title: Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study.
abstract: Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval (CI) = 1.01-2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14-2.76, P ≤ 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used.
authors.affiliation: Department of Hepatobiliary Surgery and Liver Transplantation, University Hospital of Padua, Padua, Italy. drdamico@hotmail.com
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Amico
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vitale
authors.forename: Donatella
authors.initials: D
authors.lastname: Piovan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertacco
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramirez Morales
authors.forename: Anna
authors.initials: A
authors.lastname: Chiara Frigo
authors.forename: Domenico
authors.initials: D
authors.lastname: Bassi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Bonsignore
authors.forename: Enrico
authors.initials: E
authors.lastname: Gringeri
authors.forename: Michele
authors.initials: M
authors.lastname: Valmasoni
authors.forename: Greta
authors.initials: G
authors.lastname: Garbo
authors.forename: Enrico
authors.initials: E
authors.lastname: Lodo
authors.forename: Francesco Enrico
authors.initials: FE
authors.lastname: D'Amico
authors.forename: Michele
authors.initials: M
authors.lastname: Scopelliti
authors.forename: Amedeo
authors.initials: A
authors.lastname: Carraro
authors.forename: Martina
authors.initials: M
authors.lastname: Gambato
authors.forename: Alberto
authors.initials: A
authors.lastname: Brolese
authors.forename: Giacomo
authors.initials: G
authors.lastname: Zanus
authors.forename: Daniele
authors.initials: D
authors.lastname: Neri
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007558:Italy; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D055031:Primary Graft Dysfunction / Q000209:etiology / Q000517:prevention & control; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D020858:Tissue and Organ Harvesting / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000975:Antioxidants; D000111:Acetylcysteine