Aprotinin in coronary operation with cardiopulmonary bypass: does "low-dose" aprotinin inhibit the inflammatory response?

Englberger, L.; Kipfer, B.; Berdat, P.A.; Nydegger, U.E.; Carrel, T.P.

Annals of Thoracic Surgery 73(6): 1897-1904


ISSN/ISBN: 0003-4975
PMID: 12078788
DOI: 10.1016/s0003-4975(02)03535-x
Accession: 045294982

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Cardiopulmonary bypass induces a systemic inflammatory response. Aprotinin, a nonspecific proteinase inhibitor is known to improve postoperative hemostasis and may modify the inflammatory reaction. This study evaluates the effects of low-dose aprotinin on inflammatory markers in patients scheduled for elective coronary artery bypass grafting. Patients were prospectively randomized into two groups: the control group (C) (n = 14) and the low-dose aprotinin group (A) (n = 15) with (2 x 10(6) KIU = 280 mg) aprotinin added to the pump prime. Cytokine response (interleukin-6, soluble TNF II receptor), terminal complement production (SC5b-9), and neutrophil activation (lactoferrin) were assessed up to 6 hours postoperatively. Clinical data and hemostatic factors including fibrinopeptide A, thrombin-antithrombin complex, D-dimer, and plasmin/alpha2-antiplasmin were investigated. In both study groups, a significant increase of all inflammatory markers was seen (IL-6, sTNF-IIR, SC5b-9, lactoferrin), p less than 0.001. Peak levels of complement production occurred after protamine administration, whereas cytokine increases were more pronounced postoperatively with marked elevation up to 6 hours. The markers did not differ significantly between groups throughout the study period (p > 0.05 at each time of determination). However, after protamine administration reduced fibrinolysis (D-dimer, plasmin/alpha2-antiplasmin) was detected in group A. Measurements for coagulation (fibrinopeptide A, thrombin-antithrombin complex) were not significantly influenced by aprotinin. The total amount of blood loss during the first 24 hours was significantly reduced in group A (p < 0.02). Low-dose aprotinin added to the pump prime does not inhibit the inflammatory response caused by cardiopulmonary bypass, but improves postoperative hemostasis. A potential effect of high-dose aprotinin on inflammatory markers remains to be elucidated.