Vol 4, No 2 (2019)
Review paper
Published online: 2019-08-06

open access

Page views 820
Article views/downloads 653
Get Citation

Connect on Social Media

Connect on Social Media

Targeted temperature management: State of the Art

Lukasz Szarpak1, Jacek Smereka2, Kurt Ruetzler3
Disaster Emerg Med J 2019;4(2):68-73.


One of the indicated elements of post-resuscitation care is therapeutic hypothermia or temperature treatment management. the survivability of out-of-hospital cardiac arrest (OHCA) till admission to hospital is only 23%. Efficient thermoregulatory mechanisms are the basis for maintaining optimal body temperature. Therapeutic hypothermia shows normalizing effect on metabolic processes disturbed in ischaemic conditions, including improving metabolism and maintaining glucose balance in the brain, lowering the concentration of lactates, limiting the secretion of free radicals in damaged neurons, lowering the production of pro-inflammatory cytokines, stabilizes the blood-brain barrier and reduces endothelial dysfunction preventing ischaemic damage to tissues and organs. Hypothermia has a wide multidirectional effect on the human body, which can be useful in patients. Most available scientific studies show the efficacy and benefits of hypothermia in patients with out-of-hospital sudden cardiac arrest, including especially with ventricular fibrillation. The delay in the initiation of therapeutic hypothermia and reaching target temperature significantly increased the odds of a poor neurological outcome. Current American Heart Association (AHA) and European Resuscitation Council (ERC) resuscitation guidelines recommend that targeted temperature management should be implemented in all adult coma patients with return of spontaneous circulation (ROCS) after sudden cardiac arrest. The target temperature should be between 32°C and 36°C and then maintained for at least 24 hours. In patients with coma after TTM, fever should be actively prevented. For patients with out-of-hospital cardiac arrest, it is not recommended to routinely cool patients in prehospital conditions with a rapid intravenous infusion of cold fluids after ROSC.

