Insulin and protein in critically ill children.

It has been reported that tight glucose control with insulin in adult critically ill surgical patients has reduced mortality rates. However, there is no evidence that this approach may be beneficial in critically ill children. In theory, insulin has several potential beneficial effects. It has metabolic effects (glycemic control, improve protein balance and dyslipidemia) and non-metabolic effects (protect against oxidative stress, endothelial dysfunction and regulation of inflammation). Under physiological conditions, there is a close interrelationship between protein and energy (glucose and fat) 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. Furthermore, protein requirements in critically ill children reach beyond the traditional areas of nitrogen balance and protein metabolism. Individual amino acids exert a functional impact during critical illness on which insulin might have a significant effect. The effect of tight glucose control with insulin on protein requirements, and on the regulation of substrate metabolism in critically ill septic children of all ages needs further study.


Objective:

1. To determine protein balance in septic, critically ill children at baseline and during a Hyperinsulinemic Euglycemic Clamp, while receiving standard or high protein intake based on age group;

2. To assess insulin sensitivity and response in critically ill septic children;

3. To assess the relationship between protein turnover and glucose and fat metabolism in critically ill septic children.


Study design:
A prospective, translational study.


Study population:
Critically ill septic children.


Intervention:
The study consists of a 2 day, 7-hour primed continuous intravenous tracer infusion studies of which the last three hours will be with a HEC. The protocol will consist of a tracer study ([1-13C]Leucine, [ring-2H5]Phenylalanine and [3,3 2H2]Tyrosine, [6,6 2H2]Glucose and [1,1,2,3,3 2H5]Glycerol) on two days in which they will receive parenteral nutrition with two different amounts of protein intake (according to age) in a cross over fashion.


Main study parameters/endpoints:
The main study parameter of the study is the change in protein balance between baseline and insulin infusion.

Objective:

1. To determine protein balance in septic, critically ill children at baseline and during a Hyperinsulinemic Euglycemic Clamp, while receiving standard or high protein intake based on age group;

2. To assess insulin sensitivity and response in critically ill septic children;

3. To assess the relationship between protein turnover and glucose and fat metabolism in critically ill septic children.

2 day study which starts once the subject is hemodynamically stable in the PICU. It consists of 7 hr tracer infusions of which the last 4 hrs will be with insulin infusion.

Standard vs High Amino acid intake by means of Total Parenteral Nutrition
for 24 hrs in a cross-over design. On both study days a primed ,
continuous stable isotope tracer infusion will be provided for 7 hrs, of
which the last three hours will be with insulin infusion by means of a
Hyperinsulinemic euglycemic Clamp.