Centre for Clinical Neurosciences and Neurological Research, St Vincent's Hospital, Melbourne, Victoria, Australia.
Epilepsia. 2013 Jan;54(1):45-57. doi: 10.1111/j.1528-1167.2012.03563.x. Epub 2012 Jun 27.
Practical choice in parenteral antiepileptic drugs (AEDs) remains limited despite formulation of newer intravenous agents and requirements of special patient groups. This study aims to compare the tolerability, safety, and side effect profiles of levetiracetam (LEV) against the standard agent phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting.
This prospective, randomized, single-center study with appropriate blinding comprised evaluation pertaining to intravenous use 3 days following craniotomy and at discharge, and to total intravenous-plus-oral AED regimen at 90 days. Primary tolerability end points were discontinuation because of side effect and first side effect. Safety combined end point was major side effect or seizure. Seizure occurrence and side effect profiles were compared as secondary outcomes.
Of 81 patients randomized, 74 (36 LEV, 38 PHT) received parenteral AEDs. No significant difference attributable to intravenous use was found between LEV and PHT in discontinuation because of side effect (LEV 1/36, PHT 2/38, p = 1.00) or number of patients with side effect (LEV 1/36, PHT 4/38, p = 0.36). No significant difference was found between LEV and PHT total intravenous-plus-oral regimen in discontinuation because of side effect (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.21-2.92, p = 0.72) or number of patients with side effect (HR 1.51, 95% CI 0.77-2.98, p = 0.22). More patients assigned PHT reached the undesirable clinical end point for safety of major side effect or seizure (HR 0.09, 95% CI 0.01-0.70, p = 0.002). Seizures occurred only in patients assigned PHT (n = 6, p = 0.01). Although not significant, trends were observed for major side effect in more patients assigned PHT (p = 0.08) and mild side effect in more assigned LEV (p = 0.09).
Both LEV and PHT are well-tolerated perioperatively in parenteral preparation, and in total intravenous-plus-oral prophylactic regimen. Comparative safety and differing side effect profile of intravenous LEV supports use as an alternative to intravenous PHT.
尽管有新的静脉用抗癫痫药物（AED）制剂和特殊患者群体的需求，但在选择肠外 AED 时仍然受到限制。本研究旨在比较左乙拉西坦（LEV）与标准药物苯妥英（PHT）静脉内和总方案用于神经外科预防性治疗时的耐受性、安全性和副作用特征。
这项前瞻性、随机、单中心研究采用适当的盲法，评估开颅术后 3 天和出院时的静脉内使用情况，以及 90 天时的总静脉加口服 AED 方案。主要耐受性终点为因副作用和首次副作用而停药。主要的安全性终点是严重副作用或癫痫发作。将癫痫发作的发生和副作用特征作为次要结果进行比较。
在 81 名随机患者中，74 名（36 名 LEV，38 名 PHT）接受了静脉内 AED 治疗。LEV 和 PHT 静脉内使用在因副作用停药方面（LEV 1/36，PHT 2/38，p = 1.00）或出现副作用的患者人数方面（LEV 1/36，PHT 4/38，p = 0.36）无显著差异。LEV 和 PHT 总静脉加口服方案在因副作用停药方面（风险比[HR]0.78，95%置信区间[CI]0.21-2.92，p = 0.72）或出现副作用的患者人数方面（HR 1.51，95%CI 0.77-2.98，p = 0.22）无显著差异。更多接受 PHT 治疗的患者达到了主要副作用或癫痫发作安全性的不良临床终点（HR 0.09，95%CI 0.01-0.70，p = 0.002）。只有接受 PHT 治疗的患者才出现癫痫发作（n = 6，p = 0.01）。虽然没有统计学意义，但观察到更多接受 PHT 治疗的患者出现主要副作用的趋势（p = 0.08）和更多接受 LEV 治疗的患者出现轻度副作用的趋势（p = 0.09）。
LEV 和 PHT 在围手术期的静脉制剂和总静脉加口服预防性方案中均具有良好的耐受性。静脉内 LEV 的安全性相似，但副作用特征不同，支持将其作为静脉内 PHT 的替代药物。
