Endotracheal epinephrine at standard versus high dose for resuscitation of asystolic newborn lambs.

INTRODUCTION: Endotracheal (ET) epinephrine administration is an option during neonatal resuscitation, if the preferred intravenous (IV) route is unavailable. OBJECTIVES: We assessed whether endotracheal epinephrine achieved return of spontaneous circulation (ROSC), and maintained physiological stability after ROSC, at standard and higher dose, in severely asphyxiated newborn lambs. METHODS: Near-term fetal lambs were asphyxiated until asystole. Resuscitation was commenced with ventilation and chest compressions. Lambs were randomly allocated to: IV Saline placebo (5 ml/kg), IV Epinephrine (20 micrograms/kg), Standard-dose ET Epinephrine (100 micrograms/kg), and High-dose ET Epinephrine (1 mg/kg). After three allocated treatment doses, rescue IV Epinephrine was administered if ROSC had not occurred. Lambs achieving ROSC were monitored for 60 minutes. Brain histology was assessed for microbleeds. RESULTS: ROSC in response to allocated treatment (without rescue IV Epinephrine) occurred in 1/6 Saline, 9/9 IV Epinephrine, 0/9 Standard-dose ET Epinephrine, and 7/9 High-dose ET Epinephrine lambs respectively. Blood pressure during CPR increased after treatment with IV Epinephrine and High-dose ET Epinephrine, but not Saline or Standard-dose ET Epinephrine. After ROSC, both ET Epinephrine groups had lower pH, higher lactate, and higher blood pressure than the IV Epinephrine group. Cortex microbleeds were more frequent in High-dose ET Epinephrine lambs (8/8 lambs examined, versus 3/8 in IV Epinephrine lambs). CONCLUSIONS: The currently recommended dose of ET Epinephrine was ineffective in achieving ROSC. Without convincing clinical or preclinical evidence of efficacy, use of ET Epinephrine at this dose may not be appropriate. High-dose ET Epinephrine requires further evaluation before clinical translation.

Assessing the influence of abdominal compression on time to return of circulation during resuscitation of asphyxiated newborn lambs: a randomised preclinical study.

OBJECTIVE: During neonatal resuscitation, the return of spontaneous circulation (ROSC) can be achieved using epinephrine which optimises coronary perfusion by increasing diastolic pressure. Abdominal compression (AC) applied during resuscitation could potentially increase diastolic pressure and therefore help achieve ROSC. We assessed the use of AC during resuscitation of asystolic newborn lambs, with and without epinephrine. METHODS: Near-term fetal lambs were instrumented for physiological monitoring and after delivery, asphyxiated until asystole. Resuscitation was commenced with ventilation followed by chest compressions. Lambs were randomly allocated to: intravenous epinephrine (20 µg/kg, n=9), intravenous epinephrine+continuous AC (n=8), intravenous saline placebo (5 mL/kg, n=6) and intravenous saline+AC (n=9). After three allocated treatment doses, rescue intravenous epinephrine was administered if ROSC had not occurred. Time to achieve ROSC was the primary outcome. Lambs achieving ROSC were ventilated and monitored for 60 min before euthanasia. Brain histology was assessed for micro-haemorrhage. RESULTS: Use of AC did not influence mean time to achieve ROSC (epinephrine lambs 177 s vs epinephrine+AC lambs 179 s, saline lambs 602 s vs saline+AC lambs 585 s) or rate of ROSC (nine of nine lambs, eight of eight lambs, one of six lambs and two of eight lambs, respectively). Application of AC was associated with higher diastolic blood pressure (mean value >10 mm Hg), mean and systolic blood pressure and carotid blood flow during resuscitation. Cortex and deep grey matter micro-haemorrhage was more frequent in AC lambs. CONCLUSION: Use of AC during resuscitation increased diastolic blood pressure, but did not impact time to ROSC.