Intensive Care Med (2005) 31:927–933 DOI 10.1007/s00134-005-2640-2
L. Cabr J. Mancebo J. F. Solsona P. Saura I. Gich L. Blanch G. Carrasco M. C. Martn and the Bioethics Working Group of the SEMICYUC
Received: 29 February 2004 Accepted: 6 April 2005 Published online: 26 April 2005 Springer-Verlag 2005
L. Cabr ()) · G. Carrasco Hospital de Barcelona, SCIAS, Diagonal 660, 08034 Barcelona, Spain e-mail:
[email protected] Tel.: +34-93-2542400 Fax: +34-93-2542402 J. Mancebo · I. Gich Hospital Sant Pau, Barcelona, Spain J. F. Solsona Hospital del Mar, Barcelona, Spain P. Saura · L. Blanch Hospital Parc Taul, Sabadell, Barcelona, Spain M. C. Martn Hospital General de Catalunya, Sant Cugat del Valls, Barcelona, Spain
ORIGINAL
Multicenter study of the multiple organ dysfunction syndrome in intensive care units: the usefulness of Sequential Organ Failure Assessment scores in decision making
Abstract Objective: This study examined the incidence and mortality of multiple organ dysfunction syndrome (MODS) in intensive care units, evaluated the limitation of life support in these patients, and determined whether daily measurement of the Sequential Organ Failure Assessment (SOFA) is useful for decision making. Design and setting: Prospective, observational study in 79 intensive care units. Patients and participants: Of the 7,615 patients admitted during a 2-month period we found 1,340 patients to have MODS. Measurements and results: We recorded mortality and length of stay in the intensive care unit and the hospital and the maximum and minimum total SOFA scores during MODS. Limitation of life support in MODS patients was also evaluated. Stepwise logistic regression was used to determine the factors predicting mortality. The inhospital mortality rate in patients
Introduction The Multiple organ dysfunction syndrome (MODS) is an evolving clinical syndrome triggered by various stimuli. It is the main cause of morbidity and mortality in patients admitted to intensive care units (ICU) [1]. Many severity indices have been used to assess illness severity, including the Acute Physiology and Chronic Health Evaluation (APACHE) [2], the Simplified Acute Physiology Score (SAPS) [3], and the Mortality Prediction Model (MPM) [4]. These indices enable calculation of the standardized hospital mortality, i.e., the ratio between observed mor-
with MODS was 44.6%, and some type of limitation of life support was applied in 70.6% of the patients who died. The predictive model maximizing specificity included the following variables: maximum SOFA score, minimum SOFA score, trend of the SOFA for 5 consecutive days, and age over 60 years. The model diagnostic yield was: specificity 100%, sensitivity 7.2%, positive predictive value 100%, and negative predictive value 57.3%; the area under the receiver operating characteristic curve was 0.807. Conclusions: This model showed that in our population with MODS those older than 60 years and with SOFA score higher than 9 for at least 5 days were unlikely to survive. Keywords Multiple organ dysfunction syndrome · Limiting life support
tality and expected mortality. However, these prognostic prediction models do not take the patient’s course during ICU stay into account, thus limiting their usefulness in later decision making in the course of the disease. Several instruments have been developed in recent years to quantify the severity of MODS, in particular the Multiple Organ Dysfunction Score [5], the Logistic Organ Dysfunction Score (LODS) [6], and the Sequential Organ Failure Assessment (SOFA) [7]. All evaluate the Multiple Organ Dysfunction Score as a continuous and dynamic phenomenon and quantify the dysfunction of individual organs. SOFA and the other indices are not calculated on
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Table 1 Reason for the admission of MODS patients (COPD chronic obstructive pulmonary disease) Emergency postoperative surgery Heart diseases Pneumonia Elective surgery Multiple injuries COPD exacerbation Digestive disorders Miscellaneousa
n
%
274 210 165 156 101 77 66 292
20 16 12 12 8 6 5 21
admission but rather at the onset of MODS. SOFA scores above 15 are associated with a mortality rate of over 90% [7, 8]. When patients have MODS for several consecutive days and more than three organs are affected, mortality is very high [5, 9]. While prognosis prediction models contribute significantly to defining patient cohorts, they are not particularly useful for decision making in individual cases. The practice of withholding, withdrawing, or limiting life support in critically ill patients has increased in the past few years [10]. Recent studies have reported some type of life support limitation in 4–13% of patients admitted to ICUs and in 70–90% of those who died in the ICU [11, 12, 13, 14]. The Bioethics Working Group of the Spanish Society of Intensive Medicine and Coronary Units (SEMICYUC) set the following goals in this study (presented in abstract form [14]): (a) to ascertain the incidence and mortality rate of MODS in Spanish ICUs, (b) to evaluate the use of limitation of life support measured in MODS patients, and (c) to determine whether daily SOFA measurement can assist decision making in such cases.
