Safety and Efficacy of Corticosteroids for the Treatment of Septic Shock: A Systematic Review and Meta-Analysis

Background. Septic shock is common and results in significant morbidity and mortality. Adjunctive treatment with corticosteroids is common, but definitive data are lacking. We aimed to determine the efficacy and safety of corticosteroid therapy among patients with septic shock. Methods. Medline, Embase, Cochrane Library, Web of Science, and Google Scholar were searched for randomized trials and observational studies published from January 1993 through December 2008. Studies were selected if they included adults with septic shock, discussed treatment with intravenous corticosteroids, and reported at least 1 outcome of interest (e. g., mortality, shock reversal, or incidence of superinfection). Two reviewers independently agreed on eligibility, assessed methodologic quality, and abstracted data. Results. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated for 28-day all-cause mortality, shock reversal at 7 days, and incidence of superinfection with use of random-effects models. Analyses, stratified by adrenal responsiveness, were prespecified. Eight studies (6 randomized trials) involving a total of 1876 patients were selected. Overall, corticosteroid therapy did not result in a statistically significant difference in mortality (42.2% [369 of 875 patients] vs. 38.4% [384 of 1001]; RR, 1.00; 95% CI, 0.84-1.18). A statistically significant difference in the incidence of shock reversal at 7 days was observed between patients who received corticosteroids and those who did not (64.9% [314 of 484 patients] vs. 47.5% [228 of 480]; RR, 1.41; 95% CI, 1.22-1.64), with similar point estimates for both corticotropin stimulation test responders and nonresponders. No statistically significant difference was found in the incidence of superinfection between patients treated with corticosteroids and patients not treated with corticosteroids (25.3% [114 of 450 patients] vs. 22.7% [100 of 441]; RR, 1.11; 95% CI, 0.86-1.42). Conclusions. In patients with septic shock, corticosteroid therapy appears to be safe but does not reduce 28-day all-cause mortality rates. It does, however, significantly reduce the incidence of vasopressor-dependent shock, which may be a clinically worthwhile goal.