To investigate appropriate mode and daily dose of enteral ornithine alpha-ketoglutarate (OKG) administration, 54 burn patients (total burn surface area: 20-50%) were included in a randomized controlled trial and assigned to receive either a supplement of OKG (10, 20 or 30 g/d) as bolus or continuous infusion, or a continuous infusion of an isonitrogenous amount of a soy protein mixture (Protil-1: 10, 20 or 30 g/d) in addition to their enteral diet. The influence of these treatments on clinical outcome and biological indices was evaluated. OKG administration significantly improved nitrogen balance and reduced 3-methylhistidine and hydroxyproline urinary elimination. This was associated with a gradual rise in plasma glutamine over time. Given as a bolus, OKG significantly improved wound healing, assessed both clinically [day of last graft: (mean +/- SEM) OKG bolus 23.7 +/- 2.1 d versus Protil-1, 39.9 +/- 9.9 d; P < 0.05] and by hydroxyproline excretion, and biological markers of nitrogen metabolism, and tended to reduce duration of enteral nutrition (P = 0.12). The higher catabolic status in the patients administered 20 g OKG/d at the onset of the study, despite randomization, precludes any definite conclusion (concerning the dose-effect relationship). However, based on 3-methylhistidine elimination, our data indicate a benefit of 30 g OKG/d administration over 10 g/d. This study further supports OKG supplementation in burn patients. In addition, this is the first trial based on objective data that favors bolus over continuous infusion of OKG in critically ill patients.
Ornithine alpha-ketoglutarate (OKG) has been successfully used as an enteral supplement in the treatment of catabolic states, including burn injury. However, specific questions remain unanswered concerning burn patients, including OKG metabolism and metabolite production, appropriate mode of administration, and dose. We thus performed a kinetic study and followed plasma ornithine and OKG metabolite concentrations on day 7 postburn in 42 (35 men, 7 women) consecutive burn patients aged 33 +/- 2 y with a mean (+/-SEM) total burn surface area (TBSA) of 31 +/- 1%. Patients were randomly assigned to receive OKG as a single bolus (10 g; n = 13) or in the form of a continuous gastric infusion (10, 20, or 30 g/d over 21 h; n = 13) or an isonitrogenous control (n = 16). Plasma pharmacokinetics of ornithine followed a one-compartment model with first-order input (r = 0.993, P < 0.005). OKG was extensively metabolized in these patients (absorption constant = 0.028 min-1, elimination half-life = 89 min), with the production of glutamine, arginine, and proline; proline was quantitatively the main metabolite [in OKG bolus, area under the curve (AUC)0-7h: proline, 41.4 +/- 5.6 mmol.min/L; glutamine, 20.4 +/- 5.7 mmol.min/L; and arginine, 7.3 +/- 1.9 mmol.min/L]. Proline production was dose-dependent and quantitatively similar between modes of OKG administration. Glutamine and arginine production were not dose-dependent and were higher in the bolus group than in the infusion group. Overall, the bolus mode of OKG administration appeared to be associated with higher metabolite production compared with continuous infusion in burn patients, especially for glutamine and arginine.
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