Introduction: It was shown that aprotinin (A) prevents bradykinin formation during CPB, thus improving systemic vascular resistance (SVR) . The purpose of this study was to investigate the efficiency of intraoperative A administration on postoperative prevention of haemodynamic effects of SIRS (decline of SVR) and to reveal an efficient dose of A to provide such protection.
Method: In a prospective, randomized clinical trial 73 patients (elective coronary bypass grafting with CPB) were assigned to one of three groups: group A6 (n = 25) received A intraoperatively in a total dose of 6 × 106 KIU. 1 × 106 KIU of A was infused before incision; next 2 × 106 KIU of A during surgery before CPB, and an additional dose of 3 × 106 KIU A was added to the pump prime. Group A3 (n = 24, total dose of A3 × 106 KIU) was treated with A similarly to A6 before CPB, but A was not added to the pump prime. Group A0 (n = 24) did not receive A. A non-pulsatile roller pump (Cobe, USA) and hollow-fibre oxygenator (Terumo, Japan) were used in all patients (2.5L·min−1·m−2, t = 34-35°C). If systolic blood pressure dropped below 90 mmHg postoperatively and infusion therapy was ineffective then an infusion of phenylephrine was started. Total dose of phenylephrine, duration and rate of its infusion were calculated. Haemodynamic measurements were performed using the thermodilution technique. The results were statistically analysed using ANOVA, LSD-test, chi-squared test for categorical variables, and expressed as M ± SD.
Results: Groups did not differ significantly with respect to preoperative premedication and surgical data, blood loss, and infusion therapy. Baseline SVR were: A6 1675 ± 516 dyn sec cm−5, A3 1685 ± 470, A0 2014 ± 693, P > 0.05 between groups. Dose of phenylephrine used during CPB was higher in A0 (3.2 ± 3.2mg) and A3 (2.9 ± 3.7mg) groups vs. A6 group (1.1 ± 1.2mg); P = 0.007 and P = 0.03 respectively. The dose of phenylephrine used did not differ between groups in the postoperative period. CI increased postoperatively and SVR declined in all groups. ΔCI, ΔSI, ΔSVR were calculated for each group at 12 and 24 hours postoperatively (Δ = value at 12 or 24 h. postop. - value preop.).
Conclusion: In our study only 6 × 106 KIU of A clearly diminished phenylephrine dose during CPB. Postoperatively aprotinin effectively protected SVR regardless of dose (3 or 6 × 106 KIU). We suppose that there are different mechanisms involved in the protective action of A during CPB and in the postoperative period.
1 Nagaoka H, Katori M. Inhibition of kinin formation by a kallikrein inhibitor during extracorporeal circulation in open-heart surgery. Circulation
; 2; 325-332.