Steroid use in PROWESS severe sepsis patients treated with drotrecogin alfa (activated)

Adrenocorticotropic hormone stimulation tests were not done in PROWESS. Steroids were allowed but their use was not directed. Patients were identified using AEC (all of: randomization to study drug treatment within 8 hours of shock onset; infection, fever, or hypothermia; tachycardia; systolic blood pressure <90 mmHg on vasopressors; mechanical ventilation; and one of urine <0.5 ml/kg per hour, lactic acidosis, or arterial oxygen tension/inspired fractional oxygen <280). We examined steroid use and mortality data; additional analyses were done outside the 8-hour window.Steroid-treated patients were older, had higher Acute Physiology and Chronic Health Evaluation scores and more organ dysfunctions, and were more commonly receiving mechanical ventilation. Among patients meeting AEC, regardless of steroid treatment (n = 97), mortality in the placebo and drotrecogin alfa (activated) groups was 38% (19/50) and 28% (13/47), respectively (relative risk [RR] = 0.73, 95% confidence interval [CI] 0.41–1.30). When using AEC but excluding the requirement for randomization within 8 hours of shock onset (n = 612), placebo mortality was 38% (118/313) and drotrecogin alfa (activated) mortality was 29% (88/299; RR = 0.78, 95% CI 0.62–0.98). Using AEC but excluding the 8-hour window and with steroids initiated at baseline and/or infusion (n = 228) resulted in mortality for placebo and drotrecogin alfa (activated) groups of 43% (51/118) and 33% (36/110), respectively (RR = 0.76, 95% CI 0.54–1.06).Patients with severe sepsis from the PROWESS trial who were likely to respond to low-dose steroids according to the AEC were those patients at a high risk for death. However, when using the AEC, regardless of steroid use, patients exhibited a survival benefit from treatment with drotrecogin alfa (activated).Corticosteroid therapy in sepsis and septic shock has been investigated for more than 50 years [1]. Over this period there have been dozens of trials examining various patient populations,