Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates

Abstract To study the relationship between the delay in treatment and the efficacy of phenobarbital in neonates, we re‐analyzed data from the NEOLEV2 study. Continuous video EEG (cEEG) from patients treated with phenobarbital was reviewed by neurophysiologists who marked each seizure. The time from...

Full description

Saved in:
Bibliographic Details
Main Authors: Cynthia Sharpe, Charlotte‐Rose Rennie‐Younger, Dug Yeo Han, Suzanne L. Davis, Mark Nespeca, Francesco Pisani, Jeffrey J. Gold, Gail E. Reiner, Sonya Wang, Richard H. Haas
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Epilepsia Open
Subjects:
Online Access:https://doi.org/10.1002/epi4.70020
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849690541654016000
author Cynthia Sharpe
Charlotte‐Rose Rennie‐Younger
Dug Yeo Han
Suzanne L. Davis
Mark Nespeca
Francesco Pisani
Jeffrey J. Gold
Gail E. Reiner
Sonya Wang
Richard H. Haas
author_facet Cynthia Sharpe
Charlotte‐Rose Rennie‐Younger
Dug Yeo Han
Suzanne L. Davis
Mark Nespeca
Francesco Pisani
Jeffrey J. Gold
Gail E. Reiner
Sonya Wang
Richard H. Haas
author_sort Cynthia Sharpe
collection DOAJ
description Abstract To study the relationship between the delay in treatment and the efficacy of phenobarbital in neonates, we re‐analyzed data from the NEOLEV2 study. Continuous video EEG (cEEG) from patients treated with phenobarbital was reviewed by neurophysiologists who marked each seizure. The time from seizure onset to phenobarbital, total seizure burden pre‐phenobarbital, and maximum seizure density (summed seizure burden per hour) pre‐phenobarbital were calculated and correlated with phenobarbital efficacy at 20 mg/kg and at 40 mg/kg. The time between seizure onset and phenobarbital treatment did not predict refractoriness to phenobarbital. However, the maximum seizure density per hour and total seizure burden before phenobarbital treatment were strongly correlated with efficacy. ROC curve analysis showed cut‐offs of maximum seizure density pre‐phenobarbital of 10 ½ min/h and total seizure burden pre‐phenobarbital of 36 ¼ min had excellent discriminatory ability in separating patients in whom phenobarbital would be effective from patients in whom it would not be effective (AUC 0.84, p = 0.0002 and AUC 0.85, p = 0.0051). These data suggest that whereas neonates with high seizure density must be treated as an emergency, mild‐to‐moderate seizures remain responsive to phenobarbital if treated within a time frame of several hours. Plain Language Summary Phenobarbital is very effective at stopping seizures in newborns. But if phenobarbital is given after many hours of seizures, it becomes less effective. We do not know how quickly this happens. Our study found that it does not happen over the short term (<4 h). It is more difficult to stop seizures that cumulatively last more than 10 min/h.
format Article
id doaj-art-ffa663a5ad4d4238a75b41c26f11a01d
institution DOAJ
issn 2470-9239
language English
publishDate 2025-06-01
publisher Wiley
record_format Article
series Epilepsia Open
spelling doaj-art-ffa663a5ad4d4238a75b41c26f11a01d2025-08-20T03:21:17ZengWileyEpilepsia Open2470-92392025-06-0110394895610.1002/epi4.70020Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonatesCynthia Sharpe0Charlotte‐Rose Rennie‐Younger1Dug Yeo Han2Suzanne L. Davis3Mark Nespeca4Francesco Pisani5Jeffrey J. Gold6Gail E. Reiner7Sonya Wang8Richard H. Haas9Department of Paediatric Neurology Starship Children's Health Auckland New ZealandDepartment of Paediatric Neurology Starship Children's Health Auckland New ZealandStarship Research and Innovation Starship Foundation Auckland New ZealandDepartment of Paediatric Neurology Starship Children's Health Auckland New ZealandDepartment of Neurosciences University of California San Diego, Rady Children's Hospital San Diego San Diego California USADepartment of Neuroscience Sapienza University Rome ItalyDepartment of Neurosciences University of California San Diego, Rady Children's Hospital San Diego San Diego California USADepartment of Neurosciences University of California San Diego, Rady Children's Hospital San Diego San Diego California USADepartment of Pediatric Neurology University of Minnesota School of Medicine Minneapolis Minnesota USADepartment of Neurosciences University of California San Diego, Rady Children's Hospital San Diego San Diego California USAAbstract To study the relationship between the delay in treatment and the efficacy of phenobarbital in neonates, we re‐analyzed data from the NEOLEV2 study. Continuous video EEG (cEEG) from patients treated with phenobarbital was reviewed by neurophysiologists who marked each seizure. The time from seizure onset to phenobarbital, total seizure burden pre‐phenobarbital, and maximum seizure density (summed seizure burden per hour) pre‐phenobarbital were calculated and correlated with phenobarbital efficacy at 20 mg/kg and at 40 mg/kg. The time between seizure onset and phenobarbital treatment did not predict refractoriness to phenobarbital. However, the maximum seizure density per hour and total seizure burden before phenobarbital treatment were strongly correlated with efficacy. ROC curve analysis showed cut‐offs of maximum seizure density pre‐phenobarbital of 10 ½ min/h and total seizure burden pre‐phenobarbital of 36 ¼ min had excellent discriminatory ability in separating patients in whom phenobarbital would be effective from patients in whom it would not be effective (AUC 0.84, p = 0.0002 and AUC 0.85, p = 0.0051). These data suggest that whereas neonates with high seizure density must be treated as an emergency, mild‐to‐moderate seizures remain responsive to phenobarbital if treated within a time frame of several hours. Plain Language Summary Phenobarbital is very effective at stopping seizures in newborns. But if phenobarbital is given after many hours of seizures, it becomes less effective. We do not know how quickly this happens. Our study found that it does not happen over the short term (<4 h). It is more difficult to stop seizures that cumulatively last more than 10 min/h.https://doi.org/10.1002/epi4.70020continuous EEG monitoringhypoxic ischemic encephalopathyneonatal seizuresphenobarbitalseizure
spellingShingle Cynthia Sharpe
Charlotte‐Rose Rennie‐Younger
Dug Yeo Han
Suzanne L. Davis
Mark Nespeca
Francesco Pisani
Jeffrey J. Gold
Gail E. Reiner
Sonya Wang
Richard H. Haas
Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates
Epilepsia Open
continuous EEG monitoring
hypoxic ischemic encephalopathy
neonatal seizures
phenobarbital
seizure
title Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates
title_full Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates
title_fullStr Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates
title_full_unstemmed Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates
title_short Efficacy of phenobarbital is maintained after exposure to mild‐to‐moderate seizures in neonates
title_sort efficacy of phenobarbital is maintained after exposure to mild to moderate seizures in neonates
topic continuous EEG monitoring
hypoxic ischemic encephalopathy
neonatal seizures
phenobarbital
seizure
url https://doi.org/10.1002/epi4.70020
work_keys_str_mv AT cynthiasharpe efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT charlotteroserennieyounger efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT dugyeohan efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT suzanneldavis efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT marknespeca efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT francescopisani efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT jeffreyjgold efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT gailereiner efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT sonyawang efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates
AT richardhhaas efficacyofphenobarbitalismaintainedafterexposuretomildtomoderateseizuresinneonates