“Low-Dose” Aprotinin Modifies Hemostasis but Not Proinflammatory Cytokine Release

Background. Cytokines are implicated in the pathogenesis of the “whole-body inflammatory response” that may complicate the period after cardiopulmonary bypass (CPB). Low-dose aprotinin in the pump during CPB has been shown to improve postoperative hemostasis and platelet preservation. We tested the hypothesis that low-dose aprotinin influences the inflammatory reaction (in terms of cytokine release) after CPB. Methods. In a prospective, randomized study, 38 patients undergoing elective coronary artery bypass grafting were investigated. Nineteen patients received low-dose aprotinin (2 × 106 KIU [280 mg] in the pump), and a control group of 19 did not. Complement activation, cytokine production, leukocyte elastase release, D-dimer level, full blood count, postoperative blood loss, and transfusion requirements were analyzed before, during, and after CPB. Results. Interleukin-1β was not detected in either group, whereas traces of tumor necrosis factor-α were infrequently observed. Plasma elastase, interleukin-6, interleukin-8, and neutrophil count increased (p< 0.001) during and after CPB compared with the baseline levels, reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours. Proinflammatory cytokine markers did not differ significantly (p> 0.1) between the groups throughout the study period. The C5b-9 level increased (p< 0.001) in both groups perioperatively, reaching its peak 15 minutes after protamine. Twenty-four–hour postoperative blood loss was significantly (p< 0.001) reduced in the aprotinin group in association with markedly reduced D-dimer levels (p< 0.001). Patients in the aprotinin group also received significantly less banked blood postoperatively than the control group (p< 0.01). Conclusions. Low-dose aprotinin fails to modify proinflammatory cytokine release, yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting. (Ann Thorac Surg 1997;63:68–73)