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

Area of Science:

• Critical care medicine
• Pharmacology

Background:

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Corticosteroids are used in sepsis management, but their efficacy and safety remain debated.

Purpose of the Study:

• To systematically review and meta-analyze the efficacy and safety of corticosteroids in sepsis patients.
• To evaluate the impact of different corticosteroid doses on sepsis outcomes.

Main Methods:

• A systematic search of PubMed, Embase, and Cochrane Library databases was conducted up to January 10, 2023.
• Included were 45 randomized controlled trials (RCTs) involving 9563 patients comparing corticosteroids with placebo or standard care.
• Pairwise and dose-response meta-analyses were performed, with certainty assessed using GRADE guidelines.

Main Results:

• Corticosteroids probably reduce short-term mortality (RR, 0.93) and increase shock reversal at 7 days (RR, 1.24) with high certainty.
• Potential adverse events include increased risk of hyperglycemia (RR, 1.13) and hypernatremia (RR, 1.64), with moderate certainty.
• Dose-response analysis suggested optimal mortality reduction with approximately 260 mg/day of hydrocortisone or equivalent.

Conclusions:

• Corticosteroids may be beneficial in reducing sepsis mortality and improving shock reversal.
• However, their use is associated with increased risks of hyperglycemia, hypernatremia, and neuromuscular weakness.
• Optimal corticosteroid dosing for sepsis appears to be around 260 mg/day of hydrocortisone or equivalent.