title: Withholding parenteral nutrition during critical illness increases plasma bilirubin but lowers the incidence of biliary sludge.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Hospitals of the KU Leuven, Intensive Care Medicine and Department of Molecular and Cellular Medicine, Leuven, Belgium.
authors.forename: Yoo-Mee
authors.initials: YM
authors.lastname: Vanwijngaerden
authors.forename: Lies
authors.initials: L
authors.lastname: Langouche
authors.forename: Richard
authors.initials: R
authors.lastname: Brunner
authors.forename: Yves
authors.initials: Y
authors.lastname: Debaveye
authors.forename: Marijke
authors.initials: M
authors.lastname: Gielen
authors.forename: Michael
authors.initials: M
authors.lastname: Casaer
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.forename: Sally
authors.initials: S
authors.lastname: Coulter
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Wouters
authors.forename: Alexander
authors.initials: A
authors.lastname: Wilmer
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood*; D002779:Cholestasis / Q000097:blood / Q000401:mortality / Q000517:prevention & control*; D016638:Critical Illness / Q000401:mortality / Q000628:therapy*; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000209:etiology* / Q000401:mortality; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010288:Parenteral Nutrition / Q000009:adverse effects* / Q000379:methods; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin