X2.2.1 Inhaled bronchodilators for treatment of exacerbations

Inhaled bronchodilators are effective for initial treatment of exacerbations [evidence level I, strong recommendation]

In exacerbations of COPD, the immediate bronchodilator effect is small, but may result in significant improvement in clinical symptoms in patients with severe obstruction.

Studies of acute airflow limitation in asthma indicate that beta-agonists are as effectively delivered by metered dose inhaler and spacer as by nebuliser (Cates 2006) [evidence level I]. The applicability of this evidence to patients with COPD is unknown. There is evidence in patients with a COPD exacerbation that a dry powder inhaler delivering formoterol is as effective in improving lung function as a metered dose inhaler delivering salbutamol, with or without a spacer device (Selroos 2009) [evidence level II]. An adequate dose should be used. The dose equivalent to 5 mg of salbutamol delivered by nebuliser is 8–10 puffs of 100mcg salbutamol by metered dose inhaler and spacer. Limited evidence indicates dry powder inhalers are as effective as other delivery devices for the administration of short-acting bronchodilators in the setting of exacerbations of COPD (Selroos 2009) [evidence level II]. Airflow in the nebuliser should be 6 L per minute or higher to achieve an appropriate aerosol, but using high- flow oxygen should be avoided as this may worsen carbon dioxide retention (Bardlsey 2018). High doses of beta-agonists may induce hypokalaemia and predispose to cardiac arrhythmias.

People with COPD often have cardiac co-morbidities, although these may be undiagnosed at the time of presentation with a COPD exacerbation. Such patients may be susceptible to adverse events from high dose, frequent short acting beta agonists. A review by Kopsaftis (Kopsaftis 2018b) identified 10 relevant randomised or controlled trials and demonstrated that higher (5mg versus 2.5mg) doses of salbutamol were associated with increased risk of tremors, elevated heart rate, palpitations and lower blood pressure, but without evidence of any additional benefit.  Given that elevated cardiac stress markers during COPD exacerbations are predictive of 30 day mortality (Chang 2011), the review authors recommend caution in prescribing frequent high doses of short-acting beta agonists, such as doses of salbutamol exceeding 2.5mg, when treating exacerbations of COPD [evidence level I].

A small (n=30) single centre pilot randomised controlled trial performed in New Zealand (Mukerji 2015) [evidence level II] showed that 2g IV magnesium when added to standard bronchodilator therapy in an exacerbation of COPD significantly improved FEV1 at 120 mins (mean percentage change in FEV1 was 27.07% with magnesium versus 11.39% in the placebo group, 95% CI 3.7 to 27.7, p=0.01). Asthma was excluded on clinical grounds on review of past spirometry. Larger trials with meaningful clinical endpoints are required before this can be recommended as standard therapy.