Aprotinin concentration varies significantly according to cardiopulmonary bypass conditions

Abstract

Although aprotinin is partially excreted unchanged in the urine, its primary site of metabolism is in the renal lysosomes following proximal tubule resorption. This study tested the hypothesis that plasma aprotinin concentration varies with cardiopulmonary bypass conditions. Thirty-two piglets (weight 13.2 ± 1.9 kg) received an aprotinin initial dose of 30,000 KIU/kg, a maintenance infusion of 10,000 KIU/kg/h, with a cardiopulmonary bypass (CPB) prime of 30,000 KIU/kg. Aprotinin infusion was terminated at the end of CPB and stopped during hypothermic circulatory arrest (HCA). Piglets were randomized to four groups (n = 8 per group): HCA, 60-minute period at 15°C; low-flow (LF), 10 mL/kg/min low-flow CPB at 25°C; full flow (FF), full flow CPB at 37°C; control at 37°C without CPB. Blood samples were collected at 7 time points: after induction of anesthesia (baseline), after initial dose, 10, 50 and 115 min after start of CPB, just before end of CPB and 30 min after CPB. Plasma aprotinin levels were determined by modified functional assays. Aprotinin levels in the control group were significantly lower at each point after start of CPB than all groups with CPB ( p < .001). In particular, during the reperfusion period, aprotinin levels were higher in HCA and LF groups than FF group ( p < .05). Throughout CPB, aprotinin levels in the HCA group remained unchanged ( p > .40). Bypass conditions affect plasma aprotinin concentration. Recently reported renal and neurological complications with aprotinin use during CPB may reflect excessive dosing and point to the need for real-time monitoring.