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Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis.

The authors examined the natriuretic efficiency of furosemide in rats with cirrhosis induced by carbon tetrachloride (CCl(4)). Rats were treated for 17 weeks with intraperitoneal injections of CCl(4) in groundnut oil twice a week throughout the study. Control rats were treated with vehicle (groundnut oil). Studies in metabolic cages showed that sodium retention was present from week 14. Renal clearance experiments were performed in chronically, instrumented conscious rats at the end of week 14 and at the termination of the study (end week 16) when ascites and hyponatremia were present. After 14 weeks, cirrhotic rats had sodium retention along with increased renal plasma flow, normal GFR, normal renal lithium handling, and a significantly increased diuretic (+41% vs. control) and natriuretic (+56% vs. control) response to a test dose furosemide (7.5 mg/kg b.w., intravenously). The natriuretic efficiency of furosemide, i.e., the natriuresis expressed relative to the furosemide excretion rate (triangle upU(Na)V/U(FUR)V) was increased by 51% versus control. After 17 weeks, ascites and hyponatremia had developed, and significant decreases in renal plasma flow (-33%), GFR (-30%), and fractional lithium excretion (-44%) were observed. At this stage urinary recovery of furosemide was significantly decreased and the diuretic (-27% vs. Control) and natriuretic (-38% vs. control) responses to furosemide were significantly impaired. However, the increased natriuretic efficiency of furosemide was still present (+34% vs. control). Together these results suggest that increased sodium reabsorption in the thick ascending limb of Henle's loop is involved in the renal sodium retention in cirrhosis in rats that eventually results in decompensation with the formation of ascites.

Animals↗

Induction of fetal diuresis with intraamniotic furosemide increases the clearance of intraamniotic substances: An alternative therapy aimed at reducing intraamniotic meconium concentration.

BACKGROUND/PURPOSE: Contact with amniotic fluid (AF) causes intestinal damage in gastroschisis. Intraamniotic meconium has been shown to be responsible for intestinal damage, and occurrence of this damage has been shown to depend on the concentration of intraamniotic meconium. When intraamniotic meconium concentration is lowered below threshold level by exchanging AF with saline in gastroschisis, intestinal damage can be prevented. Theoretically, induction of fetal diuresis with intraamniotic furosemide may increase AF volume and fetal swallowing rate, thus, increase absorption of AF by intestines; therefore, the clearance of meconium from the AF may increase. An experimental study was planned to investigate the effects of intraamniotic diuretic injection on the clearance of intraamniotic substances. METHODS: Pregnant rabbits on the 23rd to 25th gestational day were divided into 2 groups as furosemide and control. Technetium tc99m labeled "tin colloid" was injected into the amniotic cavity, and AF sample was taken 10 minutes later. Furosemide was injected into the amniotic cavity afterwards. Two and 6 hours later, AF samples were obtained. Intestines were harvested at the end of the study. Control group received intraamniotic saline instead of furosemide. Radioactivities of the AF samples and intestines were determined by gamma counter. Clearance of the radioisotope from AF and intestinal accumulation were calculated. RESULTS: The clearance of the radioisotope from AF was increased significantly in the furosemide group (n = 10) compared with the control group (n = 8; P <.01). Gastrointestinal accumulation of the radioisotope in the furosemide group was 4-fold higher than that the control group (P <.01). CONCLUSIONS: Induction of fetal diuresis with intraamniotic furosemide accelerates the clearance of intraamniotic substances. This is probably caused by increased urinary output rate, which increases AF volume and consequently results in increased fetal swallowing of AF. In the diseases like gastroschisis and myelomeningocele, in which the contact with AF causes tissue damage, the elimination of meconium from AF in a somewhat natural manner like this method, should be studied further because it may be an alternative minimal invasive in utero treatment modality.

Amniotic Fluid↗

Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome.

Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus. We administered this drug to 33 premature infants with the respiratory-distress syndrome, to determine whether it increased the incidence of patent ductus arteriosus. Chlorothiazide, a diuretic that does not stimulate prostaglandin E synthesis, was used as the control drug in 33 other infants. During the study, the incidence of patent ductus arteriosus was significantly higher (P less than 0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33). Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation (P greater than 0.2). An additional six infants (all from the furosemide group) who did not have evidence of a patent ductus during the study were later found to have one. Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups, respectively (P greater than 0.2). Small (less than twofold) increases in the urinary excretion of prostaglandin E were seen after the initial dose of both drugs. When the analysis was repeated after the fifth day of life, prostaglandin E excretion tripled after furosemide administration, whereas no increase occurred with chlorothiazide. We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process.

Chlorothiazide↗

Effect of furosemide infusion on renal hemodynamics and angiogenesis gene expression in acute renal ischemia/reperfusion.

Loop diuretics are known to affect renal hemodynamics and possibly gene transcription, but the specific effect of furosemide on renal angiogenesis gene expression after acute ischemia is not known. We utilized an acute renal failure model in rats to test the hypothesis that furosemide improves renal hemodynamics and alters the transcriptional signature of acute ischemic nephropathy. Twenty-four male Sprague-Dawley rats were anesthetized by the intraperitoneal administration of 50 mg/kg urethane. Animals were divided into four groups (n = 6 each): (1) sham-operated group infused with saline; (2) sham-operated group infused with 30 microg/kg/hr furosemide (equivalent to a human dosage of 2 mg/hr); (3) unilateral renal ischemia (1 hr, left renal artery cross-clamping) followed by 6 hr of reperfusion; and (4) renal ischemia/ reperfusion (I/R) with furosemide. Renal artery blood flow (RBF), renal cortical perfusion (RCP), and renal corticomedullary tissue oxygen tension (PO2) were recorded throughout. Following 6 hr of reperfusion, left kidney RNA was used to probe microarrays. Gene expression was measured as percent positive control and confirmed using reverse transcriptase polymerase chain reaction. Physiologic data were analyzed by calculating area under the curve, and gene expression data were compared by using multiple analysis of variance with Tukey's post-hoc tests. Furosemide significantly increased RBF (P < 0.05) and PO2 (P < 0.05) in postischemic kidneys. Furosemide attenuated nine of the 13 ischemia-induced and 41 of 78 ischemia-suppressed angiogenesis-related genes. This attenuation was statistically significant (P < 0.05) for 17 I/R injury-suppressed genes. Data from this rat model of ischemic nephropathy suggest that furosemide improves renal hemodynamics and attenuates ischemia-related changes in gene expression.

Acute Disease↗

Evaluation of prehospital use of furosemide in patients with respiratory distress.

OBJECTIVE: To evaluate the appropriateness of prehospital use of furosemide. METHODS: All patients over 18 years old receiving prehopsital furosemide were retrospectively identified, and cases were matched to subsequent hospital records. Data collected included ED and hospital primary and secondary diagnoses, brain-type natriuretic peptide (BNP) levels and final disposition. Furosemide was considered appropriate when the primary or secondary ED or hospital diagnoses included congestive heart failure (CHF) or pulmonary edema, or the BNP was > 400. Furosemide was considered inappropriate when none of the diagnoses included CHF, when the BNP was < 200, or when an order for IV fluid hydration was given. Furosemide was considered potentially harmful when the diagnoses included sepsis, dehydration or pneumonia, without a diagnosis of CHF or BNP > 400. RESULTS: Of the 144 included patients, a primary or secondary diagnosis of CHF was reported in 42% and 17% patients, respectively. The initial BNP was > 400 in 44% of the 120 patients in which this lab test was obtained. Sixty patients (42%) did not receive a diagnosis of CHF, 30 (25%) patients had a BNP < 200, and 33 (23%) had an order for IV fluid hydration. A diagnosis of sepsis, dehydration or pneumonia without a diagnosis of CHF or a BNP > 400 occurred in 17% of patients. Seven of the 9 deaths did not receive a diagnosis of CHF. Furosemide was considered appropriate in 58%, inappropriate in 42% and potentially harmful in 17% of patients. CONCLUSIONS: In this EMS system, prehospital furosemide was frequently administered to patients in whom its use was considered inappropriate, and not uncommonly to patients when it was considered potentially harmful. EMS systems should reconsider the appropriateness of prehospital diuretic use.

