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PubMed2000

Mannitol, furosemide, and dopamine infusion in postoperative renal failure complicating cardiac surgery.

BACKGROUND: Acute renal failure occurring in the postoperative period, requiring dialysis after cardiac surgery is an important risk factor for an early mortality, and the overall mortality of this complication is as high as 40% to 60%. Dialysis in the early postoperative period is often complicated by acute hemodynamic, metabolic, and hematologic effects that adversely affect cardiopulmonary function in patients stabilizing from recent surgery. The purpose of this study was to avoid the need for dialysis by infusion of the solution of mannitol, furosemide, and dopamine in the early postoperative period in oliguric renal failure. METHODS: One hundred patients with postoperative oliguric or anuric renal failure despite adequate postoperative cardiac output and hemodynamic function were randomized. Forty patients (group A) were given intermittent doses of diuretics (furosemide, bumetadine, and ethracrynic acid) and fluids. Sixty patients (group B) were given continuous infusion of the solution of mannitol, furosemide, and dopamine; the infusion was started within 6 hours (mean 3.5 hours) in subgroup B1 (n = 30), and later than 6 hours (mean 7.5 hours) in subgroup B2 (n = 30) after the onset of renal failure. RESULTS: Diuresis occurred in 93.3% of group B (n = 56) versus 10% in group A (n = 4; patients with preop normal renal function). Ninety percent of group A (n = 36) required dialysis versus only 6.7% of group B (n = 4; patients with preexisting renal disease of subgroup B2). Renal function returned to preoperative normal (serum creatinine 0.9 +/- 0.05, p < 0.0001) or baseline value (serum creatinine 2.5 +/- 0.01, p < 0.0001) after first postoperative week in subgroup B1 and third postoperative week in subgroup B2. CONCLUSIONS: Infusion of solution of mannitol, furosemide, and dopamine promoted diuresis in patients with acute postoperative renal failure with adequate postoperative cardiac output and had decreased the need for dialysis in the majority of patients. Early administration of this solution in acute renal failure caused early restoration of renal function to normal or baseline status. It remains to be determined whether routine administration of this solution in the early postoperative period for oliguric renal failure influences the long-term mortality and morbidity in those patients who do require dialysis.

Acute Kidney Injury↗
PubMed1997

Action of furosemide on GABA- and glycine currents in rat septal cholinergic neurons in culture.

The action of furosemide on GABA- and glycine-induced currents in rat septal cholinergic neurons in culture was examined by use of the whole-cell voltage-clamp technique. Furosemide inhibited the peak amplitude of either GABA or glycine current in a dose-dependent manner; its half-maximal concentration for them was some 2 and 1 mM, respectively. Furosemide at a concentration of 1 mM depressed the maximal peak amplitude of the dose-response curve for either GABA or glycine to about 70% of control. These results indicate that furosemide inhibits in a noncompetitive fashion GABA and glycine receptor-channels in septal neurons.

Animals↗
PubMed1998

Structure-activity relationship of furosemide-derived compounds as antagonists of cerebellum-specific GABA(A) receptors.

The Na+-K+-2Cl- cotransporter blocker furosemide inhibits gamma-aminobutyric acid (GABA)-gated chloride currents and reverses GABA-mediated inhibition of [35S]-t-butylbicyclophosphorothionate ([35S]TBPS) binding of the cerebellar alpha6 subunit-containing GABA(A) receptors much more potently than the cerebrocortical non-alpha6 subunit-containing receptors. Of the 44 compounds studied, all precursors or derivatives of diuretics, one compound [hydrazinosulfonyl-furosemide (PF 1885)] reversed 5-microM GABA-induced inhibition of [35S]TBPS binding to cerebellar and cerebrocortical receptors. Three other compounds, all of which are structurally closely related to furosemide, were selective antagonists for the cerebellar receptors comparable to the lead compound. Still, the diuretic and GABAergic structure-activity relationships differ, since we found potent diuretic structures lacking GABA antagonistic activity. Further development of the GABAergic potency of furosemide derivatives can now focus on the modification of the carboxyl group, replaceable by tetrazole but not by sulfonic or phosphinic acids and the furanyl moiety which could be substituted by thienyl and benzyl groups.

