Proefschrift Kerklaan

Chapter 8

Prevention of PN-related complications By withholding PN, complications associated with central venous access 45 and composition of PNsolutions 46 mightbeprevented. Despite theseadditional complicationsof PNadministration, only 3.5% of PICUs would withhold PN for at least 7 days (Chapter 2). Also, after the first week of PICU stay, a large proportion (38%) of the PEPaNIC children depended on PN with its added risk. The complications associated with central venous access devices are not likely to have contributed to the beneficial effects of late PN, since the percentage of central venous lines is expected to be similar between the two treatment groups. Moreover, the reduced proportion of patients with a new infection in the late PN group was not only attributable to fewer patients acquiring a blood stream infection, but also to fewer airway infections. Clinical implementation of the late PN strategy will most likely decrease the number of venous access devices and associated complications in the future, although venous access remains essential for different reasons than provision of PN in the large proportion of children with multi-organ failure and/ or underlying chronic diseases. Use of PN has also been identified as a risk factor for caloric overfeeding 47,48 . Furthermore, patients with the lowest cumulative caloric intake (lowest dose intervals) showed a similar or better outcome than any of the higher doses in post-hoc analyses of adult RCTs 19,49 . By reducing the total caloric intake with late initiation of PN (Chapter 7), the prevalence of caloric overfeeding and its complications are likely to decrease. However, it is difficult to investigate the prevalence of overfeeding and its contribution to the unfavourable outcome in the early PN group. Endogenous glucose production is presumed to match 50-75% of REE the first days after admission 50 , resulting in an uncertainty of actual energy requirements when endogenous sources are used for energy. Current definitions of overfeeding are considered inadequate because they fail to take this and several other essential patient and disease related factors into account, and even identify patients with an intake below the threshold to equilibrate nitrogen balance as overfed (Chapter 4). On the other hand, one might state that recommendations by current guidelines reflect overfeeding in the acute phase of critical illness, because providing early PN in agreement with these guidelines is clinically inferior to withholding PN during this phase. In summary, despite the lack of adequate definitions, macronutrient intake should be reduced during the acute phase, since introduction of (supplemental) PN will easily result in overfeeding 51 (Chapter 1). The role of macronutrient dose Strategies of early and late initiation of PN differed in parenteral macronutrient intake, with no provision of amino acids and lipids and reduced intake of glucose in the late PN group (Chapter 6). High parenteral intake of glucose and amino acids are known to cause multiple, mostly metabolic, side effects in children 23,52-59 .

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