Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis

Tyler Pitre, MD, MA; Katherine Drover; Dipayan Chaudhuri, MD, MSc; Dena Zeraaktkar, PhD; Kusum Menon, MD, MSc; Hayley B. Gershengorn, MD; Namita Jayaprakash, MD; Joanna L. Spencer-Segal, MD, PhD; Stephen M. Pastores, MD; Andrea M. Nei, PharmD; Djillali Annane, MD, PhD; Bram Rochwerg, MD, MSc

doi:10.1097/CCE.0000000000001000

Critical Care Explorations (Jan 2024)

Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis

Tyler Pitre, MD, MA,
Katherine Drover,
Dipayan Chaudhuri, MD, MSc,
Dena Zeraaktkar, PhD,
Kusum Menon, MD, MSc,
Hayley B. Gershengorn, MD,
Namita Jayaprakash, MD,
Joanna L. Spencer-Segal, MD, PhD,
Stephen M. Pastores, MD,
Andrea M. Nei, PharmD,
Djillali Annane, MD, PhD,
Bram Rochwerg, MD, MSc

Affiliations

Tyler Pitre, MD, MA: 1 Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
Katherine Drover: 2 Department of Health Sciences, McMaster University, Hamilton, ON, Canada.
Dipayan Chaudhuri, MD, MSc: 3 Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Dena Zeraaktkar, PhD: 3 Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Kusum Menon, MD, MSc: 6 Department of Pediatrics, University of Ottawa and Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada.
Hayley B. Gershengorn, MD: 7 Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL.
Namita Jayaprakash, MD: 9 Department of Emergency Medicine and Division of Pulmonary and Critical Care Medicine, Henry Ford Health, Detroit, MI.
Joanna L. Spencer-Segal, MD, PhD: 10 Department of Internal Medicine and Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI.
Stephen M. Pastores, MD: 11 Critical Care Center, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Andrea M. Nei, PharmD: 12 Department of Pharmacy, Mayo Clinic Hospital—Rochester, Rochester, MN.
Djillali Annane, MD, PhD: 13 General Intensive Care Unit, Raymond Poincare Hospital (APHP), Garches, France and the School of Medicine Simone Veil, University Paris Saclay—Campus UVSQ, Paris, France.
Bram Rochwerg, MD, MSc: 3 Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, ON, Canada.

DOI: https://doi.org/10.1097/CCE.0000000000001000
Journal volume & issue: Vol. 6, no. 1
p. e1000

Abstract

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OBJECTIVES:. To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis. DATA SOURCES:. We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023. STUDY SELECTION:. We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis. DATA EXTRACTION:. The critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events. DATA ANALYSIS:. We performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates. DATA SYNTHESIS:. We included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0.93; 95% CI, 0.88–0.99; moderate certainty) and increase shock reversal at 7 days (RR, 1.24; 95% CI, 1.11–1.38; high certainty). Corticosteroids may have no important effect on duration of ICU stay (mean difference, –0.6 fewer days; 95% CI, 1.48 fewer to 0.27 more; low certainty); however, probably increase the risk of hyperglycemia (RR, 1.13; 95% CI, 1.08–1.18; moderate certainty) and hypernatremia (RR, 1.64; 95% CI, 1.32–2.03; moderate certainty) and may increase the risk of neuromuscular weakness (RR, 1.21; 95% CI, 1.01–1.45; low certainty). The dose-response analysis showed a reduction in mortality with corticosteroids with optimal dosing of approximately 260 mg/d of hydrocortisone (RR, 0.90; 95% CI, 0.83–0.98) or equivalent. CONCLUSIONS:. We found that corticosteroids may reduce mortality and increase shock reversal but they may also increase the risk of hyperglycemia, hypernatremia, and neuromuscular weakness. The dose-response analysis indicates optimal dosing is around 260 mg/d of hydrocortisone or equivalent.

Published in Critical Care Explorations

ISSN: 2639-8028 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://journals.lww.com/ccejournal/pages/default.aspx

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