0.05), oxycodone (20.5mg/d vs 64.9 mg/d, p⫽0.07), and lorazepam (12.79mg/d vs 16.06mg/d, p⫽0.38) after the initiation of DEX. Conversely, patients required less fentanyl (2.98mg/d vs 2.49mg/d, p⫽ 0.63), morphine (0.42mg/d vs 0.29mg/d, p⫽0.80), and midazolam (16.98mg/d vs 12.92mg/d, p⫽0.17).Duration of mechanical ventilation was consistent prior to and following the initiation of DEX. Sedative and analgesic exposure was inconsistent following the addition of DEX as utilization of select agents decreased while others increased. It was anticipated that DEX would have consistently ameliorated sedative and analgesic requirements; this was not consistently seen and it cannot be concluded that DEX provided a drug-sparing effect.

Katie Muzevich, Virginia Commonwealth University Health System, Jonathan Fields, Walgreen’s Pharmacy, Kimberly Lee, Virginia Commonwealth University Health System Case Report: A 34-year-old morbidly obese male (265 kg) with altered mental status was admitted for respiratory failure requiring emergent intubation and treatment of community-acquired pneumonia (CAP). Admission respiratory cultures revealed Staphylcoccus aureus. Vancomycin 2500 mg (9.4 mg/kg) every 12 hours was given empirically (peak⫽27 mcg/mL, trough⫽13.9 mcg/mL). The isolate was methicillin-resistant and sensitive only to vancomycin (minimum inhibitory concentration 1 mcg/mL) and sulfamethoxazole/trimethoprim. Linezolid 600 mg administered twice daily via nasogastric tube was initiated in place of vancomycin due to concern that subtherapeutic vancomycin concentrations, potentially associated with obesity and variable renal function, were contributing to poor clinical response. After 48-hours of linzeolid monotherapy, the patient was febrile with continued leukocytosis, worsening hypoxemia, and a persistently-positive MRSA culture. Vancomycin was added back, and the patient showed quick clinical improvement (afebrile, extubated on day 9). He received 15 days of combination therapy.Steady-state linezolid peak and trough serum concentrations were 4.13 mcg/mL (12-26 mcg/mL) and 1.27 mcg/mL (2-9 mcg/mL) respectively. Linezolid levels are a send-out lab so results were not used for therapeutic intervention. Limited data on linezolid dosing in the morbidly obese shows serum drug levels less than those in non-obese patients, but no clinical failure has occurred when treating MRSA skin and soft tissue infections. To date, this is the first report of linezolid clinical and microbiologic failure when treating MRSA pneumonia in a morbidly obese patient.


961

962

AIRWAY OBSTRUCTION DUE TO MASSIVE FIBRIN CLOT

AN UNUSUAL CASE OF LACTIC ACIDOSIS

Mitchell Craft, Michael Ayers, Geisinger Medical Center, Svetolik Djurkovic, INOVA Fairfax

Afshin Sam, Oluwole Onadeko, University Medical Center, Laura Meinke, Arizona Health Sciences Center

Background: Airway obstruction is frequently encountered in the intensive care unit (ICU), and has a wide spectrum of etiologies and clinical significance. We present an unusual case of fatal airway obstruction due to a fibrin clot. Case: A 31 year old male with M1 Acute Myeloid Leukemia underwent induction, then consolidation chemotherapy. After his fourth cycle of chemotherapy, he was admitted to the Hematology service with febrile neutropenia. Blood cultures quickly grew gram negative rods. His clinical condition deteriorated rapidly despite antimicrobials, and he was transferred to the ICU, intubated and mechanical ventilated. Refractory hypoxia and elevated airway pressures ensued despite various modes of ventilation. Airway obstruction was suspected. Bronchoscopy revealed a large, gelatinous mass at the distal trachea, extending beyond both main stem bronchi. The mass was biopsied but complete extraction of the mass with forceps and suction was unsuccessful due to its friability. Prior to repeat bronchoscopy by an interventional bronchoscopist, the patient’s hypoxia worsened and cardiac arrest ensued. Autopsy revealed diffuse alveolar damage and extensive intra-alveolar hemorrhage. The mass was determined to be a fibrin clot, nearly devoid of red cells. It was dissected out as a contiguous airway cast from the main carina to the “smallest observable bronchiole.” Discussion: Intensivists are commonly confronted by endobronchial obstructions and their ramifications. The etiologies are protean and often due to blood clots, mucous plugs, or airway masses. Suctioning, mechanical removal, or advanced interventional techniques result in relief of airway obstruction in the vast majority of cases. This case was unique in that the airway obstruction was due to a dense fibrin clot without admixed blood. We are unaware of any previously reported cases of fibrin alone resulting in airway casts and airway obstruction. Conclusion: Clinicians must remain vigilant for endobronchial obstructions. In the appropriate clinical setting, fibrin clot ought to be in the differential. Further experience will be required to determine specific management strategies.

Introduction: Hemophagocytic Lymphohistiocytosis (HLH) is a known but rare presentation of Epstein Bar Virus (EBV) infection. We report an adult case of HLH complicated by severe lactic acidosis. Case Presentation: A 35 year old man was evaluated for a persistent fever and pancytopenia. He had been treated with broad spectrum antibiotics.He reported one month of fever, constitutional symptoms and mild abdominal pain. His exam was remarkable for high grade fever, tachypnea, tachycardia and mild right upper quadrant tenderness. Immunologic studies were unremarkable, and all cultures were negative. Virologic studies showed a positive EBV IgG titer and a high quantitative EBV PCR. CT revealed hepatosplenomegaly. Bone marrow biopsy was suggestive of HLH.He was found to have an increasing elevation in serum lactate levels. He was neither hypoxemic nor hypotensive, and no infection was identified. Simultaneous lactate (9.2 mmol/L) and pyruvate levels (0.41mmol/L - normal range 0.03-0.1 mmol/L) were obtained.He was started on etoposide and dexamethasone for HLH, as well as thiamine replacement, and lactate levels dropped. Shortly after initiation of chemotherapy, the patient developed alveolar hemorrhage and acute respiratory failure. His condition did not improve with high dose steroids and best supportive care. He eventually died. Discussion: HLH is a hyperinflammatory condition caused by activated, morphologically benign macrophages. Leading triggers in adults appear to be viral infections such as EBV and CMV.Two types of lactic acidosis (LA) are described and seen in clinical practice. Type B LA has been reported as a rare and often lethal complication of hematologic malignancies. Renal replacement therapy and bicarbonate infusion have been used to treat type B LA, but the mainstay of therapy remains treatment of the underlying disease. Chemotherapy with etoposide and stem cell transplantation has been reported as potentially curative in HLH. Conclusion: Type B LA should be considered in the differential when there is no evidence of tissue hypoxemia. There are no reported cases of lactic acidosis due to HLH in the current body of literature.

963

964

PERI-ENGRAFTMENT RESPIRATORY DISTRESS SYNDROME WITH ATYPICAL FEATURES

HYPERCAPNIC RESPIRATORY FAILURE IN A PATIENT WITH AUTOIMMUNE INFLAMMATORY MYOPATHY

Satish Chandrashekeran, Mayo Clinic Rochester, Francis Lytle, Mayo Clinic Department of Anesthesiology

Sindhaghatta Venkatram, Muhammad Anwer, Ahmed Elwan, Dhyanesh Pandya, Bronx Lebanon Hospital Center, Karen Weidenheim, Montefiore Hospital, Giovanni Franchin, Gilda Diaz-Fuentes, Bronx Lebanon Hospital Center

Introduction: Engraftment period is the time of neutrophil recovery following stem cell transplant (absolute neutrophil count ⬎0.5 X 109/L on 2 or more consecutive days). The constellation of skin rash, fever, diarrhea and capillary leak is called the engraftment syndrome. Acute lung injury that occurs during this period is known as the Peri-engraftment Respiratory Distress Syndrome (PERDS). We describe a case of PERDS that manifested prior to improved WBC counts and showed an atypical response to steroids. Case: A 51-year-old man presented with neutropenic fever 10 days after autologous peripheral blood stem cell transplant for multiple myeloma. He developed respiratory failure requiring intubation and mechanical ventilation. CT was negative for pulmonary embolism or obvious lung infiltrate. WBC count was 0.1X109/L. Broad spectrum antimicrobials were started. On day 12, he developed an erythematous rash on his face, neck, trunk, worsening anasarca and diarrhea. PERDS was suspected and methylprednisolone was started at 1 gm IV daily. Urine, blood and BAL cultures were negative. Antimicrobials were stopped. WBC count increased to 0.8 X 10 9 /L on day 15. The patient made slow progress and was extubated 10 days later. Discussion: PERDS occurs in about 4% of stem cell transplants. The differential diagnosis includes bacterial,viral and fungal pneumonia, ARDS, sepsis, diffuse alveolar hemorrhage, idiopathic pneumonia syndrome and cryptogenic organizing pneumonia. Fever and hypotension in PERDS are due to the massive release of cytokines - “the cytokine storm. High dose steroid therapy, 1 to 2 g/day for 3 days followed by rapid taper is the accepted treatment. Our case presents several points of interest. In the literature, the median WBC count described at the onset of symptoms is 1.3X109/L. The WBC count in our patient was much lower. Tissue infiltration with recovering leukocytes may occur before they are seen in the peripheral blood. Therefore, clinical features may precede the rise in WBC count. The response to steroids was not as rapid as expected. Majority of patients show clinical improvement within 24 hours and recover with 2-4 days of initiation of steroids.


Introduction: Respiratory complications are common in patients with Polymyositis-Dermatomyositis (PM-DM).Steroid therapy remains treatment but can cause steroid myopathy.We present a diagnostic dilemma of hypercapnic respiratory failure in the setting of PM-DM on steroid therapy. Case Report: 50 y/o female presented to ER with lethargy for three days.She had history of PM-DM with frequent flares requiring prednisone.On exam patient was lethargic,tachypnic with shallow breathing,muscle strength of 3/5 proximally and 4/5 distally.Patient had red-violacious rash on her cheeks.There was no arthritis or muscle tenderness.Remaining physical exam was normal.ABG revealed acute on chronic respiratory failure.CPK, Aldolase and toxicology screen were unremarkable.Auto immune work up was negative.CXR and HRCT revealed low lung volumes and elevated diaphragms.PFT’s revealed vital capacity of 0.5 L and 1.4 L in supine and sitting position suggesting bilateral diagrammatic weakness.Muscle biopsy was non diagnostic. EMG suggested of steroid induced myopathy.Steroids were decreased which resulted in clinical improvement. Discussion: Impaired ventilatory mechanics due to inspiratory muscle weakness is suspected in DM/PM patients without pulmonary parenchymal involvement. Respiratory muscle dysfunction has been reported in up to 1/3 of patients but frank respiratory insufficiency occurs in 5% of patients. The consequences of inspiratory muscle weakness include alveolar hypoventilation, impaired cough, atelectasis and rarely hypercapnicrespiratory failure. Treatment for this group of patients is chronic steroid therapy;which can result in steroid myopathy. Steroid myopathy presents with proximal muscle weakness and is clinically indistinguishable from the weakness of PM-DM.Muscle biopsy is usually diagnostic. In cases with non-diagnostic biopsies, EMG findings of decreased recruitment and interference in proximal muscle without any evidence of degeneration are suggestive of steroid induced myopathy.Our case is unique in that the patient had inspiratory muscle weakness out of proportion to the rest of her muscle weakness, which have not been described in either steroid myopathy or PM-DM.

965

966

IMMEDIATE RECHALLENGE WITH CROFAB (ANTIVENIN) AFTER SEVERE ANAPHYLAXIS

A CASE REPORT OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Thomas Johnson, Avera Mckennan Hospital Pharmacy Dept, Michael Heisler, Sanford School of Medicine - The University of South Dakota

Roopika Reddy, University of Utah Medical Center, Ellie Hirshberg, University of UtahIntermountail Medical Center

Case Report: CroFab antivenin is the antidote for crotalid snakebites (rattlesnakes). We report a case of immediate severe anaphylaxis to CroFab administration and subsequent rechallenge with the medication in a patient with a rattlesnake bite. A 36 year old female, 65 inches, 69 kg was bitten in the left leg by a rattlesnake. She was transported to the nearest medical facility and antivenin was administered based on standard dosing. The patient developed severe anaphylaxis during the infusion of the first bottle of antivenin resulting in hypotension requiring vasopressors, severe facial swelling, and laryngospasm severe enough to require emergent cricothyroidotomy. The patient was then flown to our facility and received the remainder of the initial dose of 6 grams antivenin enroute.At the time of arrival in our ICU, the patient’s labs were as follows: platelets 7 K/uL, aPTT 34 secs, fibrinogen 179 mg/dL, D-dimer ⬎20,000ngFEU/ml. Laboratory abnormalities combined with poor appearance of the lower left leg necessitated repeat administration of antivenin. The patient was pre-medicated with 50 mg diphenhydramine, 40 mg famotidine, 100 mg methylprednisolone 30 minutes prior to rechallenge with antivenin. IV epinephrine was available at the bedside. Antivenin 6 grams in 1 liter of NS was started at 10 ml/hr and the rate doubled every 10 minutes to an infusion rate of 250 ml/hr. The patient was observed for signs of intolerance, and appeared to have increased facial edema 1 hour into the infusion, although blood pressure and airway pressures remained unchanged. Epinephrine was then initiated at 1 mcg/min continuous infusion and stopped 3 hours after antivenin was completed. Coagulation parameters 6 hours after the antivenin infusion were plts 214 K/uL, aPTT 29 secs, fibrinogen 220 mg/dL, D-dimer 5,690ngFEU/ml. The appearance of the affected limb had also improved. The patient continued to improve and was discharged from the hospital 7 days later. This case describes a severe case of anaphylaxis from antivenin that required significant medical support and the management of re-challenge with antivenin.

Case Report: A 34yr old man with history of urethral stricture presented to an emergency department (ED) with fever and back pain and was treated with antibiotics for urinary tract infection. The following day he again presented to the ED where CT scan of abdomen/pelvis was done which was normal. Despite antibiotics, the patient’s symptoms progressed over 24 hrs to include headache and neck stiffness. He was admitted for further workup. Laboratory values included a negative lumbar puncture, pancytopenia, bilirubin 3.8mg/dl, INR 3.0, AST 627 u/l and ALT of 407 u/l. The patient deteriorated and transferred to Intermountain Medical Center for further evaluation. On arrival he was intubated with refractory hypotension on vasopressors. His course was complicated by renal failure and metabolic acidosis with lactate level of 10.8 that was treated with renal replacement therapy. AST increased to 5401, ALT to 1790 u/l, his ferritin was 122784, ammonia of 38, and fibrinogen was 102. Amylase, lipase, tylenol, salicyates and alcohol levels were normal. The patient’s hepatitis panel, EBV, CMV and HSV serology were negative. The antinuclear antibodies, serum copper, iron and alpha 1 antitrypsin level was normal. Further testing included a bone marrow biopsy which showed hemophagocytosis with no evidence of malignancy or immature cells. An interleukin 2 level was drawn to confirm the diagnosis and the patient was subsequently started on steroids, intraveous Immunoglobulin and chemotherapy which included etoposide and cyclosporine. The hospital course was further complicated by persistent ARDS, fungemia, clostridium difficile colitis, disseminated intravascular coagulation, ischemia of the toes and scrotum, seizures, and esophageal necrosis communicating with the mediastinum which was unrepairable and the family elected to withdraw support. Conclusion: HLH is rare in adults. The disease can turn fatal if early diagnosis is not made. As the disease mimics several other conditions, high index of suspicion is needed to make the diagnosis. Prompt treatment by following HLH-94 protocol has shown an overall survival in pediatric patients of 55% at a median follow-up of 3.1 years.