Adult↗

High dose furosemide in refractory cardiac failure.

High dose furosemide is commonly used in renal failure to induce diuresis but rarely employed in cardiac failure. As furosemide elimination depends largely on renal excretion, drug accumulation with attendant side-effects would be expected to occur more commonly with renal failure than with cardiac failure. Response to a combination of thiazide diuretics and lower doses of furosemide is often unpredictable, ineffective and sometimes hazardous. High dose furosemide (greater than or equal to 0.5 g day-1) was administered for at least four weeks in 24 patients with severe cardiac failure refractory to a lower dose and to other conventional therapy. Mean maintenance dose of furosemide was 0.7 g day-1 and the maximum dose of furosemide averaged 1.3 g day-1. A peak dose of 8 g day-1 was used successfully in one patient. Improvement was observed in all patients when dosage was increased to and above 0.5 g day-1. There were no major side-effects although new-onset gout (4) and tinnitus (1) were reported; hypokalaemia was readily controlled with spironolactone or potassium supplements. Average duration of therapy was 12 months with a maximum of 33 months. High dose furosemide is logical and effective therapy (with other measures) for severe cardiac failure and relatively safe when administered cautiously. The maximum safe dose is probably no less than that used in renal failure.

Blood Pressure↗

Effects of furosemide on the neuromuscular junction.

These studies investigated the direct effects of furosemide on neuromuscular transmission using the in vitro rat phrenic nerve diaphragm and the in vivo at soleus nerve muscle preparations. Furosemide (10(-6)-10(-4)m) reduced the concentration of d-tubocurarine required to achieve 50% twitch tension depression in the indirectly stimulated rat diaphragm. Intraarterial injection of furosemide had a biphasic effect on the cat neuromuscular junction. At low doses (0.1-10.0 micrograms/kg) the drug had a depressant effect, reduced the force of muscle contraction, prevented nerve and muscle responses to NaF and dibutryl cyclic AMP, and intensified the neuromuscular blockade produced by d-tubocurarine and succinylcholine. In contrast, in higher doses (1-4 mg/kg) furosemide produced stimulus-bound repetitive neural activity, initiated neural activity, increased the force of muscle contraction, enhanced nerve and muscle responses to NaF and dibutyrl cyclic AMP, and antagonized d-tubocurarine and succinylcholine blockades. Furosemide had no effect on denervated preparations. High doses of furosemide inhibit non-competitively both the high- and low-affinity forms of the enzyme cyclic AMP phosphodiesterase in both soluble and particulate fractions of cat sciatic nerve. Thus, furosemide has direct effects on neuromuscular transmission, but the direction of these effects is dose-dependent.

3',5'-Cyclic-AMP Phosphodiesterases↗

Inhaled furosemide inhibits behavioral response to airway occlusion in anesthetized cats.

BACKGROUND: A recent study showed that inhaled furosemide greatly improves experimentally induced dyspnea in humans. The objective of the current study is to test the hypothesis that inhaled furosemide suppresses the behavioral response to airway occlusion without changing the behavioral response to a somatic noxious stimulus in anesthetized animals. METHODS: In 10 spontaneously breathing cats anesthetized with isoflurane, anesthetic ED(50) was determined by measuring an end-tidal anesthetic concentration while observing escape behavior. The monitored behavior consisted of purposeful movement of the head and forearm after endotracheal tube occlusion. The duration from the start of airway occlusion to the onset of the positive response (DOCCL) was measured at the highest concentration of isoflurane permitting the positive motor response to airway occlusion before pretreatment. ED(50) values (minimum alveolar concentration) for the suppression of a somatic motor response to a noxious stimulus induced by toe pinch (toe-pinch ED(50)) were also determined. Then, the effects of inhaled furosemide or vehicle on the ED(50) for the suppression of the behavioral response to airway occlusion, DOCCL, and toe-pinch ED(50) were evaluated in a randomized, cross-over design. RESULTS: The ED(50) for the suppression of the behavioral response to airway occlusion significantly decreased (P < 0.01) and DOCCL was significantly prolonged (P < 0.01) after furosemide inhalation, whereas vehicle inhalation did not change these measurements. The decrease in ED(50) for the suppression of the behavioral response to airway occlusion after furosemide inhalation lasted 3 h. Furosemide inhalation did not affect the toe-pinch ED(50). CONCLUSION: Inhaled furosemide suppressed the behavioral response to airway occlusion in anesthetized animals without affecting the response to somatic noxious stimulus. The authors' animal model of respiratory distress may be applicable to the study of dyspnea in regard to its mechanism and treatment.

