Utility of F-15 diuretic MAG3 renography in assessment of paediatric hydronephrosis.

INTRODUCTION: Diuretic renography is crucial in evaluation of paediatric hydronephrosis. Furosemide is conventionally given 15-20 min after radiolabelled tracer (F+15/F+20 protocol), however this is equivocal in around 15% of patients. Giving furosemide 15 min prior to tracer (F-15 MAG3 protocol) has been suggested as an additional tool in the investigation of patients with suspected upper urinary tract obstruction. However, the role of this method in assessment and management of paediatric hydronephrosis is not widely reported. OBJECTIVE: To investigate utility of F-15 renograms in children with hydronephrosis being assessed for Pelvi-Ureteric Junction Obstruction (PUJO). STUDY DESIGN: Retrospective review of patients <16 years old undergoing F-15 MAG3 renogram between 2018 and 2021 in our tertiary paediatric surgical centre. Data collected included patient demographics, mode of presentation, investigations, management and outcomes. RESULTS: Eighteen patients were included. Median age at F-15 renogram was 7.3 years. Eleven patients presented with antenatal hydronephrosis, 5 with symptoms in childhood and 2 with incidental hydronephrosis on trauma imaging. Fourteen patients were symptomatic. Ten had a prior non-obstructed F+20 renogram but persisting symptoms suggestive of PUJO. Seven had previous equivocal F+20 renograms. One symptomatic patient directly underwent an F-15 renogram. A conclusive result was obtained in 16/18 (89%); 11 patients had obstructed curves and 5 non-obstructed. Two asymptomatic patients' scans were inconclusive. All symptomatic patients had conclusive scans. Of 11 patients with an obstructed F-15, 9 have undergone pyeloplasty to date. All have had post-operative resolution in symptoms and static or improved post-operative ultrasound. One patient with an inconclusive scan underwent pyeloplasty due to persisting hydronephrosis and parent preference. Three patients with non-obstructed F-15 renograms have been discharged. One symptomatic patient with a non-obstructive F-15 had a ureteric stent inserted due to persistent flank pain; 1 continues under surveillance. DISCUSSION: It is known that conventional F+20 MAG3 renograms can give equivocal results. Published experience suggests that F-15 renograms are conclusive in the majority of patients. Routine primary use is, however, discouraged as they can 'over diagnose' obstruction and limit the study of tracer transit under physiological flow rates. This study indicates that the F-15 renogram is a useful adjunct in the assessment of patients with symptoms suggestive of PUJO who have previously had an equivocal or a non-obstructed F+20 renogram. CONCLUSION: F-15 renogram was conclusive in 89% of patients. We recommend using F-15 renograms to aid surgical decision-making in children with equivocal F+20 renograms, especially in the presence of symptoms.

Prospective assessment of the impact of intraoperative diuretics in kidney transplant recipient surgery.

BACKGROUND: The use of intraoperative diuretics, such as furosemide or mannitol, during kidney transplantation has been suggested to reduce the rate of delayed graft function (DGF). The evidence base for this is sparse, however, and there is substantial variation in practice. We sought to evaluate whether the use of intraoperative diuretics during kidney transplantation translated into a reduction in DGF. METHODS: We conducted a cohort study evaluating the use of furosemide or mannitol given intraoperatively before kidney reperfusion compared with control (no diuretic). Adult patients receiving a kidney transplant for end-stage renal disease were allocated to receive furosemide, mannitol, or no diuretic. The primary outcome was DGF; secondary outcomes were graft function at 30 days and perioperative changes in potassium levels. Descriptive and comparative statistics were used where appropriate. RESULTS: A total of 162 patients who received a kidney transplant from a deceased donor (either donation after neurologic determination of death or donation after circulatory death) were included over a 2-year period, with no significant between-group differences. There was no significant difference in DGF rates between the furosemide, mannitol, and control groups. When the furosemide and mannitol groups were pooled (any diuretic use) and compared with the control group, however, there was a significant improvement in the odds that patients would be free of DGF (odds ratio 2.10, 95% confidence interval 1.06-4.16, 26% v. 44%, p = 0.03). There were no significant differences noted in any secondary outcomes. CONCLUSION: This study suggests the use of an intraoperative diuretic (furosemide or mannitol) may result in a reduction in DGF in patients undergoing kidney transplantation. Further study in the form of a randomized controlled trial is warranted.

