Increased Spironolactone in Advanced HF: Effect of Doses Greater Than 25 mg/day on Plasma Potassium Concentration. Jentzer JC, DeWald TA, Hernandez AF. Knauf H., Mutschler E. Sequential Nephron Blockade Breaks Resistance to Diuretics in Edematous States. One approach to overcome loop diuretic resistance is the addition of a thiazide-type diuretic to produce diuretic synergy via "sequential nephron blockade," first described more than 40 years ago. Andersson C, Norgaard ML, Hansen PR, Fosbol EL, Schmiegelow M, Weeke P. Heart failure severity, as determined by loop diuretic dosages, predicts the risk of developing diabetes after myocardial infarction: a nationwide cohort study. Accessed: April 1, 2015. This site needs JavaScript to work properly. Renal hemodynamic changes in HF. Side effects include increased urination and sodium loss. Bart B.A., Boyle A., Bank A.J., Anand I., Olivari M.T., Kraemer M., Mackedanz S., Sobotka P.A., Schollmeyer M., Goldsmith S.R. Treatment of refractory congestive heart failure and normokalemic hypochloremic alkalosis with acetazolamide and spironolactone. A second class of diuretics, sometimes termed aquaretics, instead inhibit water reabsorption by blocking vasopressin receptors along the . Sica D.A. 287(12):1578-80. Torasemide in comparison with thiazides in the treatment of hypertension. Available at http://www.medscape.com/viewarticle/839183#vp_1. Blocking distal tubule sodium reabsorption with thiazide diuretics can antagonize this renal adaptation to chronic loop diuretics [29,30]. The use of natriuretic doses of MRAs (e.g., spironolactone 50100 mg) therefore could be a reasonable option to treat selected diuretic resistant, volume overloaded HF patients. The transient increase in serum creatinine in HF patients during fluid overload treatment may represent short-term dehydration and actually be a hall-mark of successful treatment [25,77]. sharing sensitive information, make sure youre on a federal Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this Lloyd-Jones D., Adams R.J., Brown T.M., Carnethon M., Dai S., De Simone G., Ferguson T.B,, Ford E., Furie K., Gillespie C., Go A., et al. Description: The goal of the trial was to compare changes in body weight and patient-reported dyspnea among patients with acute decompensated heart failure (HF) receiving intravenous (IV) loop diuretics with hydrochlorothiazide (HCTZ) versus placebo. This Na/K/2Cl pump is located on the luminal side of the nephron. Activation of the neurohumoral axis. Karlheinz Peter, MD, PhD is a member of the following medical societies: American Heart Association, German Cardiac Society, Cardiac Society of Australia and New ZealandDisclosure: Nothing to disclose. Lastly, there are reports of the use of chronic peritoneal dialysis in treating refractory HF patients who are refractory to conventional therapy and have repeated rehospitalizations [80]. The patients weight should be measured at this point and be documented as the patients euvolemic (or dry) weight. 2010 Jun. Patients in both groups had the same weight loss and dyspnea score, but patients in the UF group had a significantly greater increase in serum creatinine (0.04 vs. +0.23 mg/dl, p = 0.003) and more adverse events including bleeding and vascular complications as well as the progession of renal dysfunction (72% vs. 57%, p = 0.03). Thiazideinduced hypokalemia is associated with increased blood glucose, and treatment of thiazideinduced hypokalemia may reverse glucose intolerance and possibly prevent diabetes. government site. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. In the several studies, tolvaptan consistently has demonstrated an aquaretic effect (urinary electrolyte-free water loss) in HF patients [44,45,46,47,48]. Conivaptan treatment in HF patients resulted in an increase in urine output and a decrease in pulmonary artery wedge pressure without affecting vascular resistance, blood pressure, heart rate or non-sodium plasma electrolytes [43]. 1985 Jul. The selected dose needs to be progressively higher as the GFR decreases. being able to get an erection sometimes, but not every time you want to have sex. oral furosemide.6 Bumetanide and especially torsemide are more predictably absorbed than furosemide. Moreover, sodium reabsorption is also increased in the distal tubule in HF patients, an effect which contributes to diuretic resistance [61]. On the other hand, ultrafiltration in HF patients with worsening renal function and volume overload after aggressive treatment with loop diuretics, failed to show benefit compared to a stepwise pharmacological approach, including diuretics and vasoactive drugs. Unable to load your collection due to an error, Unable to load your delegates due to an error. Bethesda, MD 20894, Web Policies Prompt recognition of diuretic resistance in patients with decompensated HF could allow for alternative strategies, such as ultrafiltration, to improve natriuresis resulting a more rapid improvement in symptoms and a shortened hospital stay. The various loop diuretics differ in intestinal absorption, especially with an edematous bowel wall present in decompensated HF. Regolisti G., Fiaccadori E. Ultrafiltration in acute decompensated heart failure: Friend or foe for the kidney? This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (, cardiac failure, diuretic resistance, diuretic combinations, ultrafiltration. Loop diuretics are the most commonly used drugs in this setting. Diuretic strategies in patients with acute decompensated HF. Loop diuretics increase calciuresis, decrease serum calcium concentration, and may contribute to osteoporosis progression. Integr. Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction: An international, multicenter, randomized, placebo-controlled trial. Pepi M., Marenzi G.C., Agostoni P.G., Doria E., Barbier P., Muratori M., Celeste F., Guazzi M.D. Many would recommend doubling the dose to 80 mg, assuring its efficacy, and then choosing a dosing interval. Again, however, plasma potassium needs to be carefully monitored to avoid hypokalemia. [18], The multicenter DOSE study explored the effects of high dose versus low dose diuretic use in acute decompensated heart failure. [QxMD MEDLINE Link]. Administration of torasemide alone significantly (P < 0.01) increased mean cumulative 24-hour excretion of sodium (from 154 +/- 30 to 232 +/- 59 mmol/24 hr) and chloride (from 128 +/- 21 to 233 +/- 84 mmol/24 hr) as compared with baseline. However, a widely accepted definition of loop diuretic resistance in HF patients is lacking. Brater D.C. 2009. [QxMD MEDLINE Link]. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR. 2011 Mar 3. 125(1):188-97. The aldosterone antagonists spironolactone and eplerenone have been shown to be effective therapies for chronic heart failure, based on the RALES and EPHESUS studies. Eur J Heart Fail. Ann Pharmacother. Torsemide provides the longest duration of action and can give even greater diuretic effects in patients with hepatic dysfunction or heart failure. [13] When choosing the dosing regimen, consider both the dose and frequency. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated HF. N Engl J Med. Among open-label studies comparing torsemide to furosemide, one demonstrated decreased mortality, one showed decreased heart failure hospitalizations, and two found improvement in New York Heart Association functional class. In patients with end-stage renal disease such fluid mobilization has been estimated to be 1215 mL/min [78]. 2007 Feb 13. J Am Coll Cardiol. However, oral absorption of furosemide may vary from patient to patient as much as 10% to 100% [21,22]. 348(14):1309-21. Ultrafiltration (UF) is another option of removing excess fluid in HF patients. Pitt B., Zannad F., Remme W.J., Cody R., Castaigne A., Perez A., Palensky J., Wittes J. Bart B.A., Goldsmith S.R., Lee K.L., Givertz M.M., O'Connor C.M., Bull D.A., Redfield M.M., Deswal A., Rouleau J.L., LeWinter M.M., et al. Diuretics, particularly thiazide-type and thiazide-like diuretics, are commonly used in the treatment of hypertension. However, there are criticisms of this study relating to the methods used. Circulation. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Dietary sodium restriction and use of loop diuretics that block sodium and water reabsorption in the proximal nephron are the cornerstones of therapy. Sarraf M., Masoumi A., Schrier R.W. Nevertheless, some patients with mild to moderate HF and preserved renal function can maintain fluid balance with thiazide diuretics. 2010 Nov 2. [26] : Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB. Electrolytes and renal function need to be frequently monitored during diuretic titration and at least every 6 months in patients on stable long-term diuretics. Often physicians will stop active diuresis once the BUN levels begin to rise. For the Randomized Aldactone Evaluation Study Investigators. doses of loop diuretics. Clin Pharmacol Ther. Minutolo R, De Nicola L, Mallamaci F, Zoccali C. Clin Kidney J. In contrast, thiazide diuretics decrease urinary calcium excretion and thereby prevent renal calculi formation. butizid. Zile M.R., Bennett T.D., St John Sutton M., Cho Y.K., Adamson P.B., Aaron M.F., Aranda J.M., Jr, Abraham W.T., Smart F.W., Stevenson L.W., et al. 6 (4):286-294. Konstam M.A., Gheorghiade M., Burnett J.C., Jr., Grinfeld L., Maggioni A.P., Swedberg K., Udelson J.E., Zannad F., Cook T., Ouyang J., et al. Kirchner K.A. Federal government websites often end in .gov or .mil. [QxMD MEDLINE Link]. Increases in serum creatinine frequently occur secondary to prerenal physiology. They may be beneficial in counteracting the hypokalemia from loop diuretics. Effectiveness of thiazide and thiazide-like diuretics in advanced chronic kidney disease: a systematic review and meta-analysis. JAMA. 2001 Nov. 111(7):513-20. Chronic treatment with loop diuretics can result in renal adaptation, which includes hypertrophy and hyperfunction of distal tubular cells with enhanced sodium uptake in addition to the stimulation of aldosterone secretion [28,29]. Konecke LL. Loop diuretics inhibit the back leak of luminal potassium and therefore are kaliuretic. Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN. Response to the amount of free diuretic in tubular fluid and the amount of filtered sodium load reaching the nephron segment determine the pharmakodynamic properties and thus the effectiveness of a diuretic [59]. UF may be indicated in some elderly HF patients with preserved left ventricular ejection fraction. Intrarenal vasoconstriction with increased proximal sodium and water reabsorption also attenuates the salt losing action of natriuretic peptides in distal tubules [8,16] (Figure 3). Absorption of . The markedly increased sodium delivery to the cortical collecting duct leads to a significant potassium wasting. Schrier R.W. Fiaccadori E., Regolisti G., Maggiore U., Parenti E., Cremaschi E., Detrenis S., Caiazza A., Cabassi A. Ultrafiltration in heart failure. Packer M. Neurohormone interaction and adaptations in congestive HF. Determining the appropriate end-point for diuresis can be challenging. However, a recent Cochrane analysis suggested that currently available data were inadequate to support this contention [24]. Interrelation of humoral factors, hemodynamics, and fluid and salt metabolism in congestive HF: Effects of extracorporeal ultrafiltration. (See "Mechanism of action of diuretics" .) If it continues for a long time, the heart and arteries may not function properly. Thus, in cases of renal insufficiency larger doses are necessary to obtain effective urinary concentrations [18]. The increase in filling pressures in atria and ventricles also results in the release of natriuretic peptides (ANP and BNP) [10]. Moreover, treatment with UF resulted in significantly fewer hospital readmissions due to HF during 90-day follow-up [72,73]. [QxMD MEDLINE Link]. Such an approach helps detect hypervolemia before symptoms develop and may prevent full exacerbations. Tolvaptan can be used in association with loop diuretics. Disclaimer. This results in reduced effectiveness of diuretics. On the 6th and 13th study days, two sham infusions were given to patients in order to assess basal 24-hour urinary electrolyte excretion. Clipboard, Search History, and several other advanced features are temporarily unavailable. [QxMD MEDLINE Link]. [19] No difference in the primary end-point of patient symptoms or change in serum creatinine concentration was seen. Combination of loop diuretics with thiazide-type diuretics in heart failure. This review will primarily focus on loop diuretic agents as the mainstays of diuretic therapy for HF, but will also discuss other adjuncts to loop diuretic therapy such as thiazides that are primarily used when there is diuretic resistance. Epub 2022 Aug 13. Silverstein M.E., Ford C.A., Lysaght M.J., Henderson L.W. [19]. 2003 Mar. The serum half-life of the drug must be considered when selecting the dosing interval. Adams K.F., Jr, Fonarow G.C., Emerman C.L., LeJemtel T.H., Costanzo M.R., Abraham W.T., Berkowitz R.L., Galvao M., Horton D.P., ADHERE Scientific Advisory Committee and Investigators Characteristics and outcomes of patients hospitalized for heart failure in the United States: Rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). The .gov means its official. Bookshelf Metalozone, however, has a variable absorption and long half-life (about 2 days), which make other thiazides easier to use [18,21]. Other strategies include diuretics that block sodium and water absorption in different segments of nephron. Heart disease and stroke statistics-2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Thus, early recognition of diuretic resistance as manifested by diminished diuretic and natriuretic response to loop diuretics and a high right atrial pressure may indicate those patients most likely to have a beneficial response to UF. [21] For patients who have a significantly reduced GFR or diuretic resistance, sequential nephron blockade can be extended to include the proximal convoluted tubule, with acetazolamide, and the cortical collecting duct, with spironolactone. Results from the Acute Heart Failure Registry (ADHERE) revealed that 33% of the patients were discharged with a weight loss of 5 pound or less, 16% were discharged with an increase in body weight and 30% were considered to be resistant to loop diuretics. [QxMD MEDLINE Link]. In a dose ranging study prior to the Randomized ALdactone Evaluation Study (RALES) the investigators demonstrated that 25 mg/day of spironolactone did not decrease sodium retention [39]. It is recommended in severe congestive heart failure (HF). 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