3Mg Trial

1. 3Mg Trial Magnesium’s role in the treatment of asthma

2. Back ground of asthma guidelines • BTS guidelines 2012 for asthma categorizes presentation into severity and helps guide treatment with regards to the category

3. BTS - Moderate exacerbation asthma • increasing symptoms • PEF >50-75% best or predicted • No features of acute severe asthma

4. BTS - Acute severe asthma • Any one of following; • PEF 33-50% best or predicted • respiratory rate ≥25/min • heart rate ≥110/min • inability to complete sentences in one breath

5. Life threatening exacerbation of asthma • In a patient with acute severe asthma with any one of • PEF <33% best or predicted • SpO2 <92% • PaO2 <8 kPa • normal PaCO2 (4.6-6.0 kPa) • silent chest/cyanosis/poor respiratory effort • Arrhythmia/exhaustion/altered conscious level

6. Near fatal asthma • Raised PaCO2 • Requiring mechanical ventilation with raised inflation pressures

7. BTS guidelines for treatment - nebulisers • Give supplementary oxygen to all hypoxaemic patients with acute asthma to maintain an SpO2 level of of 94-98% • Nebulised β2 agonist bronchodilators should be driven by oxygen. • Use high dose inhaled β2 agonists as first line agents in acute asthma and administer as early as possible. Reserve intravenous β2 agonists for those patients in whom inhaled therapy cannot be used reliably • In patients with severe asthma that is poorly responsive to an initial bolusdose of β2 agonist, consider continuous nebulisation with an appropriate nebuliser

8. BTS guidelines for treatment- steroids • Give steroids in adequate doses in all cases of acute asthma. • Continue prednisolone 40-50 mg daily for at least five days or until recovery.

9. BTS guidelines for treatment – Mg++ • Consider giving a single dose of IV magnesium sulphate for patients with: • acute severe asthma who have not had a good initial response to inhaled bronchodilator therapy • life threatening or near fatal asthma. • IV magnesium sulphate (1.2-2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

10. BTS guidelines - ANtibiotics • Routine prescription of antibiotics is not indicated for patients with acute asthma.

11. BTS guidelines – ITU referral • Refer any patient: • requiring ventilatory support • with acute severe or life threatening asthma, failing to respond to therapy, evidenced by: - deteriorating PEF - persisting or worsening hypoxia - hypercapnea + - ABG analysis showing  pH or  H - exhaustion, feeble respiration - drowsiness, confusion, altered conscious state - --respiratory arrest

12. The treatment of interest for this podcast; mg++ • As the BTS guidelines states; • ‘Consider giving a single dose of IV magnesium sulphate for patients with: • acute severe asthma who have not had a good initial response to inhaled bronchodilator therapy • life threatening or near fatal asthma’

13. The paper • Entitled ‘Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial); a double blind, randomised control trial • Published Lancet June 2013 • Lead author – Steve Goodacre

14. Authors reason for conducting the trial • Stepwise approach to exacerbations of asthma including, O2, nebulisers, steroids • They note the delay in onset of action of corticosteroids and pondered if magnesium could bridge the gap from minutes of action delivered with nebs to the hours due to steroids

15. Authors dilema re. nebulized vs iv magnesium for asthma • Neb Pro’s • Quicker onset of action • Decreased side effects • No i.v. access required • Neb Con’s • Reduced dose delivery

16. Authors reason for conducting the trial • Current evidence draws differing conclusions on the effectiveness of treatment and none had directly compared the effect of nebulisedvs intravenous administrations

17. The paper • P >15 years old attending the ED with acute severe asthma (PF<50% predicted, RR>25bpm, HR> 110 bpm, inability to complete sentences in 1 breath • Exclusions – life threatening features, CI’s to the treatment (pregnancy, hepatic/renal failure, heart block or known hypermagnesaemia. Unable to consent, previous enrollment in the 3Mg study, previous use of Mg in the past 24 hour • I Double blinded, multicentre, randomised placebo controlled trial across 34 UK ED’s of just over 1100 patients. Patients received either 2g i.v. Mg ++ (over 20 minutes)/ 1.5g nebulised Mg++ (7.5ml) at 20 minute intervals/placebo. In the first 2 groups placebos were also given being nebulised N saline and i.v. N Saline over the same timeframe. Patients also received standard BTS therapy for acute severe asthma. Data was collected until 2 hours after randomisation. Patients, staff and researchers were blinded to treatment allocations. • C 2 primary outcomes; proportion of patients admitted to hospital on that ED visit or within 7 days & breathlessness measured on a 100 mm VAS in the 2 hours after initiation of the treatment • O Hospital admission was not affected in a statistically significant manner between active treatments and placebo (i.v. Mg++ OR 0.84 95% CI 0.61-1.15, neb Mg++ OR 0.76 95% CI 0.53-1.10) • Mean improvements in VAS did not differ between active treatments and placebo (i.v. Mg++ 2.6mm 95% CI -1.6 to 6.8mm and nebulised Mg++ -2.6mm 95% CI -7.0 to 1.8mm) (NB a positive value reflects a greater improvement than placebo)

18. paper • Strengths • Double blinded RCT • Multicentre • Received current gold standard of treatment • Weaknesses • Study sample was under powered

19. How will this paper affect my practice • In the adult patient presenting with acute severe asthma there is no evidence to suggest benefit either in symptomatic relief as measured on the VAS or likelihood of hospital admission • Beware that in acute severe asthma when the BTS guidelines state • ‘consider mg++ in patients with acute severe asthma who have not had a good initial response to inhaled bronchodilator therapy’ • that there may not be a good response/any at all

20. Referneces • https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-quick-reference-guide/ • Goodacre, Steve et al. 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, no. 4 (June 2013): 293–300. doi:10.1016/S2213-2600(13)70070-5.