Effect of Normal Saline Infusion on the Diagnostic Utility of Base Deficit in Identifying Major Injury in Trauma Patients Richard Sinert, DO, Shahriar Zehtabchi, MD, Christina Bloem, MD, Michael Lucchesi, MD
Abstract Background: Base deficit (BD) is a reliable marker of metabolic acidosis and is useful in gauging hemorrhage after trauma. Resuscitation with chloride-rich solutions such as normal saline (NS) can cause a dilutional acidosis, possibly confounding the interpretation of BD. Objectives: To test the diagnostic utility of BD in distinguishing minor from major injury after administration of NS. Methods: This was a prospective observational study at a Level 1 trauma center. The authors enrolled patients with significant mechanism of injury and measured BD at triage (BD-0) and at four hours after triage (BD-4). Major injury was defined by any of the following: injury severity score of R15, drop in hematocrit of R10 points, or the patient requiring a blood transfusion. Patients were divided into a low-volume (NS < 2L) and a high-volume (NS R 2L) group. Data were reported as mean (SD). Student’s t- and Wilcoxon tests were used to compare data. Receiver operating characteristic (ROC) curves tested the utility of BD-4 in differentiating minor from major injury in the study groups. Results: Four hundred eighty-nine trauma patients (mean age, 36 [ 18] yr) were enrolled; 82% were male, and 34% had penetrating injury. Major-(20%) compared with minor-(80%) injury patients were significantly (p = 0.0001) more acidotic (BD-0 mean difference: 3.3 mmol/L; 95% confidence interval [CI] = 2.5 to 4.2). The high-volume group (n = 174) received 3,342 (1,821) mL, and the low-volume group (n = 315) received 621 (509) mL of NS. Areas under the ROC curves for the high-volume (0.63; 95% CI = 0.52 to 0.74) and low-volume (0.73; 95% CI = 0.60 to 0.86) groups were not significantly different from each other. Conclusions: Base deficit was able to distinguish minor from major injury after four hours of resuscitation, irrespective of the volume of NS infused. ACADEMIC EMERGENCY MEDICINE 2006; 13:1269–1274 ª 2006 by the Society for Academic Emergency Medicine Keywords: trauma, base deficit, normal saline, injury, diagnosis
B
ase deficit (BD) measured after hemorrhage is highly correlated to the production of lactic acid from inadequate tissue perfusion.1,2 Base deficit has been recommended as a surrogate marker for lactate because of the strong correlation between the initial BD and lactate in trauma patients.3,4 Base deficit has been shown to be a reliable indicator of blood loss,5 adequacy of resuscitation,6,7 and mortality in trauma patients.8,9 Base deficit takes on even more significance considering
From the Department of Emergency Medicine, State University of New York, Downstate Medical Center–Kings County Hospital Center (RS, SZ, CB, ML), New York, NY. Received May 26, 2006; revisions received July 7, 2006, and July 14, 2006; accepted July 17, 2006. Contact for correspondence and reprints: Richard Sinert, DO; e-mail:
[email protected].
