Steroid use in PROWESS severe sepsis patients treated with drotrecogin alfa (activated).
BACKGROUND
In a study conducted by Annane, patients with septic shock and unresponsive to adrenocorticotropic hormone stimulation receiving low-dose steroid therapy had prolonged survival but not significantly improved 28-day mortality. The present study examines intravenous steroid use in PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) patients meeting the Annane enrollment criteria (AEC).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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).
Levy
Howard
H
Acute Care, Eli Lilly and Co., Indianapolis, Indiana, USA. hlevy@lilly.com
Laterre
Pierre-Francois
PF
Bates
Becky
B
Qualy
Rebecca L
RL
D000367:Age Factors; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D006801:Humans; D008875:Middle Aged; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D013256:Steroids / Q000627:therapeutic use*; D013534:Survival; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011486:Protein C; D011994:Recombinant Proteins; D013256:Steroids; C421124:drotrecogin alfa activated