Association of Early Epinephrine with Hemodynamics and Outcome in Pediatric In-Hospital Cardiac Arrest: A Secondary Analysis of a Multicenter, Cluster-randomized Clinical Trial Intensive Care Unit Resuscitation (ICU-RESUS)

Rationale: Delayed (>5 minutes) epinephrine during pediatric in-hospital cardiac arrest (IHCA) is associated with worse outcomes. Epinephrine is nearly always given earlier, limiting 5 minutes as a quality target. Objectives: To assess early epinephrine administration (⩽2 minutes) on outcomes and hemodynamics during cardiopulmonary resuscitation (CPR) in pediatric IHCA from pulseless, nonshockable rhythms. Methods: This study leveraged the database of the ICU-RESUS (Intensive Care Unit Resuscitation) project (clinicaltrials.gov identifier NCT02837497). Primary exposure was the time to epinephrine bolus: early versus >2 minutes. Primary outcome was survival to discharge. Secondary outcomes included the return of spontaneous circulation (ROSC), survival with favorable neurologic outcome, change from baseline to discharge Functional Status Scale (FSS) score, total FSS score at discharge, new morbidity among survivors, and invasively measured blood pressure during the first 10 minutes of CPR. Results: Among 352 CPR events, median age was 1.0 (interquartile range [IQR], 0.3-8.0) year, 186 (53%) were male, and 185 (52.6%) had cardiac disease. Early epinephrine was administered in 273 (78%), and median time to administration was 1.0 (0.0-2.0) minute. Survival to discharge was similar between patients who received early epinephrine and those who did not. Early epinephrine administration was associated with higher ROSC, a change from baseline to discharge in FSS, lower total FSS scores at discharge, and lower rates of new morbidity compared with epinephrine administration at >2 minutes. The probability of ROSC and survival to discharge with favorable neurologic outcome decreased for each minute of delay in epinephrine administration. There was no difference in the invasive blood pressure targets during the first 10 minutes of CPR. Conclusions: Early epinephrine administration was common and was associated with higher ROSC and improved functional outcomes compared with epinephrine administration at >2 minutes in pediatric IHCA.