Withholding parenteral nutrition during critical illness increases plasma bilirubin but lowers the incidence of biliary sludge

Authors

  • Yoo-Mee Vanwijngaerden,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
    • These authors contributed equally to this study.

  • Lies Langouche,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
    • These authors contributed equally to this study.

  • Richard Brunner,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
  • Yves Debaveye,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
  • Marijke Gielen,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
  • Michael Casaer,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
  • Christopher Liddle,

    1. Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead NSW, Australia
    Search for more papers by this author
  • Sally Coulter,

    1. Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead NSW, Australia
    Search for more papers by this author
  • Pieter J. Wouters,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
  • Alexander Wilmer,

    1. University Hospitals of the KU Leuven, Medical Intensive Care Unit, Leuven, Belgium
    Search for more papers by this author
  • Greet Van den Berghe,

    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    Search for more papers by this author
  • Dieter Mesotten

    Corresponding author
    1. University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium
    • Address reprint requests to: Dieter Mesotten, M.D., Ph.D., University Hospitals of the KU Leuven, Intensive Care Medicine, Department of Molecular and Cellular Medicine KULeuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: dieter.mesotten@med.kuleuven.be; fax: +32-16 34 40 15.

    Search for more papers by this author

  • Potential conflict of interest: Nothing to report.

  • Supported by Research Foundation Flanders, Belgium (FWO), and by long term structural funding (GVdB) – Methusalem funding by the Flemish Government. M.C. holds a clinical fellowship and D.M. a senior clinical investigatorship from the FWO, G.VdB. holds an ERC Advanced Research Grant (EU-ERC321670).

  • See Editorial on Page 26

Abstract

Cholestatic liver dysfunction (CLD) and biliary sludge often occur during critical illness and are allegedly aggravated by parenteral nutrition (PN). Delaying initiation of PN beyond day 7 in the intensive care unit (ICU) (late PN) accelerated recovery as compared with early initiation of PN (early PN). However, the impact of nutritional strategy on biliary sludge and CLD has not been fully characterized. This was a preplanned subanalysis of a large randomized controlled trial of early PN versus late PN (n = 4,640). In all patients plasma bilirubin (daily) and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], twice weekly; n = 3,216) were quantified. In a random predefined subset of patients, plasma bile acids (BAs) were also quantified at baseline and on days 3, 5, and last ICU-day (n = 280). Biliary sludge was ultrasonographically evaluated on ICU-day 5 (n = 776). From day 1 after randomization until the end of the 7-day intervention window, bilirubin was higher in the late PN than in the early PN group (P < 0.001). In the late PN group, as soon as PN was started on day 8 bilirubin fell and the two groups became comparable. Maximum levels of GGT, ALP, and ALT were lower in the late PN group (P < 0.01). Glycine/taurine-conjugated primary BAs increased over time in ICU (P < 0.01), similarly for the two groups. Fewer patients in the late PN than in the early PN group developed biliary sludge on day 5 (37% versus 45%; P = 0.04). Conclusion: Tolerating substantial caloric deficit by withholding PN until day 8 of critical illness increased plasma bilirubin but reduced the occurrence of biliary sludge and lowered GGT, ALP, and ALT. These results suggest that hyperbilirubinemia during critical illness does not necessarily reflect cholestasis and instead may be an adaptive response that is suppressed by early PN. (Hepatology 2014;60:202–210)

Ancillary