Effect of Phenobarbitone on Amplitude-Integrated Electroencephalography in Neonates with Hypoxic-Ischemic Encephalopathy during Hypothermia

Background: Phenobarbitone induces suppression of cerebral electrical activity on amplitude-integrated electroencephalography (aEEG) in neonates with hypoxic-ischemic encephalopathy (HIE); however, its effect during therapeutic hypothermia (TH) has not been well characterized. Objective: To evaluate the effect of phenobarbitone on aEEG in neonates with HIE undergoing TH. Methods: Thirty-five neonates born at >= 35(0) weeks gestational age (GA), who received phenobarbitone as first-line antiepileptic drug during TH for >= Sarnat stage II HIE with aEEG recordings were retrospectively studied. Background pattern, upper and lower margin voltages were characterized for a 30-min period before and 30-60 min after phenobarbitone administration. Primary outcome was presence of severely abnormal aEEG pattern after phenobarbitone administration. Results: Mean (+/- SD) GA and median birth weight were 38.2 +/- 1.9 weeks and 3.1 (2.5-3.9) kg, respectively. Phenobarbitone (10-20 mg/kg), administered at median age 16.8 h, was associated with background pattern worsening in 19/29 (65.5%) cases. Severe background patterns were more prevalent in post- versus pre-phenobarbitone tracings (21/29 [72%] vs. 11/29 [38%]; p = 0.01). Presence of severe pattern versus either continuous normal voltage or discontinuous normal voltage pattern post-phenobarbitone, (20/25 [80%] vs. 3/8 [38%]; p = 0.036) was associated with death or moderate-to-severe injury on MRI brain. Median time to trace recovery, when measurable, was 4 h (45 min-72 h). Conclusions: Phenobarbitone induces significant suppression on aEEG in infants with HIE undergoing TH. Development of severe aEEG background patterns after phenobarbitone may unmask a population at greater risk of abnormal outcome. (c) 2021 The Author(s) Published by S. Karger AG, Basel

Automated summary

Phenobarbitone significantly suppresses cerebral electrical activity in infants with HIE undergoing TH, leading to worsening of background patterns on aEEG. Development of severe aEEG background patterns after phenobarbitone administration may be associated with MRI brain death or moderate-to-severe injury.