Epinephrine Dosing Intervals Are Associated With Paediatric Cardiac Arrest Outcomes

April 20, 2022

By Erika Pimentel

VIRTUAL -- April 20, 2022 -- Shorter epinephrine dosing intervals were associated with favourable outcomes in paediatric patients requiring CPR due to an in-hospital cardiac arrest, according to a study presented at the 51st Critical Care Congress, the Annual Meeting of the Society of Critical Care Medicine (SCCM).

“Epinephrine during PCR is complicated,” said Martha F. Kienzle, MD, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “Data to support its use are limited and variable. Most studies are retrospective and observational, and because cardiac arrest is heterogeneous and complex, it is a challenging event to study.”

She noted that current guidelines recommend epinephrine boluses every 3 to 5 minutes, but data to support this interval are lacking.

To get more clarity, Dr. Kienzle and colleagues conducted a retrospective cohort study of 125 index in-hospital cardiac arrests at Children’s Hospital of Philadelphia. 

“We hand calculated epinephrine dosing intervals based on documented times on bedside code sheets, rounded to the nearest minute, and created an event-level average for each patient, which we referred to as ‘calculated dosing interval,’” explained Dr. Kienzle. “We found that epinephrine dosing intervals ≤2 minutes, aka ‘frequent epi,’ were associated with our primary outcome of survival to discharge with a favourable neurologic status compared with dosing intervals >2 minutes.”

For the primary outcome, the unadjusted odds ratio (OR) was 2.85 (95% confidence interval [CI], 1.25-6.48; P = .013). After adjusting for location, age, category, initial rhythm, time of day, and delayed time to first epinephrine dose (>5 minutes), the OR was 2.56 (95% CI, 1.07-6.14; P = .036).

Frequent epinephrine was also associated with improved odds of survival to discharge (unadjusted OR = 2.67, 95% CI, 1.18-6.03, P = .018; adjusted OR = 2.69, 95% CI, 1.12-6.43; P = .027), return of spontaneous circulation (ROSC [unadjusted OR = 8.27, 95% CI, 1.86-36.8; P = .006; adjusted OR = 8.88, 95% CI, 1.91-41.3, P = .005]), and shorter CPR duration by 15 minutes (P < .01).

“In a subset of patients with arterial lines, patients exposed to frequent epi had significant increases in their diastolic blood pressure following a second dose of epinephrine, providing a plausible mechanism for fast ROSC, less low-flow time, and better neurologic survival,” said Dr. Kienzle.

With the recent conclusion of the ICU RESUS trial, the researchers then went on to investigate frequent epinephrine using multicentre data. The trial included paediatric patients who required CPR of any duration at 18 intensive care units (ICUs) across 10 clinical sites.

“We explored the relationship between estimated and calculated dosing intervals in those patients who had sufficient information available to determine both -- about a quarter of subjects,” said Dr. Kienzle. “The estimated dosing interval was indeed higher than the calculated dosing interval in many cases -- a mean of about 1 minute higher and a median of about .7 minutes higher. Thus, instead of a 2-minute cut-off like in our study, we used a 3-minute cut-off.”

Of the cardiac arrest cases available for analysis from the ICU RESUS trial, 286 received epinephrine ≥3 minutes and 96 received a more frequent dosing interval (<3 minutes). Duration of CPR was significantly shorter among patients receiving epinephrine at shorter intervals (13 vs 9 minutes; P < .001). The primary outcome of survival to discharge with favourable neurologic outcome occurred in 36% of patients in the ≥3-minute group compared with 43% in the <3-minute group. ROSC ≥20 minutes occurred in 68% versus 81%, respectively, which was statistically significant (P = .013). Survival to discharge was similar (43% vs 45%). Regression analysis found that a vasoactive infusion at the time of cardiac arrest was associated with more favourable outcomes when exposed to epinephrine.

“These results challenge the current AHA [American Heart Association] recommended dosing interval of 3 to 5 minutes, but randomised controlled trials are needed,” said Dr. Kienzle.

[Presentation title: Epinephrine Dosing Interval Is Associated With Outcomes From Pediatric In-Hospital Cardiac Arrest: a Multicenter Study]