Furosemide 20mg / Potassium chloride 750mg (potassium 10mmol) modified-release tablets

IntroductionSevere hyponatremia (sodium ≤ 120 mmol/L) poses significant clinical risks, including encephalopathy and seizures, but inadvertent rapid correction may cause osmotic demyelination syndrome (ODS). Current guidelines recommend limiting sodium correction to ≤8 mmol/L per 24 hours to minimize ODS risk. However, recent studies suggest that overcorrection may not directly contribute to mortality and could even be associated with improved outcomes.MethodsThis retrospective cohort study included 362 patients with severe hyponatremia admitted to two Brazilian tertiary hospitals. Overcorrection was defined as a serum sodium increase >8 mmol/L in 24 hours or >18 mmol/L in 48 hours. Multivariate logistic regression and propensity score-weighted analyses were used to identify predictors and outcomes associated with overcorrection.ResultsOvercorrection occurred in 38.7% of patients whereas ODS occurred in only one patient (0.28%). Independent predictors of overcorrection included younger age, lower admission sodium levels, and higher volumes of 0.9% NaCl administered in the emergency room; cancer diagnosis and furosemide use were protective factors. Overcorrection was associated with lower in-hospital mortality and shorter hospital stays, even in propensity score-weighted multivariate analyses. However, a detailed review of mortality cases revealed no direct causal link between the rate of sodium correction and death.ConclusionOvercorrection of severe hyponatremia was common and associated with better clinical outcomes, without a significant increase in the risk of ODS. However, given the observational nature of this association, randomized controlled trials are needed before the current guidelines for correction rate can be reconsidered.

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AimsIn a randomised controlled trial (RCT), we compared the effects of treatment with furosemide + small volumes of hypertonic saline solution (HSS) with those of furosemide alone in patients with decompensated heart failure (HF), and their effects on inflammatory and remodelling markers and epigenetic signatures.MethodsAll consecutive patients with acute decompensated heart failure (ADHF) due to heart failure with reduced ejection fraction (HFrEF) were enrolled. Patients were randomly assigned to treatment with i.v. furosemide plus HSS or i.v. furosemide alone. Patients were evaluated at T0 (admission), T1 (after treatment), and T2 (after a saline bolus) to determine serum concentrations of NT-proBNP, hsTnT, s-ST2, galectin-3, IL-6, and CRP and to evaluate some selected miRNA concentrations.ResultsWe enrolled 200 subjects, 107 randomized to the furosemide plus HSS, and 93 to furosemide alone. At T1, patients treated with high-dose furosemide + HSS had higher absolute delta values of IL-6, hsTnT, NT-proBNP and galectin-3. Patients treated with i.v. furosemide + HSS showed significantly lower increases in the serum concentrations of IL-6, hsTNT, sST2, galectin-3 and NT-proBNP after saline load. We observed a decrease in miR181b expression in subjects treated with i.v. furosemide plus HSS in comparison to patients treated with i.v. furosemide alone and a more significant reduction of miRNA181b expression in subjects treated with furosemide plus HSS.ConclusionsOur findings revealed that in subjects with ADHF, treatment with i.v. furosemide plus HSS significantly decreased the serum levels of IL-6, sST2, hsTnT, galectin-3, and NT-proBNP and modulated some miRNA expression.

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AimsThe Acetazolamide as a chloride-sparing Diuretic in patients Admitted with Heart Failure (ADA-HF) trial will assess the safety and diuretic effect of oral ACZ given alongside a high-dose IV loop diuretic in patients admitted to the hospital with heart failure (HF) and severe fluid retention. Hypochloraemia is common in patients with HF and is associated with worse outcomes, but there are few treatment options available: we will also assess whether ACZ reduces urine chloride loss.Methods and resultsThe ADA-HF trial is a single centre, open-label, randomized-controlled trial of ACZ 250 mg twice daily plus standard care vs. standard care alone. The trial duration is 4 days. We will recruit 50 patients with severe peripheral oedema due to HF requiring standard care (240 mg of IV furosemide per day given via continuous infusion at 10 mg per hour). The co-primary endpoints are (1) the difference in net fluid loss daily, and over 4 days; and (2) difference in serum chloride concentrations between baseline and day 4. The trial has 80% power to detect a difference in fluid balance of 500-1000 mL per day; and a difference in serum chloride concentration of 1 mmol/L per day. Secondary endpoints include but are not limited to: time to recruit per patient; rate of adverse events; rate of recruitment; and cause-specific rate of drop-out of the study.ConclusionACZ may be a useful adjunct to diuretic therapy, but the safety and diuretic efficacy of oral ACZ when used alongside high-dose loop diuretics is unknown. ADA-HF will complement the ADVOR trial and may clarify what role ACZ may have for patients with severe congestion.Trial registrationISRCTN registry. ISRCTN13060336. Registered on 09/02/2023. URL: https://doi.org/10.1186/ISRCTN13060336.

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