Maintenance of therapeutic plasma aprotinin levels during prolonged cardiopulmonary bypass using a large-dose regimen

Aprotinin concentrations in the range of 127191 kallikrein inactivator units (KIU)/mL at the end of cardiopulmonary bypass (CPB) (<2 h duration) reduce transfusion requirements. It has been suggested that prolonged CPB may require higher infusion rates which significantly increase cost. We tested the hypothesis that large-dose aprotinin maintains therapeutic plasma levels during prolonged periods of CPB (>2 h). Aprotinin was administered as follows: 2 x 10⁶ KIU upon skin incision; 0.5 x 10⁶ KIU/h x 4-h infusion on initiation of CPB; and 2 x 10⁶ KIU added to the CPB prime solution. Aprotinin activity was measured 1) 30 min after initiation of drug administration (Pre-CPB); 2) 30 min after initiation of CPB (CPB + 30); 3) 90 min after initiation of CPB (CPB + 90); and 4) at CPB termination (End CPB). CPB duration (mean ± SD) was 158 ± 51 min. Plasma aprotinin concentrations (KIU/mL, mean ± SD) were: 234 ± 30 at Pre-CPB; 229 ± 35 at CPB + 30; 184 ± 27 at CPB + 90; and 179 ± 22 at End CPB. In all patients, aprotinin levels at the completion of CPB were in the range previously reported to be effective. The authors conclude that large-dose regimen limited to 6 x 10⁶ KIU maintained therapeutic plasma aprotinin concentrations during prolonged CPB.