Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest.

Deepika Sankaran,Payam Vali,Sylvia F Gugino,Munmun Rawat,Jayasree Nair,Ziad Alhassen,Evan M Giusto,Bobby Mathew,Houssam M Joudi,Gary M Weiner,Lori Nielsen,Praveen Chandrasekharan,Peggy Chen,Lida Zeinali,Carmon Koenigsknecht,Justin Helman,Amy Lesneski ,Morgan Hardie ,Heather K Knych ,Satyanarayana Lakshminrusimha

doi:10.3390/children8060464

Abstract

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Highlights

The International Liaison Committee on Resuscitation (ILCOR) advocates use of epinephrine in neonates with severe bradycardiadespite effective positive pressure ventilation (PPV) and chest compressions (CC) if return of spontaneous circulation (ROSC) is not achieved [1,2]
Twenty-two near-term lambs were asphyxiated until cardiac arrest by umbilical cord occlusion
The current study reports that larger flush volume of 2.5-mL normal saline following epinephrine at a dose of 0.03 mg/kg is associated with 80% incidence of ROSC, following the first dose of IV epinephrine, compared to 42% with the use of 1-mL flush

Summary

Introduction

The International Liaison Committee on Resuscitation (ILCOR) advocates use of epinephrine in neonates with severe bradycardia (heart rate < 60 beats per minute [bpm])despite effective positive pressure ventilation (PPV) and chest compressions (CC) if return of spontaneous circulation (ROSC) is not achieved [1,2]. The 7th edition of the Textbook of Neonatal Resuscitation recommends 0.5-mL to 1-mL flush following IV epinephrine (0.01 to 0.03 mg/kg dose) via a low-lying UVC [6]. This flush volume may be sufficient in the setting of spontaneous cardiac activity (i.e., bradycardia), the recommended flush volume may only clear a 5 Fr UVC (internal volume = 0.55 mL) that is placed for term neonates and may not be sufficient to drive epinephrine to the heart and the circulating blood in the setting of cardiac arrest and CC [7]. Earlier ROSC following effective and quick delivery of an epinephrine dose by a route with maximum bioavailability may potentially improve survival and outcomes [8,9]

Objectives

Methods

Results

Discussion

Conclusion