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission.

Loop diuretics are a standard pharmacologic therapy in heart failure (HF) management. Although furosemide is most frequently used, torsemide and bumetanide are increasingly prescribed in clinical practice, possibly because of superior bioavailability. Few real-world comparative effectiveness studies have examined outcomes across all 3 loop diuretics. The study goal was to compare the effects of loop diuretic prescribing at HF hospitalization discharge on mortality and HF readmission. We identified patients in Medicare claims data initiating furosemide, torsemide, or bumetanide after an index HF hospitalization from 2007 to 2017. We estimated 6-month risks of all-cause mortality and a composite outcome (HF readmission or all-cause mortality) using inverse probability of treatment weighting to adjust for relevant confounders. We identified 62,632 furosemide, 1,720 torsemide, and 2,389 bumetanide initiators. The 6-month adjusted all-cause mortality risk was lowest for torsemide (13.2%), followed by furosemide (14.5%) and bumetanide (15.6%). The 6-month composite outcome risk was 21.4% for torsemide, 24.7% for furosemide, and 24.9% for bumetanide. Compared with furosemide, the 6-month all-cause mortality risk was 1.3% (95% confidence interval [CI]: -3.7, 1.0) lower for torsemide and 1.0% (95% CI: -1.2, 3.2) higher for bumetanide, and the 6-month composite outcome risk was 3.3% (95% CI: -6.3, -0.3) lower for torsemide and 0.2% (95% CI: -2.5, 2.9) higher for bumetanide. In conclusion, the findings suggested that the first prescribed loop diuretic following HF hospitalization is associated with clinically important differences in morbidity in older patients receiving torsemide, bumetanide, or furosemide. These differences were consistent for the effect of all-cause mortality alone, but were not statistically significant.

Nebulised furosemide for the treatment of patients with obstructive lung disease: a systematic review protocol.

INTRODUCTION: Obstructive lung diseases (OLDs) such as asthma and chronic obstructive pulmonary disease are major global sources of morbidity and mortality. Current treatments broadly include bronchodilators such as beta agonists/antimuscarinics and anti-inflammatory agents such as steroids. Despite therapy patients still experience exacerbations of their diseases and overall decline over time. Nebulised furosemide may have a novel use in the treatment of OLD. Multiple small studies have shown improvement in pulmonary function as well as dyspnoea. This systematic review will aim to summarise and analyse the existing literature on nebulised furosemide use in OLD to guide treatment and future studies. METHODS AND ANALYSIS: We will identify all experimental studies using nebulised/inhaled furosemide in patients with asthma or chronic obstructive pulmonary disease that report any outcome. Databases will include EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment and the NHS Economic Evaluation Database (1995-2015). We will also search ClinicalTrials.gov and the WHO-International Clinical Trials Registry Platform. Two reviewers will independently determine trial eligibility. For each included trial, we will perform duplicate independent data extraction, risk of bias assessment and evaluation of the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Ethical approval will not be applicable to this systematic review. The results of the study will be communicated through publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021284680.

Monitoring kidney size to interpret MRI-based assessment of renal oxygenation in acute pathophysiological scenarios.

AIM: Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T2 and T2 * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here, we used dynamic MRI to monitor KS for physiological interpretation of T2 * and T2 changes in acute pathophysiological scenarios. METHODS: KS was determined from T2 *, T2 mapping in rats. Six interventions that acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions that change the blood and/or tubular volume. A biophysical model was used to estimate changes in O2 saturation of hemoglobin from changes in T2 * and KS. RESULTS: Upon aortic occlusion KS decreased; this correlated with a decrease in T2 *, T2 . Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T2 *, T2 . Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T2 *, T2 . Hypoxemia induced mild reductions in KS and T2 *, T2 . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T2 *, T2 followed by a decrease. Furosemide caused T2 *, T2 elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T2 *. CONCLUSION: Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T2 *, T2 . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies.

Occurrence, ecological risk assessment and prioritization of pharmaceuticals and abuse drugs in estuarine waters along the São Paulo coast, Brazil.

