'Not One-Size-Fits-All': CHOP Research Seeks to Improve CPR in Children

The study could impact the more than 15,000 children whose hearts suddenly stop beating in U.S. hospitals every year.

In a pioneering effort to improve outcomes for children who have a cardiac arrest in the hospital, Children's Hospital of Philadelphia researchers are seeking to better understand the effects of epinephrine, the most used medication for resuscitation.

The multicenter study, funded by the National Heart Lung and Blood Institute, aims to provide critical insights that could impact the more than 15,000 children whose hearts suddenly stop beating in U.S. hospitals every year. The researchers' goal is to develop personalized cardiopulmonary resuscitation (CPR) strategies, guided by patient characteristics and real-time physiology.

One of the biggest challenges in treating children with cardiac arrest is that there is little high-quality evidence to support CPR guidelines. Not only are clinicians applying adult-derived treatments to treat pediatric patients, but since cardiac arrest is a complex condition that arises from the progression of various diseases, the way patients respond to treatments can differ widely from case to case.

"CHOP is a leader in precision medicine," said principal investigator Ryan Morgan, MD, a researcher in the Resuscitation Science Center and attending physician in CHOP's Pediatric Intensive Care Unit. "But at the time when kids are having a cardiac arrest, regardless of the personalized care they've received prior, our guidelines tell us to reach for the same algorithm off the shelf and treat them all the same. Our goal is to move beyond one-size-fits-all resuscitation and develop interventions tailored to the unique physiologic responses of children."

Most in-hospital cardiac arrests occur in intensive care units and are associated with respiratory failure or shock. While as many as 80% of patients survive the initial event, most do not survive to hospital discharge, according to Dr. Morgan.

A central component of in-hospital CPR is the administration of epinephrine, which is universally recommended during cardiac arrest. It works by constricting blood vessels, raising a patient's diastolic blood pressure, and improving circulation of blood to the heart and other organs.

A 2023 study of 150 pediatric patients conducted by Dr. Morgan and colleagues found that responses to epinephrine varied significantly from patient to patient. A 2024 study, led by CHOP Attending Physician Martha Kienzle, MD, showed that differences in how often the drug was administered also impacted patient outcomes. Those findings suggested that epinephrine could be beneficial during CPR in some clinical scenarios, and potentially harmful in others.

To fill this knowledge gap, Dr. Morgan will gather clinical data from 20 U.S. children's hospitals that are part of the Pediatric Resuscitation Quality Collaborative (pediRES-Q), a CHOP-based international network specifically designed to study in-hospital cardiac arrest. Data will include epinephrine dose timing and high-fidelity physiologic waveforms from patients' bedside monitoring systems.

"We plan to capture real-time data from every single cardiac arrest that happens in 20 pediatric ICUs across the country," Dr. Morgan said. "We'll be able to say, 'Epinephrine was given here. Here's what the patient looked like when it was administered, and here's what happened after.'"

The researchers will aim to build on their preliminary data to determine how epinephrine dosing strategies impact children of differing ages, sexes, and disease states. The researchers also will collaborate with machine-learning experts to develop models capable of predicting responses to CPR methods.

"This project will give us an unparalleled amount of information, so that we can truly understand which patients respond to epinephrine, and how that relates to their outcomes," Dr. Morgan said. "CHOP has always been the epicenter of pediatric resuscitation research, and we're continuing to work with colleagues across divisions and institutions to improve CPR outcomes for all kids."

Vinay Nadkarni, MD, founding director of the pediRES-Q network, and Robert Sutton, MD, Co-Director of the Resuscitation Science Center, will serve as co-investigators on the project.