title: Thromboelastography in patients with severe sepsis: a prospective cohort study.
abstract: OBJECTIVE
  To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis.
  
  
  METHODS
  Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox regression with time-dependent covariates and joint modelling techniques.
  
  
  RESULTS
  Of 267 eligible patients, we analysed 260 patients with TEG data. At 90 days, 68 (26 %) had bled and 139 (53 %) had died. For all TEG variables, hypocoagulability according to the reference range was significantly associated with increased risk of death. In a linear model, hazard ratios for death were 6.03 (95 % confidence interval, 1.64-22.17) for increased clot formation speed, 1.10 (1.04-1.16) for decreased angle, 1.09 (1.05-1.14) for decreased clot strength and 1.12 (1.06-1.18) for decreased fibrinogen contribution to clot strength (functional fibrinogen MA), showing that deterioration towards hypocoagulability in any TEG variable significantly increased the risk of death. Patients treated with HES had lower functional fibrinogen MA than those treated Ringer's acetate, which significantly increased the risk of subsequent bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial.
  
  
  CONCLUSIONS
  In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding.
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark, nicolai.rosenkrantz.segelcke.haase@regionh.dk.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Haase
authors.forename: Sisse Rye
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.forename: Theis
authors.initials: T
authors.lastname: Lange
authors.forename: Morten Hylander
authors.initials: MH
authors.lastname: Møller
authors.forename: Hamid
authors.initials: H
authors.lastname: Tousi
authors.forename: Morten
authors.initials: M
authors.lastname: Steensen
authors.forename: Frank
authors.initials: F
authors.lastname: Pott
authors.forename: Peter
authors.initials: P
authors.lastname: Søe-Jensen
authors.forename: Jonas
authors.initials: J
authors.lastname: Nielsen
authors.forename: Peter Buhl
authors.initials: PB
authors.lastname: Hjortrup
authors.forename: Pär Ingemar
authors.initials: PI
authors.lastname: Johansson
authors.forename: Anders
authors.initials: A
authors.lastname: Perner
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001778:Blood Coagulation Disorders / Q000175:diagnosis / Q000209:etiology; D018450:Disease Progression; D005440:Fluid Therapy; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use; D010952:Plasma Substitutes / Q000627:therapeutic use; D011446:Prospective Studies; D012151:Resuscitation / Q000379:methods; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000628:therapy; D013916:Thrombelastography; D016032:Randomized Controlled Trials as Topic; D017326:Clinical Trials, Phase III as Topic
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes