title: Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response, which is associated with postoperative morbidity and mortality. Hemoadsorption (HA) of cytokines may suppress inflammatory responses and improve outcomes. We tested a new sorbent used for HA (CytoSorb™; CytoSorbents Europe GmbH, Berlin, Germany) installed in the CPB circuit on changes of pro- and anti-inflammatory cytokines levels, inflammation markers, and differences in patients' perioperative course.
  
  
  METHODS
  In this first pilot trial, 37 blinded patients were undergoing elective CPB surgery at the Medical University of Vienna and were randomly assigned to HA (n = 19) or control group (n = 18). The primary outcome was differences of cytokine levels (IL-1β, IL-6, IL-18, TNF-α, and IL-10) within the first five postoperative days. We also analyzed whether we can observe any differences in ex vivo lipopolysaccharide (LPS)-induced TNF-α production, a reduction of high-mobility box group 1 (HMGB1), or other inflammatory markers. Additionally, measurements for fluid components, blood products, catecholamine treatment, bioelectrical impedance analysis (BIA), and 30-day mortality were analyzed.
  
  
  RESULTS
  We did not find differences in our primary outcome immediately following the HA treatment, although we observed differences for IL-10 24 hours after CPB (HA: median 0.3, interquartile range (IQR) 0-4.5; control: not traceable, P = 0.0347) and 48 hours after CPB (median 0, IQR 0-1.2 versus not traceable, P = 0.0185). We did not find any differences for IL-6 between both groups, and other cytokines were rarely expressed. We found differences in pretreatment levels of HMGB1 (HA: median 0, IQR 0-28.1; control: median 48.6, IQR 12.7-597.3, P = 0.02083) but no significant changes to post-treatment levels. No differences in inflammatory markers, fluid administration, blood substitution, catecholamines, BIA, or 30-day mortality were found.
  
  
  CONCLUSIONS
  We did not find any reduction of the pro-inflammatory response in our patients and therefore no changes in their perioperative course. However, IL-10 showed a longer-lasting anti-inflammatory effect. The clinical impact of prolonged IL-10 needs further evaluation. We also observed strong inter-individual differences in cytokine levels; therefore, patients with an exaggerated inflammatory response to CPB need to be identified. The implementation of HA during CPB was feasible.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01879176, registration date: June 7, 2013.
authors.affiliation: Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria. martin.bernardi@meduniwien.ac.at.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Bernardi
authors.affiliation: Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Rinoesl
authors.affiliation: Department of Surgery, Research Laboratories, Medical University of Vienna, Lazarettgasse 14, A-1090, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dragosits
authors.affiliation: Centre for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Spitalgasse 23, A-1090, Vienna, Austria.
authors.forename: Robin
authors.initials: R
authors.lastname: Ristl
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hoffelner
authors.affiliation: Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Opfermann
authors.affiliation: Department of Surgery, Research Laboratories, Medical University of Vienna, Lazarettgasse 14, A-1090, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Lamm
authors.affiliation: Department of Surgery, Research Laboratories, Medical University of Vienna, Lazarettgasse 14, A-1090, Vienna, Austria.
authors.forename: Falk
authors.initials: F
authors.lastname: Preißing
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wiedemann
authors.affiliation: Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hiesmayr
authors.affiliation: Department of Surgery, Research Laboratories, Medical University of Vienna, Lazarettgasse 14, A-1090, Vienna, Austria.|Core Facilities, Core Facility Flow Cytometry, Medical University of Vienna, Lazarettgasse 14, 1090, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
mesh_terms: D000327:Adsorption / Q000276:immunology*; D001604:Berlin; D015415:Biomarkers / Q000097:blood*; D002315:Cardiopulmonary Bypass / Q000379:methods* / Q000706:statistics & numerical data; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D020382:Interleukin-18; D015850:Interleukin-6; D016753:Interleukin-10
keywords: Cardiac surgery; Cardiopulmonary bypass; CytoSorb; Cytokine storm; Cytokines; Hemadsorption; High-mobility box group 1; Inflammation; Interleukin