Corticosteroids in Sepsis: An Updated Systematic Review and Meta-Analysis

Objective: This systematic review and meta-analysis addresses the efficacy and safety of corticosteroids in critically ill patients with sepsis. Data Sources: We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis. Study Selection: Reviewers conducted duplicate screening of citations, data abstraction, and, using a modified Cochrane risk of bias tool, individual study risk of bias assessment. Data Extraction: A parallel guideline committee provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. We assessed overall certainty in evidence using Grading of Recommendations Assessment, Development and Evaluation methodology and performed all analyses using random-effect models. For subgroup analyses, we performed metaregression and considered p value less than 0.05 as significant. Data Synthesis: Forty-two randomized controlled trials including 10,194 patients proved eligible. Based on low certainty, corticosteroids may achieve a small reduction or no reduction in the relative risk of dying in the short-term (28–31 d) (relative risk, 0.93; 95% CI, 0.84–1.03; 1.8% absolute risk reduction; 95% CI, 4.1% reduction to 0.8% increase), and possibly achieve a small effect on long-term mortality (60 d to 1 yr) based on moderate certainty (relative risk, 0.94; 95% CI, 0.89–1.00; 2.2% absolute risk reduction; 95% CI, 4.1% reduction to no effect). Corticosteroids probably result in small reductions in length of stay in ICU (mean difference, –0.73 d; 95% CI, –1.78 to 0.31) and hospital (mean difference, –0.73 d; 95% CI, –2.06 to 0.60) (moderate certainty). Corticosteroids result in higher rates of shock reversal at day 7 (relative risk, 1.26; 95% CI, 1.12–1.42) and lower Sequential Organ Failure Assessment scores at day 7 (mean difference, –1.39; 95% CI, –1.88 to –0.89) (high certainty). Corticosteroids likely increase the risk of hypernatremia (relative risk, 1.64; 95% CI, 1.32–2.03) and hyperglycemia (relative risk, 1.16; 95% CI, 1.08–1.24) (moderate certainty), may increase the risk of neuromuscular weakness (relative risk, 1.21; 95% CI, 1.01–1.52) (low certainty), and appear to have no other adverse effects (low or very low certainty). Subgroup analysis did not demonstrate a credible subgroup effect on any of the outcomes of interest (p > 0.05 for all). Conclusions: In critically ill patients with sepsis, corticosteroids possibly result in a small reduction in mortality while also possibly increasing the risk of neuromuscular weakness. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (https://ift.tt/29S62lw). Drs. Rochwerg and Oczkowski are supported by McMaster University Department of Medicine early career research awards. Dr. Siemieniuk disclosed off-label product use of corticosteroids (not licensed for treatment of sepsis). Dr. Sevransky’s institution received funding from the Marcus Foundation, and he received funding from the Society of Critical Care Medicine (Associate Editor stipend). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Bram Rochwerg, MD, MSc, Department of Medicine, Division of Critical Care, Juravinski Hospital, 711 Concession St, Hamilton, ON L8V 1C1, Canada. E-mail: rochwerg@mcmaster.ca Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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