The pollution of the surface waters by pharmaceuticals and personal care products (PPCPs) has attracted worldwide attention, but data regarding their occurrence and potential risks for the aquatic biota on tropical coastal rivers of South America are still scarce. In this context, the occurrence and the preliminary ecological risk assessment of eleven pharmaceuticals of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine) were investigated, for the first time, in five rivers of São Paulo, southeast Brazil, covering a coastline of about 140 km, namely Perequê River, Itinga River, Mongaguá River, Itanhaém River and Guaraú River. Although these five rivers are born in well-preserved areas of the Atlantic rainforest biome, on its way to sea and when they cross the urban perimeter, they receive untreated sewage discharges containing a complex mixture of contaminants. In addition, a "persistence, bioaccumulation and toxicity" (PBT) approach allowed to pre-select the priority PPCPs to be monitored in this coastline. Identification of several PPCPs in the samples was done using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Ten PPCPs were successfully quantified in all five rivers, namely caffeine (9.00-560.00 ng/L), acetaminophen (

Diuretic Changes, Health Care Resource Utilization, and Clinical Outcomes for Heart Failure With Reduced Ejection Fraction: From the Change the Management of Patients With Heart Failure Registry.

BACKGROUND: Diuretics are a mainstay therapy for the symptomatic treatment of heart failure. However, in contemporary US outpatient practice, the degree to which diuretic dosing changes over time and the associations with clinical outcomes and health care resource utilization are unknown. METHODS: Among 3426 US outpatients with chronic heart failure with reduced ejection fraction in the Change the Management of Patients with Heart Failure registry with complete medication data and who were prescribed a loop diuretic, diuretic dose increase was defined as: (1) change to a total daily dose higher than their previous total daily dose, (2) addition of metolazone to the regimen, (3) change from furosemide to either bumetanide or torsemide, and the change persists for at least 7 days. Adjusted hazard ratios or rate ratios along with 95% CIs were reported for clinical outcomes among patients with an increase in oral diuretic dose versus no increase in diuretic dose. RESULTS: Overall, 796 (23%) had a diuretic dose increase (18 episodes per 100 patient-years). The proportion of patients with dyspnea at rest (38% versus 26%), dyspnea at exertion (79% versus 67%), orthopnea (32% versus 21%), edema (60% versus 43%), and weight gain (40% versus 23%) were significantly (all P <0.001) higher in the diuretic increase group. Baseline angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (hazard ratio, 0.75 [95% CI, 0.65-0.87]) use were associated with lower likelihood of diuretic increase over time. Patients with a diuretic dose increase had a significantly higher number of heart failure hospitalizations (rate ratio, 2.53 [95% CI, 2.10-3.05]), emergency department visits (rate ratio, 1.84 [95% CI, 1.56-2.17]), and home health visits (rate ratio, 1.88 [95% CI, 1.39-2.54]), but not all-cause mortality (hazard ratio, 1.10 [95% CI, 0.89-1.36]). Similarly, greater furosemide dose equivalent increases were associated with greater resource utilization but not with mortality, compared with smaller increases. CONCLUSIONS: In this contemporary US registry, 1 in 4 patients with heart failure with reduced ejection fraction had outpatient escalation of diuretic therapy over longitudinal follow-up, and these patients were more likely to have sign/symptoms of congestion. Outpatient diuretic dose escalation of any magnitude was associated with heart failure hospitalizations and resource utilization, but not all-cause mortality.

Assessment of the Potential for Veverimer Drug-Drug Interactions.

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.

Assessment of glomerular and tubular function to guide fluid management in a pre-eclamptic critical patient with oliguria and volume overload: case report.

Oliguria in the setting of critically ill patients is usually treated by admini-stering fluids and furosemide [1]. Invasive therapies, namely renal replacement therapies (RRT), are reserved for patients in whom less invasive measures have failed [2], especially if acute pulmonary oedema complicates the clinical picture [1]. Intravascular volume depletion elicits a kidney response consisting of augmented sodium retention at Henle's loop and water at the collecting tubules. In such conditions, loop diuretics such as furosemide would be less effective to improve diuresis and water loss than osmotic diuretics such as mannitol [3, 4]. This case report aims to highlight the utility of the assessment of the glomerular and tubular functions to identify an ineffective diuretic strategy and to select a successful one, which prevented the use of invasive RRT. A 33-year-old female patient suffering from preeclampsia (gestational age was 35 + 6 weeks) was admitted to our Post-surgical Intensive Care Unit (PICU) after an urgent caesarean section performed under spinal anaesthesia, without further incidents.

