JC: Does Magnesium work in asthma? St.Emlyn’s

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This is a roller coaster journey  for me. Many years ago Virchester ED was one of the first hospitals to start using Magnesium for the treatment of acute severe asthma. This prompted great concern amongst some in-hospital colleagues….., and when we started using it in kids OMG (as my daughter might say) it felt as though we were trying to kill the kids!

Time goes on.

These days the first question out of the admitting teams mouths is “Have you given Magnesium yet?” and I’ve even seen MgSO4 administered to mild/moderate asthmatics in preference to Salbutamol for patients who don’t like nebulisers. I sigh and take the opportunity for learning delivery (that’s me to them…..).

Anyway, the evidence for Magnesium in asthma was never really that fantastic. Systematic reviews showed an effect but it was not quite as dramatic as some people now think. There is a nice review here in theEMJ from the Sheffield team, which informed the latest RCT pre-published in the Lancet this month.

3MG trial copy

The 3MG trial led by Steve Goodacre in Sheffield aimed to determine if nebulised Mg and IV Mg are effective in the management of acute severe asthma.

[learn_more caption=”Who was studied?”] The authors wanted to look at acute severe asthma. In this study that meant adult patients with acute asthma, with either a peak expiratory flow rate of <50% of best or predicted, respiratory rate >25 breaths per min, heart rate >110 beats per min, or inability to complete sentences in one breath. Interestingly they excluded patients with life threatening features, interesting as that’s a group that give me great anxiety. Arguably the life threatening patients are the ones where I tend to chuck the kitchen sink of therapies at (Ed – bit more technical than that I’m sure, but I know what you mean).

There were three groups in the study. All patients got an IV and a nebuliser, but the groups received.

  • IV MgSO4 and placebo neb
  • IV placebo and MgSO4 neb
  • IV placebo and placebo neb

So, a pretty good design with a placebo arm. I like this as the evidence was on the weak side from past trials and systematic reviews.

Principal outcomes were admission to hospital and breathlessness at 2 hours.

[/learn_more] [learn_more caption=”The main results”] Interesting. Read the full paper, but in essence the effect of MgSO4 in these patients appears minimal. Nebulised MgSO4 appears to have no effect at all. IV has a minimal effect on admission rates, but does not affect the patient centred outcome of breathlessness.

They also look at a bunch of other outcomes, complications, side effects and again the benefit of MgSO4 is absent in nebulised and minimal for IV. This is a very different picture to the perception of colleagues in my practice and I think this will come as a shock.

[/learn_more] [learn_more caption=”Any concerns with methodology?”] Not especially. This is a good pragmatic trial. Care in all groups was performed at the discretion of the treating teams according to British Thoracic Society guidelines, and arguably that might vary, but I like this. Pragmatic trials probably indicate the difference that we will get in practice and are a bit more ‘real world’ than some highly controlled studies. This is a good paper for teaching about such trials (I’m keeping it on my list of good trials for critical appraisal)[/learn_more] [learn_more caption=”What do the results mean for me and my clinical practice?”] Well, the rollercoaster plummets again. Is MgSO4 down and out? Well probably…

  • Nebulised MgSO4 is almost certainly not worth it in adults.
  • Nebulised MgSO4 works in kids (the MAGNETIC trial results)
  • We don’t know about patients with life threatening asthma – I’ll probably still keep giving it.
  • I am going to have some interesting conversations with the admitting teams over the next few months. Perhaps in a few years their first statement will be….‘You haven’t given Magnesium have you????’

What about you?

  1. Are you going to stop using IV Magnesium on the basis of this?
  2. Are you going to stop using Nebulised Magnesium in adults?
  3. What about patients with life threatening features?

I’d love to hear your thoughts.[/learn_more]

 

Conflict of interest – I know & respect all the authors. I don’t think it colours my judgement, but just so you know 🙂

 

Posted by Simon Carley

Professor Simon Carley MB ChB, PGDip, DipIMC (RCS Ed), FRCS (Ed)(1998), FHEA, FAcadMed, FRCEM, MPhil, MD, PhD is Creator, Webmaster, owner and Editor in Chief of the St Emlyn’s blog and podcast. He is Professor of Emergency Medicine at Manchester Metropolitan University and a Consultant in adult and paediatric Emergency Medicine at Manchester Foundation Trust. He is co-founder of BestBets, St.Emlyns and the MSc in emergency medicine at Manchester Metropolitan University. He is an Education Associate with the General Medical Council and is an Associate Editor for the Emergency Medicine Journal. His research interests include diagnostics, MedEd, Major incidents & Evidence based Emergency Medicine. He is verified on twitter as @EMManchester

  1. Damn

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  2. Interesting! Recently had a asthmatic stuck overnight in a district hospital because the retrieval team said given Magnesium and see what happens rather than do a run and scoop on fixed wing which was taking in somone else. I didn’t think magnesium did anything to change her and she was eventually flown out the next day.

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  3. Michael Stewart May 20, 2013 at 10:36 am

    If it’s life-threatening or heading that way despite treatment, I’m probably still going to give IV magnesium a try, but I suspect I will be using it less often on the basis of these results.

