In this retrospective analysis we tested the hypothesis that
aprotinin doses of more than 6 x 10(6)
kallikrein inhibiting units (KIU) per patient may be more effective in reducing
bleeding compared with the high-dose regimen of 5-6 x 10(6) KIU
aprotinin. The
aprotinin doses administered for 8281 adult cardiac surgical patients were correlated to
body weight and time of operation and calculated in KIU per kg
body weight and minute of operation. Linear and logistic regression models were designed to detect potential associations between dose and postoperative
bleeding, transfusion, and other covariates. The 6-h
chest tube drainage in the lowest quartile dosing group was 447 +/- 319 mL (mean +/- sd) compared with 360 +/- 290 mL in the highest quartile dosing group (P < 0.001). The proportion of patients requiring allogeneic
blood transfusion was reduced from 55% to 47% comparing the lowest with the highest dosing group (P < 0.01).
Aprotinin dose was also an independent predictor for rethoracotomy for
surgical hemostasis (1.9% in the highest quartile to 2.4% in the lowest dosing quartile; P < 0.01). The risk of
renal failure requiring dialysis (2.3% in the highest dosing group vs 3.3% in the lowest dosing group; P < 0.01) or impairment of renal function (
creatinine increase of >or=2 mg/dL postoperatively, 6.4% in the highest dosing group vs 10.0% in the lowest dosing group; P < 0.01) was lower with higher doses of
aprotinin. Thus, there was no association between
aprotinin dose and renal function. Our results support the hypothesis that a more individualized
aprotinin regimen with potentially higher doses may optimize the effectiveness of
aprotinin therapy in cardiac surgery.