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Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Italian Medicine Agency.

Patients with acute decompensated heart failure received intravenous furosemide at either a low or a high dose and either boluses every 12 hours or continuous infusion. At 72 hours, there was no significant difference in symptoms or in the change in creatinine level from baseline for either comparison. Acute decompensated heart failure is the most common cause of hospital admissions among patients older than 65 years of age and is responsible for more than 1 million hospitalizations annually in the United States. 1 Intravenous loop diuretics are an essential component of current treatment and are administered to approximately 90% of patients who are hospitalized with heart failure. 2 Despite decades of clinical experience with these agents, prospective data to guide the use of loop diuretics are sparse, and current guidelines are based primarily on expert opinion. 3 , 4 As a result, clinical practice varies widely with regard to both the mode . . .

Furosemide is the most commonly used diuretic in intensive care units (ICU). We aimed to evaluate the physiological effects of adjunctive acetazolamide with furosemide on diuresis and the prevention of potential furosemide-induced metabolic alkalosis. We performed a two-center, pilot, open-label, randomized trial. Where the treating physicians planned intravenous diuretic therapy, we randomized ICU patients to a bolus of furosemide (40 mg) plus acetazolamide (500 mg) (n = 15) or furosemide alone (40 mg) (n = 15). Urine output, additional furosemide use, acid-base parameters, and electrolytes were compared following a Bayesian framework. Adjunctive acetazolamide didn't increase urine output in the first six hours (mean difference: −112 ml, credible interval: [−742, 514]). However, compared with furosemide alone, it maintained a greater urine output response to furosemide over 24 h, with 100 % probability. Acetazolamide also acidified plasma (pH difference: −0.045, [−0.081, −0.008]) while alkalinizing urine (1.10, [0.04, 2.11]) at six hours, compared to furosemide alone with >95 % probability. Finally, we didn't observe severe acidosis or electrolyte disturbances over 24 h. Adjunctive acetazolamide may increase diuretic efficacy and counterbalance furosemide-induced metabolic alkalosis without safety concerns. Larger trials are warranted to verify these findings and assess their impacts on clinical outcomes. ACTRN12623000624684. A pilot trial of single versus dual diuretic therapy in the intensive care unit. •Pathophysiologic effects of adjunctive acetazolamide were assessed in this pilot RCT.•Acetazolamide may have preserved urine output response to furosemide.•Acetazolamide may have counterbalanced furosemide-induced metabolic alkalosis.•Adjunctive acetazolamide may not result in severe acidosis or electrolyte disturbance.•Larger trials to evaluate the effect of adjunctive acetazolamide appear justified.

The role of subtypes of vasopressin receptors in modulation of renal sodium reabsorption was studied in in vivo experiments on Wistar rats. Selective [V.sub.1a] receptor agonist reduced sodium reabsorption in the kidneys and expression of these receptors increased by practically 100 times. This effect was similar to the effect of furosemide. Selective V2 receptor agonist enhanced sodium reabsorption in the kidney and simultaneously increased reabsorption of solute-free water. Stimulation of V1b receptors did not affect sodium transport. Our findings attest to the key role of [V.sub.1a] receptors in the regulation of renal excretion of sodium ions. Key Words: kidney; vasopressin receptors; sodium; reabsorption

