Dichloroacetate stabilizes the intraoperative acid-base balance during liver transplantation

Robert Shangraw, Deirdre Lohan-Mannion, Agnes Hayes, Rose M. Moriarty, Rongwei (Rochelle) Fu, Stephen Robinson

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 NaHCO3 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.

Original languageEnglish (US)
Pages (from-to)989-998
Number of pages10
JournalLiver Transplantation
Volume14
Issue number7
DOIs
StatePublished - Jul 2008

Fingerprint

Acid-Base Equilibrium
Liver Transplantation
Length of Stay
Lactic Acidosis
Lactic Acid
Intensive Care Units
Placebos
Airway Extubation
Informed Consent
Pyruvic Acid
Oxidoreductases
Anesthesia
Gases
Outcome Assessment (Health Care)
Mortality
Liver
Incidence

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Dichloroacetate stabilizes the intraoperative acid-base balance during liver transplantation. / Shangraw, Robert; Lohan-Mannion, Deirdre; Hayes, Agnes; Moriarty, Rose M.; Fu, Rongwei (Rochelle); Robinson, Stephen.

In: Liver Transplantation, Vol. 14, No. 7, 07.2008, p. 989-998.

Research output: Contribution to journalArticle

@article{35c8df9fee59477a90bbdcf9951d7fc2,
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 NaHCO3 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.",
author = "Robert Shangraw and Deirdre Lohan-Mannion and Agnes Hayes and Moriarty, {Rose M.} and Fu, {Rongwei (Rochelle)} and Stephen Robinson",
year = "2008",
month = "7",
doi = "10.1002/lt.21485",
language = "English (US)",
volume = "14",
pages = "989--998",
journal = "Liver Transplantation",
issn = "1527-6465",
publisher = "John Wiley and Sons Ltd",
number = "7",

}

TY - JOUR

T1 - Dichloroacetate stabilizes the intraoperative acid-base balance during liver transplantation

AU - Shangraw, Robert

AU - Lohan-Mannion, Deirdre

AU - Hayes, Agnes

AU - Moriarty, Rose M.

AU - Fu, Rongwei (Rochelle)

AU - Robinson, Stephen

PY - 2008/7

Y1 - 2008/7

N2 - 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 NaHCO3 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.

AB - 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 NaHCO3 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.

UR - http://www.scopus.com/inward/record.url?scp=48949120213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48949120213&partnerID=8YFLogxK

U2 - 10.1002/lt.21485

DO - 10.1002/lt.21485

M3 - Article

C2 - 18581513

AN - SCOPUS:48949120213

VL - 14

SP - 989

EP - 998

JO - Liver Transplantation

JF - Liver Transplantation

SN - 1527-6465

IS - 7

ER -