1. A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic–ischemic encephalopathy
- Author
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Raman Sankar, Alexander H. Cho, Shaun A. Hussain, Teresa Chanlaw, Meena Garg, Timothy Zaki, and Lekha M. Rao
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Levetiracetam ,Encephalopathy ,Kaplan-Meier Estimate ,Hypoxic Ischemic Encephalopathy ,law.invention ,03 medical and health sciences ,Behavioral Neuroscience ,Epilepsy ,0302 clinical medicine ,Randomized controlled trial ,Hypothermia, Induced ,Seizures ,law ,030225 pediatrics ,Prohibitins ,Humans ,Medicine ,Proportional Hazards Models ,Retrospective Studies ,Univariate analysis ,business.industry ,Hazard ratio ,Infant, Newborn ,Electroencephalography ,medicine.disease ,Treatment Outcome ,Neurology ,Tolerability ,Phenobarbital ,Hypoxia-Ischemia, Brain ,Anticonvulsants ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort.We retrospectively identified consecutive newborns with HIE who were monitored with continuous video-electroencephalogram (VEEG) for the duration of therapeutic hypothermia. After identification of seizures, infants were treated with PHB or LEV at the discretion of treating physicians. We assessed time to seizure freedom as a function of AED choice, with adjustment for HIE severity and initial seizure frequency using the Kaplan-Meier procedure and multivariate Cox proportional hazards regression.We identified 78 infants with HIE. Among 44 (56%) patients who had VEEG-confirmed seizures, 34 became seizure-free during monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison with PHB, predicted a shorter interval to seizure freedom in a univariate analysis (Hazard ratio (HR) = 2.58, P = 0.007), even after adjustment for initial seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HR = 2.57, P = 0.010). This effect was recapitulated in an analysis in which patients with treatment crossover were excluded. As expected, severity of HIE was an independent predictor of longer duration to seizure freedom (HR = 0.16, P 0.001) and remained a significant predictor after adjustment for initial seizure burden and treatment agent.Despite a relatively small sample size and retrospective design, this study suggests that LEV is a viable alternative to PHB in the treatment of neonatal seizures associated with HIE. A large-scale randomized controlled trial is needed to confirm these findings.
- Published
- 2018
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