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

Abstract

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. 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. 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. 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. UK National Institute for Health Research Health Technology Assessment Programme.