ª 2006 by the Society for Academic Emergency Medicine doi: 10.1197/j.aem.2006.07.027
that traditional vital signs could be relatively insensitive to hypovolemia.10 Abou-Khalil et al. found that 85% of invasively monitored young trauma patients could maintain a normal heart rate and blood pressure even in the face of a significant oxygen debt after a large blood loss.11 Similarly, Scalea and his colleagues showed that elder trauma patients may have significant tissue hypoperfusion as a result of hemorrhage, despite maintaining normal vital signs.12 Several investigators have reported a very poor correlation between BD and arterial lactate after the initial resuscitation period.13–15 Skellet et al.16 and Brill et al.17 both have shown that saline infusion in humans may dilute the BD, falsely depress BD, unlink its correlation with lactate, and ultimately affect its correlation to tissue hypoxia. Finally, a large number of case reports have described dilutional acidosis after fluid infusion in a wide variety of clinical scenarios.18–25
ISSN 1069-6563 PII ISSN 1069-6563583
1269
1270
Because the majority of these case reports of dilutional acidosis have been in the anesthesia and the intensive-care literature, we were interested to see whether dilutional acidosis was a confounding factor during emergency department (ED) trauma resuscitations. If dilutional acidosis occurred with the volumes of saline that routinely are given during trauma resuscitations, then BD would be depressed falsely. This potentially could limit the ability of BD to efficiently distinguish severely injured patients. We tested the null hypothesis that saline infusion during the initial few hours of ED trauma resuscitation would have no effect on the utility of BD in differentiating major from minor injuries. METHODS Study Design This was a prospective observational study of trauma patients to investigate the influence of normal saline (NS) infusion on the diagnostic ability of BD to detect major injury in adult trauma patients in the ED. The study was approved by the institutional review board (IRB). The informed-consent requirement was waived by the IRB. Study Setting and Population This study was conducted from October 2004 to September 2005 at Kings County Hospital Center, an academic Level 1 trauma center with approximately 150,000 ED visits and 1,800 trauma admissions annually. We enrolled a convenience sample of trauma patients (13 yr of age or older) who required laboratory analysis as part of their diagnostic evaluation (inclusion criteria) as per the treating emergency physician. Patients who received any intravenous fluid other than NS (e.g., D5-1/2 NS, lactated Ringer’s solution, etc.) and those who were transferred from other institutions were excluded from the study. We also excluded patients who died and who were discharged or were transferred to the operating room before completion of enrollment and data collection. Study Protocol We evaluated the effect of NS infusion on BD four hours after fluid resuscitation. The four-hour period was selected as an approximation of the time that trauma patients stay in the ED for the workup and treatment before disposition. This period started with insertion of an intravenous line for fluid infusion at the beginning of resuscitation in the ED. An arterial blood sample routinely is obtained at the same time for measurement of BD and lactate (time 0; BD-0). After four hours, the volume of infused NS was recorded, and the arterial BD measurement was repeated (time 4 hours; BD-4). On designated shifts on which data abstractors (academic associates) were available, all trauma patients meeting the inclusion criteria were enrolled consecutively. Academic associates are medical students or undergraduate students who assist our department in data collection during their research elective. They were trained before the start of this study and were certified to assist in data collection after passing an online IRB certification course. Data abstractors were not involved in patient care at any level. They recorded demographic data, vital signs
Sinert et al.
NORMAL SALINE AND BASE DEFICIT
(systolic and diastolic blood pressure, pulse rate), and mechanism of injury for all patients. Upon patients’ arrival to the ED, arterial pH, BD, and lactate (Radiometer ABL 725, Copenhagen, Denmark) were measured. Data abstractors documented the results of imaging studies (radiographs and computed-tomography scans) and all other diagnostic procedures. Upon completion of the trauma workup, injury severity scores (ISS) were calculated. ISS was graded according to the 1990 revision of the Abbreviated Injury Scale (AIS).26 We also recorded the volume of NS that was administered to the patients during the study period (4 h). Outcome Measures The primary outcome measure in this study was the ability of BD to discriminate major from minor injury after four hours of saline infusion. Arterial BD was measured at baseline (BD-0) and after four hours (BD-4). We classified injuries as