Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis

Intensive Care Med. 2018 Jul;44(7):1003-1016. doi: 10.1007/s00134-018-5197-6. Epub 2018 May 14.

Abstract

Purpose: To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.

Methods: We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.

Results: There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89-1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91-1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90-1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03-2.70, p = 0.04, I2 = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) -1.52 days; 95% CI -1.71 to -1.32, p < 0.0001], duration of mechanical ventilation (MD -1.38 days; 95% CI -1.96 to -0.80, p < 0.0001), and ICU stay (MD -0.75 days; 95% CI -1.34 to -0.17, p = 0.01) were shorter with corticosteroids versus placebo.

Conclusions: In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced. PROSPERO registration no. CRD42017084037.

Keywords: Corticosteroids; Meta-analysis; Sepsis; Septic shock.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Glucocorticoids / therapeutic use*
  • Humans
  • Randomized Controlled Trials as Topic
  • Shock, Septic / drug therapy*

Substances

  • Glucocorticoids