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?
Design
- Randomised, controlled trial
- Double-blinded
- Placebo-controlled
- Multi-centre
- Intention to treat analysis
Setting
- 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
Population
- 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
- Life-threatening asthma
- 1084 patients randomised and analysed on intention to treat basis
- target was 1200 patients but terminated early because funding expired
Intervention
- Intravenous MgSO4 (2g over 20 minutes) + standard BTS/SIGN guidelines
- Nebulised MgSO4 (500mg x 3 at 20 minute intervals) + standard BTS/SIGN guidelines
Control
- 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
Outcome
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)
- No difference in rates of admission to hospital between intervention and control groups
- 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
- No difference between intervention and control groups in:
- 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.
Strengths
- 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
Weaknesses
- 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
- [original article full text]: Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial) by Goodacre
- [podcast]: Magnesium in acute severe asthma; 3Mg trial. HEFT EMCAST
- [Further reading]: BTS/SIGN Guidelines on management of asthma 2012 (NB study used 2007 guidelines)
- [Further reading]: Economic evaluation of 3Mg trial – Health Technology Assessment 2014
- [Further reading]: Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane review
- [Further reading]: Does Magnesium work in asthma? St Emelyns
Metadata
Summary author: @avkwong
Summary date: 8th July 2014
Peer-review editor: @stevemathieu75
Why is the power to detect between 84-87? Why isnt it a single number?