major if ISS was R15, if the drop in hematocrit was more than 10 points over 24 hours, or if blood transfusion was required in the first 24 hours. These criteria commonly are employed for definition of major trauma in the literature.27,28 ISS of R15 requires a single grade 4 injury on the AIS, or two AIS-3 injuries. This criterion more accurately reflects the degree of blood loss, severity of injury, and mortality than vital signs alone.11,12,29 To investigate the effect of NS infusion on BD, patients were categorized into two groups on the basis of the volume of infused NS. We chose 2 L of NS infusion as the cutoff for defining the two study groups: a low-volume group who received less than 2 L of NS during the study period and a high-volume group who received 2 L or more of NS. Data Analysis A sample-size analysis for the receiver operating characteristic (ROC) curve was determined on the basis of a desired area under the curve (AUC) of 0.75 (moderate accuracy), a = 0.05, and b = 0.20 with two tails. A minimum of 50 subjects in each group (minor vs. major injury) would produce an SE for estimated AUC of 0.04.30 The ratio of patients with and without major injury was set at 4 to 1 on the basis of the relative proportion of minor to major injury in our institution. Data were reported as means ( SD). We tested the diagnostic performance of BD-0 and BD-4 in detecting major injury in our study subjects by using ROC curves.30 Student’s t-test was used to analyze continuous variables for differences between the groups. Categorical data were analyzed by using Fisher’s exact test. Wilcoxon’s test was used to compare the AUCs. Statistical significance was defined as p < 0.05. All statistical tests were two tailed. Calculations were done by using SPSS (Chicago, IL) for Windows, release 11.0. RESULTS During the study period, a total of 639 patients met the enrollment criteria (suspected major injury and the requirement for laboratory workup). Twenty-nine patients who received fluids other than NS were excluded. Another 121 patients were excluded because the amount of infused NS at
ACAD EMERG MED
December 2006, Vol. 13, No. 12
www.aemj.org
1271
Table 1 Comparison of Baseline Characteristics of Study Patients in the Two Groups of Major and Minor Injury Characteristic
Minor Injury (n = 389)
Major Injury (n = 100)
Age, yr (SD) Gender (% male) Mechanism (% blunt) Base deficit (baseline, SD) Lactate (baseline, SD) Mortality (%) Intravenous fluid (mL, SD)
36 17 91 67 0.8 3.5 2.5 2.1 0.5 1,135 1,125
36 18 79 50 4.1 4.7 4.2 3.4 12 3,357 2,464
four hours was not documented. The final analysis was performed on the remaining 489 patients. The sample population consisted of 400 males (82%) and 89 females (18%). The mean age was 35 ( 17) years (range, 13–95 yr). One hundred patients (20%) had major injuries, and the remaining 389 patients (80%) were categorized as having minor injuries. Mechanisms of injury included penetrating trauma in 178 patients (36%) and blunt trauma in 311 patients (64%). Penetrating trauma consisted of stab wounds in 101 patients (57%), gunshot wounds in 73 patients (41%), and other penetrating injuries in 4 patients (2%). Blunt-trauma mechanisms were as follows: motor vehicle crash (n = 80; 26%), pedestrians struck (n = 61; 20%), assaults (n = 60; 19%), falls (n = 70; 23%), motorcycle crashes (n = 6; 2%), bicycle crashes (n = 10; 3%), and other (n = 24; 7%). Comparison of baseline variables among the study groups is presented in Table 1. Compared with minortrauma patients, major-trauma patients had a significantly more negative BD (mean difference: 3.3 mmol/ L, 95% CI = 2.5 to 4.2) and higher lactate levels (mean difference: 1.7 mmol/L, 95% CI = 1.1 to 2.3). The mortality rate also was higher in patients with major injury compared with the case of the minor-injury group (0.5% vs. 12%, p < 0.0001). We used analysis of ROC curves to test the diagnostic performance of admission BD (BD-0) in detecting major injury in the study subjects. The area under the ROC curve for BD-0 (AUC: 0.69; 95% CI = 0.63 to 0.77) was significantly different (p = 0.0001) from the unity line (Figure 1). At time 4 hours, 315 patients comprised the lowvolume group, receiving 621 (509) mL of NS, whereas 174 patients comprised the high-volume group, receiving 3,342 (1,821) mL. Both of the ROC curves for BD-4 in the low- and high-volume groups were successful (p < 0.001) at differentiating minor from major injury (Figures 2 and 3). However, the ROC curve for the lowvolume group (AUC: 0.73, 95% CI = 0.60 to 0.86) was not significantly different (p > 0.05) from that of the high-volume group (AUC: 0.63, 95% CI = 0.52 to 0.74).
Figure 1. Receiver operating characteristic curve for diagnostic performance of base deficit at baseline (BD-0) in distinguishing major from minor injury. AUC = area under the curve.
mL) that our study population received during routine trauma resuscitation. Dilutional acidosis may not be an accurate description of the metabolic acidosis that is seen after saline loading.
