Methionine Metabolism in Parenterally Fed Pediatric Sepsis
| Status: | Completed |
|---|---|
| Conditions: | Hospital |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | Any - 19 |
| Updated: | 4/2/2016 |
| Start Date: | October 2012 |
| End Date: | April 2015 |
| Contact: | Leticia Castillo, M.D. |
| Email: | Leticia4.castillo@utsouthwestern.edu |
| Phone: | 214-648-2228 |
Methionine Metabolism in Parenterally Fed Critically Ill Children
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.
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.
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
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