Schierhout Gillian, Roberts Ian
c/o Cochrane Injuries Group, London School of Hygiene & Tropical Medicine, London, UK.
Cochrane Database Syst Rev. 2012 Jun 13;2012(6):CD000173. doi: 10.1002/14651858.CD000173.pub2.
Seizure activity in the early post-traumatic period following head injury may cause secondary brain damage as a result of increased metabolic demands, raised intracranial pressure and excess neurotransmitter release.
To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury.
We searched the Cochrane Injuries Group specialised register, MEDLINE and the registers of the Cochrane Stroke Group and Cochrane Epilepsy Group. We contacted pharmaceutical companies who manufacture anti-epileptic agents, the National Institute of Neurological Disorders and Stroke, Epilepsy Division, and the United States' National Institute of Health.
All randomised trials of anti-epileptic agents, in which study participants had a clinically defined acute traumatic head injury of any severity. Trials in which the intervention was started more than eight weeks after injury were excluded.
Two reviewers independently extracted data and assessed the trial quality. Relative risks and 95% confidence intervals (95%CI) were calculated for each trial on an intention-to-treat basis, which included pre-drug loading exclusions. As long as statistical heterogeneity did not exist, for dichotomous data, summary relative risks and 95% confidence intervals were calculated using a fixed effects model. Where the source of heterogeneity could obviously be related to allocation concealment, drug type, or drug dose, we stratified the analyses on that dimension.
We identified 10 eligible randomised controlled trials, including 2036 participants, but data was unavailable for four unpublished trials, representing 631 participants and they were excluded. For the remaining six trials, the pooled relative risk (RR) for early seizure prevention was 0.34 (95%CI 0.21, 0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR = 1.15; 95%CI 0.89, 1.51), a reduction in death and neurological disability (RR = 1.49; 95%CI 1.06, 2.08 for carbamazepine and RR = 0.96; 95%CI 0.72, 1.26 for phenytoin) or a reduction in late seizures (pooled RR = 1.28; 95%CI 0.90, 1.81). The pooled relative risk for skin rashes was 1.57 (95%CI 0.57, 39.88).
AUTHORS' CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.
头部受伤后的创伤早期癫痫活动可能因代谢需求增加、颅内压升高和神经递质释放过多而导致继发性脑损伤。
确定预防性抗癫痫药物对急性创伤性脑损伤的影响。
我们检索了Cochrane损伤组专门注册库、MEDLINE以及Cochrane卒中组和Cochrane癫痫组的注册库。我们联系了生产抗癫痫药物的制药公司、美国国立神经疾病和中风研究所癫痫科以及美国国立卫生研究院。
所有抗癫痫药物的随机试验，其中研究参与者患有临床定义的任何严重程度的急性创伤性脑损伤。受伤八周后开始干预的试验被排除。
两名评价员独立提取数据并评估试验质量。对每个试验按意向性分析计算相对风险和95%置信区间（95%CI），其中包括药物负荷前排除的病例。只要不存在统计学异质性，对于二分数据，使用固定效应模型计算汇总相对风险和95%置信区间。在异质性来源明显与分配隐藏、药物类型或药物剂量相关的情况下，我们在该维度上进行分层分析。
我们确定了10项符合条件的随机对照试验，包括2036名参与者，但4项未发表试验的数据不可用，这些试验代表631名参与者，因此被排除。对于其余6项试验，预防早期癫痫发作的汇总相对风险（RR）为0.34（95%CI 0.21，0.54）；根据这一估计，每治疗100名患者，10名患者在第一周可无癫痫发作。急性期癫痫控制并未伴随着死亡率降低（RR = 1.15；95%CI 0.89，1.51）、死亡和神经功能障碍减少（卡马西平的RR = 1.49；95%CI 1.06，2.08，苯妥英钠的RR = 0.96；95%CI 0.72，1.26）或晚期癫痫发作减少（汇总RR = 1.28；95%CI 0.90，1.81）。皮疹的汇总相对风险为1.57（95%CI 0.57，39.88）。
预防性抗癫痫药物在减少早期癫痫发作方面有效，但没有证据表明预防性抗癫痫药物治疗可减少晚期癫痫发作的发生，或对死亡和神经功能障碍有任何影响。没有足够的证据来确定受伤后任何时间预防性治疗的净效益。
