Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Cardiovascular Anesthesia
Cardiopulmonary bypass (CPB) has been associated with development of systemic type B lactic acidosis.  Further, recovery of cardiac mechanical function after ischemia is compromised by the inhibition of pyruvate dehydrogenase (PDH), an enzyme which catalyzes pyruvate oxidation and limits accumulation of lactic acid.  We have previously found that the type B lactic acidosis during orthotopic liver transplantation (OLT) is effectively attenuated by dichloroacetate (DCA), which acts by stimulating PDH activity.  By stimulating glucose oxidative flux DCA improves mechanical function of the isolated post-ischemic heart.  This study was designed to determine the pharmacokinetics and metabolic effects of DCA during cardiac surgery in humans.
Methods: The protocol was approved by the FDA (IND #35,790); and Portland VAMC IRB. After written informed consent, 26 patients for CABG/valve or re-do CABG were randomized to receive either DCA or placebo DCA (50 mg/kg iv over 30 min) was infused after anesthesia induction, and again (30 mg/kg over 30 min) at 180 min Serial arterial blood samples were taken to determine pH, [HCO3], base excess, [glucose], [lactate] and [DCA]. [DCA] was assayed by gas chromatography-mass spectroscopy.  Data were analyzed by ANOVA or unpaired t-test.
Results: Peak [DCA] was 204 +/- 31 (SE) and 176 +/- 25 [micro sign]g/ml after the first and second DCA doses, resp. CBP time was 177 +/- 12 and 154 +/- 11 min in control and DCA-treated patients, resp. Arterial [lactate] rose from a preinduction baseline of 0.639 +/- 0.081 to 2.62 +/- 0.46 mM at 15 min after separation from CPB. Corresponding [lactate] values for DCA-treated patients were 0.820 +/- 0.050 mM (ND) and 1.64 +/- 0.31 mM (p<0.05). Base excess decreased from 1.4 +/- 0.6 mEq/l to a nadir of -1.0 mEq/l during CPB in controls, and from 1.8 +/- 0.6 mEq/l to -1.4 +/- 0.5 during CPB with DCA (ND). Intraoperative NaHCO3 consumption did not differ between groups (74 +/- 16 vs 60 +/- 20 mEq, resp). Baseline [glucose] was 94 +/- 6 mg/dl and increased to 178 +/- 24 mg/dl at the end of CPB in controls. Corresponding values in DCA-treated patients were 99 +/- 9 and 179 +/- 21 mg/dl, resp (ND)
Discussion: DCA was well-tolerated in all patients. Safe and predictable plasma [DCA] can be achieved in patients undergoing cardiac surgery with prolonged CPB. DCA reduces [lactate] in part by increasing myocardial lactate uptake.  Lactic acidosis was modest in controls, and DCA had no appreciable effect on acid-base homeostasis. Further work is warranted to assess the positive inotropic effect of DCA in cardiac surgery patients, and to identify a possible subset of these patients susceptible to lactic acidosis who may respond to DCA if the etiology involved inhibition of PDH. 
(Support: International Anesthesia Research Society)
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