In vitro Comparative Quality Assessment of Different Brands of Furosemide Tablets Marketed in Northwest Ethiopia.

BACKGROUND: The use of ineffective and poor quality drugs endangers therapeutic treatment and may lead to treatment failure. For desired therapeutic effect, drugs should contain the appropriate amount of active pharmaceutical ingredient and the required physical characteristics. AIM: The aim of this study was to evaluate quality as well as physicochemical bioequivalence of different brands of furosemide tablets marketed in Bahir Dar, Northwest Ethiopia. METHODS: Five different brands of furosemide tablets were purchased from community pharmacies in Bahir Dar city, Northwest Ethiopia. The quality control parameters of furosemide tablets were determined by identification, weight variation, disintegration, assay and dissolution tests and the results were compared with USP and BP pharmacopoeial standards. Difference (f1) and similarity (f2) factors were calculated to assess in vitro bioequivalence requirements. RESULTS: Identification test results revealed that all samples contained the stated active pharmaceutical ingredients. The results of weight variation tests indicated that all samples complied with USP specification limits. The active pharmaceutical ingredients quantitative assay showed that all the brands of furosemide tablets were between the 90% and 105% limit of label claim. Similarly, all samples fulfilled disintegration time (i.e., ≤30 min) and dissolution tolerance limits (i.e., Q ≥80% at 60 min). Hence, none of the samples were found to be counterfeit and/or substandard. Difference factor (f1) values were <15 and similarity factor (f2) values were >50 for all the tested brands of furosemide tablets. CONCLUSION: This study revealed that all the furosemide brands met the quality specification of weight variation, hardness, friability, dissolution, disintegration and assay. The study also indicated similarity in the dissolution profile of the brands of furosemide tablets with the innovator product. Hence, all of these generic brands could be substituted with the innovator product in clinical practice.

Outdoor temperature and survival benefit of empiric potassium in users of furosemide in US Medicaid enrollees: a cohort study.

OBJECTIVE: Heat is associated with elevated all-cause mortality, and furosemide-induced potassium depletion might be worsened by heat-induced sweating. Because empiric potassium is associated with a marked survival benefit in users of furosemide at a dose of ≥40 mg/day, we hypothesised that this empiric potassium's survival benefit would increase with higher temperature (≥24°C). DESIGN: Cohort study. SETTING: Outpatient setting, captured by Medicaid claims, supplemented with Medicare claims for dual enrollees, from 5 US states from 1999 to 2010, linked to meteorological data. POPULATION/PARTICIPANTS: Furosemide (≥40 mg/day) initiators among adults continuously enrolled in Medicaid for at least 1 year prior to cohort entry (defined as the day following the dispensing day of each individual's first observed furosemide prescription). EXPOSURE: Interaction between: (1) empiric potassium, dispensed the day of or the day following the dispensing of the initial furosemide prescription, and (2) daily average temperature and daily maximum temperature, examined separately. OUTCOME: All-cause mortality. RESULTS: In 1:1 propensity score matched cohorts (total n=211 878) that included 89 335 person-years and 9007 deaths, all-cause mortality rates per 1000 person-years were 96.0 (95% CI 93.2 to 98.9) and 105.8 (95% CI 102.8 to 108.9) for potassium users and non-users, respectively. The adjusted OR of all-cause mortality for potassium use declined (ie, its apparent protective effect increased) as temperature increased, from a daily average temperature of about 28°C and a daily maximum temperature of about 31°C. This relationship was not statistically significant with daily average temperature, but was statistically significant with daily maximum temperature (p values for the interaction of potassium with daily maximum temperature and daily maximum temperature squared were 0.031 and 0.028, respectively). CONCLUSIONS: The results suggest that empiric potassium's survival benefit among furosemide (≥40 mg/day) initiators may increase as daily maximum temperature increases. If this relationship is real, use of empiric potassium in Medicaid enrollees initiating furosemide might be particularly important on hot days.

Serial assessment of spot urine sodium predicts effectiveness of decongestion and outcome in patients with acute heart failure.

