"Low-dose" aprotinin modifies hemostasis but not proinflammatory cytokine release

Abstract

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, 36 patients undergoing elective coronary artery bypass grafting were investigated. Nineteen patients received low-dose aprotinin (2 x 10(6) 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 after CPB.

Results: Interleukin-1 beta was not detected in either group, whereas traces of tumor necrosis factor-alpha 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.