Impact of the route of adrenaline administration in patients suffering from out-of-hospital cardiac arrest on 30-day survival with good neurological outcome (ETIVIO study)

BACKGROUND: Over the past decades, international guidelines for cardiopulmonary resuscitation (CPR) have changed the recommendation for alternative routes for drug administration. Until now, evidence for the substantial superiority of one route with respect to treatment outcome after CPR has been lacking. The present study compares the effects of intravenous (IV), intraosseous (IO) and endotracheal (ET) adrenaline application during CPR in out-of-hospital cardiac arrest (OHCA) on clinical outcomes within the database of the German Resuscitation Registry (GRR). METHODS: This registry analysis was based on the GRR cohort of 212,228 OHCA patients between 1989 and 2020. Inclusion criteria were: OHCA, application of adrenaline, and out-of-hospital CPR. Excluded from the study were patients younger than 18 years, those who had trauma or bleeding as suspected causes of cardiac arrest, and incomplete data sets. The clinical endpoint was hospital discharge with good neurological outcome [cerebral performance category (CPC) 1/2]. Four routes of adrenaline administration were compared: IV, IO, IO + IV, ET + IV. Group comparisons were done using matched-pair analysis and binary logistic regression. RESULTS: In matched-pair group comparisons of the primary clinical outcome hospital discharge with CPC 1/2, the IV group (n = 2416) showed better results compared to IO (n = 1208), [odds ratio (OR): 2.43, 95% confidence interval (CI): 1.54–3.84, p < 0.01] and when comparing IV (n = 8706) to IO + IV (n = 4353), [OR: 1.33, 95% CI: 1.12–1.59, p < 0.01]. In contrast, no significant difference was found between IV (n = 532) and ET + IV (n = 266), [OR: 1.26, 95% CI: 0.55–2.90, p = 0.59]. Concurrently, binary logistic regression yielded a highly significant effect of vascular access type (χ² = 67.744(3), p < 0.001) on hospital discharge with CPC1/2, with negative effects for IO (regression coefficient (r.c.) = − 0.766, p = 0.001) and IO + IV (r.c. = − 0.201, p = 0,028) and no significant effect for ET + IV (r.c. = 0.117, p = 0.770) compared to IV. CONCLUSIONS: The GRR data, collected over a period of 31 years, seem to emphasize the relevance of an IV access during out-of-hospital CPR, in the event that adrenaline had to be administered. IO administration of adrenaline might be less effective. ET application, though removed in 2010 from international guidelines, could gain importance as an alternative route again.