967

968

PULMONARY KAPOSI’S SARCOMA PRESENTING AS FULMINANT RESPIRATORY FAILURE AND DIFFUSE ALVEOLAR HEMORRHAGE

MANAGEMENT OF PERIOPERATIVE DISSEMINATED INTRAVASCULAR COAGULATION (DIC) IN KLIPPELTRENAUNAY SYNDROME: A MULTIDISCIPLINARY TEAM APPROACH

Gerald Tarirah, State University of New York Downstate Medical Center Case Report: 40 yr old man without known past medical history, HIV negative 4 yrs prior, presented with increasing dyspnea, chest pain and hemoptysis. Also noted to have weight loss and skin lesions (multiple violet tinted raised lesions) of 3 months duration . In the ER, intubated for severe hypoxemic respiratory failure, noted to be febrile and hypotensive requiring pressors. The CXR showed diffuse bilateral alveolar opacities. Managed for presumed community acquired and pneumocystis pneumonia/ hemoptysis. ARDS treated initially with low tidal volume strategy and subsequently APRV. Patient remained in refractory shock and developed multi-organ failure and expired within 24 hours of hospital admission. Autopsy showed diffuse spindle cell proliferation around vessels and bronchial wall (numerous RBC) wiith consistent with Kaposi sarcoma. There were no evidence of infection on autopsy. His CD4 count was 256. With the introduction of HAART, pulmonary KS associated with HIV has been declining. Prior to HAART, pulmonary KS occurred in 10% of patients with AIDS. Most patients die due to opportunistic infections rather than the direct effects of this tumor, which makes this case unique. KS typically occurs with low CD4 cell count (⬍150) and high viral load. Our pt has a CD4⬎ 250. KS in the lung may involve the airways, parenchymal, lymph nodes and pleura which is suggested on CXR by bronchial wall thickening and nodules. Patients with thoracic KS usually have obvious mucocutaneous lesions as was in this case. This rapid deterioration of the respiratory function as was present in this case is unusual. The yield of bronchoscopic lung biopsies in the diagnosis of KS is low, fibreoptic bronchoscopy may contribute to the correct management of the patient and facilitate an accurate prognosis by differentiating between opportunistic pneumonia and pulmonary Kaposi’s sarcoma. Severe hypoxemia was a contraindication in this case. This case illustrates that primary pulmonary KS should be included in the differential diagnosis of fulminant respiratory failure. References:1) Sadaghdar H, Pulmonary Kaposi’s sarcoma presenting as fulminant respiratory failure. Chest 1991; 100:858 – 86

Jayanth Vedre, Mayo Foundation For Medical Education and Research, Mark Keegan, Juan Pulido, Mayo Clinic Department of Anesthesiology, Anil Paturi, Mayo Foundation For Medical Education and Research, John Faryna, Mayo Clinic, James Onigkeit, Mayo Clinic Department of Anesthesiology Introduction: Klippel- Trenaunay Syndrome (KTS) is a rare congenital disorder often associated with significant vascular, bony and soft tissue malformations. Hemostatic abnormalities such as disseminated intravascular coagulation (DIC) may occur and pose numerous challenges to perioperative and critical care teams. Case: A seventeen year-old male with KTWS was admitted to the intensive care unit (ICU) after transfemoral amputation of his right lower extremity. The leg had extensive vascular malformations, was non-functional, and caused severe pain. Massive bleeding occurred both intra- and post-operatively. DIC was noted, with increased D-dimers (⬎20000) and low levels of fibrinogen (89 mg/dl). The patient was transfused with sixty units of packed red blood cells intraoperatively and in the first few post-operative days. Abdominal compartment syndrome developed, requiring emergent exploratory laparotomy. In view of ongoing DIC, the patient was treated with a combination of heparin and antithrombin III infusions along with supplementation of recombinant factor VIIa. Aminocaproic acid was also used for antifibrinolysis. Due to progressive anemia, splenomegaly and thrombocytopenia the patient underwent splenic artery embolization. Because of ongoing DIC, daily transfusions with packed red blood cells, platelets, cryoprecipitate, and fresh frozen plasma were required. Hemostasis was eventually achieved at ten days after the operation. Conclusion: Intensivists should be aware of the presence of a consumptive coagulopathy in patients with KlippelTrenaunay Syndrome and recognize that massive bleeding may occur in the perioperative period. Care of such patients requires sufficient vascular access and transfusion medicine resources to allow rapid transfusion of large amounts of blood products. Consideration should be given to the use of heparin, antithrombin III, aminocaproic acid and activated factor VII as specific treatments to address the underlying coagulopathy present in such patients.


969

970

ACUTE PANCREATITIS ASSOCIATED WITH METFORMIN TOXICITY

CARDIAC ARREST SECONDARY TO SPLENIC RUPTURE POST COLONOSCOPY

Deborah Orsi, Ronen Dudaie, Peter Dicpinigaitis, Montefiore Medical Center

Dukhant Multani, Michael Gabrilovich, Aultman Hospital

Case Report: A 75-year-old woman with diabetes treated with metformin and chronic renal disease stage III, developed progressive confusion and refractory hypoglycemia at the nursing home. Two weeks prior to admission to our ICU she was treated for a urinary tract infection, followed by Clostridium difficile colitis and anorexia. On admission the patient was in shock with severe acidemia (arterial blood gas: 7.08/10/148), hypothermia (T 92.4 F rectally) and oliguria. Relevant laboratory values included: lactate 20 mmol/L, bicarbonate ⬍6 meq/L, potassium 6.6 meq/L, BUN/creatinine 69/7 mg/dL, SGOT 130 U/L, amylase 438 U/L, lipase 4955 U/L. Despite fluid resuscitation, she required initiation of hemodynamic support with norepinephrine, vasopressin and was started on bicarbonate infusion. Computed tomography of abdomen and pelvis showed edematous pancreas with surrounding peripancreatic fluid and diffuse colonic wall thickening. Performance of emergent bicarbonate buffering hemodialysis was followed by prompt weaning of vasopressor support and decrease of serum pancreatic enzymes within the subsequent 24 hours. She was discharged after 13 days at her baseline condition. Discussion: Only 4 published case reports have described the association of acute pancreatitis and metformin toxicity, and only one case reported a probable idiosyncratic reaction at a therapeutic dose. Our patient was at high risk for metformin toxicity and metformin associated lactic acidosis due to her preexisting renal failure. Although metformin and lactate levels do not correlate with prognosis, it remains unclear whether a toxic threshold needs to be reached in order to induce pancreatitis. Although our patient’s daily medications included drugs that are commonly associated with pancreatitis (acetaminophen, oxycodone, metronidaziole), the prompt restoration of normal hemodynamics, rebound hyperglycemia and normalization of pancreatic enzymes after hemodialysis strongly suggest metformin toxic effect. Prompt initiation of hemodialysis had a profound therapeutic impact on her hemodynamic status and was followed by swift resolution of acute pancreatitis.

Case Report: Colonoscopy is a common and well toreated diagnostic and therapeutic procedure but carries a risk of potentially devastating complications. 60 year old female presented next day after having colonoscopy at tertiary referral center with worsening diffuse abdominal pain, shortness of breath, generalized weakness and syncopal episode earlier that morning. While being evaluated in the emergency department she went to PEA arrest and was resuscitated, intubated and admitted to the medical intensive care unit in multiorgan failure and severe acidosis with arterial pH of 6.7. A CT scan of the abdomen demosntrated splenic rupture. She was deemed to be non-operative candidate by trauma surgeon’s evaluation. After initial stabilization with saline, vasopressors and blood product, an emergent splenic artery embolization was performed. Twelve hours later patient was off vasopressors and extubated. Neurological status was preserved and kidney function has normalized. Patient was followed with serial CT scans of the abdomen and no further evidence of bleeding from spleen was detected. Patient was discharged to rehabilitation facility and then home in stable condition. Elective splenectomy is scheduled. Splenic rupture is a very rare complication of colonoscopy although it considered underreported. Proposed mechanisms include excessive traction on the splenocolic ligament and direct trauma by colonoscope in splenic flexure. Sedation affecting patient’s perception of pain may also contribute in complication development. We identified less than 60 cases of splenic rupture in the literature since first reported in 1974. This disease entity can present as immediate or delayed complication. Most of the cases were treated with emergent splenectomy but 3 cases when splenic artery embolization was used (1 patient died) were identified. With increasing number of colonoscopies in today’s world the number of complications of this procedure is on the rise. CT scan of the abdomen is the test of the choice to diagnose splenic rupture. Due to its high mortality if there is a delay in diagnosis and management, this rare complication should always be considered by the astute clinicians.

971 CASE OF MASSIVE BLEEDING

PEDIATRIC

972 GASTROINTESTINAL

Elizabeth Mack, Palmetto Health Children’s Hospital Case Report: A previously healthy 8yo Caucasian male presented to the emergency department with 9 days of non-bloody non-bilious emesis, weight loss, and epigastric pain. He had no fever, diarrhea, melena, hematochezia, rash, sick contacts, or recent travel. He did have maternal grandmother and two cousins with Crohn’s disease. On exam, vital signs were normal and the abdomen was diffusely tender to palpation. Laboratory data were remarkable for albumin 2.4 and evidence of dehydration. He had otherwise normal liver function, renal function, CBC, and urinalysis. Abdominal CT revealed a markedly abnormal appearance of the duodenum with hyperenhancement, wall thickening, and mild dilatation. There was also a moderate amount of free fluid in the pelvis. He was admitted to the floor and given intravenous fluids, ondansetron, proton pump inhibitor, and 25% albumin. The pain and vomiting persisted and with the significant family history, he underwent endoscopy which revealed gastric and duodenal erosions and inflammation. On day 11 of the illness he became febrile, tachycardic, tachypneic, lethargic, and developed hematochezia. He had 500-1000 mL of bright red blood per rectum every 1-2hrs and his hemoglobin dropped precipitously. He was transferred to the PICU, a nasogastric tube was placed, packed red blood cells were given. There was no evidence of intussuception. A few hours later he developed a petechial rash on the dorsum of his hand, which was initially attributed to a tourniquet. The rash progressed to the feet and legs, and skin biopsy was consistent with IgA deposition confirming the diagnosis of Henoch Schonlein purpura. He was treated with methylprednisolone and his fever, emesis, and gastrointestinal bleeding resolved within one day. He never developed renal disease and has had no recurrence at 6 month follow-up.


SEVERE, PROLONGED BACLOFEN WITHDRAWAL FOLLOWING A SECOND CATHETER FAILURE IN A PATIENT WITH STIFF-PERSON SYNDROME Cara McDaniel, Thomas Jefferson University Hospital Case Report: This report describes severe, prolonged baclofen withdrawal in a patient with Stiff-Person Syndrome (SPS). A 54-year-old woman with severe progressive spasticity secondary to SPS using intrathecal baclofen (ITB) therapy presented with hyperthermia, increased tone, and lethargy attributed to urosepsis. Despite treatment, she developed tachycardia, autonomic instability, confusion, increasing episodes of severe spasticity and rigidity, an elevated CPK with continued hyperthermia. Her symptoms were consistent with acute baclofen withdrawal. Intubation was necessary to maintain a patent airway and allow for highdose sedation. She ultimately required high-dose infusions of midazolam, fentanyl, and propofol as well as high-dose oral baclofen, tizanidine, dantrolene, and cyproheptadine to control symptoms and allow for adequate ventilation. She also required intermittent blood pressure support with vasopressors. Imaging, interrogation, and open surgery revealed catheter failure with subsequent system replacement. ITB therapy was restarted and titrated in a step-wise fashion to achieve symptom control. Weaning of IV and PO agents was complicated by frequent episodes of acute stiffening, spasms, and autonomic instability, requiring additional sedative rescue doses. Due to persistent hypertonicity and recurrent episodes of spasticity, dystonic posturing, and autonomic dysfunction, her ITB was titrated to 1200mcg/day and she still required oral baclofen, diazepam, tizanidine, and cyproheptadine. On day 80, she was discharged to a LTAC. This was her second admission in ⬍1 year for acute baclofen withdrawal due to intrathecal catheter failure, with this event being more severe and requiring significantly more medications. Sudden baclofen withdrawal can lead to a life-threatening syndrome in any patient with chronic baclofen exposure. Autonomic dysfunction, common in SPS, paired with acute baclofen withdrawal may further induce autonomic failure, adding to the severity of withdrawal symptoms and potentially complicating recovery. Quick recognition and aggressive management of acute baclofen withdrawal is essential to prevent potentially life threatening complications.

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974

PROFOUND THROMBOCYTOPENIA IN A TRAVELER

A RARE CAUSE OF CARDIAC TAMPONADE

N Dolly, R Manickam, R Loganathan, LHC

Haala Rokadia, Shikhar Agarwal, Rudy Tedja, Chaim Moeller, Diego Conci, Madhu Sasidhar, Cleveland Clinic

Case Report: A 32 year old healthy male presented with myalgias & fevers for 1 day. Exam & lab tests was normal. He was diagnosed with viral syndrome & discharged on oseltamivir. 3-days later, patient returned with abdominal pain & vomiting. Skin revealed rare petechiea, tourniquet test was negative. Pulse: 102,BP121/78Temp 97.8. Since his prior admission, platelets(PLTs) dropped from 200K to12K with no schiztocytes. Hemolysis & coagulation studies were normal. Creatinine(1.4),BUN(28), Mild transaminitis and Albumin:4.0. Sono revealed hepatomagaly. He was hydrated(8L) and transfused 1 unit single-donor PLTs. Further questioning revealed recent travel to the Dominican-Republic, had returned to the US 4-days prior to first admission. Dengue-Fever(DF) testing showed elevated IgM, PCR positive for type-2 Dengue virus. PLTs began to rise by day-3 and was discharged with normal PLTs.This is an unusual presentation of DF with profound but asymptomatic TH & minor systemic features. Travel history to an endemic area led to a prompt diagnosis. PLT ⬍100 K is established criterion among patients with Dengue-Hemorrhagic-fever(DHF), but is much less common & severe in DF. Although prior studies have reported correlation of degree of TH with other organ failures & hypoalbuminemia, our patient presented with dangerously low PLTs without these features. Awareness of this presentation is important in light of recent rise in DF in the US.

Case Report: 55 year old male with history of small cell lung cancer, recently treated with carboplatin/etoposide and radiation therapy presented with acute onset dypsnea. Past medical history included Klinefelter’s syndrome, renal cell carcinoma post left nephrectomy, and smoking related chronic obstructive pulmonary disease. Due to severe refractory thrombocytopenia post-chemotherapy, the patient had recently received daily dose therapy with oprelvekin, recombinant human interleukin-11 (IL-11) agonist that stimulates thrombopoiesis. The patient reported acute worsening in symptoms after oprelvekin therapy. Physical exam was significant for tachypnea with reduced breath sounds, elevated jugular venous pressure, and severe bipedal and abdominal wall edema.Workup included computed tomography of the chest which showed multiple small subsegmental pulmonary emboli in the right lower lobe and a moderate-large pericardial effusion. Echocardiogram showed increased intrapericardial pressures and early tamponade. Specifically, there was presence of a large circumferential pericardial effusion, brief right atrial inversion during late diastole, 31% inspiratory decline in mitral valve velocity, a 56% expiratory decline in tricuspid valve velocity, and a plethoric inferior vena cava with no inspiratory collapse. Pericardiocentesis was withheld given severe thrombocytopenia refractory to platelet transfusions. The patient subsequently developed hypercarbic respiratory failure but denied intubation. Code status was changed to comfort care and patient expired two days later.IL-11 is a thrombopoietic cytokine that facilitates proliferation of megakaryocyte progenitor cells and induces megakaryocyte maturation. Oprelvekin is a recombinant form of IL-11 approved for the management of chemotherapy related thrombocytopenia. Common adverse effects described include peripheral edema, pleural effusion and fluid retention which are generally response to salt restriction and diuretic therapy. To the best of our knowledge, the occurrence of massive pericardial effusion leading to tamponade secondary to use of oprelvekin therapy is novel and not described in the literature before.

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PURULENT PERICARDITIS DUE TO CA-MRSA IN A PREVIOUSLY HEALTHY INFANT

A RARE CAUSE OF ACUTE LIVER FAILURE: HERPES HEPATITIS

Jeffrey Lutmer, Margaret Chase, Todd Karsies, Nationwide Children’s Hospital/ The Ohio State University College of Medicine

Mitchell Craft, Mary Reed, William Loder, Geisinger Medical Center

Case Report: A 7 month female was brought to an outside facility for evaluation after 4 days of fever to 104F, worsening irritability and abnormal breathing. She progressed to respiratory failure, requiring transfer to our ED. PMH was remarkable for hospitalization at 5 weeks for RSV. Family history included mom with pregnancy-related cardiomyopathy. In our ED she received volume therapy for shock and metabolic acidosis. CXR showed right sided infiltrate and pleural effusion. In the PICU, she required shock treatment (epinephrine, dobutamine, steroids) and antibiotics including vancomycin. Diffuse ST elevation suggested pericarditis and ECHO showed circumferential effusion without clear tamponade. Other findings included AKI with hyperkalemia. Her acidosis worsened, requiring escalating pressor support & fluids ⬎200 mL/kg. Deterioration in lung compliance necessitated transition to HFOV. Peritoneal drain placement for abdominal compartment syndrome improved lung compliance, and improved ECHO windows confirmed strong clinical suspicion of tamponade. Pericardial drain evacuated 60 ml of purulent fluid and immediately improved hemodynamics,. Blood, trach, pleural and pericardial cx grew CA-MRSA so rifampin and gentamicin were added. Fever and bacteremia persisted despite appropriate antibiotics, prompting VATS with pericardial window on day 5; cultures became negative within 72h. The remainder of her immune and infectious workup was negative. She was extubated day 11, pericardial drain removed day 15, and left the PICU day 17. Her renal function and ECHO normalized. She was discharged day 21 to complete 4 weeks of antibiotics. Purulent pericarditis is extremely rare in children, with CA-MRSA infection in healthy infants even more unusual. Presentation includes fever, tachycardia, diffuse ST changes, and wide mediastinum on CXR, but diagnosis can be delayed by lack of classic symptoms. Staph aureus is the most common pathogen. Definitive diagnosis requires pericardial fluid culture, and survival hinges on rapid recognition and drainage, often requiring pericardial window. The rising prevalence of invasive CA-MRSA requires increased awareness of this rare but lethal condition.

