The Route to ROSC: Evaluating the Impact of Route and Timing of Epinephrine Administration in Out-of-Hospital Cardiac Arrest Outcomes

Objectives: Previous investigations comparing intraosseous (IO) and intravenous (IV) epinephrine delivery in out-of-hospital cardiac arrest (OHCA) suggest that epinephrine is oftentimes more expeditiously administered via the IO route, but this temporal benefit doesn't always translate to clinical benefit. However, very few studies adequately controlled for indication and resuscitation time biases, making the influence of first epinephrine route on OHCA outcomes unclear. To determine the association between first epinephrine route and return of spontaneous circulation (ROSC) while controlling for resuscitation time bias and other potential confounders. Methods: We conducted a retrospective analysis using the 2020 ESO Data Collaborative dataset. Adult patients with a witnessed, non-traumatic OHCA prior to EMS arrival were included. Logistic regression was used to determine the association between medication route and ROSC. Linear regression was then used to calculate the probability of ROSC for each route across all call receipt-to-drug delivery intervals. Using these linear equations, the call receipt-to-drug delivery intervals were calculated that would yield equivalent probabilities of ROSC between the IV and IO routes. Results: Data were available for 10,350 patients, of which 27.4% presented with a shockable rhythm, 29.7% received bystander CPR, and 39.6% experienced ROSC. After controlling for confounders, IO epinephrine was associated with decreased likelihood of ROSC (OR = 0.77, p < 0.001). The linear regression models provided differing slope coefficients for ROSC between each route, with the IV route associated with a higher likelihood of ROSC for any given call receipt-to-drug-delivery interval. From these equations, the additional time allowed to establish an IV and administer epinephrine intravenously beyond the time required for IO delivery, yet with an equivalent predicted probability of ROSC via the IO route, was calculated. This additional time interval for intravenous administration declined linearly from 9 min at a call receipt-to-intraosseous epinephrine interval of 4 min to no additional time at a call receipt-to-intraosseous epinephrine interval of 29 min. Conclusions: This retrospective analysis of a national EMS database revealed that IO epinephrine was negatively associated with ROSC. Additionally, there appears to be a finite time window during which intravenous epinephrine remains superior to the intraosseous route even if there are brief initial delays in IV drug delivery.