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.

• Authors: Spyros D Mentzelopoulos, Iosifina Koliantzaki, Marios Karvouniaris, Charikleia Vrettou, Nicolas Mongardon, George Karlis, Demosthenes Makris, Epaminondas Zakynthinos, Sotirios Sourlas, Stavros Aloizos, Theodoros Xanthos, Spyros G Zakynthinos
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 32 Issue 4 Pg. 339-351 (08 2018) ISSN: 1573-7241 [Electronic] United States
• PMID: 30084038 (Publication Type: Journal Article)

Chemical References

• Drug Combinations
• Steroids
• Vasopressins
• Epinephrine

Topics

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