Introduction: Acute liver failure (ALF) is frequently encountered in the intensive care unit (ICU), particularly at liver transplant centers. The etiology is often evident with a thorough history and focused laboratory testing. We present a rare cause of ALF; Herpes Simplex Virus (HSV) in a patient without a profound immunocompromised status. Case: 79 year old male with a history of squamous cell cancer of his neck, treated with chemotherapy and radiation therapy 2 years prior. He presented with neck erythema and fullness, with concurrent worsening of his chronic mucositis. He was diagnosed with cellulitis and treated with Cephalexin followed by Amoxicillin Clavulanate. He returned with fevers and diarrhea and was noted to have marked transaminitis, levels greater than 1000. A liver ultrasound was unremarkable and drug (Amoxicillin Clavulanate) induced hepatitis was diagnosed. On day 4, he had progressive respiratory failure and shock, and was transferred to our ICU. Laboratory evaluation also revealed: acute renal failure, lactic acidosis and coagulopathy. He was treated for presumed septic shock. His CT scan revealed findings consistent with acute cholecystitis, although surgery felt this was an improbable source of his multi-system organ failure (MSOF). However, he underwent an exploratory laparotomy due to evidence of abdominal compartment syndrome. The source of shock was not elucidated operatively, though his liver appeared homogenously pale and was biopsied. Severe hepatic necrosis with diffuse inclusion bodies consistent with herpetic hepatitis was found. His coagulopathy and MSOF worsened post operatively and he ultimately succumbed. Post mortem, both serum polymerase chain reaction and liver tissue immunohistochemical analysis confirmed HSV 1 infection. Discussion: Herpes hepatitis causing ALF is rare and often lethal. Historically, many cases are diagnosed post mortem, and anti-virals had not been initiated. There is however some evidence that suggests superior outcomes with anti-virals. Therefore, early consideration of HSV is essential when an alternate etiology of ALF is deficient.


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SEVERE ENCEPHALITIS WITH ASSOCIATED MRI FINDINGS IN AN 8YO WITH ROCKY MOUNTAIN SPOTTED FEVER (RMSF)

A LETHAL COUGH: PRESUMED PERTUSSIS CAUSING FRACTURED RIBS, LUNG HERNIATION, HEMOTHORAX AND FATAL ARDS

Rodney Daniels, Ken Tegtmeyer, Cincinnati Children’s Hospital

Anupa Nadkarni, Geisinger Medical Center, Omar Rahman, Geisinger Health System

Case Report: An 8 yo male presented to our ED with fever, malaise, body aches and headache, along with a diffuse truncal rash that had progressed over the prior 7 days. Symptoms began 10 days prior to admission, when he presented to his PMD with a “few spots” on his chest, low grade fever, body aches and headache. There was no travel history identified. His PMD suspected VZV and prescribed acyclovir, although he had been immunized with Varivax.On the day of admission he was brought to the ED due to persistent fever and worsening malaise. On exam he was ill-appearing and agitated, but interactive. He was tachypneic and tachycardic, with dry mucous membranes, and had diffuse petechia over all body surfaces, including his palms and the soles of his feet. He was given 60ml/kg of normal saline, IV ceftriaxone and doxycyline but remained hypotensive, so he was started on epinephrine and transferred to the PICU.Subsequent evaluation was remarkable for acute kidney injury, significant metabolic acidosis, and electrolyte disturbances, as well as leukocytosis with evidence of DIC. He was irritable but oriented to person and place, with equal, reactive pupils and normal reflexes. His AKI improved with volume resuscitation, but his mental status deteriorated and he was intubated on the night of admission for neurological decline. Head CT noted incidental findings of an absent corpus callosum with interhemispheric lipomas, but no edema or hemorrhage.On HD#2 Brain MRI demonstrated multifocal regions of punctate, linear, confluent signal abnormality involving the supra- and infratentorial brain, cerebral edema, and sulci effacement. He was treated presumptively for increased ICP and an ICP monitor was placed, confirming this suspicion. He had 2 generalized tonic-clonic seizures on HD#4 and was started on Levetiracetam with no subsequent seizures. On HD#7 RMSF serologies returned positive.He was successfully extubated on HD#15, but continued to have significant neuro deficits with frequent storming episodes. He was transferred to rehab on HD#19 and went home on HD#63. He continues to receive extensive rehab support and home care.

Case Report: Violent coughing has been associated with rib fractures and lung herniation. Herniation is typically the protrusion of the lung through an abnormal weakness in the chest wall. Most cases are managed surgically or conservatively without significant impact on mortality. We present a case of severe complications arising from intractable coughing. A 57 year old diabetic man presented with paroxysmal episodic cough for 4 weeks, chest pain and progressively worsening dyspnea. On exam he had respiratory distress, decreased air entry at lung bases, conjunctival hemorrhages and lid ecchymosis. He was treated for presumed pertussis. Chest X-ray showed right sided pleural effusion. He developed shock and respiratory failure acutely and was intubated. Chest CT scan showed right hemothorax and upper lobe herniation. Tube thoracostomy drained 1 liter of blood and VATS was done. Costochondral junctions along the right side were found to be fractured from ribs 3 to 7 without active hemorrhage. Post operative course was complicated by rapidly progressive refractory hypoxemic respiratory failure due to right pulmonary consolidation/ contusion followed by ARDS. He developed pseudomonas pneumonia on day 14 of mechanical ventilation and died on day 18. Lung herniation has been described with chest trauma and intractable cough associated with COPD. Our patient had no such history. Infectious causes including B.pertussis could not be fully excluded as he met clinical but not lab criteria.. Lung herniation in association with intractable cough due to pertussis or like syndromes can lead to hemothorax and rapid clinical deterioration.

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980

MULTIORGAN INVOLVEMENT OF ERDHEIM CHESTER DISEASE

CASE REPORT OF 11 CASES OF TETANUS MANAGED IN ALAIN HOSPITAL ICU DURING A PERIOD OF 8 YEARS FROM 2002 TO 2010

Haala Rokadia, Shikhar Agarwal, Cleveland Clinic Case Report: 66 year old male with history of systolic and diastolic congestive heart failure and nephrogenic diabetes insipidus presented with 7 month history of dyspnea and orthopnea. Three months prior, he had developed obstructive uropathy necessitating transurethral resection of prostate with bilateral ureteral stent placement. Despite this intervention, renal function declined requiring hemodialysis.Admission chest Xray showed increased reticular markings diffusely with bilateral pleural effusions. Computed tomography (CT) of the chest demonstrated diffuse smooth septal thickening with patchy ground glass opacities, which remained unchanged after ultrafiltration, indicating an infiltrative process and/or fibrosis. CT abdomen revealed bilateral hydronephrosis with patent ureteral stents, and diffuse perinephric, mesenteric and retroperitoneal stranding with soft tissue prominence. Positron emission tomography (PET) scan with 18-fluro-deoxy-glucose (FDG) uptake was done to evaluate for malignancy. It demonstrated diffuse uptake in the thoracic and abdominal aorta with focal uptake in the aortic arch and heterogeneous uptake in the carotid arteries. Increased uptake was noted in bilateral lungs and pleura, adrenal glands, enlarged kidneys, and scattered mediastinal and retroperitoneal lymph nodes. No abnormal FDG uptake was seen in bone. Radiologic findings were suspicious for Erdheim-Chester disease (ECD). Lower extremity Xrays showed cortical thickening and expansion of bilateral tibia. There was bilateral epiphyseal and metaphyseal sclerosis with diffuse lucency within the intramedullary canals. CT head incidentally showed extensive infiltrative soft tissue prominence in the retroorbital space. Due to worsening renal failure, a kidney biopsy was performed. It demonstrated chronic inflammation, composed of histiocytes, lymphocytes, andplasma cells, with interstitial fibrosis. Immunohistochemical stains for Langerin, S100, and CD1a, did not demonstrate a Langerhans cell population.The above consortium of clinical, radiologic and pathologic findings suggested ECD as a unifying diagnosis. Steroid therapy was started with rapid improvement of dyspnea and renal failure.


Suma Gopalakrishnan, ICU, Kamal Idrees, Joshy Zacharia, Alain Hospital Case Reports: A report of 11 cases of tetanus managed in ICU Alain Hospital , UAE during a period of 8 years from 2002-2010. Alain Hospital is a specialised acute care & emergency hospital having a bed capacity of 412 with 30 medical departments and a 14 bedded ICU. Out of the 11 cases, 3 were of mild form of Tetanus who stayed in ICU for 3-5 days & were managed without ventilationThe rest 8 were severe form of Tetanus who needed ventilatory support for a considerable period of time. There was one mortality. This patient had cardiorespiratory arrest in the ward followed by a prolonged resuscitation time & was admitted to ICU after that.All cases were males. Age ranged from 5-50 years. All of them needed ventilatory support for a period varying from 18 – 46 days. Length of stay in ICU ranged 33-70 days. All except one patient gave a history of injury in the form of nail prick, wound foot, face. All received Tetanus immunoglobulin , were intubted & ventilated early. All except one were tracheostomised & received magnesium sulphate. Associated problems encountered during management included Severe autonomic dysfunctionVentilator associated pneumonia Syndrome of inappropriate ADH Diabetes Insipedus Claustridium Defficile infection. All patients recovered without any disability & went home after the long ICU & hospital stayIn summary, the severe Tetanus cases managed by early intubation &ventilation, adequate sedation, early tracheostomy when appropriate & use of MgSo4 helped in achieving a good outcome for these patients.

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PERCUTANEOUS DILATIONAL TRACHEOTOMY FOR IMPOSSIBLE AIRWAY MANAGEMENT IN A NEWBORN WITH PIERRE-ROBIN SYNDROME

TWO CASES OF CRITICAL AIRWAY MANAGEMENT IN EXTREMELY OBESE CHILDREN

Arash Pirat, Selim Candan, Aytekin Unlukaplan, Ogur Komurcu, Selim Kuslu, Gulnaz Arslan, Baskent University, Faculty of Medicine Case Report: Pierre-Robin syndrome (PRS) is a rare congenital sequence of facial abnormalities characterized by glossoptosis, micrognathia, and retrognathia. Because of the facial abnormalities, both mask ventilation and endotracheal intubation may be extremely difficult in patients with PRS. We present airway management of a newborn with PRS and extreme obstructive dyspnea due to a mass extending from the base of the tongue to the posterior pharyngeal wall. A 2 days old term newborn with PRS was admitted to the neonatal intensive care unit (NICU) for respiratory distress. At 3 A.M. the anesthesiology team was consulted for airway management of the newborn after several unsuccessful intubation attempts by NICU team. The child had severe obstructive dyspnea. He was receiving 2 L/min of oxygen through nasal cannula and his oxygen saturation was 85%-90%. A direct laryngoscopy revealed a rudimentary tongue and a mass extending from base of the tongue to the posterior pharyngeal wall. The child was spontaneously breathing through a 2 mm diameter fistula in the center of this mass. It was attempted to pass a stylet through the opening of the fistula to perform a blinded endotracheal intubation. However, it seemed that the fistula had a tortuous shape and it was not possible to thread the stylet through it. At this point it was decided that translaryngeal endotracheal intubation is impossible and a percutaneous dilational tracheotomy (PDT) was planned. After midline subcutaneous infiltration of 0.5 mL of 1% lidocaine, trachea of the newborn was cannulated, using a 20 gauge peripheral venous catheter. Successful cannulation of the trachea was confirmed by aspirating air through the catheter. 5 F, 7 F, and 9 F central venous catheterization kits and a size 3 tracheotomy cannula were used to perform the PDT. The newborn was successfully ventilated through her tracheotomy tube until surgical resection of the airway obstructing mass was performed. This case demonstrates that in newborns with impossible translaryngeal airway management, PDT may be considered as a rescue airway management technique.

Nam Young-Chung, UMDNJ-Robert Wood Johnson Medical School, Colin O’Reilly, Robert Wood Johnson Medical School, Vicki Craig, UMDNJ-Robert Wood Johnson Medical School, Lisanne Hauck, RWJMS - RWJ University Hospital Case Reports: Case 1: 11 year-old boy was admitted to the Pediatric Intensive Care Unit (PICU) after tibia-fibula osteotomy with post operative respiratory failure. History included autism, asthma, extreme obesity, and Blount’s disease. Height 140cm,wieght 112 kg, body mass index (BMI) 58. The anesthesia team reported difficult intubation. Attempts to wean from ventilator support were unsuccessful and tracheostomy was performed. Difficulty during the procedure led to ventricular arrhythmias and cardiac arrest in the OR. Resuscitation was successful, and an endotracheal tube was placed through the fresh stoma until a custom tracheostomy tube could be ordered. This patient suffered multiple complications during his PICU course including pneumonia, tracheitis, and skin ulceration. Length of stay 122 days. Case 2: 13 year-old boy with autism, obstructive sleep apnea, and extreme obesity was admitted to the PICU with respiratory distress and altered mental status. Height 157 cm, weight 159 kg, BMI 65. Oxygen saturation was 80% on room air in the ED. CT angiography to rule out pulmonary embolism showed bibasilar atelectasis only. Initial arterial blood gas showed a pH of 7.05, PaCO2 150 mmHg, PaO2 101 mm Hg. BiPAP was initiated, and his mental status slowly improved. Eventually he was referred on night time BiPAP for pulmonary rehabilitation and continued weight loss efforts. Length of stay 40 days. Discussion: These cases demonstrate severe life-threatening respiratory and airway complications secondary to extreme obesity (BMI greater than 40) in pediatric patients which directly contributed to long length of stay and increased cost of healthcare. There is little information in the literature on this patient population in the PICU. Studies are needed to delineate risk factors for chronic respiratory failure, cardiovascular complications and other potential problems after surgery. Understanding of the anatomic and physiologic challenges associated with extreme obesity and strategies for care that minimize morbidity during critical illness are essential for the safe care of these children. This patient population presents new challenges in the PICU and warrants further study.

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METHYLNALTREXONE RELIEVES OPIOID-INDUCED CONSTIPATION AND UNDIAGNOSED C. DIFFICILE SEPTIC ILEUS IN A CRITICALLY ILL PATIENT

ACUTE RESPIRATORY DISTRESS SYNDROME SECONDARY TO ACUTE LITHIUM INTOXICATION

David Dickerson, Mark Nunnally, University of Chicago/Department of Anesthesiology and Critical Care

Ankit Kansagra, North Shore Medical Center, Sudheer Nambiar, Newark Beth Isreal Medical Center, Eric Yang, North Shore Medical Center, Pratik Patel, Newark Beth Israel Medical Center, Monroe Karetzky, The Bronx Medical Ctr

Case Report: Methylnaltrexone bromide (MNTX) is a peripherally acting ␮-opioid receptor antagonist (PAMORA) that selectively targets the peripheral side effects of opioids while preserving central analgesia[1]. MNTX is approved for the treatment of opioid-induced constipation (OIC) in patients receiving palliative care when laxative therapy has been inadequate. We report a case of a critically ill patient with septic ileus rapidly relieved with MNTX. A 78-yr-old man with diabetes, hypertension, and repaired aortic stenosis was in the intensive care unit (ICU) for 4 months recovering from 20% total body surface area burns to his pelvis and lower extremities. His course was complicated by encephalopathy, respiratory failure, renal injury, osteomyelitis, skin graft rejection and sepsis. He received high-volume tube feedings with occasional gastric distention responsive to conventional therapy. His non-healing wounds led to amputation below one knee after which he remained intubated and required a 100 ␮g/hr fentanyl infusion for 36 hours. After extubation, he was more lethargic with impaired glucose regulation, abdominal distention and intolerance to feeds. Abdominal x-ray showed diffusely dilated loops of bowel without evidence of obstruction. MNTX, 12 mg, was administered subcutaneously. Within an hour, laxation revealed voluminous liquid stool positive for C. difficile toxin antigen. The next day, encephalopathy, distention and hyperglycemia improved. The need for analgesia during mechanical ventilation often exposes critically ill patients to opioid infusion. Several case reports and a recent randomized trial suggest that MNTX reverses OIC in critically ill patients: within 24 hours of MNTX, 6 of 7 patients laxated[2-4]. Rapid correction of OIC in ICU patients is necessary to optimize caloric intake, decrease time of mechanical ventilation, shorten duration of critical illness, and in our case, possibly relieve a developing septic ileus[5]. The use of PAMORAs in this setting merits additional study. References: 1. Mayo Clin Proc, 2008;83:1116.2. Crit Care, 2010;14:486.3. Anesth Analg, 2008;107:1965.4. Int J Gynecol Cancer, 2010; 20:308.5. Br J Anaesth, 2003;91:815-9.

