Diuretics-Induced Acute Pancreatitis: Case Series with a Review of the Literature.

BACKGROUND: Although diuretic-induced Acute Pancreatitis (AP) cases are typically mild to moderate, severe and potentially fatal occurrences can arise. Case Series and Literature Review: We have, herein, presented a series of diuretic-induced AP cases from March 2018 to February 2024 of a 54-year-old woman treated with chlorthalidone, a 45-year-old male treated with hydrochlorothiazide, and a 48-year-old male treated with frusemide. The literature search has identified 26 cases published to date, 10 from frusemide and 16 from thiazide diuretics. The Naranjo adverse reaction probability scale has categorized all three drugs as "probable". All cases have responded to conservative treatment and cessation of the offending drug. Various mechanisms, such as hypersensitization, ischemia, direct cytotoxic effects, hypercalcemia, and dose-dependent idiosyncrasy, have been found to lead to intrapancreatic activation of pancreatic enzymes, resulting in drug-induced AP. CONCLUSION: Further research into the mechanisms and genetic factors contributing to diureticinduced AP is essential for enabling early diagnosis and management of diuretic-induced AP.

Diagnostic Performance and Interobserver Agreement of Diuretic 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Upper Urinary Tract Cancer.

BACKGROUND: Previous reports attempted to evaluate bladder cancer using 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) by washing out the excreted FDG with a diuretic. The purpose of this study was to evaluate the value of diuretic FDG PET/plain CT (drtPET/CT) and diuretic FDG PET/contrast-enhanced CT (drtPET/ceCT) in the assessment of upper urinary tract cancers. MATERIALS AND METHODS: A total of 66 patients underwent drtPET/CT for suspected upper urinary tract cancer (UUTC). The study targeted 29 patients who were strongly suspected of having UUTC and underwent magnetic resonance imaging (MRI) of the upper urinary tract. A total of 29 (24 male, five female) patients, with a mean ± SD age of 73 ± 3 (range, 43-84) years, had a suspected neoplasm in the upper urinary tract. They underwent FDG PET/plain and contrast-enhanced CT before and after a diuretic and MRI including diffusion-weighted imaging (DWI). A urologist and a physician board-certified in nuclear medicine and radiology independently interpreted the standard PET/CT (stdPET/CT), drtPET/CT, drtPET/ceCT, ceCT, and MRI with DWI images. Interobserver agreement and the diagnostic performance of each modality were evaluated. RESULTS: The kappa values of stdPET/CT, drtPET/CT, drtPET/ceCT, ceCT, and MRI were 0.381, 0.567, 0.7031, 0.448, and 0.185, respectively, with drtPET/ceCT showing the highest kappa value and the only one with good interobserver agreement (>60%). The area under the curve of drtPET/ceCT was 0.92, which was significantly higher than those of stdPET/CT (P=0.027) and MRI (P=0.047). CONCLUSIONS: In the present study, drtPET/ceCT had the best diagnostic performance and the highest interobserver agreement for detecting upper urinary tract urothelial cancers.

The Role of Subcutaneous Furosemide in Heart Failure Management: A Systematic Review.

BACKGROUND: Acute decompensated heart failure (ADHF) patients with symptomatic congestion often require in-hospital admission for intravenous (IV) diuretic, impacting both patient well-being and healthcare expenses. Subcutaneous (SC) furosemide has a potential to facilitate outpatient management of ADHF patients. Thus, this study aims to assess the efficacy and safety of SC furosemide utilization, offering a potential alternative to traditional IV administration. METHODS: A systematic search was conducted until April 14 2024 across scientific databases. This review included studies comparing SC furosemide with oral and IV formulations in adult HF patients. RESULTS: This study analyzed 687 patients from 20 studies. The results demonstrate that SC furosemide can effectively manage symptomatic congestion in HF patients and results in significant cost reductions, symptom relief, and improved quality of life. Although further investigation into mortality rates is needed, SC furosemide demonstrates efficacy comparable to IV furosemide in diuresis and weight loss, with similar bioavailability and natriuretic effects. Adverse events are generally minor, predominantly related to skin irritation. Innovative strategies, such as developing isotonic alkaline solutions and improved infusion devices, are being explored to address these challenges. CONCLUSION: SC furosemide offers a promising alternative for managing ADHF, particularly in symptomatic HF patients with volume overload. The integration of SC furosemide into routine clinical practice and future guidelines, could optimize the management of HF, reducing hospital admission and improving patient outcomes.

