Input rate as a major determinant of furosemide pharmacodynamics: Influence of fluid replacement and hypoalbuminemia

To investigate how the response to a bolus and an infusion of furosemide is modulated by the rate of fluid replacement and by hypoalbuminemia, rabbits received 5 mg/kg of furosemide as a bolus or infused over 60 min, whereas diuresis was replaced with 13, 121, or 238 ml/h NaCl 0.9%/glucose 5% (50:50 ). Natriuretic and diuretic efficiencies were greater with the infusion tha n with the bolus of furosemide. Fluid replacement increased natriuretic and diuretic efficiency of furosemide bolus but only diuretic efficiency of fu rosemide infusion. Furosemide net fluid depletion reached a plateau when fl uid replacement increased beyond 121 ml/h. Repeated plasmapheresis decrease d plasma albumin by 30% (P < .05) and increased furosemide unbound fraction (P < .05). Compared with control rabbits, hypoalbuminemia decreased the na triuresis of the bolus (22.7 +/- 1.5-16.6 +/- 1.3 mmol, P < .05) but not th at elicited by furosemide infusion (26.2 +/- 1.8 mmol). Given as a bolus, f urosemide natriuretic and diuretic response as a function of its urinary ra te of excretion exhibited an hyperbolic relationship, and after its infusio n a clockwise hysteresis, denoting tolerance. Plasma renin activity was inc reased by the bolus and the infusion of furosemide, even in the presence of 121 ml/h of fluid replacement. It is concluded that: 1) the increase in na triuretic/diuretic efficiency of the bolus induced by fluid replacement is greater than when furosemide is infused, 2) furosemide net effect does not increase proportionally to fluid replacement, and 3) the infusion of furose mide prevents the hypoalbuminemia-induced decrease in response of furosemid e given as a bolus.