Furosemide acutely decreases airways resistance in chronic bronchopulmonary dysplasia

Kao, Lily C.; Warburton, David; Sargent, Charles W.; Platzker, Arnold C. G.; Keens, Thomas G.

doi:10.1016/s0022-3476(83)80602-7

Cited by 144 publications

(70 citation statements)

References 28 publications

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“…This water was derived primarily from the interstitial space, presumably including lung IW. We postulate that the mobilization of IW observed in this study accounts, at least partly, for the acute effects of furosemide on lung function observed by other investigators (2)(3)(4).…”

Section: Discussionsupporting

confidence: 78%

Effects of Furosemide on Body Water Compartments in Infants with Bronchopulmonary Dysplasia

O'donovan

Bell

1989

Pediatr Res

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ABSTRACT. We studied the effects of a single dose ofStudies in adults with pulmonary edema (5-7) have shown intravenous furosemide on the body water compartments variable effects of furosemide on plasma volume. Davidor et al.of nine infants with bronchopulmonary dysplasia. We (5) measured plasma vol in patients with refractory edema 2 h measured total body water, extracellular water, and plasma after an intravenous dose of furosemide. These patients had a volume using deuterium oxide, sodium bromide, and Evans mean decrease of 25% in plasma volume. Figueros and Weil(6) blue dye, respectively. From the results of these measure-found that the plasma volume of adults with acute cardiogenic ments, we calculated cell water, interstitial water, red cell pulmonary edema was lower than normal before therapy but volume, and total blood volume. We performed these meas-rose after treatment with furosemide, oxygen, and morphine.urements on the first day of the study and again 28 h later, Schuster et al. (7) measured blood volume in 2 1 patients with 4 h after an intravenous dose of furosemide (1 mglkg). All pulmonary edema who had either normal or decreased renal infants had a brisk diuresis in the first hour after the dose, function. The patients who had normal renal function, as indibut urine output was no greater during the 24-h period cated by a good diuresis, had no change in plasma volume 4 to after the dose than during the preceding 24-h period. Total 6 h after a single intravenous dose of furosemide. Patients who body water, extracellular water, and interstitial water were did not have a good diuresis had a rise in plasma volume. significantly decreased 4 h after furosemide. There was no There have been no similar studies in infants. Infants with change in plasma volume, red cell volume, or total blood BPD are often fluid restricted with the hope that this will reduce volume (Pediatr Res 26: 121-124, 1989) pulmonary edema. It would be of practical value to know whether furosemide causes a decrease in plasma volume in these Abbreviations infants, because hypovolumeemia might compromise organ perfusion and activate the compensatory mechanisms that stimulate BPD, bronchopulmonary dysplasia water and sodium retention. Our study was undertaken to assess TBW, total body water the effects of a single intravenous dose of furosemide on the IW, interstitial water plasma volume and other body water compartments of infants ECW, extracellular water with BPD. PV, plasma volume CBS, corrected bromide space Br, bromide MATERIALS AND METHODS

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Section: Discussionsupporting

confidence: 78%

Effects of Furosemide on Body Water Compartments in Infants with Bronchopulmonary Dysplasia

O'donovan

Bell

1989

Pediatr Res

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“…This abnormality of water balance may explain some of the nonpulmonary signs and symptoms in infants with chronic BPD, and may explain why some infants with chronic BPD can have improved lung function when treated with diuretics (6,20).…”

Section: Methodsmentioning

confidence: 99%

Control of Water Balance in Infants with Bronchopulmonary Dysplasia: Role of Endogenous Vasopressin

