Levetiracetam Versus Phenytoin or Fosphenytoin for Second-Line Treatment of Pediatric Status Epilepticus: A Meta-Analysis

Abstract

To synthesize the available evidence examining the efficacy and safety of levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine-refractory pediatric status epilepticus. DATA SOURCES:We searched (from inception until April 27, 2020) Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials.STUDY SELECTION: Two reviewers, independently and in duplicate, screened citations and manuscripts for eligible randomized controlled trials. DATA EXTRACTION AND SYNTHESIS:Independently and in duplicate, we performed data abstraction, risk of bias assessment, and certainty assessment using Grading of Recommendations, Assessment, Development, and Evaluation. We performed meta-analyses using randomeffect models or, if insufficient data, presented findings narratively. RESULTS:We identified seven randomized controlled trials (n = 1,575). Pooled analysis demonstrated low certainty evidence for no difference of levetiracetam on time to seizure cessation (mean difference, -3.11 min; 95% CI, -6.67 to 0.45), early seizure cessation (relative risk, 1.09, 95% CI, 0.95-1.26), or late seizure cessation (relative risk, 1.05; 95% CI, 0.93-1.18). Adverse event outcomes were limited by low event numbers. We found low certainty evidence for less respiratory depression with levetiracetam (relative risk, 0.28; 95% CI, 0.12-0.69). CONCLUSIONS:The efficacy of levetiracetam is comparable with phenytoin or fosphenytoin in children with benzodiazepine-refractory status epilepticus (low certainty evidence). Levetiracetam may cause less respiratory depression. Clinicians and guideline developers should weigh safety profiles when choosing between these agents.

Recent updates on Levetiracetam

“…68 Pooled analysis of RCTs found that the risk of respiratory depression was also lesser with Levetiracetam compared to Phenytoin or fosphenytoin. 66 There were no significant laboratory or clinical abnormalities with IV Levetiracetam administration. 23 Early exposure to Phenobarbitone used to treat neonatal seizures may negatively impact neurodevelopmental outcomes (motor, cognitive, and language performance) at 2 years of age using the Bayley Scales of Infant Development (BSID).…”

“…65 Similar to Phenobarbitone and valproate, a meta-analysis of data from seven RCTs did not find any significant difference in seizure cessation between Levetiracetam, Phenytoin, and Fosphenytoin. 66 An open-label, single-arm study found that about two-thirds (62.9%) of children had no recurrence of seizure after treatment with IV Levetiracetam. 23 Thus, though the efficacy parameters showed no significant differences between Levetiracetam and Phenytoin, the use of the former is associated with several advantages.…”

Standardizing the Treatment for Pediatric Status Epilepticus: A Quality Improvement Study

“…During the last 4 months of the project, we changed our recommended second-line agent in the order set from fosphenytoin to levetiracetam based on a meta-analysis published at that time that showed levetiracetam to be noninferior. 9 A query of the PICU database, which is part of the Virtual Pediatric Systems (LLC) database, was performed using the diagnosis of status epilepticus after the initial 24-month period. 12 The electronic health records of the patients identified were reviewed and only those who failed treatment with benzodiazepines and required a second-line anticonvulsant medication were included in the analysis.…”

Levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine‐refractory pediatric status epilepticus

“…The meta‐analysis summarized here examined data from randomized controlled trials (RCTs) comparing levetiracetam with phenytoin or fosphenytoin for status epilepticus refractory to at least one dose of benzodiazepine 10 . Authors included data from trials enrolling primarily patients under age 18 years or else reported the results of a pediatric subgroup from trials enrolling patients of all ages.…”

“…There are several limitations associated with this meta‐analysis 10 . First, seizure etiology varied, including central nervous system infection, cryptogenic seizure, epilepsy, and febrile seizure.…”