gluconeogenesis rates and its precursors in pediatric sepsis

Conditions: Sepsis; Hyperglycemia; Critical Illness

Summary: critically ill children have abnormal utilization of nutrients such as glucose, lipids and protein. often sick children have increased glucose concentrations in blood. however, the origin of the high glucose has not been determined in these populations. there is a close interrelationship between protein and energy metabolism. an increase in the energy supply will not promote nitrogen retention unless the amino acid supply is adequate, and conversely, an increased amino acid supply will be useless if energy is limiting, hence the importance of adequate protein and energy intake. our study aims to investigate the protein-energy interactions in critically ill septic children and adolescents with the objective to eventually provide the best nutritional support for these patients.

this is an observational study, aimed at exploring: i) gluconeogenesis rates ii) sources of gluconeogenesis and pyruvate cycling, and iii) protein kinetics in critically ill children and adolescents, and its differences by age group, as well as in comparison to healthy adolescents. the study size will include 45 critically ill septic, pediatric patients (22 children at 5-12 years of age and 23 adolescents' 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 17kg. additionally, 30 healthy adolescents matched by age, gender, bmi and tanner stage will be studied at the clinical translational research center at zale lipshy hospital, to serve as healthy adolescent controls. the number of subjects includes an expected drop out rate of about 20%, in order to obtain 18 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.

Eligibility criteria:
septic pediatric patients: inclusion criteria: 1. children age 5-19 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. indwelling central and/or arterial venous access as per clinical indication. exclusion criteria: 1. patients with metabolic diseases (i.e.: urea cycle disorders, cystinuria, insulin dependent diabetes mellitus, etc.). 2. pregnancy. 3. primary liver failure. healthy children: inclusion criteria: 1. age 13-19 years. 2. evidence of health as assessed by physical exam, and laboratory tests, including: hematocrit no less than 36% for males and no less than 37% for females, white blood cell count from 5-10,000. 3. chemistries within normal range, normal urine analysis, and fasting plasma glucose level no less than 60 or greater than 104 mg/dl. 4. lean children with bmi of 18-24. 5. obese children with bmi of 30 or greater. exclusion criteria: 1. tobacco use. 2. pregnancy. 3. taking any prescription medication that affects amino acid metabolism, i.e., glucocorticoids. 4. history of acute or chronic illness.

Keywords: gluconeogenesis glycogenolysis pyruvate cycling glucose production rates mitochondria acylcarnitines