title: Markers of endothelial damage and coagulation impairment in patients with severe sepsis resuscitated with hydroxyethyl starch 130/0.42 vs Ringer acetate.
abstract: OBJECTIVE
  The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased mortality in patients resuscitated with hydroxyethyl starch 130/0.42 (HES) vs Ringer acetate. Different effects of the fluids on the endothelium may have contributed to the observed outcome. We aimed to investigate associations between HES vs Ringer and changes in plasma biomarkers reflecting endothelial damage and coagulation impairment.
  
  
  METHODS
  Six biomarkers, including soluble thrombomodulin (sTM) and plasminogen activator inhibitor 1 (PAI-1), were assessed in a subgroup of 208 patients from the 6S trial. We analyzed differences in plasma concentration in the 2 intervention groups using linear or logistic regression models.
  
  
  RESULTS
  The increase in plasma sTM was lower in the HES group (-1.8 ng/mL; 95% confidence interval, -2.9 to -0.7; P = .002). The change was not statistically significant associated with mortality whereas increase in plasminogen activator inhibitor 1 was (odds ratio for 1-unit increase, 1.04; 95% confidence interval, 1.01-1.08; P = .01).
  
  
  CONCLUSIONS
  Resuscitation with HES vs Ringer decreased early endothelial damage. Although this finding should be interpreted with caution, it indicates that the increased mortality observed with HES in the 6S trial may not be explained by endothelial damage and it emphasizes the challenge of using surrogate markers as outcome.
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark. Electronic address: rasmus.muller@regionh.dk.
authors.forename: Rasmus Beier
authors.initials: RB
authors.lastname: Müller
authors.affiliation: Section for Transfusion Medicine, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Sisse Rye
authors.initials: SR
authors.lastname: Ostrowski
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Haase
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital-Rigshospitalet DK-2100 Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Perner
authors.affiliation: Section for Transfusion Medicine, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark; Department of Surgery, University of Texas Health Medical School, Houston, TX 77030.
authors.forename: Pär Ingemar
authors.initials: PI
authors.lastname: Johansson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000009:adverse effects*; D007552:Isotonic Solutions / Q000008:administration & dosage / Q000009:adverse effects*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010952:Plasma Substitutes / Q000008:administration & dosage / Q000009:adverse effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012151:Resuscitation / Q000379:methods / Q000401:mortality; D018805:Sepsis / Q000097:blood / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D018180:Thrombomodulin / Q000097:blood; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D017395:Plasminogen Activator Inhibitor 1; C028570:Ringer's acetate; C051321:SERPINE1 protein, human; C546931:THBD protein, human; D018180:Thrombomodulin
keywords: Colloids; Endothelial damage; Hydroxyethyl starch; Resuscitation; Severe sepsis