The effect of aerosolized furosemide in infants with chronic lung disease. Nebulized furosemide in infants with bronchopulmonary dysplasia. Pulmonary effect of inhaled furosemide in ventilated infants with severe bronchopulmonary dysplasia. Dose-dependent evaluation of the effects of nebulized furosemide on pulmonary function in ventilated preterm infants. Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants.
To investigate whether aerosolized furosemide would improve pulmonary function in premature infants with chronic lung disease, we enrolled eight preterm ventilator-dependent infants in a cross-over, double-blind, placebo-controlled trial. Either aerosolized furosemide (2 mg/kg) or placebo (0.9% saline) was administered, and serial pulmonary function tests were performed before and at 1 and 2 h after each inhalation. After furosemide inhalation, static respiratory compliance increased significantly by 24.3% and 23.2% as percentage change from the baseline value at 1 and 2 h (p = 0.014 and 0.022, respectively). Also, tidal volume increased significantly by 33.8% and 28.7% at 1 and 2 h, respectively (p = 0.004 and 0.009). In contrast, no changes were observed in them after placebo inhalation. Total respiratory resistance was unchanged after both furosemide and placebo inhalation. There were no differences in urine volume in two groups. These data suggested that aerosolized furosemide improved pulmonary function in infants with chronic lung disease without excessive diuresis. The effects of 0.1 mg, 0.25 mg, 0.50 mg, and 1.0 mg of nebulized furosemide per kilogram of body weight on pulmonary functions were studied in eight preterm infants with bronchopulmonary dysplasia who were supported by mechanical ventilation. Doses of 1 mg/kg significantly improved lung compliance (51% at 2 hours after nebulization), pulmonary resistance (28% at 1 hour), and tidal volume (43% at 1 hour), starting as early as 30 minutes after the dose; the effect lasted for at least 4 hours in many of the infants and was not associated with diuresis or renal side effects. When administered parenterally, furosemide, a loop diuretic, results in improved lung compliance and decreased airway resistance in infants with bronchopulmonary dysplasia (BPD). However, furosemide-induced diuresis results in hypokalemia, chloride deficiency, hypercalciuria, nephrocalcinosis, and rickets. In patients with asthma, inhaled furosemide has recently been demonstrated to inhibit the bronchoconstrictive effects of exercise, cold air hyperventilation, and antigen challenge. We hypothesized that inhaled furosemide will result in improved pulmonary mechanics in ventilated infants with BPD and will prevent the systemic complications of parenteral furosemide.
                To determine the efficacy and safety of a single dose of inhaled furosemide on pulmonary mechanics in infants with severe BPD who are ventilator dependent at 21 days of age.
                A randomized, double-blind, crossover study was performed on 9 infants with BPD, each serving as his own control. Each patient was randomized to receive an aerosol dose of furosemide (1 mg/kg in 2 mL of saline) or placebo (2 mL of saline) on the first day of the study and the other agent the following day of the study. Pulmonary mechanics were measured before and 1 and 2 hours after the inhalation using the Pulmonary Evaluation and Diagnostics System.
                Gestational age (mean +/- SEM) was 29 +/- 1 weeks; birth weight was 1.1 +/- 0.1 kg; age at study was 47 +/- 6 days; and weight at study was 1.8 +/- 0.2 kg. There was no significant change in the pulmonary function measurements before treatment and 1 or 2 hours after treatment with either placebo or furosemide. Baseline and 2-hour values were: dynamic compliance (mL/ cm H2O per kilogram): 0.46 +/- .03 to 0.50 +/- .03 (placebo) and 0.50 +/- 0.02 to 0.51 +/- 0.02 (furosemide); dynamic resistance (cm H2O/L per second): 118 +/- 9 to 106 +/- 7 (placebo) and 111 +/- 8 to 105 +/- 7 (furosemide); and tidal volume (mL/kg): 8.6 +/- 0.5 to 8.9 +/- 0.5 (placebo) and 8.9 +/- 0.2 to 9.4 +/- 0.3 (furosemide).
                We conclude that, under the conditions of our study, a single dose of 1 mg/kg inhaled furosemide does not improve the pulmonary mechanics in ventilator-dependent infants with severe BPD. We have previously shown that a single dose of nebulized furosemide improves tidal volume and pulmonary compliance for up to a 2-hour study period. This study is undertaken in order to find out (a) whether increasing the dose of nebulized furosemide from 1 to 2 mg/kg of body weight will further improve the pulmonary mechanics in premature infants with evolving chronic lung disease and (b) whether the effects of a single dose of nebulized furosemide last beyond 2 hours.
                The effect of nebulized furosemide on pulmonary mechanics was studied at a mean postnatal age of 24 days (range 14 to 50 days) in 13 premature infants, 24 to 28 weeks' gestational age, who had been dependent on mechanical ventilation since birth. Furosemide was administered by nebulization at doses of 1 and 2 mg/kg of body weight, in random order, on two separate days 24 hours apart. Pulmonary function studies were performed before and 2, 4, and 6 hours after the nebulization. Urine was collected for 6 hours immediately before and for 6 hours after the nebulization.
                Furosemide by nebulization at 1 and 2 mg/kg of body weight resulted in significant improvement in tidal volume and compliance. There was no difference in the magnitude of response between the two doses. Neither 1 nor 2 mg/kg of body weight of nebulized furosemide had any effect on airway resistance. The improvement was maximum for up to 4 hours and lasted for up to 6 hours after the nebulization and was not associated with diuresis or increased excretion of urinary electrolytes.
                A single dose of nebulized furosemide improves pulmonary function for up to 6 hours after its administration. Increasing the dose from 1 to 2 mg/kg of body weight results in no further improvement in the pulmonary function. The pulmonary effects of nebulized furosemide are independent of its diuretic action. To compare the effects of a single dose of frusemide administered either intravenously or by nebulisation on pulmonary mechanics in premature infants with evolving chronic lung disease.
                The effect of frusemide on pulmonary mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19 premature infants at 24 to 30 weeks gestational age, who had been dependent on mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was administered, in random order, intravenously and by nebulisation, on two separate occasions 24 hours apart. Pulmonary function studies were performed before and at 30, 60, and 120 minutes after administration of frusemide. Urine was collected for six hours immediately before and for six hours after administration of frusemide.
                Nebulised frusemide increased the tidal volume 31 (SE 11.5)% and compliance 34 (SE 12)% after two hours, whereas no change in either was noted for up to two hours after intravenous frusemide administration. Neither intravenous nor nebulised frusemide had any effect on airway resistance. Six hour urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8) ml/kg/hour following intravenous frusemide administration while nebulised frusemide had no effect on urine output. Urinary sodium, potassium, and chloride losses were also significantly higher after intravenous frusemide, whereas nebulised frusemide did not increase urinary electrolyte losses.
                Single dose nebulised frusemide improves pulmonary function in premature infants with evolving chronic lung disease without adverse effects on fluid and electrolyte balance.