Successful bronchodilator therapy with a metered-dose inhaler (MDI) in intubated, mechanically ventilated patients requires adequate delivery of aerosol to the lower respiratory tract. We determined the effect of ventilator mode, inspiratory flow pattern, humidity, and spontaneous respiratory effort on albuterol delivery in a model of the trachea and bronchi. The model was ventilated through an endotracheal tube during controlled mechanical ventilation (CMV), assist control (AC), pressure support (PS), and continuous positive airway pressure (CPAP), separately with a dry and humidified ventilator circuit. Delivery of albuterol administered by a MDI and spacer on filter placed at the ends of the bronchi was measured by spectrophotometry (246 nm). Under dry conditions and with a frequency of 10 breaths/min, albuterol delivery with CMV (VT, 800 ml; 30.3 +/- 3.4%), AC (VT, 800 ml; 31.9 +/- 1.3%), PS 10 cm H2O (VT, 700 ml; 28.8 +/- 4.5%), or PS 20 cm H2O (VT, 800 ml; 30.9 +/- 1.8%) was lower than that observed with simulated spontaneous breaths with CPAP (VT, 800 ml; 39.2 +/- 1.4%) (p < 0.01 for all modes). Delivery was greater under dry (28.8 to 39%) than under humidified conditions (15.9 to 20.2%) (p < 0.005 in all modes). Albuterol delivery showed a linear correlation with both inspiratory time and duty cycle (r > 0.91). Lower respiratory tract delivery of aerosol from a MDI varied from 4.9 to 39.2%. We conclude that in addition to other known factors such as dose, type of spacer, and its position the technique of administering MDIs in mechanically ventilated patients markedly influences lower respiratory tract aerosol delivery.

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In nonintubated patients, metered-dose inhalers (MDIs) are accepted as the most convenient, efficient, and cost effective method of administering inhaled bronchodilators. Recent studies have demonstrated the efficacy of MDIs in ventilator-supported patients; however, the optimal dose of a bronchodilator from a MDI is unknown. We determined the response to increasing doses of albuterol administered by a MDI and cylindrical spacer to 12 mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). Four, eight, and 16 puffs of albuterol were given at 15-min intervals. Rapid airway occlusion were performed before and at 5-min intervals after albuterol for 80 min. Respiratory mechanics were also measured for 60 min in another group of seven patients with COPD who received four puffs of albuterol. Significant decrease in airways resistance occurred after administration of albuterol (p < 0.001). The decrease in airway resistance with four puffs of albuterol was comparable to that observed with cumulative doses of 12 puffs (p = 0.12) and 28 puffs (p = 0.25). Heart rate increased significantly (p < 0.01) after a cumulative dose of 28 puffs. The decrease in airway resistance was sustained for 60 min in the group that received only four puffs of albuterol (p < 0.003). In conclusion, four puffs of albuterol given by a MDI and spacer provided the best combination of bronchodilator effect and safety in stable mechanically ventilated patients with COPD.

Using high‐pressure liquid chromatography, we have quantitated the theophylline metabolites in the 24‐hr urines of 15 patients in a clinical ward who had been receiving 800 or 1,200 mg of aminophylline /24 hr in divided oral doses. Mean values for the theophylline‐derived urine products were as follows: unchanged theophylline, 7.7 ± 6.1%; 3‐methylxanthine, 36.2 ± 7.3%; 1,3‐dimethyluric acid, 39.6 ± 4.5%; and 1‐methyluric acid, 16.5 ± 3.3%. These data are consistent with those earlier reported for theophylline metabolism in man with other methodology. The fractional contents of urine products were variably related to trough serum theophylline levels, the latter determined by the Schack and Waxler method. There was a significant direct correlation between serum theophylline levels and the urine theophylline fraction, and a significant inverse correlation between serum theophylline and the urine 3‐methylxanthine fraction. Urinary 3‐methylxanthine and 1,3‐dimethyluric acid were inversely related, implicating competition for substrate. The urine content of 1,3‐dimethyluric acid and 1‐methyluric acid diverged as serum theophylline increased, suggesting that the former may give rise to the latter by a rate‐limiting demethylation reaction. The data suggest that the 1‐demethylation of theophylline to 3‐methylxanthine is the dominant reaction determining serum theophylline.