Case Report: Lithium carbonate is a widely administered anti-manic drug. Despite lithium’s established clinical efficacy, its prescription must be approached with caution due to its narrow therapeutic index. With mild toxicity (1.5 to 2 mmol/L), GI and neuromuscular symptoms are observed, at moderate toxicity (2 to 2.5 mmol/L), CNS and cardiac involvement predominate, and at severe toxicity (⬎2.5 mmol/L), grave CNS manifestations such as seizures, and coma, along with renal insufficiency and death are observed. We describe a rather rare but fatal side effect of lithium: Acute Respiratory Distress Syndrome (ARDS). A 46 year female with history of bipolar disorder on lithium is referred for generalized weakness, diarrhea and shortness of breadth for 2-3 week, was found to have BP 90/54 mmHg, HR 60bpm, saturating 95% on 2L nasal canula and lab data showed sodium130mmol/l, potassium 4.7mmol/l, BUN 82mg/100ml, Creatnine 4.16mg/dl and lithium level of 3.3. Emergent dialysis was undertaken with improvement in lithium level to 1.0, though a rebound was noted to 2.2 within 24hrs. Subsequently she developed hypoxic respiratory failure requiring intubation. Chest X ray showed new bilateral pulmonary edema, CT scan showing extensive alveolar consolidations, V/Q scan was negative for pulmonary embolism, and thallium and gallium scan where also negative. Echo cardiogram showed RV systolic 70mm/hg, PA pressure 62mmHg with normal LV function. She underwent 3 dialysis sessions, supportive care and was extubated in 5 days. To our knowledge, four cases of ARDS following lithium toxicity have been documented. All patients presented with altered mental status at serum lithium level ranging from 3.8 to 4.9 mmol/L and cardiogenic etiologies in addition to other likely causes of ARDS were ruled out in each case. Patients were treated by normal saline hydration (50%) or hemodialysis (50%), indicating that hemodialysis may be a permissive factor in lithium-associated ARDS development rather than a required component. Taken together, we believe lithium is a likely culprit to the initiation of ARDS, and propose the addition of ARDS to the family of clinical manifestations of severe lithium toxicity.


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APPLYING NITRIC OXIDE VIA HEATED, HIGH FLOW NASAL CANNULA

PURULENT PERICARDITIS ATTRIBUTED TO COMMUNITY ACQUIRED MRSA

Michael Hewitt, Melissa Fulton, Katie Rincon, St. Joseph’s Hospitals

Maria Sobolev, Ariel Shiloh, Alina Dulu, Richard Savel, Montefiore Medical Center/The Albert Einstein College of Medicine

Introduction: We present a case where a nonintubated pediatric patient with complex health issues underwent successful application of Nitric Oxide through the OptiFlow® high flow, heated nasal cannula system. Case Summary: The patient is a 2.5 y.o. female whose chronic health issues include short gut syndrome, intestinal hemangiomas, bi-directional VSD with PA banding, severe pulmonary hypertension and failure to thrive.This admission to the PICU was for viral upper respiratory infection/pneumonia, fever, exacerbation of her pulmonary hypertension and hypoxia with a plan to stabilize saturations at a level ⬎80%, avoiding intubation while undergoing antibiotic therapy. The patient required high FIO2 via NRB. The patient’s CXR upon admission was unremarkable but over the next several days deteriorated, from a left sided infiltrate/pneumonia to a bilateral multifocal process. The patient’s oxygen status deteriorated secondary to her pulmonary hypertension crisis. Nitric Oxide was initiated through a nasal cannula with supplemental oxygen flow of up to 6 lpm. Over the hours following initiation of the Nitric Oxide, the patient developed a dry cough and agitation, thought to be a result of the dry oxygen from the cannula.. The decision was made to attempt a trial of Nitric Oxide through the OptiFlow® system. Following appropriate pre-warming of the system, Nitric Oxide was applied with a supplemental oxygen flow up to 7 lpm. The therapy was well tolerated and continued for several days with gradual weaning of both the Nitric Oxide and FIO2 with saturations of 85-88%. The patient was transitioned to a traditional nasal cannula, and discharged home on day 14, with her typical home regimen of .5 lpm nasal cannula. Discussion: The application of this high flow, heated & humidified oxygen delivery system integrated with Nitric Oxide appeared to benefit this particularly complex patient. Further investigation is warranted into the effectiveness of this approach to sever pulmonary hypertension.

Case Report: A 26-year-old healthy man presented with altered mental status and a two week history of fever, malaise, and joint pain. There was no history of drug use, travel, sick contacts, or environmental exposures. On physical examination he was confused, febrile, hypotensive, tachycardic, and tachypneic. Scleral icterus, elbow and ankle joint swelling, and diffuse pustules on the skin were present. Cardiopulmonary exam was unremarkable. Laboratory results were significant for leukocytosis, lactic acidosis, and acute renal failure. Initial EKG was noncontributory. Chest CT revealed a small pericardial effusion, lung nodules with cavitations, and hepatosplenomegaly. Initial echocardiogram confirmed a small pericardial effusion with no evidence of tamponade. Empiric broad spectrum antibiotic therapy was initiated. Methicillin resistant Staphylococcus aureus (MRSA) was isolated from blood, urine, and skin cultures. Progressive respiratory and hemodynamic compromise required intubation and transfer to an ICU on hospital day seven. Echocardiogram performed in the ICU revealed a large pericardial effusion, with new cardiac tamponade, and a tricuspid valve mass. Surgical pericardial drainage evacuated 950 ml of purulent fluid, which was culture positive for MRSA. The patient made a complete recovery after completing a 6-week course of intravenous vancomycin. Discussion: We present an unusual case of purulent pericarditis – with tamponade physiology – attributed to community acquired MRSA (CA-MRSA) endocarditis. This case presents two rare entities: purulent pericarditis (rarely seen in the modern antibiotic era), and specifically purulent pericarditis caused by a community acquired nosocomial pathogen. The pathogenesis includes: extension of an an intrathoracic, myocardial, or subdiaphragmatic suppurative focus, hematogenous spread, or direct infection from trauma or surgery. Hemodynamic compromise due to cardiac tamponade requires immediate pericardial drainage. The critical care clinician must have a high index of suspicion for virulent community acquired pathogens; diagnostic and therapeutic windows are present but can quickly close, with devastating consequences.

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THERAPEUTIC HYPOTHERMIA AFTER INTRAOPERATIVE CARDIAC ARREST - A CASE REPORT

PROLONGED HYPOTENSION FROM EPINEPHRINE TOXICITY IN THE TREATMENT OF ANAPHYLAXIS

Sarah Thomas, Russell Langdon, Michael Hosking, University of Tennessee Medical Center

Jennifer McCann, Ryan Venis, St. Vincent Indianapolis Hospital

Case Report: A fifteen year-old male with an unremarkable previous medical history experienced a sudden onset severe headache which rapidly progressed to loss of consciousness, complicated by pulmonary aspiration. He was found to have a ruptured arteriovenous malformation resulting in cerebellar hemorrhage with intraventricular extension. The patient underwent an emergency posterior fossa craniotomy for AVM resection and clot evacuation. During surgery he developed acidosis (pH 7.109, bicarbonate 17mEq/L), hyperkalemia (potassium 6.6 mmol/L) and elevated temperature (38.5° C from 36.3° C). Treatment for suspected malignant hyperthermia syndrome was initiated immediately using dantrolene. As a repeat dose of dantrolene was begun, the patient developed a wide complex QRS, followed by ventricular tachycardia and ventricular fibrillation. CPR was conducted for approximately fifteen minutes. The surgical resection was resumed after return of spontaneous circulation. Following conclusion of the surgical procedure therapeutic cooling using an Alsius CoolGuard 3000® (ICY® catheter) was initiated according to our hospital protocol for cardiac arrest. The patient was treated with mild hypothermia (33° C) for 24 hours and then re-warmed over a period of 16 hours. Despite the development of a pontine infarction four days after surgery, the patient eventually recovered good cognitive function. He successfully returned to his grade level in high school, although his initial cerebellar insult resulted in limited motor recovery. This case demonstrates a good functional outcome following treatment with therapeutic hypothermia for intraoperative cardiac arrest. Although intraoperative cardiac arrest is an infrequent event, the use of mild hypothermia to mitigate brain injury due to anoxia and ischemic insults should be considered in patients who have experienced cardiac arrest and other types of hypoxic injury during induction of anesthesia and/or surgical procedures, as it has been proven efficacious in out-of-hospital cardiac arrest.


Background: The emergent nature of anaphylaxis creates an environment of heightened risk for epinephrine medication misadventures to occur. Literature to date has focused on the immediate adverse outcomes associated with epinephrine dosing and administration errors, with limited data available on prolonged consequences.Objective: We present a unique case of refractory hypotension associated with the administration of high dose epinephrine for the treatment of anaphylaxis. Case Report: A 29 year old presented to an immediate care facility for treatment of anaphylaxis including two doses of epinephrine 1 mg (1:1000) intramuscularly. The patient was subsequently transported to our adult emergency department and developed isolated hypotension refractory to fluid resuscitation. The patient was then admitted to the medical intensive care unit with a diagnosis of epinephrine toxicity. The prolonged hypotensive response seen in this patient is believed to be a result of residual stimulation of the more sensitive beta receptors by high doses of epinephrine administered to the patient resulting in a prolonged vasodilatory response. Conclusion: Epinephrine is a high alert medication widely used for the treatment of anaphylaxis. Proactive evaluation of current processes among emergency departments is recommended in order to minimize dosing and administration errors with epinephrine as these errors can lead to substantial harm to patients.

989

990

SEVERE IMMUNE-MEDIATED THROMBOCYTOPENIA PRESENTING WITH SUPRACHOROIDAL,VITREAL AND SUBRETINAL HEMORRHAGE

GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR (GM-CSF) AS ADJUVANT THERAPY FOR UNRESOLVING INFECTION IN CRITICALLY ILL CHILDREN

Ankit Kansagra, Chad Dubois, North Shore Medical Center

Kristin Greathouse, The Research Institute at Nationwide Children’s Hospital, Jennifer Muszynski, Cheryl Sargel, Mark Hall, Nationwide Children’s Hospital

Case Report: Primary Immune Thrombocytopenia (ITP) is an acquired immune mediated disorder characterized by platelet count less than 100 x 10 9 /L, with no underlying cause of thrombocytopenia. A 91yr female presents with sudden loss of vision in her left eye. She initially noticed several blood blisters in her mouth followed by sudden clouding of vision. She has a history significant for hypertension and wet macular degeneration of both eyes on treatment with lisinopril and aspirin. On examination she was found to have lower extremity petechiae, hemorrhagic bullae in oral cavity. Her ophthalmological exam showed detached inferior retina, vitreal and choroidal hemorrhage and macular involvement. Lab data showed platelet count of 8000, Hg 13.9, normal renal & liver function test and LDH. Peripheral smear showed normal red cell morphology without shistocytes, and no platelets. CT scan of orbit confirmed the finding. She received emergent platelet transfusion, high dose decadron, and IVIg. She was closely observed for any new bleeding or worsening of hemorrhage. Excellent response was seen with platelet count rising to 72,000 in 5 days. She is planned to undergo closed vitrectomy. ITP has an incidence of 66 per 10 5 /year and mortality of 5% in adult which markedly increases with age ⬎60yr. Ophthalmic involvement is exceptionally rare. Our review of literature has shown that severe hypertension, anemia and macular degeneration are risk factors for subretinal hemorrhage, but ITP without anemia, presenting as suprachoroidal, vitreal and subretinal hemorrhage on top of macular degeneration has not been reported. First line therapy with dexamethasone has showed 86% response rate. Severe cases of ITP with bleeding needs platelet transfusion which has shown to increase count by more than 20x10 9 /L and concurrent administration of IVIg is associated with resolution of bleeding and rapid restoration of platelet count.Thrombopoietin-receptor agonists are newly emerging second line options with 88% response rate, gives sustained response and reduce steroid use. This case emphasizes detailed investigation of vision loss, and early and intense management of ITP for improving prognosis.

Case Reports: Persistent infection is a leading cause of morbidity and mortality in critically ill children. The innate immunostimulant GM-CSF has been shown to speed clearance of infection in critically ill adults but pediatric data are limited. We present our institutional experience with the use of GM-CSF as adjuvant therapy (in addition to antibacterials and source control) for the treatment of persistent infection in critically ill children. Data are presented as median (IQR). From 2003 to 2010, nine critically ill children underwent therapy with GM-CSF for the purpose of augmenting immune function in the setting of persistent culture positivity (age: 0.9 [0.3-9] years, 55% female). Sites of infection included lung (n⫽4) and bloodstream (n⫽5). Pathogens included Candida species (n⫽4), Pseudomonas species (n⫽4), and MRSA (n⫽1). Duration of culture positivity prior to initiation of GM-CSF therapy was 9 (8-15) days. Duration of GM-CSF therapy was 5 (3-6) days. Dosing was by IV infusion in all patients with doses ranging from 125-150 ␮g/m2/day. Two children were receiving extracorporeal membrane oxygenation support at the time of GM-CSF initiation. Clearance of infection was achieved in 7/9 children (78%), with a median time to clearance (among the 7 responders) of 2.5 (2-4) days from the time of GM-CSF initiation. There was one relapse of infection among responders. 28-day mortality (from the time of GM-CSF initiation) was 100% in the non-responders (n⫽2) and 43% in the responders. Oxygenation index, modified inotrope score, pediatric logistic organ dysfunction score, and white blood cell count values were similar pre- and post-GM-CSF therapy (p⫽0.62, 0.46,0.75, and 0.68 respectively). Our case series suggests that GM-CSF therapy may have a role in facilitating clearance of unresolving infection in critically ill children. Its use was not associated with worsening of organ failure. Prospective randomized, controlled trials are needed to evaluate the efficacy of GM-CSF in this setting.

991

992

DRUG-INDUCED RHABDOMYOLYSIS FOLLOWING VORICONAZOLE THERAPY: A CASE REPORT

AN INCIDENTAL FINDING OF LEFT VENTRICULAR THROMBUS IN THE SPIRAL CT ANGIOGRAM OF THE CHEST

Sarah Nelson, Virginia Commonwealth University Medical Center, Katie Muzevich, Virginia Commonwealth University Health System Case Report: Voriconazole is the drug of choice for the treatment of invasive aspergillosis. Like other azole antifungal agents, it is associated with elevations in liver function tests; however, there is only one published case report of voriconazole-associated myositis. We report a case of a suspected voriconazole-induced rhabdomyolysis following coadministration of voriconazole and sirolimus. A 42year-old female with a past medical history significant for orthotopic liver transplant, stage IV chronic kidney disease and portal vein thrombosis was admitted to the hospital with altered mental status, nausea, visual disturbances, and fatigue. Ten days prior to admission, she had been prescribed voriconazole, 300 mg every 12 hours (3.5 mg/kg/dose), for pulmonary aspergillosis. Upon presentation, several laboratory abnormalities were identified including an elevated creatinine kinase (24,400 IU/L, increased from baseline 61 IU/L), elevated liver function tests (AST/ALT 1198/168 units/L, increased from baseline 32/15 units/L) and an elevated serum creatinine (5.8 mg/dL, increased from baseline 3.5 mg/dL). Both voriconazole and sirolimus levels were supratherapeutic (12.62 mcg/mL, reference 1-6 mcg/mL and 21.5 ng/mL, previously 7.5 ng/mL) and were subsequently held. In this case, a drug-drug interaction between voriconazole and sirolimus likely resulted in voriconazole and sirolimus toxicities. Both voriconazole and sirolimus are substrates and inhibitors of cytochrome P450 enzymes. Coadminstration of voriconazole and sirolimus is contraindicated, as sirolimus levels increased markedly in pharmacokinetic studies. Ultimately, the patient experienced fulminant hepatic failure and acute on chronic renal failure resulting in death. This is the first case of voriconazole-induced rhabdomyolysis and illustrates the necessity of close and adequate drug therapy monitoring.

Thaslim Ahamed Kassim, Isaac Opoku-Asaare, Brian Curry, Michael Greenberg, Howard University Hospital Clinical Presentation: 47 year old female with no significant past medical history was admitted to our hospital with complaints of fever, dyspnea on exertion and right sided chest pain for four days. On examination, patient was afebrile with normal blood pressure and pulse rate of 133 per minute. Rest of the physical examamination was within normal limits. Laboratory tests were positive for leucocytosis of 10500/dl and low platelets of 70000. Sepsis workup revealed no obvious source of infection. A helical CT angiography of the chest done to rule out pulmonary embolism revealed no segmental pulmonary embolism but a rounded 2 cm hypodensity at the apex of left ventricle suspicious of thrombus. A two dimensional (2D) echocardiogram revealed a mobile 1.5 x 1.5 apical echodensity with independent motion suggestive of apical thrombus. In addition, there was severe global left ventricular systolic dysfunction with an ejection fraction (EF) of 30% to 35% and moderate mitral regurgitation. Patient was transferred to cardiac intensive care unit for further management. The patient was started on anticoagulation with unfractionated heparin and subsequently warfarin. A 2D echocardiogram was repeated after 14 days which showed complete resolution of LV thrombus and EF of 25. She was discharged with warfarin and is to be followed up in the cardiology clinic. Discussion: CT pulmonary angiography done to diagnose pulmonary emboli may rarely show cardiovascular abnormalities such as left ventricular (LV) thrombus, which may be related or unrelated to the patients’ presenting complaints. (1) Patients with LV systolic dysfunction are predisposed to LV thrombus formation, while severe mitral regurgitation may have a protective effect by decreasing stasis. Warfarin therapy has been shown to reduce embolic events in some observational studies. (2) References: 1. Michael B et al Incidentally Detected Cardiovascular Abnormalities on Helical CT Pulmonary Angiography: Spectrum of Findings. Am. J. Roentgenol. 2001; 176: 421 - 427.2. Fuster Vet al. The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol 1981 Mar; 47(3): 525-31.


993

994

SEPTIC ARTHRITIS IN A CHILD WITH VENTRICULAR ASSIST DEVICE

A 65 YEAR OLD MALE WITH ACUTE ONSET OF RIGHT UPPER EXTREMITY WEAKNESS, WITH DEEP VENOUS THROMBOSIS, PULMONARY EMBOLI, AND RIGHT HEMISPHERIC ISCHEMIC STROKE

Girdhar Kaliki Venkata, Nicholas Slamon, University of Florida College of Medicine Case Report: This is the first case being reported in the literature. A 16 month old female child with Acute Dilated Cardiomyopathy of unknown etiology developed malignant ventricular tachyarrythmias that were resistant to defibrillation, epinephrine, lidocaine and amiodarone. She was emergently resuscitated with extracorporeal membrane oxygenation (ECMO), which supported her for the following 4 days. Later she was weaned off the ECMO and was decannulated. Unfortunately her heart function and arrythmogenicity did not improve. Hence she was listed for heart transplant and was supported with a ventricular assist device (Berlin Heart). While on advanced cardiac support, she developed stroke and multiple blood stream infections. One day, on routine examination she was noted to have restricted movements in the left lower extremity. Since fibrin and clots form easily in reservoir of the ventricular assist device, a possiblity of new stroke was entertained. However on closer examination she was noted to have left hip swelling, intense tenderness to touch and actively resisted passive movements. The diagnosis of septic arthritis was made by clinical exam (non-weight bearing and restriction of movements) and high white count with elevated CRP (Kocher Criteria). The patient did not have fevers during the episode. Upon incising the joint capsule, frank milky white pus emanated from the joint space. The joint fluid was sent to the lab for analysis. Since she was being treated with Cefepime, Vancomycin, Clindamycin and Caspofungin for 20 days prior to the arthritis, the culture results were negative for bacteria, acid fast bacilli and fungal elements. She subsequently recieved physiotherapy and recovered her range of motion. This case eloquently illustrates the need for exceptional vigilance while caring for children supported with ventricular assist devices.

Natalie Calcatera, Harry Anderson, III, Wright State University Boonshoft School of Medicine, Jason Pasley, Los Angeles County / University of Southern California Medical Center, Jonathan Saxe, Wright State University Boonshoft School of Medicine Case Report: This 65 year old male was admitted with complaints of being lightheaded, and also with the acute onset of right upper extremity weakness, approximately 3 weeks after undergoing left total knee arthroplasty for osteoarthritis. The patient was found to have bilateral pulmonary emboli, and acute right subclavian thromboembolism with occlusion. He underwent emergent thromboembolectomy of the right upper extremity, and subsequently started on systemic anticoagulation. On postoperative day 2 the patient developed acute mental status changes and seizure, for which CT scanning of the head revealed right hemispheric multifocal infarct. Transthoracic echocardiography was non-diagnostic for patent foramen ovale, revealed no intracardiac thrombus, but demonstrated a markedly dilated right ventricle. Transesophageal echocardiography with bubble study was diagnostic for a patent foramen ovale. The workup for hypercoagulable state was non-diagnostic. The patient subsequently underwent placement of an inferior vena cava filter, during which the initial contrast study of the iliofemoral venous system revealed multiple foci of non-occlusive clot in both the right common femoral and external iliac veins. The patient was maintained on heparin anticoagulation, eventually started on warfarin, and recovered significant neurological function. He was discharged to an extended care facility. Conclusion: Paradoxical embolism is an uncommon cause of acute arterial occlusion, but should be suspected with the constellation of deep venous thrombosis, pulmonary embolism, and acute arterial embolic findings.

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996

CARDIAC ARREST AND PERSISTENT SINUS BRADYCARDIA AFTER THE INITIATION OF BORTEZOMIB THERAPY FOR MULTIPLE MYELOMA

THYROID STORM MANIFESTING AS CONGESTIVE HEART FAILURE IN A PREVIOUSLY HEALTHY ADOLESCENT FEMALE: A CASE REPORT

Jacob Hampton, Kamila Dell, University of Utah College of Pharmacy

Robert Abdullah, Mercer University School of Medicine, Catherine Preissig, Medical Center of Central Georgia

Case Report: Bortezomib (Velcade) is a proteasome inhibitor currently approved for the treatment of mantle cell lymphoma and multiple myeloma. Case reports of bortezomib-related cardiac toxicity have begun to surface in recent years, including cases of congestive heart failure, arrhythmias, and atrioventricular block. While causation has not yet been established, the evidence of correlation of cardiovascular complications with bortezomib administration continues to rise. A 69 year old white male with a past medical history of atrial fibrillation and stroke presented to the emergency department with a history of syncope following a diagnosis of multiple myeloma and the subsequent initiation of bortezomib therapy. The patient reported syncope symptoms starting about the same time as bortezomib therapy and he had received a total of 6 doses of bortezomib 2.4 mg (1.3 mg/m2) per dose upon presentation. Patient was admitted in normal sinus rhythm (NSR) with a ventricular rate of 63 beats per minute and QTc of 521 ms. On hospital day 2, patient reverted to atrial fibrillation with heart rates increasing to the 120’s and home metoprolol was restarted. Following 3 doses of metoprolol, patient’s heart rate slowed to the 90’s. One hour later, patient was found down in cardiac arrest due to ventricular tachycardia. CPR and cardioversion were performed with return of pulse and NSR. Amiodarone was started. Patient had another cardiac arrest and was treated with CPR, one dose of epinephrine, and dopamine was started for hemodynamic instability. Dopamine was weaned off on day 4 and amiodarone was continued. On day 5, patient began to have bradycardic episodes with rates as low as the 30’s. Metoprolol was discontinued and an automatic implantable cardioverter-defibrillator was placed prior to hospital discharge on day 12. To our knowledge, we present the first case of bortezomib associated bradycardia induced ventricular tachycardia leading to cardiac arrest. Close monitoring of heart rate and rhythm, along with cautious dosing regimens of bortezomib should be used in patients, particularly when cardiac co-morbidities are present.


Case Presentation: A 17 yo previously healthy AAF presented to our ED with acute respiratory distress. Past medical history was significant for upper respiratory symptoms. She denied history of palpitations, recent weight loss, heat intolerance, and change in appetitel. Family history was negative for cardiac, pulmonary, and endocrine disease.On exam the patient was in moderate distress, thin, sitting upright for comfort. Vital signs were as follows: T 97, HR 189, RR 34, BP 187/62, oxygen saturation 79%. She had bilateral crackles on auscultation, bounding peripheral pulses, wide pulse pressure, and an audible S3 gallop. Blood work including cell counts and electrolytes were all wnl. Chest radiography revealed cardiomegaly and bilateral infiltrates. Transthoracic echocardiogram demonstrated structurally normal heart, decreased left ventricular function, ejection fraction of 14%, and dilated right atrium. The patient progressed to respiratory failure, was intubated, placed on mechanical ventilation, and transferred to the pediatric ICU for further management with furosemide, milrinone, and supportive care. A more detailed physical exam revealed subtle evidence of goiter as well as exophthalmos.Thyroid studies revealed markedly elevated thyroid hormone and low thyroid stimulating hormone consistent with primary hyperthyroidism. She was then successfully managed with anti-thyroid medications and conservative use of beta-blockers. Further work-up revealed the presence of auto-antibodies consistent with Grave’s disease. Discussion: Congestive heart failure is a rare cause of respiratory distress in pediatric critical care, and is usually due to myocarditis, cardiomyopathy, or acquired heart disease. While hyperthyroidism affects as many as 5% of adults, this endocrinopathy is rare in children and adolescents. Thyrotoxicosis is a known, potentially fatal complication in patients with hyperthyroidism, but rarely leads to congestive heart failure.The pediatric critical care physician must have a heightened awareness for thyrotoxicosis in children with congestive heart failure of unknown origin, as this condition while rare, can be fatal if not treated appropriately.

997

998

AN UNEXPECTED CASE OF ADULT POLYGLUCOSAN BODY DISEASE

MACROPHAGE ACTIVATIONS SYNDROME, AN IMPORTANT DIFFERENTIAL DIAGNOSIS FOR SEPTIC SHOCK

Michael Nicholaus Van Haute, Gerardo Carino, Warren Alpert Medical School of Brown University

Srinivasarao Badugu, University of Florida College of Medicine, Tara Smith, University of Florida-Shands Hospital

Case Report: Adult polyglucosan body disease (APBD) is a rare, adult-onset type of glycogen storage disease which has an autosomal recessive mode of inheritance. Patients generally present with signs and symptoms of upper and lower motor neuron involvement as well as progressive dementia. Diagnosis is most commonly made by sural nerve biopsy with the identification of the typical polyglucosan inclusion bodies. These bodies can also be found in the cortex and white matter of the whole brain. Here we report an unexpected case of APBD which was diagnosed post-mortem in one of our critically-ill patients. Our case is of a functional 77-year-old woman with no neurologic manifestations who presents with a severe left hand cellulitis. She had a very complicated course with an acute myocardial infarction, right lower lobe pneumonia, rapid atrial fibrillation, congestive heart failure, and development of a thrombus in the left atrial appendage. She developed a large GI bleed and decreased mental status after the initiation of heparin and required respiratory support. She did not immediately regain alertness despite sedation weaning, and was noted to have right arm weakness and loss of vision after she was extubated. An MRI showed multifocal areas of restricted diffusion involving the bilateral occipital lobes, which was felt strongly to be consistent with embolic stroke. Unfortunately, the patient further deteriorated after this and expired one week later despite aggressive measures. The postmortem examination was met with an unexpected finding of extensive polyglucosan body accumulation throughout the white matter cores of the cerebral cortices, cerebellum, and spinal cord.APBD, also known as glycogen storage disease, type IV, is a slowly progressive autosomal recessive disorder. There is a germline mutation in the glycogen branching enzyme gene GBE1 resulting in the accumulation of very long, un-branched glucose chains in glycogen. These molecules are very minimally soluble and thus precipitate in the brain and other organs. Our case is extremely rare as our patient had extensive disease, however was generally asymptomatic, before developing her acute illness.

Case Report: 3-year-old Caucasian female presents to the pediatrician with fever and sore throat; a course of amoxicillin is prescribed. She is evaluated in the emergency department 3 days later with persistent fevers and abdominal pain and admitted for possible urosepsis with a differential diagnosis of acute surgical abdomen. She did not have hepatosplenomegaly, gallop or cardiac murmurs on examination. Ultrasound of abdomen and kidneys is reported as unremarkable and CT scan of the abdomen revealed mesenteric adenitis and ruled out acute surgical causes of abdominal pain. She continued to have high-grade fevers despite antibiotics and subsequently demonstrated symptoms consistent with warm septic shock requiring admission to the PICU. She is supported with vasopressors and broad-spectrum antibiotics and underwent an extensive workup including urine, blood cultures, viral studies, and pediatric ANA panel; all studies were negative. She is discharged after 2 weeks of hospitalization with a tentative diagnosis of shock secondary to a viral syndrome. Just prior to discharge she develops a polymorphic, erythematous macular rash over theabdomen, which becomes more prominent after discharge. She is readmitted within 48 hours with fever, generalized, myalgias, arthralgias, respiratory distress and shock and is transferred to the PICU; intubated and again requires hemodynamic support with vasopressors in addition to stress dose steroids. An extensive workup for infectious diseases and for possible vasculitis is again negative;an ECHO did not show any coronary abnormalities. Bone marrow biopsy did not show evidence of leukemia, lymphoma or hemophagocytes. Macrophage activation syndrome was established with the criteria of fever, elevated ferritin (6300ng/ml), elevated triglycerides (277 mg/dl), low natural killer cellactivity and soluble-IL2 receptors (⬎3000 pg/ml). Arthritis becomes more prominent and she receives intravenous immunoglobulins to treat newly diagnosed SJIA. She continues to have arthritis after high dose steroids, immunoglobulins and received etanercept. She responded well to pulse steroids and cyclosporine and her ferritin levels decreased with treatment.

999

1000

PERSISTENT METHEMOGLOBINEMIA ASSOCIATED WITH THE USE OF PRIMAQUINE FOR PNEUMOCYSTIS PNEUMONIA

SEVERE METABOLIC ALKALOSIS INDUCED BY DAILY PLASMAPHERESIS IN A PATIENT WITH THROMBOTIC THROMBOCYTOPENIC PURPURA

Nader Mina, Wayne State University School of Medicine, Linda Browning, Detroit Medical Center

Ankit Kansagra, North Shore Medical Center, Sudheer Nambiar, Newark Beth Isreal Medical Center, killol patel, Newrak Beth Israel Medical center, Pratik Patel, Newark Beth Israel Medical Center, Monroe Karetzky, The Bronx Medical Ctr

Case Report: Methemoglobinemia refers to the oxidation of ferrous iron (Fe⫹⫹) to the ferric (Fe⫹⫹⫹) state within the hemoglobin molecule. Exposure to an oxidizing chemical is a common cause of methemoglobinemia especially in those with G6PD deficiency. A 51 year old male with HIV/AIDS (CD4 count of zero) was admitted for hypoxic respiratory failure secondary to Pneumocystis pneumonia (PCP). The patient developed acute kidney injury and hyperkalemia while receiving sulfamethoxazole/trimethoprim and corticosteroids. A quantitative G6PD activity assay was sent to an outside laboratory and treatment was changed to primaquine 30 mg daily and clindamycin 600 mg every 8 hours on day 11 of hospitalization. Arterial blood testing obtained that day revealed pH 7.304, pCO2 39.5 mm Hg, pO2 82.9 mm Hg, bicarbonate 19.3 mEq/L, fractional oxyhemoglobin saturation 96% and methemoglobin 1.5% (reference range ⬍3%). Four days later, the G6PD result was reported as 16.7 units/g of hemoglobin (reference range 7.0 –20.5; Arup Laboratories, Salt Lake City, UT). Methemoglobin began to rise on the fourth day of primaquine therapy (3.3%) and ranged from 2.1 to 9.5% throughout the course of treatment. No other medications known to cause methemoglobinemia were given at this time. The patient remained on primaquine for 19 days as he did not display adverse sequelae from the methemoglobinemia. Ascorbic acid therapy was started; however methemoglobin remained elevated despite discontinuing primaquine. The patient eventually was extubated and later died due to severe pulmonary fibrosis.This case illustrates the development of methemoglobinemia in the absence of G6PD deficiency in a patient with HIV receiving primaquine for PCP.

