顺序左乙拉西坦和苯妥英治疗对苯巴比妥无反应的新生儿癫痫发作：印度一项多中心前瞻性观察研究

IF 5 Q1 HEALTH CARE SCIENCES & SERVICES The Lancet regional health. Southeast Asia Pub Date : 2024-06-01 DOI:10.1016/j.lansea.2024.100371

Vaisakh Krishnan , Vidya Ujjanappa , Hemadri Vegda , Manjesh K. Annayappa , Pooja Wali , Sudhindrashayana Fattepur , Savitha Chandriah , Sahana Devadas , Mallesh Kariappa , Veluthedath Kuzhiyil Gireeshan , Ajithkumar Vellani Thamunni , Paolo Montaldo , Constance Burgod , Reema Garegrat , Pallavi Muraleedharan , Stuti Pant , Charles R. Newton , J Helen Cross , Paul Bassett , Seetha Shankaran , Ronit M. Pressler

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引用次数: 0

摘要

背景虽然左乙拉西坦和苯妥英是新生儿中广泛使用的抗癫痫药物（ASM），但它们对癫痫发作自由度的疗效尚不明确。我们在 2020 年 6 月 20 日至 2022 年 7 月 31 日期间从印度三家医院招募了出生≥35 周、年龄为 72 h、服用苯巴比妥后仍有电图癫痫发作的新生儿，评估了他们在连续服用左乙拉西坦和苯妥英后的癫痫发作自由度。这些新生儿接受静脉注射左乙拉西坦（20 毫克/千克 x 2 次，二线治疗）治疗，如果癫痫持续发作，则接受苯妥英（20 毫克/千克 x 2 次，三线治疗）治疗。主要结果是完全无癫痫发作，即自输液开始 40 分钟内，脑电图至少 60 分钟无癫痫发作。其中1例脑电图缺失，47例（31.1%）处于癫痫状态，145例获得了主要结果数据。20例（13.8%；95% CI 8.6%-20.5%）新生儿在服用左乙拉西坦后摆脱了癫痫发作；16例（80.0%）对第一剂有反应，4例（20.0%）对第二剂有反应。在125名服用左乙拉西坦后癫痫持续发作的新生儿中，114名在脑电图监测下接受了苯妥英治疗。其中 104 例获得了主要结果数据。59例（56.7%；95% CI 46.7%-66.4%）新生儿无癫痫发作；54例（91.5%）对第一剂有反应，5例（8.5%）对第二剂有反应。在使用左乙拉西坦的同时辅以苯妥英治疗，又有57%的新生儿获得了癫痫发作自由。更高剂量左乙拉西坦的安全性和疗效应在精心设计的随机对照试验中进行评估。

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Sequential levetiracetam and phenytoin in electroencephalographic neonatal seizures unresponsive to phenobarbital: a multicenter prospective observational study in India

Background

Although levetiracetam and phenytoin are widely used antiseizure medications (ASM) in neonates, their efficacy on seizure freedom is unclear. We evaluated electroencephalographic (EEG) seizure freedom following sequential levetiracetam and phenytoin in neonatal seizures unresponsive to phenobarbital.

Methods

We recruited neonates born ≥35 weeks and aged <72 h who had continued electrographic seizures despite phenobarbital, from three Indian hospitals, between 20 June 2020 and 31 July 2022. The neonates were treated with intravenous levetiracetam (20 mg/kg x 2 doses, second line) followed by phenytoin (20 mg/kg x 2 doses, third line) if seizures persisted. The primary outcome was complete seizure freedom, defined as an absence of seizures on EEG for at least 60 min within 40 min from the start of infusion.

Findings

Of the 206 neonates with continued seizures despite phenobarbital, 152 received levetiracetam with EEG. Of these one EEG was missing, 47 (31.1%) were in status epilepticus, and primary outcome data were available in 145. Seizure freedom occurred in 20 (13.8%; 95% CI 8.6%–20.5%) after levetiracetam; 16 (80.0%) responded to the first dose and 4 (20.0%) to the second dose. Of the 125 neonates with persisting seizures after levetiracetam, 114 received phenytoin under EEG monitoring. Of these, the primary outcome data were available in 104. Seizure freedom occurred in 59 (56.7%; 95% CI 46.7%–66.4%) neonates; 54 (91.5%) responded to the first dose and 5 (8.5%) to the second dose.

Interpretation

With the conventional doses, levetiracetam was associated with immediate EEG seizure cessation in only 14% of phenobarbital unresponsive neonatal seizures. Additional treatment with phenytoin along with levetiracetam attained seizure freedom in further 57%. Safety and efficacy of higher doses of levetiracetam should be evaluated in well-designed randomised controlled trials.