Administration, Inhalation↗

Effect of lung water content, manipulated by intratracheal furosemide, surfactant, or a mixture of both, on compliance and viscoelastic tissue forces in lung-lavaged newborn piglets.

OBJECTIVE: To study the impact of lung water content and its reduction by a topically applied diuretic on respiratory and lung tissue mechanics in comparison with surfactant administration in surfactant-deficient newborn piglets with lavage-induced lung injury. DESIGN: Controlled, randomized study. SETTING: Animal research facility. SUBJECTS: Newborn piglets. TREATMENT Piglets were surfactant depleted by lung lavage and, after a pretreatment period, randomly treated with intratracheal furosemide, furosemide and surfactant, or with surfactant alone. MEASUREMENTS AND MAIN RESULTS: Dynamic compliance (C(DYN)), static compliance (C(ST)), stress-adaptation pressures (P(DIFF)) and post mortem lung water content were determined. Static compliance in the furosemide-surfactant group was not significantly higher than in the surfactant group. At the end of the study, C(ST) did not differ between the three groups because C(ST) in the furosemide group had increased to values similar to those of the surfactant-containing treatment groups: C(ST) F+S: 0.73 +/- 0.2 mL/cm H2O/kg body weight (BW); C(ST) S: 0.61 +/- 0.11 mL/cm H2O/kg BW; and C(ST) F: 0.60 +/- 0.19 mL/cm H2O/kg BW). Compliance was inversely and P(DIFF) was directly correlated to lung water (LW) content (C(ST) vs. LW: r2 = .59, p = .001; C(DYN) vs. LW: r2 = .49, p = .006; P(DIFF) vs. LW: r2 = .37, p = .059), independent of the type of treatment. Changes in C(ST) and C(DYN) were inversely related to changes in P(DIFF). Intrapulmonary furosemide was more rapidly absorbed when administered to the surfactant-depleted lung alone compared with the mixture with surfactant, and intrapulmonary furosemide had a rapid systemic effect. CONCLUSION: Although the combination of surfactant with a diuretic failed to increase respiratory compliance to a significantly larger extent than surfactant alone, furosemide at the end of the study increased respiratory compliance to a level similar to surfactant-containing treatments. Lung water content and, to a lesser extent, the absence or presence of surfactant appeared to determine lung mechanics, and its impact on lung mechanics was similar to surfactant administration.

Animals↗

The effect of furosemide infusion on serum epidermal growth factor concentration after acute lung injury.

Acute lung injury and its more severe form, acute respiratory distress syndrome, are clinical syndromes of progressive hypoxemia and ventilation-perfusion mismatch with decreasing pulmonary compliance in the absence of congestive heart failure. Epidermal growth factor is involved in the pathogenesis of airway inflammation as well as a proinflammatory effect in other tissues. Furosemide has been shown to improve pulmonary gas exchange and intrapulmonary shunt by a nondiuretic mechanism in animal models of acute respiratory distress syndrome. The current study was undertaken to clarify whether furosemide attenuates the inflammatory response by changing the epidermal growth factor level in patients with acute lung injury. A prospective, randomized clinical trial involving 30 patients with acute lung injury was designed and conducted over 7 days. The measured outcomes included hemodynamics, acute physiology and chronic health evaluation (APACHE II) scores, and oxygenation. The serum specimens were analyzed with enzyme-linked immunoassay (ELISA) for epidermal growth factor at baseline, then 3 and 7 days after acute lung injury. The ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FIO2) improved in the furosemide-treated group within 24 hours (from 180 to 264; P = .01). The mean arterial pressure and heart rate was greater in this group than in the control group (that received no furosemide) on day 7 (P = .027). The mean arterial pressure increased and the heart rate decreased over time in the treatment group, but not significantly. Serum epidermal growth factor levels also were not significantly different between the furosemide treatment group and the control group (P > .05). Continuous furosemide infusion improves oxygenation and hemodynamics in patients with acute lung injury, but not through a change in the serum epidermal growth factor level. Further study is needed to determine the exact mechanism of furosemide action in patients with acute lung injury and acute respiratory distress syndrome.

