Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage

 

Abstract

Background

Corticosteroids, particularly dexamethasone, are commonly used for treatments in patients with subarachnoid haemorrhage (SAH) and primary intracerebral haemorrhage (PICH) despite the lack of evidence.

Objectives

To determine: (1) whether corticosteroid therapy reduces the proportion of patients who die or have a poor outcome at one to six months after the onset of SAH or PICH; (2) whether corticosteroid therapy reduces the frequency of delayed cerebral ischaemia in patients with SAH; (3) the frequency of adverse effects of corticosteroid therapy in patients with SAH or PICH within six months of the onset of the event.

Search methods

We searched the Cochrane Stroke Group Trials Register (last searched November 2003). In addition, we searched MEDLINE (1966 to March 2004) and EMBASE (1980 to March 2004), and searched reference lists of relevant studies identified. We attempted to identify any relevant ongoing and published or unpublished studies by contacting trialists and pharmaceutical companies.

Selection criteria

We sought to identify all randomised or quasi-randomised clinical trials of corticosteroid therapy, in patients with SAH or PICH, that have a placebo or standard strategy arm as control. Data were analysed both separately and combined for computed tomography (CT)/magnetic resonance imaging (MRI)/autopsy/angiography verified patients.

Data collection and analysis

Data extracted from eligible clinical trials included: (1) death and poor outcome (death, severe disability, or vegetative state) within the first one to six months of the event onset (primary outcomes); (2) development of delayed cerebral ischaemia in patients with SAH; and (3) adverse effects of the treatment during the scheduled treatment or follow-up period (secondary outcomes). A pooled estimate of the effect size was computed, and the test for heterogeneity between trial results was carried out. Intention-to-treat analysis was carried out whenever possible.

Main results

Eight trials, with 256 randomised patients in three SAH trials and 206 patients in five PICH trials, were included. The studies differed substantially with regard to the study populations and drugs, and methodological quality. The number of patients allocated to either hydrocortisone or fludrocortisone acetate treatment in patients with SAH, or to dexamethasone treatment in patients with PICH, was too small to make any definitive conclusions.

Authors' conclusions

Overall, there is no evidence of a beneficial or adverse effect of corticosteroids in patients with either SAH or PICH. Confidence intervals are wide and include clinically significant effects in both directions.

 

Plain language summary

Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage

There is no evidence of benefit from corticosteroids for patients with stroke due to bleeding. About one fifth of all strokes are due to bursting of an artery. The burst artery causes bleeding into the brain itself (called intracerebral haemorrhage) or into the space around the brain (called subarachnoid haemorrhage). After either type of bleed the brain tissue may become swollen. The swelling causes a rise in pressure which can cause further brain damage or even death. Corticosteroids could reduce swelling after brain haemorrhage and so improve the chances of the patient recovering. However, corticosteroids can also have important adverse effects such as increased blood sugars, infection, and gastrointestinal bleeding. The trials included in this review had too few participants to provide reliable evidence on any benefits weighed against harms of this treatment for patients with stroke due to bleeding in the brain.

 

摘要

背景

皮質類固醇之於動脈瘤性的蛛網膜下出血和原發性腦內出血

皮質類固醇，特別是dexamethasone，儘管缺乏證據，通常用於治療患者的蛛網膜下腔出血(SAH)和原發性腦出血(PICH)。

目標

這項審查的目的為：(1)判斷在發生SAH或PICH後1到6個月的病人身上使用皮質類固醇是否能減少死亡或是預後不佳發生的比例; (2)判斷使用皮質類固醇是否能減低遲發性腦缺血(DCI)的發生頻率(3)判定在發生SAH或PICH六個月內的病人身上使用皮質類固醇的副作用發生頻率。

搜尋策略

我們搜尋了Cochrane Stroke Group Trials Register (最後到2003年11月). 另外，我們搜尋了MEDLINE (1966 年到2004年3月 nd EMBASE (1980年到2004年3月)，並檢索了相關研究的參考書籍目錄。我們也連絡試驗者和製藥公司，試圖找出任何相關正在進行的和未發表的研究報告。

選擇標準

我們試圖確定所有以SAH或PICH病人為對象的隨機或半隨機臨床試驗的類固醇治療有安慰劑或標準控制策略。不論年紀或性別，於臨床上(床邊)診斷為PICH以及有腦脊髓液記錄診斷的SAH的病人都被納入分析。這些資料是針對以computed tomography (CT)/magnetic resonance imaging(MRI) / autopsy /angiograph 確診的病人而被個別地分開以及合併加以分析。

資料收集與分析

由合格的臨床試驗提取的數據包括：(1)在第1個到第6個月所產生之死亡和預後不佳的結果(死亡，嚴重殘疾或植物人狀態)(主要預後結果); (2)在SAH患者遲發性腦缺血(由試驗者定義)的進展，; 及(3)在治療計劃期間或追蹤期間的治療產生之副作用(次要預後結果)。匯集計算了影響的規模，試驗結果之間的異質性利用了The Cochrane Collaboration's Review Manager software, RevMan 4.2做過了測試。只要可行，都作了意圖治療分析法。

主要結論

有八個試驗(三個試驗包含隨機SAH的病人256個以及五個試驗包含PICH的病人206個)符合資格標準。這些研究在研究對象，藥物的研究以及方法學的品質上差別很大，。使用hydrocortisone或 ludrocortisone acetate的SAH病人數以及使用dexamethasone的PICH病人數都太小以至於無法作出明確的結論(對於任何的預後結果的信心區間都很寬)。

作者結論

總的來說，沒有證據顯示皮質類固醇的使用對於SAH或PICH病人是不是有益。信心區間非常寬而且包含了雙向的臨床意義。

翻譯人

本摘要由奇美醫院黃志傑翻譯。

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

總結

沒有證據表明出血性中風使用病人皮質類固醇是有益的，約有五分之一的中風是由於血管爆裂的。動脈破裂引起的出血進入大腦本身(稱為腦內出血)，或到大腦附近空間的(稱為蛛網膜下腔出血)。任何類型出血後，腦組織可能會變得腫脹。腫脹導致上升的壓力，可造成進一步的腦損傷，甚至死亡。糖皮質激素可減少腫脹和腦出血的機會，以便提高病人的康復機會。然而，皮質類固醇也可以有重要的不利影響，例如血糖增加，感染，以及消化道出血。此次檢審中的試驗中參與者提供太少對於腦出血的中風患者使用這種療法是利大於弊的可靠證據。