Aminosteroids for acute traumatic brain injury

 

Abstract

Background

Traumatic brain injury is a leading cause of premature death and disability. Post-traumatic membrane lipid peroxidation has been proposed as one mechanism leading to secondary brain damage following head injury. Aminosteroids have been shown to inhibit lipid peroxidation in laboratory animals and have the potential to improve outcome following head injury.

Objectives

To quantify the effectiveness and safety of aminosteroids in the treatment of acute traumatic brain injury.

Search methods

We searched the Cochrane Injuries Group specialised register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the National Research Register, Web of Science, web-based trials databases and conducted a general internet search. We contacted experts in the field and the company that manufactures tirilazad. The searches were last updated in March 2006.

Selection criteria

We sought to identify all randomised controlled trials of aminosteroids versus placebo in the treatment of acute traumatic brain injury. Studies using a quasi-random form of allocation, such as alternation, were excluded from the review.

Data collection and analysis

One author examined the electronic search results for reports of possibly relevant trials for retrieval in full. Two authors (IR and PA) applied the selection criteria independently to the trial report, with no disagreement.

Main results

Two randomised controlled trials have examined the effect of the aminosteroid tirilazad mesylate on death and disability following head injury. To date, only the results of one of these trials are available for analysis. The risk of death in patients treated with tirilazad was almost identical to those given placebo RR = 1.05 (95% confidence interval 0.86 to 1.29). The risk of death and severe disability in patients treated with tirilazad was again almost identical to those given placebo RR = 1.07 (95% confidence interval 0.93 to 1.23).

Authors' conclusions

There is no evidence to support the routine use of aminosteroids in the management of traumatic head injury. On the basis of the existing evidence from randomised trials of aminosteroids in head injury, it is not possible to refute the possibility of moderate but potentially clinically important benefits or harms. A further randomised controlled trial of tirilazad mesylate with 1156 participants has been completed, the results of which should become available in the near future.

 

Plain language summary

Use of aminosteroids to treat traumatic brain injury

Traumatic brain injury is a leading cause of death and disability. After the initial blow to the head, additional brain damage can occur through a reduction of oxygen to the brain tissues (cerebral hypoxia). Chemicals called aminosteroids have been shown to help stop cell membrane damage and cell death in animals.

The review author searched the medical literature to find out if aminosteroids help people with traumatic brain injury when given within seven days of the injury. The author looked for randomised controlled trials in which one group of patients received a treatment (aminosteroids) while a similar group received non-active treatment (placebo) in addition to standard care. To reduce possible bias, each patient is randomly assigned to a group. The author found two such studies, which used the aminosteroid tirilazad mesylate, but the results of one of the studies were not available at the time of review. The completed study involved 1131 patients. The results of this study showed no benefit from the aminosteroid. The aminosteroid group did not have more side effects than the placebo group but aminosteroids are fairly new drugs that may have unknown less common side effects.

More research is needed on the use of aminosteroids to treat traumatic brain injury but currently there is no evidence to recommend their use.

 

摘要

背景

Aminosteroids治療急性腦創傷

腦創傷是死亡和失能以主因。創傷後膜脂質過度氧化被認為是腦部受傷後造成二度傷害的機轉之ㄧ。動物研究已證實胺基固醇(Aminosteroids)能抑制脂質過度氧化，具改善腦部受傷的潛力。

目標

評估胺基固醇治療急性腦創傷的療效與安全。

搜尋策略

搜尋考科藍外傷組專科註冊者、考科藍控制實驗註冊中心、MEDLINE、EMBASE、國家研究註冊者、科學網絡、網絡行試驗資料庫和一般網路搜尋，並連繫此領域的專家及替拉扎特(Tirilazad)的製藥廠。本研究更新於2003年三月。

選擇標準

確認所有胺基固醇與安慰劑相較於治療急性腦創傷的隨機控制試驗，凡使用如交替用藥等半隨機分配研究會於審查時排除。

資料收集與分析

一位作者檢視電子化搜尋結果中數據可能有意義的報告，兩位作者在無歧見下各自應用篩選標準審閱。

主要結論

兩個隨機控制試驗檢視胺基固醇於腦部受傷後降低死亡和失能的效果。到目前為止，只有一個試驗可供分析，以替拉扎特治療的死亡風險與安慰劑相近RR = 1.05(95%CI 0.86 – 1.29)，死亡和嚴重失能的風險亦然RR = 1.07(95%CI 0.93 – 1.23)。

作者結論

無證據支持常規使用胺基固醇治療腦創傷。就現有使用胺基固醇治療腦創傷的隨機試驗結果觀之，無法否認使用此藥的合理性、潛在重要的好處與傷害，1156位參與者已完成替拉扎特的隨機控制試驗，結果將應用於可見未來。

翻譯人

本摘要由高雄榮民總醫院毛志民翻譯。

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

總結

腦創傷是死亡和身障的主因：在對頭部的最初一擊之後，大腦損傷造成腦組織的供氧減少(腦缺氧)。名為胺基固醇的化合物於動物實驗中顯示有助於停止細胞膜損害和細胞死亡。作者就搜尋醫學文獻審閱評讀，以釐清若是腦損傷患者7 天內給與胺基固醇是否有益？尋找隨機控制試驗，於標準照護中一組接受胺基固醇治療，另一組則接受安慰劑。為了降低可能的偏見，每位病患被隨機分組。作者找到兩項這樣的研究，使用胺基固醇替拉扎特，但是研究之一的結果在回顧期間未取得。完成的研究計收入1131位患者，研究的結果顯示使用胺基固醇無益。與安慰劑組相比，胺基固醇組並沒有更多的副作用，但胺基固醇是以相當新的藥，可能還有較少發生的副作用未被發現。使用胺基固醇治療腦創傷需要更多的研究，但是目前沒有證據建議使用。