Bronchodilator Response to Ipratropium Bromide in Infants with Bronchopulmonary Dysplasia

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Abstract
Although the muscarinic antagonist ipratropium bromide is used clinically as a bronchodilator in infants ventilated because of bronchopulmonary dysplasia (BPD), no studies have compared the response or efficacy of different dosages or its effectiveness in combination with .beta.-adrenergic agonists. We measured the response of respiratory system mechanics in 10 ventilated infants (25 .+-. 2 days of age) to 75, 125, and 175 .mu.g ipratropium bromide (IB), 125 .mu.g IB plus 0.04 mg salbutamol (SAL), 175 .mu.g IB plus 0.04 mg SAL, and saline vehicle, delivered via nebulizer into the ventilator circuit. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive flow-volume technique. Rrs and Crs were measured before and at 1 to 2 h and at 4 h after delivery of the five drug dosages or saline. All six studies were completed within a 72-h period. Saline had no significant effect on mechanics. Significant responses to ipratropium alone were seen only after 175 .mu.g where Rrs decreased 20 .+-. 3% (SEM) (p < 0.05) at 1 to 2 h and 16 .+-. 5% (p < 0.05) at 4 h. After 125 .mu.g IB + SAL and 175 .mu.g IB + SAL, Rrs was significantly decreased both at 1 to 2 h and at 4 h, and Crs was significantly increased 20 .+-. 6% and 20 .+-. 4%, respectively, at 1 to 2 h. The greatest decrease in Rrs (26 .+-. 6%) was seen 1 to 2 h after 175 .mu.g IB + salbutamol. We conclude that muscarinic receptors contribute to the increased bronchomotor tone of infants with BPD and that a combined dose of 175 .mu.g IB and SAL should be used with this delivery system to ensure that the most effective and long-lasting bronchodilation is obtained in the majority of premature infants.