Cotton Bryan A, Kao Lillian S, Kozar Rosemary, Holcomb John B
Department of Surgery and The Center for Translational Injury Research, The University of Texas Health Science Center, Houston, Texas 77030, USA.
J Trauma. 2011 Aug;71(2):375-9. doi: 10.1097/TA.0b013e318224d307.
The standard for early posttraumatic brain injury (TBI) seizure prophylaxis is phenytoin. Despite its effectiveness, some argue for the use of newer antiepileptics (e.g., levetiracetam) because phenytoin requires close monitoring to maintain its therapeutic window and is associated with rare cutaneous hypersensitivity reactions. The purpose of this study was to evaluate whether phenytoin or levetiracetam would be more cost-effective in preventing early post-TBI seizures and reducing their negative impact on TBI outcomes.
Cost-effectiveness analysis with the following base case assumptions: (1) phenytoin patients receive 1.0 g fosphenytoin load + 3 days of 100 mg three times a day (TID), have level drawn on day 3, "therapeutic" patients receive 100 mg TID on days 4 to 7, and "subtherapeutic" patients receive 200 mg TID on days 4 to 7; (2) levetiracetam patients receive 500 mg load + 7 days of 500 mg two times a day. Glasgow Outcome Scale (GOS) scores 4 to 5 represent good outcome, and GOS scores 2 to 3 represent poor outcome. Patients who develop early seizures: 40% good outcome, 50% poor outcome, and 10% death. Those who do not develop seizures: 75% good outcome, 20% poor outcome, and 5% death. Quality of life outcomes by GOS: good = 0.7, poor = 0.3, and death = 0.0. Severe adverse events and those impacting costs are rare for each agent. Assumptions were obtained through hospital query and exhaustive literature review.
The cost of a 7-day course of fosphenytoin, phenytoin, and free phenytoin level was $37.50, whereas the cost of a 7-day course of levetiracetam was $480.00. Literature review noted phenytoin to be as effective as levetiracetam in preventing early post-TBI seizures (and more effective in subclinical seizures). Quality-adjusted life years (QALY) were 23.6 for phenytoin and 23.2 for levetiracetam. As a result, the cost/effectiveness ratios were $1.58/QALY for phenytoin and $20.72/QALY for levetiracetam. All sensitivity analyses favored phenytoin unless levetiracetam prevented 100% of seizures and cost <$400 for 7-day course.
Phenytoin is more cost-effective than levetiracetam at all reasonable prices and at all clinically plausible reductions in post-TBI seizure potential.
创伤性脑损伤（TBI）后早期癫痫预防的标准药物是苯妥英钠。尽管其疗效显著，但一些人主张使用更新的抗癫痫药物（如左乙拉西坦），因为苯妥英钠需要密切监测以维持其治疗窗，且与罕见的皮肤过敏反应有关。本研究的目的是评估苯妥英钠或左乙拉西坦在预防TBI后早期癫痫发作以及减少其对TBI预后的负面影响方面是否更具成本效益。
进行成本效益分析，采用以下基础病例假设：（1）苯妥英钠组患者接受1.0g磷苯妥英负荷剂量+3天每日三次100mg（TID），在第3天进行血药浓度检测，“治疗有效”的患者在第4至7天接受每日三次100mg治疗，“治疗无效”的患者在第4至7天接受每日三次200mg治疗；（2）左乙拉西坦组患者接受500mg负荷剂量+7天每日两次500mg治疗。格拉斯哥预后量表（GOS）评分4至5表示预后良好，GOS评分2至3表示预后不良。发生早期癫痫发作的患者：40%预后良好，50%预后不良，10%死亡。未发生癫痫发作的患者：75%预后良好，20%预后不良，5%死亡。根据GOS评估的生活质量结果：良好=0.7，不良=0.3，死亡=0.0。每种药物发生严重不良事件及影响成本的情况均罕见。假设通过医院查询和详尽的文献综述获得。
一个7天疗程的磷苯妥英钠、苯妥英钠及苯妥英钠血药浓度检测费用为37.50美元，而一个7天疗程的左乙拉西坦费用为480.00美元。文献综述指出，苯妥英钠在预防TBI后早期癫痫发作方面与左乙拉西坦效果相当（在亚临床癫痫发作方面更有效）。苯妥英钠的质量调整生命年（QALY）为23.6，左乙拉西坦为23.2。因此，苯妥英钠的成本效益比为1.58美元/QALY，左乙拉西坦为20.72美元/QALY。所有敏感性分析均支持苯妥英钠，除非左乙拉西坦能预防100%的癫痫发作且7天疗程费用低于400美元。
在所有合理价格以及所有临床上可能降低TBI后癫痫发作风险的情况下，苯妥英钠比左乙拉西坦更具成本效益。
