High-dose Inhaled Albuterol in Severe Chronic Airflow Limitation

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Abstract
Higher doses of inhaled aibuterol have been shown to cause slightly more bronchodilatation than standard doses from a metered-dose inhaler in patients with severe chronic airflow limitation. Higher doses, however, carry an increased risk of side effects, and the optimum dose balancing benefit and adverse effects have yet to be established. We have therefore looked at objective and subjective evidence of beneficial and adverse effects after 4 doses of albuterol in 30 patients with chronic bronchitis, severe airflow limitation, and less than 200 ml increase in FEV, after 200 .mu.g inhaled albuterol. Subjects were given placebo, 400 .mu.g, 1 mg, 2 mg, and 4 mg albuterol by dry powder inhaler in random order on separate days in a double-blind study, and FEV1, relaxed VC, PEFR, 12-min walk distance, finger tremor, oxygen saturation, heart rate, and arrhythmias were measured at intervals over 6 h. With increasing doses of albuterol, there was a significant dose-related increase in FEV1, VC, and PEFR, the maximal mean changes being 196 ml, 480 ml, and 50 L/min, respectively. The duration of effect was longer with the higher doses. There was a dose-related increase in heart rate, tremor amplitude, and supraventricular ectopic beats and a dose-related fall in oxygen saturation. There was no drug-related effect on the frequency of ventricular ectopic beats either at rest or during the walk tests. The largest increase in walk distance occurred after the 1 and 2 mg doses and the least after the 4 mg dose. VAS scores were highest for subjective benefit after the 1 mg dose and for side effects after the 4 mg dose. Thus, in this single-dose study, 1 mg albuterol appeared to offer the best balance between beneficial and adverse effects.