title: Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation.
abstract: The goal of this report is to evaluate in a prospective randomized fashion the effect of flushing hepatic allografts with tacrolimus before transplantation. A prospective, double-blinded, randomized trial was performed. Twenty patients receiving orthotopic liver transplants from October 2000 to October 2001 were randomized into two groups. Group 1 (active) was administered tacrolimus, 20 ng/mL, plus Plasma-lyte A (Baxter Healthcare Corp, Deerfield, IL) liver flush solution; and group 2 (placebo) was administered only Plasma-lyte A. Ischemia/reperfusion injury was assessed in both groups after transplantation by means of serum laboratory values to assess hepatocellular damage, synthetic function, and ion transport capacity. Peak values were recorded for each parameter, and their distributions were compared. There were no statistically significant differences between groups for age, sex, total ischemia time, or cause of liver disease. Global multivariate comparison of peak changes in all measures of liver function indicated liver injury was significantly lower with tacrolimus treatment than placebo (P =.01). The sample median for group 1 was less than for group 2 in all parameters measured. Individual statistical comparison showed that peak changes from baseline aspartate aminotransferase and activated partial thromboplastin time values were significantly improved (P </=.05) with tacrolimus treatment than placebo treatment. In this prospective, double-blinded, randomized trial, we show that flushing the liver before transplantation with Plasma-lyte A containing tacrolimus results in superior early graft function and decreased hepatocellular injury after reperfusion compared with flushing with Plasma-lyte A alone.
authors.affiliation: Department of Transplant Surgery, Mayo Clinic Scottsdale, AZ.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: St  Peter
authors.forename: David J
authors.initials: DJ
authors.lastname: Post
authors.forename: Manuel I
authors.initials: MI
authors.lastname: Rodriguez-Davalos
authors.forename: David D
authors.initials: DD
authors.lastname: Douglas
authors.forename: Adyr A
authors.initials: AA
authors.lastname: Moss
authors.forename: David C
authors.initials: DC
authors.lastname: Mulligan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011517:Prothrombin Time; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D012996:Solutions; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D012996:Solutions; D001663:Bilirubin; D016559:Tacrolimus