Efficacy and Safety of Levetiracetam vs. Phenytoin as Second Line Antiseizure Medication for Pediatric Convulsive Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Objective: To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE).

Data source: PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials.

Study selection: Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020.

Data extraction: The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO.

Data synthesis: Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias.

Conclusion: The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.

Keywords: levetiracetam; pediatrics; phenytoin; seizure recurrence; status epilepticus; ventilation.