背景:癫痫持续状态(SE)可能危及生命,然而,目前尚不清楚哪些抗癫痫药物(AEDs)应该用作二线AEDs.
目的:我们进行了一项网络荟萃分析(NMA)的随机对照试验(RCTs),比较多个二线AED对SE的疗效。
方法:我们搜索了MEDLINE,中部,ClinicalTrials.gov,和世界卫生组织国际临床试验平台搜索门户,并于2023年12月31日纳入了年龄≥15岁SE患者的随机对照试验。我们比较了SE的多个二线AED,包括fphenytoin(fPHT),拉科沙胺(LCM),左乙拉西坦(LEV),苯妥英(PHT),苯巴比妥(PHB),和丙戊酸盐(VPA)。主要和次要结果是癫痫发作终止,包括在30分钟和60分钟没有癫痫发作复发。以及与AED相关的不良事件,分别,以95%置信区间(CI)表示为相对风险(RR)。我们使用基于频率的方法和多元随机效应进行了NMA,并根据建议的等级评估确定性,评估,发展,和评估框架。
结果:包括七个RCT(n=780),并且在VPA与PHB(RR,0.67;95%CI,0.53-0.85;确定性非常低),fPHTvs.PHB(RR,0.66;95%CI,0.48-0.90;确定性非常低),LCMvs.PHB(RR,0.62;95%CI,0.41-0.93;确定性非常低),和LEVvs.PHB(RR,0.69;95%CI,0.51-0.94;确定性非常低)。此外,PHB在癫痫发作终止排名中最高。对于不良事件,由于AED的选择,没有观察到显著的减少,虽然PHB的排名最低。
结论:PHB作为成人SE患者的二线AED可能是最有效的癫痫发作终止方法。然而,几乎所有比较的确定性都是“非常低”,仔细的解释是必不可少的。
BACKGROUND: Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs.
OBJECTIVE: We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs.
METHODS: We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework.
RESULTS: Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest.
CONCLUSIONS: PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was \"very low\", and careful interpretation is essential.