Corticosteroids for managing tuberculous meningitis

 

Abstract

Background

Tuberculous meningitis, a serious form of tuberculosis that affects the meninges covering the brain and spinal cord, is associated with high mortality and disability among survivors. Corticosteroids have been used as an adjunct to antituberculous drugs to improve the outcome, but their role is controversial.

Objectives

To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis.

Search methods

In September 2007, we searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2007, Issue 3); MEDLINE; EMBASE; LILACS and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists.

Selection criteria

Randomized controlled trials comparing a corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculosis meningitis and which include death and/or disability as outcome measures.

Data collection and analysis

We independently assessed search results and methodological quality, and independently extracted data. We analysed the data using risk ratios (RR) with 95% confidence intervals (CI) and the fixed-effect model. We also conducted complete-case and best-worst case analyses.

Main results

Seven trials involving 1140 participants (with 411 deaths) met the inclusion criteria. All used dexamethasone or prednisolone. Overall, corticosteroids reduced the risk of death (RR 0.78, 95% CI 0.67 to 0.91; 1140 participants, 7 trials). Data on disabling residual neurological deficit from three trials showed that corticosteroids reduce the risk of death or disabling residual neurological deficit (RR 0.82, 95% CI 0.70 to 0.97; 720 participants, 3 trials). Adverse events included gastrointestinal bleeding, bacterial and fungal infections and hyperglycaemia, but they were mild and treatable.

Authors' conclusions

Corticosteroids should be routinely used in HIV-negative people with tuberculous meningitis to reduce death and disabling residual neurological deficit amongst survivors. However, there is not enough evidence to support or refute a similar conclusion for those who are HIV positive.

 

Plain language summary

Corticosteroids for managing tuberculous meningitis

Tuberculous meningitis is a serious form of tuberculosis affecting the meninges covering the brain and spinal cord. The clinical outcome is poor even when treated with conventional antituberculous drugs. Corticosteroids are commonly used in addition to antituberculous drugs for treating the condition. They help reduce swelling and congestion of the meninges, and thus decrease pressure inside the brain and the attendant risk of death or disabling residual neurological deficit among survivors. This review identified seven trials involving 1140 people that evaluated either dexamethasone or prednisolone given in addition to antituberculous drugs; only one trial was of high quality. Overall, the trials showed that corticosteroids help reduce the risk of death or a risk of death or disabling residual neurological deficit. Only one trial evaluated the effects of corticosteroids in HIV-positive people, but the effects were unclear. Given the results of the review, all HIV-negative people with tuberculous meningitis should receive corticosteroids, but more trials are needed in HIV-positive people.

 

摘要

背景

類固醇在治療結核性腦膜炎的角色

結核性腦膜炎是一種嚴重的結核菌感染，主要影響大腦及脊髓的腦脊髓膜，進而造成高死亡率及存活者的功能喪失。類固醇已經被用來輔助抗結核菌藥物以改善預後，但其角色仍然是受爭議的。

目標

評估結核性腦膜炎病患使用類固醇作為輔助治療之死亡率及嚴重功能喪失之療效。

搜尋策略

在2007年9月份，我們搜尋了有關的資料庫，包括the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007年 Issue 3), MEDLINE, EMBASE, LILACS, and Current Controlled Trials。 此外也連絡相關領域的研究員與機構，並且核對文獻的參考文獻。

選擇標準

只收納比較臨床上診斷為結核性腦膜炎的病人中，使用類固醇合併抗結核藥物治療與單獨使用抗結核藥物的成效，並以「死亡」及或「功能喪失」為結果衡量的隨機對照試驗(Randomized controlled trials； RCTs)。

資料收集與分析

我們獨立評估文獻搜索的結果、方法學品質並萃取研究資料。我們分析數據是使用相對風險(RR)及95%的信賴區間(CI)和固定效果模式。我們也分別進行完成試驗的狀況及最好/最壞狀況的個案分析。

主要結論

7個臨床試驗，包括1140人符合納入標準(其中411人死亡)。所有的參加者皆使用dexamethasone或prednisolone治療。整體而言，使用類固醇可減少死亡的危險(RR 0.78 ， 95% CI為0.67至0.91; 1140參與者，7個試驗)。從其中3個試驗，針對殘廢性神經功能缺損的數據顯示，類固醇可減少死亡的危險或殘廢性神經功能缺損的機率(RR 0.82，95%CI的信賴區間為0.70至0.97 ; 720參與者，3個試驗) 。副作用包括胃腸道出血，細菌與真菌感染和高血糖症，但這些副作用是輕微及可治療的。

作者結論

類固醇應該常規使用於人類後天免疫不全病毒陰性的結核性腦膜炎的病人，以降低死亡與存活者殘廢性的神經功能缺損。然而沒有足夠證據可以支持或反駁在人類後天免疫不全病毒陽性的結核性腦膜炎的病人身上有相同的結論。

翻譯人

本摘要由三軍總醫院黃子權翻譯。

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

總結

結核性腦膜炎是一種嚴重的結核菌感染，主要影響大腦及脊髓的腦膜。用傳統的抗結核藥物治療，其臨床的預後仍然是差的。類固醇常被用來輔助抗結核菌藥物以改善預後。它們可以降低腦脊髓膜的腫脹與充血，因而降低腦內壓以及伴隨而來的死亡或殘廢性的神經功能缺損。這篇文獻回顧檢視了7個臨床試驗，包括1140人，評估prednisolone或dexamethasone合併抗結核藥物治療的功效。只有1個臨床試驗的設計是嚴謹的。整體而言，這些試驗顯示，類固醇有助於減少死亡的危險，或殘廢性神經功能缺損。只有一個臨床試驗評估類固醇在人類後天免疫不全病毒陽性者的治療成效，但效果尚不清楚。由回顧的結果，所有的人類後天免疫不全病毒陰性的結核性腦膜炎的病人應接受類固醇治療，但對於人類後天免疫不全病毒陽性的病患則需要更多的臨床試驗去評估。