Citrullinemia for the Prediction of Enteral Nutrition Tolerance Among Critically Ill Patients

Citrulline is an amino acid mainly produced by enterocytes from glutamine.

Citrullinemia ≤ 20μmol/L is a biomarker of enterocyte mass reduction, secondary to the reduction of small bowel length or secondary to villous atrophy diseases. A patient with low citrullinemia is probably at risk of enteral nutrition malabsorption.

Citrulline generation test consists of measuring the course of citrullinemia after an oral or intravenous administration of glutamine, the main precursor of citrulline. When the small bowel is functional, administration of glutamine is followed by the elevation of citrullinemia. On the contrary, when there is enterocyte dysfunction or reduction, citrullinemia does not vary after glutamine administration. Peeters et al have shown the feasibility of carrying out the citrulline generation test in patients hospitalized in the ICU. In this context, intravenous administration of glutamine (20 gr of 10% N2-L-Alanyl-L-Glutamine, dilution in 200 ml of water for injection, IV infusion over 30 minutes) followed by monitoring of citrullinemia (basal time and then after 90 minutes, on arterial sampling) is feasible and reproducible.

There is currently no data available on the relationship between citrullinemia measured at ICU admission and tolerance to enteral nutrition in the days following ICU admission. Similarly, the value of the citrulline generation test for evaluating enteral nutrition tolerance is unknown.

The investigators hypothesize that patients with low citrullinemia at ICU admission, as well as those with a decreased citrullinemia elevation after Dipeptiven bolus, will have less tolerance to enteral nutrition than patients with normal citrullinemia.

PREDICT is the first study evaluating the interest of citrullinemia and the citrulline generation test to predict feeding tolerance among critically ill patients.

• N2-L-Alanyl-L-Glutamine (Substance) (Drug), also known as Dipeptiven: 20 gr of 10% N2-L-Alanyl-L-Glutamine, dilution in 200 ml of water for injection, intravenous perfusion over 30 minutes

Primary outcomes

• Feeding intolerance at day-3 and citrulline generation test [Day 3]: Feeding intolerance evaluated at day-3 of enteral nutrition Citrulline generation test: variation of citrullinemia/90 minutes

Secondary outcomes

• Feeding intolerance at dat 3 and basal plasma citrulline [Day 3]: Feeding intolerance at day-3 of enteral nutrition Citrullinemia measured the first day just before initiation of enteral nutrition
• Citrullinemia and cumulative amount of enteral nutrition [Day 3]: Link between citrullinemia and cumulative amount of enteral nutrition administred during the first three days of ICU stay
• Citrullinemia and enteral nutrition complications occurrence [First week]: Link between citrullinemia levels and occurrence of acute mesenteric ischemia and inhalation pneumopathy during the first week of enteral nutrition

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* 18 years old or older
* patient admited to ICU
* expected hospital stay of at least 3 days
* indication of enteral nutrition.
* presence of an arterial catheter
* signed informed consent

Exclusion Criteria:

* contraindication to enteral nutrition (e.g. non-functional digestive tract, mesenteric ischemia, occlusion, digestive fistula, active gastrointestinal bleeding)
* pregnancy ;
* chronic renal failure;
* chronic intestinal pathology

• Gaël PITON, MD, Principal investigator, CHU DE BESANCON