Does High-Dose Continuous Albuterol Therapy Improve Outcome in the ED?

Abstract & Commentary

Source: Stein J, et al. A randomized, controlled double-blind trial of usual-dose versus high-dose albuterol via continuous nebulization in patients with acute bronchospasm. Acad Emerg Med 2003;10:31-36.

This randomized, double-blinded trial compared the efficacy of albuterol delivered by continuous nebulization at 7.5 mg/hr (usual-dose therapy) and 15 mg/hr (high-dose therapy). Adult patients were eligible for enrollment if they presented to the emergency department (ED) complaining of acute bronchospasm and had peak expiratory flow rates less than 75% of predicted values. All participants received prednisone 60 mg (or methylprednisolone 125 mg IV) and nebulized ipratropium bromide at 1 mg/hr. Nebulized albuterol was delivered continuously until the symptoms resolved, the patient was intubated, or three hours elapsed, whichever came first. The primary outcome variable was change in peak flow rate over time.

One hundred-eighteen patients were included in the analysis. Baseline characteristics of the usual-dose and high-dose groups were comparable. The mean improvement in one-hour peak flow in the usual-dose group was 51 L/min, which did not differ significantly from the 45 L/min change in the high-dose group. Rates of hospitalization were similar in the two groups (71% and 65%, respectively), as were dyspnea scores, patient satisfaction scores, and time to disposition. Vital sign changes and rates of adverse events were similarly without statistical difference. The authors conclude that ED patients with moderately severe bronchospasm do not significantly benefit from high-dose continuous albuterol therapy.

Commentary by David J. Karras, MD

Trials of asthma therapy in ED patients often find no intergroup differences unless the study is restricted to more severely ill patients. Prior investigations studying continuous vs. intermittent beta-agonist therapy, anticholinergic inhalers, and magnesium have typically found no difference in outcomes unless the study (or subgroup analysis) looked specifically at patients with severe asthma exacerbations. A reasonable conclusion is that it is difficult to significantly improve outcomes by fine-tuning therapy in patients with mild or moderately severe asthma. Patients with severe disease exacerbations are more likely to benefit from more intense medical therapy, but unfortunately, practical considerations make this group very difficult to study.

This study is unusually nonselective in including all ED patients with acute bronchospastic exacerbations—enrollment criteria that invariably included patients with chronic obstructive lung disease as well as those with asthma. These diseases differ in their responsiveness to bronchodilators and other therapies. Failure to detect a benefit to high-dose beta-agonist therapy may be attributable to heterogeneity of the study group. The authors did not attempt to perform a separate analysis of patients with a history of asthma, or of those with more severe bronchospasm. The 70% hospitalization rate is strikingly high and further suggests that this was not a group comprised primarily of patients with asthma.

Dr. Karras, Associate Professor of Emergency Medicine, Department of Emergency Medicine Temple University School of Medicine, Director of Emergency Medicine Research, Temple University Hospital, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.