Case Report: Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease characterized by pentad of thrombocytopenia, hemolytic anemia, renal failure, fever and other neurological symptoms. Plasmapheresis (PP), steroids, anti-platlets agents, vincristine and splenectomy are widely known treatment options. One of the problems with PP is development of metabolic alkalosis caused by large amount of citrate in fresh frozen plasma (FFP) which is used as a replacement fluid. A 33 year old female was admitted after an episode of syncope while getting off a 6 hour long flight. She is a healthy young female with no significant past history except on oral contraceptive 4 months ago, currently on her vacation. On arrival she was found to have low grade fever, platelet count of 21,000 and renal failure. Lab data showed LDH 1792, with schistocytes in peripheral smear. With diagnosis of TTP, she was soon started on PP. While on PP she developed marked alkalosis nadir pH of 7.6. No other cause of metabolic alkalosis, such as alkali therapy, nasogastric suction, vomiting or hyperkalemia was found. Peak pH measured after completion of PP (pH 7.53, pCO2 33, pO2 116, HCO3- 28.6) and blood gas failed to return to normal by next time of next PP. Acetazolamide was minimally helpful in reducing pH from 7.47 to 7.45 in 5 hours. Reducing citrate concentrate in anticoagulant helped initially, and substituting heparin was greatly adventitious. Unfortunately she required dialysis secondary to worsening renal failure, which showed to reduce pH to as low 7.44 post dialysis. Risk factors for development of severe alkalosis are renal and liver failure. Acid base balance should be closely monitored in patients undergoing repeated PP. Various measures like modification of PP procedure like using heparin instead of citrate, calcium supplementation to prevent hypocalcaemia, lower amount of citrate along with acetazolamide and dialysis as used in our patient should be considered in high risk patients. In summary we recommend close monitoring of pH on patients with PP and use above measures to prevent serious metabolic alkalosis.


1001

1002

MINIMALLY INVASIVE OESOPHAGECTOMY: THE CRITICAL CARE PERSPECTIVE ON A COMPLICATED CASE

A UNIQUE PRESENTATION OF PNEUMOPERICARDIUM AFTER ROUX-EN-Y GASTRIC BYPASS

Sanchia Goonewardene, University Hospital Coventry and Warwickshire, Nilesh Parekh, University Hospital Birmingham NHS Foundation Trust

Crystal Manohar, Cleveland Clinic Foundation

Introduction: University Hospital Birmingham NHS Foundation Trust is a tertiary referral centre, with a collaboration of specialists involved in development of cutting edge surgical procedures and critical care. Oesophageal cancer is the ninth commonest cancer in the UK but the fifth most common cause of mortality. Treatment includes oesophagectomy, with associated morbidity and mortality. As a result minimally invasive procedures are not widely used. Critical care plays a major role in the post operative care of these patients. The current first line imaging modality for pulmonary complications is X-ray. However the one dimensional xray image can be very difficult to interpret and very often has to be taken in conjunction with clinical findings. CT scanning however, gives a much more definitive diagnosis. Case report: We present the case of a 57 year old gentleman who underwent the newly developed minimally invasive procedure for oesophagectomy.: Although there have been several reported cases of respiratory complications, there have been none presenting with an encysted hydro-pneumothorax resulting in failure of lung re-expansion post operatively, with impact on respiratory function and weaning as in this case. Discussion: We present this case and discuss the difficulties in detecting a diagnosis of encysted hydro-pneumothorax on one dimensional xray imaging and the role of CT scanning.

Case Report: Pneumopericardium from gastropericardial fistula secondary to peptic ulcer or gastric carcinoma is quite rare. We present a unique case of a non-traumatic pneumopericardium that occurred as a result of a gastropericardial fistula from a gastric ulcer nine years after gastric bypass surgery. Our patient presented to an outside facility in December 2009 with a 5-day history of abdominal pain, emesis, bloody diarrhea and was hypotensive, tachycardiac, and in acute renal failure. He was transferred to the Cleveland Clinic for further management and chest radiography revealed a large pneumopericardium. He was diagnosed with septic shock with multi-system organ failure secondary to cardiac tamponade that occurred from an ischemic gastrojejunal ulcer with free perforation into the pericardium. The patient subsequently underwent an emergent pericardial window and total gastrectomy, resection of gastropericardial fistula and Rouxen-Y gastrojejunostomy, splenectomy, and end cervical esophagostomy. The patient recovered from his surgery and was ultimately discharged to a skilled nursing facility in January 2010.

1003

1004

COOLER HEADS PREVAIL: A CASE OF INTRACTABLE INTRACRANIAL HYPERTENSION AFTER LIVER TRANSPLANTATION TREATED WITH THERAPEUTIC HYPOTHERMIA

ACUTE QUADRIPLEGIC PARALYSIS AFTER CABG SURGERY

Nikolai Tolstoy, Hospital of the University of Pennsylvania, Angela Mills, Creighton University Medical Center, Adam Fox, Hospital of the University of Pennsylvania, Joshua Levine, Hospital of the Univ. of Pennsylvania, Daniel Holena, Hospital of the University of Pennsylvania

Case Report: A 75 year old male underwent CABG surgery for history of symptomatic CAD complicated by NSTEMI, CHF with an EF of 25%. He also had ESRD requiring HD. Surgery was complicated by postoperative bleeding necessitating mediastinal re-exploration. During the course of both surgeries the patient received 17 units of RBCs, 12 units of FFP, 6 x 10-packs of platelets, 1x 10-pack cryoprecipitate, 32 mcg DDAVP, 30 g AMICAR, 9.6 mg factor 7, and 20 mg estrogen. The ICU course was remarkable for delayed awakening despite lack of sedation as well as generalized flaccid quadriplegic paralysis. HD was performed daily in the ICU and on postoperative day 5 the patient became more responsive and was successfully extubated. Neurological exam revealed profound muscle weakness affecting the proximal more than the distal muscle groups, with intact comprehension, memory, cranial nerves and sensory nerves. MRI studies with DWI failed to reveal a definitive etiology to explain the clinical findings. Findings on repeat neurological exam were unchanged at the time of his hospital discharge and on follow-up exams 6 and 12 months later. A muscle biopsy was performed and findings were consistent with critical illness myopathy (CIM). CIM, also known as acute quadriplegic myopathy, is associated with catabolic conditions like sepsis, MODS, SIRS, chronic inflammatory conditions, cancer, therapy with myopathy-inducing drugs like steroids, neuromuscular blockers, AMICAR. AMICAR is a commonly used antifibrinolytic agent administered during cardiac surgery. Common side effects include rhabdomyolysis, hyperkalemia, ARF. AMICAR is renally cleared and its dose needs to be adjusted in renal failure patients. There are no recent recommendations for dosing of AMICR in dialysis-dependent patients. However, sparse remote data recommend reducing the total AMICAR dose to only 20% of standard recommended dose in dialysisdependent patients. We believe that this patient’s critical illness myopathy might have been precipitated or worsened by the large dose of AMICAR he received. Further studies specifically addressing dosing of AMICAR in dialysis-dependent patients undergoing cardiac surgery are needed.

Background: We describe a patient with intractable intracranial hypertension treated with therapeutic hypothermia after liver transplantation for acute liver failure. Methods: Case Report. Results: A comatose 23-year-old woman with acute liver failure (ALF) from acetaminophen toxicity developed signs of intracranial hypertension and underwent liver transplantation. Her level of arousal did not improve and on postoperative day 1 she developed clinical signs of cerebral herniation. An intracranial pressure (ICP) monitor was placed and intracranial hypertension documented. Intracranial pressure elevations persisted despite maximal osmotherapy, and therapeutic hypothermia was initiated with rapid normalization of ICP. The patient’s neurologic exam improved and she was discharged from the hospital neurologically intact. Conclusion: Therapeutic hypothermia may be effective in treating refractory intracranial hypertension in postoperative liver transplant patients.


Maggy Riad, David Geffen School of Medicine at UCLA, Duraiyah Thangathurai, Keck School of Medicine of USC

1005

1006

A CASE OF ASEPTIC MENINGITIS ASSOCIATED WITH AN INTRATHECAL STEM CELL TRANSPLANTATION FOR SMA TYPE 1

REPEATED FIRE EVACUATION OF A REHABILITATION HOSPITAL IN GERMANY

Samuel Lehman, PAAMG, Adam Holmes, Children’s Hospital Central Califonia

Dirk Maybauer, Marc Maybauer, University of Texas Medical Branch, Georg Kafka, Notarztdienst Gu¨nzburg, Germany

Introduction: Infantile spinal muscular atrophy type 1 (SMA I) also know as Werdnig-Hoffmann disease is a degenerative disease of motor neurons that results in profound weakness and hypotonia. This autosomal recessive condition results in infants with normal intelligence that progressively become weaker and most die by the age of two. Stem cell therapy may hold some promise as a treatment for patients with SMA I as indicated by animal studies but has not been FDA approved in the United States. Some families are taking their children out of the country seeking this therapy for their children. Case Description: The patient is an eight month old girl with SMA I who was returning from Mexico after receiving an intrathecal injection of a stem cells that had apparently been pretreated to create a neuronal stem cell line. They had obtained the stem cells in the United States, flown to Mexico where a physician did an intrathecal injection of 1.5 million stem cells. That same day on the airplane ride home developed a high fever and irritability. Upon her return her symptoms did not improve and therefore was brought to an emergency department for further evaluation. She presented with irritability, fever of 39 C, severe hypotonia and weakness. A lumbar puncture was performed demonstrating a CSF white blood cell 8250 cells/␮L, RBC 420 cells/␮L, protein 164, and glucose 78. The CSF gram stain showed no organisms. The patient was treated with dexamethasone, vancomycin, and ceftriaxone and admitted to the pediatric intensive care unit. Blood and spinal fluid cultures had no growth, antibiotics were discontinued after 72 hours and the infant was observed in the hospital for another 72 hours. Her symptoms of fever and irritability resolved without further evidence of infection. Discussion: The etiology of this child’s meningitis was either infectious or a reaction to the intrathecal treatment she received. Since no bacteria or fungus ever grew on the standard media culture and the proximity of the meningitis symptoms to the timing if the intrathecal injection, it is more likely that the meningitis represents an inflammatory reaction to the stem cell treatment.

Introduction: In September 2007, the rehabilitation hospital at Ichenhausen, Germany was threatened by a fire and had to be evacuated. A similar scenario happened three years earlier in the same hospital. The evacuation in both cases was organized by the same chief emergency physician. Hypothesis: Valuable lessons had been learned from both evacuations of this hospital. Methods: Retrospective data analysis of patients’ evacuation, treatment, and transport, as well as resources and logistics used. Results: On September 7, 2007, local firefighters, EMS paramedics, ambulance officers, physicians, and a “rapid response unit” of the German Red Cross were sent on scene. One of three buildings of the hospital was engaged in flames in the basement. Heavy smoke development forced the hospital staff to start a horizontal evacuation. When the chief emergency physician arrived on scene, he began patient triage, and organized the scene. It turned out that the fire was minor and could be erased. A second triage was performed. The total duration of the evacuation was 4h 51min. One hundred twenty two patients were triaged, two patients and two physio-therapists suffered smoke inhalation injury, without burns, all other patients and staff were not injured. Of the 122 patients, none was transported to other hospitals. The number of medical personnel used was 112 (10 emergency physicians, 62 paramedics, and 40 EMTs). Five emergency ambulances staffed with emergency physicians, one rescue helicopter staffed with a physician, as well as 33 ambulances and 2 other vehicles from the Red Cross fleet were held ready. Conclusion: Difficulties faced on scene were 1) a lack of patients’ paper records, and 2) the initial horizontal evacuation was confused and uncoordinated. However, with arrival of the chief emergency physician, an established disaster plan and logistics were initiated, which proved crucial for the final success of the evacuation. Critical lessons were learned from the previous evacuation of this hospital, including appointment of a chief emergency physician, adequate communication systems on-scene, and organization of hospital beds in surrounding counties.

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PSYCHOTROPIC MEDICATIONS ASSOCIATED WITH SEVERE NEUTROPENIA AND FATAL SEPTIC SHOCK

ACUTE INTRAVASCULAR HEMOLYSIS DURING HEMODIALYSIS

Lama Nazer, Taghreed Al Najjar, King Hussein Cancer Center, Gollapudi Shankar, Western University of Health Sciences

Deborah Orsi, Alina Dulu, Alan Friedman, Montefiore Medical Center

Case Report: Neutropenia has been reported as an adverse drug reaction with many psychotropic medications used for the treatment of depressive disorders. We report a case of fatal severe neutropenia associated with the combination of mirtazapine, quetiapine, lamotrigine, and venlafaxine. A 40-year-old woman with a major depressive disorder was started on the following medications: mirtazapine, quetiapine, lamotrigine, and venlafaxine. Two weeks later, the patient developed severe ocular cellulitis, followed by a few episodes of recurrent pharyngitis, for which she was treated with oral antibiotics and instructed to continue taking her other medications. Approximately 4 weeks later, she developed a severe oral thrush, persistent fever, chills, rigors and a productive cough. After one week, she was taken to the Emergency Department, found to be neutropenic, and admitted for management of febrile neutropenia. Her stay was complicated by a seizure and cardiac arrest. Upon transfer to the ICU, she was unresponsive, febrile, hypotensive on vasopressors, and on mechanical ventilation. The CBC revealed WBC 600/mm3, ANC 18/mm3, Hb 9.6 g/dL, and platelets 161,000/ mm3. Her computed tomography (CT) of the chest revealed multilobar nodular infiltrates. Her peripheral blood culture grew Enterococcus faecium and the tracheal aspirate culture grew aspergillus and candida. The patient was treated with imipenem/cilastatin, voriconazole, vancomycin, and levofloxacin. No specific medical cause for neutropenia was identified; two bone marrow biopsies ruled out leukemia. The patient’s condition continued to deteriorate; she developed multiorgan dysfunction syndrome and died 4 days later of suspected druginduced severe neutropenia and septic shock. Discussion: To our knowledge, this is the first reported case of fatal neutropenia associated with the combination of mirtazapine, quetiapine, lamotrigine, and venlafaxine. It is unclear whether neutropenia was due to one drug or the combination of all. Nevertheless, early recognition of this serious side effect is very important in order to avoid serious and potentially fatal outcomes.

Case Report: A 67-year-old male with end stage renal disease and diabetes developed severe abdominal pain, hematemesis and gross hematuria at the end of routine hemodialysis session. He was concluding a 4-hour dialysis through Phoenix dialysis machine with blood flow of 450cc/minute through AV fistula. The patient had no recent illness, nor traveled abroad. On admission he was febrile, tachycardic but stable hemodynamically. Laboratory values showed hemoglobin and hematocrit 7.8 and 17.4 g/dL from baseline of 10 and 30 g/dL, thrombocytosis and mild leukocytosis. Total bilirubin was 4.9 mg/dL, indirect 1.9 mg/dL, SGOT 474 mg/dL and SGPT 97 mg/dL. Haptoglobin was 48 mg/dL, LDH 4256 U/L, plasma free hemoglobin 1410 mg/dL, lipase 1630 U/L. Urine analysis showed large blood and no RBCs. Peripheral smear revealed schistocytes, with reticulocytosis, no spherocytes nor evidence of agglutination, Heinz bodies or plasmodium. Admitted to the intensive care unit, received supportive blood transfusions. Blood cultures, viral hepatitis panel, direct, indirect Coombs, cold agglutinin and antibody titers against EBV and Mycoplasma were negative. CD55, CD53 levels, hemoglobin electrophoresis and ADAMTS13 activity were normal. Patient had complete remission of hemolysis within the next 48 hrs. Discussion: We described an unusual case of severe acute intravascular hemolysis induced by hemodialysis. The acute onset of hemolysis during hemodialysis, its prompt resolution, and a negative workup for all other etiologies supports our diagnosis. Multiple mechanisms were described in the past: dialysate tonicity, contamination with oxidants and mechanical causes. The occurrence of acute pancreatitis during hemolytic crisis has been sporadically documented and hypothetically due to the proinflamatory action of free heme molecule. In our case no abnormality in the dialysate nor mechanical defect were found. We hypothesize that a leak in the filter membrane may have caused mixing of dialysate and blood and trigger a subsequent hemolysis. Recognition of acute intravascular hemolysis during hemodialysis should prompt termination of dialysis to avoid further exposure and severe complications.


