Proefschrift Kerklaan

General discussion

Hypoglycaemia with parenteral nutrient restriction Despite the clinical benefits, late PN increased the incidence of hypoglycaemia from 4.8% to 9.1% (Chapter 7). However, experiencing hypoglycaemia with late PN did not reduce its impact on any of the primary or secondary outcomes (Supplementary appendix, chapter 7). Previous studies have shown that brief episodes of hypoglycaemia, either during paediatric critical illness or in premature/mature newborns, did not negatively affect long-term neurocognitive outcomes 80,81 . A follow-up study of all PEPaNIC patients is currently conducted to evaluate functional, physical and neurocognitive outcome 2 and 4 years after admission to the PICU (Chapter 6). Data will be compared between the two treatment groups, but also between PEPaNIC patients and matched healthy controls. Results from this study will provide more insight in the long-term effects of critical illness in general and nutritional support in the PICU in particular. Future research The results described in this thesis have provided some important answers, but also raised questions. The PEPaNIC trial has provided the long awaited evidence for use of (supplemental) PN in critically ill children of all age groups and diagnoses during the first week of PICU stay. The rigid study protocol, although practical for large clinical trials, is unlikely to have represented an optimal nutritional strategy for every individual patient, but has provided a strategy that is generally applicable with a risk of being unfocused. Pre-planned subgroup analyses from the PEPaNIC trial might support specific evidence-based guidelines in respect to disease and settings, in order to individualise nutritional support on the PICU. The following subgroups will be investigated: cardiac patients, patients with sepsis, malnourished patients and children with contra-indication for EN on admission. Also, the enhanced beneficial effect of late PN in neonates (Chapter 7) will be further analysed. Pre-planned mechanistic studies on endocrine, inflammatory and genetic markers and a dose- and macronutrient dependency analysis might unravel underlying mechanisms of the beneficial effect of early parenteral nutrient restriction. In order to translate nutritional recommendations to clinical practice, it is essential to make a distinction between the phases of critical illness (Chapter 1). For the PEPaNIC trial, the acute phase was defined as the first 7 days after PICU admission. However, in the majority of the children the acute phase was shorter because they had left the PICU within the first 7 days (Chapter 7) or because enteral caloric intake was already sufficient to meet caloric goals on day 8 (60% of children present at day 8). FUTURE PERSPECTIVES

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