Methionine Metabolism in Parenterally Fed Pediatric Sepsis
Methionine Metabolism in Parenterally Fed Pediatric Sepsis
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.
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.
Inclusion Criteria:

 1. Age 1 month-19 years

 2. Diagnosis of severe sepsis diagnosed as clinical sepsis syndrome (requires two of the
 following criteria):

 -  Source of infection

 -  Fever or Hypothermia

 -  Leukocytosis or Leucopenia

 -  Poor organ perfusion (such as delayed capillary refill or decreased urine output
 or hypotension)

 -  Bacteremic sepsis demonstrated by positive blood culture

 3. Weight greater or equal to 4 kg

 4. Need for parenteral nutrition

 5. Presence of central and/or arterial venous access as per clinical indication

 Exclusion Criteria:

 1. Patients with metabolic diseases (i.e. Insulin dependent diabetes mellitus, urea cycle
 disorders, cystinuria, etc.)

 2. Pregnancy

 3. Primary liver failure

 4. Primary renal failure

 5. Patients on enteral feedings greater than 20% of daily requirement

 6. Weight less than 4.0 kg