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1010

CLOPIDOGREL NON RESPONSIVENESS IN A HYPOTHERMIC PATIENT FOLLOWING CARDIAC ARREST

A 44 YEAR OLD MALE WITH RECURRENT CEREBRAL EDEMA

Kristine Willett, Massachusetts College Of Pharmacy, Mary Sanford, Catholic Medical Center, Cheryl Durand, Massachusetts College of Pharmacy & Health Sciences

Justin Mitchell, University of South Carolina School of Medicine, William Owens, Philip Lowman, University of South Carolina

Background: Dual antiplatelet therapy with aspirin and clopidogrel is recommended in patients undergoing coronary artery stenting. Despite these measures, stent thrombosis occurs in up to 2% of patients. The causes of clopidogrel non responsiveness may be attributed to pharmacokinetics of clopidogrel, genetic variations in the enzyme that metabolizes clopidogrel (CYP 2C19*2 allele), as well as cellular factors such as rapid platelet turnover. We present a case of clopidogrel non responsiveness in patient following cardiac arrest. Case Description: A 52 year old man urgently underwent percutaneous coronary intervention (PCI) following a witnessed cardiac arrest with subsequent return of spontaneous circulation. Pre intervention he received ASA 325 mg and clopidogrel 600 mg via orogastric tube (OGT). A 3.512 mm Veriflex® bare metal stent was deployed in the proximal LAD. Therapeutic hypothermia, initiated immediately post stent deployment, was utilized for 24 hours. The patient received 2 subsequent doses of clopidogrel 75 mg via OGT at 7 hours and 31 hours after initial load. Thirty seven hours after PCI new ST segment elevation was noted. During repeat catheterization a 100% in-stent thrombosis was discovered. Restenting of the proximal LAD following extraction thrombectomy was performed. A thromboelastogram obtained after the procedure demonstrated 40.3% level of inhibition. This case provides evidence for the variability in responses to platelet inhibitors and may also have been further complicated by induced hypothermia.

Case Reports: 44-year-old male without past medical history, presented with a 2-month history of worsening headache, blurry vision, an episode of instability. He had nausea with vomiting, becoming intractable the day of admission. A social history included 20-pack years of tobacco and alcohol consumption 3-4 times weekly. He denied high-risk behavior. Physical exam was incomplete due to confusion and altered mental status. Fundoscopic exam was incomplete due to confusion. He denied a stiff neck and had no changes in range of motion. Cardiovascular, respiratory and abdominal exams were normal. He had bilateral non-tender inguinal lymphadenopathy. No penile lesions or discharge were noted. Neurologic testing was non-focal. CT of his head showed sulci and lateral ventricle effacement. A chest CT showed a 2.5 cm right upper lobe lung mass. MRI of the brain showed innumerable small nodular opacities, and a small brain-stem lesion. Bronchoscopy was performed. The patient was started on broad-spectrum antibiotics, Acyclovir and Dexamethasone. The patient’s intracranial swelling improved, allowing for a lumbar puncture. His opening pressure was 35 cm H2O. HIV, TB, RPR and Toxoplasma tests were all negative. His CD4 count was 248 u/L. Cerebral spinal fluid was positive for Cryptococcus Neoformans antigen. Pathology found Cryptococcus Neofromans in lung tissue from biopsy, consistent with a broncho-pulmonary Cryptococcoma. Amphotericin B, Flucytosine and Dexamethasone were started. His condition improved, and he was discharged on long-term oral Fluconazole therapy. The patient required two subsequent MICU admissions over a three month period for cryptococcal meningitis, with increased intracranial pressure. An emergent ventriculoperitoneal shunt was placed, with subsequent clinical improvement. Two months later his symptoms recurred. A repeat lumbar puncture showed an opening pressure of 30 cm of H2O. A Contralateral ventriculoparitoneal shunt was placed. Ventriculograms demonstrated continued patency of the ventriculoparitoneal shunts, though he had multiple admissions with increased intracranial pressure since his initial diagnosis.

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INTRACARDIAC INVASION OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN A 9-YEAR-OLD FEMALE

EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) FOR SEVERE ARDS SECONDARY TO STAPHYLOCOCCAL OSTEOMYELITIS

Brian Bridges, Vanderbilt University Medical Center, Pradip Kamat, Emory University School of Medicine Case Report: A 9-year-old female presented at an outside hospital with a 2-day history of vomiting. She had a past medical history significant for biliary atresia requiring an orthotopic liver transplant over 8 1⁄2 years earlier. Her immunosuppressant regimen consisted of prednisone and tacrolimus. She had also been experiencing increasing fatigue, shortness of breath, and exercise intolerance for a month prior to her presentation. At the admitting hospital, she was noted to have cardiomegaly on chest x-ray. An echocardiogram performed at this facility was notable for a pericardial effusion and a mass that seemed to be invading the heart. A pericardial drain was placed and 430 ml of fluid was immediately drained. The patient was transferred to our facility where she originally received her liver transplant. A CT scan of the chest revealed a large mediastinal mass that had invaded into the right atrium. An echocardiogram performed at our institution also showed that this mass extended into the right ventricular free wall, extending from the lateral border of the right atrium inferoposteriorly to the mid right ventricle, with envelopment of the great vessels. In addition, there was a mobile portion of the mass within the right atrium measuring 3 mm X 10 mm. A PET scan revealed a large hypermetabolic anterior mediastinal chest mass, hypermetabolic foci in the left pleural space, right breast, left buccal space, and nodes in the right upper quadrant and pelvis. Her pleural fluid showed sheets of malignant hematopoietic elements consistent with lymphoma/post-transplant lymphoproliferative disease. An EBV PCR performed on plasma showed greater than 1.3 million copies, and the pericardial fluid was shown to have lymphoblastic elements and CD 20⫹ cells. The patient’s tacrolimus was discontinued, and after a lumbar puncture and a bone marrow biopsy were performed, she was started on a low dose chemotherapy regimen consisting of cyclophosphamide, rituximab, and prednisone. The patient was discharged home on prednisone after 18 days in the hospital. A repeat PET scan performed approximately 6 weeks after her initial admission showed that she was free of disease.


Shivanand Medar, Iris Toedt-Pingel, The Children’s Hospital At Montefiore Introduction: We describe a rare case of lower extremity compartment syndrome secondary to staphylococcal osteomyelitis with severe ARDS requiring Extracorporeal Membrane Oxygenation (ECMO) support. Case Report: A 9 year old boy recently emigrated from West Africa with no significant past medical history presented to the emergency room with one day history of fever and acute onset of left leg pain and swelling. He was diagnosed with compartment syndrome of the left leg secondary to tibial osteomyelitis requiring emergent fasciotomy. Subsequently he developed septic shock and remained intubated. He required vasopressors for 24 hours. He developed bilateral pulmonary infiltrates consistent with Acute respiratory distress syndrome (ARDS). A chest CT revealed extensive bilateral consolidations with air lucencies suspicious for septic emboli and bilateral necrotizing pneumonia. The blood, respiratory and wound cultures grew Staphylococcus Aureus (MSSA). His respiratory status worsened on conventional ventilation, hence he was switched to high frequency oscillatory ventilation (HFOV). In view of persistent hypoxemic respiratory failure (OI ⫽ 48) despite maximal ventilatory support, extracorporeal membrane oxygenation (ECMO) was instituted on hospital day 9. Veno-venous (V-V) ECMO was initiated with percutaneous cannulation of the right internal jugular vein. Oxygenation improved after initiation of ECMO. Blood cultures became negative after 6 days of antibiotics. After 19 days on ECMO the patient’s pulmonary status improved, hence he was decannulated. He was placed on HFOV for 3 days and then switched to conventional ventilation. A tracheostomy was performed as prolonged respiratory support was anticipated. He was weaned off ventilator support after another 2 weeks. After completion of his antibiotic course, inpatient rehabilitation therapy and decannulation of his tracheostomy he was discharged home. Discussion: It is well described that venovenous ECMO can be a rescue method for patients with ARDS that is refractory to conventional treatments. Our case demonstrates successful use of ECMO in severe ARDS secondary to Staphylococcal osteomyelitis.

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PNEUMOCYSTIS JIROVECII PNEUMONIA IN AN IMMUNOCOMPROMISED HOST WITH INTERSTITIAL PULMONARY AMYLOIDOSIS

TANSIENT SEVERE LV DYSFUNCTION FOLLOWING PERICARDIOCENTESIS

Muralikrishna Gopal, Albert Einstein College of Medicine- Montefiore/Jacobi Medical Center, George Lominadze, Montefiore, David Appel, Montefiore Medical Center

Case Report: The patient is a 71 y.o. man with a history of malignant mesothelioma, treated with right extrapleural pneumonectomy, resection and repair of pericardium and diaphragm. Post-op follow up and cardiac evaluation was normal. Several months later he developed SOB and w/u revealed new moderate size pericardial effusion with normal LV function and impaired hemodynamics. He underwent a pericardial window. Initially he did well, and then developed hypotension, with atrial fibrillation with RVR 130’s. He was cardioverted to ST 110’s. However he remained hypotensive and vasopressors were initiated. A bedside TTE revealed severe LV dysfunction with EF ⬍20%, and inotropes were initiated. Troponin and MB CPK levels were negative. Over the course of the next 3 days he steadily improved and inotropes and vasopressors were weaned off. Repeat echocardiogram showed improved LV function with EF ⬎50%. Discussion: The patient had normal cardiac function as shown by preoperative echo. At the diagnosis patient had normal LV function with impaired hemodynamic and with cardiac tamponade. Initially after pericardiocentesis there was an improvement in hemodynamic status before the development of a low cardiac output state. There is no concensus as to the cause of low cardiac output state following pericardiocentesis. The pathophysiologic mechanism may be the same as that after pericardiocentesis for constrictive pericarditis; the sudden pericardial decompression resulting in ventricular dilation and failure. With inotropic and vasopressor support there was a return to baseline LV function.

Case Report: A 49 year old woman presented to the hospital with complaints of low grade fevers, shortness of breath, productive cough and fatigue of one week duration. Her past medical history was significant for Non-ischemic cardiomyopathy and orthotopic heart transplantation 18 months prior to admission, as well as treatment with Velcade and autologous stem cell transplantation 10 months before this admission. Her physical exam upon admission showed an oxygen saturation of 88% on room air. Patient underwent CT scan of the chest showing patchy foci of ground-glass opacities throughout both lungs and mild tubular bronchiectasis within the lower lobes. Patient was started on amphoterecin and solumedrol. Bronchoscopy with trans-bronchial biopsy was performed and was complicated with significant bleeding. Pathology smears using H&E and GMS stains showed alveolar spaces filled with frothy eosinophilic material with cell debris and proliferating fungi with cup or boat shaped cysts. Congo red staining revealed apple green birefringence under polarized light microscopy. Diagnosis of Pneumocystis jirovecii pneumonia and concomitant interstitial pulmonary amyloidosis was made at that point. Patient was treated with steroids and bactrim. Interstitial pulmonary amyloidosis is usually a fatal disease, with median survival of 16 months. Fiberoptic bronchoscopy and biopsy is generally considered a safe approach for the diagnosis of pulmonary amyloid, although the biopsy must be carried out with caution due to a high risk of bleeding. In the Mayo clinic series, 11 patients had tranbronchial biopsy, with only two patients having had bleeding in excess of 100 cc. Treatment options for pulmonary amyloid include chemotherapy and stem cell transplantation. There is a 40% incidence rate of PCP pneumonia in recipients of solid organ transplants. Prognosis is worse when compared to PCP pneumonia in HIV patients, with mortality rates of 30-50%. Combination of PCP and pulmonary amyloidosis has not been reported in literature. Each disorder alone carries a significant mortality risk, and their concommitant occurence significantly increases mortality.

Anahita Dabo-Trubelja, Memorial Sloan-Kettering Cancer Center

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ABDOMINAL WALL HEMATOMA CAUSED BY LOW MOLECULAR WEIGHT HEPARIN (LMWH): TWO CASE REPORTS AND LITERATURE REVIEW

SEPSIS-INDUCED RIGHT VENTRICULAR DYSFUNCTION IN REFRACTORY SEPTIC SHOCK

Evamaria Nourbakhsh, Texas Tech, Kenneth Nugent, Texas Tech University, Reza Anvari, New York Medical College Introduction: Abdominal wall hematoma can occur with LMWH injections. This risk increases with concurrent illness, abdominal straining, use of platelet inhibitors, and renal disease. The complications of these hematomas include hemorrhagic shock, muscle necrosis, obstructive uropathy, MI, abdominal compartment syndrome and death. Our review of the literature recovered 30 case reports and we also report two cases seen in our hospital. Hypothesis: Hematomas secondary to injected LMWH can cause significant morbidity and mortality. Methods: We used PubMed to identify articles. Dates ranged from inception to June 2010. MeSH terms were abdominal wall hematomas, rectus sheath hematomas, enoxaparin, LMWH. Language restriction was English, but two nonEnglish articles were included. Results: Case 1 is a 70-year-old woman on full dose LMWH and Coumadin for atrial fibrillation who developed RSH complicated by abdominal compartment syndrome and was treated surgically. Case 2 is an 88-year- old woman with cough placed on full dose LMWH for possible PE who developed RSH complicated by shock and was treated conservatively. Thirty-two cases were found; 86% were female. The mean age was 72 years. Therapeutic doses were given to 21 patients. Nineteen received antiplatelet or other anticoagulation therapy. Renal disease was present in 15 patients; nine had cough, and four had COPD. The most common imaging study used was CT. Eleven patients were treated conservatively; epigastric artery embolization was performed in four patients; eleven underwent surgical intervention. Complications included shock, AKI, respiratory failure, abdominal compartment syndrome, peritoneal bleed, arrhythmia and death. Conclusions: The most common clinical manifestations of RSH include abdominal wall ecchymoses, abdominal pain, and a drop in hemoglobin. A combination of diminished wall compliance, transfusions and fluid resuscitations puts patients at risk for abdominal compartment syndrome. Treatment of choice is conservative, although surgery is recommended in patients who are hemodynamically unstable. The mortality rate is low, but clinicians should remain attentive to this possibility when using LMWH in the high risk patients.

Jaime Hernandez-Montfort, Geetika Sachdeva, Ashish Arora, Baystate Medical Center Case Report: 55 year-old gentleman with history of cerebral palsy and renal cell carcinoma on chemotherapy transferred from an inpatient rehabilitation facility for acute respiratory distress. Vital signs on admission: 102 F, 150 bpm, 70/54 mmHg and 33 bpm. Laboratory studies: WBC 400 k/mm3, Hb 13.3 Gm/dL, Hct 38.2%, PLT 23,000 k/mm3, BUN 21, Cr 1.2 mg/dL and D-dimer 1.57 mg/dL. Cardiac biomarkers were not elevated. INR and fibrinogen were normal. ABG on 100% 02 showed 7.36/32/60/18. EKG showed sinus tachycardia. CXR was relevant for left lower lobe opacity. Patient was intubated, resuscitated with 4 L of crystalloid and placed on IV vancomycin and piperacillin/tazobactam. In our ICU, additional 6 L of crystalloid were given, following norepinephrine infusion and stress dose corticosteroids. Transthoracic echocardiogram (TTE) revealed right ventricular (RV) systolic dysfunction with dilation. V/Q scan reported low probability for pulmonary embolism (PE). Vasoactive agent requirements increased in the next 48 hrs, despite additional vasopressin, with no changes in mechanical ventilation requirements, CXR and repeat TTE. In the setting of refractory shock, CT angiogram was performed which showed extensive bilateral posterior pleural effusions with consolidation and no PE. Inotropic support with dobutamine followed dramatic improvement in hemodynamics, leading to down titration of vasoactive agents, extubation and transfer to the medical floor in the next 7 days. RV dysfunction in sepsis results from decreased myocardial contractility and elevated pulmonary vascular resistance (PVR) despite a concomitant decrease in systemic vascular resistance. Diagnosis via bedside TTE usually reveals RV dilation and paradoxical septal motion. Treatment includes correcting the underlying cause of sepsis, fluid repletion, reversal of circulatory shock and correcting reversible causes of elevated PVR such as hypoxia, acidosis and lung hyperinflation. Addition of inotropic agents such as dobutamine or milrinone are considered a reasonable approach, however further research is needed to support this strategy which in our patient was proven to be effective.


