Diuretic efficacy of high dose furosemide in severe heart failure: Bolus injection versus continuous infusion

Objectives. The efficacy of high dose furosemide as continuous infusion was compared with bolus injection of equal dose in patients with severe heart failure. Background. The delivery rate of furosemide into the nephron has been proved to be determinant of diuretic efficacy in healthy volunteers. Methods. In randomized crossover study we compared the efficacy of continuous infusion of high dose furosemide (mean daily dosage 690 mg, range 250 to 2,000) versus single bolus injection of an equal dose in 20 patients with severe heart failure. The patients received an equal dosage, either as single intravenous bolus injection or as an 8-h continuous infusion preceded by loading dose (20% of total dosage). Results. Mean (±SEM) daily urinary volume (infusion 2,860 ± 240 ml, bolus 2,260 ± 150 ml, p = 0.0005) and sodium excretion (infusion 210 ± 40 mmol, bolus 150 ± 20 mmol, p = 0.0045) were significantly higher after treatment with continuous infusion than with bolus injection, despite significantly lower urinary furosemide excretion (infusion 310 ± 60 mg every 24 h, bolus 330 ± 60 mg every 24 h, p = 0.0195). The maximal plasm furosemide concentration was significantly higher after bolus injection than during continuous infusion (infusion 24 ± 5 μg/ml, bolus 95 ± 20 μg/ml, p < 0.0001). Short-term, completely reversible hearing loss was reported only after bolus injection in 5 patients. Conclusions. We conclude that in patients with severe heart failure, high dose furosemide administered as continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.