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 (MgSO4) might improve respiratory function in patients with acute asthma. We aimed to determine whether intravenous or nebulised MgSO4 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 MgSO4 (2 g in 20 min) or nebulised MgSO4 (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 MgSO4 were admitted to hospital before 7 days, as were 285 (72%) of 394 patients allocated intravenous MgSO4 and 281 (78%) of 358 controls. Breathlessness was assessed in 296 (89%) patients allocated nebulised MgSO4, 357 (91%) patients allocated intravenous MgSO4, and 323 (90%) controls. Rates of hospital admission did not differ between patients treated with either form of MgSO4 compared with controls or between those treated with nebulised MgSO4 and intravenous MgSO4. Change in VAS breathlessness did not differ between active treatments and control, but change in VAS was greater for patients in the intravenous MgSO4 group than it was in the nebulised MgSO4 group (5·1 mm, 0·8 to 9·4; p=0·019). Intravenous or nebulised MgSO4 did not significantly decrease rates of hospital admission and breathlessness compared with placebo: intravenous MgSO4 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 MgSO4 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 MgSO4 has no role in the management of severe acute asthma in adults and at best suggest only a limited role for intravenous MgSO4 in this setting. © 2013 Elsevier Ltd.

Citation

Goodacre, S., Cohen, J., Bradburn, M., Gray, A., Benger, J., & Coats, T. (2013). Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial. The lancet. Respiratory medicine, 1(4), 293-300. https://doi.org/10.1016/S2213-2600%2813%2970070-5

• Journal Article Type: Article
• Acceptance Date: Mar 1, 2013
• Online Publication Date: May 17, 2013
• Publication Date: 2013-06
• Deposit Date: Apr 12, 2019
• Publicly Available Date: Feb 24, 2021
• 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
• Public URL: https://hull-repository.worktribe.com/output/1592920
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2213260013700705
• Additional Information: This article is maintained by: Elsevier; Article Title: Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial; Journal Title: The Lancet Respiratory Medicine; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/S2213-2600(13)70070-5; CrossRef DOI link to the associated document: https://doi.org/10.1016/S2213-2600(13)70097-3; Content Type: article; Copyright: Copyright © 2013 Elsevier Ltd.