Aim of the study: This study sought to determine whether prehospital administration of amiodarone improves outcomes among adult patients with out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). The analysis accounted for time-dependent confounding and resuscitation time bias using real-world registry data.
Material and methods: We conducted a multicenter, retrospective cohort study using a nationwide Japanese OHCA database, including adult nontraumatic shockable rhythms. The exposure was prehospital amiodarone administration at a given time, and the comparator was no amiodarone at the same time point. The comparison reflects amiodarone administration at that time versus no amiodarone, not ‘amiodarone versus never-amiodarone‘. The primary and secondary endpoints were favorable neurological status and survival at 30 days. Patients were matched 1:3 using time-dependent propensity score matching, followed by generalized estimating equations to address intrahospital clustering. Sensitivity analyses included covariates with standardized mean differences greater than 0.25 after matching. Associations were expressed as risk ratios (RRs) with 95% confidence intervals (CIs).
Results: Among 9,909 eligible patients, 56 (0.6%) remained after matching, including 19 (0.2%) who received amiodarone at the index time point. Median (IQR) age was 65 (52–76) years, and 81.8% were male. The median interval from first medical contact to drug administration was 27 (22–32) minutes. In models adjusted for timing variables and hospital clustering, amiodarone was not significantly related to favorable neurological recovery (RR, 0.45 [95% CI, 0.14–1.47]) or survival (RR, 0.74 [95% CI, 0.31–1.73]). Sensitivity analyses yielded consistent findings, though survival model convergence was limited. 
Conclusions: Prehospital administration of amiodarone in adult OHCA patients with shockable rhythms was not associated with improved neurological or survival outcomes. However, these findings should be interpreted with caution, and further studies are warranted to confirm and extend these observations.