Role of clinical evaluation committees in sepsis trials: from 'valid cohort' assessment to subgroup analysis

In this issue of Critical Care, the study from Laterre and colleagues offers suggestions for the role of clinical evaluation committees (CECs) in future sepsis trials. Despite encouraging preliminary results, all randomized controlled trials (RCTs) devoted to potential compounds in severe sepsis have failed to show survival benefit. One of the reasons might be related to RCT-related factors that inevitably occur within a heterogeneous septic patient population. A patient population free from confounding events would seem to provide the most suitable platform upon which to judge therapeutic effect. To solve this issue, CECs have been introduced into RCTs in sepsis to ensure uniform data for analysis and to identify such 'optimal cohorts' for which the therapy was initially designed to treat. More recently, some RCTs have reported positive results in sepsis. The role of CECs has shifted to become a more integral part of the detailed analysis of drug safety and efficacy in large databases, and to identify subgroups of patients in which a therapy might be less or more effective and/or safe. As an example, the retrospective analysis by Laterre and colleagues focuses on patients with severe community-acquired pneumonia (sCAP) within a large, failed RCT (on recombinant tissue factor pathway inhibitor (rTFPI)). However, the results should be interpreted with great caution, and should be viewed as exploratory and a hypothesis-generating activity. This question of potential benefit of rTFPI in patients with sCAP will be definitively answered by the results of the recently completed RCP

Influence of Overweight on ICU Mortality* A Prospective Study

Study objective: Overweight patients seem to have a poorer outcome and a higher risk of complications during their stay in the ICU. We conducted a prospective study in order to examine the relationship between body mass index (BMI) and mortality among these patients. Design: Prospective clinical study. Setting: A 24-bed medical ICU in a university-affiliated hospital. Methods: All patients hospitalized in the ICU over a 1-year period were included except those dying or being discharged from the hospital within 24 h of admission. Overweight patients were defined as those having a BMI > 75th percentile of this selected ICU population. Other data collected were demographic and ICU-related data. The Mann-Whitney test was used to compare numeric data between groups (ie, obese and nonobese populations). Variables that were significantly associated with ICU mortality by univariate analysis were entered into a multiple logistic regression model, allowing the determination of independent predictors. Results: Eight hundred thirteen patients were included in the study. The limit of the upper quartile of the BMI was 27. This value was used to separate obese (n ‫؍‬ 215) and nonobese (n ‫؍‬ 598) groups. Significant differences between obese and nonobese patients were observed in age, length of stay in the ICU, simplified acute physiology score (SAPS) II, and ICU mortality. The observed mortality of obese patients was significantly higher than that predicted by SAPS II (32% vs 18%, respectively; p ‫؍‬ 0.001). No difference was observed in frequency of nosocomial infection or duration of mechanical ventilation for mortality in ICU patients. Using a multivariate analysis, the predictive factors of mortality were SAPS II (p < 0.0001) and BMI > 27 (p < 0.01). Conclusion: This is the first prospective study showing high BMI value as an independent prognostic factor of mortality for ICU patients. The prognostic scoring systems currently in use, which were designed to predict the mortality of ICU patients, do not include BMI or do not consider obesity. These may underestimate, therefore, the risk for the specific population of obese patients. (CHEST 2004; 125:1441-1445) Key words: body mass index; critical illness; mortality; obesity; overweight; prognostic index Abbreviations: APACHE ϭ acute physiology and chronic health evaluation; BMI ϭ body mass index; LOS ϭ length of stay; SAPS ϭ simplified acute physiology scor

Risk factors for post-ICU red blood cell transfusion: a prospective study

INTRODUCTION: Factors predictive of the need for red blood cell (RBC) transfusion in the intensive care unit (ICU) have been identified, but risk factors for transfusion after ICU discharge are unknown. This study aims identifies risk factors for RBC transfusion after discharge from the ICU. METHODS: A prospective, monocentric observational study was conducted over a 6-month period in a 24-bed medical ICU in a French university hospital. Between June and December 2003, 550 critically ill patients were consecutively enrolled in the study. RESULTS: A total of 428 patients survived after treatment in the ICU; 47 (11% of the survivors, 8.5% of the whole population) required RBC transfusion within 7 days after ICU discharge. Admission for sepsis (odds ratio [OR] 341.60, 95% confidence interval [CI] 20.35–5734.51), presence of an underlying malignancy (OR 32.6, 95%CI 3.8–280.1), female sex (OR 5.4, 95% CI 1.2–24.9), Logistic Organ Dysfunction score at ICU discharge (OR 1.45, 95% CI 1.1–1.9) and age (OR 1.06, 95% CI 1.02–1.12) were independently associated with RBC transfusion after ICU stay. Haemoglobin level at discharge predicted the need for delayed RBC transfusion. Use of vasopressors (OR 0.01, 95%CI 0.001–0.17) and haemoglobin level at discharge from the ICU (OR 0.02, 95% CI 0.007–0.09; P < 0.001) were strong independent predictors of transfusion of RBC 1 week after ICU discharge. CONCLUSION: Sepsis, underlying conditions, unresolved organ failures and haemoglobin level at discharge were related to an increased risk for RBC transfusion after ICU stay. We suggest that strategies to prevent transfusion should focus on homogeneous subgroups of patients and take into account post-ICU needs for RBC transfusion

Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]

INTRODUCTION: PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care). METHODS: Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism. RESULTS: Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin–antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days. CONCLUSION: Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups

Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control

Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe