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Parenteral veterinary furosemide is a 50-mg/mL solution with a pH of 8.0-9.3. The purpose of this study was to determine whether a commonly used veterinary formulation of 50 mg/mL of furosemide solution could be diluted in vitro without precipitation. Furosemide 50 mg/mL was diluted to concentrations of 10 and 5 mg/mL with 5% dextrose in water (D5W), 0.9% saline, lactated Ringer solution (LRS), and sterile water. Acidic sterile water and basic sterile water solutions were made by the addition of hydrochloric acid and sodium hydroxide, respectively, for use as controls to assess the effect of pH extremes for each concentration. After furosemide dilution, the final pH of each sample was measured, and samples were grossly and microscopically examined for clarity and crystal formation immediately and 1, 3, 5, and 8 hours after dilution. Gross precipitation and microscopic crystals were immediately observed in the acidic controls. Solutions of 5 mg/mL in LRS and 0.9% saline became slightly cloudy immediately, but no crystals were observed microscopically for 8 hours. Solutions of 10 mg/mL in D5W, 0.9% saline, LRS, and sterile water and solutions of 5 mg/mL in D5W and sterile water and the basic control were grossly clear, and no microscopic crystals were observed for 8 hours. On the basis of the results obtained in this in vitro investigation, this veterinary formulation of furosemide 50 mg/mL can be diluted without precipitation to a concentration of 10 mg/mL with D5W, 0.9% saline, LRS, or sterile water and to 5 mg/mL with D5W or sterile water and held for 8 hours.  相似文献   
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Introduction

Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide.

Animals

Six healthy male dogs.

Methods

Raw data and stored samples from one arm of a previously published study were further analyzed to mechanistically investigate causes of diuretic braking in these dogs. Urine volume was recorded hourly during a 5-h furosemide CRI. Urine and blood samples were collected hourly to measure serum and urine electrolytes, urine aldosterone, and plasma and urine furosemide. Serum electrolyte fractional excretion was calculated. Urine sodium concentration was indexed to urine potassium (uNa:uK) and urine furosemide (uNa:uFur) concentrations, plasma furosemide concentration was indexed to urine furosemide concentration (pFur:uFur), and urine aldosterone was indexed to urine creatinine (UAldo:C). Temporal change and the relationship to urine volume were evaluated for these measured and calculated variables.

Results

Urine volume was significantly correlated with urine electrolyte amounts and with uNa:uK. The ratio of pFur:uFur decreased during the infusion, whereas furosemide excretion was unchanged.

Conclusions

There was a strong relationship between urine volume and absolute urine electrolyte excretion. Urine volume was strongly correlated to uNa:uK, giving it potential as a spot indicator of urine production during diuresis. The decrease in uNa:uK over time during the infusion is consistent with mineralocorticoid modification of urinary electrolyte excretion, supporting renin–angiotensin–aldosterone activation as a cause of diuretic braking in this model.  相似文献   
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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.  相似文献   
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Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.  相似文献   
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Objective

The goal of this study was to investigate the short-term safety and diuretic efficacy of furosemide constant rate infusion (CRI) diluted with 5% dextrose in water (D5W) compared to dilution with 2.4% hypertonic saline in healthy dogs.

Animals

Six healthy dogs.

Methods

Dogs were studied in a randomized, blinded, crossover manner. Furosemide 3.3mg/kg was diluted to 2.2mg/mL with either 1.5mL/kg D5W for the DEX method or with 1.0mL/kg D5W and 0.5mL/kg of 7.2% hypertonic saline for the H-SAL method. After a 0.66mg/kg furosemide IV bolus, the infusion rate was 0.3 mL/kg/hr for 5 h such that both methods delivered 0.66 mg/kg/hr (total 3.3mg/kg) furosemide in equal volume for the study duration. Urine output, water intake, central venous pressure (CVP), physical parameters, furosemide concentrations, blood and urine electrolytes, and urine aldosterone to creatinine ratio (UAldo:C) were evaluated.

Results

Measured variables were not different between methods but showed changes over time consistent with diuresis. Mean CVP decreased over time similarly for both methods. Plasma furosemide and urine concentrations were stable and not different between methods. Both furosemide CRI methods showed an increase in the UAldo:C, however, the rise was greater for DEX than for H-SAL.

Conclusions

Diuresis was similar for both furosemide CRI methods; however, the H-SAL method induced less renin-angiotensin-aldosterone system activation than the DEX method. The absence of intravascular volume expansion based on CVP suggests that dilution of a furosemide CRI with 2.4% hypertonic saline may be well tolerated in heart failure.  相似文献   
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