Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill Children and the Impact of Delaying Parenteral Nutrition

Objectives: In the Early versus Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial, delaying parenteral nutrition to beyond day 7 (late parenteral nutrition) was clinically superior to supplemental parenteral nutrition initiated within 24 hours (early parenteral nutrition), but resulted in a higher rise in bilirubin. We aimed to document prevalence and prognostic value of abnormal liver tests in the PICU and the impact hereon of withholding early parenteral nutrition. Design: Preplanned secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial. Total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase plasma concentrations were measured systematically in PICU. Liver test analyses were adjusted for baseline characteristics including severity of illness. Setting: Three PICUs in Belgium, the Netherlands, and Canada. Patients: As neonatal jaundice was considered a confounder, only the 1,231 of the 1,440 Early versus Late Parenteral Nutrition in the Pediatric ICU-patients 28 days to 17 years old were included. Interventions: Late parenteral nutrition as compared with early parenteral nutrition. Measurements and Main Results: During the first seven PICU days, the prevalence of cholestasis (> 2 mg/dL [34.2 μmol/L] bilirubin) ranged between 3.8% and 4.9% and of hypoxic hepatitis (≥ 20-fold upper limit of normality for alanine aminotransferase and aspartate aminotransferase) between 0.8% and 2.2%, both unaffected by the use of parenteral nutrition. Throughout the first week in PICU plasma bilirubin concentrations were higher in late parenteral nutrition patients (p 13 μmol/L) (p ≤ 0.01). Conclusions: Overt cholestasis and hypoxic hepatitis were rare and unrelated to the nutritional strategy. However, withholding parenteral nutrition up to 1 week in PICU increased plasma bilirubin. A mild elevation of bilirubin on the first PICU day was associated with lower risk of death and may reflect a stress response, rather than true cholestasis. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Drs. Langouche and Van den Berghe had equal contribution. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (https://ift.tt/2gIrZ5Y). Supported, in part, by the Methusalem Program of the Flemish Government (Drs. Langouche and Van den Berghe) via the KU Leuven University (METH/08/07); by an ERC Advanced grant (AdvG-2012–321670) to Dr. Van den Berghe from the Ideas Program of the European Union 7th framework program. Dr. Van den Berghe’s institution received funding from Flemish Government (METHUSALEM) and European Research Council. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: greet.vandenberghe@kuleuven.be ©2018The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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