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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 -
Journal of Clinical Medicine Sep 2021Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both...
BACKGROUND
Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both conditions have a detrimental impact on prognosis and hospitalization.
AIMS
This retrospective, multicenter study evaluates the effect of the addition of oral metolazone on diuretic response (DR), clinical congestion, NTproBNP values, and renal function over hospitalization phase. Follow-up analysis for a 6-month follow-up period was performed.
METHODS
We enrolled 132 patients with acute decompensated heart failure (ADHF) in advanced NYHA class with reduced ejection fraction (EF < 40%) taking a mean furosemide amount of 250 ± 120 mg/day. Sixty-five patients received traditional loop diuretic treatment plus metolazone (Group M). The mean dose ranged from 7.5 to 15 mg for one week. Sixty-seven patients continued the furosemide (Group F). Congestion score was evaluated according to the ESC recommendations. DR was assessed by the formula diuresis/40 mg of furosemide.
RESULTS
Patients in Group M and patients in Group F showed a similar prevalence of baseline clinical congestion (3.1 ± 0.7 in Group F vs. 3 ± 0.8 in Group M) and chronic kidney disease (CKD) (51% in Group M vs. 57% in Group F; = 0.38). Patients in Group M experienced a better congestion score at discharge compared to patients in Group F (C score: 1 ± 1 in Group M vs. 3 ± 1 in Group F > 0.05). Clinical congestion resolution was also associated with weight reduction (-6 ± 2 in Group M vs. -3 ± 1 kg in Group F, < 0.05). Better DR response was observed in Group M compared to F (940 ± 149 mL/40 mgFUROSEMIDE/die vs. 541 ± 314 mL/40 mgFUROSEMIDE/die; < 0.01), whereas median ΔNTproBNP remained similar between the two groups (-4819 ± 8718 in Group M vs. -3954 ± 5560 pg/mL in Group F NS). These data were associated with better daily diuresis during hospitalization in Group M (2820 ± 900 vs. 2050 ± 1120 mL < 0.05). No differences were found in terms of WRF development and electrolyte unbalance at discharge, although Group M had a significant saline solution administration during hospitalization. Follow-up analysis did not differ between the group but a reduced trend for recurrent hospitalization was observed in the M group (26% vs. 38%).
CONCLUSIONS
Metolazone administration could be helpful in patients taking an elevated loop diuretics dose. Use of thiazide therapy is associated with better decongestion and DR. Current findings could suggest positive insights due to the reduced amount of loop diuretics in patients with advanced HF.
PubMed: 34575318
DOI: 10.3390/jcm10184207 -
Journal of Clinical and Diagnostic... Mar 2016Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe mucocutaneous disease with high mortality rate. It is characterised by severe necrosis and...
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe mucocutaneous disease with high mortality rate. It is characterised by severe necrosis and detachment of the epidermis. Drugs are the most common triggering agent for SJS/TEN. These are commonly reported with the use of aromatic antiepileptics, antiretrovirals, allopurinol, NSAID'S and sulfonamide antibiotics. Non antibiotic sulfonamides rarely cause SJS/TEN. Metolazone is a well known diuretic and is extensively used by clinicians. Although this drug is in market for last several decades, no case of SJS/TEN has been reported till date. We report a rare case of metolazone induced SJS/TEN overlap in a 55-year-old lady.
PubMed: 27134890
DOI: 10.7860/JCDR/2016/17768.7404 -
Molecules (Basel, Switzerland) Jan 2023Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an...
Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used it to determine the drug concentrations in the plasma of rats after intravenous dosing in different genders and dosages. After pretreating the plasma samples with an acetonitrile-water-ammonia solution (70:30:1.25, //), liquid chromatographic separations were efficiently achieved with a XBridge C18 column using a 5 min gradient system of aqueous ammonium bicarbonate and 95% acetonitrile-water solution (95:5, /) as the eluent. The GMDTC and metolazone (internal standard, IS) detection were carried out using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS), monitored at / 390.06-324.1 (for the GMDTC, tR: 2.03 min) and / 366.0-259.2 (for IS, tR: 3.88 min). The GMDTC was stable under various testing conditions, and this analytical method conforms to the verification standard of biological analysis methods. The half-life (t) was determined to be 0.54-0.65 h for the intravenous, mean distribution volume and clearances were 1.08-2.08 L/kg and 1-3 L/h/kg, respectively. The AUC and AUC found after increasing the dosage exhibited a linear relationship with the administered dose. There were no statistically significant differences in the values obtained for the different genders at dosages of 50, 100 and 250 mg/kg, respectively ( > 0.05). This is the first report of a bioanalytical method to quantify GMDTC in rat plasma using LC-MS/MS, which provides useful information for the study of its pharmacological effects and clinical applications.