DISCUSSION The results of our study indicate that BD remains an accurate surrogate marker for major injury after trauma, even after saline infusion. Base deficit correlated well with degree of injury, in both patients with and without saline loading. It does not appear that dilutional acidosis occurred with the volume of saline (approximately 2,416
Figure 2. Receiver operating characteristic curve for diagnostic performance of base deficit four hours after injury (BD-4) in distinguishing major from minor injury in the low-volume group. AUC = area under the curve.
1272
Figure 3. Receiver operating characteristic curve for diagnostic performance of base deficit at four hours after injury (BD-4) in distinguishing major from minor injury in the highvolume group. AUC = area under the curve.
Waters and Bernstein studied the role of so-called dilution in dilutional acidosis via a crossover experiment.18 They measured the acid–base status of 11 healthy volunteers after volume loading (15 mL/kg) with two different colloid solutions. In this study, infusion of hetastarch, a chloride-rich fluid (Na+ = 154 mEq/L, Cl = 154 mEq/L), was compared with an equal amount of salt-poor albumin (Na+ = 154 mEq/L, Cl = 93 mEq/L). Plasma volumes before and after infusion were estimated by the change in hemoglobin and hematocrit. Hetastarch and albumin both equally diluted the plasma volume, but only hetastarch, the chloride-rich fluid, resulted in acidosis in the study subjects. Waters and Bernstein concluded that dilutional acidosis was not related to the diluting effect of the infused fluid but that the acidosis was a direct result of an increase in serum chloride.18 Unfortunately, the classic approach to acid–base balance, the Henderson-Hasselbalch equation, cannot adequately explain hyperchloremic acidosis.31 In 1983, Stewart32 published an alternative approach to the Henderson-Hasselbalch theory of acid–base balance. Stewart based his description of acid–base disorders on the requirement that all solutions must have an equal balance of dissociated cations and anions (law of electroneutrality). Stewart described all acid–base disturbances by the relation of the concentrations of the most dissociated plasma ions, the so-called strong ions (Na+, Ca++, Mg++, K+, Cl , and lactate), pCO2, and the weak acids (mostly albumin). Changes in the concentrations of any of the strong ions would alter the balance of cations to anions. The law of electroneutrality then requires reciprocal changes in the dissociation of plasma water to rebalance
Sinert et al.
NORMAL SALINE AND BASE DEFICIT
the solution. Stewart coined the term strong ion difference (SID; SID = [Na + Ca + Mg + K] [Cl + Lactate]) to describe the relationship of the strong cations to anions in the plasma. Increases in measured (Cl + Lactate) or unmeasured anions decreases the SID, which must be balanced by increases in free hydrogen to maintain plasma electroneutrality. Hyperchloremic acidosis then is a direct consequence of the increased dissociation of water, raising the free-hydrogen concentration to balance a higher serum chloride. This approach to acid–base balance provides us with a quantifiable relationship between serum chloride and acidosis, which does not depend upon so-called dilution. Using the SID explanation of hyperchloremic acidosis allows us to analyze the previous literature on dilutional acidosis with respect to the amount of chloride infused. Our patients did not appear to have a dilutional acidosis after an average infusion of 2.5 L of saline, which corresponds to approximately 385 mEq of chloride. Yet larger infusions of chloride in studies by Waters et al.24 (w593 mEq of chloride) and Scheingraber et al.25 (w924 mEq of chloride) both resulted in significant decreases in BD of 3.49 mmol/L and 6.7 mmol/L, respectively. Scheingraber et al.25 found that only NS (chloride = 154 mEq/L) compared with lactated Ringer’s (chloride = 90 mEq/L) could increase serum chloride sufficiently to cause a hyperchloremic acidosis. Waters et al.24 went on to show a significant (p < 0.0001) correlation (r2 = 0.93) between the amount of chloride infused and the change in BD. We believe that we did not see the hyperchloremic acidosis in our patients because during a typical trauma resuscitation in a real clinical setting, only a small load of chloride is infused to the patients. Once the chloride is infused, the natural buffering capacity of the kidneys and plasma will begin to repair the hyperchloremic acidosis. In the Waters and Bernstein study,18 the hyperchloremic acidosis was only evident up to 210 minutes after infusion; by the end of the 300minute observation period, the hyperchloremic acidosis in the hetastarch group had disappeared. So the timing of the acid–base measurement, in addition to the dose of chloride infused, may impact both the presence and severity of the hyperchloremic acidosis. We tested the BD of our trauma patients four hours after triage, which also may explain why we did not see their hyperchloremic metabolic acidosis. In summary, the lack of a hyperchloremic metabolic acidosis in our patients after typical trauma resuscitations maintained the ability of BD to effectively differentiate major from minor injuries ever after four hours of fluid therapy. This is not to say that significantly larger volumes of NS, especially in closer proximity to the infusion time, may not falsely depress the BD. The emergency physician should be cognizant of saline-induced hyperchloremic acidosis and should not confuse a decreasing BD with the more ominous causes of metabolic acidosis. Although the first impression for a worsening acidosis in a trauma patient should be the possibility of continued hemorrhage, a hyperchloremic acidosis from saline should be kept in mind before the clinician reflexively begins a volume challenge. By using the principles of Stewart’s SID,32 the acidosis quickly can be identified as being from hyperchloremia or from a more serious cause.
