Comparing Drugs for Out-of-hospital, Shock-refractory Cardiac Arrest: Systematic Review and Network Meta-analysis of Randomized Controlled Trials

INTRODUCTION: The benefit of medications used in out-of-hospital, shock-refractory cardiac arrest remains controversial. This study aims to compare the treatment outcomes of medications for out-of-hospital, shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). METHODS: The inclusion criteria were randomized controlled trials of participants older than eight years old who had atraumatic, out-of-hospital, shock-refractory VF/pVT in which at least one studied group received a medication. We conducted a database search on October 28, 2019, that included PubMed, Scopus, Web of Science, CINAHL Complete, and Cochrane CENTRAL. Citations of relevant meta-analyses were also searched. We performed frequentist network meta-analysis (NMA) to combine the comparisons. The outcomes were analyzed by using odds ratios (OR) and compared to placebo. The primary outcome was survival to hospital discharge. The secondary outcomes included the return of spontaneous circulation (ROSC), survival to hospital admission, and the neurological outcome at discharge. We ranked all outcomes using surface under the cumulative ranking score. RESULTS: We included 18 studies with 6,582 participants. The NMA of 20 comparisons included 12 medications and placebo. Only norepinephrine showed a significant increase of ROSC (OR = 8.91, 95% confidence interval [CI], 1.88–42.29). Amiodarone significantly improved survival to hospital admission (OR = 1.53, 95% CI, 1.01–2.32). The ROSC and survival-to-hospital admission data were significantly heterogeneous with the I2 of 55.1% and 59.1%, respectively. This NMA satisfied the assumption of transitivity. CONCLUSION: No medication was associated with improved survival to hospital discharge from out-of-hospital, shock-refractory cardiac arrest. For the secondary outcomes, norepinephrine was associated with improved ROSC and amiodarone was associated with an increased likelihood of survival to hospital admission in the NMA.