Thoracic Fluid Content as an Indicator of High Intravenous Diuretic Requirements in Hospitalized Patients with Decompensated Heart Failure.

Background: The main cause of hospitalization in patients with heart failure is hypervolemia. Therefore, the primary treatment strategy involves diuretic therapy using intravenous loop diuretics to achieve decongestion and euvolemia. Some patients with acutely decompensated heart failure (ADHF) do not respond well to diuretic treatment, which may be due to diuretic resistance (DR). Such cases require high doses of diuretic medications and combination therapy with diuretics of different mechanisms of action. Although certain predisposing factors for diuretic resistance have been identified (such as hypotension, type 2 diabetes, impaired renal function, and hyponatremia), further research is needed to identify other pathophysiological markers of DR. Objective: This study aims to identify admission markers that can predict a high requirement for intravenous diuretics in hospitalized patients with decompensated heart failure. Methods: This study included 102 adult patients hospitalized for ADHF. At admission, patients underwent clinical assessment, laboratory parameter evaluation (including the N-terminal prohormone of brain natriuretic peptide [NT-proBNP] levels), and hemodynamic assessment using impedance cardiography (ICG). Hemodynamic profiles were based on the use of parameters such as heart rate (HR), blood pressure (BP), and thoracic fluid content (TFC) as markers of volume status. The analysis included 97 patients with documented doses of intravenous diuretic use. Patients were stratified into two groups based on median diuretic consumption (equivalent to 540 mg of intravenous furosemide): the high-loop diuretic utilization (LDU) group (n = 49) and the low-LDU group (n = 48). Results: Compared to low-LDU patients, high-LDU patients had greater thoracic fluid content at admission, both quantitatively (37.4 ± 8.1 vs. 34.1 ± 6.9 kOhm-1; p = 0.024) and qualitatively (TFC ≥ 35 kOhm-1: 59.2% vs. 33.3%; p = 0.011). Anemia was more common in the high-LDU group (67.4% vs. 43.8%; p = 0.019), as was elevated NT-proBNP (≥median of 3952 pg/mL: 60.4% vs. 37.5%; p = 0.024). High LDU was associated with a significantly longer hospitalization duration (12.9 ± 6.4 vs. 7.0 ± 2.6 days; p < 0.001). Logistic regression analysis identified anemia, elevated NT-proBNP, and high TFC as predictors of high LDU (HR: 2.65, 2.54, and 2.90, respectively). In a multifactorial model, only high TFC remained an independent predictor (HR: 2.60, 95% CI 1.04-6.49; p = 0.038). Conclusions: TFC was the sole independent admission marker of a high requirement for intravenous diuretics in patients hospitalized for decompensated heart failure. An objective assessment of volume status by impedance cardiography may support intensive personalized decongestion therapy.

The role of urine sodium in acutely decompensated heart failure.

Background: Diuretic resistance is common and results in poor outcome. Spot urine sodium (UrNa) is suggested as a tool to tailor diuretics and improve efficacy of therapy. We prospectively evaluate the prevalence of diuretic resistance, predictors of low spot-UrNa and the prognostic value of spot-UrNa in an unselected ADHF population. Methods: Patients admitted for ADHF and treated with iv diuretics were included. Spot-UrNa was collected 2 h after administration of an IV diuretic bolus. The main endpoint was a composite of HF re-hospitalizations and all-cause mortality at 90 days follow-up. Results: 143 patients were included in this study (median age 81 [75 - 85] years, 55 % male), of which 50 % were newly diagnosed with HF. Low spot-UrNa was independently associated with worse renal function, low serum sodium, and systolic blood pressure, previous loop diuretic and SGLT2i use and loop diuretic administered dose. Both absolute spot-UrNa (HR 0.87, 95 % CI 0.79 - 0.95, P=0.003 per 10 mmol/L increase) and a urinary sodium ≥ 100 mmol/l (HR=0.51, 95 % CI 0.27 - 0.97, P=0.04) significantly predicted the composite endpoint. This association was no longer significant after correction for confounders. Patients with low spot-UrNa attained longer IV diuretic treatment and a higher cumulative IV diuretic dose. Conclusions: Spot-UrNa is prevalent and occurs more often in patients with more progressed cardio-renal disease. Spot-UrNa significantly predicts 90-day HF hospital-free survival in ADHF. Further studies are needed evaluating the effect of UrNa guided diuretic treatment on clinical endpoints.

