Intravenous corticosteroid treatment in adult patients with sepsis defined by the Sepsis-3 criteria: a systematic review and meta-analysis

Objectives: To summarize the effects of intravenous corticosteroid treatment for sepsis defined by the Sepsis-3 criteria in adult patients. Design: Systematic review and meta-analysis. Methods: We searched RCTs from PubMed, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Web of Science, and International Clinical Trials Registry Platform from inception to July 12th, 2019 and updated on June 28th, 2020. Conference proceedings from relevant societies and the reference lists of previous reviews were manually screened. Abstract or full-text articles were screened by two independent investigators. We included RCTs where (1) the participants had infections and the baseline Sequential Organ Failure Assessment (SOFA) score ≥ 2 (the Sepsis-3 definitions) (2) the intervention involved any intravenous corticosteroids; (3) the control group received placebo or standard of care (4) the outcomes of interest included mortality or clinical recovery. We chose the 28-day mortality as the pre-specified primary outcome and risk ratio (RR) as the effect measure. We followed PRISMA guidelines and chose random-effects models for the pooled analyses. Results: This study included 24 RCTs and 19 of them (7,115 participants) reported the 28-day mortality. Pooled analyses showed that intravenous corticosteroid treatment compared to placebo or standard of care was not associated with a lower risk of 28-day mortality (RR, 0.88; 95%CI, 0.73 to 1.05), but with a higher risk of hyperglycemia (RR, 1.16; 95%CI, 1.06 to 1.27). Sensitivity analysis of high-quality studies revealed a similar result for the 28-day mortality (RR, 0.95; 95%CI, 0.86 to 1.05). Conclusions: Our findings suggested that intravenous corticosteroids compared to placebo or standard of care may not reduce the 28-day mortality in adult patients with sepsis defined by the Sepsis-3 criteria. Further studies are warranted to clarify the roles of disease severity and treatment timing in the effects of corticosteroid treatment in this population. PROSPERO registration number: CRD42019143083