These authors contributed equally to this study.
Autoimmune, Cholestatic and Biliary Disease
Withholding parenteral nutrition during critical illness increases plasma bilirubin but lowers the incidence of biliary sludge
Article first published online: 26 FEB 2014
© 2014 by the American Association for the Study of Liver Diseases
Volume 60, Issue 1, pages 202–210, July 2014
How to Cite
Vanwijngaerden, Y.-M., Langouche, L., Brunner, R., Debaveye, Y., Gielen, M., Casaer, M., Liddle, C., Coulter, S., Wouters, P. J., Wilmer, A., Van den Berghe, G. and Mesotten, D. (2014), Withholding parenteral nutrition during critical illness increases plasma bilirubin but lowers the incidence of biliary sludge. Hepatology, 60: 202–210. doi: 10.1002/hep.26928
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
- Issue published online: 26 JUN 2014
- Article first published online: 26 FEB 2014
- Accepted manuscript online: 9 NOV 2013 04:00AM EST
- Manuscript Accepted: 3 NOV 2013
- Manuscript Received: 4 SEP 2013
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)