The Efficacy, Safety, and Optimal Regimen of Corticosteroids in Sepsis: A Bayesian Network Meta-Analysis

Abstract

Conventional systematic reviews have indicated that corticosteroids might result in a slight reduction in mortality in sepsis. However, the efficacy, safety, and optimal regimen of different corticosteroids partly remain unknown. In this study, we conducted a Bayesian network meta-analysis for a head-to-head comparison of the therapeutic efficacy and safety of currently used corticosteroids in sepsis.

Design: A Bayesian network meta-analysis for a head-to-head comparison of the therapeutic efficacy and safety of currently used corticosteroids in sepsis.

Setting: A total of 35 eligible randomized controlled trials of corticosteroid use in sepsis.

Patients: The present Bayesian network meta-analysis included 8,859 patients with sepsis.

Interventions: Randomized controlled trials were screened from PubMed, Embase, and the Cochrane Library up to December 28, 2019. A head-to-head comparison of the therapeutic efficacy and safety between the different categories of corticosteroids from the trials was conducted by Bayesian network meta-analysis. An empirical Bayesian meta-regression and a post hoc Bayesian network meta-analysis were performed to explore the appropriate dose and therapeutic duration of steroids for sepsis.

Measurements and main results: A total of 35 randomized controlled trials including 8,859 patients with sepsis were enrolled in the final analysis. Bayesian network meta-analysis revealed that methylprednisolone and dexamethasone might be more effective in reducing short-term mortality in sepsis than placebo: methylprednisolone versus placebo (relative risk, 0.65, 95% credible interval 0.40-0.93), dexamethasone versus placebo (relative risk, 0.42, 95% credible interval, 0.24-0.84). Hydrocortisone and hydrocortisone plus fludrocortisone were superior to placebo in days to shock resolution (e-Table 5, Supplemental Digital Content 1, http://links.lww.com/CCX/A150): hydrocortisone versus placebo (mean difference, -1.70, 95% credible interval, -2.83 to -0.92), hydrocortisone plus fludrocortisone versus placebo (mean difference, -2.54, 95% credible interval, -4.19 to -0.84). Hydrocortisone was superior to placebo in reducing the length of stay in the ICU (mean difference, -1.43, 95% credible interval, -3.36 to -0.15). Methylprednisolone was superior to placebo in improving ventilation-free days (mean difference, 7.71, 95% credible interval, 1.15-14.42). In addition, further analysis indicated that the optimal therapeutic dosage was 200-400 mg per day of hydrocortisones or equivalents (relative risk, 0.83, 95% credible interval, 0.64-0.98), and the appropriate therapeutic duration was 4-7 days (relative risk, 0.78; 95% credible interval, 0.57-0.96).

Conclusions: This study provided moderate evidence that the dosage of 200-400 mg per day of hydrocortisone or equivalent for 4-7 days was most likely to benefit septic patients.

Keywords: Bayesian network analyses; corticosteroids; meta-regression; optimal regimen; sepsis.

Figure 1.

Flow diagram of process in search and reasons for exclusion of studies. RCT = randomized clinical trial.