Animals↗
PubMed1982

Furosemide prevents the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus.

To determine if furosemide would prevent the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus, 19 premature infants were randomized into two groups: nine received indomethacin alone, and ten received indomethacin followed immediately by furosemide. There was no significant difference between the groups in birth weight, gestational age, postnatal age, and in cardiopulmonary or renal status at the time of study. Infants who received indomethacin and furosemide had significantly higher urine output (P less than 0.05), higher FENa and FECl (P less than 0.01), and higher glomerular filtration rate (P less than 0.05) than those of infants who received indomethacin alone. Seven infants in each group responded to indomethacin therapy with disappearance of PDA murmur and improvement of cardiovascular status. The results of this study suggest that furosemide may prevent the renal side effects of indomethacin therapy and yet not affect the efficacy of indomethacin in the closure of a PDA.

Drug Therapy, Combination↗
PubMed1983

Pulmonary effects of furosemide in preterm infants with lung disease.

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.

Furosemide↗
PubMed1983

Plasma and urinary kinetics of furosemide in newborn infants.

Plasma and urinary furosemide kinetics were assayed by high-power liquid chromatography in six newborn infants receiving furosemide (1 mg/kg body weight IV) for the treatment of fluid overload. Mean +/- SD for plasma half-life, apparent volume of distribution, and plasma clearance were, respectively, 9.5 +/- 4.4 hours, 173 +/- 28 ml/kg, and 15.3 +/- 8.4 ml/hr/kg. There was close correspondence between plasma and urinary half-lives and between plasma clearance and renal clearance. In the first 24 hours, mean estimated urinary recovery of unchanged furosemide was 90% of the injected dose (range 61% to 106%). The results suggest that in the newborn infant furosemide is virtually all excreted unchanged in the urine and that the absence of significant nonrenal elimination, together with the immaturity of neonatal renal function, accounts for its prolonged half-life in newborn infants.

Furosemide↗
PubMed1984

Early furosemide therapy in premature infants (less than or equal to 2000 gm) with respiratory distress syndrome: a randomized controlled trial.

Pulmonary edema has been demonstrated in the early stages of respiratory distress syndrome in premature infants. To evaluate whether early furosemide therapy (0 to 8 hours after birth) would affect the electrolyte balance, pulmonary status, and outcome, 57 infants (less than or equal to 2000 gm) with respiratory distress syndrome who required mechanical ventilation shortly after birth were randomized into two groups: 29 given furosemide (1 mg/kg/day intravenously for three doses) and 27 control. The clinical, biochemical, and laboratory characteristics of the groups were comparable before entry into the study. Administration of furosemide significantly enhanced the urinary excretion of Na and Cl at 0 to 24, 24 to 48 and 48 to 72 hours and of Ca at 24 to 48 and 48 to 72 hours after drug administration. There was no significant difference between the groups in urinary excretion of K and in serum Na, Cl, K, and Ca values. A spontaneous increase in urine output occurred in the control group at 48 to 72 hours after the initiation of the study (mean +/- SD 7.0 +/- 3.5 hours postnatal age), along with a decrease in mean airway pressure for mechanical ventilation. The use of furosemide (7.3 +/- 3.5 hours postnatal age) enhanced urine output at 24 to 48 and 48 to 72 hours after medication, resulting in further decrease in mean airway pressure and facilitating extubation. There was, however, no significant difference between the groups with respect to incidence of patent ductus arteriosus, morbidity from bronchopulmonary dysplasia, and mortality.

Bronchopulmonary Dysplasia↗
PubMed1988

Prophylactic furosemide in severe respiratory distress syndrome: blinded prospective study.

