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Eur Heart J. 1996 Dec;17(12):1867-74.

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

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  • 1Department of Internal Medicine, University Hospital, Nijmegen, The Netherlands.



We studied the synergism between high-dose furosemide and hydrochlorothiazide in patients with severe congestive heart failure and impaired renal function showing diuretic resistance to a daily dose of furosemide of at least 250 mg.


An open study. A general hospital in The Netherlands.


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 medication unchanged. After correction of the hydration state, hydrochlorothiazide was withdrawn. Variables included body weight, serum electrolytes, renal function and natriuresis.


Addition of hydrochlorothiazide resulted in a mean (+/-standard deviation) body weight reduction of 6.7 +/- 3.3 kg per patient. Mean daily urine volume increased from 1899 +/- 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 ml. min-1.1.73 m-2 to 27.6 +/- 22.5 ml. min-1.1.73 m-2.


Addition of hydrochlorothiazide to high-dose 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 setting.

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