LACTIC-ACIDOSIS DURING SEPSIS IS RELATED TO INCREASED PYRUVATE PRODUCTION, NOT DEFICITS IN TISSUE OXYGEN AVAILABILITY

Objective The purpose of this study was to quantitate the derangements in intermediary carbohydrate metabolism and oxygen use in severely se ptic patients in comparison with healthy volunteers. Summary Backgroun d Data It commonly has been assumed that the development of lactic aci dosis during sepsis results from a deficit in tissue oxygen availabili ty. Dichloroacetate (DCA), which is known to increase pyruvate oxidati on but only when tissue oxygen is available, provides a means to asses s the role of hypoxia in lactate production. Methods Stable isotope tr acer methodology and indirect calorimetry was used to determine the ra tes of intermediary carbohydrate metabolism and oxygen use in five sev erely septic patients with lactic acidosis and six healthy volunteers before and after administration of DCA. Results Oxygen consumption and the rates of glucose and pyruvate production and oxidation were subst antially greater (p < 0.05) in the septic patient compared with health y volunteers. Administration of DCA resulted in a further increase in oxygen consumption and the percentage of glucose and pyruvate directed toward oxidation. Dichloroacetate also decreased glucose and pyruvate production, with a corresponding decrease in plasma lactate concentra tion. Conclusions These findings clearly indicate that the accumulatio n of lactate during sepsis is not the result of limitations in tissue oxygenation, but is a sequelae to the markedly increased rate of pyruv ate production. Furthermore, the substantially higher rate of pyruvate oxidation in the septic patients refutes the notion of a sepsis-induc ed impairment in pyruvate dehydrogenase activity.