Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study
Authors: O’Halloran Amanda J. , Reeder Ron W. , Berg Robert A. , Ahmed Tageldin , Bell Michael J. , Bishop Robert , Bochkoris Matthew , Burns Candice , Carcillo Joseph A. , Carpenter Todd C. , Dean J. Michael , Diddle J. Wesley , Federman Myke , Fernandez Richard , Fink Ericka L. , Franzon Deborah , Frazier Aisha H. , Friess Stuart H. , Graham Kathryn , Hall Mark , Hehir David A. , Horvat Christopher M. , Huard Leanna L. , Kienzle Martha F. , Kilbaugh Todd J. , Maa Tensing , Manga Arushi , McQuillen Patrick S. , Meert Kathleen L. , Mourani Peter M. , Nadkarni Vinay M. , Naim Maryam Y. , Notterman Daniel , Pollack Murray M. , Sapru Anil , Schneiter Carleen , Sharron Matthew P. , Srivastava Neeraj , Tilford Bradley , Topjian Alexis A. , Viteri Shirley , Wessel David , Wolfe Heather A. , Yates Andrew R. , Zuppa Athena F. , Sutton Robert M. , Morgan Ryan W. 
Published: July 2024

Abstract
Background
Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness.

Methods
Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016–March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status.

Results
Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001).

Conclusions
In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset.