左乙拉西坦和咪达唑仑与咪达唑仑单独治疗全面性癫痫持续状态儿童的一线治疗（Lev-Mid 研究）：一项随机对照试验。

Levetiracetam and Midazolam vs Midazolam Alone for First-Line Treatment of Children With Generalized Convulsive Status Epilepticus (Lev-Mid Study): A Randomized Controlled Trial.

机构信息

Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.

Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt. Correspondence to: Dr Elsayed Abdelkreem, Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag 82524, Egypt.

出版信息

Indian Pediatr. 2023 Aug 15;60(8):630-636. Epub 2023 Mar 20.

PMID:37211889

Abstract

BACKGROUND

Benzodiazepines are the first-line anti-seizure medication (ASM) for generalized convulsive status epilepticus (GCSE), but they fail to end seizures in a third of cases. Combining benzodiazepines with another ASM that acts by a different pathway could be a potential strategy for rapid control of GCSE.

OBJECTIVES

To evaluate the efficacy of adding levetiracetam to midazolam in the initial treatment of pediatric GCSE.

DESIGN

Double-blind randomized controlled trial.

SETTING

Pediatric emergency room at Sohag University Hospital between June, 2021 and August, 2022.

PARTICIPANTS

Children aged between 1 month and 16 years with GCSE lasting more than 5 min.

INTERVENTIONS

Intravenous levetiracetam (60 mg/kg over 5 min) and midazolam (Lev-Mid group) or placebo and midazolam (Pla-Mid group) as first-line anticonvulsive therapy.

OUTCOME MEASURES

Primary: cessation of clinical seizures at 20-min study time point. Secondary: cessation of clinical seizures at 40-min study time point, need for a second midazolam dose, seizure control at 24-hr, need for intubation, and adverse effects.

RESULTS

Cessation of clinical seizures at 20-min occurred in 55 children (76%) in Lev-Mid group compared with 50 (69%) in the Pla-Mid group [RR (95% CI) 1.1 (0.9-1.34); P=0.35]. No significant difference was found between the two groups regarding the need for a second midazolam dose [44.4% vs 55.6%; RR (95% CI) 0.8 (0.58-1.11); P=0.18] as well as cessation of clinical seizures at 40-min [96% vs 92%; RR (95% CI)1.05 (0.96-1.14); P=0.49] and seizure control at 24-hr [85% vs 76%; RR (95% CI) 1.12 (0.94-1.3); P=0.21]. Intubation was required for three patients in the Lev-Mid group and six patients in the Pla-Mid group [RR (95%CI) 0.5 (0.13- 1.92); P=0.49]. No other adverse effects or mortality were observed during the 24-hour study timeframe.

CONCLUSION

Combined levetiracetam and midazolam for initial management of pediatric GCSE presents no significant advantage over midazolam alone in cessation of clinical seizures at 20-min.

摘要

背景

苯二氮䓬类药物是全身性惊厥性癫痫持续状态（GCSE）的一线抗癫痫药物（ASM），但它们在三分之一的病例中无法终止癫痫发作。将苯二氮䓬类药物与另一种通过不同途径起作用的 ASM 联合使用可能是快速控制 GCSE 的潜在策略。

目的

评估左乙拉西坦联合咪达唑仑在儿科 GCSE 初始治疗中的疗效。

设计

双盲随机对照试验。

地点

2021 年 6 月至 2022 年 8 月在索哈格大学医院的儿科急诊室。

参与者

年龄在 1 个月至 16 岁之间、GCSE 持续时间超过 5 分钟的儿童。

干预措施

静脉注射左乙拉西坦（60mg/kg 持续 5 分钟）和咪达唑仑（Lev-Mid 组）或安慰剂和咪达唑仑（Pla-Mid 组）作为一线抗惊厥治疗。

结局测量

主要结局：在 20 分钟的研究时间点停止临床癫痫发作。次要结局：在 40 分钟的研究时间点停止临床癫痫发作、需要第二次咪达唑仑剂量、24 小时内癫痫控制、需要插管和不良反应。

结果

Lev-Mid 组 55 名儿童（76%）在 20 分钟时停止临床癫痫发作，而 Pla-Mid 组 50 名儿童（69%）[RR（95%CI）1.1（0.9-1.34）；P=0.35]。两组在需要第二次咪达唑仑剂量方面没有显著差异[44.4%比 55.6%；RR（95%CI）0.8（0.58-1.11）；P=0.18]，以及在 40 分钟时停止临床癫痫发作[96%比 92%；RR（95%CI）1.05（0.96-1.14）；P=0.49]和 24 小时内癫痫控制[85%比 76%；RR（95%CI）1.12（0.94-1.3）；P=0.21]。Lev-Mid 组有 3 名患者和 Pla-Mid 组有 6 名患者需要插管[RR（95%CI）0.5（0.13-1.92）；P=0.49]。在 24 小时的研究时间内，没有观察到其他不良反应或死亡。