Plasma amino acids of the transsulfuration pathway and plasma lactate in septic patients

OBJECTIVES: In sepsis increasing plasma lactate, even if unrelated to hypoperfusion and hypoxia, is a cause of concern. Among the patterns associated with increasing lactate, several plasma amino acid (AA) abnormalities, more in particular those of sulfur AAs, have remained unexplored, and their assessment has been the purpose of our study. MATERIALS AND METHODS: A systematic and detailed analysis of 183 simultaneous determinations of plasma AA-grams and lactate, from 12 trauma surgery patients who had developed sepsis, was performed. Sepsis severity ranged from moderate to extreme illness. Correlations between changes in lactate and in AA levels were assessed by regression analysis. RESULTS: Increasing lactate was related to increasing alanine, proline, asparagine, tyrosine, cystathionine, histidine, glutamine, citrulline, methionine, phenylalanine and hydroxyproline (r from 0.62 to 0.36, p < 0.001 for all) and to decreasing taurine (r = -0.62, p < 0.001). Furthermore, increasing lactate was strongly related to increasing cystathionine/taurine ratio (r = 0.77, p < 0.001). These correlations were independent of the simultaneous relationship found between increasing lactate and decreasing mixed venous O2 tension. CONCLUSIONS: The overall findings and the correlation with the cystathionine/taurine ratio support the hypothesis that increasing lactate in sepsis may be paralleled by impaired hepatic AA transsulfuration. Because this may disable antioxidant protection by limiting glutathione and taurine availability, the metabolic perturbations associated with septic hyperlactatemia may include enhanced exposure to oxidative stress.