Protein and energy interactions 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. Endothelial health and protection against oxidative stress
are some of these *non-protein* functions exerted by amino acids. 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.

1) To assess insulin sensitivity and response in critically ill septic neonates
and children.
2) 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.
3) To assess the relationship between protein turnover and glucose and fat
metabolism in critically ill septic children.
4) To compare the continuous subcutaneous glucometer with standard plasma
glucose monitoring during a Hyperinsulinemic Euglycemic Clamp in septic
neonates.
5) To determine the fractional (FSR) and absolute (ASR) of albumin and
C-reactive protein at baseline and during HEC with standard and high protein
intake in critically ill septic children.

Neonates: The study consists of one day, where they will receive an intravenous
bolus of 2H2O and a primed 7-hour continuous intravenous study with [6,6
2H2]Glucose, [1-13C]Leucine, [ring-2H5]Phenylalanine and [3,3 2H2]Tyrosine of
which the last three hours will be with insulin (HEC; Hyperinsulinemic
Euglycemic Clamp). Glycemic control will be achieved by using a continuous
subcutaneous glucometer in comparison with the standard plasma glucose.

Children: 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.

Children:
The subjects will be studied in two occasions, 24 h apart while receiving TPN
at two different amounts of protein intake (standard vs. higher protein intake)
with a Hyperinsulinemic Euglycemic Clamp.

Neonates:
The subjects will be studied on one occasion, with a Hyperinsulinemic
Euglycemic Clamp.

The risk of insulin infusion is hypoglycemia and hypokalemia.

During the insulin infusion, small blood samples will be obtained from the
indwelling I.V. catheter every 5 minutes to monitor whole blood glucose
concentration, at the bedside with the aid of a Y.S.I. stat plus analyzer.
Blood glucose concentration will be maintained between 90 to 110 mg/dl (the
amount of blood drawn during the 3 hour HEC for blood glucose determination
will be approximately 2 ml total). If the plasma glucose concentration reaches
6.1mM (110mg/dl), the glucose infusion will be decreased to maintain the plasma
glucose concentration between 5.0 - 6.1 mM (90-110 mg/dl).

Whole blood potassium will be checked at 30, 60 and 120 minutes after the
beginning of the insulin infusion; if the potassium concentration is below 3
mmol/L, a potassium chloride infusion will be administered intravenously at a
dose of 0.5 mEq/kg of body weight , no more than 15 mEq over 1 h, followed by
further potassium concentration monitoring. If the potassium concentration is
again below 3 mmol/L, then a second dose of potassium chloride will be
administered at the same dose and it will be monitored again 1 hour later.

There will be no direct benefit to the subject. The goal for the future is a
general advice on nutrition and specifically protein intake based on agegroups
in critically ill children who receive insulin in the neonatal and pediatric
critical care.