Tao Xue1, Luxin Wei2, Xiaotian Shen3, Zilan Wang1, Zhouqing Chen4, Zhong Wang5. 1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. 2. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. 3. Shanghai Medical College, Fudan University, Shanghai, 200032, China. 4. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. zqchen6@163.com. 5. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. wangzhong761@163.com.
Abstract
BACKGROUND: Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with phenytoin. Therefore, a meta-analysis was carried out to assess the value of levetiracetam versus phenytoin in the pharmacotherapy of benzodiazepine-refractory SE. OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the efficacy and safety of levetiracetam and phenytoin in the treatment of benzodiazepine-refractory SE. METHODS: The MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that had been conducted to evaluate levetiracetam versus phenytoin for benzodiazepine-refractory SE, to April 2020. The data were assessed using Review Manager 5.3 software. The risk ratio (RR) was analyzed using dichotomous outcomes, and calculated using a random-effect model. RESULTS: We pooled 1850 patients from 12 RCTs. Patients in the levetiracetam group had a significantly higher rate of clinical seizure cessation than in the phenytoin group (75.2% vs. 67.8%; RR 1.14, 95% confidence interval [CI] 1.05-1.25, p = 0.003). Moreover, less adverse events were observed in the levetiracetam group than in the phenytoin group (17.8% vs. 21.4%; RR 0.82, 95% CI 0.70-0.97, p = 0.02). In subgroup analysis, clinical seizure cessation was achieved more frequently with a higher dose of levetiracetam (> 30 mg/kg) [RR 1.15, 95% CI 1.00-1.32, p = 0.05]. Furthermore, in the subgroup of children, levetiracetam showed a higher rate of clinical seizure cessation than phenytoin (RR 1.13, 95% CI 1.02-1.25, p = 0.02). CONCLUSION: Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.
BACKGROUND: Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with phenytoin. Therefore, a meta-analysis was carried out to assess the value of levetiracetam versus phenytoin in the pharmacotherapy of benzodiazepine-refractory SE. OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the efficacy and safety of levetiracetam and phenytoin in the treatment of benzodiazepine-refractory SE. METHODS: The MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that had been conducted to evaluate levetiracetam versus phenytoin for benzodiazepine-refractory SE, to April 2020. The data were assessed using Review Manager 5.3 software. The risk ratio (RR) was analyzed using dichotomous outcomes, and calculated using a random-effect model. RESULTS: We pooled 1850 patients from 12 RCTs. Patients in the levetiracetam group had a significantly higher rate of clinical seizure cessation than in the phenytoin group (75.2% vs. 67.8%; RR 1.14, 95% confidence interval [CI] 1.05-1.25, p = 0.003). Moreover, less adverse events were observed in the levetiracetam group than in the phenytoin group (17.8% vs. 21.4%; RR 0.82, 95% CI 0.70-0.97, p = 0.02). In subgroup analysis, clinical seizure cessation was achieved more frequently with a higher dose of levetiracetam (> 30 mg/kg) [RR 1.15, 95% CI 1.00-1.32, p = 0.05]. Furthermore, in the subgroup of children, levetiracetam showed a higher rate of clinical seizure cessation than phenytoin (RR 1.13, 95% CI 1.02-1.25, p = 0.02). CONCLUSION: Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.