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

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. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.