Mild induced hypothermia: Effects on sepsis-related coagulopathy -results from a randomized controlled trial

TY - JOUR

T1 - Mild induced hypothermia

T2 - Effects on sepsis-related coagulopathy -results from a randomized controlled trial

AU - Johansen, Maria Egede

AU - Jensen, Jens Ulrik Stæhr

AU - Bestle, Morten H

AU - Ostrowski, Sisse R

AU - Thormar, Katrin

AU - Christensen, Henrik

AU - Pedersen, Henrik Planck

AU - Poulsen, Lone

AU - Mohr, Thomas

AU - Kjær, Jesper

AU - Cozzi-Lepri, Alessandro

AU - Møller, Kirsten

AU - Tønnesen, Else

AU - Lundgren, Jens D

AU - Johansson, Pär I

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Introduction 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. Materials and 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 24 hours) or control (uncontrolled temperature). Trial registration: 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 68 years) 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). Conclusion 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.

AB - Introduction 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. Materials and 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 24 hours) or control (uncontrolled temperature). Trial registration: 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 68 years) 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). Conclusion 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.

KW - Aged

KW - Blood Coagulation

KW - Blood Coagulation Disorders

KW - Elasticity

KW - Female

KW - Humans

KW - Hypothermia, Induced

KW - Male

KW - Middle Aged

KW - Sepsis

KW - Shock, Septic

KW - Temperature

KW - Thrombelastography

KW - Thrombophilia

KW - Treatment Outcome

KW - Viscosity

U2 - 10.1016/j.thromres.2014.10.028

DO - 10.1016/j.thromres.2014.10.028

M3 - Journal article

C2 - 25466837

SN - 0049-3848

VL - 135

SP - 175

EP - 182

JO - Thrombosis Research

JF - Thrombosis Research

IS - 1

ER -