Proefschrift Kerklaan

Chapter 8

To further individualise and thereby optimise nutritional support, (bio)markers involved in the neuro-endocrine, immunologic/inflammatory and metabolic part of the stress response, could be used to identify the onset of the different phases within each child. Due to the insufficient sensitivity, specificity or availability of most (bio)markers, integration of several markers combined with clinical characteristics might be most promising to optimise individualised nutritional therapy in the PICU. To investigate the effect of such a patient-tailored approach on short-, and preferably also long-termclinical outcomes, clinical trials are needed to compare a strategy of marker-targeted feeding with the current generally applied nutritional practices. This information will add valuable evidence to current guidelines, that as of now do not distinguishbetweenphaseofcriticalillness,severityofillnessanddiagnoses.Recommendations derived from the high-level evidence provided by the PEPaNIC trial are also generally applicable, but provide specific recommendations on provision of PN in respect to phase of illness. Because recommendations on other aspects of nutritional support, such as enteral caloric and macronutrient goals, should take these phases into account as well 51,82 (Chapter 1), an update of current guidelines is urgently needed. Until other studies have provided evidence to individualise nutritional support to disease and settings, these updated guidelines should be used as a foundation for nutritional therapy, whilst considering the physiology of the individual patient. In the PEPaNIC trial, the strategy of withholding PN was limited to the period following PICU admission. One might question if deterioration of clinical status beyond this period might evoke a similar acute stress response and therefore if the child might benefit from parenteral nutrient restriction as well. When more insight can be provided into the relation between the stress response and the beneficial effects of late PN based on the PEPaNIC trial, application of this strategy later during PICU stay might need to be investigated. Finally, since we have shown that permissive parenteral underfeeding is beneficial early in critical illness, avoidance of overfeeding has become even more significant. In order to improve its detection, a new definition of overfeeding is urgently needed and should take into account the age and nutritional status of the child, the phase of critical illness, and possibly also the route of nutrition. However, to develop such a phase-dependent definition, adequate identification of these phases is essential. In a subset of PEPaNIC patients, results from REE measurements by IC will be analysed to gain more insight in the concept of overfeeding on the PICU.

Other nutritional aspects in critically ill children that were beyond the scope of this thesis, but in profound need of high-level evidence, are the optimal amount of EN early in critical illness

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