To test the hypothesis that spironolactone-hydrochlorothiazide (Aldactazide) will improve urine output and lung function in infants with bronchopulmonary dysplasia, we studied 21 hospitalized, spontaneously breathing, oxygen-dependent infants with chronic bronchopulmonary dysplasia. Infants were randomly assigned to receive either a 1:1 mixture of spironolactone and hydrochlorothiazide orally (n = 12) (3 mg/kg/day of both compounds) or no treatment (n = 9) for 6 to 8 days each. Dynamic lung compliance, total pulmonary resistance, and hemoglobin oxygen saturation were measured on the first and last days of each study period. Fluid intake and urine output were measured each day. Although the treatment significantly increased urine output, neither lung mechanics nor oxygenation were improved by the drug. The magnitude of the diuresis achieved with spironolactone-hydrochlorothiazide treatment was comparable to the diuresis achieved in a previous study of furosemide treatment (J Pediatr 1986:109;1034-9). Statistical analysis indicated that a type II error was an unlikely explanation for our failure to detect a beneficial effect. In three patients, doubling the oral dose did not improve lung mechanics or oxygenation. We speculate that diuresis per se is not responsible for lung function improvement during treatment with other drugs with diuretic properties.

A retrospective analysis of infants with bronchopulmonary dysplasia requiring prolonged hospitalization (greater than 100 days) was carried out to determine those factors associated with fatal outcome. Twenty-three infants made up the study population. Eleven infants died and 12 survived (survivors). No differences were noted between the groups regarding ventilator requirement, radiographic changes, and medication use (digoxin, aldactazide), except for furosemide which was used twice as frequently in the group of infants who died v the group of infants who survived (P less than .001). Differences noted between the groups included moderate hypochloremia (chloride less than 80 mEq/L) in all 11 infants who died v six of 12 survivors, severe hypochloremia (chloride less than 70 mEq/L) in the nine of 11 infants who died v two of 12 survivors, metabolic alkalosis (pH greater than 7.45) in nine of 11 infants who died v three of 12 survivors, hypertension (systolic BP greater than 113 mm Hg) in eight of 11 infants who died v one of 12 survivors, decrease in head growth in ten of the 11 infants who died v one of the 12 survivors; these differences were all significant (P less than .001). The metabolic alkalosis and head growth changes appear to be related to the hypochloremia. The data suggest that chloride deficiency may be an important contributing factor in the genesis of poor outcome in infants with bronchopulmonary dysplasia and that close attention to chloride supplementation might influence outcome.

A patient with probable hydrochlorothiazide-induced pulmonary edema is described. A 70-year-old woman experienced nausea, diaphoresis, and severe respiratory distress approximately 1/2 hour after taking an Aldactazide tablet. She had experienced a flu-like syndrome after taking a single tablet two weeks previously. The patient was mildly tachycardic with a blood pressure of 74/0 mm Hg. A chest X-ray revealed cardiomegaly and bilateral pulmonary edema suggestive of congestive heart failure. The pulmonary capillary wedge pressure was normal. It was felt that the patient had developed a noncardiac pulmonary edema possibly secondary to hydrochlorothiazide ingestion. Nine other cases reported in the literature also are described. Pharmacists should be aware of this potential life-threatening reaction and avoid patient reexposure to the drug.

In a single-blind, randomized cross-over study the bioavailability of Spironothiazid (50 mg spironolactone, 50 mg hydrochlorothiazide) was investigated in six healthy male volunteers by comparing the same dose of the well-established drugs Aldactone dragees, 50 mg, and Esidrex tablets, 25 mg. After 6 days treatment with 2 X 1 Spironothiazid or 2 X 1 Aldactone dragees, 50 mg, plus Esidrex tablets, 25 mg daly, orally, the serum concentrations and the cumulative renal excretion of the active substances were measured after the morning dose on the 7th day of the study. Canrenone (the main metabolite of spironolactone) was measured fluorimetrically, hydrochlorothiazide was determined by gas chromatography. There was no statistically significant difference between the investigated drugs, neither in the areas under the curves nor in the cumulative renal excretion, thus indicating an identical bioavailability.

In 14 elderly male residents of a veterans' care complex who were receiving diuretic therapy for cardiac failure, oral potassium (K) supplements were withdrawn. Plasma and erythrocyte K levels were measured immediately before and six weeks after withdrawal of the supplements (38 mEq K daily). The controls comprised 19 elderly residents without disease and not taking drugs likely to influence K status. Study subjects and controls were receiving the same diet (average daily K content 100 mEq). After withdrawal of K supplements, the mean plasma K level fell significantly but the mean erythrocyte K level remained unchanged and did not differ from the control values. For a further six weeks after the withdrawal period, 7 subjects were treated with Aldactazide (diuretic hydrochlorothiazide plus K-sparing spironolactone). The plasma K level increased significantly but the erythrocyte K level remained unchanged. It was concluded that, in this setting, diuretic-induced hypokalemia is not necessarily accompanied by intracellular K depletion and that routine prophylaxis with K supplements or K-sparing agents is unnecessary and not without risk. Such therapy should be reserved for patients considered at special risk of K depletion because of known poor dietary intake, advanced liver disease, secondary hyperaldosteronism with renovascular hypertension, gastrointestinal losses, or nondiuretic medication known to affect K status adversely.