Levetiracetam versus phenytoin for the treatment of established status epilepticus: A systematic review and meta-analysis of randomized controlled trials

Objectives: To compare the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. Methods: In this systematic review, we searched Medline, Embase, and Cochrane databases from their inception with no language restrictions until May 8, 2019 and updated on February 5, 2020, for randomized controlled trials comparing the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. A Meta-analysis was conducted to calculate the risk ratio (RR) using random-effects models. Results: We identified 7 trials with a total of 1028 participants. Levetiracetam was not associated with an increased rate of clinical seizure cessation within 60 min compared with phenytoin (RR, 1.02; 95 %CI, 0.92-1.13; I-2 = 3%; 60.0 % [309/515] vs 59.3 % [275/463];12 more events [95 % CI, -48 to 77] per 1000 participants; moderate-quality evidence). Results were similar in the subgroup analysis of adults and children. The sample size met the optimum size in trial sequential analysis. There were also no statistically significant effects on good functional outcome (RR, 1.05; 95 % CI, 0.90-1.23), admission to critical care (RR, 1.09; 95 % CI, 0.95-1.24), or all-cause mortality (RR, 1.09; 95 % CI, 0.55-2.16). Conclusions: Moderate-quality evidence suggested that levetiracetam was not significantly superior to phenytoin in seizure cessation in patients with established status epilepticus.