Reduced need for vasopressors in patients receiving aprotinin during orthotopic liver transplantation

Background: Graft reperfusion in orthotopic liver transplantation is often associated with significant hemodynamic changes, including decreased system ic vascular resistance and arterial blood pressure. Vasopressive drugs are often required to maintain adequate perfusion pressure during the early pos treperfusion period. The exact mechanism of this postreperfusion syndrome i s unknown, but release of bradykinin, a potent vasodilatator, via the kalli krein system may play a role. Aprotinin is a broad-spectrum inhibitor of se rine proteases such as kallikrein and therefore may ameliorate the postrepe rfusion syndrome and reduce the need for vasopressors. Methods: In a randomized, double-blind study, the authors compared hemodyna mic variables (systemic vascular resistance, cardiac index, arterial blood pressure, mean pulmonary artery pressure, central venous pressure) and the requirement of epinephrine during transplantation in 67 patients who receiv ed either high-dose aprotinin (2 x 10(6) kallikrein inhibitor units [KIU] a t induction, continuous infusion of 1 x 10(6) KIU/h, 1 x 10(6) KIU before r eperfusion; n = 24), regular-dose aprotinin (2 x 10(6) KIU at induction, co ntinuous infusion of 0.5 x 10(6) KIU/h; n = 21), or placebo (n = 22). Results: Baseline characteristics were similar for all three groups. Erythr ocyte transfusion requirement was significantly higher in the placebo group compared with both aprotinin-treated groups. No major differences in hemod ynamic variables were found between the three groups. The total amount of e pinephrine (median, range) used during transplantation, however, was signif icantly lower in patients who received aprotinin (high dose, 20, 0-170 mug; regular dose, 30, 0-140 mug), compared with patients who received placebo (70, 0-2,970 mug; P = 0.0017). This difference was largely attributable to differences in the early postreperfusion period. Conclusions: Prophylactic use of aprotinin ameliorates the postreperfusion syndrome in orthotopic liver transplantation, as reflected by a significant reduction in vasopressor requirements.