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 bolus
dose 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
Neb Con’s
• Quicker onset of
action
• Reduced dose
delivery
• Decreased side
effects
• No i.v. access
required
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 PAPER
P
>15 years old attending the ED with acute severe
110 bpm, inability to complete sentences in 1 breath
asthma (PF<50% predicted,
RR>25bpm, HR>
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)
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)
at
PAPER
Strengths
Weaknesses
• Double blinded RCT
• Study sample was
under powered
• Multicentre
• Received current
gold standard of
treatment
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/clinicalinformation/asthma/btssign-asthma-guideline-quickreference-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.