The Effect of Epinephrine Dosing Intervals on Outcomes from Pediatric In-Hospital Cardiac Arrest

Am J Respir Crit Care Med. 2021 Oct 15;204(8):977-985. doi: 10.1164/rccm.202012-4437OC.


Rationale: Animal studies of cardiac arrest suggest that shorter epinephrine dosing intervals than currently recommended (every 3-5 min) may be beneficial in select circumstances. Objectives: To evaluate the association between epinephrine dosing intervals and pediatric cardiac arrest outcomes. Methods: Single-center retrospective cohort study of children (<18 years of age) who received ⩾1 minute of cardiopulmonary resuscitation and ⩾2 doses of epinephrine for an index in-hospital cardiac arrest. Exposure was epinephrine dosing interval ⩽2 minutes (frequent epinephrine) versus >2 minutes. The primary outcome was survival to hospital discharge with a favorable neurobehavioral outcome (Pediatric Cerebral Performance Category score 1-2 or unchanged). Logistic regression evaluated the association between dosing interval and outcomes; additional analyses explored duration of cardiopulmonary resuscitation (CPR) as a mediator. In a subgroup, the effect of dosing interval on diastolic blood pressure was investigated. Measurements and Main Results: Between January 2011 and December 2018, 125 patients met inclusion/exclusion criteria; 33 (26%) received frequent epinephrine. Frequent epinephrine was associated with increased odds of survival with favorable neurobehavioral outcome (adjusted odds ratio, 2.56; 95% confidence interval, 1.07-6.14; P = 0.036), with 66% of the association mediated by CPR duration. Delta diastolic blood pressure was greater after the second dose of epinephrine among patients who received frequent epinephrine (median [interquartile range], 6.3 [4.1 to 16.9] vs. 0.13 [-2.3 to 1.9] mm Hg; P = 0.034). Conclusions: In patients who received at least two doses of epinephrine, dosing intervals ⩽2 minutes were associated with improved neurobehavioral outcomes compared with dosing intervals >2 minutes. Mediation analysis suggests that improved outcomes are largely due to frequent epinephrine shortening duration of CPR.

Keywords: child; epinephrine; heart arrest.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cardiopulmonary Resuscitation
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Drug Administration Schedule
  • Epinephrine / administration & dosage*
  • Epinephrine / therapeutic use
  • Female
  • Heart Arrest / drug therapy*
  • Heart Arrest / mortality
  • Heart Arrest / therapy
  • Hospital Mortality
  • Humans
  • Infant
  • Infant, Newborn
  • Logistic Models
  • Male
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Vasoconstrictor Agents / administration & dosage*
  • Vasoconstrictor Agents / therapeutic use


  • Vasoconstrictor Agents
  • Epinephrine