静脉注射或雾化硫酸镁与标准疗法治疗重症急性哮喘（3Mg 试验）：一项双盲、随机对照试验。

Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial.

机构信息

School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.

出版信息

Lancet Respir Med. 2013 Jun;1(4):293-300. doi: 10.1016/S2213-2600(13)70070-5. Epub 2013 May 17.

DOI:10.1016/S2213-2600(13)70070-5

PMID:24429154

Abstract

BACKGROUND

Previous studies suggested intravenous or nebulised magnesium sulphate (MgSO(4)) might improve respiratory function in patients with acute asthma. We aimed to determine whether intravenous or nebulised MgSO(4) improve symptoms of breathlessness and reduce the need for hospital admission in adults with severe acute asthma.

METHODS

In our double-blind, placebo-controlled trial, we enrolled adults (aged ≥16 years) with severe acute asthma at emergency departments of 34 hospitals in the UK. We excluded patients with life-threatening features or contraindication to study drugs. We used a central randomisation system to allocate participants to intravenous MgSO(4) (2 g in 20 min) or nebulised MgSO(4) (three 500 mg doses in 1 h) alongside standard therapy including salbutamol, or placebo control plus standard therapy alone. We assessed two primary outcome measures in all eligible participants who started treatment, according to assigned treatment group: the proportion of patients admitted to hospital within 7 days and breathlessness measured on a 100 mm visual analogue scale (VAS) in the 2 h after initiation of treatment. We adjusted for multiple testing using Simes's method. The trial stopped before recruitment was completed because funding expired. This study is registered, number ISRCTN04417063.

FINDINGS

Between July 30, 2008, and June 30, 2012, we recruited 1109 (92%) of 1200 patients proposed by the power calculation. 261 (79%) of 332 patients allocated nebulised MgSO(4) were admitted to hospital before 7 days, as were 285 (72%) of 394 patients allocated intravenous MgSO(4) and 281 (78%) of 358 controls. Breathlessness was assessed in 296 (89%) patients allocated nebulised MgSO(4), 357 (91%) patients allocated intravenous MgSO(4), and 323 (90%) controls. Rates of hospital admission did not differ between patients treated with either form of MgSO(4) compared with controls or between those treated with nebulised MgSO(4) and intravenous MgSO(4). Change in VAS breathlessness did not differ between active treatments and control, but change in VAS was greater for patients in the intravenous MgSO(4) group than it was in the nebulised MgSO(4) group (5·1 mm, 0·8 to 9·4; p=0·019). Intravenous or nebulised MgSO(4) did not significantly decrease rates of hospital admission and breathlessness compared with placebo: intravenous MgSO(4) was associated with an odds ratio of 0·73 (95% CI 0·51 to 1·04; p=0·083) for hospital admission and a change in VAS breathlessness of 2·6 mm (-1·6 to 6·8; p=0·231) compared with placebo; nebulised MgSO(4) was associated with an odds ratio of 0·96 (0·65 to 1·40; p=0·819) for hospital admission and a change in VAS breathlessness of -2·6 mm (-7·0 to 1·8; p=0·253) compared with placebo.

INTERPRETATION

Our findings suggest nebulised MgSO(4) has no role in the management of severe acute asthma in adults and at best suggest only a limited role for intravenous MgSO(4) in this setting.

FUNDING

UK National Institute for Health Research Health Technology Assessment Programme.

摘要

背景

先前的研究表明，静脉注射或雾化硫酸镁（MgSO4）可能改善急性哮喘患者的呼吸功能。我们旨在确定静脉注射或雾化 MgSO4 是否能改善呼吸困难症状并降低成人严重急性哮喘的住院需求。

方法

在我们的双盲、安慰剂对照试验中，我们在英国 34 家医院的急诊科招募了成年（年龄≥16 岁）严重急性哮喘患者。我们排除了有生命威胁特征或研究药物禁忌证的患者。我们使用中央随机系统将参与者随机分配到静脉注射 MgSO4（2 g 在 20 分钟内）或雾化 MgSO4（3 次 500 mg 剂量在 1 小时内）联合包括沙丁胺醇在内的标准治疗，或安慰剂对照加单独的标准治疗。我们评估了所有符合条件的参与者的两个主要结局指标，根据分配的治疗组：在开始治疗后的 2 小时内，7 天内住院的患者比例和呼吸困难，用 100mm 视觉模拟量表（VAS）测量。我们使用 Simes 方法进行了多次测试调整。由于资金到期，试验在完成招募之前停止。这项研究已经注册，编号 ISRCTN04417063。

结果

在 2008 年 7 月 30 日至 2012 年 6 月 30 日之间，我们按照计算的能力招募了 1109 名（92%）拟招募的 1200 名患者中的 92%。与静脉注射硫酸镁组（285 名，72%）和对照组（281 名，78%）相比，接受雾化硫酸镁治疗的 332 名患者中有 261 名（79%）在 7 天内住院，接受静脉注射硫酸镁治疗的 394 名患者中有 285 名（72%）。在接受雾化硫酸镁治疗的 296 名（89%）患者、接受静脉注射硫酸镁治疗的 357 名（91%）患者和接受对照组的 323 名（90%）患者中评估了呼吸困难情况。与对照组相比，两种形式的硫酸镁治疗与对照组相比，患者的住院率没有差异，也没有差异雾化硫酸镁和静脉硫酸镁治疗之间的差异。与对照组相比，两种治疗方法的 VAS 呼吸困难变化没有差异，但静脉硫酸镁组的 VAS 变化大于雾化硫酸镁组（5·1mm，0·8 至 9·4；p=0·019）。与安慰剂相比，静脉或雾化硫酸镁治疗并未显著降低住院率和呼吸困难率：与安慰剂相比，静脉硫酸镁治疗的住院率的优势比为 0·73（95%CI 0·51 至 1·04；p=0·083），VAS 呼吸困难变化为 2·6mm（-1·6 至 6·8；p=0·231）；与安慰剂相比，雾化硫酸镁治疗的住院率的优势比为 0·96（0·65 至 1·40；p=0·819），VAS 呼吸困难变化为-2·6mm（-7·0 至 1·8；p=0·253）。