Article available in PDF format

View PDF Download PDF file


  1. Lippert FK, Raffay V, Georgiou M, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 10. The ethics of resuscitation and end-of-life decisions. Resuscitation. 2010; 81(10): 1445–1451.
  2. Sasson C, Rogers MAM, Dahl J, et al. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010; 3(1): 63–81.
  3. Peberdy MA, Callaway CW, Neumar RW, et al. American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010; 122(18 Suppl 3): S768–S786.
  4. Gagge AP, Fobelets AP, Berglund LG. A standard predictive index of human response to the thermal environment. ASHARE Trans. 1986; 92: 709–711.
  5. Luo Y, Sun W, Feng X, et al. (-)-menthol increases excitatory transmission by activating both TRPM8 and TRPA1 channels in mouse spinal lamina II layer. Biochem Biophys Res Commun. 2019; 516(3): 825–830.
  6. Blanquart S, Borowiec AS, Delcourt P, et al. Evolution of the human cold/menthol receptor, TRPM8. Mol Phylogenet Evol. 2019; 136: 104–118.
  7. Ordás P, Hernández-Ortego P, Vara H, et al. Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits. J Comp Neurol. 2019 [Epub ahead of print].
  8. Xu X, Tikuisis P. Thermoregulatory modeling for cold stress. Compr Physiol. 2014; 4(3): 1057–1081.
  9. Noël J, Zimmermann K, Busserolles J, et al. The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. EMBO J. 2009; 28(9): 1308–1318.
  10. Stebe S, Schellig K, Lesage F, et al. The thermosensitive potassium channel TREK-1 contributes to coolness-evoked responses of Grueneberg ganglion neurons. Cell Mol Neurobiol. 2014; 34(1): 113–122.
  11. Reimúndez A, Fernández-Peña C, García G, et al. Deletion of the Cold Thermoreceptor TRPM8 Increases Heat Loss and Food Intake Leading to Reduced Body Temperature and Obesity in Mice. J Neurosci. 2018; 38(15): 3643–3656.
  12. Romanovsky AA. The thermoregulation system and how it works. Handb Clin Neurol. 2018; 156: 3–43.
  13. Lenhardt R. Body temperature regulation and anesthesia. Handb Clin Neurol. 2018; 157: 635–644.
  14. Zhang HB, Cheng SX, Tu Y, et al. Protective effect of mild-induced hypothermia against moderate traumatic brain injury in rats involved in necroptotic and apoptotic pathways. Brain Inj. 2017; 31(3): 406–415.
  15. Zhao K, Li R, Bi S, et al. Combination of mild therapeutic hypothermia and adipose-derived stem cells for ischemic brain injury. Neural Regen Res. 2018; 13(10): 1759–1770.
  16. Zhao CC, Wang CF, Li WP, et al. Mild Hypothermia Promotes Pericontusion Neuronal Sprouting via Suppressing Suppressor of Cytokine Signaling 3 Expression after Moderate Traumatic Brain Injury. J Neurotrauma. 2017; 34(8): 1636–1644.
  17. Torres M, Zúñiga R, Gutierrez M, et al. Mild hypothermia upregulates myc and xbp1s expression and improves anti-TNFα production in CHO cells. PLoS One. 2018; 13(3): e0194510.
  18. Guillot X, Martin H, Seguin-Py S, et al. Local cryotherapy improves adjuvant-induced arthritis through down-regulation of IL-6 / IL-17 pathway but independently of TNFα. PLoS One. 2017; 12(7): e0178668.
  19. Shaikh H, Boudes E, Khoja Z, et al. Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia. PLoS One. 2015; 10(5): e0128028.
  20. Shaikh H, Lechpammer M, Jensen FE, et al. Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis? Transl Stroke Res. 2015; 6(3): 224–233.
  21. Yenari MA, Han HS. Influence of therapeutic hypothermia on regeneration after cerebral ischemia. Front Neurol Neurosci. 2013; 32: 122–128.
  22. Xie YC, Li CY, Li T, et al. Effect of mild hypothermia on angiogenesis in rats with focal cerebral ischemia. Neurosci Lett. 2007; 422(2): 87–90.
  23. Ikonomidou C, Kirvassilis G, Swiney BS, et al. Mild hypothermia ameliorates anesthesia toxicity in the neonatal macaque brain. Neurobiol Dis. 2019 [Epub ahead of print]; 130: 104489.
  24. Huun MU, Garberg H, Løberg EM, et al. DHA and therapeutic hypothermia in a short-term follow-up piglet model of hypoxia-ischemia: Effects on H+MRS biomarkers. PLoS One. 2018; 13(8): e0201895.
  25. Wang CF, Zhao CC, He Yi, et al. Mild hypothermia reduces endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after severe traumatic brain injury. Brain Behav. 2019; 9(4): e01248.
  26. Yu H, Wang L, Zhang H, et al. Effect of mild hypothermia on cerebral microcirculation in a murine cardiopulmonary resuscitation model. Microcirculation. 2019 [Epub ahead of print].
  27. BENSON DW, WILLIAMS GR, SPENCER FC, et al. The use of hypothermia after cardiac arrest. Anesth Analg. 1959; 38: 423–428.
  28. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002; 346(8): 557–563.
  29. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002; 346(8): 549–556.
  30. Storm C, Steffen I, Schefold JC, et al. Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls. Crit Care. 2008; 12(3): R78.
  31. Storm C, Nee J, Krueger A, et al. 2-year survival of patients undergoing mild hypothermia treatment after ventricular fibrillation cardiac arrest is significantly improved compared to historical controls. Scand J Trauma Resusc Emerg Med. 2010; 18: 2.
  32. Storm C, Nee J, Roser M, et al. Mild hypothermia treatment in patients resuscitated from non-shockable cardiac arrest. Emerg Med J. 2012; 29(2): 100–103.
  33. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med. 2013; 369(23): 2197–2206.
  34. Arrich J. European Resuscitation Council Hypothermia After Cardiac Arrest Registry Study Group. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007; 35(4): 1041–1047.
  35. Maze R, Le May MR, Froeschl M, et al. CArdiovascular Percutaneous Intervention TriAL (CAPITAL) investigators. Endovascular cooling catheter related thrombosis in patients undergoing therapeutic hypothermia for out of hospital cardiac arrest. Resuscitation. 2014; 85(10): 1354–1358.
  36. Mooney MR, Unger BT, Boland LL, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling. Circulation. 2011; 124(2): 206–214.
  37. Sendelbach S, Hearst MO, Johnson PJo, et al. Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation. 2012; 83(7): 829–834.
  38. Pittl U, Schratter A, Desch S, et al. Invasive versus non-invasive cooling after in- and out-of-hospital cardiac arrest: a randomized trial. Clin Res Cardiol. 2013; 102(8): 607–614.

Disaster and Emergency Medicine Journal