Chlorthalidone as Secondary Treatment in HFpEF?

This review addresses important issues that face practitioners today concerning the treatment of HFpEF. It points out how the accepted efficacy of HFpEF medication treatment has changed. Medications are now recommended for use in HFpEF that have diuretic properties and are significant because of a reduction in the frequency of the development of heart failure (not mortality). This heart failure incidence reduction appears predictable and is valuable, but it raises the question of the use of chlorthalidone in the treatment of HFpEF. Chlorthalidone has previously been demonstrated to reduce heart failure incidence in the treatment of hypertensive patients which is a similar patient population. Chlorthalidone, possibly with a generic mineralocorticoid antagonist, could be an acceptable low-cost alternate therapy as secondary treatment for HFpEF. Of course, chlorthalidone does not have the other theoretic benefits of the SGLT2 inhibitors or finerenone. It would be helpful if this was discussed in the upcoming HFpEF guidelines especially for use in patients who cannot afford or tolerate the new HFpEF medications.

Morin hydrate mitigates calcium oxalate urolithiasis by inhibiting oxalate synthesis and modulating crystal formation.

Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones.

Prevalence and characteristics of upfront diuretic resistance in acute heart failure: The P-Value-AHF study.

AIMS: Diuretic resistance (i.e., insufficient diuretic and natriuretic response to an appropriate dose of intravenously administered loop diuretic) is a major cause of insufficient decongestion in acute heart failure (AHF). Early assessment of diuretic and natriuretic response already after the first administration of loop diuretic is currently recommended, but few data exist on the prevalence and characteristics of upfront diuretic resistance in AHF. The aim of this sub-study of the P-Value-AHF randomized clinical trial was to investigate the prevalence and characteristics of upfront diuretic resistance in patients presenting with AHF in the emergency department (ED). METHODS: Consecutive patients presenting with a clinical diagnosis of AHF, ≥1 sign of congestion, and NT-proBNP >1000 ng/L between February and June 2024 were prospectively screened. Loop diuretics were administered per protocol: 40 mg furosemide i.v. in diuretic-naïve patients and those on oral torasemide <40 mg, 80 mg furosemide i.v. in patients on oral torasemide ≥40 mg daily. Urine output was measured over the following 2 h and in patients with urine volume <300 mL, urine sodium concentration was additionally measured in a spot sample. Upfront diuretic resistance was defined as urine volume <300 mL in 2 h and urine sodium concentration <70 mmol/L. RESULTS: From a total of 127 screened AHF patients presenting to the ED, 17 subjects were excluded after denial of informed consent and 17 could not be treated according to the protocol due to one or more exclusion criteria. Of the remaining 93 per-protocol-treated patients, 91 showed an adequate diuretic response either in terms of urine volume or urine sodium concentration. Only two of 93 patients (2.2%) met the criteria of upfront diuretic resistance. In a post-hoc analysis, patients with diuretic resistance had higher prevalence of chronic kidney or liver diseases, markedly lower blood pressure and heart rate, markedly higher serum creatinine and potassium levels, and lower serum sodium. Notably, clinical signs of congestion, circulating NT-proBNP, and left-ventricular ejection fraction were similar in both groups. CONCLUSIONS: Upfront diuretic resistance in an unselected population of AHF patients presenting to the ED affects only a minority of patients. These data highlight the importance of a standardized, protocolized approach to decongestive treatment in AHF, which includes the rapid administration of loop diuretics in an adequate dose. Pre-existing chronic kidney disease and high creatinine levels were more prevalent in patients with diuretic resistance.

Relationship between magnesium dosage and the preventive effect on cisplatin-induced nephrotoxicity: meta-analysis and meta-regression analysis.