ACAD EMERG MED
December 2006, Vol. 13, No. 12
www.aemj.org
LIMITATIONS Our study is limited by convenient sampling of an uncontrolled observational methodology. We did not prospectively require a fluid resuscitation protocol. Instead, the volume of intravenous fluid was determined at the discretion of the emergency physicians. We also excluded trauma patients with minimal mechanisms of injury and those with obvious severe injuries who died or were transferred to the operating room before completion of the four-hour observation. Finally, preponderance of male gender in our study sample, selection of arbitrary cutoff of 2 L of NS infusion for categorizing the patients into low-volume and high-volume groups, and exclusion of a large number of patients because of inadequate documentation should be considered as limitations of this study. Strict inclusion criteria, optimal data collection, and standardization of infusion practices could have altered our findings. It is possible that measurement of the BD before four hours would have shown the hyperchloremic acidosis that was missed at the four-hour measurement point. Our inclusion requirement of repeat BD four hours after triage excluded patients who died or went to surgery before the collection of this data point. This skewed our sample population toward a less acutely injured trauma group.
CONCLUSIONS Normal saline given during the initial trauma resuscitations does not affect the ability of BD to differentiate minor from major injury. We also did not find a significant dilutional acidosis at the usual volumes of saline that are infused during the initial four hours of trauma resuscitations.
References 1. Davis JW. The relationship of base deficit to lactate in porcine hemorrhagic shock and resuscitation. J Trauma. 1994; 36:168–72. 2. Dunham CM, Siegel JH, Weireter L, et al. Oxygen debt and metabolic acidemia as quantitative predictors of mortality and the severity of the ischemic insult in hemorrhagic shock. Crit Care Med. 1991; 19:231–43. 3. Aslar AK, Kuzu MA, Elhan AH, Tanik A, Hengirmen S. Admission lactate level and the APACHE II score are the most useful predictors of prognosis following torso trauma. Injury. 2004; 35:746–52. 4. Kincaid EH, Miller PR, Meredith JW, Rahman N, Chang MC. Elevated arterial base deficit in trauma patients: a marker of impaired oxygen utilization. J Am Coll Surg. 1998; 187:384–92. 5. Davis JW, Parks SN, Kaups KL, Gladen HE, O’Donnell-Nicol S. Admission base deficit predicts transfusion requirements and risk of complications. J Trauma. 1996; 41:769–74. 6. Davis JW, Shackford SR, Holbrook TL. Base deficit as a sensitive indicator of compensated shock and tissue oxygen utilization. Surg Gynecol Obstet. 1991; 173: 473–6.
