title: Mild induced hypothermia: effects on sepsis-related coagulopathy--results from a randomized controlled trial.
abstract: BACKGROUND
  Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy.
  
  
  METHODS
  Interim analysis data from an ongoing randomized controlled trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature).
  
  
  BACKGROUND
  NCT01455116. Thrombelastography (TEG) is performed three times during the first day after study enrollment in all patients. Reaction time (R), maximum amplitude (MA) and patients' characteristics are here reported.
  
  
  RESULTS
  One hundred patients (control n=50 and intervention n=50; male n=59; median age 68years) with complete TEG during follow-up were included. At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients with hypocoagulation (correlation between ΔR and initial R: rho=-0.60, p<0.0001 and correlation between ΔMA and initial MA: rho=-0.50, p=0.0002). Similar results were not observed in the control group neither for R (rho=-0.03, p=0.8247) nor MA (rho=-0.15, p=0.3115).
  
  
  CONCLUSIONS
  Mild induced hypothermia did seem to improve functional coagulopathy in septic patients. This improvement of functional coagulopathy parameters during the hypothermia intervention persisted after rewarming. Randomized trials are warranted to determine whether the positive effect on sepsis-related coagulopathy can be transformed to improved survival.
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Reumathology, Rigshospitalet,University of Copenhagen, Copenhagen, Denmark. Electronic address: Maria.Egede.Johansen@regionh.dk.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansen
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Reumathology, Rigshospitalet,University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens-Ulrik
authors.initials: JU
authors.lastname: Jensen
authors.affiliation: Department of Anesthesia and Intensive Care, Nordsjaellands hospital, Denmark.
authors.forename: Morten H
authors.initials: MH
authors.lastname: Bestle
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Denmark.
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.affiliation: Department of Anesthesia and Intensive Care, Bispebjerg Hospital, Denmark.
authors.forename: Katrin
authors.initials: K
authors.lastname: Thormar
authors.affiliation: Department of Anesthesia and Intensive Care, University Hospital Herlev, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Christensen
authors.affiliation: Department of Anesthesia and Intensive Care, University Hospital Roskilde, Denmark.
authors.forename: Henrik Planck
authors.initials: HP
authors.lastname: Pedersen
authors.affiliation: Department of Anesthesia and Intensive Care, University Hospital Køge, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Poulsen
authors.affiliation: Department of Anesthesia and Intensive Care, University Hospital Gentofte, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mohr
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Reumathology, Rigshospitalet,University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjær
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Reumathology, Rigshospitalet,University of Copenhagen, Copenhagen, Denmark; Department of Virology, Royal Free and University College Medical School London, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Neurointensive Care Unit 2093, Department of Neuroanaesthesiology, University Hospital Rigshospitalet, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Denmark.
authors.forename: Else
authors.initials: E
authors.lastname: Tønnesen
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Reumathology, Rigshospitalet,University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Denmark; Department of Surgery, University of Texas Medical School at Houston, TX, USA.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
mesh_terms: D000368:Aged; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000628:therapy*; D004548:Elasticity; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000503:physiopathology* / Q000628:therapy*; D012772:Shock, Septic / Q000503:physiopathology; D013696:Temperature; D013916:Thrombelastography; D019851:Thrombophilia / Q000628:therapy*; D016896:Treatment Outcome; D014783:Viscosity
keywords: Coagulopathy; Mild induced hypothermia; Randomized controlled trial; Sepsis; Thrombelastography