Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia

• Published in: The Journal of pediatrics Vol. 124; no. 5; pp. 772 - 781
• Main Authors: Kao, Lily C., Durand, David J., McCrea, Ray C., Birch, Martha, Powers, Richard J., Nickerson, Bruce G.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-05-1994; Elsevier
• Subjects: Analysis of Variance; Biological and medical sciences; Bronchopulmonary Dysplasia - drug therapy; Bronchopulmonary Dysplasia - physiopathology; Bronchopulmonary Dysplasia - therapy; Chlorothiazide - pharmacology; Chlorothiazide - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Furosemide - therapeutic use; Humans; Infant; Infant, Newborn; Medical sciences; Oxygen Inhalation Therapy; Pharmacology. Drug treatments; Prospective Studies; Respiratory Mechanics - drug effects; Respiratory system; Spironolactone - pharmacology; Spironolactone - therapeutic use; TGV; v̇maxFRC; FIO2; FRC; BPD; Cdyn; Raw; PFT; Human; Premature; Lung disease; Respiratory disease; Treatment efficiency; Long term; Diuretic; Oxygenotherapy; Newborn diseases; Chemotherapy; Randomization; Newborn; Treatment; Prematurity; Bronchus disease; Complication; Bronchopulmonary dysplasia; Respiratory distress; Combined treatment
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(05)81373-3

Study objective: To determine whether long-term oral diuretic therapy would improve the pulmonary function of preterm infants with bronchopulmonary dysplasia. Design: Randomized, double-blind, placebo-controlled study. Setting: Level III intensive care nursery. Intervention: We randomly selected 43 stable patients with oxygen-dependent bronchopulmonary dysplasia to receive either orally administered spironolactone and chlorothiazide or placebo. These drugs were continued until the patients no longer required supplemental oxygen. Both groups received furosemide as needed. Measurements and results: Each infant had pulmonary function tests at study entry, 4 weeks after study entry, 1 week and 8 weeks after being weaned to room air and off study drugs, and at 1 year of corrected age. Pulmonary function tests included dynamic pulmonary compliance, airway resistance, thoracic gas volume, and maximal expiratory flow at functional residual capacity; most of the infants had functional residual capacity measured. Between the first and second pulmonary function tests (while the infants were receiving diuretic or placebo), the infants in the diuretic group had a significant improvement in dynamic pulmonary compliance (46%; p <0.001) and airway resistance (31%; p <0.05); there were no changes in compliance or resistance in the placebo group. Although patients in both the diuretic and the placebo groups required progressively less supplemental oxygen, by 4 weeks after study entry the patients in the diuretic group needed less supplemental oxygen than did those in the placebo group (p <0.01). There were no significant differences in results of serial pulmonary function tests in either group after discontinuation of diuretic therapy. Despite the significant differences in pulmonary function between the two groups, there was no significant difference between them in the total number of days that supplemental oxygen was required. Significantly more infantsin the placebo group received more than 10 doses of furosemide on an as needed basis. Conclusions: Long-term diuretic therapy in stable infants with oxygen-dependent bronchopulmonary dyslasia, after extubation, improves their pulmonary function and decreases their fractional inspired oxygen requirement, but does not decrease the number of days that they require supplemental oxygen. The improvement in pulmonary function associated with diuretic therapy is not maintained after treatment is discontinued. (J PEDIATR 1994;124:772-81)