Epinephrine vs placebo in neonatal resuscitation: ROSC and brain MRS/MRI in term piglets

HB Andersen, M Andersen, TCK Andelius… - Pediatric …, 2023 - nature.com
HB Andersen, M Andersen, TCK Andelius, MV Pedersen, B Løfgren, M Pedersen
Pediatric Research, 2023nature.com
Background We aimed to investigate the effect of epinephrine vs placebo on return of
spontaneous circulation (ROSC) and brain magnetic resonance spectroscopy and imaging
(MRS/MRI) in newborn piglets with hypoxic cardiac arrest (CA). Methods Twenty-five piglets
underwent hypoxia induced by endotracheal tube clamping until CA. The animals were
randomized to CPR+ intravenous epinephrine or CPR+ placebo (normal saline). The
primary outcome was ROSC, and secondary outcomes included time-to-ROSC, brain …
Background
We aimed to investigate the effect of epinephrine vs placebo on return of spontaneous circulation (ROSC) and brain magnetic resonance spectroscopy and imaging (MRS/MRI) in newborn piglets with hypoxic cardiac arrest (CA).
Methods
Twenty-five piglets underwent hypoxia induced by endotracheal tube clamping until CA. The animals were randomized to CPR + intravenous epinephrine or CPR + placebo (normal saline). The primary outcome was ROSC, and secondary outcomes included time-to-ROSC, brain MRS/MRI, and composite endpoint of death or severe brain MRS/MRI abnormality.
Results
ROSC was more frequent in animals treated with epinephrine than placebo; 10/13 vs 4/12, RR = 2.31 (95% CI: 1.09–5.77). We found no difference in time-to-ROSC (120 (113–211) vs 153 (116–503) seconds, p = 0.7) or 6-h survival (7/13 vs 3/12, p = 0.2). Among survivors, there was no difference between groups in brain MRS/MRI. We found no difference in the composite endpoint of death or severe brain MRS/MRI abnormality; RR = 0.7 (95% CI: 0.37–1.19).
Conclusions
Resuscitation with epinephrine compared to placebo improved ROSC frequency after hypoxic CA in newborn piglets. We found no difference in time-to-ROSC or the composite endpoint of death or severe brain MRS/MRI abnormality.
Impact
  • In a newborn piglet model of hypoxic cardiac arrest, resuscitation with epinephrine compared to placebo improved the rate of return of spontaneous circulation and more than doubled the 6-h survival.
  • Brain MRS/MRI biomarkers were used to evaluate the effect of epinephrine vs placebo. We found no difference between groups in the composite endpoint of death or severe brain MRS/MRI abnormality.
  • This study adds to the limited evidence regarding the effect and safety of epinephrine; the lack of high-quality evidence from randomized clinical trials was highlighted in the latest ILCOR 2020 guidelines, and newborn animal studies were specifically requested.
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