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

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, 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 1st January 2000 to 30th 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.