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

Objective 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. 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 medication 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 After correction of the hydration state, hydrochlorothiazide was withdrawn.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 (± 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 Conclusions 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.