Engelhardt

1988

Pediatr Res

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ABSTRACT. Babies with chronic bronchopulmonary dysplasia (BPD) can sometimes develop pallor, systemic and pulmonary edema, oliguria, and hyponatremia not attributable to cardiopulmonary or renal impairment. These signs and symptoms might, however, be explained by inappropriate control of vasopressin secretion. To test this hypothesis, we measured plasma vasopressin and osmolality, serum sodium and potassium concentrations, urine output and osmolality, and free water clearance in 26 normoxic infants with BPD aged 1-4 months. All of these infants required supplemental oxygen (FiOz 0.41 2 0.03, mean -C 1 S E ) to maintain O 2 saturation of >88%, and six infants also required mechanical ventilation. As controls, 1 0 infants of similar age but without B P D were also studied. None of the infants had been discharged from the nursery and was receiving any medications, and all were clinically stable when studied. Compared to control infants, infants with BPD had significantly elevated plasma vasopressin concentrations (control 5.2 2 0.9 pg/ml; BPD 42.4 k 5.1; mean k SE, p < 0.05). Moreover, infants with B P D had hyponatremia and hypotonic plasma, and both urine output and free water clearance were significantly reduced. These data suggest that some infants with chronic BPD have elevated vasopressin levels that are functionally significant. W e speculate that excessive stimulation of vasopressin secretion may explain some of the pulmonary and nonpulmonary signs and symptoms in infants with chronic BPD. (Pediatr Res 23: 86-88,1988) Abbreviations BPD, bronchopulmonary dysplasia ADH, antidiuretic hormone CPAP, continuous positive airway pressure FiOz, inspired oxygen concentration PaC02, arterial P C 0 2 tension Babies with chronic BPD can sometimes develop systemic and pulmonary edema, oliguria, hyponatremia, and hypertension that cannot be attributed to chronic congestive heart failure or to renal disease. In some infants with BPD, treatment with diuretics has resulted in improvement in lung function and in systemic edema (1, 2). Some of these signs and symptoms are

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“…Taken together, this provides evidence that furosemide has a direct, nonepithelial-dependent effect on airway smooth muscle tone. Systemically administered furosemide improves pulmonary mechanics and gas exchange in infants with chronic lung disease independent of its diuretic effects (1,2). Studies demonstrating a reduction of bronchoconstrictive responses in pediatric (3) and adult asthmatics (4, 5) with aerosolized furosemide further support the notion that a nondiuretic effect may produce improvements in pulmonary function.…”

mentioning

confidence: 92%

Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways

2001

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This study was designed to test the hypotheses that furosemide directly causes relaxation in human fetal airway and that delivery of loop diuretics to either the adventitial or epithelial surface of newborn mouse airway results in equivalent relaxation. Isometric tension changes were measured in human fetal (11-16 wk) trachea and mainstem bronchus rings exposed to furosemide (300 M) or saline after acetylcholine or leukotriene D 4 constriction. Significant decreases in isometric tension to furosemide were demonstrated after constriction with acetylcholine or leukotriene D 4 . To examine the site of effect and mimic aerosolized and systemic administration, furosemide (3-300 M) and bumetanide (0.3-30 M) were applied separately to epithelial and adventitial surfaces of newborn mouse airways. No differences in airway diameter changes to epithelial or adventitial furosemide or bumetanide were observed, but a 10-fold difference in potency was found. In summary, human fetal airway relaxed to furosemide when constricted with either neurotransmitter or inflammatory mediator in vitro. Further, no differences in relaxation to equimolar epithelial and adventitial furosemide were observed in isolated newborn mouse airway. Taken together, this provides evidence that furosemide has a direct, nonepithelial-dependent effect on airway smooth muscle tone. Systemically administered furosemide improves pulmonary mechanics and gas exchange in infants with chronic lung disease independent of its diuretic effects (1, 2). Studies demonstrating a reduction of bronchoconstrictive responses in pediatric (3) and adult asthmatics (4, 5) with aerosolized furosemide further support the notion that a nondiuretic effect may produce improvements in pulmonary function. Indeed, the in vitro airway relaxation to furosemide that is observed in animal models (6 -8) suggests that there may be a direct effect on airway smooth muscle.However, a bronchodilatory response to inhaled furosemide is not consistently observed in infants with chronic lung disease (9, 10). Although aerosolized administration of furosemide could minimize systemic effects while producing localized bronchodilation, it is not widely accepted that inhaled furosemide has therapeutic efficacy during acute bronchoconstriction. Taken together, it is presently unclear whether these inconsistent results are because of species differences or inadequate concentrations of drug that reach the airway with aerosolized treatment, or because furosemide in fact does not act via a mechanism of direct airway smooth muscle relaxation (11). Therefore, the potential relevance of previous in vitro animal findings requires validation by the study of human airway response (12), with the first objective to test the hypothesis that furosemide causes direct relaxation of human fetal airway.In addition to demonstrating a direct relaxing effect on airway smooth muscle, further support for the bronchodilatory response to furosemide via aerosolization would require evidence that mechanisms can be activated from th...

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Furosemide acutely decreases airways resistance in chronic bronchopulmonary dysplasia

Cited by 144 publications

References 28 publications

Effects of Furosemide on Body Water Compartments in Infants with Bronchopulmonary Dysplasia

Effects of Furosemide on Body Water Compartments in Infants with Bronchopulmonary Dysplasia

Control of Water Balance in Infants with Bronchopulmonary Dysplasia: Role of Endogenous Vasopressin

Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways

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