Conditioning with volatile anesthetics in liver transplantation: a prospective randomized controlled trial

• Grant number: 11/10375-6
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2011 - October 31, 2013
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Luiz Augusto Carneiro D'Albuquerque
• Grantee: Luiz Augusto Carneiro D'Albuquerque
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Estela Regina Ramos Figueira ; Joel Avancini Rocha Filho ; José Otávio Costa Auler Junior ; Maria José Carvalho Carmona ; Vincenzo Pugliese

Abstract

The shortage of organs for liver transplantation from deceased donors has driven strategies, allowing an increase in the number of viable organs for transplantation. One strategy to minimize the shortage of organs is the use of expanded criteria donor grafts. The pharmacological conditioning of the liver is a proposed method for protecting the ischemic liver transplantation with the potencial advantage to increase the safe use of non-ideal grafts. The volatile anesthetics such as isoflurane or sevoflurane have been shown to be beneficial in the attenuation of cardiac dysfunction and in the reduction of microstructural damage consequent to myocyte ischemia. It has been demonstrated in rats that the use of volatile anesthetics (isoflurane or sevoflurane) before induction of ischemia protects the liver from hepatic ischemia/reperfusion. A prospective clinical study demonstrated the protective effect of volatile anesthetics in liver surgery with reduction of serum transaminases levels and with reduction of postoperative complications. So far there are no studies that demonstrate the influence of anesthetic technique on postoperative outcomes after liver transplantation. Both inhalatory anesthetic agents or intravenous propofol are used routinely by transplant centers and the choice of one over the other is prerogative of each service. Currently there are no published data on the impact of volatile anesthetics in the evolution of ischemia/reperfusion injury during liver transplantation, but the data and the clinical experience on the use of sevoflurane attenuating ischemia/reperfusion in cardiac and liver surgery corroborate the hypothesis of a beneficial effect of this agent in liver transplantation. The primary objective of the study is to compare the postoperative serum levels of aspartate aminotransferase in patients undergoing liver transplantation anesthetized with sevoflurane versus anesthetized with propofol. The secondary objectives are to compare the perioperative complications, graft function, coagulation, inflammation, and ICU and hospital length of stay. Methods: This is an international multicenter prospective study from the University of Zurich and University of Sao Paulo. One hundred and six patients will be studied. Patients from Hospital das Clinicas FMUSP listed for liver transplantation, will be randomized at the time of transplantation into two groups: group 1 - anesthesia with propofol and group 2 - anesthesia with sevoflurane. It will analyzed during intra-and postoperatively up to 7 days: liver enzymes (transaminases and alkaline phosphatase), clotting factors (INR, Factor V, platelets), factor vWF, Ang-1, Ang-2, anticoagulant factors (protein C and S, antithrombin), thromboelastography, inflammatory mediators (TNF-’, IL-6, IL-8, MCP-1) and complement factors (MBL, Bb, C4, C3, C5b-9) and creatinine. Two liver biopsies will be taken, one before the organ implantation and the other after liver reperfusion. Operative complications, ICU and hospital length of stay will be evaluated. (AU)