Comparative effectiveness of vasopressin, steroids, and epinephrine-based regimens in cardiac arrest: A network Meta-analysis of clinical trials - 11/12/25

Doi : 10.1016/j.ajem.2025.09.040

Fatemeh Saghafi ^a, Mohammad Hossein Dehghani ^b, Sajjad Erami ^c, Amin Salehi-Abargouei ^d,^e, Mohammad Ali Omrani ^f, Farahnaz Hoseinzade ^g, Maryam Shojaeifard ^h, Adeleh Sahebnasagh ^i,^{^⁎}

^a Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

^b Department of Anesthesiology and Critical Care, Shahid Rahnemoun Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

^c School of Medicine, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

^d Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

^e Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

^f School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

^g Pharmaceutical Sciences Research Center, School of Pharmacy, Student Research Committee, Esfahan University of Medical Sciences, Esfahan, Iran

^h Department of Cardiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

ⁱ Clinical Research Center, School of Medicine, Department of Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

^⁎ Corresponding author at: Department of Internal Medicine, Faculty of Medicine, Imam Ali Hospital, Shahriar Street, North Khorasan Province University of Medical Sciences, Bojnourd, Iran. Department of Internal Medicine Faculty of Medicine Imam Ali Hospital North Khorasan Province University of Medical Sciences Shahriar Street Bojnourd Iran

Abstract

Background

Despite extensive efforts to improve survival in cardiac arrest (CA), the optimal pharmacologic strategy during resuscitation remains uncertain. While prior meta-analyses have explored individual drug classes, the relative effectiveness of combined regimens remains inadequately defined. This network meta-analysis (NMA) aims to evaluate and compare the efficacy of triple therapy with vasopressin (VP), steroids, and epinephrine (EP) in CA patients.

Methods

A comprehensive electronic search was conducted in PubMed, Scopus, ISI Web of Science, the Cochrane Central Register of Controlled Trials, Google Scholar, and other bibliographic databases. Randomized clinical trials (RCTs) evaluating the use of steroids, epinephrine, and vasopressin in CA patients were included. In trials that involved additional agents (e.g., lidocaine), only the data pertaining to epinephrine/vasopressor-based interventions were extracted and synthesized to ensure comparability with the study scope. Out of 3453 identified studies, 36 RCTs involving 21,768 patients were included. Interventions during cardiopulmonary resuscitation were categorized as monotherapy, double therapy, or triple therapy (VSE). Primary outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, 24-h survival, and survival to hospital discharge. Neurological outcomes were also evaluated to determine functional recovery, when consistently reported, although heterogeneity of measurement tools precluded quantitative synthesis.

Results

Triple therapy (VSE) and the combination of epinephrine plus steroids demonstrated the highest probability of improving all major survival outcomes. Ranking analysis consistently favored VSE over monotherapies to improve clinical outcomes of CA patients.

Conclusion

This NMA provides comparative evidence supporting the superiority of epinephrine-steroid double therapy and VSE triple therapy in improving resuscitation outcomes in cardiac arrest. These findings may inform future guidelines and clinical decision-making.

Prospero registration

CRD42022296508.

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Keywords : Cardiac arrest, Corticosteroid, Vasopressin, Epinephrine, Survival, Return of spontaneous circulation, Triple therapy, Cardiopulmonary resuscitation

Abbreviations : ROSC, CA, VP, EP, RCT, CPR, OHCA, IHCA, PCAS, BLS, HPA, PROSPERO