title: The effect of methylene blue during orthotopic liver transplantation on post reperfusion syndrome and postoperative graft function.
abstract: OBJECTIVE
  In orthotopic liver transplantation (OLT), a major component of the post-reperfusion syndrome is hypotension, which may lead to additional graft liver ischemia-reperfusion injury. A proposed mechanism of reperfusion hypotension is the massive induction of oxidative stress triggering the release of pro-inflammatory mediators, including nitric oxide (NO). Methylene blue (MB) is an inhibitor of inducible NO synthase and an NO scavenger that has been shown to attenuate reperfusion hypotension. Of note, recent reports have shown that the exogenous administration of NO during OLT significantly improved the recovery of the graft liver. Therefore, we sought to investigate the effects of MB on the functional recovery of the graft liver following OLT.
  
  
  METHODS
  We analyzed retrospective data from 715 patients who underwent OLT between 2003 and 2008. We classified patients into those who received a 1-1.5 mg/kg intravenous bolus of MB immediately prior to reperfusion (MB group) and those who did not (control group). Propensity score matching was used to adjust for differences between patients who received intraoperative MB and those who did not, and these data were used to determine the association between a single MB bolus during OLT and postoperative graft dysfunction.
  
  
  RESULTS
  Our study cohort consisted of 715 OLT patients, of whom 105 received MB and 610 did not. After propensity score matching, demographic and donor data were similar in the two groups, except for the older age of recipients in the MB group (55.5 ± 0.9 vs 53.1 ± 0.8 years, p = 0.026). No differences were seen in mean arterial pressure changes after reperfusion and no differences were found in vasopressor requirements (bolus or infusion) or transfusion requirements. In addition, there was no significant difference in the incidence of primary nonfunction, retransplantation within 60 days, acute rejection, or graft survival between the groups by multivariate analysis or Kaplan-Meier survival analysis.
  
  
  CONCLUSIONS
  In our study, the administration of MB at 1-1.5 mg/kg immediately prior to reperfusion did not prevent post-reperfusion hypotension and did not decrease vasopressor usage or transfusion requirements after reperfusion. Also, MB did not have any impact on postoperative graft function. These findings may argue against the routine use of MB during OLT.
authors.affiliation: Division of Solid Organ Transplantation, Department of Anesthesiology, Preoperative and Pain Management, Leonard Miller School of Medicine, University of Miami, 1611 NW 12th Avenue, D318, Miami, FL 33136, USA. kfukazawa@med.miami.edu
authors.forename: Kyota
authors.initials: K
authors.lastname: Fukazawa
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Pretto
mesh_terms: D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D007262:Infusions, Intravenous; D007432:Intraoperative Period; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage*; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II; D008751:Methylene Blue