Low-dose steroids for septic shock and severe sepsis: the use of Bayesian statistics to resolve clinical trial controversies

Intensive Care Med. 2011 Mar;37(3):420-9. doi: 10.1007/s00134-010-2121-0. Epub 2011 Jan 18.

Abstract

Purpose: Low-dose steroids have shown contradictory results in trials and three recent meta-analyses. We aimed to assess the efficacy and safety of low-dose steroids for severe sepsis and septic shock by Bayesian methodology.

Methods: Randomized trials from three published meta-analyses were reviewed and entered in both classic and Bayesian databases to estimate relative risk reduction (RRR) for 28-day mortality, and relative risk increase (RRI) for shock reversal and side effects.

Results: In septic shock trials only (Marik meta-analysis; N = 965), the probability that low-dose steroids decrease mortality by more than 15% (i.e., RRR > 15%) was 0.41 (0.24 for RRR > 20% and 0.14 for RRR > 25%). For severe sepsis and septic shock trials combined, the results were as follows: (1) for the Annane meta-analysis (N = 1,228), the probabilities were 0.57 (RRR > 15%), 0.32 (RRR > 20%), and 0.13 (RRR > 25%); (2) for the Minneci meta-analysis (N = 1,171), the probability was 0.57 to achieve mortality RRR > 15%, 0.32 (RRR > 20%), and 0.14 (RRR > 25%). The removal of the Sprung trial from each analysis did not change the overall results. The probability of achieving shock reversal ranged from 65 to 92%. The probability of developing steroid-induced side effects was as follows: for gastrointestinal bleeding (N = 924), there was a 0.73 probability of steroids causing an RRI > 1%, 0.70 for RRI > 2%, and 0.67 for RRI > 5%; for superinfections (N = 964), probabilities were 0.81 (RRI > 1%), 0.76 (RRI > 2%), and 0.70 (RRI > 5%); and for hyperglycemia (N = 540), 0.99 (RRI > 1%), 0.97 (RRI > 2%), and 0.94 (RRI > 5%).

Conclusions: Based on clinically meaningful thresholds (RRR > 15-25%) for mortality reduction in severe sepsis or septic shock, the Bayesian approach to all three meta-analyses consistently showed that low-dose steroids were not associated with survival benefits. The probabilities of developing steroid-induced side effects (superinfections, bleeding, and hyperglycemia) were high for all analyses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bayes Theorem
  • Clinical Trials as Topic*
  • Humans
  • Meta-Analysis as Topic
  • Odds Ratio
  • Outcome Assessment, Health Care
  • Randomized Controlled Trials as Topic
  • Reproducibility of Results
  • Risk Assessment
  • Severity of Illness Index
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Shock, Septic / physiopathology
  • Steroids / administration & dosage*
  • Steroids / adverse effects
  • Steroids / therapeutic use
  • United States / epidemiology

Substances

  • Steroids