•The bioavailability of furosemide 80 mg/mL SC injection is equivalent to that of furosemide 80 mg IV.•Diuresis, natriuresis, and kaliuresis are similar with furosemide 80 mg/mL SC injection and furosemide 80 mg IV.•Furosemide 80 mg/mL SC injection was generally well tolerated. Furoscix (furosemide injection) 80 mg/10 mL is a pH neutral formulation administered subcutaneously (SC) over 5 hours to treat edema in adults with chronic HF or chronic kidney disease. Furosemide 80 mg/mL is a novel concentrated formulation administered as a single 1.0-mL SC injection that could improve convenience for patients. This randomized, open-label, phase 1 study assessed the pharmacokinetics, bioavailability, pharmacodynamics, and safety of furosemide 80 mg/mL SC versus furosemide 80 mg administered intravenously (IV). Healthy volunteers were randomized 1:1 to furosemide 80 mg/mL SC or furosemide 80 mg IV (two 40-mg boluses, 2 hours apart), and after a 3-day washout, received the opposite treatment. Plasma furosemide pharmacokinetics, urine output, and urinary sodium and potassium excretion were measured through 12 hours post-dose. Bioavailability (the primary endpoint) was assessed as the least-squares mean ratio (LSMR) of area under the curve (AUC) from time 0−last (AUClast) and 0−infinity (AUCinf) between furosemide SC and furosemide IV. Plasma furosemide pharmacokinetics were assessed noncompartmentally. Pharmacodynamics were assessed using a repeated measures, mixed model analysis. Safety was assessed through end of study. Twenty-one participants were randomized (furosemide SC/IV, n = 10; furosemide IV/SC, n = 11). The furosemide SC/IV LSMR (90% confidence interval [CI]) AUClast was 106.1% (102.7%, 109.6%), and LSMR (90% CI) AUCinf was 107.3% (103.9%, 110.8%). Furosemide 80 mg/mL SC had bioavailability equivalent to furosemide 80 mg IV, as the CIs fell within 80.0%–125.0%. Mean (SD) Cmax was 4532.9 (1497.7) ng/mL with furosemide 80 mg/mL SC and 10,087.6 (2804.7) ng/mL with furosemide IV. The therapeutic effects of furosemide 80 mg/mL SC on diuresis, natriuresis, and kaliuresis occurred within 1 hour of treatment and were consistent with those of furosemide IV at all time points. There was no significant difference between furosemide 80 mg/mL SC versus furosemide IV in total urine output or urinary sodium or potassium excretion at 0–6 hours, 0–8 hours, or 0–12 hours. Adverse events (AEs) occurred in 14 (66.7%) participants (furosemide SC, n = 11 [52.4%]; furosemide IV, n = 7 [35.0%]) and were mild or moderate. Ten (47.6%) participants had injection site AEs, all of which were treatment-related, mild, non-serious, and resolved. Injection site pain scores graded on a Likert 11-point scale remained low (mean, <0.4; median, 0) at all time points, were similar between groups, and decreased over time. Furosemide 80 mg/mL SC injection was generally well tolerated and had bioavailability, diuresis, natriuresis, and kaliuresis consistent with those of furosemide IV.

Furosemide (FUR) is a loop diuretic widely used in pediatric care. However, no standardized oral liquid formulation exists due to degradation concerns, particularly the formation of furosemide-related compound B (FUR-B). This study aimed to develop and validate the HPLC method for the simultaneous quantification of FUR, FUR-B, methylparaben (MP), and propylparaben (PP) in pediatric extemporaneous oral solutions. Chromatographic separation was achieved using a Symmetry® C18 column (4.6 × 250 mm, 5 µm) with a mobile phase of 0.1% acetic acid in water and acetonitrile (60:40, v/v) at 1.0 mL/min of flow with injection volume at 10 µL. Detection at 272 nm provided optimal sensitivity, especially for low concentrations of FUR-B. Forced degradation confirmed baseline separation of FUR from its degradation products. The condition showed high linearity (R2 > 0.995), accuracy (recoveries 98.2–101.0%), and precision (RSD ≤ 2%). Robustness and ruggedness tests under varied conditions, analysts, and intra-day yielded consistent performance. Application to extemporaneous formulations showed that refrigeration (2–8 °C) retained initial composition, while elevated temperatures (30 °C and 40 °C) promoted FUR degradation, with FUR-B increasing to 6.84% after 90 days and greater MP and PP degradation. This validated method offers a reliable analytical tool for monitoring chemical changes and supporting quality control of pediatric FUR extemporaneous formulations.

