EXCEPT FOR ALANINE, MUSCLE PROTEIN CATABOLISM IS NOT INFLUENCED BY ALTERATIONS IN GLUCOSE-METABOLISM DURING SEPSIS

Objective: To assess any relationship between hyperglycemia and muscle protein catabolism associated with critical illness. Design: Cohort analytic study. Setting: Clinical research center and intensive care unit of a university hospital. Participants: Six healthy volunteers and five patients with severe sepsis. Interventions: Study subjects were given infusions of 6,6,d(2) glucose and N-15 lysine for 6 hours. After infusion of the stable isotopes for 2 hours (basal period), dichloroacetate, which accelerates pyruvate oxidation, was given (dichloroacetate period). Leg blood flow was measured by indocyanine green dye dilution, and femoral artery and vein substrate concentrations were quantitated. Main Outcome Measures: The metabolic rates of glucose production, oxidation, and clearance; the whole-body protein breakdown rate; and the net efflux of amino acids from the leg were determined. Results: In comparison with the healthy volunteers, septic patients had significant elevations in glucose production, oxidation, and clearance, accelerated protein catabolism, and greater net peripheral efflux of amino acids. Dichloroacetate significantly decreased glucose production and increased the percentage of glucose directed toward oxidation in both healthy volunteers and septic patients. However, this dichloroacetate-induced perturbation of glucose utilization had no significant effect on whole-body protein breakdown or the efflux of specific amino acids from the leg except for alanine, whose net efflux doubled (p less than or equal to.05). Conclusions: The findings of this study demonstrate a universal acceleration in the metabolic rates of both intermediary glucose metabolism and protein/amino acid catabolism during sepsis. Except for alanine, however, there appears to be no coupling between these two physiologic responses to sepsis.