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General discussion
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8
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 PERSPECTIVES
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).