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 systemic vascular resistance and arterial blood pressure. Vasopressive drugs are often required to maintain adequate perfusion pressure during the early postreperfusion period. The exact mechanism of this postreperfusion syndrome is unknown, but release of bradykinin, a potent vasodilatator, via the kallikrein system may play a role. Aprotinin 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 resistance, 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 x 10(6) kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 x 10(6) KIU/h, 1 x 10(6) KIU before reperfusion; n = 24), regular-dose aprotinin (2 x 10(6) KIU at induction, continuous infusion of 0.5 x 10(6) 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, however, was significantly lower in patients who received aprotinin (high dose, 20, 0-170 microg; regular dose, 30, 0-140 microg), compared with patients who received placebo (70, 0-2,970 microg; 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.
Molenaar
I Q
IQ
Department of Surgery, Leiden University Medical Center, The Netherlands.
Begliomini
B
B
Martinelli
G
G
Putter
H
H
Terpstra
O T
OT
Porte
R J
RJ
D000328:Adult; D007611:Aprotinin / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007432:Intraoperative Period; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015427:Reperfusion Injury / Q000517:prevention & control; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D015842:Serine Proteinase Inhibitors; D014662:Vasoconstrictor Agents; D007611:Aprotinin