BACKGROUND The optimal method of delivering bronchodilators in mechanically ventilated patients is unclear. The purpose of this study was to compare the pulmonary bioavailability of albuterol delivered by the nebulizer, the metered-dose inhaler (MDI) and spacer, and the right-angle MDI adaptor in ventilated patients using urinary analysis of drug levels. METHODS Mechanically ventilated patients who had not received a bronchodilator in the previous 48 h and who had normal renal function were randomized to receive the following: (1) five puffs (450 microg) of albuterol delivered by the MDI with a small volume spacer; (2) five puffs of albuterol delivered by the MDI port on a right-angle adaptor; or (3) 2.5 mg albuterol delivered by a nebulizer. Urine was collected 6 h after the administration of the drug, and the amounts of albuterol and its sulfate conjugate were determined in the urine by a chromatographic assay. RESULTS Thirty patients were studied, 10 in each group: their mean age and serum creatinine level were 62 years and 1.3 mg/dL, respectively. With the MDI and spacer, (mean +/- SD) 169+/-129 microg albuterol (38%) was recovered in the urine; with the nebulizer, 409+/-515 microg albuterol (16%) was recovered in the urine; and with the MDI port on the right-angle adaptor, 41+/-61 microg albuterol (9%) was recovered in the urine (p = 0.02 between groups). The level of albuterol in the urine was below the level of detection in four patients in whom the drug was delivered using the right-angle MDI adaptor. CONCLUSIONS The three delivery systems varied markedly in their efficiency of drug delivery to the lung. As previous studies have confirmed, this study has demonstrated that using an MDI and spacer is an efficient method for delivering inhaled bronchodilators to the lung. The pulmonary bioavailability was poor with the right-angle MDI port. This port should not be used to deliver bronchodilators in mechanically ventilated patients.