APACHE↗

Pharmacokinetic and pharmacodynamic interaction between furosemide and metolazone in man.

In various clinical situations a poor diuretic response to furosemide may be improved by the addition of metolazone. The mechanism of this additive effect is unclear. The purpose of the present investigation was to establish whether metolazone changes the pharmacokinetics of furosemide and by this mechanism enhances the diuretic effect. Eight volunteers were given an intravenous infusion of 4 mg h-1 of furosemide for 12 h. After 6 h 2.5 mg metolazone were administered orally. The addition of metolazone increased diuresis, urinary excretion of sodium and chloride (P less than 0.01), but decreased urinary excretion of calcium (P less than 0.01), while furosemide excretion remained unchanged. Total body clearance and renal clearance values of furosemide were similar before and after administration of metolazone. Our data confirm the additive diuretic effect of the combination treatment metolazone-furosemide and show for the first time a distinct hypocalciuric action of metolazone, similar to thiazides. Moreover metolazone does not affect the pharmacokinetics of furosemide.

Calcium↗

The binding of furosemide to serum proteins in elderly patients: displacing effect of phenprocoumon.

The percentual binding of furosemide (5 micrograms/ml) was slightly but significantly lower in serum from elderly patients than in serum from normal blood donors (96.5 +/- 0.7 versus 97.9 +/- 0.3). A significant positive correlation was demonstrated between protein binding and albumin concentration in serum. The reduced binding in the elderly could be explained by an observed decrease in the concentration of albumin in the elderly. The percentual binding did not change in samples obtained during the first hour after the intravenous administration of 40 mg furosemide. Of 4-chloro-5-sulfamoyl antranilic acid (CSA) and antranilic acid (A) about 60% were bound to serum proteins in vitro and none of these two compounds affected the protein binding of furosemide. The addition of phenprocoumon (PPC) caused significant decreases in the percentual binding of furosemide in serum (5 microgram/ml) at PPC values of 10 microgram/ml and more. The effect of PPC on the binding of furosemide was studied in vivo in 7 patients receiving 40 mg furosemide intravenously without and with the simultaneous intravenous administration of PPC (3 mg per 10 kg body weight). In good accordance with the in vitro experiments the modest average decrease in furosemide binding, caused by concentrations of PPC not exceeding 6.2 micrograms/ml, was not significant.

4-Hydroxycoumarins↗

Mechanisms behind the relaxing effect of furosemide on the isolated rabbit ear artery.

The effect of furosemide on isometric contraction and 86Rb uptake were studied in the isolated rabbit central ear artery (CEA). A concentration-dependent relaxing effect of furosemide (0.06 mM-1.0 mM) was found in vessel segments with intact endothelium. The maximal relaxation was 28.6 +/- 3.9% (10). The effect was not diminished in segments deprived of endothelium, and removal of endothelium itself caused no change of the force development to electrical field stimulation. The relaxing effect was time-dependent and stimulation-dependent and was not significantly affected by membrane depolarization induced by increasing external [K+] from 10 to 120 mM. The 86Rb uptake was inhibited by both furosemide and ouabain (8.0 +/- 0.5(8) and 5.3 +/- 0.5(8) versus 12.8 +/- 0.9(16) nmol (K+).mm-1.(10 min.)-1 in the furosemide (1.0 mM), ouabain (1.0 mM) and control groups, respectively) without interaction between the two drugs. The 86Rb uptake was not further inhibited by increasing the furosemide concentration from 0.12 mM to 1.0 mM. Our results suggest: firstly, the direct relaxing effect of furosemide on isolated vessel segments is endothelium-independent and secondly, the inhibition of the Na(+)-K(+)-Cl- cotransport and a possible consequent hyperpolarization of the membrane is unlikely to be the sole mechanism responsible for the vasorelaxant effect of furosemide. The demonstrated direct effect on vascular tone may be of clinical importance in situations with very high plasma concentrations of the drug or very low concentrations of serum albumin.

