title: Dichloroacetate stabilizes the intraoperative acid-base balance during liver transplantation.
abstract: Lactic acidosis occurs during orthotopic liver transplantation (OLT), especially during the anhepatic and early postreperfusion phases. Dichloroacetate (DCA) inhibits pyruvate dehydrogenase kinase-1, indirectly activating mitochondrial pyruvate dehydrogenase. This, in turn, markedly reduces systemic lactate production and, to a lesser extent, increases hepatic lactate uptake. The result is moderation of lactic acidosis in many clinical conditions. This study evaluated the efficacy of DCA in controlling lactic acidosis during OLT and improving perioperative outcome from OLT. After informed consent, 250 patients for OLT received either intraoperative DCA or placebo. DCA (40 mg/kg intravenously) or placebo was administered after anesthesia induction and repeated 4 hours later. Intraoperative measures were arterial blood gases, lactate, and Na+ and utilization of blood products, CaCl2, and NaHCO3. Outcome measures were time to tracheal extubation, intensive care unit length of stay, hospital length of stay, requirement for postoperative plasma transfusion, retransplantation, and perioperative mortality. DCA reduced the arterial lactic acid concentration by an average of 44% (1.8 mmol L(-1), P < 0.001), stabilized the acid-base balance, and reduced NaHCO(3) administration by 80% (P < 0.001). Postoperatively, DCA-treated patients required 50% less postoperative plasma transfusion (2 versus 4 units, respectively, P = 0.016), but the incidence of transfusion was similar in both groups (62% versus 60%, P = 0.381). DCA did not alter time to extubation, intensive care unit length of stay, or hospital length of stay. In conclusion, DCA attenuated lactic acidosis during OLT, stabilizing the intraoperative acid-base balance and decreasing NaHCO3 use. DCA decreased postoperative plasma transfusion requirement but otherwise had no measurable effect on perioperative outcome parameters.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239-3098, USA. shangraw@ohsu.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Shangraw
authors.forename: Deirdre
authors.initials: D
authors.lastname: Lohan-Mannion
authors.forename: Agnes
authors.initials: A
authors.lastname: Hayes
authors.forename: Rose M
authors.initials: RM
authors.lastname: Moriarty
authors.forename: Rongwei
authors.initials: R
authors.lastname: Fu
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Robinson
mesh_terms: D000140:Acidosis, Lactic / Q000209:etiology / Q000517:prevention & control*; D000328:Adult; D000471:Alkalosis / Q000517:prevention & control*; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period
chemical_list: D003999:Dichloroacetic Acid