AIMS: The clinical significance of the measurement of urine sodium concentration (UNa+ ) in response to loop diuretic administration in patients with acute heart failure (AHF) is still unsettled. We studied the association of serial measurements of spot UNa+ during the first 48 h of AHF treatment with the indices of decongestion, renal function, and prognosis. METHODS AND RESULTS: We enrolled 111 AHF patients, all of whom received intravenous furosemide on admission. The mean spot UNa+ significantly increased in the 6 h sample (P < 0.05 vs. baseline) and returned to baseline values in the 24 and 48 h samples. Based on the increase or decrease/no change of UNa+ in the 6 and 48 h samples vs. baseline, patients were divided into two groups at each time point, respectively. Patients did not differ in baseline clinical and laboratory characteristics. Patients with a decrease/no change of UNa+ in the 6 and 48 h samples had a lower weight loss during hospitalization. Patients with a decrease/no change of UNa+ in the 48 h sample had a poorer diuretic response and a significant increase in the urinary levels of the tubular biomarkers: kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Low UNa+ and decrease/no change in UNa+ in the 6 and 48 h samples were independent predictors of higher risk of all-cause mortality during 1-year follow-up (all P < 0.05). CONCLUSION: In AHF, low spot UNa+ and lack to increase UNa+ in response to intravenous diuretics are associated with poor diuretic response, markers of tubular injury and high risk of 1-year mortality.

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.

AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

Subcutaneous furosemide for the treatment of heart failure: a state-of-the art review.

The prevalence of heart failure (HF) is on the rise. By 2030, over eight million Americans (46% increase from current prevalence) will have heart failure. In the USA, approximately 30 billion dollars is spent annually on heart failure and this number will likely double in 2030. Thus, HF represents a significant economic burden. Acute decompensated heart failure (ADHF) is a clinical spectrum, which refers to increasing symptoms and signs of heart failure prompting an emergency room visit or hospitalization. In ADHF, inpatient administration of intravenous diuretic is the standard of care due to the variability in the absorption of oral diuretics. Within 30 days, 25-30% of these patients are readmitted with recurrent ADHF. Recent efforts have focused in reducing HF readmission, and thereby decreasing costs; hence, innovative outpatient treatment options have emerged. Subcutaneous furosemide use will potentially overcome the need to place intravenous lines, reduce associated expenses, and enable management of ADHF at home. This review presents data on the pharmacodynamics and pharmacokinetics of subcutaneous furosemide, scientific evidence on the use of this therapy in the palliative and hospice population, and its experimental use as an outpatient therapy and/or as a bridge from inpatient to home.

Edema of Advanced Cancer: Prevalence, Etiology, and Conservative Management-A Single Hospice Cross-Sectional Study.

CONTEXT: Edema of advanced cancer, seldom recognized in the literature, significantly impairs patient quality of life. OBJECTIVES: The purpose was to assess edema frequency, etiology, and impact on common symptoms and present its conservative management. METHODS: A prospective analysis of 784 patients admitted to a hospice was performed, of whom 119 were diagnosed with edema. For 18 patients with short life prognosis, an individually tailored physiotherapy (limb elevation, bandaging, manual lymphatic drainage, and Kinesio Taping) or subcutaneous needle drainage was administered. Forty-six patients with longer prognosis were treated by standardized limb bandaging (5-7 days) and re-evaluated, 28 of them with venous congestion resistant to enteral diuretics received supplementary furosemide infusion. RESULTS: Among those admitted with edema (96.6% with advanced cancer), 81.5% had bilateral and 10.9% generalized edema, 10.9% had lymphorrhea, 5.9% skin ulcerations, and in 27.7% edema was the main problem. The high mean comorbidity C3-index score (2.97) was observed. The main precipitating factors of the edema were chronic immobilization (79.8%) medications (58.8%), and congestive heart failure (28.6%). Before admission, 47.9% had received diuretics for edema and only 4.2% had physiotherapy. Among those re-evaluated (46 patients [84 limbs]), the mean reduction of limb volume (1.18L; 16.6%; P < 0.001) was accompanied by a decrease of edema symptoms/signs intensity and ESAS-Core by median 1 point (P < 0.002). CONCLUSION: Limb edema of advanced cancer occasionally treated by physical therapy concerns patients with numerous comorbidities and precipitating factors. It can be managed sufficiently with decongestive or supportive physiotherapy, depending on patients' life prognosis, symptom burden, edema stage, and progression.

[Prescription of furosemide in general medicine in Aquitaine: Prospective practice survey among universities general practitioners]. / Prescription de furosémide en médecine générale en Aquitaine. Enquête de pratique auprès des médecins généralistes maîtres de stages universitaires.

