Steroid controversy in sepsis and septic shock

OBJECTIVE: The use of corticosteroids in patients with sepsis or septic shock has been controversial for many decades. Clinical studies have reported beneficial, as well as negative results. We conducted a meta-analysis to assess the clinical evidence and to evaluate treatment effects in specific subgroups of patients. DESIGN: Meta-analysis. DATA SOURCES: A comprehensive search of the literature revealed 49 publications investigating the effect of corticosteroids in patients with sepsis and septic shock. STUDY SELECTION: Only ten of the 49 publications were prospective, randomized, controlled trials with an exact description of dosage and regimen. DATA EXTRACTION: Treatment effects on mortality were calculated as rate differences in each study (negative values favor steroids), and were combined with respect to the variability in each study. DATA SYNTHESIS: Only one study showed a significantly positive effect of steroid treatment. Overall, no positive effect was observed: -0.2% (95% confidence interval: -9.2, 8.8). There were no differences observed when comparing low- vs. high-dose or type of corticosteroid used. Comparing patients with proven Gram-positive or Gram-negative infection showed a slight but not significant difference. The Gram-negative group demonstrated better outcome (-5.6% vs. 1.8%). A quality rating of each trial showed a remarkable increase in quality over time. Adverse events (gastrointestinal bleeding, secondary infections, hyperglycemia) were not more frequent in patients treated with steroids compared with controls. CONCLUSIONS: No overall beneficial effect of corticosteroids in patients with septic shock was observed; however, there is some evidence for a positive effect in patients with Gram-negative septicemia.