Topics: Rats; Female; Male; Animals; Chromatography, Liquid; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Indicators and Reagents; Cadmium; Reproducibility of Results
PubMed: 36770860
DOI: 10.3390/molecules28031191 -
BMC Nephrology Jun 2018There are no guidelines for transitioning patients from chronic kidney disease stage 5 to hemodialysis. We conducted this study to determine if there are uniform...
BACKGROUND
There are no guidelines for transitioning patients from chronic kidney disease stage 5 to hemodialysis. We conducted this study to determine if there are uniform patterns in how nephrologists transition patients to dialysis.
METHODS
We designed an electronic survey with 39 questions and sent it to a database of practicing nephrologists at the National Kidney Foundation. Factors that were important for transitioning a patient to hemodialysis were evaluated, including medication changes on dialysis initiation, dry weight and dialysis prescription.
RESULTS
160 US Nephrologists replied to the survey; 18% (29/160) of the responses were completed via social media sites. Prior to dialysis, 74% (118/160), prescribed furosemide and 67% (107/160) used furosemide with metolazone. Once dialysis started, only 46% (74/160) of the responders continued patients on diuretics daily. Hypertension medications prescribed in dialysis were calcium channel blockers 69% (112/160), beta blockers 36% (58/160), angiotensin converting enzyme inhibitor 32% (53/160), angiotensin receptor blocker 29% (46/160) and diuretics 25% (42/160). Once dialysis started, 68% (109/160) routinely changed medications. Most, 67% (107/160) ordered patients to avoid anti-hypertensive medications on dialysis days to allow for ultrafiltration. Dry weight was determined in the first week by 29% (46/160) and in the first month by 53% (85/160). Most, 59% (94/160) felt that multiple causes lead to hypertension. Most nephrologists would prescribe small dialyzers and a shorter period of time for the first dialysis session.
CONCLUSION
The transition period to chronic hemodialysis has variations in practice patterns and may benefit from further studies to optimize clinical practice.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Female; Humans; Male; Nephrologists; Patient Transfer; Renal Dialysis; Renal Insufficiency, Chronic; Surveys and Questionnaires; United States
PubMed: 29929485
DOI: 10.1186/s12882-018-0943-0 -
American Journal of Perinatology Jan 2015Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia. We examined their use and safety in this...
OBJECTIVE
Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia. We examined their use and safety in this group.
STUDY DESIGN
Retrospective cohort study of infants < 32 weeks gestation and < 1,500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997 to 2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and fraction of inspired oxygen on the first day of each course of diuretic use were identified.
RESULTS
About 37% (39,357/107,542) infants were exposed to at least one diuretic; furosemide was the most commonly used (93% with ≥ 1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. About 74% patients were exposed to one diuretic at a time, 19% to two diuretics simultaneously, and 6% to three diuretics simultaneously. The most common combination was furosemide/spironolactone, followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants were not receiving mechanical ventilation on the first day of each new course of furosemide (47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%). Any adverse event occurred on 42 per 1,000 infant-days for any diuretic and 35 per 1,000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1,000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia.
CONCLUSION
Despite no Food and Drug Administration (FDA) indication and little safety data, over one-third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support.
Topics: Acetazolamide; Amiloride; Bronchopulmonary Dysplasia; Chlorothiazide; Cohort Studies; Diazoxide; Diuretics; Drug Therapy, Combination; Ethacrynic Acid; Female; Furosemide; Humans; Hydrochlorothiazide; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Male; Mannitol; Metolazone; Off-Label Use; Respiration, Artificial; Retrospective Studies; Spironolactone; Thrombocytopenia
PubMed: 24801161
DOI: 10.1055/s-0034-1373845 -
Scientia Pharmaceutica 2015The monitoring of the plasmatic concentrations of cardiovascular drugs is crucial for understanding their pharmacokinetics and pharmacodynamics. A simple, sensitive,...
Simultaneous Determination and Pharmacokinetic Study of Losartan, Losartan Carboxylic Acid, Ramipril, Ramiprilat, and Hydrochlorothiazide in Rat Plasma by a Liquid Chromatography/Tandem Mass Spectrometry Method.
