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Chapter 1
14
Autophagy
The benefits of withholding artificial nutritional support during the acute phase may also
be explained by the stimulating effect on autophagy
44,45
. Autophagy is an essential survival
mechanismbywhichcells breakdown their own (damaged) components to recycle intracellular
nutrients and generate energy during starvation
46-49
. Besides its role as cellular housekeeper,
autophagy is involved in protein quality control of tissue and organs. Additionally, it regulates
both innate and adaptive immune responses, partly by efficient clearance of intracellular
pathogens. Activation of autophagy by withholding parenteral nutrition during acute critical
illness might result in a better, more balanced physiological response with greater protein
synthesis, energy production and maintenance of cell structure
41,44,45,49
. On the other hand,
when autophagy is suppressed by forced overfeeding early in critical illness, the risk of organ
failure and cell death may increase, resulting in worse clinical outcome. Preservation of
autophagy in skeletal muscle partially explained why parenteral nutrient restriction reduced
ICU-acquired weakness and enhanced recovery
38
. Although nutrient restriction is regarded as
a risk factor for muscle atrophy, increased energy intake is associated with worsened muscle
function in critically ill adults and animal models
38,44
. Prolonged upregulation of autophagy
may lead to increased degradation of organelles and a failure to maintain energy provision,
resulting in increased apoptosis and cell death
50
. The beneficial effects of nutrient restriction
are therefore likely to be limited to the acute phase of critical illness.
Early enteral nutrition in critically ill children
Enteral nutrition is positioned as the preferred route over parenteral nutrition in critically
ill children, and guidelines recommend initiation within 48 hours
4
. It prevents gut atrophy,
preserves gut integrity and immunity, and hence decreases the risk for bacterial translocation
and systemic infection
51,52
. In a retrospective study of 5105 critically ill children, early enteral
nutrition, defined as the provision of 25% of target calories enterally over the first 48 hours of
admission, was shown to be associated with a lower mortality rate in those with a PICU length
of stay of at least 96 hours
53
. However, the observational design calls for caution in assuming
that this association is causal, since patients who tolerate enteral nutrition early, are likely to
have a better prognosis. In children with burns, early enteral nutrition (started within 3-6 hours)
was clinically superior to late enteral nutrition (after 48 hours) with a lower mortality rate,
shorter hospital stay and less weight loss
54
, but data from this distinct patient group cannot
automatically be applied to the general PICU population. Despite the current tendency to
provide early enteral nutrition during PICU stay, initiation is often delayed and administration
is frequently interrupted due to clinical procedures, gastro-intestinal intolerance and a number
of misconceptions (Table 2)
55-59
.
This results in a discrepancy between the amount of prescribed and delivered calories, with
overall 50-60%of the prescribed calories not being delivered when using the enteral route
2,71,72
.