Using activated clotting time to estimate intraoperative aprotinin concentration

Abstract

The use of aprotinin during cardiopulmonary bypass may be associated with renal dysfunction due to renal excretion of excess drug. We hypothesized that the difference between standard celite activated clotting time (ACT), which is prolonged by aprotinin, and kaolin ACT could provide an estimate of aprotinin blood level. Fresh porcine blood was collected from six donor pigs and heparinized. Blood was stored at 4 degrees Celsius, rewarmed and aprotinin was added: 0, 100, 200, and 400 kallikrein inhibitor units/ml. Specimens were incubated at 37 degrees Celsius. Two pairs of ACT tubes (one celite and one kaolin) were measured at 37 degrees Celsius and 20 degrees Celsius using two Hemochron 401 machines. A generalized estimating equation (GEE) statistical approach was used to estimate actual aprotinin from differences in celite and kaolin ACT. There was a significant relationship of the form y = exp(a+bx) between aprotinin concentration and the difference between celite and kaolin ACT at both 37 degrees Celsius (R(2) = 0.858) and 20 degrees Celsius (R(2) = 0.743). The time difference between celite and kaolin ACT may be a simple and inexpensive method for measuring the blood level of aprotinin during cardiopulmonary bypass. This technique may improve patient-specific dosing of aprotinin and reduce the risk of postoperative renal complications.