Association of Timing of Epinephrine Administration With Outcomes in Adults With Out-of-Hospital Cardiac Arrest

Abstract

Importance: Administration of epinephrine has been found to be associated with an increased chance of survival after out-of-hospital cardiac arrest (OHCA), but the optimal timing of administration has not been fully investigated.

Objective: To ascertain whether there is an association between timing of epinephrine administration and patient outcomes after OHCA.

Design, setting, and participants: This cohort study included adults 18 years or older with OHCA treated by emergency medical services (EMS) personnel from April 1, 2011, to June 30, 2015. Initial cardiac rhythm was stratified as either initially shockable (ventricular defibrillation or pulseless ventricular tachycardia) or nonshockable (pulseless electrical activity or asystole). Eligible individuals were identified from among publicly available, deidentified patient-level data from the Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry, a prospective registry of adults with EMS-treated, nontraumatic OHCA with 10 sites in North America. Data analysis was conducted from May 2019 to April 2021.

Exposures: Interval between advanced life support (ALS)-trained EMS personnel arrival at the scene and the first prehospital intravenous or intraosseous administration of epinephrine.

Main outcomes and measures: The primary outcome was survival to hospital discharge. In each cohort of initial cardiac rhythms, patients who received epinephrine at any period (minutes) after EMS arrival at the scene were matched with patients who were at risk of receiving epinephrine within the same period using time-dependent propensity scores calculated from patient demographic characteristics, arrest characteristics, and EMS interventions.

Results: Of 41 079 eligible individuals (median [interquartile range] age, 67 [55-79] years), 26 579 (64.7%) were men. A total of 10 088 individuals (24.6%) initially had shockable cardiac rhythms, and 30 991 (75.4%) had nonshockable rhythms. Those who received epinephrine included 8223 patients (81.5%) with shockable cardiac rhythms and 27 901 (90.0%) with nonshockable rhythms. In the shockable cardiac rhythm cohort, the risk ratio (RR) for receipt of epinephrine with survival to hospital discharge was highest between 0 and 5 minutes after EMS arrival (1.12; 95% CI, 0.99-1.26) across the categorized timing of the administration of epinephrine by 5-minute intervals after EMS arrival; however, that finding was not statistically significant. Treating the timing of epinephrine administration as a continuous variable, the RR for survival to hospital discharge decreased 5.5% (95% CI, 3.4%-7.5%; P < .001 for the interaction between epinephrine administration and time to matching) per minute after EMS arrival. In the nonshockable cardiac rhythm cohort, the RR for the association of receipt of epinephrine with survival to hospital discharge was the highest between 0 and 5 minutes (1.28; 95% CI, 0.95-1.72), although not statistically significant, and decreased 4.4% (95% CI, 0.8%-7.9%; P for interaction = .02) per minute after EMS arrival.

Conclusions and relevance: Among adults with OHCA, survival to hospital discharge differed across the timing of epinephrine administration and decreased with delayed administration for both shockable and nonshockable rhythms.

Figure 1.. Survival to Hospital Discharge, Favorable Functional Outcome at Hospital Discharge, and Prehospital Return of Spontaneous Circulation (ROSC) Stratified by Timing of Epinephrine Administration in Patients With Out-of-Hospital Cardiac Arrest and Initial Shockable Cardiac Rhythms

Figure shows the risk ratio (RR) point estimates (squares) with the 95% CIs (upper and lower bounds indicated by the blue dashed lines) for administration of epinephrine after arrival of emergency medical services personnel at the scene associated with survival to hospital discharge (A), favorable functional status at discharge (B), and ROSC (C). Timing of epinephrine administration was treated as a continuous variable. A, The RR per minute decreased 5.5% (95% CI, 3.4%-7.5%; P < .001 for the interaction). B, The RR per minute decreased 6.4% (95% CI, 3.8%-8.9%; P < .001 for the interaction). C, The RR per minute increased 1.4% (95% CI, 0.2%-2.7%; P = .02 for the interaction). The solid line represents the outcome. Risk ratios greater than 1.00 (horizontal line) favored receiving epinephrine; those less than 1.00, not receiving epinephrine. The error bars indicate 95% CIs.

Figure 2.. Survival to Hospital Discharge, Favorable Functional Outcome at Hospital Discharge, and Prehospital Return of Spontaneous Circulation (ROSC) Stratified by the Timing of Epinephrine Administration in Patients With Out-of-Hospital Cardiac Arrest and Initial Nonshockable Cardiac Rhythms

Figure shows the risk ratio point estimates (squares) with the 95% CIs (upper and lower bounds indicated by the blue dashed lines) associated with survival to hospital discharge (A), favorable functional status at discharge (B), and ROSC (C). Timing of epinephrine administration was treated as a continuous variable. A, The RR per minute decreased 4.4% (95% CI, 0.8%-7.9%; P = .02 for the interaction). B, The RR per minute decreased 7.1% (95% CI, 1.7%-12.3%; P = .01 for the interaction). C, The RR per minute increased 1.5% (95% CI, 0.6%-2.4%; P = .001 for the interaction). The solid line represents the outcome. Risk ratios greater than 1.00 (horizontal line) favored receiving epinephrine; those less than 1.00, not receiving epinephrine. The error bars indicate 95% CIs.