Corticosteroids for sepsis and septic shock: a meta-analysis of 18 RCTs with dose-stratified and fludrocortisone subgroup evaluation

Abstract

Background: The therapeutic benefit of corticosteroids in managing sepsis and septic shock remains controversial, particularly concerning optimal dosing strategies and the role of adjunctive fludrocortisone. Recent large-scale trials and updated guidelines underscore the need for a dose-stratified synthesis. This meta-analysis aimed to comprehensively evaluate the effects of corticosteroids on short-term mortality in sepsis, with subgroup analyses by steroid type, dosage, and geographic region. Methods: This study followed the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing corticosteroids with placebo in adult patients with sepsis or septic shock were included. Subgroup analyses were pre-specified for daily hydrocortisone-equivalent dose (≤ 200 mg, 201–300 mg, > 300 mg), steroid type (hydrocortisone alone vs. hydrocortisone plus fludrocortisone), and region (China vs. non-China). Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using a random-effects model. Results: Eighteen RCTs comprising 7,982 patients were included. Corticosteroid therapy was associated with reduced 28-day mortality (RR = 0.88; 95% CI: 0.79–0.98; I² = 39%). The 28-day mortality was 31.0% in the corticosteroid group versus 35.5% in the control group.The most pronounced benefit was seen with 201–300 mg/day regimens (RR = 0.86; I² = 0%) and with combination therapy including fludrocortisone (RR = 0.89). Regional analysis showed weaker effects in trials conducted in China. Conclusion: Moderate-dose corticosteroids, especially when used in conjunction with fludrocortisone, significantly reduce short-term mortality in septic shock. Findings support guideline-endorsed steroid use and highlight the importance of individualized treatment strategies.