title: Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure--a prospective, randomised crossover study.
abstract: BACKGROUND
  The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure.
  
  
  METHODS
  Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4% albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model.
  
  
  RESULTS
  Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median -68 μmol/L, interquartile range [IQR] -107.5 to -33.5, p = 0.001; SPAD: -59 μmol/L, -84.5 to +36.5, p = 0.001). However, bile acids (MARS: -39 μmol/L, -105.6 to -8.3, p < 0.001; SPAD: -9 μmol/L, -36.9 to +11.4, p = 0.131), creatinine (MARS: -24 μmol/L, -46.5 to -8.0, p < 0.001; SPAD: -2 μmol/L, -9.0 to +7.0/L, p = 0.314) and urea (MARS: -0.9 mmol/L, -1.93 to -0.10, p = 0.024; SPAD: -0.1 mmol/L, -1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10%, -0.8 to +20.9%, p < 0.001; SPAD: +7%, -7.5 to +15.5%, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD.
  
  
  CONCLUSIONS
  Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation.
  
  
  BACKGROUND
  German Clinical Trials Register ( www.drks.de) DRKS00000371. Registered 8 April 2010.
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. christoph.sponholz@med.uni-jena.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sponholz
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. katja.matthes@uni-jena.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Matthes
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. dina.rupp@uni-jena.de.
authors.forename: Dina
authors.initials: D
authors.lastname: Rupp
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. wolf.backaus@uni-jena.de.
authors.forename: Wolf
authors.initials: W
authors.lastname: Backaus
authors.affiliation: Charité Research Organisation, Berlin, Germany. sebastian.klammt@charite-research.org.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Klammt
authors.affiliation: Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany. diana.karailieva@med.uni-jena.de.|Center for Sepsis Control and Care, Integrated Treatment and Research Center, Jena University Hospital, Jena, Germany. diana.karailieva@med.uni-jena.de.
authors.forename: Diana
authors.initials: D
authors.lastname: Karailieva
authors.affiliation: Division of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany. astrid.bauschke@med.uni-jena.de.
authors.forename: Astrid
authors.initials: A
authors.lastname: Bauschke
authors.affiliation: Division of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany. utz.settmacher@med.uni-jena.de.
authors.forename: Utz
authors.initials: U
authors.lastname: Settmacher
authors.affiliation: Department of Medical and Life Sciences, Furtwangen University, Villingen-Schwenningen, Germany. matthias.kohl@hs-furtwangen.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohl
authors.affiliation: Center for Sepsis Control and Care, Integrated Treatment and Research Center, Jena University Hospital, Jena, Germany. mgclemen@uncc.edu.|The Liver-Biliary-Pancreatic Center, Carolinas Medical Center, Charlotte, NC, USA. mgclemen@uncc.edu.|Department of Biology, University of North Carolina at Charlotte, Charlotte, NC, USA. mgclemen@uncc.edu.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Clemens
authors.affiliation: Division of Nephrology, Department of Medicine, Rostock University Medical Centre, Rostock, Germany. steffen.mitzner@med.uni-rostock.de.|Fraunhofer Institute for Cell Therapy and Immunology, Extracorporeal Immunomodulation Project Group, Rostock, Germany. steffen.mitzner@med.uni-rostock.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Mitzner
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. michael.bauer@med.uni-jena.de.|Center for Sepsis Control and Care, Integrated Treatment and Research Center, Jena University Hospital, Jena, Germany. michael.bauer@med.uni-jena.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. andreas.kortgen@med.uni-jena.de.|Center for Sepsis Control and Care, Integrated Treatment and Research Center, Jena University Hospital, Jena, Germany. andreas.kortgen@med.uni-jena.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kortgen
mesh_terms: D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D005112:Extracorporeal Circulation / Q000379:methods; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods; D006801:Humans; D017093:Liver Failure / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects* / Q000592:standards*; D012709:Serum Albumin / Q000378:metabolism*; D014508:Urea / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D012709:Serum Albumin; D014508:Urea; D003404:Creatinine; D001663:Bilirubin