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The Canadian Journal of Hospital... 2024Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate... (Review)
Review
BACKGROUND
Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate inpatient decongestion is an important contributor to high readmission rates. There is little evidence concerning diuresis to guide clinicians in caring for patients with acute decompensated heart failure. Contemporary diuretic strategies have been defined by expert opinion and older landmark clinical trials.
OBJECTIVE
To present a narrative review of contemporary recommendations, along with their underlying evidence and pharmacologic rationale, for diuretic strategies in inpatients with acute decompensated heart failure.
DATA SOURCES
PubMed, OVID, and Embase databases were searched from inception to December 22, 2022, with the following search terms: heart failure, acute heart failure, decompensated heart failure, furosemide, bumetanide, ethacrynic acid, hydrochlorothiazide, indapamide, metolazone, chlorthalidone, spironolactone, eplerenone, and acetazolamide.
STUDY SELECTION
Randomized controlled trials and systematic reviews involving at least 100 adult patients (> 18 years) were included. Trials involving torsemide, chlorothiazide, and tolvaptan were excluded.
DATA SYNTHESIS
Early, aggressive administration of a loop diuretic has been associated with expedited symptom resolution, shorter length of stay, and possibly reduced mortality. Guidelines make recommendations about dose and frequency but do not recommend any particular loop diuretic over another; however, furosemide is most commonly used. Guidelines recommend that the initial furosemide dose (on admission) be 2-2.5 times the patient's home dose. A satisfactory diuretic response can be defined as spot urine sodium content greater than 50-70 mmol/L at 2 hours; urine output greater than 100-150 mL/h in the first 6 hours or 3-5 L in 24 hours; or a change in weight of 0.5-1.5 kg in 24 hours. If congestion persists after the maximization of loop diuretic therapy over the first 24-48 hours, an adjunctive diuretic such as thiazide or acetazolamide should be added. If decongestion targets are not met, continuous infusion of furosemide may be considered.
CONCLUSIONS
Heart failure with congestion can be managed with careful administration of high-dose loop diuretics, supported by thiazides and acetazolamide when necessary. Clinical trials are underway to further evaluate this strategy.
PubMed: 38204501
DOI: 10.4212/cjhp.3323 -
Current Therapeutic Research, Clinical... Sep 1976
Clinical Trial Comparative Study
Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Clinical Trials as Topic; Diuretics; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Metolazone; Middle Aged; Placebos; Potassium; Reserpine
PubMed: 822985
DOI: No ID Found -
Journal of Chromatographic Science Oct 2015For the first time, we developed and validated a highly sensitive, selective and rapid HPLC-ESI-MS-MS method for simultaneous quantification of metolazone (MET),...
For the first time, we developed and validated a highly sensitive, selective and rapid HPLC-ESI-MS-MS method for simultaneous quantification of metolazone (MET), losartan (LOS) and its metabolite losartan carboxylic acid (LCA) in rat plasma. After solid-phase extraction, the analytes and internal standard (irbesartan) were extracted from 100 µL plasma sample on an Agilent Poroshell 120, EC-C18 (50 × 4.6 mm, i.d., 2.7 µm) column using 5 µL injection volume with a total run time of 3 min. Acidified methanol/water mixture was used as a mobile phase. The parent → product ion transitions for MET (m/z 366.0 → 258.9), LOS (m/z 423.2 → 207.0), LCA (m/z 437.0 → 235.1) and IS (m/z 429.2 → 207.0) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ion mode. The method was found to be linear in the range of 0.05-250 for MET, 2-3,000 for LOS and 4-3,500 ng/mL for LCA. The method was validated with respect to selectivity, linearity, accuracy, precision, recovery and stability according to accepted regulatory guidelines. The described method was successfully applied to preclinical pharmacokinetic studies of analytes after an oral administration of mixture of MET (1 mg/kg) and LOS (10 mg/kg) in rats.
Topics: Animals; Chromatography, High Pressure Liquid; Linear Models; Losartan; Male; Metolazone; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 25947361
DOI: 10.1093/chromsci/bmv047 -
Journal of the American Heart... Sep 2018Background In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out...
Background In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high-dose loop diuretics. Methods and Results Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity-adjusted analysis of all-cause mortality. Secondary outcomes included hyponatremia (sodium <135 mE q/L), hypokalemia (potassium <3.5 mE q/L) and worsening renal function (a ≥20% decrease in estimated glomerular filtration rate). Of 13 898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function ( P<0.0001 for all) with minimal effect attenuation following covariate and propensity adjustment. Metolazone remained associated with increased mortality after multivariate and propensity adjustment (hazard ratio=1.20, 95% confidence interval 1.04-1.39, P=0.01). High-dose loop diuretics were associated with hypokalemia and hyponatremia ( P<0.002) but only worsening renal function retained significance ( P<0.001) after propensity adjustment. High-dose loop diuretics were not associated with reduced survival after multivariate and propensity adjustment (hazard ratio=0.97 per 100 mg of IV furosemide, 95% confidence interval 0.90-1.06, P=0.52). Conclusions During acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high-dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate.
