Effect of adjunctive corticosteroids on clinical outcomes in adult patients with septic shock - a meta-analysis of randomized controlled trials and trial sequential analysis

Purpose: To assess the effect of corticosteroids on clinical outcomes in patients with septic shock. Materials and methods: We searched databases for eligible randomized controlled trials (RCTs) published prior to March 12, 2018. The relative risk (RR), mean difference (MD) and 95% confidence intervals (CI) were determined. Trial sequential analysis (TSA) were performed. Results: Seventeen RCTs were identified. Overall, corticosteroid therapy was not associated with a lower short-term mortality compared with placebo. Sub-analysis of trials with a low risk of bias demonstrated a beneficial effect of corticosteroids in reducing short-term mortality. Sub-analysis revealed that a daily dose of 200 mg hydrocortisone provided no benefit in reducing short-term mortality (random-effects RR = 0.98, 95% CI: 0.90-1.06, P = 0.555; TSA-adjusted CI: 0.88-1.09; I-2 = 0%), and the boundary for futility was crossed. However, a significant reduction in short-term mortality was found in a subgroup of trials that received dual corticosteroids (random-effects RR = 0.88; 95% CI: 0.79-0.97, P = 0.013; I-2 = 0%), but this benefit disappeared after adjustment with TSA (TSA-adjusted CI: 0.76-1.02). Conclusions: Future trials are unlikely to detect a reduction in short-term mortality at a daily doses of 200 mg hydrocortisone. More evidence is required to confirm the beneficial effects of dual corticosteroid therapy. (C) 2018 Elsevier Inc. All rights reserved.