Effects of prehospital epinephrine administration on neurologically intact survival in bystander-witnessed out-of-hospital cardiac arrest patients with non-shockable rhythm depend on prehospital cardiopulmonary resuscitation duration required to hospital arrival

The effects of prehospital epinephrine administration on post-arrest neurological outcome in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm remain unclear. To examine the time-dependent effectiveness of prehospital epinephrine administration, we analyzed 118,396 bystander-witnessed OHCA patients with non-shockable rhythm from the prospectively recorded all-Japan OHCA registry between 2011 and 2014. Patients who achieved prehospital return of spontaneous circulation without prehospital epinephrine administration were excluded. Patients with prehospital epinephrine administration were stratified according to the time from the initiation of cardiopulmonary resuscitation (CPR) by emergency medical service (EMS) providers to the first epinephrine administration (≤ 10, 11–19, and ≥ 20 min). Patients without prehospital epinephrine administration were stratified according to the time from CPR initiation by EMS providers to hospital arrival (≤ 10, 11–19, and ≥ 20 min). The primary outcome was 1-month neurologically intact survival (cerebral performance category 1 or 2; CPC 1–2). Multivariate logistic regression analysis demonstrated that there was no significant difference in the chance of 1-month CPC 1–2 between patients who arrived at hospital in ≤ 10 min without prehospital epinephrine administration and patients with time to epinephrine administration ≤ 19 min. However, compared to patients who arrived at hospital in ≤ 10 min without prehospital epinephrine administration, patients with time to epinephrine administration ≥ 20 min and patients who arrived at hospital in 11–19, and ≥ 20 min without prehospital epinephrine administration were significantly associated with decreased chance of 1-month CPC 1–2 ( p < 0.05, < 0.05, and < 0.001, respectively). In conclusion, when prehospital CPR duration from CPR initiation by EMS providers to hospital arrival estimated to be ≥ 11 min, prehospital epinephrine administered ≤ 19 min from CPR initiation by EMS providers could improve neurologically intact survival in bystander-witnessed OHCA patients with non-shockable rhythm.