Submitted to: SHOCK
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/13/2008
Publication Date: 7/7/2009
Citation: Kao, C.C., Guntupalli, K.K., Bandi, V., Jahoor, F. 2009. Whole-body CO2 production as an index of the metabolic response to sepsis. SHOCK. 32(1):23-28. Interpretive Summary: Sepsis occurs as a response to severe infection. The body’s metabolic response to sepsis can be variable. Because the production of carbon dioxide (CO2) in the body is a measure of how much energy is being used by the body, and reflects the use of nutrients for energy, changes in whole-body CO2 production may provide information about changes in the production, and consumption of energy during sepsis. The goal of this study was to determine CO2 production in the whole body and its relationship to protein and glucose metabolism in septic patients admitted to a medical intensive care unit. We found an association between low metabolic response and mortality. In addition, CO2 production was correlated with rates of protein breakdown, protein synthesis, and glucose uptake in the body. These findings suggest that CO2 production in sepsis may serve as a marker of an inadequate response and an increased risk of death.
Technical Abstract: Whole-body carbon dioxide (CO2) production (RaCO2) is an index of substrate oxidation and energy expenditure; therefore, it may provide information about the metabolic response to sepsis. Using stable isotope techniques, we determined RaCO2 and its relationship to protein and glucose metabolism in medical patients with sepsis and septic shock. Whole-body CO2 production, an index of basal metabolic rate, was measured in 13 patients with sepsis or septic shock, and 7 healthy controls using an i.v. infusion of 13C-sodium bicarbonate. Endogenous leucine flux, leucine xidation, and nonoxidative disposal, indices of whole-body protein breakdown, catabolism, and synthesis, were measured with an infusion of 1-13C-leucine, and glucose production and clearance were measured with an infusion of 2H2-glucose. There was no difference in mean RaCO2 between the patients and controls, but the patients had a wider range of values. The four patients with the lowest RaCO2 died. Protein breakdown, synthesis, and glucose production were significantly faster in patients than in controls (P < 0.05). Whole-body CO2 production was positively correlated with protein breakdown (P = 0.001), protein synthesis (P < 0.01), and glucose clearance (P = 0.01). Patients with low metabolic rates (mean - 2 SDs of controls) had slower protein breakdown and decreased glucose clearance compared with patients with high metabolic rates (mean + 2 SDs of controls). Septic patients were both hypometabolic and hypermetabolic. The correlation between RaCO2 and protein breakdown and synthesis, as well as glucose clearance suggests that RaCO2 can provide information about substrate metabolism in septic patients. Because hypometabolism was associated with mortality and changes in protein and glucose metabolism in septic patients, it may be a useful clinical indicator of an inadequate metabolic response.