Acute asthma

Asthma management is not cut-and-dried – there is a huge variation in treatments and doses. Babl 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 the lovely podcasts by Andy Neill (Emergency Medicine Ireland), Scott Weingart (EMCrit), and Colin Parker (EMPEM). This post (Part I) focuses on the medical management of asthma, and Part II is on ventilation strategies.

Inhaled medications

Inhaled salbutamol

We are familiar with inhaled or nebulised salbutamol and know that it stimulates beta receptors to give bronchodilation. The thinking is that continuous nebulisation is optimal for inhaled treatment, as intermittent nebs can cause rebound bronchoconstriction.

Use it.

Inhaled ipratropium bromide

This is an anticholinergic and is often given inhaled along with salbutamol.

In 2005, Rodrigo reviewed children treated with salbutamol and ipratropium bromide (1800 children across 10 studies). They found significantly lower admission rates for those treated with ipratropium bromide (NNT 13).

In 2006, Munro looked at acute childhood asthma treated with salbutamol and ipratropium bromide. The study showed reduced time to recovery and discharge, and lower admission rates, in the moderate-to-severe groups. However, a Cochrane review showed only mild benefits.

It’s unclear whether ipratropium is fabulous or how long to give it. In the ICU, we do not give it because its anticholinergic effect dries up secretions, causing plugging and ventilation problems.

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.

Intravenous medications

IV magnesium sulphate

Magnesium sulphate is a smooth muscle relaxant, but its exact mechanism of action is unknown.

A 2009 Cochrane review (660 patients, a mix of kids and adults) concluded that magnesium should not be used routinely but can help with more severe exacerbations. In 2008, Rowe demonstrated that a single dose of IV magnesium effectively reduces hospitalisation rates.

BestBet asked the question (2004): Does IV magnesium sulphate in status asthmaticus reduce admission rates? Three of four 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 so severe as 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 the ED to help stave off an ICU admission—it is a relatively safe drug.

Aminophylline

Aminophylline is from the dark ages, but people still use it (it’s a phosphodiesterase inhibitor). Be careful, though, because, unlike magnesium sulphate, it can cause adverse effects.

A 2012 Cochrane review in adults (817 patients across 15 studies) found no significant bronchodilator effect when added to salbutamol. But worse than that, for every 100 treated, 20 had vomiting, and 15 had arrhythmias or palpitations.

In 2009, Mitra conducted a Cochrane review in children. This was in children with severe asthma and looked at IV aminophylline + nebulised beta agonists +/—steroids (380 children across seven 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.

IV salbutamol

Some people hate this stuff because of its systemic side effects. It increases oxygen consumption and the acid load on top of a pre-existing respiratory acidosis. If you expect your patient to improve, yet they seem to be worsening, consider IV salbutamol as the cause.

There have been a few papers examining this, with varying results.

Lawford (1978) showed no difference in recovery rates between nebulised and IV salbutamol, but IV salbutamol was associated with worse side effects. A 2012 Cochrane review (100 adult patients across three studies) seems to support this by concluding that there was no significant benefit to using IV salbutamol.

At the Children’s Hospital at Westmead (Sydney), Gary Browne has published 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 recovery time (off 30 30-minute nebs) and less need for oxygen supplementation. A further study by him in 2002 (55 children) showed reduced recovery time, lower oxygen use at 12 hours, and earlier discharge from hospital (>1 day).

References

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.

Lawford P, Milledge JS. Intravenous versus inhaled salbutamol. Lancet. 1978;1(8058):269.

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.

Markovitz B. Does magnesium sulphate have a role in the management of paediatric status asthmaticus? BestBets. 2004.

Mitra AAD, Bassler D, Watts K, Lasserson TJ, Ducharme FM. Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators. Cochrane Review. 2009.

Munro A, Maconochie I. Best evidence topic reports. Beta-agonists with or without anti-cholinergics in the treatment of acute childhood asthma? Emerg Med J. 2006;23(6):470.

Nair P, Milan SJ, Rowe BH. Does an aminophylline injection in addition to bronchodilators for an asthma attack improve lung function and other outcomes or cause harm? Cochrane Review. 2012.

Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005;60(9):740-6.

Rowe BH, Bretzlaff J, Bourdon C, Bota G, Blitz S, Camargo CA. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Review. 2009.

Rowe BH, Camargo CA Jr. The role of magnesium sulfate in the acute and chronic management of asthma. Curr Opin Pulm Med. 2008 Jan;14(1):70-6.

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.

Stather DR, Stewart TE. Clinical review: Mechanical ventilation in severe asthma. Critical Care 2005;9:581-587.