Randomized Controlled Trial

. 2024 Jul 16;28(1):242.

doi: 10.1186/s13054-024-05018-7.

Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study

Amanda J O'Halloran¹, Ron W Reeder², Robert A Berg³, Tageldin Ahmed⁴, Michael J Bell⁵, Robert Bishop⁶, Matthew Bochkoris⁷, Candice Burns⁸, Joseph A Carcillo⁷, Todd C Carpenter⁶, J Michael Dean², J Wesley Diddle³, Myke Federman⁹, Richard Fernandez¹⁰, Ericka L Fink⁷, Deborah Franzon¹¹, Aisha H Frazier^{12

13}, Stuart H Friess¹⁴, Kathryn Graham³, Mark Hall¹⁰, David A Hehir³, Christopher M Horvat⁷, Leanna L Huard⁹, Martha F Kienzle³, Todd J Kilbaugh³, Tensing Maa¹⁰, Arushi Manga¹⁴, Patrick S McQuillen¹¹, Kathleen L Meert⁴, Peter M Mourani¹⁵, Vinay M Nadkarni³, Maryam Y Naim³, Daniel Notterman¹⁶, Murray M Pollack⁵, Anil Sapru⁹, Carleen Schneiter⁶, Matthew P Sharron⁵, Neeraj Srivastava⁹, Bradley Tilford⁴, Alexis A Topjian³, Shirley Viteri¹⁷, David Wessel⁵, Heather A Wolfe³, Andrew R Yates¹⁰, Athena F Zuppa³, Robert M Sutton^#³, Ryan W Morgan^#³

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA. ohallorana@chop.edu.
² Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
³ Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
⁴ Department of Pediatrics, Children's Hospital of Michigan, Central Michigan University, Detroit, MI, USA.
⁵ Department of Pediatrics, Children's National Hospital, George Washington University School of Medicine, Washington, D.C., DC, USA.
⁶ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
⁷ Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI, USA.
⁹ Department of Pediatrics, Mattel Children's Hospital, University of California Los Angeles, Los Angeles, CA, USA.
¹⁰ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
¹¹ Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA, USA.
¹² Nemours Cardiac Center, Nemours Children's Health, Wilmington, DE, USA.
¹³ Department of Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
¹⁴ Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.
¹⁶ Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
¹⁷ Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children and Thomas Jefferson University, Wilmington, DE, USA.

^# Contributed equally.

PMID: 39010134
PMCID: PMC11251231
DOI: 10.1186/s13054-024-05018-7

Randomized Controlled Trial

Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study

Amanda J O'Halloran et al. Crit Care. 2024.

. 2024 Jul 16;28(1):242.

doi: 10.1186/s13054-024-05018-7.

Authors

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA. ohallorana@chop.edu.
² Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
³ Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
⁴ Department of Pediatrics, Children's Hospital of Michigan, Central Michigan University, Detroit, MI, USA.
⁵ Department of Pediatrics, Children's National Hospital, George Washington University School of Medicine, Washington, D.C., DC, USA.
⁶ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
⁷ Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI, USA.
⁹ Department of Pediatrics, Mattel Children's Hospital, University of California Los Angeles, Los Angeles, CA, USA.
¹⁰ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
¹¹ Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA, USA.
¹² Nemours Cardiac Center, Nemours Children's Health, Wilmington, DE, USA.
¹³ Department of Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
¹⁴ Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.
¹⁶ Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
¹⁷ Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children and Thomas Jefferson University, Wilmington, DE, USA.

^# Contributed equally.

PMID: 39010134
PMCID: PMC11251231
DOI: 10.1186/s13054-024-05018-7

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.

Keywords: Bradycardia; Cardiopulmonary resuscitation; Epinephrine; Heart arrest; Hemodynamics; Pediatric intensive care units.

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Conflict of interest statement

Drs. Reeder’s, Carcillo’s, Carpenter’s, Dean’s, Fink’s, Frazier’s, Friess’, Hall’s, Manga’s, Morgan’s, Mourani’s, Nadkarni’s, Naim’s, Palmer’s, Pollack’s, Wessel’s, Wolfe’s, Yates’, Zuppa’s, Sutton’s, and Meert’s institutions received funding from the National Institutes of Health (NIH). Drs. Reeder, Berg, Carcillo, Carpenter, Dean, Fink, Frazier, Friess, Hall, Horvat, Maa, McQuillen, Meert, Morgan, Mourani, Nadkarni, Naim, Pollack, Wessel, Wolfe, Yates, and Zuppa received support for article research from the NIH. Dr. Berg’s institution received funding from the National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network grant and the National Heart, Lung, and Blood Institute (NHLBI) ICU-RESUS trial grant. Dr. Fink’s institution received funding from the Neurocritical Care Society; she received funding from the American Board of Pediatrics and the Child Neurology Society. Dr. Friess received funding from an expert witness testimony. Dr. Hall received funding from Abbvie, La Jolla Pharmaceuticals, and Kiadis. Drs. Horvat, Maa, and McQuillen’s institutions received funding from the NICHD. Dr. Horvat’s institution received funding from the National Institute of Neurological Disorders and Stroke. Dr. Maa’s institution received funding from the NHLBI. Dr. Mourani disclosed the off-label product use of sodium bicarbonate. Dr. Pollack disclosed work for hire. Dr. Wolfe received funding from The Debriefing Academy and Zoll. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

**Fig. 2**
Temporal evolution of CPR rhythms and outcomes. Subjects include the 186 patients in the cohort with evaluable arterial line waveform data. Stacked band plot of subjects' rhythm status over the first 10 minutes of CPR. A cross-section at any moment in time shows the percentage of subjects iwth each status at that time

See this image and copyright information in PMC

References

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Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study

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Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study

Authors

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Abstract

Conflict of interest statement

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