A 9 year old boy is rushed into ED with what is clearly a severe exacerbation of his asthma. His sats are 80%, his RR is 60-70 and he is not looking great. You can hear some air entry with a bit of wheeze. He clearly needs some good treatment and he needs it quickly. Which drugs you choose? What is the evidence for asthma treatment and what are the principles of managing the critical asthmatic?
The first thing to note is that asthma management is not cut and dry – there is huge variation in treatment and doses. A study by Babel et al (2007) found 39 different dosing regimes for IV salbutamol and a highly variable practice for severe asthma. The reason for that is that the evidence is not strong.
The post is based on very lovely podcasts by Andy Neill (Emergency Medicine Ireland), Scott Weingart (EMCrit) and Colin Parker (EMPEM). This post (Part I) focuses on medical management of asthma. Part II is on ventilation strategies.
We are all familiar with using inhaled or nebulised salbutamol and know that it stimulates beta receptors to give bronchodilation. The thinking now is that giving continuous nebulisation is optimal for inhaled treatment, as intermittent nebs can cause a rebound bronchoconstriction.
Inhaled ipratropium bromide
This is an anticholinergic and is often given inhaled along with salbutamol.
In 2005, Rodrigo looked at children treated with salbutamol and ipratropium bromide (there were 1800 children across 10 studies). It found significantly lower admission rates for those treated with ipratropium bromide too (NNT 13).
And in 2006, Munro looked at acute childhood asthma being treated with salbutamol and iptratropium bromide. It did show a reduction in time to recovery and discharge, and it reduced admission rates in the moderate to severe groups. A Cochrane review showed only mild benefits.
It’s not clear that ipratropium is fabulous or even how long to keep giving it for. In ICU we do not give it, and that is because the anti-cholinergic effect dries up secretions causing plugging and problems with ventilation.
The best advice is to give it with the first three salbutamol nebs as it may have a good effect on moderate to severe asthma.
IV magnesium sulphate
Magnesium sulphate is a smooth muscle relaxant but we do not know its exact mechanism of action.
A Cochrane review in 2009 (660 patients but a mix of kids and adults) concluded that whilst magnesium should not be used routinely, it can help with more severe exacerbations. And Rowe in 2008 demonstrated that a single dose of IV magnesium is effective in reducing hospitalisation rates.
BestBet asked the question (2004) – does IV magnesium sulphate in status asthmaticus reduce admission rates? 3 of 4 studies showed a significant reduction in hospitalisation rates. The NNT here was an astounding 3. As discussed in the empem.org podcast – this seems like a strange question…surely everyone receiving magnesium sulphate will be severe enough to require admission anyway? So there are questions about this that have left many people stumped.
The evidence is sketchy but it does seem that a single dose of IV magnesium can be used effectively. It’s certainly worth a try in ED to help stave off an ICU admission – it is a relatively safe drug.
Aminophylline is from the dark ages but people still use it (it’s a phophodiesterase inhibitor). Be careful though because, unlike magnesium sulphate, it can cause adverse effects.
A 2012 Cochrane review in adults (817 patients across 15 studies) showed it had no significant bronchodilator effect when used on top of salbutamol. But worse than that – for every 100 people treated, 20 had vomiting and 15 had arrhythmias or palpitations.
In children, Mitra conducted a Cochrane review in 2009. This was in children with severe asthma and looked at IV aminophylline + nebulised beta agonists +/- steroids (380 children across 7 studies). It did show improved lung function within six hours but no difference in the length of stay, the number of nebulisers or symptom improvement. And there was a significant risk of vomiting.
Be aware of the side effects when you use it.
Some people really hate this stuff. And that’s because of the systemic side effects. It increases oxygen consumption and increases the acid load on top of a pre-existing respiratory acidosis. If you’re expecting your patient to improve and yet they seem to be getting worse – consider IV salbutamol as the cause.
There have been a few papers looking at this with varying results.
Lawford (1978) showed no difference in recovery rates between nebulised and IV salbutamol – but IV salbutamol had worse side effects. And a Cochrane review in 2012 seems to back this up (100 adult patients across 3 studies) by concluding that there was no significant benefit in using IV salbutamol.
At Children’s Hospital, Westmead (Sydney), Gary Browne has published some research on this. In 1997 his trial (29 children) of IV saline versus IV salbutamol demonstrated an improvement for the IV salbutamol group. There was a shorter time to recovery (off 30 minutely nebs) and less need for oxygen supplementation. And a further study from him in 2002 (55 children) showed a reduced recovery time, less oxygen at 12 hours and an earlier discharged from hospital (>1 day).
Adrenaline was used long before IV salbutamol was. It can be given by lots of routes but it seems to be used mainly in the nebulised form to help reduce airway oedema.
Inhalational anaesthetics can also be used.
There is little (or no) evidence to support these, but the options are there.
Lawford P, Milledge JS. Intravenous versus inhaled salbutamol. Lancet. 1978;1(8058):269.
Salmeron S, Brochard L, Mal H, Tenaillon A, Henry-Amar M, Renon D, Duroux P, Simonneau G. Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study. Am J Respir Crit Care Med. 1994 Jun;149(6):1466-70.
Browne GJ, Penna AS, Phung X, Soo M. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children. Lancet. 1997 Feb 1;349(9048):301-5.
Browne GJ, Trieu L, Van Asperen P. Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department. Crit Care Med. 2002 Feb;30(2):448-53.
Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, Rowe BH, Smith BJ. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Review. 2012.