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

Abstract

<b>Rationale:</b> Animal studies of cardiac arrest suggest that shorter epinephrine dosing intervals than currently recommended (every 3-5 min) may be beneficial in select circumstances. <b>Objectives:</b> To evaluate the association between epinephrine dosing intervals and pediatric cardiac arrest outcomes. <b>Methods:</b> 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. <b>Measurements and Main Results:</b> 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; <i>P</i> = 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; <i>P</i> = 0.034). <b>Conclusions:</b> 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.