Assistant Professor University of Miami Miller School of Medicine Miami, Florida
Rationale: Preterm newborns have higher prevalence of seizures and are at increased risk of neurodevelopmental complications when compared to term infants. Limited therapeutic options are available for seizure management in premature infants. The aim of this study was to assess the safety of Lacosamide (LCS) as an adjunctive therapy for neonatal seizures in preterm infants. Methods: A retrospective chart review was conducted in the Level IV NICU at Holtz Children’s Hospital, from January 2017 to June 2020. The inclusion criteria was as follows: premature infants (< 37 wks ega) admitted to the NICU within the first 24 hours of life; findings of refractory clinical and/or electrographic seizures as diagnosed by multi-channel continuous video-EEG (vEEG) monitoring; infants with seizures recorded despite multiple antiepileptic agents, which included Phenobarbital, Levetiracetam, Phenytoin and/or Midazolam, as well as Pyridoxine. LCS was then used as an adjunctive therapy. Infants with complex cerebral, cardiac malformations and hepatic impairment were excluded from the analyses. Results: Eighteen patients with refractory clinical and electrographic seizures were identified. Mean gestational age was 24.6 weeks (range: 23 to 27 weeks) and 53% were male. Sixty-one percent (11/18) of patients had imaging consistent with intraventricular hemorrhage. Eleven percent (2/18) of patients were treated with four antiepileptic drugs (AEDs), 83% (15/18) received three AEDs, and one patient was treated with one AED at the time LCS was added. Loading doses were administered intravenously over 30 minutes and ranged from 3 to 10 mg/kg (mean 4.6 mg/kg). Maintenance doses ranged from 2 to 15 mg/kg/day (mean 7 mg/kg/day). Electrocardiogram (EKG) data was available for 78% of the patients (14/18). Of those, 57% had normal sinus rhythm in EKGs obtained after exposure to LCS. There were no acute adverse events that prompted change in the rate of infusion at the time of administration or discontinuation of LCS as an antiepileptic agent. Specifically, no PR interval prolongation, atrioventricular block or tachyarrhythmias were noted. Preliminary analysis of vEEG of a representative dataset showed a greater than 50% reduction in seizure burden after LCS administration. Conclusions: Lacosamide can be a safe and well-tolerated adjunctive antiepileptic therapy for management of refractory seizures and status epilepticus of various etiologies in premature infants. Preliminary analysis of vEEG data shows a trend towards a greater than 50% decrease in seizure burden after LCS administration. Prospective randomized clinical trials are needed to further characterize its efficacy in preterm and term infants. Funding: Please list any funding that was received in support of this abstract.: There was no external funding for this study.
