Modulation of Systemic Inflammatory Response in Critically Ill Children After Glutamine Supplementation

This study aims to describe the use of glutamine supplementation in the modulation of inflammatory response in critically ill pediatric patients and to determine if this decrease leads to clinical improvement in morbidity and mortality in these patients. Thus, these patients' diet could be supplemented with glutamine in order to improve their evolution.

Hypothesis:

From the data obtained in the study of the literature the investigators consider that:

Critically ill patients have a deficit of glutamine either because of an increase in its consumption or a decrease in its availability, and therefore blood glutamine levels are low.

Critically ill patients have elevated blood levels of pro-inflammatory substances (IL-6).

In these patients tissue lesion inhibitors (HSP-70) in the blood are decreased. The administration of glutamine supplements to these patients decreases oxidative stress due to the increase in HSP-70.

Inflammation inhibitory substances (IL-10) in the blood are decreased in these patients.

The administration of glutamine supplements in these patients increase IL-10 levels.

Glutamine supplements decrease the inflammatory response with a decrease in IL-6 levels.

Objective

This study aims to describe the use of glutamine supplementation in the modulation of inflammatory response in critically ill pediatric patients and to determine if this decrease leads to clinical improvement in morbidity and mortality in these patients. Thus, these patients' diet could be supplemented with glutamine in order to improve their evolution.

In recent years numerous studies have been conducted and published on the different factors, amongst them glutamine, that could modulate the inflammatory response of critically ill patients thus reducing the impact this response has and its progression to multi-organ failure.

Glutamine (Gln) is the most abundant amino acid in the body and is mainly synthesised in skeletal muscle. It is a non-essential amino acid that is produced is sufficient quantities in good states of health. Plasma levels are above 0.6 mmol/L, and 50% is found in the free form in plasma1. This amino acid not only acts as a source of energy but it is also involved in the synthesis of other amino acids, nucleotides, nucleic acids, sugars, amines, proteins and different biologically active molecules2. Other functions are: maintenance of the internal acid-base homeostasis, urea synthesis, glyconeogenesis, neurotransmission, and cell differentiation and proliferation. It is also the main energy substrate for the rapidly proliferating cells (enterocytes) and of multiple immune cells (macrophages, monocytes, lymphocytes). It also takes part in the protection of cells and tissues inducing expression of the heat shock proteins3.

In recent years, numerous studies have been performed to determine the effect of Gln, both by enteral and parenteral route, on the evolution of critically ill patients. These studies were conducted in animals and in humans, mainly adults. However, there is little reference in the literature to studies in children. The studies are based on the use of glutamine as a dietary supplement mainly in patients with neoplastic disease or inflammatory bowel disease. It has also been studied as a supplement in premature infants, but there are very few studies in critically ill children.

In the last year many studies have been published on the use of glutamine. The effect of glutamine supplementation on the intestinal mucosal barrier in rabbits under haemorrhagic shock was studied. Shock was induced by blood withdrawing from the femoral artery; the rabbits were randomised to three groups (control, low dose glutamine and high dose glutamine). Plasma levels of diamine oxidase and IL-8 were measured and a histological examination of the terminal ileum was performed. The results demonstrated a lower inflammatory and oxidative response in the rabbits who had received Gln supplementation37. Another study in rats measured the effect of the dipeptide Arginin - Gln on endothelial cell growth factor levels in retinal pigment epithelial cell cultures and on the inhibition of neovascularisation in oxygen-induced retinopathy. The authors concluded that they decreased with the administration of this dipeptide38. Another factor studied in critically ill patients was the oxidative activity measured as diamine oxidase activity and D-lactate content39. Protection against infection and decrease in insulin resistance in critically ill patients is still being studied 21,22, 32, 40, 41. Contradictory findings have been reported therefore new studies are required in systematic reviews.

Eligibility Criteria:
Inclusion Criteria:

1. Patients aged between 1 month and 14 years who require parenteral nutrition according to the criteria of our unit and who comply with the following diagnoses:

* Local or systemic infection
* Post abdominal surgery
* Polytraumatised

Parenteral nutrition indications:

* Intestinal resections
* Bowel obstruction or post-surgery
* Risk of intestinal ischaemia due to hypotension of hypoxaemia

Exclusion Criteria:

1. Legal representative does not give consent.
2. Patients with previous underlying diseases (renal impairment, hepatic impairment, inflammatory bowel disease, rheumatic diseases, metabolic diseases, immunocompromised).
3. Mild liver impairment on admittance (hepatitis, colostasis).
4. Post cardiac surgery with extracorporeal circulation.
5. Patients referred from other hospitals with a clinical evolution of over 48 hours.
6. Patients aged less than one month and over 14 years.