Intervention Review

Calcium channel blockers for acute traumatic brain injury

  1. Julia Langham1,*,
  2. Caroline Goldfrad2,
  3. Graham Teasdale3,
  4. Donald Shaw4,
  5. Kathy Rowan2

Editorial Group: Cochrane Injuries Group

Published Online: 20 OCT 2003

Assessed as up-to-date: 31 OCT 2005

DOI: 10.1002/14651858.CD000565

How to Cite

Langham J, Goldfrad C, Teasdale G, Shaw D, Rowan K. Calcium channel blockers for acute traumatic brain injury. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD000565. DOI: 10.1002/14651858.CD000565.

Author Information

  1. 1

    London School of Hygiene & Tropical Medicine, HSRU, London, UK

  2. 2

    Intensive Care National Audit and Research Centre, London, UK

  3. 3

    The Southern General Hospital, Department of Neurosurgery, Glasgow, UK

  4. 4

    Walton Centre for Neurology & Neurosurgery, Liverpool, UK

*Julia Langham, HSRU, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1B 7HT, UK. julia.langham@lshtm.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 20 OCT 2003

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers (calcium antagonists) have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain, and so prevent further damage.

Objectives

To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury, and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage.

Search methods

We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and the reference lists of relevant articles. We also contacted experts in the field. The searches were updated in November 2005.

Selection criteria

Randomised controlled trials (RCTs) in patients with all levels of severity of clinically diagnosed acute traumatic brain injury.

Data collection and analysis

Two authors independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method.

Main results

Six RCTs involving 1862 participants were included. The effect of calcium channel blockers on the risk of death was reported in five of the RCTs. The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval [95% CI] 0.70 to 1.16). For the five RCTs that reported death and severe disability (unfavourable outcome), the pooled OR 0.97 (95%CI 0.81 to 1.18). In the two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid haemorrhage patients, the pooled OR 0.59 (95% CI 0.37 to 0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled OR 0.67 (95% CI 0.46 to 0.98).

Authors' conclusions

This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Does a group of drugs known as calcium channel blockers reduce mortality and unfavourable complications in patients with traumatic brain injury?

Acute traumatic brain injury is a major cause of death and disability. Not all damage to the brain occurs at the moment of injury; reduction of blood flow and oxygen supply to the brain can occur afterwards and cause further brain damage, which is an important cause of avoidable death and disability. In the early stages after injury it is therefore important that efforts are made to minimise secondary brain damage and to provide the best chances of recovery from established brain damage.

The use of calcium channel blockers has been proposed for the prevention or treatment of cerebral vasospasm (that is, sudden narrowing of blood vessels in the brain), which can occur after brain injury and cause secondary brain damage due to a reduction in blood flow.

It is important to determine whether or not calcium channel blockers might be effective in reducing mortality and unfavourable outcomes in head-injured patients.

This review looked at all high quality trials comparing the use of calcium channel blockers with a control, in head-injured patients of any age. The authors also looked at trials involving patients suffering from subarachnoid haemorrhage (that is, bleeding into the space between the brain and the skull) caused by an injury, as a subgroup.

The authors found six eligible trials involving 1862 patients. The results indicate that there is insufficient evidence to support the use of calcium channel blockers. The authors conclude that there is some evidence that a calcium channel blocker called nimodipine may be beneficial for some patients with subarachnoid haemorrhage. However, there is also an indication of certain adverse reactions amongst patients treated with nimodipine which may mean that the drug is harmful for some individuals.

The authors recommend that the promising results in patients with subarachnoid haemorrhage are replicated in a larger well designed trial, before any firm conclusions about the effectiveness of the drug can be drawn. In future trials, data on outcomes other than death and severe disability, such as quality of life of the survivors and the economic utility of the drug, should be measured; such outcomes have not been considered in existing research.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

鈣離子通道阻斷劑對於急性腦部創傷的作用

急性腦部創傷是造成死亡及殘障的主要原因。鈣離子通道阻斷劑一直以來被用來防止大腦血管痙攣,維持腦部血流並且防止更進一步的傷害。

目標

評估鈣離子阻斷劑對於急性腦部創傷及伴隨蜘蛛膜下腔出血的腦部受損病人的作用。

搜尋策略

我們搜尋了the Cochrane Injuries Group's Specialised Register、 Cochrane Central Register of Controlled Trials以及MEDLINE、 EMBASE及其相關參考資料。我們也請教了這方面領域的專家且資料更新到2005年11月。

選擇標準

臨床診斷為急性腦部創傷的病人(包括各種嚴重度)的隨機對照試驗。

資料收集與分析

由兩位作者分別評估已確認之研究的合格性並選取其中的數據。簡述採用MantelHaenszel方法取得的odds ratios 。

主要結論

六個隨機對照試驗包含1862個病人被選取。五個隨機對照試驗中有提到鈣離子通道阻斷劑對於死亡風險的影響。 五個研究歸納出的OR為0.91 [95% CI 0.70 to 1.16)且死亡與嚴重殘障(預後不佳)的OR為0.97。 兩個有提到蜘蛛膜下腔出血的隨機對照試驗,其死亡風險的OR為0.59 (95% CI 0.37 to 0.94)。三個以死亡併嚴重殘障為結果的隨機對照試驗,其歸納出的OR為0.67 (95% CI 0.46 to 0.98)。

作者結論

這篇系統性回顧文章綜合許多隨機對照試驗,針對鈣離子通道阻斷劑在急性腦部創傷病人的效果仍保持相當的不確定性。而Nimodipine對於腦部受損伴隨蜘蛛膜下腔出血病人的族群顯示一個有益的影響,即使在某些病人上有藥物的副作用增加的情形。

翻譯人

本摘要由高雄榮民總醫院洪碧蓮翻譯。

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

總結

鈣離子通道阻斷劑對於急性腦部創傷的病人是否能減少死亡率和併發症呢? 急性腦部創傷是主要造成死亡及殘障的原因。然而並非所有的腦部傷害都發生在受傷的當下;發生在腦部受傷之後,腦部的血液和氧氣的供給量降低是致死與致殘的要原因,而這是可以避免的。因此能在早期做好減低腦部的二次傷害以及提供一個最好的腦部恢復的機會是重要的影響因素。 而鈣離子通道阻斷劑一直被推測可以防範或治療腦血管痙攣(也就是突然腦血管的直徑變狹窄),而腦血管痙攣常發生在大腦損傷之後且可能因為腦血流降低造成二次傷害。 對於確定鈣離子通道阻斷劑是否能降低腦傷的死亡率及不好的併發症是重要的。這篇回顧的文章著重在:1.所有年齡層的腦傷患者在用鈣離子通道阻斷劑和控制組比較。2.有腦傷並且有蜘蛛膜下腔出血(即有出血在顱骨及腦的空間之間)的病人,作為一次族群。雖然作者取得六篇合乎標準的試驗文章,其結果對於鈣離子通道阻斷劑也是無充足的證據。另外雖然作者結論說Nimodipine對於腦部受損伴隨蜘蛛膜下腔出血病人的族群顯示一個有益的影響,但仍有資料指出對於一些個案Nimodipine為一有害的藥物因為它的副作用。作者建議,大有可為的結果在蛛網膜下腔出血患者被複製在更大的精心設計的試驗下,得到一個更堅定的有關藥物效果的結論。在未來的研究試驗,比起死亡併嚴重殘障的結果,之前沒提過的結果像生存下來的病患之生活品質以及藥物的經濟效應應該拿來當測驗。