title: Association between sympathoadrenal activation, fibrinolysis, and endothelial damage in septic patients: a prospective study.
abstract: OBJECTIVE
  The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and coagulopathy in septic patients.
  
  
  METHODS
  Septic patients included in the Scandinavian Starch for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation and damage, natural anticoagulation, fibrinolysis, cell damage, and platelet activation.
  
  
  RESULTS
  Sixty-seven patients were included, of whom 14 turned out to receive noradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5-fold higher than patients not receiving catecholamines (n=53), whereas no other baseline preintervention biomarkers differed. In the 53 patients not receiving catecholamines at blood sampling, endogenous p-noradrenaline correlated positively with adrenaline, syndecan 1, soluble vascular endothelial growth factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all P<.05) and was independently associated with syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all P<.05), and 28- and 90-day mortality (P<.05).
  
  
  CONCLUSIONS
  In septic patients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarction patients. The catecholamine surge in critical illness may contribute to balance endothelial damage and procoagulation with hypocoagulability and hyperfibrinolysis in the circulating blood.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Surgery, Division of Acute Care Surgery, Centre for Translational Injury Research (CeTIR), University of Texas Medical School at Houston, TX, USA. Electronic address: per.johansson@regionh.dk.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Haase
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Perner
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D002395:Catecholamines / Q000008:administration & dosage*; D004730:Endothelium, Vascular; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage* / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D012769:Shock; D053667:Syndecans / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D002395:Catecholamines; D017395:Plasminogen Activator Inhibitor 1; D053667:Syndecans; D042461:Vascular Endothelial Growth Factor A; D023201:CD40 Ligand; D040281:Vascular Endothelial Growth Factor Receptor-1; D010959:Tissue Plasminogen Activator; D009638:Norepinephrine
keywords: Catecholamines; Coagulopathy; Endothelium; Sepsis; Sympathoadrenal activation