Levetiracetam vs phenytoin prophylaxis in severe traumatic brain injury: Systematic review and meta-analysis

Background Prophylaxis against seizures has been recommended in the guidelines for severe traumatic brain injury. Levetiracetam has been suggested as an alternative pharmacotherapy to phenytoin due to more favorable side effects profile. The aim of this study is to compare the evidence for levetiracetam versus phenytoin for the prophylaxis of early seizures after severe brain trauma. Methods We searched the EMBASE, MEDLINE and COCHRANE databases for relevant articles from inception to February 16, 2021 using key words related to traumatic brain injury, levetiracetam and phenytoin. Studies retrieved were screened to include observational studies or randomized controlled trials of adult patients with severe brain trauma with comparison of levetiracetam and phenytoin for the prophylaxis of seizures within the first week after trauma. Study characteristics and outcomes were extracted from each included study. The meta-analysis was conducted in compliance with PRISMA guidelines using a random-effects model programmed in R. Data were independently extracted by 2. The primary outcome was seizure incidence within the first 7 days after admission. Secondary outcomes include mortality rate and hypotension incidence. Results 485 articles were screened via abstract and title, after which 67 were screened by full text. 5 articles were included in the meta-analysis. There was no significant difference found between levetiracetam and phenytoin for the outcomes of early seizure, mortality, or hypotension. GRADE analysis showed very low-quality evidence for all three outcomes, with limitations primarily due to risk of bias, and inconsistency. Furthermore, seizures and hypotension can be considered indirect measures for long-term functional outcomes. Conclusions High quality, well powered randomized clinical trials comparing levetiracetam and phenytoin, preferably with long-term functional outcomes, need to be performed to improve the quality of the evidence for early seizure prophylaxis in severe traumatic brain injury. Level of evidence Systematic Review, level IV, therapeutic.