To further characterize the place for furosemide in the treatment of newborn infants with respiratory distress syndrome requiring mechanical ventilation, we conducted a blinded, prospective study comparing early prophylactic use (1 mg/kg every 12 hours for four doses beginning at 24 hours of age) with prn use of this drug. Prophylactic administration of furosemide produced no beneficial effect on any measure of pulmonary function compared with use of this drug as needed (prn). However, patients receiving the prophylactic furosemide regimen were found to have more rapid postnatal weight loss, higher pulse rate, and greater sympathomimetic drug requirement during the period of diuretic administration. Patients in the prophylactic group did not demonstrate the moderate expansion in plasma volume between 48 and 96 hours of age seen in the control group. These data suggest that the prophylactic regimen produced an undesirable degree of volume depletion. Further studies should be conducted to develop objective criteria for the selection of the subgroup of patients with respiratory distress syndrome who may benefit from furosemide.

Body Weight↗
PubMed1997

Partial ureteral obstruction: effect of intravenous normal saline and furosemide upon the renal resistive index.

OBJECTIVE: To investigate the effect of intravenous normal saline fluid load, with and without furosemide, upon the renal resistive index (RI) of obstructed and nonobstructed kidneys. METHODS: Right partial ureteral obstruction was induced in 10 dogs. Grade 1 (mild) obstruction was performed in 5 dogs (group A), and grade 3 (severe) obstruction was carried out to the remaining 5 dogs (group B). Evaluation by Doppler ultrasonography was performed before induction of ureteral obstruction and by the end of the 8th week of obstruction. Every obstructed animal was subjected to bilateral renal Doppler ultrasonography 3 times in one setting: 1) before infusion of normal saline, 2) 30-60 minutes after intravenous infusion of normal saline (15 ml./kg.) given in a rate of 1 ml./kg./min. and 3) 10 minutes after admission of furosemide (1 mg./kg.). RESULTS: After induction of right partial ureteral obstruction, there was a significant increase of the RI of the right kidney and a significant decrease of the RI of the left kidney compared to baseline RI in both groups. Infusion of normal saline and administration of furosemide caused a further significant increase of the RI of the obstructed kidney and a further significant decrease of the RI in the nonobstructed kidney in both groups. CONCLUSION: In unilateral partial ureteral obstruction, addition of intravenous normal saline and furosemide cause the RI to increase in obstructed kidney and to decrease in nonobstructed kidney. Such a divergent response may be useful for the development of a pharmacologically challenged Doppler examination to diagnose better potentially obstructed kidneys.

Animals↗
PubMed1994

Temporal changes in rabbit urinary bladder function and DNA synthesis during chronic treatment with furosemide.

In a preliminary study we showed that 14 days of furosemide infusion in rabbits caused increases in bladder mass and contractile responses of bladder body strips to field stimulation, bethanechol, ATP and KCl. The present study investigated the temporal effects of furosemide-induced diuresis on micturition, bladder mass, bladder wall proliferation activity and DNA synthesis. In addition, contractile responses of bladder body strips were monitored. Furosemide-containing osmotic pumps were implanted in male New Zealand White rabbits. Micturition was monitored for 7 days. Biochemical analyses were done 3, 7 and 14 days after implantation. Contractile responses were measured at 3 and 7 days. Polyuria and polydipsia started within 1 day after implantation of furosemide-containing osmotic pumps and continued at the same level for 7 days. Bladder mass was significantly increased at 3 and 7 days. Diuresis stimulated 3H-thymidine uptake and caused an increase in bladder DNA concentration at 3 days. However, both DNA concentrations and 3H-thymidine levels returned to control levels by 7 days. Contractile responses to field stimulation and agonists were increased at 7 days but unchanged at 3 days. The data confirm that modest increases in bladder mass and the ensuing increases in contractile function are a normal and beneficial physiological response to diuresis.

Adenosine Triphosphate↗
PubMed1996

Renal Doppler ultrasound in children with normal upper urinary tracts: effect of fasting, hydration with normal saline, and furosemide administration.

