Proefschrift Kerklaan

Chapter 1

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 .

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