Background: Septic shock causing or complicating critical surgical illness results in high mortality. Drotrecogin alfa (activated), known also as recombinant human activated protein C (rhAPC) has become controversial as therapy, owing to persisting questions of efficacy and safety. We hypothesized rhAPC to be effective therapy for critically ill surgical patients with septic shock. Methods: Open-label therapy with rhAPC (by predefined criteria) of 108 critically ill surgical patients. Treated patients were matched individually in prospect for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE)-II and -III scores, site of infection, and organism (0-2 points each, maximum 12 points) with 108 patients from our 15,000-patient surgical intensive care unit database who did not receive rhAPC. No match was accepted if <6 points. Multiple organ dysfunction (MOD) scores and data regarding cortisol concentrations, bleeding complications, and transfusion requirements were collected. The primary endpoint was 28-day mortality, with mortality for hospitalization and resolution of organ dysfunction as secondary endpoints. Statistical analyses included ANOVA, c statistic, binary logistic regression, and Kaplan-Meier time-to-event and Cox proportional hazards analyses; alpha = 0.05. Results: The mean match score was 9.2 +/- 0.1 points (range, 6-12 points). Patients were well matched by all criteria, including baseline MOD score (9.5 +/- 0.7 vs. 9.8 +/- 0.3 points, p = 0.66). Mean age was 68.1 +/- 1.1 years (p = 0.49), Mean APACHE-III score was 99.6 +/- 1.5 points (p = 0.87). Mean time to rhAPC administration was 25 +/- 3 h. Survival at 28 days after rhAPC was 71.3% vs. 49.1% (p = 0.001); hospital survival was 57.4% vs. 40.7% (p = 0.02). By logistic regression, rhAPC therapy resulted in improved 28-day survival (OR 2.57, 95% CI 1.46-4.52, p = 0.001) (model chi(2) 11.244, p = 0.001); and hospital survival (OR 1.96, 95% CI 1.14-3.36, p = 0.015) (model chi(2) 6.03, p = 0.014). The MOD score decreased significantly (p = 0.012) during rhAPC therapy. Conclusion: Therapy with rhAPC appeared to improve survival in surgical ICU patients with life-threatening infection characterized by septic shock and organ dysfunction.
