Increased dependence of leucine in posttraumatic sepsis: Leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome

The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parneteral nutrition (TNP) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n=10) or without (n=16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p<0.01) and methionine, proline, phenylalanine, and tyrosine (p<0.05 for all). In contrast the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p<0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p<0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p<0.0001), was an indicator of severity, and, if persistent, was a manifestation of fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.