Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine Combination Versus Epinephrine Alone

Cardiovasc Drugs Ther. 2018 Aug;32(4):339-351. doi: 10.1007/s10557-018-6811-0.

Abstract

Purpose: Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock.

Methods: We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressor-requiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an "as-treated" principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88).

Results: Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as "hypotension and/or myocardial ischemia" did not appreciably affect the aforementioned CSHRs.

Conclusions: In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Keywords: Heart arrest; Septic; Shock; Steroids; Vasopressins.

MeSH terms

  • Aged
  • Cardiopulmonary Resuscitation / adverse effects*
  • Cardiopulmonary Resuscitation / mortality
  • Drug Combinations
  • Epinephrine / administration & dosage*
  • Epinephrine / adverse effects
  • Female
  • Heart Arrest / diagnosis
  • Heart Arrest / mortality
  • Heart Arrest / physiopathology
  • Heart Arrest / therapy*
  • Humans
  • Male
  • Middle Aged
  • Patient Admission*
  • Protective Factors
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Factors
  • Shock, Septic / diagnosis
  • Shock, Septic / microbiology
  • Shock, Septic / mortality
  • Shock, Septic / prevention & control*
  • Steroids / administration & dosage*
  • Steroids / adverse effects
  • Time Factors
  • Treatment Outcome
  • Vasopressins / administration & dosage*
  • Vasopressins / adverse effects

Substances

  • Drug Combinations
  • Steroids
  • Vasopressins
  • Epinephrine