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CRITICAL CARE CASES: ACUTE DISSEMINATING ENCEPHALOMYETLITIS: THE DIFFICULTIES IN DIAGNOSIS FROM A JUNIOR DOCTORS’ PERSPECTIVE

A CASE REPORT OF OPSI (OVERWHELMING POST SPLENECTOMY INFECTION) SYNDROME

Sanchia Goonewardene, Nikhil Bhasin, University Hospital Coventry and Warwickshire Introduction: Acute disseminated encephalomyelitis (ADEM) is an immunemediated inflammatory disorder of the central nervous system. It is associated with a disseminating pattern of demyelination, in a multifocal pattern involving white matter of the brain and spinal cord. The presenting features of this condition vary extensively. ADEM can present as acute onset of neurologic abnormalities including decreased mental alertness, multifocal neurological signs and deficits. This condition usually has a monophasic course, although recurrent cases have been reported. There are clinical and radiologic diagnostic features associated with ADEM, however, controversy regarding diagnosis still exists. The condition is such that delay in diagnosis can threaten a patients’ life. Case Report: We present the case of a 30 year old male, initially presenting with antisocial behaviour for which he had been jailed, prior to admission. However after presenting with a mixture of atypical neurological symptoms, he was then diagnosed with acute demyelinating encephalomyelitis. Discussion: We discuss his critical care management and outcome and the difficulties involved with diagnosis. This case is important as it highlights the importance of a rapid diagnosis of ADEM, and what may result if this condition is missed, or treatment is delayed from a junior doctors’ perspective.

Sinoj John, Rajeev Fernando, Dartmouth-Hitchcock Medical Center, Randy Loftus, Dartmouth Hitchcock Medical Center Case Report: OPSI (Overwhelming Post Splenectomy Infection) is a rare, fulminant sepsis which occurs in asplenic or hyposplenic patients, with mortality rate up to 50% and requires urgent treatment. Encapsulated organisms account for more than half of the cases and streptococcus pneumoniae is the most identified pathogen. Other organisms such as haemophilus influenza B and meningococcal C pathogens cause OPSI less frequently. A 31 year old woman with history of splenectomy two years ago and chronic transaminitis was transferred to our ICU for suspected cholangitis. Her immunizations were current. She reported a four day history of fevers, chills, epigastric pain and jaundice. Lab values were notable for a wbc 31,000, ALT/AST 383/286, alkaline phosphatase 282, total bilirubin 5.5 (direct 4.5) and lactate 6.8. The patient was febrile to 40°C with a blood pressure 80/40 mmHg despite aggressive fluid resuscitation, broad spectrum antibiotics and vasopressors. She ultimately required intubation for respiratory failure. A chest X-ray was unremarkable and cholangitis was excluded by abdominal imaging. She gradually improved with supportive therapy and was successfully extubated on ICU day seven. All cultures including peritoneal fluid were negative with no clear source of infection, but the patient had received five days of doxycycline before admission. The clinical diagnosis of OPSI from pneumococcal infection was supported by a history of her child having pneumonia and ear infection prior to the onset of her illness.The exact pathogenesis of OPSI is unclear, but loss of mechanical filtration by the spleen seems more important than immunologic deficiencies. Minimizing spleen removed by newer surgical techniques may reduce the incidence. Strategies to prevent OPSI include education, vaccination against encapsulated organisms such as streptococcus pneumoniae, haemophilus influenzae B, neisseria meningitidis and influenza (annually), daily antibiotics for at least two years postsplenectomy and emergency antibiotics for infection. Education regarding animal handling is required because of increased risk of OPSI due to capnocytophaga canimorsus from dog, cat or other animal bites.

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TWO IN ONE-HLH IN SEPSIS AND ACUTE MYELOFIBROSIS

CRITICAL CARE CASES: GAS IN THE PORTAL SYSTEM AND PORTAL VEIN PYAEMIA: A RARE CONDITION

Asma Siddiqui, Geisinger Medical Center, Omar Rahman, Geisinger Health System Background: A hemophagocytic syndrome is a rare process characterized by fever, hepatosplenomegaly, and cytopenias.Typically, a polyclonal activation of T lymphocytes and macrophages infiltrates the liver, spleen, bone marrow, and other sites.In adults, It is most often precipitated by viral infections, autoimmune disorders, or neoplastic diseases. Case Presentation: We present a case of a 47 year old caucasian male with fever, chills, weakness, presenting with ’ signs of sepsis’, maculopapular rash, severe neutropenia, anemia and splenomegaly. Pt was diagnosed as having MRSA bacteremia, HLH and acute primary myelofibrosis. Started on Vancomycin,Cefepime, Neupogen and doxycycline. Later referred for chemotherapy and immunotherapy after sepsis was resolved.WBC 0.4Plts:119 No BCR/ABL transcriptsNo JAK2 V617F Mutation was detected.Hb 8.0. Flow Cytometry: B cell population with no aberrent antigen or definitive evidence of light chain restriction.No abnormal T cell or Myeloid cell populations identified. Cytochemical Stains: Reticulin stains:severe diffuse fibrosis c/w acute myelofibrosis. Bone Marrow Biopsy: Increase in megakaryocytes and plasma cells. Hemophagocytosis of red cells and white cells. Diffuse fibrosisFerritin 1400Blood Cx MRSAMono spot and HIV: negativeLupus- negRetic count:0.5%Peripheral smear: macrophages engulfing white/ red blood cells. Marked leucopenia. Discussion: HLH has been associated with infections, collagen vascular diseases and malignancies. This diversity has suggested that HLH secondary to an underlying medical illness should be a reactive hemophagocytic syndrome. It mimics infections such as bacterial sepsis and leptospirosis and therefore obscures the diagnosis. Conclusion: HLH is a very syndrome that can be overlooked in severe sepsis. Better understanding of the pathophysiology may clarify the interations between the immune system and infectious agents. For patients with reactive HLH, supportive care and treatment of the underlying infection is associated with recovery in 60%-70% , otherwise death results from hemorrhage, infection, or multiorgan failure


Sanchia Goonewardene, Nikhil Bhasin, University Hospital Coventry and Warwickshire Introduction: Portal pyaemia is an incredibly rare condition. The mortality rate of patients with portal venous gas depends on the underlying cause, but it has been associated with fatal outcome. Factors which may lead to this include intestinal wall alterations, bowel distention, and sepsis. Case Report: We present the case of a 74 year old lady admitted to critical care,, initailly presenting with abdominalsymptoms over a one month period, and a known history of diverticulitis. She was diagnosed as having a portal pyaemia radiologically. We discuss this condition, the mechanism by which it may have arisen in this case and the importance for early surgery. Discussion: In order to determine the mechanism behind what occurred, we have to first understand the underlying pathology. It is possible that the ongoing intraabdominal sepsis, caused by the diverticulitis would have also resulted in obstruction, creating distension of the bowel wall and conduction of gas into the porto-mesenteric system. On top of that, the bowel wall was disrupted, demonstrated by gastric ulceration and GI bleeding. In addition this patient also had a pericolic abcess, which may have created a perforation in the mesocolic veins, resulting in gas entry. Also contributing to formation of the portal pyaemia would have been the partial thrombosis of the SMV. All of this would have culminated in the patients untimely demise added to the fact that the patient had suffered these symptoms for at least a month previously. We present this case,examine the mechanisms causing the pathology and the need for early surgery and critical care management.

1021 A RARE COMPLICATION OF RENAL BIOPSY Mustafa Albayrak, Aukje Huurman, Maasstad Ziekenhuis Introduction: Renal biopsy is a commonly used diagnostic tool in patients presenting with renal failure of unknown origin. However, this technique is not without risk. We present a case of fatal infectious pancreatitis, a rare complication of renal biopsy. Methods: A 42 year old male presented to our hospital with hypertension and renal failure. During the diagnostic process the patient underwent a renal biopsy procedure and was discharged the next day for further outpatient follow-up. After a few days the patient presented to our hospital with circulatory shock. A CT-scan revealed a large retroperitoneal hematoma and ongoing bleeding of the kidney that was biopsied. The bleeding kidney was successfully coiled by our interventional radiologist, stopping the blood loss. Results: The pathological result of the kidney biopt revealed hypertensive nephropathy and offered no further therapeutic benefits. A few days later the patient displayed symptoms of sepsis and he was admitted to our intensive care unit (ICU) for mechanical ventilation and hemodynamic support. A CT-scan revealed infection of the retroperitoneal hematoma and secondary severe infectious pancreatitis with multiple retroperitoneal and intra-abdominal fluid collections. He was treated with antibiotics, drainage of the fluid collections and eventually surgical laparotomy. During his treatment on our ICU the patient developed massive blood loss in one of the drained fluid collections and was successfully coiled again by our interventional radiologist. He also developed colonisation and infections at several sites with multi-resistant pseudomonas, ESBL positive klebsiella and vancomycin resistant enterococci. After a treatment of 3,5 months on our ICU the patient died of therapy resistant sepsis, multi-organ failure and failure to thrive. Conclusions: To our knowledge, infectious pancreatitis has never been reported before as a complication following renal biopsy and should be added to the list of possible adverse outcomes. The indication of renal biopsy should be critically appraised and the benefits carefully weighed against the risks before it is attempted.

1022 NEAR-FATAL ANGIOEDEMA COMPROMISING THE AIRWAY IN A PATIENT FOLLOWING ACEI SUBSTITUTION Harris Shaikh, RWJMS/UMDNJ, John Denny, Robert Wood Johnson Medical School/UMDNJ, Sana Shaikh, Maria Negron, RWJMS/UMDNJ, Julia Denny, St. Peters University Hospital, Bo-Lu Zhou, RWJMS/UMDNJ, Steven Ginsberg, Robert Wood Johnson Medical School/UMDNJ, Angela Denny, The College of New Jersey, Sharon Morgan, Robert Wood Johnson Medical School/ UMDNJ Case Report: Angioedema (AE) is a side effect of ACE Inhibitor therapy. We report a rare case in which a patient who had tolerated years of therapy with enalapril, developed life-threatening AE after being switched to lisinopril in the hospital. Patient is an 81 y.o. with PMH of PVD, DM, HTN, CHF, s/p CABG, AFib, and TIA. Pt was s/p femoral art. endarterectomy which became infected requiring an I⫹D and flap. The patient was extubated. Her home Rx of Enalapril was substituted with Ramipril. Six hours later, pt developed AE with stridor. Pt. received nebulized Epinephrine, Benadryl and Hydrocortisone. With the tongue swelling, the patient was correctly identified as a “difficult airway,” (DA) and Anesthesia was called stat to evaluate the patient. Since the patient’s respiratory status was deteriorating but still temporarily adequate, and likely a DA, an awake endotracheal intubation was elected. A glidescope was used to advance a 6.0 ET tube after 2 previous attempts failed. Pt. was started on a steroid taper and weaned. She was extubated uneventfully three days later. Discussion: 1) AE is a medical emergency and requires close monitoring as is routinely provided in an intensive care unit. 2.) Identification of patients with suspected DA before considering giving “intubating drugs,” or sedation is of utmost importance. 3) Anticipating difficulty in one’s ability to readily secure an airway requires the presence of professionals and equipment that will facilitate adherence to the ASA algorithm for DA management. Rendering this patient unconscious with drugs would likely have produced a catatrophic situation where the patient could not be easily intubated, nor could be mask ventilated. This cannot ventilate, cannot intubate situation, can rapidly progress to desaturation and cardiac arrest. This is especially true in intensive care unit patients (even with normal airways) who commonly have very limited reserves. 4) ACEI can cause AE even after prolonged use. In this case, an acute change in the ACEI prescribed likely triggered the AE. It may be appropriate to be cautious in switching ACEI’s without a compelling reason.

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1024

A CASE OF POSTOPERATIVE THYROTOXICOSIS MIMICKING ACUTE PULMONARY THROMBOEMBOLISM - A DIAGNOSTIC DILEMMA

ACUTE PERICARDITIS AND TAMPONADE CAUSED BY PNEUMOCOCCUS IN A 6 MONTH OLD CHILD

Sujatha Pentakota, Lashonda Williams, Brigham and Women’s Hospital, Selwyn Rogers, Brigham & Women’s Hospital Case Report: Our patient is a 57yo male s/p revision left hip arthroplasty who developed fever and asymptomatic supraventricular tachycardia (HR 120-160) with relative hypotension on POD#2. His physical exam was unremarkable.He was saturating 99% on room air and denied palpitations, dyspnea or chest pain. His CBC, electrolytes and cardiac enzymes were within normal limits. His CXR was normal. EKG revealed SVT/atrial flutter with variable conduction. His history was significant for hypertension and some thyroid abnormality for which he was being worked up by his PCP. As per the patient his PCP had felt his thyroid gland abnormal on palpation and had referred him to an endocrinologist who in turn had done some tests. The patient was unaware of the results of the tests. He was not on any thyroid meds preop. His tachycardia was refractory to intravenous fluids, beta blockers and calcium channel blockers. He was transferred to SICU for further care. In the ICU he developed atrial fibrillation with rapid ventricular rate and hemodynamic instability. He did not respond to electric cardioversion. Intravenous amiodarone slowed down his ventricular rate to 120s and hence was started on an amiodarone drip. A transthoracic echo revealed right ventricular dysfunction with pulmonary arterial hypertension. There was no previous echo for comparison. Thyroid function studies were sent off. The patient was asymptomatic during this entire event. A differential of pulmonary embolism was considered and as his pretest probability for PE was high (hip surgery, immobilization⬎48hrs, acute RV strain and pulmonary hypertension), he was anticoagulated with heparin and underwent CTA. The study was negative for PE. He spontaneously reverted to sinus tachycardia a few hours later.Meanwhile his thyroid function test results revealed T4 hyperthyroidism. His endocrinologist was contacted and his old records accessed. His thyroid profile done a few months earlier was suggestive of hyperthyroidism and his thyroid scan was suggestive of Graves’ disease. He was started on methimazole and beta blockers. His heart rate slowed down to 100-120 and remained so until his discharge from the hospital three days later.

Srinivasarao Badugu, Jai Udassi, Nicholas Slamon, University of Florida College of Medicine Case Report: A 6-month-old male, previously healthy infant presented to the emergency room with a one-week history of fever and breathing difficulty. He was born at term, had normal growth, development and immunizations (including 2, 4 month doses of prevnar). He was presumed to have a viral upper respiratory tract infection and was discharged home. As the symptoms persisted, he was brought back to medical attention and was given an intramuscular dose of ceftriaxone for presumed bacterial infection. He was admitted that night to the local hospital with worsening respiratory distress. On physical examination at the time of admission, he had respiratory distress, no hemodynamic compromise, and chest radiograph showed an enlarged cardiac silhouette with right pleural effusion. He was started on with ceftriaxone and vancomycin for pneumonia and sepsis. Overnight his respiratory status deteriorated, he was intubated for respiratory failure and was transferred to the referral hospital. Upon admission to the teaching hospital, he was noted to have tachycardia, poor peripheral pulses and significant hepatomegaly. He soon decompensated despite the fluid boluses and escalating inotropes (dopamine and norepinephrine). Electrocardiogram showed generalized ST-segment elevation. A bedside echocardiographic study showed a significant pericardial effusion with tamponade physiology. An emergency pericardiocentesis was performed under echo guidance with the removal of cloudy, yellow and thick pericardial fluid. Hemodynamic status and the ventricular function improved immediately after the pericardiocentesis. Pericardial fluid showed diplococci and culture subsequently grew pneumococci. Peripheral blood cultures grew S.pneumoniae and he was treated with ceftriaxone and rifampin. The S. pneumoniae isolate had penicillin sensitivity. The immunological workup was unremarkable and the patient was HIV-negative. Patient received mechanical ventilatory support for 19 days and his clinical course was complicated by further bacteremia with E.cloacae, pleural thickening and constrictive pericarditis.


1025 CRITICAL CARE CASES: ARTERIAL LINE REMOVAL AND CARPAL TUNNEL SYNDROME: A NEW CAUSE Sanchia Goonewardene, Nikhil Bhasin, University Hospital Coventry and Warwickshire Introduction: Carpal tunnel syndrome (CTS) is one of the most common upper limb compression neuropathies [8] caused by compression of the median nerve as it runs through the carpal tunnel in the wrist. The exact pathogenesis of CTS is unclear, with a number of theories. There are over 2000 case reports on causes of carpal tunnel syndrome, yet none describe carpal tunnel syndrome secondary to removal and haemorrhage from a radial artery line. Case Report: We present the case of a 55 year old male patient, initially admitted to University Hospital Coventry and Wariwckshire Critical care unit as a transfer after being involved in an RTC, who presented with a case of carpal tunnel syndrome secondary to radial artery line removal, with associated neurological symptoms, which resolved after 48 hrs. Discussion: We discuss reasons for why this may have occurred in line with a number of theories including mechanical compression, micro-vascular insufficiency and vibration theories. This case is important as this is a never before reported complication of radial artery compression.
