Division of Neurology, "Franz Tappeiner" Hospital, Merano, Bolzano, Italy; Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy.
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Epilepsy Behav. 2019 Dec;101(Pt B):106466. doi: 10.1016/j.yebeh.2019.106466. Epub 2019 Aug 25.
The aim of this study was to estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in adults with benzodiazepine-resistant convulsive status epilepticus (SE).
MEDLINE, CENTRAL, ClinicalTrials.gov, and Opengrey.eu were searched (from inception to 3rd April, 2018) for randomized controlled trials (RCTs) of AEDs used intravenously to treat benzodiazepine-resistant SE in adults. Efficacy outcomes were SE cessation within 1 h from drug administration and seizure freedom at 24 h. Safety outcomes were respiratory depression and hypotension. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks.
Five RCTs were considered, involving 349 patients. Included interventions were valproate (VPA; 20-30 mg/kg), phenytoin (PHT; 20 mg/kg), diazepam (DZP; 0.2 mg/kg, then 4 mg/h), phenobarbital (PHB; 20 mg/kg, then 100 mg every 6 h), lacosamide (LCM; 400 mg), and levetiracetam (LEV; 20 mg/kg); PHB was superior to PHT, VPA, DZP, LEV, and LCM with respect to SE cessation and performed better than VPA, DZP, and LCM in the achievement of seizure freedom at 24 h. No differences were noted between drugs in the occurrence of respiratory depression and hypotension. According to SUCRA, PHB had the greatest probabilities of being best in the achievement of SE control and seizure freedom, whereas VPA and LCM ranked best for the safety outcomes.
Our study suggests that high-dose PHB is effective in controlling SE and preventing seizure recurrence, and LCM and VPA could be better tolerated options. Further head-to-head comparative studies are strongly required to provide more definitive evidence. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".
本研究旨在评估抗癫痫药物（AEDs）在苯二氮䓬类药物难治性惊厥性癫痫持续状态（SE）成人患者中的疗效和安全性。
检索 MEDLINE、CENTRAL、ClinicalTrials.gov 和 Opengrey.eu 数据库（从建库至 2018 年 4 月 3 日），以获取 AED 静脉治疗成人苯二氮䓬类药物难治性 SE 的随机对照试验（RCTs）。疗效终点为药物治疗后 1 小时内 SE 终止和 24 小时时无癫痫发作。安全性终点为呼吸抑制和低血压。使用基于频率论的网络荟萃分析估计效果大小。通过累积排序曲线下面积（SUCRA）和平均秩确定竞争性干预措施的等级。
纳入了 5 项 RCT，共 349 例患者。纳入的干预措施为丙戊酸钠（VPA；20-30mg/kg）、苯妥英（PHT；20mg/kg）、地西泮（DZP；0.2mg/kg，然后 4mg/h）、苯巴比妥（PHB；20mg/kg，然后每 6 小时 100mg）、拉科酰胺（LCM；400mg）和左乙拉西坦（LEV；20mg/kg）。与 PHT、VPA、DZP、LEV 和 LCM 相比，PHB 更有助于 SE 终止，在 24 小时时达到无癫痫发作的效果优于 VPA、DZP 和 LCM。药物之间在呼吸抑制和低血压的发生方面无差异。根据 SUCRA，PHB 在控制 SE 和预防癫痫发作复发方面最有可能是最佳选择，而 VPA 和 LCM 在安全性结局方面排名最佳。
本研究表明，大剂量 PHB 可有效控制 SE 并预防癫痫复发，LCM 和 VPA 可能是更能耐受的选择。需要进一步进行头对头比较研究以提供更明确的证据。本文是“第 7 届伦敦-因斯布鲁克癫痫持续状态和急性发作研讨会特刊”的一部分。
