Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia. Comparison of 6-hour infusion versus bolus furosemide in premature infants. Furosemide acutely decreases airways resistance in chronic bronchopulmonary dysplasia. Controlled trial of furosemide therapy in infants with chronic lung disease. Pulmonary effects of furosemide in preterm infants with lung disease.
To test the hypothesis that alternate-day administration of furosemide will result in a sustained improvement in pulmonary function without causing alterations in electrolyte or mineral homeostasis, we conducted a randomized, double-blind, placebo-controlled study of 11 hospitalized, oxygen-dependent, spontaneously breathing infants with chronic bronchopulmonary dysplasia. Infants were randomly selected to receive either furosemide, 4 mg/kg in two divided doses on alternate days orally, or placebo for 8 days, followed by crossover to the alternate-therapy for an additional 8-day period. The two study periods were separated by a 48-hour washout period. Dynamic compliance, total pulmonary resistance, the concentration of electrolytes in serum, and the concentrations of calcium and creatinine in urine were measured on nontreatment days. Alternate-day furosemide therapy increased dynamic lung compliance by 76 +/- 112% and decreased total pulmonary resistance by 20 +/- 39%, compared with placebo (both variables p = 0.032). Alternate-day furosemide therapy did not result in increased urine output, electrolyte abnormalities, or increased urinary calcium excretion. We conclude that this simplified treatment regimen may be useful in the management of infants with chronic bronchopulmonary dysplasia. The results support our previous speculation that furosemide improves pulmonary function by mechanisms unrelated to its diuretic properties. To compare the renal, hemodynamic, and pulmonary effects of a 6-hour infusion of furosemide versus conventional bolus administration in premature infants.
                Prospective, blinded, placebo-controlled, randomized study.
                Two level III, university-based neonatal intensive care units.
                Thirty premature infants with significant lung disease, requiring furosemide after a red cell infusion.
                Infants received furosemide 1 mg/kg over 2 minutes, followed by a 6-hour placebo infusion, or a small loading dose of 0.1 mg/kg, followed by a slow infusion of 0.9 mg/kg over 6 hours. Serum and urine were collected to determine percentage fractional excretion of sodium (FENa).
                Urine output and blood pressure were measured every 2 hours after furosemide administration. Percentage FENa was measured immediately before furosemide and compared with pooled urine from an 8-hour collection after furosemide administration. Serum sodium, creatinine, and calcium were measured before and 24 hours after drug administration. Mean airway pressure and percentage inspired oxygen were compared before, 1-4 hours after, and 4-12 hours after drug administration. No significant differences were detected between the two methods of drug administration.
                Our data suggest that a 6-hour infusion of furosemide does not offer substantial clinical advantage over conventional bolus administration in premature infants when focusing on urine output, blood pressure, FENa, or pulmonary effect. We studied the effects of furosemide on pulmonary mechanics in 10 infants with bronchopulmonary dysplasia aged 41 +/- 1 (SE) weeks post-conception, gestational age at birth 30 +/- 1 wk, birth weight 1370 +/- 200 gm. Thoracic gas volume, airways resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured using an esophageal balloon. Infants with BPD had greater Raw, lower SGaw, and lower Cdyn than did 16 normal control infants. Within one hour after administration of furosemide 1 mg/kg IV to infants with BPD, Raw fell 36 +/- 13%, SGaw increased 84 +/- 22%, and Cdyn increased 54 +/- 13%; TGV did not change. Diuretic treatment of BPD in infants is associated with rapid, short-term improvement in Raw and Cdyn. To study the effects of furosemide therapy in infants with chronic lung disease (CLD), a double-blind controlled trial was designed. Seventeen infants with evidence of CLD (oxygen requirements greater than 30% at greater than 3 weeks of age and chest radiographic findings consistent with CLD) were studied. Pulmonary function was measured immediately before, and after 48 hours and 7 days of treatment with furosemide (1 mg/kg/12 hr intravenously or 2 mg/kg/12 hr orally) or placebo. Clinical status improved in six of seven infants who received furosemide and in two of 10 infants who received placebo (P less than 0.002). In the furosemide group, ventilator and oxygen requirements decreased (P less than 0.003); minute ventilation, alveolar ventilation, and dynamic compliance increased; and venous admixture decreased (P less than 0.05). There were no significant changes in the placebo group. Our findings suggest that furosemide significantly improves lung function during therapy in infants with CLD and allows earlier weaning from ventilatory support and supplemental oxygen. Twenty preterm infants recovering from respiratory distress syndrome at 1 week of age were randomized in this study either to a control or a treatment group. Those treated received a single daily dose of furosemide (1 mg/kg) intravenously. Pulmonary compliance was observed to improve significantly at two hours in the treated group, as compared with that in the controls. The calculated alveolar-arterial oxygen gradient was noted to decrease two hours after furosemide and to remain decreased over the four-day period in the treated group. This improvement in lung function was not secondary to diuresis in the infants treated with furosemide. We conclude that furosemide may have a direct pulmonary effect and improve lung function acutely as well as with chronic administration.
In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of systemic loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence.
Randomized trials are needed to assess the effects of furosemide administration on survival, duration of ventilatory support and oxygen administration, length of hospital stay, potential complications and long-term outcome.