Levetiracetam: Safety and efficacy in neonatal seizures
Levetiracetam: Safety and efficacy in neonatal seizures
复制标题
DOI：
10.1016/j.ejpn.2010.10.003
复制
发表时间：
2011-01-01
影响因子：
3.1
通讯作者：
Dinger, Juergen
中科院分区：
文献类型：
--
作者：
Ramantani, Georgia;Ikonomidou, Chrysanthy;Dinger, Juergen
目的：新生儿癫痫发作是常见的，特别是在早产儿。苯巴比妥（PB）目前是抗癫痫药物（AED）的首选，尽管它与动物模型中的神经元凋亡增加和人类受试者的认知障碍有关。左乙拉西坦（LEV）可能具有更有利的前景，因为它不会引起幼鼠的神经元凋亡。方法：在一项前瞻性可行性研究中，在排除低血糖、低钙、低镁和吡哆素依赖后，将LEV作为一线治疗方法应用于38例脑电图确诊癫痫发作的新生儿。初始静脉注射剂量为10mg /kg LEV，在3天内逐渐增加到30mg /kg，并在一周结束时进一步滴定至45- 60mg /kg。在LEV滴定期间，可耐受至多2次静脉注射20mg /kg的PB的急性干预。一旦婴儿的情况允许，LEV就转为口服。根据临床观察、脑电图（aEEG/常规脑电图）和实验室数据，评估12个月的药物安全性和抗惊厥疗效。结果：19例新生儿单次给药20mg /kg， 3例新生儿2次给药。30例患儿在第一周末无癫痫发作，27例患儿在第四周无癫痫发作，24例患儿在第四周脑电图明显改善。19例在2-4周后停用LEV， 7例在3个月后停用LEV。未观察到严重的不良反应。结论：这些结果说明了LEV治疗新生儿癫痫发作（包括早产）的安全性，并提示LEV抗惊厥的有效性。由于PB的抗惊厥疗效延长，额外的PB治疗无疑构成了方法学上的缺陷。需要双盲前瞻性对照研究和认知结果的长期评估。(C) 2010年欧洲儿科神经病学学会。Elsevier Ltd.出版。版权所有。
Purpose: Neonatal seizures are common, especially in prematurity. Phenobarbital (PB) currently represents the antiepileptic drug (AED) of choice, despite being related to increased neuronal apoptosis in animal models and cognitive impairment in human subjects. Levetiracetam (LEV) may have a more favorable profile since it does not cause neuronal apoptosis in infant rodents.Methods: In a prospective feasibility study, LEV was applied as first-line treatment in 38 newborns with EEG-confirmed seizures, after ruling out hypoglycemia, hypocalcaemia, hypomagnesaemia and pyridoxin dependency. Initial intravenous doses of 10 mg/kg LEV were gradually increased to 30 mg/kg over 3 days with a further titration to 45-60 mg/kg at the end of the week. Acute intervention with up to 2 intravenous doses of PB 20 mg/kg was tolerated during LEV titration. LEV was switched to oral as soon as the infants' condition allowed. Based on clinical observation, EEG tracings (aEEG/rcutine EEGs), and lab data, drug safety and anticonvulsant efficacy were assessed over 12 months.Results: In 19 newborns a single PB dose of 20 mg/kg was administered, while 3 newborns received 2 PB doses. 30 infants were seizure free under LEV at the end of the first week and 27 remained seizure free at four weeks, while EEGs markedly improved in 24 patients at 4 weeks. In 19 cases, LEV was discontinued after 2-4 weeks, while 7 infants received LEV up to 3 months. No severe adverse effects were observed.Conclusions: These results illustrate the safety of LEV treatment in neonatal seizures, including prematurity and suggest LEV anticonvulsant efficacy. Additional PB treatment admittedly constitutes a methodological shortcoming due to the prolonged anticonvulsive efficacy of PB. Double blind prospective controlled studies and long-term evaluation of cognitive outcome are called for. (C) 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.