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Three Part Question

In [patients presenting with an acute exacerbation of COPD] is nebulisation of [a beta 2 agonist alone, ipratropium bromide alone or a combination of the two] more effective at [controlling and improving symptoms]?

Clinical Scenario

A 59 year old man presents with an exacerbation of COPD. You wonder whether it is better to nebulise salbutamol or ipratropium bromide alone, or a combination of the two.

Search Strategy

Medline 1966-11/00 using the OVID interface.
{{[(exp chronic disease OR exp hospitals, chronic disease OR chronic.mp) AND (exp lung disease, obstructive OR obstructive.mp)] OR exp emphysema OR exp pulmonary emphysema OR emphysema.mp OR exp bronchitis OR bronchitis.mp OR exp COPD.mp OR COAD.mp OR airway obstruction.mp)} AND (acute.mp or exacerbation.mp)} AND (exp ipratropium OR ipratropium bromide.mp OR atrovent.mp OR antimuscarinic.mp OR exp. muscarinic antagonist OR exp brochodilators agents OR bronchodilators.mp OR exp albuterol OR salbutamol.mp OR beta 2 agonist.mp OR exp terbutaline) AND (exp nebulisers OR vaporises.mp OR exp respiratory therapy OR nebulisers.mp) NOT (exp child OR children.mp OR exp paediatrics OR paediatric.mp) LIMIT to human AND english.

Search Outcome

162 papers found of which 157 were irrelevant or of insufficient quality. The remaining 5 papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Rebuck AS et al, 1987, Canada	51 patients with an acute exacerbation of COPD (148 asthmatics also recruited) Ipratropium vs fenoterol vs both (all nebulised).	PRCT	FVC, FEV1, MMEFR, PEFR, cardiovascular markers at 45 min	No significant difference	No sample size calculation. Small groups in each of the treatment arms, thus small differences may go undetected.
			FVC, FEV1, MMEFR, PEFR, cardiovascular markers at 90 min	No significant difference
O'Driscoll BR et al, 1989, UK	47 patients with COPD (an asthmatic group also recruited) Salbutamol vs salbutamol plus ipratropium bromide	PRCT	PEFR on arrival and at one hour	No difference in improvement (P>0.55)	No sample size calculation, small groups in each treatment arm, thus important effects can be overlooked. No defined inclusion or exclusion criteria. 20 patients admitted, excluded from study. No actual figures given.
Shrestha M et al, 1991, USA	55 COPD patients with an acute exacerbation (FEV1 <40% of predicted) Isoetharine plus placebo vs isoetharine plus ipratropium bromide (inhaled)	PRCT	Times to discharge from ED.	Time to discharge 91 minutes less in the salbutamol plus ipratropium group (P<0.05)	No sample size calculation. Small numbers. Inhaled therapy
			FVC, FEV1	No difference
Moayyedi P et al, 1995, UK	62 COPD patients with an acute exacerbation Salbutamol vs salbutamol plus ipratropium bromide (nebulised)	PRCT	Length of hospital stay	No significant difference	Power study retrospectively completed.
			Duration of nebuliser therapy	No significant difference
			FVC, FEV1	No significant difference
			Subjective improvement on days 1, 3, 7 and 14.	No significant difference
Koutsogiannis Z and Kelly A-M, 2000, Australia	?patients presenting to ED with an acute exacerbation of COPD. All patients started with salbutamol and ipratropium nebulisers and then salbutamol vs ipratropium vs salbutamol plus ipratropium.	PRCT	Absolute and percentage change in FEV1 at 90 min	No difference between the 2 groups. P=0.36 for absolute change, P=0.56 for % change)	No patient numbers given. No sample size calculation. Groups are small thus any differences may be overlooked. All patients had both drugs initially.

Comment(s)

There are 5 randomised trials that address the three-part question. All of the studies are of reasonable quality.

Clinical Bottom Line

Initial therapy can be either salbutamol or ipratropium nebulisers alone. There is no evidence to suggest that using both has additional benefit.

References

1. Rebuck AS, Chapman KR, Abboud R et al. Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Am J Med 1987;82:59-64.
2. O'Driscoll BR, Taylor RJ, Horsley MG et al. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet 1989;1:1418-20.
3. Shrestha M, O'Brien T, Haddox R et al Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to beta-agonist therapy. Ann Emerg Med 1991;20:1206-9.
4. Moayyedi P, Congleton J, Page RL et al. Comparison of nebulised salbutamol and ipratropium bromide with salbutamol alone in the treatment of chronic obstructive pulmonary disease Thorax 1995;50:834-7.
5. Koutsogiannis Z, Kelly AM. Does high dose ipratropium bromide added to salbutamol improve pulmonary function for patients with chronic obstructive airways disease in the emergency department? Aus New Zealand Med J 2000;30:38-40.