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  4. Hi Nat
    I have been using Mg in the severe end of the asthma spectrum ( ie those who look like they might earn a blue cigar).
    The rationale I have been lab outing under is that Mg might limit some of the cardiac effects / toxicity of all the B2a we throw at them
    Some limited poor quality evidence to support it.
    Sellers, Br Journ Anaesth 2010
    Anecdotally it does seem to help the haemodynamics and allow us to flog the adrenaline receptors a bit more.
    But. Only in the severe disease – they were left out of the Lancet study you are talking about – doh!
    Casey

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  5. Excluding severe asthma and being a little light-on with the dose detract from the real world validity or applicability of this trial, which is unfortunate. Still certainly makes you question the presence or size of a treatment effect for Mg2+ in asthma, though.

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  6. Interesting only ever potentially used Mg2+ nebuliser when recruiting patients. Certainly wont now. IV magnesium will use for life threatening asthma, as nothing to lose. Actually waiting for a bad one to try nebuliser adrenaline after listening to EMRAP podcast.

    Will this study change behaviour? For some probably but not all. People are still using NIV despite this groups previous study showing little patient outcome benefits.
    In my current trust have seen respiratory guys using IV aminophyline for COPD and I can remember a cochrane review ten years ago showing no benefit.

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  7. Meant to qualify NIV for acute pulmonary oedema

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  8. […] Since making this, StEmlyns have scuppered my take on Mag by reporting the 3MG trial which gave a big great ‘hmpph’ to mag and suggest very little, if any benefit. Check out their take.  […]

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  9. I echo Casey’s “d’oh!”: still none the wiser in the group of patients I give it to. Good on these guys for doing the science, but a shame that it’s unlikely to influence the guidelines. I’m still going to use it in the sickies.

    I can’t get access to Lancet Respiratory – did they look at effect on tachycardia? As Casey says, http://resus.me/index.php?s=limits+tachycardia – so it would be very interesting to see if this was borne out in an RCT.

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    1. Hi Cliff, I can’t see anything specific about tachycardia in the published trial but it might be encompassed in table 6 that looks at side effects (but groups them together).

      As for use in the life threatening patients then this does not tell us….., but how good is the old evidence for that group of patients???

      S

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  10. Hey gang

    Any study that has TWO primary outcomes is immediately suspect in my book.
    IMO this is only possible if two power calculations are made – one for each outcome – and the sample size used powers the study sufficiently to assess both outcomes.

    One of these ‘primary’ outcomes is ‘admitted to hospital before 7 days’. I have used mag plenty times for asthma – all the patients were admitted to hospital… because they were SICK – that’s why they got magnesium!!!

    This study is borderline meaningless for the patients I would consider giving mag too.

    Chris

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    1. I’d agree and disagree 😉 if I can cheekily suggest that there is some meaning here for us.

      Agree that this did not tx the patients with life threatening features.

      Disagree that it’s meaningless. It’s only lacking impact because the result is negative, and negative trials are just as important as positive ones. We need these to counter the publication bias that pervades much medical publishing.

      I think I am stretching your point so my apologies, I think yo will agree. I just wanted to say that I love negative trials just as much as positive ones :-))

      S

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    2. Also past studies and meta analysis suggested benefit in acute severe so this trial did look at a group previously thought to benefit,

      S

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  11. Hello,

    Thanks for bringing this paper to my screen.

    I don’t see any benefit in this study (as per the abstract, and abstracts are usually way more optimistic than actual results).

    The authors state:

    “Intravenous or nebulised MgSO4 did not significantly decrease rates of hospital admission and breathlessness compared with placebo”

    ” 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”

    So we dont care a … oops , we don’t really care about next words ” but change in VAS was greater for patients in the intravenous MgSO4 group than it was in the nebulised MgSO4 group” . Since Mg is’nt better than placebo as previously written, this statement appears quite er …. odd .

    Maybe the full paper reports peak expiratory flow results, and I wonder why this wasn’t an endpoint.

    Take home message for me, after reading this abstract: don’t give any Mg to patients such as those included in the study.

    But as I haven’t read the full paper… maybe I missed something.

    If there were anything statistically significant in the full paper I’d be curious about the effect size (clinically meaningful ? ) and NNTs that tell me more than odds ratios.

    I’m still not going to use Mg, then.

    Disclaimer: a “negative” abstract is less likely to be isleading than one boasting postive results, but it is still an abstract.

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    1. Full paper now available via the Sheffield website. Click on box top right 🙂

      S

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  12. […] even know this trial was being done till Simon Carley posted on it. It came just too late to be added to be talk on the Crashing Asthmatic but there you […]

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  13. […] Magnesium: Looks like it works for kids, looks like it doesn’t work for severe asthma in adults ? still a role in life threatening asthma.  http://www.stemlynsblog.org/2013/05/jc-does-magnesium-work-in-asthma-st-emlyns/ […]

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  14. […] Maximise medical therapy (this was done in this case) eg steroids,  IV salbutamol (25omcg bolus then 5mcg/minute titrated up to 20mcg/minute) or albuterol, frequent or continuous nebulisers (salbutamol or albuterol and ipratropium), oxygen as required, ? IV magnesium – probably ineffective in adults but hasn’t been trialled in life threatening asthma […]

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  15. Dr Sciddhartha Koonwar M.D. , Fellow of Pediatric Intensive Care KGMU., Dr. Sciddhartha Koonwar Assistant Professor Pediatrics King George's Medical University Lucknow India September 12, 2014 at 6:28 am

    Wondering what different physiology in children makes them respond them better on positive side as compared to the adults in reference to effect of magnesium sulphate on acute life threatening asthma ?

    Reply

  16. […] JC: Does Magnesium work in asthma? on St. Emlyn’s […]

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