RESUMO
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 include 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 dysplasia, 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.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Clorotiazida/uso terapêutico , Espironolactona/uso terapêutico , Análise de Variância , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Clorotiazida/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Furosemida/uso terapêutico , Humanos , Lactente , Recém-Nascido , Oxigenoterapia , Estudos Prospectivos , Mecânica Respiratória/efeitos dos fármacos , Espironolactona/farmacologiaRESUMO
To determine whether the high oxygen consumption VO2 in infants with bronchopulmonary dysplasia (BPD) is caused by increased mechanical power of breathing, and if improvement of pulmonary mechanics would reduce mechanical power of breathing and VO2 we gave 16 infants with oxygen-dependent BPD at 19.5 +/- 10.7 (mean +/- SD) weeks of age placebo, theophylline, and orally administered diuretics or theophylline plus diuretics. Pulmonary mechanics, mechanical power of breathing, and VO2 were measured at the beginning and end of each study period. In the placebo group, all infants had elevated VO2 (7.4 +/- 1.4 mL/kg/min) and carbon dioxide production (6.6 +/- 1.2 mL/kg/min), increased airway resistance (59 +/- 30 cm H2O/L/sec), decreased dynamic compliance (0.073 +/- 0.024 mL/cm H2O/cm), increase respiratory rate (52 +/- 11), and increased mechanical power of breathing (2.22 +/- 1.05 kg.cm/kg/min). Treatment with theophylline, diuretics, and theophylline plus diuretics resulted in a significant improvement in pulmonary mechanics and mechanical power of breathing, but not in VO2. These results suggest that the increased VO2 in infants with BPD is not secondary to increased mechanical power of breathing.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Consumo de Oxigênio/efeitos dos fármacos , Teofilina/farmacologia , Displasia Broncopulmonar/fisiopatologia , Diuréticos/farmacologia , Método Duplo-Cego , Humanos , Recém-Nascido , Testes de Função RespiratóriaRESUMO
We studied the effects of orally administered theophylline and diuretics (chlorothiazide and spironolactone) on pulmonary mechanics in 16 infants with bronchopulmonary dysplasia. Their gestational age (mean +/- SD) was 28.5 +/- 3.4 weeks, and postnatal age at the time of study 19.5 +/- 10.7 weeks. The infants were randomized to two groups. Group 1 received successively placebo, theophylline, and theophylline plus diuretics; Group 2 received theophylline, placebo, and placebo plus diuretics on successive 4-day periods. Pulmonary function was measured before beginning the study (baseline) and at the end of each 4-day period. No significant changes in pulmonary function were noted after treatment with placebo. After treatment with theophylline, dynamic compliance (Cdyn) increased from baseline (mean +/- SD) 0.075 +/- 0.017 to 0.091 +/- 0.028 mL/cm H2O/cm (P less than 0.01), airway resistance (Raw) decreased from 67.19 +/- 36.71 to 41.44 +/- 22.50 cm H2O/L/sec (P less than 0.001), maximal expiratory flow at functional residual capacity (VmaxFRC) increased from 0.261 +/- 0.240 to 0.357 +/- 0.299 thoracic gas volume (TGV)/sec (P less than 0.01), and time constant decreased from 0.312 +/- 0.224 to 0.275 +/- 0.247 sec (P less than 0.02). After treatment with combined placebo and diuretics, Cdyn increased to 0.103 +/- 0.023 mL/cm H2O/cm (P less than 0.05), Raw decreased to 31.76 +/- 24.90 cm H2O/L/sec (P less than 0.001), VmaxFRC increased to 0.638 +/- 0.595 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.141 sec (P less than 0.05). After treatment with combined theophylline and diuretics, Cdyn increased to 0.118 +/- 0.017 mL/cm H2O/cm (P less than 0.001), Raw decreased to 35.98 +/- 25.85 cm H2O/L/sec (P less than 0.02), VmaxFRC increased to 0.479 +/- 0.377 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.137 sec (P less than 0.01). We conclude that theophylline and diuretics have additive effects on the improvement of pulmonary function in infants with bronchopulmonary dysplasia.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Clorotiazida/uso terapêutico , Pulmão/efeitos dos fármacos , Espironolactona/uso terapêutico , Teofilina/uso terapêutico , Administração Oral , Ensaios Clínicos como Assunto , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Lactente , Recém-Nascido , Medidas de Volume Pulmonar , Ventilação Pulmonar/efeitos dos fármacos , Distribuição AleatóriaRESUMO
We compared intermittent (8 hours/day) versus continuous (24 hours/day) isocaloric lipid infusion regimens in 28 neonates. The lipid dose was increased incrementally by 0.5 gm/kg/day to either 3 gm/kg/day or until fat contributed 40% of daily calories. Serum total triglycerides, free fatty acids, free fatty acids/albumin molar ratio, and total cholesterol levels were measured prior to the daily lipid infusion, at the end of the intermittent infusion, and at 8 hours during the continuous infusion. Neonates less than 32 weeks postconception had significant fluctuation of triglycerides, free fatty acids, and free fatty acids/albumin molar ratio during the intermittent regimen at all lipid doses, but not during the continuous regimen. Neonates greater than or equal to 32 weeks postconception had significant fluctuation of serum triglycerides, free fatty acids, and free fatty acids/albumin molar ratio during the intermittent regimen with a lipid dose greater than or equal to 2 gm/kg/day, but not during the continuous regimen at all lipid doses. Serum free fatty acids correlated closely with serum triglycerides during both regimens (r = 0.89, P less than 0.001). Serum total cholesterol rose with increasing lipid doses during both regimens (f = 8.16, P less than 0.05). We conclude that neonates less than 32 weeks postconception tolerate the continuous regimen better than the intermittent regimen at all lipid doses; neonates greater than or equal to 32 weeks postconception tolerate both regimens well at lipid dose less than 2 gm/kg/day, but tolerate a continuous regimen better with lipid dose greater than or equal to 2 gm/kg/day.
Assuntos
Colesterol/sangue , Emulsões Gordurosas Intravenosas/administração & dosagem , Ácidos Graxos não Esterificados/sangue , Recém-Nascido de Baixo Peso , Albumina Sérica/análise , Triglicerídeos/sangue , Ensaios Clínicos como Assunto , Esquema de Medicação , Emulsões Gordurosas Intravenosas/efeitos adversos , Feminino , Humanos , Recém-Nascido , Masculino , Edema Pulmonar/etiologia , Distribuição Aleatória , Fatores de TempoRESUMO
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.