Abstract Body:
Introduction: Acute hypotension in the PICU is often treated with low-dose peri-arrest bolus epinephrine (PBE) to prevent cardiac arrest. As an infusion, the hemodynamic effects of epinephrine typically increase with higher dosing. However, two retrospective studies showed no relationship between the weight-based dose of PBE and change in SBP. Additionally, the initial response to PBE has been shown to be associated with hospital survival. Therefore, we performed an RCT to compare the change in SBP before and after two commonly used doses of PBE. We hypothesized that the higher dose would result in greater increases in SBP.

Methods: Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial (EPI Dose) was a single-center, randomized, double-blind, dose-effect trial comparing an initial PBE dose of 1mcg/kg vs 0.5mcg/kg. Blinded treatment packs of either 10mcg/mL or 5mcg/mL of epinephrine were prepared. Clinicians were instructed to use 0.1mL/kg of the experimental drug for the initial PBE dose in eligible patients with acute hypotension. Exception From Informed Consent was used. The primary endpoint was the change in SBP from 5 minutes before to 5 minutes after the initial PBE dose. The secondary endpoint was frequency of Stage II hypertension for age. Analyses were performed per intention-to-treat. Additional prespecified analyses were performed.

Results: The trial was stopped early due to insufficient funds. Fifteen patients received the study intervention, including 6 in the 1mcg/kg group and 9 in the 0.5mcg/kg group. The groups were balanced with respect to baseline characteristics (Table 1). The mean change in SBP was 83±61mmHg in the 1mcg/kg group vs 36±18mmHg in the 0.5mcg/kg group (p=0.12; Table 2 and Figure 1). Four (67%) patients in the 1mcg/kg group vs 2 (22%) in the 0.5mcg/kg group experienced Stage II hypertension or greater (p=0.14).

All patients survived the resuscitation event. One patient (17%) in the 1mcg/kg group required additional PBE doses compared to 6 (67%) in the 0.5mcg/kg group (p=0.12; Table 2). One patient in the 0.5mcg/kg group required chest compressions 2 minutes after study drug.

Conclusions: Change in SBP after 1mcg/kg of PBE was numerically higher than that after 0.5mcg/kg but did not reach statistical significance in this abbreviated trial. Numerically more patients in the 1mcg/kg group experienced hypertension but fewer required additional PBE doses during the event compared to the 0.5mcg/kg group.