Methionine Metabolism in Parenterally Fed Pediatric Sepsis
Condition: Sepsis; Critical Illness
MeSH terms: Sepsis; Critical Illness
Study type: Observational

Summary: 
      Critically ill children have abnormal utilization of nutrients such as glucose, lipids and
      protein. Protein synthesis is increased mainly in the form of immune and signaling proteins,
      while synthesis of muscle and structural proteins is decreased. The metabolism of sulfur
      amino acids and specifically methionine and cysteine have not been investigated in critically
      ill septic children, despite that sulfur amino acids have important roles on thiol,
      antioxidant and epigenetic reactions, as well as precursor of glutathione (GSH). Methionine
      metabolism in critically ill children will be influenced by its rate of utilization through
      the transmethylation, remethylation and transsulfuration pathways, which are the major
      pathways of methionine metabolism.

      The investigators study aims to investigate the metabolism of methionine and cysteine in
      parenterally fed critically ill septic children. The investigators aim to determine the rates
      of transmethylation, remethylation, transsulfuration and GSH synthesis rates in critically
      ill septic children, to determine in vivo, whole body sulfur amino acid metabolism when
      sulfur amino acids are supplied by the parenteral route. The objective is to determine
      whether current parenteral intakes support GSH synthesis and if methionine metabolism differs
      when supplied by the parenteral versus the enteral route. Methionine parenteral requirements
      will be also studied by using the indicator amino acid oxidation and balance technique.
    

Detailed description: 
      This is a prospective, translational study on whole body methionine metabolism and
      requirements when administered by the parenteral route in critically ill septic children. The
      study size will include 45 critically ill septic, pediatric patients (15 infants at 1 month-3
      years of age, 15 children at 4-12 years of age and 15 adolescent at 13-19 years of age, male
      and females admitted to the pediatric intensive care unit (PICU) at Children's Medical
      Center, Dallas. The minimal subject's weight will be 4 kg. The number of subjects includes an
      expected drop out rate of about 20%, in order to obtain 12 patients with complete data in
      each group. Patients will receive nutritional support as per standard care. This study will
      yield important knowledge and may lead in the future to changes in the current practice on
      the management of critically ill pediatric patients in the PICU.

      Study Aim#1: Determine the parenteral requirements of methionine, in the presence of
      cysteine, in critically ill septic patients' required extended use of TPN, by using the
      indicator amino acid oxidation and balance technique.

      Study Aim#2: Determine methionine metabolism through the rates of transmethylation,
      transsulfuration and remethylation at the current standard intakes of methionine of 120
      mg.kg.d. with negligible amounts of cysteine.
    

Intervention name(s): Observational
Intervention type(s): Other
Intervention description(s): Observational, Translational non-treatment study
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Septic pediatric patients: A total of 45 critically ill children age 1 month-19 years with
        diagnosis of sepsis, as defined by the International Sepsis Consensus Conference.
      
Biospecimen description: 
      Blood Samples.
    
Keywords: Methionine Metabolism; Parenteral Nutrition; Pediatric; Pediatrics; Sepsis; Observational Study