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Activated protein C and septic shock: a propensity-matched cohort study*
Emily Rimmer1, Anand Kumar, Steve Doucette
1Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Critical Care Medicine
|August 31, 2012
Summary
Early use of recombinant human activated protein C (drotrecogin alfa) was linked to decreased mortality in septic shock patients. Improved care, like faster antibiotic delivery, may explain why earlier trials showed no benefit.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Epidemiology
Background:
- Septic shock is a life-threatening condition characterized by inflammation and coagulation issues.
- Recombinant human activated protein C (drotrecogin alfa) showed initial promise in reducing mortality in severe sepsis but failed in subsequent trials for septic shock.
- Inconsistent results necessitate further investigation into drotrecogin alfa's efficacy in septic shock.
Purpose of the Study:
- To assess the effectiveness of recombinant human activated protein C in reducing mortality among septic shock patients.
- To investigate potential reasons for the conflicting outcomes observed in previous clinical trials.
- To analyze the association between drotrecogin alfa administration and patient survival in a large cohort.
Main Methods:
- Retrospective, multicenter cohort study design with a 2:1 propensity-matched analysis.
- Inclusion of 7,392 adult patients with septic shock across 29 intensive care units in three countries.
- Analysis of 349 patients who received recombinant human activated protein C within 48 hours of ICU admission between 1997 and 2007.
Main Results:
- A significant 6.1% absolute reduction in 30-day mortality was observed with recombinant human activated protein C use (34.7% vs. 40.8%).
- Propensity-matched analysis revealed a hazard ratio of 0.72 (95% CI, 0.52-1.00; p = .05) for 30-day mortality.
- Consistent mortality reductions were noted across all Acute Physiology and Chronic Health Evaluation II score quartiles.
Conclusions:
- Early administration of recombinant human activated protein C was associated with reduced mortality in patients with septic shock.
- Improvements in overall quality of care, particularly the timely administration of antimicrobials, may have influenced study outcomes.
- These findings suggest that enhanced supportive care might have contributed to the null results in prior randomized controlled trials.
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