High-dose firosemide is considered effective in primary renal sodium re tention but is not generally recom mended in congestive heart failure. In order to evaluate efficacy and safety of high-dose furosemide (>500 mg/day), the authors studied 20 patients (pts) resistant to therapy (including furose mide <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 im paired 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, dopa mine, 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 syn drome 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 di uresis increase of 88±57% oc curred. The maximal dose of furosemide did not correlate with serum creatinine but did correlate with BUN/creatinine ratio (r = 0.78, p<.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 ex cess water and salt in "furosemide-re sistant" congestive heart failure. The relationship between renal impair ment and maximal furosemide doses seems to confirm the role of renal pharmacokinetics in the appearance of furosemide resistance.
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References
1.
Lee WH, Packer M.: Prognostic importance of serum sodium concentration and its modification by converting-enzime inhibition in patients with severe chronic heart failure . Circulation73: 257-267, 1986.
2.
Dzau VJ, Colucci WS, Hollernberg NK, et al: Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure. Circulation63:645-652, 1981.
3.
Packer M., Lee WH, Kessler PD, et al: Identification of hyponatremia as a risk factor for development of functional renal insufficiency during converting enzyme inhibition in severe chronic heart failure. J Am Coll Cardiol10:837-844, 1987.
4.
Mc Fate Smith W.: Epidemiology of congestive heart failure . Am J Cardiol55:3A-8A, 1985.
5.
Donato L., Biagini A., Contini C., et al: Treatment of endstage congestive heart failure by extracorporeal ultrafiltration. Am J Cardiol59:379-380, 1987.
6.
Kuchar DL, O'Rourke MF: High dose furosemide in refractory cardiac failure. Eur Heart J6:954-958, 1985.
7.
Gerlag Pgg, Van Meijel JJM: High-dose furosemide in the treatment of refractory congestive heart failure . Arch Intern Med148:286-291, 1988.
8.
Smith TW, Braunwald E., Kelly RA: The management of heart failure. In: Heart Disease: A Textbook of Cardiovascular Medicine, ed. by Braunwald E.Philadelphia: WB Saunders Co, 1988, pp 485-543.
9.
Rose BD: Clinical physiology of acid-base and electrolyte disorders, ed 2. New York: McGraw-Hill International Book Co, 1984.
10.
Brater DC, Chennavasin P., Seiwell R.: Furosemide in patients with heart failure: A shift in dose-response curves . Clin Pharmacol Ther28:182-186, 1980.
11.
Brater DC: Resistance to loop diuretics: Why it happens and what to do about it. Drugs30:427-443, 1985.
12.
Brenner BM, Rector FC Jr: The Kidney: Philadelphia: WB Saunders Co, 1986, p 764.
13.
Brater DC, Seiwell R., Anderson S., et al: Absorption and disposition of furosemide in congestive heart failure. Kidney Int22:171-176, 1982.
14.
Puschett JB : Clinical pharmacologic implications in diuretic selection. Am J Cardiol57: 6A-13A, 1986.
15.
Wollam GL, Tarazi RC, Bravo EL, et al: Diuretic potency of combined hydrochlorthiazide and furosemide therapy in patients with azotemia. Am J Med72: 929-938, 1982.
16.
Epstein M., Lepp BA, Hoffman DS, et al: Potentiation of furosemide by metolazone in refractory edema . Curr Ther Res21:656-667, 1977.
