Concise Critical Appraisal: Epinephrine Dosing Intervals on Outcomes From Pediatric In-Hospital Cardiac Arrest

Kienzle et al sought to evaluate the association between epinephrine dosing intervals and outcomes in pediatric IHCA.⁶ Their primary hypotheses were that pediatric patients in cardiac arrest would have improved outcomes and intra-arrest DBP from more frequent epinephrine dosing (e.g., ≤ 2 minutes) than from the current standard and that this effect would be most evident during the first 10 minutes of resuscitation.
 
In this retrospective single-center cohort study, the authors reviewed prospectively collected data in subjects younger than 18 years who had an IHCA and who received at least 2 doses of epinephrine and 1 minute of CPR. Patients were excluded if they had missing data, were given any other vasopressors, or required initiation of extracorporeal membrane oxygenation to obtain return of circulation. Epinephrine dosing times were abstracted from bedside records, and DBPs were obtained from bedside monitor data. The primary outcome was survival to hospital discharge with a favorable neurobehavioral outcome, as defined by a Pediatric Cerebral Performance Category score of 1-2 or by a lack of change from baseline. Other measured outcomes included survival to hospital discharge, return of spontaneous circulation (ROSC) > 20 minutes, DBP, and CPR duration.
 
The authors looked at records from January 2011 through December 2018 and ultimately included 125 subjects in the final cohort. There were no significant patient characteristic differences between those who received frequent epinephrine doses (≤ 2 minutes) compared to the standard intervals. The authors found an association between frequent dosing in survival with favorable neurobehavioral outcomes, survival to discharge, ROSC, and duration of CPR. Of note, when stratified by the presence of vasoactive infusions during the arrest, the associations remained, although only the association with the duration of CPR was statistically significant.
 
The authors also determined the indirect effect of CPR duration as a mediator of improved neurobehavioral outcomes and found that it explained 66% of the total effect frequent epinephrine had on this measure. In addition, although data were available from only 16 patients, DBP was found to have increased significantly in the frequent epinephrine group after a second dose of epinephrine, compared with the less frequent epinephrine group, which had no significant change. Finally, the benefits found with frequent epinephrine dosing were not found in more frequent groups in the standard dosing cohort (i.e., 3-minute vs. 5-minute intervals).
 
This study provides novel insight into the current body of literature regarding the most efficacious epinephrine dosing interval in pediatric cardiac arrest. The authors note that other studies that demonstrated outcome improvement with less frequent epinephrine dosing controlled for CPR duration, unlike their study, which found that CPR duration was a significant factor in improvement. This is important because the cumulative dose of epinephrine may be deleterious to a pediatric patient in cardiac arrest, and the cumulative dose of epinephrine in the frequent dosing group was less than in the standard group. Some of the limitations to this study include its retrospective nature, its single-center scope, and reliance on chart documentation data, which may not be accurate. However, this study provides a good physiologically based treatment recommendation for pediatric patients in cardiac arrest who have a high mortality risk.

References

1. Holmberg MJ, Ross CE, Fitzmaurice GM, et al; American Heart Association’s Get With the Guidelines - Resuscitation Investigators. Annual incidence of adult and pediatric in-hospital cardiac arrest in the United States. Circ Cardiovasc Qual Outcomes. 2019 Jul 9;12(7):e005580. https://pubmed.ncbi.nlm.nih.gov/31545574/
2. Holmberg MJ, Wiberg S, Ross CE, et al. Trends in survival after pediatric in-hospital cardiac arrest in the United States. Circulation. 2019 Oct 22;140(17):1398-1408. https://pubmed.ncbi.nlm.nih.gov/31542952/
3. Berg RA, Nadkarni VM, Clark AE, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Incidence and outcomes of cardiopulmonary resuscitation in PICUs. Crit Care Med. 2016 Apr;44(4):798-808. https://pubmed.ncbi.nlm.nih.gov/26646466/
4. Grunau B, Kawano T, Scheuermeyer FX, et al. The association of the average epinephrine dosing interval and survival with favorable neurologic status at hospital discharge in out-of-hospital cardiac arrest. Ann Emerg Med. 2019 Dec;74(6):797-806. https://pubmed.ncbi.nlm.nih.gov/31248676/
5. Hoyme DB, Patel SS, Samson RA, et al; American Heart Association’s Get With the Guidelines - Resuscitation Investigators. Epinephrine dosing interval and survival outcomes during pediatric in-hospital cardiac arrest. Resuscitation. 2017 Aug;117:18-23. https://pubmed.ncbi.nlm.nih.gov/28552658/
6. Kienzle MF, Morgan RW, Faerber JA, et al. The effect of epinephrine dosing intervals on outcomes from pediatric in-hospital cardiac arrest. Am J Respir Crit Care Med. 2021 Jul 15. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/34265230/