OBJECTIVES: To study the age dependency of renal resistive index (RI) and to study the effect on the renal RI of fasting, intravenous infusion of normal saline, and administration of furosemide in children with normal upper urinary tracts. METHODS: The study included 28 nonobstructed renal units in 15 boys ranging in age from 3 to 11 years. Diuretic renography and Doppler ultrasonography were attempted in all children. Doppler ultrasonography was carried out under three different conditions: fasting state, 30 to 60 minutes after intravenous infusion of normal saline (15 mL/kg), and 10 minutes after administration of furosemide (1 mg/kg; maximum, 40 mg). RESULTS: There was an inverse correlation between age and RI of both renal units under the three conditions of Doppler studies. At fasting state mean RI was 0.70 +/- 0.04, whereas 15 of 28 renal units (54%) had an RI of 0.70 or higher. Intravenous infusion of normal saline significantly decreased the RI to 0.63 +/- 0.04 (P < 0.000001). Injection of furosemide caused a further significant decrease of RI from 0.63 +/- 0.04 to 0.60 +/- 0.04 (P < 0.002). CONCLUSIONS: The renal RI in healthy children is age dependent. In the fasting state, 54% of nonobstructed renal units in children have an RI of 0.70 or higher. Intravenous infusion of normal saline and administration of furosemide can independently cause a significant decrease of the RI in nonobstructed renal units in children.

Child↗
PubMed1975

Antagonism of the effects of furosemide by indomethacin in normal and hypertensive man.

Furosemide and the prostaglandin synthetase inhibitor, indomethacin, were administered singly and in combination to four normal subjects and six patients with essential hypertension in order to determine whether the antihypertensive, natriuretic and other effects of furosemide could be altered by inhibition of prostaglandin synthesis. In all subjects indomethacin treatment alone resulted in a significant elevation of blood pressure and a fall in plasma renin without any change in sodium excretion. Furosemide alone resulted in a significant blood pressure fall with a rise in plasma renin and urinary aldosterone with a marked increase in urinary sodium loss. These effects were either obviated or blunted by addition of indomethacin. The results are compatible with hypothesis that the antihypertensive and natriuretic effects of furosemide might be mediated at least in part by prostaglandin synthesis. In addition, the effects of indomethacin should be considered when using this drug in hypertensive patients and in subjects requiring diuretic therapy.

Aldosterone↗
PubMed1995

Steroid-sparing effect of inhaled lysine acetylsalicylate and furosemide in high-dose beclomethasone-dependent asthma.

BACKGROUND: Inhaled lysine acetylsalicylate and furosemide exert a mutually potentiating protective activity on experimentally induced bronchoconstriction in asthma. OBJECTIVE: Our purpose was to investigate the clinical effectiveness of combined treatment of asthma with inhaled lysine acetylsalicylate and furosemide. METHODS: We performed a randomized, double-blind, crossover study in nine patients with chronic asthma requiring a high dose (2 mg/day) of inhaled beclomethasone for clinical control. Patients were treated with a combination of 720 mg inhaled lysine acetylsalicylate and 40 mg furosemide twice daily, or with matched placebo in addition to inhaled steroids. The dose of inhaled steroids was reduced by half every 15 days and eventually suspended unless a patient's respiratory condition worsened. RESULTS: During treatment with placebo, all patients had worsening of asthma at dosages of 1 or 0.5 mg/day beclomethasone (mean +/- SE, 833 +/- 83 micrograms/day). During combined treatment complete suspension of inhaled steroids in two patients and reduction to 0.5 to 0.25 mg in the remaining seven patients (mean, 250 +/- 72 micrograms/day) was achieved, with a mean reduction of 71% +/- 7%. Forced expiratory volume in 1 second, weekly peak expiratory flow rate, symptom score, and bronchodilator intake remained significantly better with combined treatment than with placebo. CONCLUSIONS: Treatment with inhaled lysine acetylsalicylate and furosemide allows a considerable sparing of inhaled steroids without significant side effects in patients with severe asthma.

Administration, Inhalation↗
PubMed1997

Comparative efficacy of inhaled furosemide and disodium cromoglycate in the treatment of exercise-induced asthma in children.

