Reduced Need for Vasopressors in Patients Receiving Aprotinin during Orthotopic Liver Transplantation

Background: Graft reperfusion in orthotopic liver transplan- tation is often associated with significant hemodynamic changes, including decreased systemic vascular resistance and arterial blood pressure. Vasopressive drugs are often required to maintain adequate perfusion pressure during the early post- reperfusion period. The exact mechanism of this postreperfu- sion syndrome is unknown, but release of bradykinin, a potent vasodilatator, via the kallikrein system may play a role. Apro- tinin is a broad-spectrum inhibitor of serine proteases such as kallikrein and therefore may ameliorate the postreperfusion syndrome and reduce the need for vasopressors. Methods: In a randomized, double-blind study, the authors compared hemodynamic variables (systemic vascular resis- tance, cardiac index, arterial blood pressure, mean pulmonary artery pressure, central venous pressure) and the requirement of epinephrine during transplantation in 67 patients who received either high-dose aprotinin (2 106 kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 106 KIU/h, 1 106 KIU before reperfusion; n 24), regular-dose aprotinin (2 106 KIU at induction, continuous infusion of 0.5 106 KIU/h; n 21), or placebo (n 22). Results: Baseline characteristics were similar for all three groups. Erythrocyte transfusion requirement was significantly higher in the placebo group compared with both aprotinin- treated groups. No major differences in hemodynamic variables were found between the three groups. The total amount of epinephrine (median, range) used during transplantation, how- ever, was significantly lower in patients who received aprotinin (high dose, 20, 0 –170 g; regular dose, 30, 0 –140 g), compared with patients who received placebo (70, 0–2,970 g; 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.