Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion.
OBJECTIVE
The efficacy of high dose furosemide as a continuous infusion was compared with a 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 a determinant of diuretic efficacy in healthy volunteers.


METHODS
In a randomized crossover study we compared the efficacy of a continuous infusion of high dose furosemide (mean daily dosage 690 mg, range 250 to 2,000) versus a single bolus injection of an equal dose in 20 patients with severe heart failure. The patients received an equal dosage, either as a single intravenous bolus injection or as an 8-h continuous infusion preceded by a 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 plasma furosemide concentration was significantly higher after bolus injection than during continuous infusion (infusion 24 +/- 5 micrograms/ml, bolus 95 +/- 20 micrograms/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 a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.
Dormans
T P
TP
Department of Pharmacology, University of Nijmegen, The Netherlands.
van Meyel
J J
JJ
Gerlag
P G
PG
Tan
Y
Y
Russel
F G
FG
Smits
P
P
D000368:Aged; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006311:Hearing Disorders / Q000139:chemically induced; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D014012:Tinnitus / Q000139:chemically induced
D004232:Diuretics; D005665:Furosemide