BACKGROUND: Inhaled furosemide has been shown, in patients with asthma, to have prophylactic properties similar to those of disodium cromoglycate. OBJECTIVE: The aim of this study was to evaluate the protective effect of these drugs in the treatment of exercise-induced asthma. METHODS: Fifteen children with exercise-induced asthma (mean age, 10.8 years) underwent exercise challenge after a single dose of nebulized placebo, furosemide (20 mg/m7 body area), or disodium cromoglycate (20 mg), 2 days apart, in a single-blind crossover trial. RESULTS: Both furosemide and disodium cromoglycate exerted significant protection against the bronchial response to exercise challenge, with a mean maximum percentage falls in FEV1 of 4.66% and 7.22%, respectively (p < 0.05). On the placebo day, the mean maximum percentage fall in FEV1 was 34.50% (p < 0.05). CONCLUSION: The results of this study suggest that furosemide and disodium cromoglycate provide comparable efficacy in preventing exercise-induced asthma in children, with no side effects.

Administration, Inhalation↗
PubMed2003

Nano-encapsulation of furosemide microcrystals for controlled drug release.

Furosemide microcrystals were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 5-microm drug microcrystals through layer-by-layer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin/PSS bilayers with corresponding capsule wall thicknesses ranging from 45 to 115 nm. The release of furosemide from the coated microparticles was measured in aqueous solutions of pH 1.4 and 7.4. At both pH values, the release rate of furosemide from the encapsulated particles was reduced by 50-300 times (for capsules coated with two to six bilayers) compared to uncoated furosemide. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug microcrystals.

Crystallization↗
PubMed1993

Effects of imidazole-salicylate on renal function and the diuretic action of furosemide in cirrhotic patients with ascites.

Imidazole-salicylate is a non-steroidal anti-inflammatory drug with limited inhibitory effects on prostaglandin synthesis. The renal effects of this drug were investigated by a double-blind cross-over study in 10 patients with cirrhosis and ascites. Two therapeutic doses of imidazole-salicylate (750 mg each) were given at midnight and 08:00 h and 80 mg of furosemide were injected intravenously at 09:00 h. The same procedure was followed on another day but a placebo replaced imidazole-salicylate. Renal function (creatinine clearance, free water and electrolyte excretions) and urinary excretion of prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were evaluated for 8 h after the first dose of the drug and for 2 h after furosemide injection. Platelet thromboxane production was also determined 9 h after the first administration of drug or placebo. Imidazole-salicylate did not affect renal function or inhibit kidney prostanoid production either under basal conditions or after the stimulating effect of furosemide. On the contrary, imidazole-salicylate significantly inhibited platelet thromboxane production (45.8 +/- 9 vs. 69.4 +/- 7.5 ng/ml, P < 0.05). These results suggest that imidazole-salicylate is an anti-inflammatory drug that can be given to patients with decompensated cirrhosis without risk of inhibiting kidney prostaglandin synthesis or the renal response to furosemide.

Adult↗
PubMed1980

Characterization of the concanavalin A-induced increase in lymphocyte cell membrane permeability by furosemide.

The effect of ConA on passive 42K+ fluxes in human lymphocytes was analysed by treatment with furosemide and ouabain. Furosemide has no effect on net K+ transport and pump flux. The component of passive efflux of 42K+ which depends on K+-K+ exchange is inhibited by furosemide; its mechanism is discussed in detail. The 42K+ uptake in lymphocytes consists of 1. an ouabain-sensitive pump influx, 2. an ouabain-insensitive leak influx and 3. a furosemide-sensitive K+-K+-exchange. Only the first two components of 42K+ uptake are stimulated by ConA.

Biological Transport↗
PubMed1982

Improved method for the analysis of furosemide in plasma by high-performance liquid chromatography.

Modifications of existing rapid high-performance liquid chromatographic procedures for the determination of furosemide in plasma were made in order to achieve greater sensitivity. To a small volume of plasma was added in internal standard structurally related to furosemide. Then, following previously described procedures, acetonitrile was added to precipitate the proteins and the clear supernatant was separated. However prior to injection of the supernatant the pH and composition of the sample were adjusted. This modification of the sample enabled an injection volume of up to 300 microliters of the supernatant to be injected onto the chromatographic column. The effluent was monitored spectrofluorimetrically. A standard linear calibration curve with a mean precision of +/- 4.4% was obtained for plasma samples containing 20--900 ng/ml of furosemide. Two structurally related compounds were used as internal standards in the furosemide assay.

Administration, Oral↗