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

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.