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.

Objective of the 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.

Study design:
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.

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.

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.