Combination of high-dose furosemide and hydrochlorothiazide in the treatment of refractory congestive heart failure

Abstract

Objective We studied the synergism between high-dose furosemide and hydrochlorothiazide in patients with severe congestive heart failure and impaired renal function show ing diuretic resistance to a daily dose of furosemide of at least 250 mg. Design and setting An open study. A general hospital in The Netherlands.Methods In 20 patients with severe congestive heart failure (stage III-IV according to the New York Heart Association) with an oedematous mass of more than 5 kg and a proven diuretic resistance to high-dose furosemide, hydrochlorothiazide (25-100 mg daily) was added to the medication for 3-12 days, leaving the other medica tion unchanged. After correction of the hydration state, hydrochlorothiazide was withdrawn. Variables included body weight, serum electrolytes, renal function and natriuresis.Results Addition of hydrochlorothiazide resulted in a mean (it standard deviation) body weight reduction of 6*7 ± 3*3 kg per patient. Mean daily urine volume increased from 1899 dt 958 ml to 3065 ± 925 ml (P<0*001). Fractional sodium excretion increased significantly from 3-5 ±3-2% to 11*5 ± 9*0% (P<0-001), The most important side effect of this combination therapy appeared to be hypokalaemia. Mean endogenous creatinine clearance decreased (not significantly) from 32*7 ± 22*5 m l. min ~ 1 . 1*73 m " 2 to 27*6 ± 22-5 ml . min" 1 , 1*73 m~2.Conclusions Addition of hydrochlorothiazide to highdose furosemide is a powerful diuretic tool, even in patients with a significantly reduced renal function. Because of its potentially dangerous side effects (hypokalaemia), it should be used in a carefully controlled

Comparison of Metolazone Versus Chlorothiazide in Acute Decompensated Heart Failure with Diuretic Resistance

“…Consequently, the timing and choice of thiazide-type diuretics is often empiric, clinician-dependent, and not sufficiently data driven. Most of the studies and/or case series that do exist are quite small, usually lack comparator groups, and investigated a variety of different, older, and less commonly used thiazide-type diuretics compared to the agents more frequently used today [10][11][12][13][14][15][16][17][18][19][20][21][22]. In fact, to the best of our knowledge, not even a single study has been published comparing the effectivenes and safety of two of the most commonly utilized thiazide diuretics in HF, metolazone or chlorothiazide, as add-on therapy to loop diuretics in ADHF.…”

The use of diuretics in acute heart failure: Evidence based therapy?

“…These include: changing the route of administration from oral to intravenous (thus overcoming bioavailability issues); continuous infusion of loop diuretic rather than intermittent bolus injections (minor effect); using higher doses of intravenous loop diuretics to increase dose reaching the tubules, particularly when glomerular filtration is poor; sequential nephron blockade by using a combination of diuretics [47][48][49][50] such as metolazone or bendroflumethazide in addition to a loop diuretic. Two of these randomized studies are summarized in Figure 2.…”

Inpatient management of patients with volume overload and high filling pressures

“…16 Extreme care must be taken to avoid overdiuresis, but this combination can be helpful to treat diuretic resistance. 17 The third class of agents are the so-called potassium-sparing diuretics, which block sodium reuptake in the final portion of the nephron (the collecting ducts), resulting in an obligatory reuptake of potassium. These agents include the aldosterone receptor blocker spironolactone and eplerenone, which act primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule.…”