title: Trigger mechanisms of secondary sclerosing cholangitis in critically ill patients.
abstract: BACKGROUND
  In recent years the development of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has increasingly been perceived as a separate disease entity. About possible trigger mechanisms of SSC-CIP has been speculated, systematic investigations on this issue are still lacking. The purpose of this study was to evaluate the prevalence and influence of promoting factors.
  
  
  METHODS
  Temporality, consistency and biological plausibility are essential prerequisites for causality. In this study, we investigated the temporality and consistency of possible triggers of SSC-CIP in a large case series. Biological plausibility of the individual triggers is discussed in a scientific context. SSC-CIP cases were recruited retrospectively from 2633 patients who underwent or were scheduled for liver transplantation at the University Hospital Charité, Berlin. All patients who developed secondary sclerosing cholangitis in association with intensive care treatment were included. Possible trigger factors during the course of the initial intensive care treatment were recorded.
  
  
  RESULTS
  Sixteen patients (68% males, mean age 45.87 ± 14.64 years) with a confirmed diagnosis of SSC-CIP were identified. Of the 19 risk factors investigated, particularly severe hypotension with a prolonged decrease in mean arterial blood pressure (MAP) to <65 mmHg and systemic inflammatory response syndrome (SIRS) were established as possible triggers of SSC-CIP. The occurrence of severe hypotension appears to be the first and most significant step in the pathogenesis. It seems that severe hypotension has a critical effect on the blood supply of bile ducts when it occurs together with additional microcirculatory disturbances.
  
  
  CONCLUSIONS
  In critically ill patients with newly acquired cholestasis the differential diagnosis of SSC-CIP should be considered when they have had an episode of haemodynamic instability with a prolonged decrease in MAP, initial need for large amounts of blood transfusions or colloids, and early development of a SIRS.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. Silke.Leonhardt@med.uni-duesseldorf.de.|Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Moorenstrasse 5, Düsseldorf, 40225, Germany. Silke.Leonhardt@med.uni-duesseldorf.de.
authors.forename: Silke
authors.initials: S
authors.lastname: Leonhardt
authors.affiliation: Endoscopy Unit, Department of Gastroenterology and Hepatology, Endocrinology, Diabetes and Metabolic Diseases, Charité- Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. wilfried.veltzke-schlieker@charite.de.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Veltzke-Schlieker
authors.affiliation: Endoscopy Unit, Department of Gastroenterology and Hepatology, Endocrinology, Diabetes and Metabolic Diseases, Charité- Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. andreas.adler@charite.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Adler
authors.affiliation: Endoscopy Unit, Department of Gastroenterology and Hepatology, Endocrinology, Diabetes and Metabolic Diseases, Charité- Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. eckart.schott@charite.de.
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. hetzer@dhzb.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Unfallkrankenhaus Berlin, Warener Strasse 7, Berlin, 12638, Germany. walter.schaffartzik@ukb.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffartzik
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Klinikum Kassel, Mönchebergstrasse 41, Kassel, 34125, Germany. michael.tryba@klinikum-kassel.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Tryba
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. peter.neuhaus@charite.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany. daniel.seehofer@charite.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer
mesh_terms: D000328:Adult; D000368:Aged; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D003422:Critical Care; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D006801:Humans; D007022:Hypotension / Q000150:complications; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications; D016896:Treatment Outcome