Epinephrine associated with out-of-hospital cardiac arrest survival to discharge

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Epinephrine administration is associated with survival to hospital discharge among pediatric patients with out-of-hospital cardiac arrest (OHCA), though timing of administration was not associated with survival, according to a recent study published in Jama Network Open.

An estimated 7,000 to 23,000 infants and children experience OHCA annually. Rates of survival to hospital discharge and good functional recovery at hospital discharge after emergency medical services (EMS)-treated pediatric OHCA are estimated to be 11.3% and 8.6%, respectively.

Epinephrine is commonly administered via intravenous (IV) and intraosseous (IO) routes during cardiopulmonary resuscitation. The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommendations for epinephrine administration continue to be reaffirmed, study authors wrote, emphasizing early administration. Guidelines suggest administering the initial dose of epinephrine for pediatric cardiac arrest within 5 minutes from the start of chest compressions. Evidence related to the benefits and optimal timing of epinephrine administration is limited.

This cohort study’s primary outcome was to evaluate the association between prehospital IV or IO epinephrine administration and patient outcomes. Secondary objectives were determining whether timing of administration was associated with patient outcomes and favorable functional outcomes at hospital discharge, defined as modified Rankin scale score of 3 or greater and prehospital return of spontaneous circulation (ROSC). Investigators used the Resuscitation Outcomes Consortium (ROC) Epidemiologic Registry-Cardiac Arrest, a prospective standardized data collection of consecutive patients with OHCA. The ROC is a clinical research network that studied the treatment and outcomes of patients with OHCA at 10 regional coordinating sites in the United States and Canada.

A total of 1032 pediatric patients less than 18 years of age with EMS-treated, nontraumatic OHCA from April 2011 to June 2015, defined as resuscitation attempts with shock delivery by external defibrillator or chest compressions, were included. Patients who had termination of resuscitation (TOR) because of preexisting do-not-resuscitate orders, whose initial rhythm was unknown, and whose epinephrine administration status was unknown were excluded. Further, patients that were administered vasopressin, that received epinephrine administered via endotracheal tube, that had missing or negative resuscitation interval variables, and patients with missing data about survival to hospital discharge were not included.

To evaluate the association between epinephrine administration and outcomes, investigators performed time-dependent propensity score (PS) and risk-set matching analyses. According to the study, investigators divided the whole cohort into 2 age groups, younger than 1 year and 1 year or older, and carried out the time-dependent PS and risk-set matching in each group, avoiding matching across age groups. According to authors, “To evaluate the association of epinephrine administration with outcomes, we performed 1:1 risk-set matching with replacement using the calculated time-dependent PS.” Each patient that received epinephrine at any given minute after advanced life support (ALS) arrival was sequentially matched with a patient who was at risk of receiving epinephrine with a similar PS at the same minute. “At-risk patients could have been matched multiple times as at-risk patients or patients receiving epinephrine (only if the patients received epinephrine) until receiving epinephrine (matching with replacement),” authors wrote. Investigators subsequently combined the matched cohort of each age group and created the whole matched cohort.

Of the 1032 eligible patients in the analysis (median [IQR] age, 1[0-10] years) 625 (60.6%) were male. A total of 765 individuals (74.1%) received epinephrine while 267 (25.9%) did not. The IQR time interval between ALS arrival and epinephrine administration was 9 (6.2-12.1) minutes.

Using risk-set matching, 716 patients that received epinephrine were matched with patients who were at risk of receiving epinephrine in the same minutes. Among those matched as at-risk patients, 483 (67.5%) received epinephrine after matching. The IQR time interval between ALS arrival and administration of epinephrine was 8 (6-11) minutes for patients in the epinephrine group and 12 (9.5-16) in the at-risk group.

In the PS-matched cohort (1432 patients total), survival to hospital discharge was higher in the epinephrine group (45 of 716 [6.3%]) compared with the at-risk group (29 of 716 [4.1%]) (risk ratios, 2.09; 95% CI, 1.29-3.40). The timing of epinephrine administration was not associated with survival to hospital discharge after ALS arrival (P = .34 [interaction between epinephrine administration and time to matching]).

Authors conclude these findings demonstrated that epinephrine administration was associated with survival to hospital discharge and prehospital ROSC, but favorable functional outcome at hospital discharge was not. The timing of epinephrine administration was not associated with survival to hospital discharge, favorable functional outcome, or prehospital ROSC.

“Overall, these findings support the administration of epinephrine for pediatric OHCA,” authors wrote.

Reference:

Amoako J, Komukai S, Izawa J, Callaway CW, Okubo M. Evaluation of use of epinephrine and time to first dose and outcomes in pediatric patients with out-of-hospital cardiac arrest. JAMA Netw Open. 2023;6(3):e235187. doi:10.1001/jamanetworkopen.2023.5187