Modulation of Systemic Inflammatory Response in Critically Ill Children After Glutamine Supplementation
Condition: Inflammatory Response; Multi-organ Failure
MeSH terms: Multiple Organ Failure
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): solution of amino acids supplemented with glutamine; amino acids not supplemented with glutamine
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): parenteral nutrition by range of ages (recommendation from ESPGHAN and ESPEN:1 month to 3 years, 3 to 5 years, 6 to 12 and standard adult).Study Parenteral nutrition will be assessed the first 5 days.; parenteral nutrition by range of ages (recommendation from ESPGHAN and ESPEN:1 month to 3 years, 3 to 5 years, 6 to 12 and standard adult).Study Parenteral nutrition will be assessed the first 5 days.
Other intervention name(s): (Aminoven Infant® or Vamin®) with glutamine (Dipeptiven®); (Aminoven Infant® or Vamin®) with glutamine (Dipeptiven®)
Intervention MeSH terms: Amino-acid, glucose, and electrolyte solution
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: inflammatory response; parenteral nutrition; glutamine; amino acid; pediatric; intensive care; systemic infection; abdominal surgery; polytraumatised; mortality; mean stay in the intensive care unit; occurrence of infections