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

Abstract

PurposeTo assess the effect of corticosteroids on clinical outcomes in patients with septic shock. Materials and methodsWe 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. ResultsSeventeen 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; I2 = 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; I2 = 0%), but this benefit disappeared after adjustment with TSA (TSA-adjusted CI: 0.76–1.02). ConclusionsFuture 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.