Effect of high-dose furosemide in refractory congestive heart failure. High-dose firosemide is considered effective in primary renal sodium retention but is not generally recommended in congestive heart failure. In order to evaluate efficacy and safety of high-dose furosemide (greater than 500 mg/day), the authors studied 20 patients (pts) resistant to therapy (including furosemide less than 500 mg/day) selected from 161 pts admitted for chronic heart failure. All refractory pts (15 men and 5 women, mean age sixty +/- 12 years) were in NYHA class IV and showed hyponatremia (130 +/- 5 mEq/L) and impaired renal function (BUN 31 +/- 14 mg/dL, serum creatinine 1.3 +/- 0.3 mg/dL and BUN/creatinine ratio 23 +/- 7). In addition to digitalis, dopamine, angiotensin-converting enzyme inhibitors, or vasodilators, IV high-dose furosemide (775 +/- 419 mg/day, 500-2000) was given for ten +/- five days under daily clinical and laboratory monitoring. Three pts died of low-output syndrome while 16 pts were upgraded to NYHA class III and 1 pt to class II; a mean weight reduction of 7.3 +/- 2.9 kg in ten + five days (0.80 +/- 0.4 kg/day) and a mean diuresis increase of 88 +/- 57% occurred. The maximal dose of furosemide did not correlate with serum creatinine but did correlate with BUN/creatinine ratio (r = 0.78, p less than .001). Pts were discharged on with chronic heart failure, and 43% in the subgroup in NYHA class IV with hyponatremia. High dose furosemide was effective for rapid removal of excess water and salt in "furosemide-resistant" congestive heart failure. The relationship between renal impairment and maximal furosemide doses seems to confirm the role of renal pharmacokinetics in the appearance of furosemide resistance. 