• Marc Jenniskens, Fabian Güiza, Renata Haghedooren, Sascha Verbruggen, Koen Joosten, Lies Langouche, and Greet Van den Berghe.
• Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Belgium.
• Pediatr Crit Care Me. 2018 Dec 1; 19 (12): 1120-1129.

ObjectivesIn 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.DesignPreplanned 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.SettingThree PICUs in Belgium, the Netherlands, and Canada.PatientsAs 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.InterventionsLate parenteral nutrition as compared with early parenteral nutrition.Measurements And Main ResultsDuring 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 < 0.05), but became comparable to early parenteral nutrition patients as soon as parenteral nutrition was started on day 8. Plasma concentrations of gamma-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were unaffected by parenteral nutrition. High day 1 plasma concentrations of gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase (p ≤ 0.01), but not alkaline phosphatase, were independent risk factors for PICU mortality. Day 1 plasma bilirubin concentrations displayed a U-shaped association with PICU mortality, with higher mortality associated with bilirubin less than 0.20 mg/dL and greater than 0.76 mg/dL (< 3.42 μmol/L and > 13 μmol/L) (p ≤ 0.01).ConclusionsOvert 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.

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