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Rodrigo et al. A Meta-analysis of the Effects of Ipratropium Bromide in Adults with Acute Asthma. American Journal of Medicine. 1999;107:363–370
Stoodley. The Role of Ipratropium Bromide in the Emergency Management of Acute Asthma Exacerbation: A Metaanalysis of Randomized Clinical Trials. Annals of Emergency Medicine. 1999; 34(1) 8-18.
Rodrigo GJ, Rodrigo C. First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department. American Journal of Respiratory and Critical Care Medicine 2000; 161:1862-8.
Cydulka. RK et al. Levalbuterol versus levaalbuterol plus ipatropium in the treatment of severe acute asthma. Journal of Asthma. 2010 Dec; 47(10):1094-100.
Salo, D. A randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma. Journal of Emergency Medicine. 2006 Nov; 31(4):371-6.

Efficacy Endpoints

Need for hospitalization

Harm Endpoints

Medication side effects

Narrative

Acute asthma exacerbation is responsible for an estimated 1.6 million emergency department visits and over 440,000 hospital admissions per year1. The cornerstone of management remains aerosolized, short acting, β2-agonists and systemic corticosteroids2. Anticholinergic agents such as ipratropium bromide, are effective bronchodilators, but comparative studies suggest that they are not as effective as β2-agonists3. The studies reviewed here examined whether adding ipratropium reduced hospitalizations for adults with acute asthma exacerbation.

The review included seven randomized trials of almost 1500 subjects comparing the addition of ipratropium or the addition of placebo to β2-agonists therapy (albuterol, levalbuterol, or salmeterol). There may be a small benefit to adding ipratropium with a decrease in hospital admissions by ~9% (range 1%-39%). This means that for every 11.5 patients treated with combination therapy, there will be one less hospitalization admission. There was no increased incidence of adverse events reported.

Caveats

These data should be interpreted with caution as most studies did not specifically study hospitalization as their primary outcome. In fact, many recorded hospitalization but did not report this as a study outcome, focusing instead on surrogate markers of lung function (FEV1 or PEF). Admission decisions were often made after additional treatment, separate from the study protocol, at the discretion of the treating physician.4 5 6 7 8 9. Furthermore, there was significant clinical heterogeneity in these trials: β2-agonists and ipratropium doses varied, and use of systemic corticosteroids was not standardized.

Lastly, though hospitalization is a patient-oriented outcome, it is rarely based on a priori criteria10. Admission rates varied from 8.4-30%, which may be due to setting, patient, or physician characteristics. Therefore these data should be considered hypothesis generating rather than conclusive. However, national guidelines recommend the use of ipratropium in the management of acute asthma10, specifically to reduce hospital admissions. While this seems a reasonable ‘best guess’ based on the available evidence, we feel it is important to emphasize the somewhat conjectural nature of recommendations based on this evidence. Since ipratropium is relatively inexpensive, safe, and does suggest a benefit in a patient oriented outcome, it is a reasonable adjunct therapy in the treatment of an acute asthma exacerbation.

Author

Koustav Mukherjee, MD

Published/Updated

January 30, 2012