BACKGROUND: Cisplatin (CDDP) is an anticancer drug used to treat several types of cancer. CDDP-induced nephrotoxicity (CIN) is a serious adverse effect of CDDP treatment. Although magnesium sulfate (Mg) premedication has been proven to prevent CIN, the relationship between Mg dosage and its preventive effects on CIN are unknown. Therefore, we have evaluated this relationship using meta-analysis and meta-regression analysis to optimize cancer chemotherapies, including CDDP. METHODS: We selected candidate studies, generated a forest plot to evaluate the preventive effects of Mg on CIN, and performed subgroup analyses. Moreover, a meta-regression analysis was conducted to reveal the relationship between Mg dosage and its preventive effects on CIN. RESULTS: We identified 17 related studies and the total odds ratio (OR) of Mg premedication on CIN was 0.26 and the 95% confidence interval (95% CI) was 0.17-0.41 (p < 0.00001) although funnel plot suggested asymmetry. In subgroup analysis by forest plot, total OR with 95% CI of low Mg dosage administration (less than 10 mEq) and high Mg dosage administration (10 mEq or higher) was 0.35 (0.16-0.77, p = 0.0169) and 0.12 (0.07-0.21, p < 0.0001), respectively. In addition, meta-regression analysis was performed on Mg dosage and the OR of related studies, indicating a relationship between Mg dosage and OR (p = 0.0349). CONCLUSION: This study has revealed that premedication with Mg prevented CIN in a dose-dependent manner.

Diuretic resistance in acute heart failure: proposal for a new urinary sodium-based definition.

BACKGROUND: Diuretic resistance is a relevant clinical issue in acute heart failure (AHF), but a standardized, quantitative definition is still missing. The aim of this analysis was to highlight discrepancies between previously proposed definitions of diuretic response and to propose a new urinary sodium (NaU)-based definition of diuretic efficiency (DE) to identify diuretic resistant (DR) patients. METHODS: Three historical definitions of diuretic response and a new NaU-based DE definition, evaluating total NaU after the first diuretic bolus per 40 mg furosemide administered, were applied in a retrospective analysis to an AHF population treated with intravenous (i.v.) loop diuretics. Baseline characteristics, in-hospital clinical data and outcomes at discharge and mid-term follow-up were collected and compared among DR and non-DR patients for each definition. RESULTS: Among 53 patients, 39 (73.6%), 51 (96.2%) and 3 (5.7%) were DR according to weight-derived, diuresis-derived, and spot NaU definition, respectively. The median value of the new NaU-based definition was 31 mmol/40 mg and patients were stratified accordingly. DR patients showed lower cumulative diuresis (5200 mL, 3300-6700 vs 9825 mL, 6200-12200, p = 0.007) and weight loss (4 kg, 1-5 vs 6 kg, 3-8.5, p = 0.023), higher BNP levels (808 pg/mL, 443-1037 vs 351 pg/mL, 209-859, p = 0.062) at the conclusion of protocol-guided i.v diuretic therapy, which was less frequently stopped due to decongestion in DR as compared to non-DR patients (57.7% vs 85.2%, p = 0.026). Six-months mortality or HF hospitalizations were more frequent in DR patients (OR 18.6, 95% CI 2.1-161.2, p = 0.008). CONCLUSIONS: The NaU-based DE definition might solve discrepancies of other previously proposed definitions.

Prediction of cardiac surgery associated acute kidney injury using response to loop diuretic and urine neutrophil gelatinase associated lipocalin.

