15 / 208
Introduction
13
1
Immunologic and metabolic response
The metabolic response is hypercatabolism. To guarantee substrate delivery to vital tissues,
free amino acids and fatty acids (FFA) are mobilised by muscle protein breakdown and lipolysis,
caused by elevated levels of cortisol and other counter-regulatory hormones (catecholamines
and glucagon)
19,22,23
. This results in increased triglycerides levels and reduced high- and low-
density-lipoproteins, especially in children with sepsis
24
. Hyperglycaemia develops due to
increased endogenous glucose production and peripheral insulin resistance
25
. Hypercata-
bolism in the acute phase is primarily induced by inflammation and is more pronounced in
multiorgan failure
26
. After the initial cytokine release, other markers of immune cell activation
become apparent, such as acute phase CD64
+
expression on neutrophils and monocytes
27
.
When comparing measured to predicted resting energy expenditure (REE), different metabolic
patterns appear to interchange within the child during the clinical course of severe illness
28-32
.
This might be explained by the varying and often opposing effects of the different components
of the acute phase response on metabolic rate.
Duration of the stress response
This first phase can take hours to days after an event (such as trauma, sepsis or surgery) and,
based on circumstantial evidence, might last shorter in surviving critically ill children than
in critically ill adults. In the majority of children with meningococcal disease, blood glucose,
cortisol and ACTH levels normalise within 48 hours suggesting an early resolution of the stress
response concerning counter-regulatory hormones and glucose metabolism
33,34
.
In critically ill and post-surgical neonates, the plasma levels of catecholamines, thyroid
hormones and IGF-1 return to baseline even faster than in older children
35,36
, with the earliest
return of anabolic protein metabolism found after acute injury in preterm neonates
37
.
Nutrient administration in the acute phase of critical illness
The acute stress response is affected by nutrition. However, in contrast to previous ideas,
hypercatabolism and subsequent muscle atrophy are not reversed with increased provision of
nutrients during this phase
26,38
. Recent high-quality trials in adults have extensively investigated
the provision of artificial nutrition during this phase
11,12
, and showed no beneficial effects of
early initiation of parenteral nutrition
39-41
. Nutrient restriction early in critical illness enhanced
the central and peripheral neuro-endocrine response by further lowering T3, thyroxine (T4)
and TSH levels as well as the T3 (active thyroid hormone)/reverseT3 (inactive thyroid hormone)
ratio. The T3/rT3 ratio was also further reduced by the application of a tight glucose control
protocol in critically ill children
42
. This decrease in T3/rT3 ratio was associated with a better
outcome both in critically ill adults and children
42,43
, possibly indicating that changing the
peripheral conversion of T4 frommetabolically active T3 to inactive rT3 during the first days of
critical illness is adaptive and beneficial for recovery
42
.