High-Dose Epinephrine in Pediatric Out-of-Hospital Cardiopulmonary Arrest
Authors: Dieckmann Ronald A. , Vardis Ralph 
Published: December 2021

Objective. To compare the efficacy of high-dose epinephrine (HDE) and standard-dose epinephrine (SDE) for out-of-hospital treatment of pediatric cardiopulmonary arrest (CPA).
Design. Forty-eight-month retrospective cohort study.
Setting. Prehospital emergency medical services (EMS) system of a large metropolitan region.
Patients. All children younger than 18 years of age, who suffered nontraumatic CPA, did not meet local EMS criteria for death in the field, and were treated by paramedics according to EMS pediatric CPA protocols.
Interventions. Paramedics administered HDE (&gt;0.1 mg/kg), SDE (&lt;0.1 mg/kg), or no epinephrine (NE), based on base hospital physician order and availability of access for drug delivery. Protocols permitted either HDE or SDE. The drug was given through an endotracheal tube, intraosseous line, or intravenous line.
Main outcome measures. Return of spontaneous circulation (ROSC) and return of an organized electrical rhythm (ROER) in the ambulance and emergency department, hospital admission, hospital discharge, and short-and long-term neurologic outcome by pediatric cerebral performance category (PCPC) score.
Results. During the study period, 65 children met inclusion criteria and underwent attempted out-of-hospital resuscitation. Forty patients (62%) received HDE (mean dose ± SD, 0.19 ± 0.06 mg/kg); 13 patients (20%) received SDE (mean dose ± SD, 0.02 ± 0.02 mg/kg); and 12 patients (18%) received NE. The HDE and SDE groups were statistically different only in epinephrine dose but not in age, gender, proportion of asystolic presenting rhythms, success of endotracheal tube intubation or intraosseous line insertion, rate of ROSC, rate of ROER, survival, or proportion of sudden infant death syndrome final diagnoses. Fifty-four children (83%) presented in asystole, 5 (8%) had pulseless electrical activity (PEA), and 6 (9%) had ventricular fibrillation (VF). None presented with either supraventricular tachycardia or ventricular tachycardia. Thirty-nine patients receiving HDE had asystole or VF as presenting rhythms, 4 (10%) had ROER, and 1 had ROSC. The single child receiving HDE presenting with PEA did not have ROSC. Ten patients receiving SDE had asystole or VF, 2 (20%) had ROER, and none had ROSC. There were 3 children receiving SDE who had PEA, and 1 had ROSC. Eleven patients receiving NE had asystole or VF, and none had ROER. One child receiving NE had PEA and ROSC. Altogether, 1 patient receiving HDE, 1 receiving SDE, and 1 receiving NE had ROSC in the field, which continued in the emergency department; all 3 were admitted to the hospital. Two children (3%), 1 receiving HDE and 1 receiving SDE, survived to hospital discharge. The survivor receiving HDE had spastic quadriplegia and profound neurologic handicaps at discharge, with a PCPC score of 4 (severe disability with daily living milestones below the 10th percentile and excessive dependence on others for provision of activities of daily living); at a 1-year follow-up, she had a PCPC score of 4. The survivor receiving SDE was neurologically healthy at discharge; at discharge and at follow-up at age 1 year, she had a PCPC score of 1 (age-appropriate level of functioning and developmentally appropriate).
Conclusions. HDE does not seem to improve the rates of ROER and ROSC, hospital admission, survival, or neurologic outcome when compared with SDE for treatment of out-of-hospital pediatric CPA. A large, blinded prospective clinical trial testing different epinephrine doses is necessary to determine drug efficacy and safety. Future pediatric CPA studies must standardize reporting of core data elements, using the adult Utstein criteria modified for pediatrics, to allow valid treatment comparisons. Overall, survival in out-of-hospital pediatric CPA is dismal. When strict inclusion criteria for cardiac standstill are observed, outcome from out-of-hospital pediatric CPA may be significantly worse than previously reported. Like adults, children failing out-of-hospital advanced life support are extremely unlikely to have meaningful survival. Out-of-hospital pediatric treatment and transport policies should assure delivery of appropriate advanced life support; in some well-controlled situations, termination of resuscitation without hospital transport may be possible. Immediate grief counseling for the parents and critical incident stress debriefing for ambulance personnel are essential.