1273
7. Davis JW, Kaups KL, Parks SN. Base deficit is superior to pH in evaluating clearance of acidosis after traumatic shock. J Trauma. 1998; 44:114–8. 8. Rutherford EJ, Morris JA Jr, Reed GW, Hall KS. Base deficit stratifies mortality and determines therapy. J Trauma. 1992; 33:417–23. 9. Tremblay LN, Feliciano DV, Rozycki GS. Assessment of initial base deficit as a predictor of outcome: mechanism of injury does make a difference. Am Surg. 2002; 68:689–93. 10. McGee S, Abernethy WB 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic? JAMA. 1999; 281:1022–9. 11. Abou-Khalil B, Scalea TM, Trooskin SZ, Henry SM, Hitchcock R. Hemodynamic responses to shock in young trauma patients: need for invasive monitoring. Crit Care Med. 1994; 22:633–9. 12. Scalea TM, Simon HM, Duncan AO, et al. Geriatric blunt multiple trauma: improved survival with early invasive monitoring. J Trauma. 1990; 30:129–34. 13. Mikulaschek A, Henry SM, Donovan R, Scalea TM. Serum lactate is not predicted by anion gap or base excess after trauma resuscitation. J Trauma. 1996; 40:218–24. 14. Martin MJ, Fitzsullivan E, Salim A, Brown CV, Demetriades D, Long W. Discordance between lactate and base deficit in the surgical intensive care unit: which one do you trust? Am J Surg. 2006; 191:625–30. 15. Jeng JC, Jablonski K, Bridgeman A, Jordan MH. Serum lactate, not base deficit, rapidly predicts survival after major burns. Burns. 2002; 28:161–6. 16. Skellett S, Mayer A, Durward A, Tibby SM, Murdoch IA. Chasing the base deficit: Hyperchloraemic acidosis following 0.9% saline fluid resuscitation. Arch Dis Child. 2000; 83:514–6. 17. Brill SA, Stewart TR, Brundage SI, Schreiber MA. Base deficit does not predict mortality when secondary to hyperchloremic acidosis. Shock. 2002; 17: 459–62. 18. Waters JH, Bernstein CA. Dilutional acidosis following hetastarch or albumin in healthy volunteers. Anesthesiology. 2000; 93:1184–7. 19. Mirza BI, Sahani M, Leehey DJ, Patel SB, Yang VL, Ing TS. Saline-induced dilutional acidosis in a maintenance hemodialysis patient. Int J Artif Organs. 1999; 22:676–8. 20. Oh MS, Banerji MA, Carroll HJ. The mechanism of hyperchloremic acidosis during the recovery phase of diabetic ketoacidosis. Diabetes. 1981; 30: 310–3. 21. Liskaser FJ, Bellomo R, Hayhoe M, et al. Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis. Anesthesiology. 2000; 93:1170–3. 22. Jaber BL, Madias NE. Marked dilutional acidosis complicating management of right ventricular myocardial infarction. Am J Kidney Dis. 1997; 30:561–7. 23. Mathes DD, Morell RC, Rohr MS. Dilutional acidosis: is it a real clinical entity? Anesthesiology. 1997; 86: 501–3. 24. Waters JH, Miller LR, Clack S, Kim JV. Cause of metabolic acidosis in prolonged surgery. Crit Care Med. 1999; 27:2142–6.
1274
25. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology. 1999; 90:1265–70. 26. Association for the Advancement of Automotive Medicine. The Abbreviated Injury Scale, 1990 Revision. Des Plaines, IL: Association for the Advancement of Automotive Medicine, 1990. 27. Dunham CM, Watson LA, Cooper C. Base deficit level indicating major injury is increased with ethanol. J Emerg Med. 2000; 18:165–71. 28. Zehtabchi S, Baron BJ, Sinert R, et al. Ethanol and illicit drugs do not affect the diagnostic utility of base deficit and lactate in differentiating minor from major
Sinert et al.
29.
30.
31.
32.
NORMAL SALINE AND BASE DEFICIT
injury in trauma patients. Acad Emerg Med. 2004; 11: 1014–20. Baker SP, O’Neill B, Haddon W Jr, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974; 14:187–96. Hanely JA, McNeil BJ. The meaning and the use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982; 143:29–36. Constable PD. Hyperchloremic acidosis: the classic example of strong ion acidosis. Anesth Analg. 2003; 96:919. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983; 61:1444–61.
