Evaluation of Use of Epinephrine and Time to First Dose and Outcomes in Pediatric Patients With Out-of-Hospital Cardiac Arrest

Abstract

Importance: While epinephrine has been widely used in prehospital resuscitation for pediatric patients with out-of-hospital cardiac arrest (OHCA), the benefit and optimal timing of epinephrine administration have not been fully investigated.

Objectives: To evaluate the association between epinephrine administration and patient outcomes and to ascertain whether the timing of epinephrine administration was associated with patient outcomes after pediatric OHCA.

Design, setting, and participants: This cohort study included pediatric patients (<18 years) with OHCA treated by emergency medical services (EMS) from April 2011 to June 2015. Eligible patients were identified from the Resuscitation Outcomes Consortium Epidemiologic Registry, a prospective OHCA registry at 10 sites in the US and Canada. Data analysis was performed from May 2021 to January 2023.

Exposures: The main exposures were prehospital intravenous or intraosseous epinephrine administration and the interval between arrival of an advanced life support (ALS)-capable EMS clinician (ALS arrival) and the first administration of epinephrine.

Main outcomes and measures: The primary outcome was survival to hospital discharge. Patients who received epinephrine at any given minute after ALS arrival were matched with patients who were at risk of receiving epinephrine within the same minute using time-dependent propensity scores calculated from patient demographics, arrest characteristics, and EMS interventions.

Results: Of 1032 eligible individuals (median [IQR] age, 1 [0-10] years), 625 (60.6%) were male. 765 patients (74.1%) received epinephrine and 267 (25.9%) did not. The median (IQR) time interval between ALS arrival and epinephrine administration was 9 (6.2-12.1) minutes. In the propensity score-matched cohort (1432 patients), survival to hospital discharge was higher in the epinephrine group compared with the at-risk group (epinephrine: 45 of 716 [6.3%] vs at-risk: 29 of 716 [4.1%]; risk ratio, 2.09; 95% CI, 1.29-3.40). The timing of epinephrine administration was also not associated with survival to hospital discharge after ALS arrival (P for the interaction between epinephrine administration and time to matching = .34).

Conclusions and relevance: In this study of pediatric patients with OHCA in the US and Canada, epinephrine administration was associated with survival to hospital discharge, while timing of the administration was not associated with survival.

Figure 1.. Flow Diagram of Cohort Selection

ALS indicated advanced life support; DNR, do-not-resuscitate; EMS, emergency medical services; OHCA, out-of-hospital cardiac arrest.

Figure 2.. Survival to Hospital Discharge Stratified by Timing of Epinephrine Administration in Primary Analysis and Sensitivity Analysis (Excluding Those Who Had Return of Spontaneous Circulation or Termination of Resuscitation Within 5 Minutes of Advanced Life Support Arrival)

Point estimates of the association of epinephrine with the outcome (solid lines) were reported with 95% CIs (dashed lines), treating timing of epinephrine administration after ALS arrival as a continuous variable. Squares indicate point estimates of the association of epinephrine with the outcome with 95% CIs, treating timing as a categorical variable. Figure 2A, P = .34 for the interaction between epinephrine administration and time to matching. Figure 2B, P = .03 for the interaction between epinephrine administration and time to matching. ALS indicates advanced life support; EMS emergency medical services.