Efficacy and safety of levetiracetam versus phenytoin as second line antiepileptic agent in Pediatric convulsive status epilepticus: A systematic review and meta-analysis of randomized controlled trials

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, 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 st January 2000 to 30 th September 2020. Data extraction The data was pooled regarding the proportion of children achieving seizure cessation within 5-60 minutes of completion of study drug infusion (primary outcome); and seizure cessation within 5 minutes, time to achieve seizure cessation, seizure recurrence between 1-24 hours, intubation, and cardiovascular instability (secondary outcomes). Data was analysed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was submitted to PROSPERO for registration. Data synthesis Eleven RCTs with 2177 children (1024 received LEV and 988 received PHT) were enrolled. Seizure cessation within 5-60 minutes was similar with both the drugs [81% in LEV vs. 76% in PHT, risk ratio (RR)=1.04, 95% CI 0.9-1.13, p=0.29]. Seizure recurrences within 1-24 hours was higher with PHT as comparison to LEV (15% vs 9%, RR=0.64, 95% CI 0.42-0.99, p=0.04). Seizure cessation within 5 minutes, time to achieve seizure cessation, requirement of intubation/mechanical ventilation, and cardiovascular instability were similar with both the drugs. Three studies had low risk of bias and eight studies had high risk of bias. Conclusion The efficacy and safety of LEV is not superior to PHT as second line ASM medication for Pediatric convulsive SE. However, the seizure recurrences between 1-24 hours were significantly higher with PHT in comparison to LEV.