左乙拉西坦与苯妥英钠序贯治疗对苯巴比妥无反应的新生儿脑电图痫性发作：印度一项多中心前瞻性观察研究
Sequential levetiracetam and phenytoin in electroencephalographic neonatal seizures unresponsive to phenobarbital: a multicenter prospective observational study in India.
作者信息
Krishnan Vaisakh, Ujjanappa Vidya, Vegda Hemadri, Annayappa Manjesh K, Wali Pooja, Fattepur Sudhindrashayana, Chandriah Savitha, Devadas Sahana, Kariappa Mallesh, Gireeshan Veluthedath Kuzhiyil, Thamunni Ajithkumar Vellani, Montaldo Paolo, Burgod Constance, Garegrat Reema, Muraleedharan Pallavi, Pant Stuti, Newton Charles R, Cross J Helen, Bassett Paul, Shankaran Seetha, Thayyil Sudhin, Pressler Ronit M
机构信息
Centre for Perinatal Neuroscience, Imperial College, London, United Kingdom.
Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubballi, India.
出版信息
Lancet Reg Health Southeast Asia. 2024 Feb 15;25:100371. doi: 10.1016/j.lansea.2024.100371. eCollection 2024 Jun.
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.
FUNDING
National Institute for Health and Care Research (NIHR) Research and Innovation for Global Health Transformation (NIHR200144).
背景
尽管左乙拉西坦和苯妥英钠是新生儿中广泛使用的抗癫痫药物（ASM），但其对癫痫发作缓解的疗效尚不清楚。我们评估了在对苯巴比妥无反应的新生儿癫痫中，序贯使用左乙拉西坦和苯妥英钠后脑电图（EEG）癫痫发作缓解情况。
方法
我们招募了2020年6月20日至2022年7月31日期间，来自印度三家医院的出生≥35周且年龄<72小时、尽管使用苯巴比妥仍持续存在脑电图癫痫发作的新生儿。如果癫痫持续，新生儿先接受静脉注射左乙拉西坦（20mg/kg×2剂，二线用药），然后接受苯妥英钠（20mg/kg×2剂，三线用药）治疗。主要结局是完全癫痫发作缓解，定义为从输注开始后40分钟内至少60分钟脑电图无癫痫发作。
结果
在206例尽管使用苯巴比妥仍持续癫痫发作的新生儿中，152例接受了左乙拉西坦并进行了脑电图检查。其中一份脑电图缺失，47例（31.1%）处于癫痫持续状态，145例可获得主要结局数据。左乙拉西坦治疗后，20例（13.8%；95%CI 8.6%-20.5%）实现癫痫发作缓解；16例（80.0%）对第一剂有反应，4例（20.0%）对第二剂有反应。在左乙拉西坦治疗后仍持续癫痫发作的125例新生儿中，114例在脑电图监测下接受了苯妥英钠治疗。其中，104例可获得主要结局数据。59例（56.7%；95%CI 46.7%-66.4%）新生儿实现癫痫发作缓解；54例（91.5%）对第一剂有反应，5例（8.5%）对第二剂有反应。
解读
使用常规剂量时，左乙拉西坦仅使14%对苯巴比妥无反应的新生儿癫痫发作立即在脑电图上停止。左乙拉西坦联合苯妥英钠进一步治疗使另外57%的患者实现癫痫发作缓解。应在精心设计的随机对照试验中评估更高剂量左乙拉西坦的安全性和疗效。
资助
英国国家健康与照护研究中心（NIHR）全球健康转型研究与创新（NIHR200144）。
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