OBJECTIVES: Furosemide is essential in the management of patients with congestive heart failure, and provides important iatrogenic complications. We described the prescription of this treatment in general medicine, and tried to identify areas for optimizing its use. PATIENTS AND METHOD: We carried out a prospective inventory of the prescription of furosemide with the general practitioners of the universities of Bordeaux, between May 1, 2017 and July 30, 2017. RESULTS: We obtained data from 119 prescriptions of furosemide. The indications seemed well known, largely dominated by heart failure (67%) and its associated signs (24%). Clinical and biological follow-up (52%) and therapeutic education (42%) seemed relatively infrequent. CONCLUSIONS: Our study confirms the central role of the general practitioner in the prescription of furosemide, the predominant place of heart failure in its indications and the iatrogeny observed. We identified areas of optimization of the safety and effectiveness of the treatment. The reinforcement of training concerning heart failure and its treatments, a better communication between specialties, the implementation of reference systems dedicated to the prescription of furosemide and prescription support software seem promising.

Pharmacodynamic assessment of diuretic efficacy and braking in a furosemide continuous infusion model.

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.

[Transfusion practices in elderly patients: A descriptive study about 241 patients at the university hospital of Brest]. / Transfusion sanguine chez les personnes âgées : étude descriptive à propos de 241 patients au CHRU de Brest.

Red blood cell transfusion is commonly required for elderly patients with little specific guidelines for this population. We wished to study the transfusion practices for patients aged≥75 years transfused with red blood cells in all units of our institution. The aim of this work is to describe this population of patients and to compare the transfusion practices to the HAS and ANSM guidelines published in 2014. METHODS: An observational study was performed including patients≥75 years, transfused with red blood cells between 27th January to 27th March 2014. Analysis of data included the patients' typology, the characteristics of anemia, the indications and transfusion practices, and the adequation with the guidelines. RESULTS: Two hundred and forty-one patients were transfused during the period with 422 transfusion episodes (mean age 83±5.2 years, sex-ratio women/men 1.4 with 4.4±2 pathologies and 6.7±3.2 treatments). Only 4.5% of the patients were transfused in geriatric wards. In 61% of the cases, the anemia is acute and chronic in 39%. Fatigue was reported in 50.6% of the cases and dyspnee in 31.7%. A percentage of 31.1 of the patients were prescribed furosemide for transfusion. The mean transfusion recovery was 1.2±0.5g/dL. Two adverse events were reported. Overall, only 10.4% of the prescriptions were not compliant with the guidelines of 2014. CONCLUSION: In this study, we describe transfusion practices for patients aged≥75 years. Although the non-compliance with the guidelines is weak, it is possible to improve the transfusion practices taking care of the geriatric characteristics. Prospective studies on a larger scale have to be done to converge on a more consensual management.

Comparison of salt with low-dose furosemide and carperitide for treating acute decompensated heart failure: a single-center retrospective cohort study.

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as carperitide in terms of clinical outcome and is a cost-effective therapeutic strategy for the treatment of ADHF.

Microbial biotransformation of furosemide for environmental risk assessment: identification of metabolites and toxicological evaluation.

Some widely prescribed drugs are sparsely metabolized and end up in the environment. They can thus be a focal point of ecotoxicity, either themselves or their environmental transformation products. In this context, we present a study concerning furosemide, a diuretic, which is mainly excreted unchanged. We investigated its biotransformation by two environmental fungi, Aspergillus candidus and Cunninghamella echinulata. The assessment of its ecotoxicity and that of its metabolites was performed using the Microtox test (ISO 11348-3) with Vibrio fischeri marine bacteria. Three metabolites were identified by means of HPLC-MS and 1H/13C NMR analysis: saluamine, a known pyridinium derivative and a hydroxy-ketone product, the latter having not been previously described. This hydroxy-ketone metabolite was obtained with C. echinulata and was further slowly transformed into saluamine. The pyridinium derivative was obtained in low amount with both strains. Metabolites, excepting saluamine, exhibited higher toxicity than furosemide, being the pyridinium structure the one with the most elevated toxic levels (EC50 = 34.40 ± 6.84 mg L-1). These results demonstrate that biotic environmental transformation products may present a higher environmental risk than the starting drug, hence highlighting the importance of boosting toxicological risk assessment related to the impact of pharmaceutical waste.