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Chapter 1
16
encountered with high parenteral protein intake (3 g/kg/day), raising concerns of an increased
insulin resistance
76
. High doses of parenteral glucose are associated with side-effects, as
lipogenesis and hyperglycaemia, which can safely be prevented by amounts of parenteral
glucose belowcurrent guidelines
77,78
.Therefore, it remains unclear whether insufficient nutrient
administration by the enteral route should be supplemented with parenteral nutrition.
The stable and recovery phase of critical illness
The stable phase
The stable phase of critical illness is represented by stabilisation or weaning of vital organ
support, whereas the different aspects of the stress response are not (completely) resolved.
In addition to persistent low peripheral hormone levels, this phase is also characterised by a
central suppression of the different endocrine axes (Fig. 1)
14
. In contrast to the target organ
resistance marking the acute phase, peripheral tissues respond to low T3 concentrations by
increase of local hormone availability and effects
79,80
. Despite increased effect of this anabolic
hormone, large amounts of protein continue to be wasted, whereas fat stores remain relatively
intact
81
. Plasma cytokine concentrations are substantially decreased, but immune cell function
remains affected, as shown by persistent alterations in glycoprotein expression. The duration
of this phase can range from days to weeks, depending on the age and diagnosis of the child
82
.
In mixed populations of critically ill children, levels of anabolic hormones such as T3, growth
hormone and (bioavailable) IGF-1 already increase during the first week of admission
36,83
.
Recovery of anabolism appears to be in concert with the resolution of inflammation, as shown
by the relation between T3 and C-reactive protein (CRP) levels
36
and between early metabolic
markers, such as triglycerides levels, and immunologic parameters such as acute phase CD64
+
expression on neutrophils
24
.
However, despite early normalisation of the catabolic counter-regulatory hormone levels,
other parameters of the neuro-endocrine, metabolic and immunologic stress response might
need more time to resolve.
The recovery phase
Clinical mobilisation of the child, that is no longer in need of vital organ support, together
with resolution of the stress response, marks the onset of the recovery phase. This final phase
may last weeks to months. Hormone levels gradually return to normal (Fig. 1). The body shifts
from catabolism to anabolism with protein synthesis exceeding protein breakdown, resulting
in positive nitrogen balance, tissue repair and (catch-up) growth. Restoration of mitochondrial
function is achieved with accelerated stimulation of mitochondrial protein (biogenesis)
84
.
However, in children with burns a persistent hypermetabolic state is known to delay anabolism
and growth
85
, and suppressed insulin receptor signalling can be detected up to 250 days
postburn
86
.