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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Englberger
Lars
L
Department of Cardiovascular Surgery, University Hospital (Inselspital), Berne, Switzerland. lars.englberger@insel.ch
Kipfer
Beat
B
Berdat
Pascal A
PA
Nydegger
Urs E
UE
Carrel
Thierry P
TP
D007611:Aprotinin / Q000008:administration & dosage* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology
D018836:Inflammation Mediators; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin