3Mg trial

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

Goodacre. Lancet Respir Med 2013; 1: 293–300

Clinical Question

  • Does intravenous or nebulised MgSO4 improve symptoms of breathlessness and reduce the need for hospital admission in adults with severe acute asthma?


  • Randomised, controlled trial
  • Double-blinded
  • Placebo-controlled
  • Multi-centre
  • Intention to treat analysis


  • 34 Emergency Departments in the UK
    • over 1/3 recruitments were from 3 ED’s (Edinburgh, Sheffield and Bath)
  • 30th July 2008 to 30th June 2012


  • Adults, aged over 16
  • ED attendees
  • Severe acute asthma as defined by BTS Guidelines
    • PEFR < 50% best or predicted
    • RR > 25/min
    • HR > 110/min
    • Inability to complete sentences in 1 breath
  • Exclusions
    • Life-threatening asthma
      • O2 sats < 92%; Silent chest; Cyanosis; Poor respiratory effort; Bradycardia; Arrhythmia; Hypotension; Exhaustion; Coma; Confusion
    • Contraindication to either nebulised or intravenous MgSO4
    • Patients unable to give verbal or written consent
    • Previous participant in 3Mg trial
  • 1084 patients randomised and analysed on intention to treat basis
    • target was 1200 patients but terminated early because funding expired


  • Intravenous MgSO4 (2g over 20 minutes) + standard BTS/SIGN guidelines
  • Nebulised MgSO4 (500mg x 3 at 20 minute intervals) + standard BTS/SIGN guidelines


  • Placebo + standard BTS/SIGN guidelines
BTS/Sign standard therapy – oxygen, nebulised salbutamol (5mg), nebulised ipratropium (500mcg) and oral prednisilone. Other treatments were at the discretion of the clinician


In words

  • Primary outcomes
    • No difference in rates of admission to hospital between intervention and control groups
      • 285/394 (72%)  vs. 261/332 (79%) vs. vs. 281/358 (78%) patients were admitted to hospital before 7 days in the intravenous vs. nebulised vs. placebo group
      • Odds ratio of 0.84 (CI 0.61 – 1.15; p=0.276)
    • No difference in patient-reported visual analogue score (VAS) for breathlessness between intervention and control at 2 hours
      • 0mm (CI -1.9 – 1.9; p=0.999)
  • Secondary outcomes
    • No difference between intervention and control groups in:
      • Mortality (1 death each in intervention groups and none in control)
      • Use of ventilation/respiratory support
      • Length of hospital stay
      • Admission to HDU or ICU
      • Change in PEFR and physiological variables
  • Increased incidence of side-effects up to 30 days in intervention compared to control groups
  • To be reported:
    • Change in quality of life at 1 month
    • Number of unscheduled health-care contacts over subsequent month
    • Satisfaction with care

In numbers

Authors’ Conclusions

  • Nebulised MgSO4 has no role in the management of severe acute asthma in adults and at best, only a limited role for intravenous MgSO4 in this setting.


  • Double blinded randomised controlled trial
    • treatment packs used which all contained an intravenous infusion and three nebuliser solutions
  • Multi-centred
  • Control group of established recommendations (BTS/SIGN)
  • Study registered ISRCTN04417063


  • Recruitment was terminated early as funding expired
  • Underpowered: Designed to detect a 10% difference in admission rates
    • recruitment of 1200 patients would have meant 90% power to detect the planned 10% absolute reduction in proportion of patients admitted to hospital from ED.
    • recruitment of 1084 patients meant 84-87% power to detect a 10% absolute reduction in admission rate for interventions versus control
  • Protocol amendment during the trial to also include individuals who had received MgSO4 in the 24 hour before recruitment

The Bottom Line

  • This is the largest trial looking at the role of MgSO4 in the treatment of acute severe asthma in adults. I have never used nebulised MgSO4 to treat asthma in adults and this won’t change. The use of intravenous MgSO4 in severe acute asthmatics is not without its side effects but I would still continue to use it in patients with life-threatening asthma. My expectation of achieving any significant clinical impact by giving 2g magnesium will remain low

External Links


Summary author: @avkwong
Summary date: 8th July 2014
Peer-review editor: @stevemathieu75

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