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 septic patients in comparison with healthy volunteers.


BACKGROUND
It commonly has been assumed that the development of lactic acidosis during sepsis results from a deficit in tissue oxygen availability. Dichloroacetate (DCA), which is known to increase pyruvate oxidation but only when tissue oxygen is available, provides a means to assess the role of hypoxia in lactate production.


METHODS
Stable isotope tracer methodology and indirect calorimetry was used to determine the rates of intermediary carbohydrate metabolism and oxygen use in five severely 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 substantially greater (p < 0.05) in the septic patient compared with healthy 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 concentration.


CONCLUSIONS
These findings clearly indicate that the accumulation of lactate during sepsis is not the result of limitations in tissue oxygenation, but is a sequelae to the markedly increased rate of pyruvate production. Furthermore, the substantially higher rate of pyruvate oxidation in the septic patients refutes the notion of a sepsis-induced impairment in pyruvate dehydrogenase activity.
Gore
D C
DC
Department of Surgery Medical College of Virginia, Richmond, USA.
Jahoor
F
F
Hibbert
J M
JM
DeMaria
E J
EJ
D000140:Acidosis, Lactic / Q000209:etiology* / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D001944:Breath Tests; D002153:Calorimetry, Indirect; D003999:Dichloroacetic Acid / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007773:Lactates / Q000097:blood; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000097:blood*; D018805:Sepsis / Q000150:complications* / Q000378:metabolism; D013997:Time Factors
D001786:Blood Glucose; D007773:Lactates; D011773:Pyruvates; D003999:Dichloroacetic Acid; D010100:Oxygen