BACKGROUND: Cardiac surgery associated acute kidney injury (CS-AKI) is common. Urine response to loop diuretic and urine neutrophil gelatinase associated lipocalin (uNGAL) are separately associated with CS-AKI. We aimed to determine whether urine response to loop diuretic and uNGAL together were associated with postoperative day 2-4 CS-AKI. METHODS: Two-center prospective observational study (ages 0-18 years). uNGAL (8-12 h after admission) (ng/mL) and urine response to loop diuretic (6 h for bolus furosemide and 12 h for infusion bumetanide) (mL/kg/hr) were measured. All diuretic doses were converted to furosemide equivalents. The primary outcome was day 2-4 CS-AKI. Patients were sub-phenotyped using a priori cutoffs (uNGAL + ≥ 100 ng/mL and UOP + < 1.5 mL/kg/hr) and optimal cutoffs (uNGAL + ≥ 127 ng/mL and UOP + ≤ 0.79 mL/kg/hr): 1) uNGAL-/UOP-, 2) uNGAL-/UOP + , 3) uNGAL + /UOP-, and 4) uNGAL + /UOP + . Multivariable regression was used to assess the association of uNGAL, UOP and each sub-phenotype with outcomes. RESULTS: 476 patients were included. CS-AKI occurred in 52 (10.9%). uNGAL was associated with 2.59-fold greater odds (95%CI: 1.52-4.41) of CS-AKI. UOP was not associated with CS-AKI. Compared with uNGAL + alone, uNGAL + /UOP + improved prediction of CS-AKI using a priori and optimal cutoffs respectively (AUC 0.70 vs. 0.75). Both uNGAL + /UOP + (IQR OR:4.63, 95%CI: 1.74-12.32) and uNGAL + /UOP- (IQR OR:5.94, 95%CI: 2.09-16.84) were associated with CS-AKI when compared with uNGAL-/UOP-. CONCLUSIONS: uNGAL is associated with CS-AKI. The sub-phenotype association was largely driven by uNGAL. Future studies standardizing diuretic dose and timing may be needed to refine the combined performance for clinical decision making.

Diuretic Treatment in Heart Failure: A Practical Guide for Clinicians.

Congestion and fluid retention are the hallmarks of decompensated heart failure and the major reason for the hospitalization of patients with heart failure. Diuretics have been used in heart failure for decades, and they remain the backbone of the contemporary management of heart failure. Loop diuretics is the preferred diuretic, and it has been given a class I recommendation by clinical guidelines for the relief of congestion symptoms. Although loop diuretics have been used virtually among all patients with acute decompensated heart failure, there is still very limited clinical evidence to guide the optimized diuretics use. This is a sharp contrast to the rapidly growing evidence of the rest of the guideline-directed medical therapy of heart failure and calls for further studies. The loop diuretics possess a unique pharmacology and pharmacokinetics that lay the ground for different strategies to increase diuretic efficiency. However, many of these approaches have not been evaluated in randomized clinical trials. In recent years, a stepped and protocolized diuretics dosing has been suggested to have superior benefits over an individual clinician-based strategy. Diuretic resistance has been a major challenge to decongestion therapy for patients with heart failure and is associated with a poor clinical prognosis. Recently, therapy options have emerged to help overcome diuretic resistance to loop diuretics and have been evaluated in randomized clinical trials. In this review, we aim to provide a comprehensive review of the pharmacology and clinical use of loop diuretics in the context of heart failure, with attention to its side effects, and adjuncts, as well as the challenges and future direction.

The utility of urine sodium-guided diuresis during acute decompensated heart failure.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry-guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium-guided strategies.

General Anesthesia for Patients With Cyclic Vomiting Syndrome and Obesity: A Case Report.

Cyclic vomiting syndrome (CVS) is a chronic digestive disorder characterized by recurrent episodes of severe nausea and vomiting. The perioperative management of patients with CVS undergoing general anesthesia is challenging, especially when combined with obesity. This case report describes the successful management of a patient with CVS and obesity who underwent dental surgery under general anesthesia. A 21-year-old woman with CVS, obesity (body mass index, 35), and intellectual disability was scheduled for tooth extraction and composite resin restoration under general anesthesia. The patient was diagnosed with CVS at the age of 20 years with frequent vomiting attacks requiring hospitalization. Surgery was scheduled during the CVS remission to reduce the risk of perioperative vomiting. Preoperative laboratory test results were normal, including serum adrenocorticotropic hormone (ACTH), anti-diuretic hormone (ADH), and cortisol levels. General anesthesia was induced using remifentanil and propofol. Nasal endotracheal intubation was performed after rocuronium administration. Local anesthesia (2% lidocaine with 1:80,000 epinephrine) was used for all dental procedures. Postoperatively, midazolam was administered to control agitation. No postoperative vomiting occurred. Serum ACTH, ADH, and cortisol levels showed no significant changes before and after anesthesia, suggesting that hypothalamic-pituitary-adrenal (HPA) axis activation due to surgical stress did not occur. This case highlights the importance of careful perioperative planning and monitoring stress-related hormone levels in patients with CVS or obesity. An anesthetic approach using midazolam may effectively suppress HPA axis activation and prevent postoperative vomiting.

