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Amino acid kinetics in patients with sepsis^1,2,3

¹ From Medical Department III, the Division of Nephrology, Vienna General Hospital, Austria; the Department of Pharmacokinetics and Metabolism, Boehringer Ingelheim, Biberach/ Riss, Germany; and Medical Department II, the County Hospital of Steyr, Steyr, Austria.

Background: In patients with sepsis and systemic inflammatory response syndrome, amino acid extraction by the liver is enhanced, resulting in decreased plasma amino acid concentrations. Systematic investigations of the elimination of intravenously infused amino acids have not been performed.

Objective: The objective of this study was to compare the elimination of 17 amino acids in patients with sepsis and in healthy control subjects.

Design: Elimination of amino acids was evaluated in 9 patients with sepsis and in 8 healthy control subjects by using a combined loading and maintenance infusion of 375 mg amino acids/kg body wt for 60 min. Pharmacokinetic variables were analyzed from plasma curves.

Results: With the exception of lysine, methionine, glutamate, ornithine, phenylalanine, and tyrosine, plasma concentrations of amino acids were lower in the patients with sepsis than in the control subjects; phenylalanine was the only amino acid whose plasma concentration increased (P < 0.001). In patients with sepsis, whole-body clearance (Cl_tot) of total amino acids was 74% higher than in control subjects ( ± SEM: 13161 ± 1659 and 7566 ± 91 mL/min, respectively; P < 0.01), the Cl_tot of essential amino acids was 64% higher (P < 0.02), that of nonessential amino acids was 82% higher (P < 0.01), and that of both branched-chain amino acids and glucogenic amino acids was 97% higher (P < 0.001). With the exception of phenylalanine, ornithine, proline, and glutamate, the Cl_tot of all amino acids was elevated. The Cl_tot of phenylalanine and ornithine decreased slightly (NS).

Conclusions: In patients with sepsis, plasma concentrations of most amino acids are greatly decreased and the elimination of amino acids from the intravascular space during intravenous infusion is greatly enhanced.

Key Words: Sepsis • hypermetabolism • amino acid metabolism • plasma amino acids amino acid elimination • amino acid clearance

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