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

Goodacre, Steve; Cohen, Judith; Bradburn, Mike; Gray, Alasdair; Benger, Jonathan; Coats, Timothy

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. © 2013 Elsevier Ltd.

• Journal Article Type: Article
• Publication Date: Jun 1, 2013
• Journal: The Lancet Respiratory Medicine
• Print ISSN: 2213-2600
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 1
• Issue: 4
• Pages: 293-300
• DOI: https://doi.org/10.1016/S2213-2600%2813%2970070-5
• Keywords: intravenous, nebulised magnesium sulphate, standard therapy, severe acute asthma, randomised controlled trial
• Public URL: https://uwe-repository.worktribe.com/output/931813
• Publisher URL: http://dx.doi.org/10.1016/S2213-2600(13)70070-5