3MG TRIAL

MAGNESIUM’S ROLE IN THE TREATMENT OF ASTHMA

BACK GROUND OF ASTHMA GUIDELINES

BTS guidelines 2012 for asthma categorizes presentation into severity and helps guide treatment with regards to the category

BTS - MODERATE EXACERBATION ASTHMA• increasing symptoms

• PEF >50-75% best or predicted

• No features of acute severe asthma

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

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

NEAR FATAL ASTHMA

• Raised PaCO2

• Requiring mechanical ventilation with raised inflation pressures

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

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.

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.

BTS GUIDELINES - ANTIBIOTICS

Routine prescription of antibiotics is not indicated for patients with acute asthma.

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

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’

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

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

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

AUTHORS REASON FOR CONDUCTING THE TRIAL

Current evidence draws differing conclusions on the effectiveness of treatment and none had directly compared the effect of nebulised vs intravenous administrations

THE PAPERP >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)

PAPERStrengths

• Double blinded RCT

• Multicentre

• Received current gold standard of treatment

Weaknesses

• Study sample was under powered

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

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.