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Corticosteroids in Sepsis

An Updated Systematic Review and Meta-Analysis

Rochwerg, Bram, MD, MSc1,2; Oczkowski, Simon J., MD, MSc, MHSc1; Siemieniuk, Reed A. C., MD2; Agoritsas, Thomas, MD, PhD2,3,4; Belley-Cote, Emilie, MD1,2; D’Aragon, Frédérick, MD, MSc5; Duan, Erick, MD, MSc1,2; English, Shane, MD, MSc6,7; Gossack-Keenan, Kira, BSc1; Alghuroba, Mashari, MSc1; Szczeklik, Wojciech, MD, PhD1,8; Menon, Kusum, MD, MSc9; Alhazzani, Waleed, MD, MSc1,2; Sevransky, Jonathan, MD10; Vandvik, Per Olav, MD, PhD11; Annane, Djillali, MD, PhD12; Guyatt, Gordon, MD, MSc1,2

doi: 10.1097/CCM.0000000000003262
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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Data Sources: We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis.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.

1Department of Medicine, McMaster University, Hamilton, ON, Canada.

2Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

3Division of General Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland.

4Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland.

5Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke et Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada.

6Department of Medicine (Critical Care), University of Ottawa, Ottawa, ON, Canada.

7Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

8Department of Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland.

9Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.

10Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Emory University, Atlanta, GA.

11Department of Medicine, Innlandet Hospital Trust-Division, Gjøvik, Norway.

12Hôpital Raymond Poincaré, Laboratory of Infection and Inflammation, University of Versailles, Garches, France.

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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:

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