Background The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT. Methods FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT. Results FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died ( P  <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P  = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm ( P  = 0.002). Conclusion The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation. Trial registration clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.

Background Although current guidelines for AKI suggested against the use of furosemide in AKI management, the effect of furosemide on outcomes in real-world clinical settings remains uncertain. The aim of the present study was to investigate the association between furosemide administration and outcomes in critically ill patients with AKI using real-world data. Methods Critically ill patients with AKI were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) matched analysis was used to match patients receiving furosemide to those without diuretics treatment. Linear regression, logistic regression model, and Cox proportional hazards model were used to assess the associations between furosemide and length of stay, recovery of renal function, and in-hospital and 90-day mortality, respectively. Results A total of 14,154 AKI patients were included in the data analysis. After PS matching, 4427 pairs of patients were matched between the patients who received furosemide and those without diuretics treatment. Furosemide was associated with reduced in-hospital mortality [hazard ratio (HR) 0.67; 95% CI 0.61–0.74; P  < 0.001] and 90-day mortality [HR 0.69; 95% CI 0.64–0.75; P  < 0.001], and it was also associated with the recovery of renal function [HR 1.44; 95% CI 1.31–1.57; P  < 0.001] in over-all AKI patients. Nevertheless, results illustrated that furosemide was not associated with reduced in-hospital mortality in patients with AKI stage 0–1 defined by UO criteria, AKI stage 2–3 according to SCr criteria, and in those with acute-on-chronic (A-on-C) renal injury. Conclusions Furosemide administration was associated with improved short-term survival and recovery of renal function in critically ill patients with AKI. Furosemide was especially effective in patients with AKI UO stage 2–3 degree. However, it was not effective in those with AKI SCr stage 2–3 and chronic kidney disease. The results need to be verified in randomized controlled trials.

Background The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated. Results We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74–0.87) and 0.88 (95% CI 0.82–0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96–7.50), the pooled negative LR was 0.26 (95% CI 0.19–0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00–51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72–0.91) and 0.77 (95% CI 0.64–0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06–4.86) and 0.25 (95% CI 0.14–0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74–32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1–2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51–13.33). Conclusion The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.

The act of filling the bladder prior to obtaining an ultrasound is often the rate limiting factor in the diagnosis of ovarian torsion in pediatric females. The objective of this study was to evaluate if low dose furosemide plus IV fluid administration results in faster bladder filling time in comparison to IV fluid administration alone in females age 8–18 with suspected ovarian torsion. This was a randomized, placebo controlled, single blinded pilot study using convenience sampling to target females ages 8 to 18 years seen in the pediatric emergency department and undergoing a trans-abdominal pelvic US to assess for ovarian torsion. Enrolled patients were assigned to the experimental group, receiving 0.1 mg/kg (max 5 mg) of furosemide, or the control group, receiving a 5 mL normal saline (NS) flush. Point of Care Ultrasound (POCUS) evaluation of the bladder was performed every 30 min until the bladder was determined to be of adequate size and morphology to perform the trans-abdominal pelvic US. Bladder filling as confirmed by POCUS occurred a median of 90 min sooner in the furosemide group compared with the control group (p ≤0.001). Compared with the control group, radiology-performed US occurred 92 min sooner (p ≤0.001) and US interpretation by a radiologist occurred 94 min sooner (p ≤0.001) for individuals receiving furosemide. Furosemide administration leads to a statistically and clinically significant difference in the time to fill the bladder of pediatric females awaiting pelvic US and leads to more rapid ultrasonography and interpretation by a radiologist in our setting. •Bladder filling is time consuming for pediatric females awaiting pelvic ultrasound.•Evaluation of furosemide versus intravenous fluids for bladder filling.•Bladder shape, size, and volume evaluated with point-of-care ultrasound.•Furosemide lead to a 90 min faster bladder filling time.