Low-dose steroids for septic shock and severe sepsis

The use of Bayesian statistics to resolve clinical trial controversies

Andre C Kalil, Junfeng Sun

Research output: Contribution to journalReview article

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalIntensive Care Medicine
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2011

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Septic Shock
Sepsis
Steroids
Clinical Trials
Risk Reduction Behavior
Meta-Analysis
Superinfection
Mortality
Hyperglycemia
Shock
Hemorrhage
Bayes Theorem

Keywords

  • Sepsis
  • Shock
  • Steroids

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Low-dose steroids for septic shock and severe sepsis : The use of Bayesian statistics to resolve clinical trial controversies. / Kalil, Andre C; Sun, Junfeng.

In: Intensive Care Medicine, Vol. 37, No. 3, 01.03.2011, p. 420-429.

Research output: Contribution to journalReview article

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title = "Low-dose steroids for septic shock and severe sepsis: The use of Bayesian statistics to resolve clinical trial controversies",
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.",
keywords = "Sepsis, Shock, Steroids",
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AU - Sun, Junfeng

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N2 - 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.

AB - 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.

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