Material and methods A prospective, observational, multicenter study was performed in 75 ICUs in Spain, (approx. one-third of all Spanish ICUs), and 4 ICUs in Latin America. These ICUs have a total of 800 beds. This study was approved by the Ethics Committee of the Hospital de Barcelona, Spain, and informed consent was waived in each participating ICU due to the epidemiological and noninterventional nature of the study. A total of 7,615 patients were admitted to the ICUs during February and March 2001, and 1,340 of these (17.6%) had MODS; 16 patients were excluded because they did not meet the study’s inclusion criteria. The mean age of the study population was 62.2 years (60% men, 40% women). Reasons for admission of MODS patients are presented in Table 1. The mean length of all patients’ stay was 5.4€2.2 days and that of the patients with MODS 13.2€13.65 days). The clinical diagnosis of MODS was established on the basis of the SOFA score, with a minimum score of 3 and more than two organs affected. Patients admitted to the ICU for less than 24 h and those scheduled for surgery requiring less than 2 days of hospitalization were excluded. Daily total SOFA scores were recorded as described by Vincent and coworkers [7]. The SOFA score is composed of scores from six organ systems, graded from 0 to 4 according to the degree of dysfunction/failure. Organ systems considered in the SOFA score are: respiratory (PO22/FIO2), car-
diovascular (blood pressure, vasoactive drugs), renal (creatinine and diuresis), hematological (platelet count), neurological (Glasgow Come Score) and liver (bilirubin) [7]. Physicians were unblinded regarding to SOFA score when decisions on limiting life support were made. These data were used to calculate the trend, minimum, maximum and average values during the period in which patients presented MODS. The mean SOFA was calculated as the mean of the SOFA scores recorded each day during multiple organ dysfunction. The SOFA trend was recorded every day during multiple organ dysfunction as follows: a value of 0 was given when the SOFA score was unchanged from the previous day, +1 when the SOFA score was higher than on the previous day, and 1 when it was lower. The overall trend was obtained by adding the scores and categorizing this score as either a positive trend (positive sum), unchanged trend (zero sum), or negative trend (negative sum). This means that the trend in SOFA was calculated independently of the magnitude of change. All incidents of life support limitation were also recorded. Decisions on limiting life support were implemented at the discretion of the attending physicians. These were orders to withdraw or withhold therapy (renal dialysis, vasoactive drugs, high FIO2, mechanical ventilation, artificial nutrition), and/or not to resuscitate. A do-not-resuscitate order means an explicit written treatment on the clinical record of the patient. No performance means a donot-resuscitate action in a patient without a written statement on his/her clinical record. High FIO2 means breathing through a reservoir mask at high oxygen concentrations and mechanical ventilation refers only to intubation plus mechanical ventilation. A specific form was designed for collecting the data. These forms were processed automatically to recover all the items using Teleform 7.0 Elite (available at: http://www.cardiff.com). The first 100 forms were also double-checked manually by independent investigators for quality control. Logistic regression was used to analyze the predictive power of the variables with respect to mortality. We used the forward method to enter variables into the model. Variables were removed from the model based on the significance of the change in the likelihood ratio. In the preliminary analysis variables were considered in their original continuous form. In the subsequent analysis such variables were considered to be categorical (e.g., maximum SOFA score, or a maximum SOFA score 1 þ eð3:189þð0:034AGEÞþð1:491TRENDÞþð0:299SOFA minÞÞ < Variables with p value of 0.05 or less were included in the model. From the model of logistic regression we constructed receiver operating characteristic curves, and their discriminatant power together with confidence intervals were calculated from the area under the curve. We extracted from this area under the curve the sensitivity and specificity, and different models were assessed using the categorical variables with the aim of identifying those that showed a specificity close to 100% while maintaining a sensitivity as high as possible. In the overall test the two-tailed level of significance was fixed at 5% (a=0.05). Analyses used the SPSS (version 10.0) statistical software program.
prob ¼
Results ICU mortality among MODS patients was 37.3% and hospital mortality 44.6%. Some type of life support limitation was applied in 70.6% of the MODS patients who died. The percentage of life support limitation in survivors was 18%. As shown in Table 2, the most frequent
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Table 2 Percentage of limitation of life support measures in MODS patients who died % Resuscitation orders Renal dialysis Vasoactive drugs High FIO2 Mechanical ventilation Cardiopulmonary resuscitation Nutrition Some kind of limitation
54.2 36.1 30.4 27.9 18.5 14.9 13.3 70.6
life support limitation instructions were not to resuscitate (54.2%) and to withhold renal dialysis (36.1%). When life support limitation and mortality were used as a dependent and independent variable, respectively, the model yielded an area under the receiver operating characteristic curve of 0.804 (p10, Model (n=34) Model 2 (n=43)
Sensitivity
Specificity
Positive PV
Negative PV
5.7 (0.7–19.7) 7.2 (1.5–19.1)
100 (89.7–100.0) 100 (91.8–100.0)
100 (89.7–100.0) 100 (91.8–100.0)
56.9 (37.9–72.8) 57.3 (42.1–73.0)
Table 4 The area under the corresponding receiver operating characteristic curve (ROC AUC) for each of these models (model 1 continuous variables: minimum SOFA, positive SOFA trend over 5 days, age, maximum SOFA; model 2 categorical variables: maximum SOFA >13, minimum SOFA >10, positive SOFA trend over 5 days, age >60 years; model 3 categorical variables: maximum SOFA >10, minimum SOFA >10, positive SOFA trend over 5 days, age >60 years; parentheses 95% confidence interval)
Model 1 Model 2 Model 3
minimum SOFA 10, positive SOFA trend, age >60 years; PV predictive value, parentheses 95% confidence interval)
ROC AUC
p
0.807 (0.784–0.830) 0.750 (0.724–0.777) 0.758(0.732–0.784)
