Antiepileptic drugs for preventing seizures following acute traumatic brain injury

 

Abstract

Background

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.

Objectives

To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury.

Search methods

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.

Selection criteria

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.

Data collection and analysis

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.

Main results

We identified 10 eligible randomised controlled trials, including 2036 participants, but data was unavailable for four unpublished trials, representing 631 participants and they were excluded.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.

 

Plain language summary

Anti-epileptic drugs can reduce seizures after head injury, but more research is needed to establish whether this leads to a reduction in deaths or disability

Severe head injury can injure the brain. The damage can be worsened by seizures (abnormal electrical brain discharges) happening after the initial injury. Often, anti-epileptic drugs are used to try to prevent seizures and further damage in people who have had a traumatic brain injury. The review found that using anti-epileptic drugs in the early stages after traumatic brain injury does decrease seizures. However, more evidence is still needed to determine whether this decreases death or disability.

 

摘要

背景

抗癲癇藥物(Antiepileptic drugs)用以預防急性腦部外傷(acute traumatic brain injury)後癲癇發作(seizure)

頭部外傷後創傷早期的癲癇活動也許會因為代謝需求增加，腦內壓升高以及釋放過多的神經傳遞物質而造成二次的腦部傷害。

目標

確定預防性抗癲癇製劑對於急性頭部外傷的效果。

搜尋策略

我們檢索了the Cochrane Injuries Group的專科登記資料庫，MEDLINE及the Cochrane Stroke Group與Cochrane Epilepsy Group的登記資料庫。我們聯絡了研發抗癲癇製劑的藥廠，the National Institute of Neurological Disorders and Stroke，Epilepsy Division，及美國的National Institute of Health。

選擇標準

所有抗癲癇製劑的隨機臨床試驗，研究對象為臨床確診之任何嚴重度的急性頭部外傷患者。排除在頭部外傷後八週才開始介入措施的試驗。

資料收集與分析

兩名回顧者分別摘錄資料並評估試驗品質。每一篇試驗根據意圖治療(intentiontotreat)計算relative risks及confidence intervals (95%CI)，其中包括排除預載藥。只要二分資料沒有統計上的異質性，則使用固定效果模型計算95% confidence intervals。當異質性的來源很明顯地與隱匿分配，藥物種類，或藥物劑量有關時，這部分我們採用分層分析。

主要結論

我們找到了10篇合格的隨機對照臨床試驗，共包括2036名研究對象，但無法獲得其中四篇未發表試驗的資料，其中包含631名研究對象，他們被排除在外。剩下的六篇試驗，早期預防癲癇的pooled relative risk (RR)為0.34 (95%CI為0.21至0.54)；根據這項估計，每治療100名病患，其中10名將在第一週免於癲癇的發作。在急性階段控制癲癇時並未減少死亡率(RR = 1.15；95% CI為0.89至1.51)，減少死亡及神經失能(carbamazepine的RR = 1.49；95% CI為1.06至2.08，而phenytoin的RR = 0.96；95% CI為0.72至1.26)或減少晚期癲癇發作(pooled RR = 1.28；95% CI為0.90至1.81)。皮膚紅疹的pooled relative risk為1.57 (95% CI為0.57至39.88)。

作者結論

預防性抗癲癇藥物對於減少早期癲癇發作是有效的，但沒有證據顯示使用預防性抗癲癇藥物治療可以減少晚期癲癇發作，或對於死亡及神經失能有任何作用。無法獲得足夠的證據以建立受傷後任何時間使用預防性治療的淨效益。

翻譯人

本摘要由高雄榮民總醫院金沁琳翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

抗癲癇藥物可以減少頭部受傷後癲癇發作，但需要更多的研究以確定是否這將減少死亡或失能。嚴重的頭部外傷可能使腦部受傷。受傷後初期的癲癇(腦部釋放異常的電流)可能會加重傷害。通常，腦部外傷者使用抗癲癇藥物用來嘗試預防癲癇及更嚴重的傷害。回顧發現在腦部外傷後及早使用抗癲癇藥物可以減少癲癇發作。然而，需要更多的證據以確定是否確實減少死亡或失能。