Use of N-Acetylcysteine During Liver Procurement

Infusione Sistemica e Loco-regionale di N-Acetilcisteina Nel Prelievo di Fegato: Uno Studio Prospettico Randomizzato Controllato. Fase II.

Randomized prospective study on the impact on the post-LT outcome by the infusion of N-acetylcysteine (NAC) during the liver procurement procedure, as an anti-oxidant agent to reduce the ischemia-reperfusion damage of organs for liver transplantation (LT).

Anti-oxidant agents have the potential to reduce the ischemia-reperfusion damage of organs for liver transplantation (LT). In this randomized prospective study, we seek to study the impact on the post-LT outcome of the infusion of N-acetylcysteine (NAC) during the liver procurement procedure. Potential grafts, assigned to adult candidates with chronic liver disease enlisted for first LT, will randomly be included in a one-to-one ratio with a sequential closed envelope single-blinded assignation procedure to either the NAC protocol or in the standard procedure (without NAC). The NAC protocol comprises: a systemic NAC infusion (30 mg/kg) one hour before the beginning of liver procurement; a loco-regional NAC infusion (300 mg through the portal vein) just before cross-clamping.

Liver Transplantation, Graft Survival, Graft Rejection, Primary Graft Dysfunction, Tissue and Organ Harvesting, Tissue and Organ Procurement, Tissue Donors, Cold Ischemia

The allocated organ, in addition to the standard procedure, was treated with a systemic NAC infusion before initiating the liver harvesting procedure, and a loco-regional infusion into the portal vein before cross-clamping.

Allocated organ was treated according to the centre's standard procurement procedure: a modified double perfusion technique, where donor livers are gravity-perfused in situ via the aorta and portal vein with Celsior solution at 4 °C. After hepatectomy, donor livers were further perfused at the back-table with Celsior solution and then stored in conventional bags containing the same solution at 4 °C until transplantation.

Fluimucil (Zambon, Italy), ACC (Hexal AG), Acemuc (Betapharm, Germany), Acetyst (Ristert, Germany), Acetadote (Cumberland Pharmaceuticals), Asist (Bilim Pharmaceuticals, Turkey), Brunac eyedrops (Bruschettini, Italy), Fluimukan (Lek, Slovenia), Flumil (Pharmazam, Spain), Lysox (Menarini), Mucinac (Cipla, India), Mucohelp (Neiss Labs, India), Mucolysin (Sandoz), Mucomelt (Venus Remedies, India), MUCOMIX (Samarth Life Sciences, India), Mucomyst (Bristol-Myers Squibb), Nytex (Pharos,Indonesia), Parvolex (GSK), PharmaNAC (BioAdvantex Pharma Inc., North America), Rheunac (Tree Of Life, Israel), Solmucaïne (IBSA, Switzerland), Trebon N (Uni-pharma)

15 min systemic NAC infusion of the donor (30 mg/kg, maximum dose 3000 mg) diluted into 500 ml 5 % glucose solution, 30 min before initiating the liver harvesting procedure, and a loco-regional infusion (150 mg/kg of estimated liver weight, maximum dose 300 mg) into the portal vein 5 min before cross-clamping.

Inclusion Criteria: all consecutive subjects with chronic liver disease undergoing first Liver Transplantation receiving deceased donor livers Exclusion Criteria: recipients with acute liver disease; paediatric patients or adult patients receiving a liver from a paediatric donor; patients undergoing multiple-organ transplantation; patients undergoing re-transplantation of the Liver; patients undergoing living donor Liver Transplantation

D'Amico F, Vitale A, Gringeri E, Valmasoni M, Carraro A, Brolese A, Zanus G, Neri D, Boccagni P, Violi P, Pauletto A, D'Amico FE, D'Amico DF, Cillo U. SYSTEMIC AND LOCO-REGIONAL INFUSION OF N-ACETILCISTEINA DURING LIVER PROCUREMENT: A PROSPECTIVE RANDOMIZED CONTROLLED STUDY (Abstract# 488), The International Liver Transplantation Society: 14th Annual International Congress, July 9-12, 2008, Paris, France. Liver Transplantation, 14: S1-S269. doi: 10.1002/lt.21569

D'Amico F, Vitale A, Piovan D, Bertacco A, Ramirez Morales R, Chiara Frigo A, Bassi D, Bonsignore P, Gringeri E, Valmasoni M, Garbo G, Lodo E, D'Amico FE, Scopelliti M, Carraro A, Gambato M, Brolese A, Zanus G, Neri D, Cillo U. Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study. Liver Transpl. 2013 Feb;19(2):135-44. doi: 10.1002/lt.23527. Epub 2012 Sep 26.