Clinical paperEpinephrine dosing strategies during pediatric extracorporeal cardiopulmonary resuscitation reveal novel impacts on survival: A multicenter study utilizing time-stamped epinephrine dosing records
Introduction
Cardiopulmonary resuscitation (CPR) guidelines recommend dosing of epinephrine every 3–5 minutes during cardiac arrest, though literature to support this practice is lacking and several recent publications have challenged these guidelines.1, 2, 3, 4 While prior attempts to understand best practices surrounding epinephrine dosing during CPR have been reported, a common challenge encountered while investigating epinephrine’s role in resuscitation is the lack of time-stamped dosing data. This limitation necessitates the use of calculated average epinephrine interval as the variable of interest. This method assumes that doses are evenly distributed throughout the event and may introduce biases that lead to incorrect conclusions regarding the efficacy or harm of epinephrine.
Understanding the true frequency of epinephrine dosing and how it is distributed through resuscitation is vital in cases of extracorporeal cardiopulmonary resuscitation (ECPR), which involves lengthy periods of CPR as the patient is cannulated onto extracorporeal membrane oxygenation (ECMO). Due to the length of ECPR events patients can be exposed to high amounts of cumulative epinephrine that may increase the risk for cerebrovascular injury.5, 6 In a survey of pediatric providers with experience utilizing ECPR for children with underlying cardiac disease, 36% reported giving epinephrine doses less frequently than is recommended.7
To date there are few published reports investigating actual practice using epinephrine dosing time-stamps or the impact of epinephrine dosing strategy on pediatric ECPR outcomes. We sought to describe epinephrine dosing distribution and its impact on survival after ECPR in children. We hypothesized that epinephrine doses would not be uniformly distributed throughout ECPR events and that increased spacing between doses are resuscitation progressed would be associated with improved hospital survival.
Section snippets
Study design and patients
This study was approved or deemed exempt with waiver of consent by the respective institutional review boards at each participating center. This was a retrospective review of in-hospital ECPR events from January 2012 to December 2019. Patients less than 18 years of age were included if they suffered a cardiac arrest ending with successful cannulation onto ECMO. Patients with return of spontaneous circulation (ROSC) >20 minutes prior to cannulation were excluded. Events where CPR started before
Results
A total of 204 patients from 5 centers met inclusion criteria; thirteen were excluded for only receiving 0 or 1 doses of epinephrine, leaving 191 patients for analysis. Overall survival to hospital discharge was 43%. Median age (IQR) for all patients was 5 months (0.7–44) and median weight 6 kg (3.5–9.5). Patient and resuscitation event characteristics grouped by survival are presented in Table 1. Survivors were younger, more likely to be surgical cardiac patients, had better baseline
Discussion
In this multi-center study of pediatric patients undergoing ECPR for in-hospital cardiac arrest, we observed significant variation in practice between centers. Deviation from advanced life support guidelines for administration of epinephrine was common, with doses typically given at least every 5 minutes early in the event but then less frequently as the event progressed. Our analysis is the first to demonstrate a skewed distribution of epinephrine doses given across ECPR events, suggesting
Conclusions
In this multi-center retrospective study of children undergoing in-hospital ECPR, epinephrine dosing frequency often did not follow recommended guidelines and doses were not evenly distributed throughout the duration of ECPR. Survivors consistently received fewer epinephrine doses than non-survivors after the first 10 minutes of resuscitation, and continued epinephrine dosing after 10 minutes did not improve survival. The prior conventional approach to ECPR analyses that assume epinephrine
Financial disclosure
The authors have no disclosures to report.
Funding
This study was funded by the Department of Pediatrics, University of Nebraska Medical Center.
CRediT authorship contribution statement
Laura A. Ortmann: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing. Ron W. Reeder: Methodology, Writing – review & editing. Tia T. Raymond: Investigation, Methodology, Writing – review & editing, Data curation. Marissa A. Brunetti: Data curation, Methodology, Writing – review & editing. Adam Himebauch: Data curation, Investigation, Writing – review & editing. Rupal Bhakta: Data curation,
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
We thank Matthew Sandbulte, PhD of the Child Health Research Institute at Children’s Hospital & Medical Center and the University of Nebraska Medical Center for manuscript review and editing and Elizabeth Lyden, MS of the University of Nebraska Medical Center College of Public Health for statistical support.
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