Topics: Acute Disease; Aged; Cause of Death; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Guideline Adherence; Heart Failure; Humans; Injections, Intravenous; Male; Metolazone; Propensity Score; Retrospective Studies; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Survival Rate; Treatment Outcome; United States
PubMed: 30371181
DOI: 10.1161/JAHA.118.009149 -
Drug and Therapeutics Bulletin Jun 1974
Clinical Trial
Topics: Bumetanide; Clinical Trials as Topic; Diuretics; Edema; Humans; Metolazone
PubMed: 4616810
DOI: No ID Found -
Kidney International Jun 1996Recently the molecular identification of the major electroneutral sodium-potassium-chloride entry mechanisms present on apical membranes of distal nephron segments of... (Review)
Review
Recently the molecular identification of the major electroneutral sodium-potassium-chloride entry mechanisms present on apical membranes of distal nephron segments of the mammalian kidney, on basolateral membranes of many non-renal epithelial cells and on certain non-epithelial tissues has been achieved. These transporters represent a major pathway for cellular uptake of chloride critical for chloride absorptive and secretory processes and for cell volume regulation following cell shrinkage. In the mammalian kidney, these sodium-coupled chloride cotransporters represent the major target sites for clinically useful diuretics including the "loop" diuretics [furosemide (Lasix) and bumetanide (Bumex)] and thiazides (such as, chlorothiazide, hydrochlorothiazide and metolazone). Although these Na-(K)-Cl cotransporters exhibit functional and pharmacological differences, they clearly evolved from a common ancestral gene and thus form a new gene family. This information is already advancing our understanding of the evolution, structure and function of these transporters both in renal handling of sodium and in hypertension.
Topics: Animals; Carrier Proteins; Chlorides; Electrochemistry; Ion Channel Gating; Membrane Proteins; Potassium; Sodium; Sodium-Potassium-Chloride Symporters
PubMed: 8743468
DOI: 10.1038/ki.1996.238 -
Kidney International Mar 1972
Comparative Study
Topics: Acid-Base Equilibrium; Acidosis; Alkalosis; Ammonia; Ammonium Chloride; Carbon Dioxide; Cell Membrane Permeability; Depression, Chemical; Gluconeogenesis; Glutamate Dehydrogenase; Glutamates; Glutaminase; Glutamine; Humans; Hydrogen-Ion Concentration; Ketoglutaric Acids; Kidney; Kidney Tubules; Male; Urine
PubMed: 4671220
DOI: 10.1038/ki.1972.24 -
Current Therapeutic Research, Clinical... Aug 1974
Clinical Trial
Topics: Adult; Antihypertensive Agents; Blood Pressure; Body Weight; Clinical Trials as Topic; Diuretics; Humans; Hypertension; Male; Middle Aged; Placebos; Quinazolines; Sulfonamides; Time Factors
PubMed: 4217244
DOI: No ID Found -
British Medical Journal (Clinical... Jul 1985
Topics: Diabetic Coma; Diuretics; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Hypertension; Metolazone; Middle Aged
PubMed: 3926049
DOI: 10.1136/bmj.291.6487.25-a -
American Journal of Health-system... Sep 1996The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Ketoconazole 20 mg/mL, metolazone 1...
The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Ketoconazole 20 mg/mL, metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone 25 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in 120-mL polyethylene terephthalate bottles. The sources of the drugs were powder, capsules, and tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle immediately after preparation and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 93% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Ketoconazole 20 mg/mL, metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone 25 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids. INDEX TERMS: Anti-infective agents; Antifungals; Capsules; Cardiac drugs; Cherry syrup; Compounding; Containers; Diuretics; Incompatibilities; Ketoconazole; Liquids; Metolazone; Metronidazole; Polyethylene terephthalate; Powders; Procainamide hydrochloride; Spironolactone; Stability; Storage; Suspending agents; Tablets; Temperature; Vehicles.
Topics: Administration, Oral; Anti-Arrhythmia Agents; Antifungal Agents; Antihypertensive Agents; Antitrichomonal Agents; Chromatography, High Pressure Liquid; Diuretics; Dosage Forms; Drug Compounding; Drug Stability; Humans; Hydrogen-Ion Concentration; Ketoconazole; Metolazone; Metronidazole; Pharmaceutical Vehicles; Procainamide; Solubility; Spironolactone; Suspensions
PubMed: 8870895
DOI: 10.1093/ajhp/53.17.2073