Abstract
Background: Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol. Methods: In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia. Results: Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia. Conclusion: Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia.
Original language | English |
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Article number | 251 |
Journal | Critical Care |
Volume | 27 |
Issue number | 1 |
DOIs | |
Publication status | Published - 26 Jun 2023 |
Bibliographical note
Funding Information:This work was supported by ERC Advanced Grants from the Horizon 2020 Programme (AdvG-2012-321670 and AdvG-2017-785809) to GVdB; by the Methusalem Programme of the Flemish Government (through the University of Leuven to GVdB, LL, and IV, METH14/06); by the Agency for Innovation through Science and Technology, Flanders, Belgium (through the University of Leuven to GVdB, IWT/110685/TBM and IWT/150181/TBM); by the University Hospitals Leuven (postdoctoral research fellowship by the Clinical Research and Education Council to JG); by the Sophia Children’s Hospital Foundation (SSWO) to SCV; by the Stichting Agis Zorginnovatie to SCV; by the Erasmus Trustfonds to SCV; and by a European Society for Parenteral and Enteral Nutrition (ESPEN) research grant to SCV. The funders of the study had no role in the design of the study, in the collection, analysis or interpretation of the data, or in the writing of the report.
Publisher Copyright:
© 2023, The Author(s).