Association between the timing of prehospital epinephrine administration and patient outcomes after out-of-hospital cardiac arrest in Korea: a nationwide observational study

OBJECTIVE: The optimal timing of epinephrine during out-of-hospital cardiac arrest (OHCA) remains uncertain, particularly for neurological recovery. We examined the association between time-to-epinephrine and clinical outcomes in adult OHCA in Korea. METHODS: We conducted a nationwide retrospective cohort of emergency medical service (EMS)-treated, non-traumatic adult OHCA (2019-2021). Patients were classified as early (≤20 min) or delayed (>20 min) based on arrest-to-first epinephrine. The primary outcome was favourable neurological status at discharge (Cerebral Performance Category (CPC) 1-2); secondary outcomes were return of spontaneous circulation (ROSC) and survival to discharge. We applied 1:1 propensity-score matching and multivariable logistic regression, including continuous (per 1-minute and 5-minute delays) and 5-minute bin analyses of time-to-epinephrine, with effect modification assessed by initial rhythm. RESULTS: Among 10 726 patients, 3589 (33.5%) received epinephrine within 20 min. In the matched cohort (n = 5,734), delayed administration was associated with lower survival (4.46% vs 7.74%; aOR 0.56, 95% CI 0.44-0.71) and lower likelihood of favourable neurological outcome (2.13% vs 3.77%; aOR 0.56, 95% CI 0.40-0.79), compared with early administration. In continuous models, each 1-minute delay was associated with lower odds of good CPC (aOR 0.964, 95% CI 0.942 to 0.987); a 5-minute delay corresponded to aOR 0.833 (95% CI 0.741 to 0.937) and bin-wise estimates showed a marked drop beyond 30 min (aOR 0.048, 95% CI 0.006 to 0.393). CONCLUSION: Early epinephrine administration within 20 min of cardiac arrest onset was associated with higher rates of ROSC, survival to discharge and favourable neurological recovery in this EMS setting. These findings support the importance of timely advanced life support delivery, including early epinephrine, although cautious interpretation is warranted.