Assessment of the Diuretic Effect of the Leaves of Cucumis Dipsaceus Ehrenb (Cucurbitaceae) in Rats: Using Aqueous and 80% Methanol Extracts.

Background: The diuretic activity of the Cucumis dipsaceus leaf, which is used in indigenous medicine, has been claimed but has not yet undergone scientific evaluation. Objective: The objective of this study was to assess the diuretic activity of the aqueous and 80% methanol extracts derived from the leaves of Cucumis dipsaceus in rats. Methods: For the extraction process, the maceration technique was employed to obtain the aqueous and 80% methanol extracts from the Cucumis dipsaceus leaves. Male rats were then divided randomly into eight groups, with six rats in each group. These groups consisted of a negative control group, a positive control group, and three different groups for each extract at varying doses. The urine output volumes, the concentrations of urinary electrolytes (sodium, potassium, and chloride) and urinary pH, were measured and analysed to compare the results among the different groups. Results: Both the aqueous and 80% methanol extracts of Cucumis dipsaceus leaves demonstrated a significant increase in urinary output at doses of 200mg/kg body weight (p<0.01) and 400mg/kg body weight (p<0.001). When comparing the urinary electrolyte excretion with the negative control group, the groups treated with the 400mg/kg body weight dose of the aqueous extract showed significant differences in the urinary excretion of sodium (p<0.05), chloride (p<0.01), and K+ (p<0.01). Similarly, the urinary excretion of K+ and Cl- also exhibited significant differences at moderate doses (K+: p<0.01, Cl-: p<0.05) and the highest doses (both: p<0.01) of the 80% methanol extract. Furthermore, the highest doses of both the aqueous (p<0.01) and 80% methanol (p<0.01) extracts demonstrated significant differences in saluretic effect. Conclusion: Both crude extracts of C. dipsaceus leaves have significant diuretic activity, providing support for the traditional use of the plant as a diuretic agent.

Serum Chloride and the Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload: A Post Hoc Analysis From the ADVOR Trial.

BACKGROUND: Chloride plays a crucial role in renal salt sensing. This study investigates whether serum chloride is associated with clinical outcomes and decongestive response to acetazolamide in patients with acute decompensated heart failure. METHODS: This post hoc analysis includes all 519 patients from the ADVOR trial (Acetazolamide in Decompensated Heart Failure With Volume Overload), randomized to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The impact of baseline serum chloride on the main trial end points and the treatment effect of acetazolamide was assessed, as was the evolution of serum chloride under decongestive treatment. RESULTS: Hypochloremia (<96 mmol/L) and hyperchloremia (>106 mmol/L) were present in 80 (15%) and 53 (10%), respectively, at baseline. Hypochloremia was associated with significantly slower decongestion, a longer length of hospital stay, and increased risk of all-cause mortality and heart failure readmissions. Acetazolamide increased the odds of successful decongestion and reduced length of stay irrespectively of baseline serum chloride levels. No statistically significant interaction between serum chloride levels and the effect of acetazolamide on death or heart failure readmissions was observed. The placebo group exhibited a progressive decline in serum chloride, which was effectively prevented by acetazolamide (P<0.001). CONCLUSIONS: Hypochloremia is associated with diuretic resistance and worse clinical outcomes. Add-on acetazolamide therapy improves decongestion across the entire range of serum chloride and prevents the drop in chloride levels caused by loop diuretic monotherapy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03505788.

The effects of bolus isosorbide dinitrate on pulmonary hypertension with cardiopulmonary comorbidities.

