Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 8. Efficacy and safety of recombinant human activated protein C for severe sepsis

摘要

>Objective: To find out whether activated recombinant protein C reduces the death rate from all causes at 28 days among patients with severe sepsis. >Design: A randomized, double-blind, placebo-controlled trial. >Setting: Multicentre; 164 centres in 11 countries. >Patients: The study comprised 1690 patients (840 in the control group and 850 in the treatment group) who had known or suspected infection based on clinical data, plus 3 or more signs of systemic inflammation and sepsis-induced organ dysfunction for at least 24 hours. >Intervention: Patients were randomized to intravenous infusion of drotrecogin α activated (24 μg/kg body weight hourly) for a total of 96 hours or placebo. >Main outcome measure: Death from any cause at 28 days. >Results: The death rate in the treatment group was 24.7% (95% confidence interval [CI] 22%–28%) and in the control group was 30.8% (95% CI 28%–34%). Treatment with activated protein C was associated with a reduction in the relative risk of death of 19.4% (95% CI 6.6%–30.5%) and absolute reduction in the risk of death of 6.1% (p = 0.005). Serious bleeding occurred in 3.5% of patients in the drotrecogin α activated group compared with 2.0% in the placebo group (p = 0.06). >Conclusion: Treatment with activated protein C significantly reduces mortality (6.1% absolute reduction) with severe sepsis but may be associated with an increased risk of bleeding (treatment group 3.2%, p = 0.06).