Animals↗

Intermittent bolus injection versus continuous infusion of furosemide in normal adult greyhound dogs.

Several studies in human subjects have demonstrated greater diuresis with constant rate infusion (CRI) furosemide than intermittent bolus (IB) furosemide. This study was conducted to compare the diuretic efficacy of the same total dose of IB furosemide and CRI furosemide in 6 healthy, adult Greyhound dogs in a randomized crossover design with a 2-week washout period between treatments. For IB administration, dogs received 3 mg/kg at 0 and 4 hours. For CRI administration, dogs received a 0.66 mg/kg loading dose followed by 0.66 mg/kg/h over 8 hours. The same volume of fluid was administered for both methods. Urine output was quantified hourly. Urine electrolyte concentrations, urine specific gravity (USG), packed cell volume (PCV), total protein (TP), serum electrolyte concentrations, total carbon dioxide (TCO2), serum creatinine (sCr), and blood urea nitrogen (BUN) were determined every 2 hours. Urine production and water intake were greater (P < or = 0.05) for CRI than IB. Urine sodium and calcium losses were greater (P < 0.05) and urine potassium loss was less (P = 0.03) for CRI than IB, but there was no evidence of a difference between methods for urine magnesium and chloride losses. Serum chloride concentration was less (P < 0.001), sCr concentration greater (P = 0.04). TP greater (P = 0.01), and PCV greater (P = 0.003) for CRI than IB. No differences in USG, TCO2, BUN, or serum potassium, sodium, and magnesium concentrations were detected between methods. The same total dose of CRI furosemide resulted in more diuresis, natriuresis, and calciuresis and less kaliuresis than IB furosemide in these normal Greyhound dogs over 8 hours, suggesting that furosemide is a more effective diuretic when administered by CRI than by IB.

Animals↗

Furosemide-induced renal medullary hypoperfusion in the rat: role of tissue tonicity, prostaglandins and angiotensin II.

Furosemide (frusemide)-induced renal medullary hypoperfusion provides a model for studies of the dependence of local circulation on tissue tonicity. We examined the role of medullary prostaglandins (PG) and adenosine (Ado) as possible mediators of the response to furosemide. Furosemide was infused i.v. at 0.25 mg kg(-1) h(-1) in anaesthetized rats, untreated or treated with intramedullary indomethacin (Indo) or Ado. An integrated set-up was used to measure renal medullary laser-Doppler flux (MBF) and medullary ionic tonicity (electrical admittance, Y), and to infuse Indo and Ado directly into the medulla. The cortical flux was measured on kidney surface. The excretion of water, sodium and total solute was also determined. Intramedullary Indo (1 mg kg(-1) h(-1)) decreased MBF 18 +/- 5% and increased tissue Y 14 +/- 3% (both significant); the treatment abolished the post-furosemide decrease in MBF (-22% in untreated group) and enhanced slightly the increase in renal excretion. Intramedullary Ado (5 mg kg(-1) h(-1)) did not change baseline MBF or Y; the post-furosemide decreases in MBF (-22%) and Y, and the increase in renal excretion were preserved. We conclude that a decrease in intramedullary PG activity secondary to decreased medullary hypertonicity mediates the fall in medullary perfusion in response to furosemide; the hypoperfusion may help restore the initial tonicity. Together with the earlier evidence on the dependence of post-furosemide medullary hypoperfusion on angiotensin II, the study exposes its interaction with PG in the control of medullary circulation. Adenosine is not involved in medullary vascular responses to decreased tissue hypertonicity.

Angiotensin II↗

Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans.