The monitoring of the plasmatic concentrations of cardiovascular drugs is crucial for understanding their pharmacokinetics and pharmacodynamics. A simple, sensitive, specific, and high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous estimation and pharmacokinetic study of losartan (LOS), losartan carboxylic acid (LCA), ramipril (RAM), ramiprilate (RPT), and hydrochlorothiazide (HCZ) in rat plasma using irbesartan (IBS) and metolazone (MET) as internal standards (ISs). After solid phase extraction (SPE), analytes and ISs were separated on an Agilent Poroshell 120, EC-C18 (50 mm × 4.6 mm, i.d., 2.7 μm) column with a mobile phase consisting of methanol/water (85:15, v/v) containing 5 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.4 mL/min. The precursor → product ion transitions for the analytes and ISs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) mode and switching the electrospray ionization (ESI) mode during chromatography from positive (to detect LOS, LCA, RAM, RPT, and IBS) to negative (to detect HCZ and MET). The method was validated as per the FDA guidelines and it exhibited sufficient specificity, accuracy, and precision. The method was found to be linear in the range of 3-3000 ng/mL for LOS and LCA, 0.1-200 ng/mL for RAM and RPT, and 1-1500 ng/mL for HCZ. The described method was successfully applied to the preclinical pharmacokinetic study of analytes after oral administration of a mixture of LOS (10 mg/kg), RAM (1 mg/kg), and HCZ (2.5 mg/kg) in rats.
PubMed: 26839805
DOI: 10.3797/scipharm.1410-15 -
Cureus Apr 2020Hyponatraemia is the most common electrolyte imbalance found in hospital population and worldwide thiazide and loop-diuretics are among the most widely used drugs....
Hyponatraemia is the most common electrolyte imbalance found in hospital population and worldwide thiazide and loop-diuretics are among the most widely used drugs. Syndrome of inappropriate antidiuresis diagnosis (SIAD) is complicated in the presence of diuretic therapy due to the misleading clinical assessment of the extracellular volume status, and in order to make SIAD diagnosis it is often necessary to withdraw diuretic therapy. Our study aimed to investigate the diagnostic role of these alternative markers of volume status, serum uric acid (sUA) and fractional excretion of uric acid (FEUA), in hyponatraemic patients treated with different diuretic drugs. Eighty-nine patients were enrolled with the diagnosis of SIAD, diuretic-induced hyponatremia (DIH, treated with furosemide and potassium canrenoate) or thiazide-induced hyponatremia (TIH, treated with hydrochlorothiazide, metolazone or indapamide) and investigated with receiver operating characteristic analysis and a sensitivity test. Our results show that FEUA discriminated better than sUA between SIAD and DIH patients (area under curve 0.96, <0.001 vs. 0.88, <0.001) while it was a poor marker to discriminate between SIAD and TIH (0.65, NS vs. 0.67, NS). In conclusions, FEUA is an excellent marker to discriminate SIAD vs. sodium depleted patients treated with furosemide and/or potassium canrenoate while the diuretic withdrawal, beyond obtaining a serum Na normalization, is still mandatory for differential diagnosis of sodium depleted patients affected by thiazide-induced hyponatraemia.
PubMed: 32455079
DOI: 10.7759/cureus.7762 -
European Review For Medical and... Apr 2021Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF.
MATERIALS AND METHODS
We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases.
RESULTS
Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison.
CONCLUSIONS
None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.
Topics: Acute Disease; Carbonic Anhydrase Inhibitors; Diuretics; Drug Resistance; Heart Failure; Humans; Randomized Controlled Trials as Topic
PubMed: 33877660
DOI: 10.26355/eurrev_202104_25550 -
Cureus Sep 2022Cardiac resynchronization therapy-defibrillator (CRT-D) and/or cardiac resynchronization therapy-pacemaker (CRT-P) play an important role in improving cardiac...
Cardiac resynchronization therapy-defibrillator (CRT-D) and/or cardiac resynchronization therapy-pacemaker (CRT-P) play an important role in improving cardiac synchronization and reducing the risk of ventricular fibrillation arrest (VFA) in patients with severe left ventricular systolic dysfunction (LVSD). Patients with LVSD may notice worsening symptoms when CRT-D or CRT-P is in dyssynchrony. We present a case of 59-year-old patient who presented with worsening shortness of breath (SOB) and progressive exertional dyspnea for the past few weeks accompanied by pink, frothy sputum, occasional urinary incontinence and urge. He was known to have severe LVSD with an ejection fraction of 10% and had CRT-D in situ. Clinical examination revealed bilateral crepitation and normal heart sounds. A chest radiograph showed pulmonary oedema. An electrocardiogram (ECG) showed atrial fibrillation (AF)/flutter with wide QRS complexes. The patient was treated for acute pulmonary oedema and had CRT-D reprogrammed to achieve biventricular synchrony. He was treated with intravenous furosemide and alternate day metolazone initially. He showed significant subjective and objective improvement and was planned for outpatient synchronized intra-device cardioversion. This case is important because patients with severe LVSD with malfunctioning cardiac resynchronization therapy can result in worsening heart failure (HF) leading to higher morbidity and mortality.
PubMed: 36258951
DOI: 10.7759/cureus.29096