A retrospective comparison of phenobarbital and levetiracetam for the treatment of seizures following cardiac surgery in neonates

Abstract

Objective: To compare the safety and efficacy of phenobarbital and levetiracetam in a cohort of neonates with seizures following cardiac surgery. Methods: We performed a retrospective single-center study of consecutive neonates with electrographically confirmed seizures managed with antiseizure medication after cardiac surgery from June 15, 2012 to December 31, 2018. We compared the safety and efficacy of phenobarbital and levetiracetam as first-line therapy. Results: First-line therapy was phenobarbital in 31 neonates and levetiracetam in 22 neonates. Phenobarbital was associated with more adverse events (P = .006).Eight neonates (14%) experienced an adverse event related to phenobarbital use, including seven with hypotension and one with respiratory depression. No adverse events were reported with levetiracetam use. The cessation of electrographic seizures was similar in both groups, including 18 neonates (58%) with seizure cessation after phenobarbital and 12 neonates (55%) with seizure cessation after levetiracetam (P = 1.0). The combined cessation rates of phenobarbital and levetiracetam when used as first-or second-line therapy were 58% and 47%, respectively (P = .47). Significance: Phenobarbital was associated with more adverse events than levetiracetam, and the two drugs were equally but incompletely effective in treating electrographically confirmed seizures in neonates following cardiac surgery.Given its more acceptable safety profile and potential noninferiority, levetiracetam may be a reasonable option for first-line therapy for treatment of seizures in this population. Further prospective studies are needed to confirm these results. K E Y W O R D Scardiology, congenital, critical care, heart diseases, infant 628 | THIBAULT eT AL.

Levetiracetam as the first‐line treatment for neonatal seizures: a systematic review and meta‐analysis

“…Studies using clinical criteria alone to diagnose seizures or evaluate its response to treatment reported a higher seizure cessation rate compared to those using exclusively EEG (clinical criteria alone: 59% [23–95%]; 23–25 EEG criteria alone: 40% [30–50%]) 26,29–31,33,34,36 . There was statistically significant between‐study heterogeneity in levetiracetam response when EEG was not used (Fig.…”

“…Only four observational studies 29,34–36 and one RCT 25 enrolled a homogenous group of neonates with similar aetiology. Proportion‐based meta‐analysis of the included studies showed that the efficacy of levetiracetam was relatively lower in studies that enrolled neonates with HIE or stroke (30% [19–40%]) 26,27 and intraventricular haemorrhage (28% [17–38%]), 34,35 when compared to its overall pooled efficacy (48% [34–62%]) (Fig.…”

Population Pharmacokinetics of Phenobarbital in Neonates and Infants on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy

“…At our institution, phenobarbital is usually administered as a loading dose of 10–20 mg/kg, with additional boluses as needed to terminate seizures. The loading dose is often divided into smaller aliquots of 5 mg/kg in children with hemodynamic instability to limit the potential hypotensive effect associated with phenobarbital administration 21 . This is typically followed by maintenance doses of 5 mg/kg/day administered as divided doses every 12 hours.…”

“…The loading dose is often divided into smaller aliquots of 5 mg/kg in children with hemodynamic instability to limit the potential hypotensive effect associated with phenobarbital administration. 21 This is typically followed by maintenance doses of 5 mg/kg/day administered as divided doses every 12 hours. Phenobarbital is infused at a rate of 1 mg/kg/min, and TDM is routinely done per standard care.…”

Seizures in the neonate: A review of etiologies and outcomes

“…Despite a mere 50-64 % response rate over the first 48 h after seizure onset in neonates [138,139], phenobarbital is still the drug of first choice for the management of acute symptomatic neonatal seizures [140], due to an older randomized controlled trial comparing phenobarbital to phenytoin [138] and a more recent randomized controlled trial comparing phenobarbital to levetiracetam [139] as well as due to the clinical experience accumulated over the last decades [141]. On the other hand, several anti-seizure medications, such as levetiracetam [21,142,143] and topiramate [144], have emerged as viable alternatives with the potential to address age-specific mechanisms and challenges, whereas other anti-seizure drugs such as lidocaine and bumetanide are still under scrutiny due to cardiotoxicity [145][146][147] and ototoxicity [148,149] concerns.…”