We analyzed data from three prospective, controlled, randomized, double-blind clinical trails to determine whether furosemide increases the nephrotoxicity and auditory toxicity of aminoglycosides. All patients who received at least 72 h of treatment and who had no other cause for nephrotoxicity or auditory toxicity were included in the analysis. Nephrotoxicity developed in 10 of 50 (20.0%) patients given furosemide and in 38 of 222 (17.1%) patients not given furosemide (P greater than 0.3). Auditory toxicity developed in 5 of 23 patients (21.7%) given furosemide and in 28 of 119 patients (23.5%) not given furosemide (P greater than 0.3). In each case, the groups receiving and not receiving furosemide did not differ in mean age, initial creatinine, duration of aminoglycoside therapy, mean change in auditory acuity or creatinine, mean number of days to the development of toxicity, the frequency with which gentamicin, tobramycin, amikacin, or cephalothin was administered, or the mean predose and 1-h postdose plasma aminoglycoside levels. We conclude that furosemide use should not be considered a major risk factor for the development of aminoglycoside-induced nephrotoxicity or auditory toxicity.

Aminoglycosides↗

Renal and renin responses to furosemide in conscious lambs during postnatal maturation.

Despite the widespread use of furosemide in the treatment of various fluid and electrolyte disorders in the preterm and term human infant and child, the physiological effects of this potent diuretic agent on renal function and renin release during postnatal maturation are poorly understood. To test the hypothesis that the renal and renin responses to furosemide are altered during postnatal maturation, experiments were carried out in conscious chronically instrumented newborn lambs (11 +/- 3 days, n = 7) and older lambs (28 +/- 3 days, n = 6), at least 5 days after surgery under halothane anesthesia for placement of catheters. Renal function and plasma renin activity (PRA) were measured for 1 h before and 2 h after intravenous injection of furosemide (2 mg/kg; 0.2 mL/kg) or vehicle (0.2 mL/kg). Glomerular filtration rate (GFR) decreased after furosemide administration to both groups of lambs. However, the time course of this decrease in GFR was different, occurring sooner in older lambs (30 min) than in newborns (90 min). GFR remained significantly decreased after 150 min in both age-groups. The natriuretic and diuretic responses to furosemide were similar in newborns and older lambs, peak diuretic and natriuretic responses occurring within 30 min. PRA increased dramatically in both age-groups after furosemide; the response was accentuated in newborns. After 2 h, PRA was still elevated in newborns but returned towards control levels in older lambs. These data demonstrate that both the GFR and renin responses to furosemide are altered during ontogeny.

Animals↗

Multi-detector row CT urography of normal urinary collecting system: furosemide versus saline as adjunct to contrast medium.

PURPOSE: To retrospectively evaluate whether intravenous furosemide, either alone or in addition to intravenous saline, improved depiction of the normal urinary collecting system at multi-detector row computed tomographic (CT) urography. MATERIALS AND METHODS: Institutional review board approval for review of patient images and medical records was obtained; informed consent was not required for this HIPAA-compliant study. Excretory phase images from multi-detector row CT urography in 87 patients (44 women, 43 men; age range, 21-83 years; mean, 53 years) were reviewed. Examinations were performed with, in addition to intravenous contrast medium, 250 mL of intravenous normal saline alone (n = 35), both 250 mL of normal saline and 10 mg of intravenous furosemide (n = 26), or 10 mg of furosemide alone (n = 26). Three readers, blinded to the imaging technique used, individually assigned opacification scores to each of six urinary collecting system segments. Urinary distention was assessed by one reader by measuring transverse widths of the proximal, middle, and distal ureteral segments. Mean opacification scores for each segment and mean ureteral width measurements for each technique were compared by using the Student t test. RESULTS: Mean opacification scores achieved with furosemide were significantly higher than those achieved with saline for the middle (P </= .008) and distal (P < .001) ureteral segments. Similarly, mean ureteral widths were significantly higher with furosemide than with saline for the middle (P </= .04) and distal segments (P = .01). There was no overall benefit of administering both saline and furosemide. CONCLUSION: To optimize opacification and distention of the normal urinary collecting system, contrast material-enhanced multi-detector row CT urography may be supplemented with intravenous furosemide alone.

Adult↗