The contribution of glutamine to citrulline and arginine synthesis, when alanyl-glutamine is supplied in an enteral dose of 0.5 g/kg, in critically ill patients.

Critically ill patients are likely to benefit from additional glutamine. Novak
et al. demonstrated in their meta analysis that glutamine administration
reduced morbidity and Oudemans-van Straaten showed that the magnitude of
glutamine deficiency correlates with ICU mortality. In addition, low arginine
and citrulline levels correlate with severity of inflammation in children.
Although arginine administration can be beneficial for some groups of trauma
and cancer surgery patients, its action as substrate for nitric oxide
synthesis and subsequent hemodynamic instability and oxidative stress, may be
responsible for doubtful results when supplied to severe critically ill
patients. Since glutamine can generate arginine by the citrulline pathway in
the kidney, supplying glutamine potentially may be a more physiologic and safe
way to administer arginine in the metabolically stressed ICU patient. Hence,
positive effects of glutamine could be partially due to the substrate that
glutamine delivers for the synthesis of arginine.
We hypothesize that exogenous, enteral provided glutamine contributes
substantially to the de novo synthesis of arginine in critically ill patients.

The objective of this clinical study is: To study whether glutamine given
enterally as the dipeptide alanyl-glutamine enhances de novo arginine synthesis
in critically ill patients.
Secondary objective is to determine the contribution of the splanchnic bed to
this metabolic route.

Design:
This is an randomized, clinical trial with 2 groups of 10 critically ill
patients
Patients are randomly assigned to one of the two groups:
Group 1 (control group): 10 patients receive enteral nutrition in the small
intestine.
Group 2 (treatment group): 10 patients receive isonitrogenous enteral nutrition
including 0.5 g/kg alanyl-glutamine/hr (=0.325 g/kg glutamine) in the small
intestine

Group 1 (control group): patients will receive enteral tube feeding, containing
1.5 g/kg protein/day ( including 0,15 g/kg/day glutamine) for at least 5 days.
Group 2 (treatment group): patients will receive enteral tube feeding for 5
days + 0.5 g/24hr alanyl-glutamine containing 1.5 g/kg protein (including 0.15
g/kg/day glutamine).
Both groups: the tracer protocol will be performed on the 4th and 5th day after
(after at least 3 days of enteral feeding). In randomized order the glutamine
tracer will be given enterally or parenterally. The tracer protocol will be
started between 8:00 and 10:00 in the morning and last 2.5 hours.

Potential risk is estimated at a minimum, morover potential benefits of
glutamine administration are documented