Lowering mean pulmonary arterial pressure (mPAP) without reducing cardiac output is essential in treating pulmonary hypertension (PH). Isosorbide dinitrate (ISDN) potentially achieves this in post-capillary PH but can decrease cardiac output and blood pressure (BP), especially in pre-capillary PH. However, post-capillary PH and pre-capillary PH can overlap, and their clear discrimination is difficult. The aim of the study was to examine to what extent bolus ISDN injection reduces mPAP and BP, and changes mixed venous oxygen saturation (SvO2), an indicator of cardiac output in PH with various cardiopulmonary comorbidities in the context of treatment modifications. We retrospectively examined the hemodynamic effects of bolus ISDN injection in patients with PH who underwent right heart catheterization and their subsequent treatment modification. Our sample comprised 13 PH patients. In seven with pre-capillary PH, ISDN significantly lowered mPAP from the median 34 (interquartile range 32-39) to 28 (28-30) mmHg and the mean BP (mBP) from 90 (79-92) to 72 (68-87) mmHg. In six with post-capillary PH, ISDN lowered mPAP from 40 (29-44) to 27 (23-31) mmHg and mBP from 91 (87-110) to 87 (82-104) mmHg. There was a significant decrease in SvO2 from 69.8% (64.9%-78.1%) to 63.9% (60.5%-71.5%) in pre-capillary PH, but not in post-capillary PH including combined post- and pre-capillary PH and some patients showed a large increase in SvO2. In all patients showing an SvO2 increase, diuretics or hemodialysis were up-titrated or continued. Bolus ISDN injection lowered mPAP. However, in pre-capillary PH, it caused a significant decrease in SvO2 and a notable reduction in blood pressure. In post-capillary PH, including combined post- and pre-capillary PH, it clarified whether systemic preload and afterload reduction increased or decreased SvO2 in each patient, which may aid in treatment modification.

Clinical Outcomes of Metabolic Surgery on Diuretic Use in Patients With Heart Failure.

The beneficial impacts of metabolic surgery (MS) on patients with heart failure (HF) are incompletely characterized. We aimed to describe the cardiac and metabolic effects of MS in patients with HF and hypothesized that patients with HF would experience both improved metabolic and HF profiles using glycemic control and diuretic dependency as surrogate markers. In this single-center, university-affiliated academic study in the United States, a review of 2,342 hospital records of patients who underwent MS (2017 to 2023) identified 63 patients with a medical history of HF. Preoperative characteristics, 30-day outcomes, and up to 2-year biometric and metabolic outcomes, medication usage, and emergency department utilization were collected. At 24 months, mean body mass index change was -16 kg/m2 (p <0.001) that corresponded to a mean percentage total body weight loss of 29% (p <0.001). Weight loss was accompanied by significant reductions in hemoglobin A1c (p <0.001) and a 65% decrease in diuretic use at 24 months after surgery (p <0.001). Similarly, emergency visits for cardiac conditions (p = 0.06) and intravenous diuresis (p = 0.07) trended favorably at 1 year after surgery compared with 1 year before surgery but were not statistically significant. In conclusion, in patients with HF who were carefully selected, MS appears to provide significant reduction in oral diuretic dependency, and metabolic improvements with trends toward lower rates of emergency department utilization.

Hypertonic saline and heart failure: "sodium-centric" or "chlorine-centric"?

Up to 50% of patients admitted for heart failure (HF) have congestion at discharge despite diagnostic and therapeutic advances. Both persistent congestion and diuretic resistance are associated with worse prognosis. The combination of hypertonic saline and loop diuretic has shown promising results in different studies. However, it has not yet achieved a standardized use, partly because of the great heterogeneity in the concentration of sodium chloride, the dose of diuretic or the amount of sodium in the diet. Classically, the movement of water from the intracellular space due to an increase in extracellular osmolarity has been postulated as the main mechanism involved. However, chloride deficit is postulated as the main up-regulator of plasma volume changes, and its correction may be the main mechanism involved. This "chloride centric" approach to heart failure opens the door to therapeutic strategies that would include diuretics to correct hypochloremia, as well as sodium free chloride supplementation.

Pharmacological mechanisms involved in the diuretic activity of the ethanol-soluble fraction of Baccharis milleflora (Less.) DC. - An ethnopharmacological investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated. AIM: Investigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats. MATERIALS AND METHODS: Cladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na+/K+/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide. RESULTS: From LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM. CONCLUSION: This study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed.