Dichloroacetate administration in the treatment of endotoxin shock

Abstract

Dichloroacetate (DCA), an activator of the pyruvate dehydrogenase complex, has been shown to reduce blood lactate levels effectively in various conditions. DCA administration has also sometimes resulted in beneficial cardiovascular effects. To assess its potential value in the routine management of septic shock, we studied the effects of DCA on a canine endotoxic shock model associated with moderate lactic acidosis. Eighteen dogs were pentobarbitone anesthetized, intubated, and mechanically ventilated. Thirty minutes after the administration of 3 mg/kg of Escherichia coli endotoxin, 10 dogs received 100 mg/kg followed by 100 mg/kg/hr of DCA, and eight dogs served as control. In all animals, fluid administration was titrated according to the left-sided filling pressures. In the DCA-treated animals, lactate levels rapidly fell from 3.1 +/- 1.2 to 1.3 +/- 0.8 mEq/liter after 30 min. The bolus of DCA was usually followed by a very transient increase in arterial pressure, but no sustained hemodynamic change was noted. Oxygen consumption (measured from the exhaled gases) was not affected. Four dogs in the DCA group and one dog in the control group survived the next morning (difference not significant). The present study confirms that DCA can effectively reduce blood lactate levels in endotoxic shock and might therefore be useful in severe lactic acidosis related to septic shock. However, the routine use of DCA in septic shock to improve hemodynamic status is not supported by the present findings.