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

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

doi:10.1097/CCE.0000000000001000

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

Crit Care Explor. 2024 Jan 19;6(1):e1000. doi: 10.1097/CCE.0000000000001000. eCollection 2024 Jan.

Authors

Tyler Pitre¹, Katherine Drover², Dipayan Chaudhuri^{3

4}, Dena Zeraaktkar^{3

5}, Kusum Menon⁶, Hayley B Gershengorn^{7

8}, Namita Jayaprakash⁹, Joanna L Spencer-Segal¹⁰, Stephen M Pastores¹¹, Andrea M Nei¹², Djillali Annane¹³, Bram Rochwerg^{3

4}

Affiliations

¹ Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Department of Health Sciences, McMaster University, Hamilton, ON, Canada.
³ Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, ON, Canada.
⁴ Department of Critical Care, McMaster University, Hamilton, ON, Canada.
⁵ Department of Anesthesiology, McMaster University, Hamilton, ON, Canada.
⁶ Department of Pediatrics, University of Ottawa and Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
⁷ Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL.
⁸ Division of Critical Care Medicine, Albert Einstein College of Medicine, Bronx, NY.
⁹ Department of Emergency Medicine and Division of Pulmonary and Critical Care Medicine, Henry Ford Health, Detroit, MI.
¹⁰ Department of Internal Medicine and Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI.
¹¹ Critical Care Center, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
¹² Department of Pharmacy, Mayo Clinic Hospital-Rochester, Rochester, MN.
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.

Abstract

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.

Keywords: corticosteroids; critical illness; meta-analysis; sepsis; septic shock.

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States