Mild Therapeutic Hypothermia after Cardiac Arrest

  • T. Pellis
  • V. Mione
  • W. P. Mercante
Conference paper


Cardiovascular disease is the world’s leading cause of death. Such deaths are often caused by sudden cardiac arrest, and the estimated number of out-of-hospital cardiac arrest cases is 300,000 per year in the United States, where median rate of survival to hospital discharge is 7.9% [1]. Favourable outcome of patients admitted to the hospital ranges between 11% and 48% [2, 3], indicating a large number of patients die after successful resuscitation during hospital stay or develop permanent severe brain damage. The only therapy that has been shown to improve survival and neurological outcome after sudden cardiac arrest is induction of mild therapeutic hypothermia for 12–24 h [4, 5].


Percutaneous Coronary Intervention Cardiac Arrest Ventricular Fibrillation Therapeutic Hypothermia Mild Hypothermia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Lloyd-Jones D, Adams R, Carnethon M et al (2009) Heart disease and stroke statistics — 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3):480–486PubMedCrossRefGoogle Scholar
  2. 2.
    de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI et al (1997) Out-of-hospital cardiac arrest in the 1990’s: a population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol 30(6):1500–1505PubMedCrossRefGoogle Scholar
  3. 3.
    Becker LB, Smith DW, Rhodes KV (1993) Incidence of cardiac arrest: a neglected factor in evaluating survival rates. Ann Emerg Med 22(1):86–91PubMedCrossRefGoogle Scholar
  4. 4.
    Hypothermia After Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346(8):549-556Google Scholar
  5. 5.
    Bernard SA, Gray TW, Buist MD, Jones BM et al (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346(8):557–563PubMedCrossRefGoogle Scholar
  6. 6.
    Abella BS, Rhee JW, Huang KN et al (2005) Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey. Resuscitation 64(2):181–186PubMedCrossRefGoogle Scholar
  7. 7.
    Merchant RM, Soar J, Skrifvars MB et al (2006) Therapeutic hypothermia utilization among physicians after resuscitation from cardiac arrest. Crit Care Med 34(7):1935–1940PubMedCrossRefGoogle Scholar
  8. 8.
    Rosomoff HL, Holaday DA (1954) Cerebral blood flow and cerebral oxygen consumption during hypothermia. Am J Physiol 179(1):85–88PubMedGoogle Scholar
  9. 9.
    Lanier WL (1995) Cerebral metabolic rate and hypothermia: their relationship with ischaemic neurologic injury. J Neurosurg Anesthesiol 7(3):216–221PubMedCrossRefGoogle Scholar
  10. 10.
    Busto R, Globus MY, Dietrich WD et al (1989) Effect of mild hypothermia on ischaemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 20(7):904–910PubMedCrossRefGoogle Scholar
  11. 11.
    Siesjo BK, Bengtsson F, Grampp W et al (1989) Calcium, excitotoxins, and neuronal death in the brain. Ann N Y Acad Sci 568:234–251PubMedCrossRefGoogle Scholar
  12. 12.
    Illievich UM, Zornow MH, Choi KT et al (1994) Effects of hypothermic metabolic suppression on hippocampal glutamate concentrations after transient global cerebral ischaemia. Anesth Analg 78(5):905–911PubMedCrossRefGoogle Scholar
  13. 13.
    Hachimi-Idrissi S, Van Hemelrijck A, Michotte A et al (2004) Postischaemic mild hypothermia reduces neurotransmitter release and astroglial cell proliferation during reperfusion after asphyxial cardiac arrest in rats. Brain Res 1019(1-2):217–225PubMedCrossRefGoogle Scholar
  14. 14.
    Vosler PS, Logue ES, Repine MJ et al (2005) Delayed hypothermia preferentially increases expression of brain-derived neurotrophic factor exon III in rat hippocampus after asphyxial cardiac arrest. Brain Res Mol Brain Res 135(1–2):21–29PubMedCrossRefGoogle Scholar
  15. 15.
    Berger C, Schabitz WR, Wolf M et al (2004) Hypothermia and brain-derived neurotrophic factor reduce glutamate synergistically in acute stroke. Exp Neurol 185(2):305–312PubMedCrossRefGoogle Scholar
  16. 16.
    Globus MY, Busto R, Lin B et al (1995) Detection of free radical activity during transient global ischaemia and recirculation: effects of intraischaemic brain temperature modulation. J Neurochem 65(3):1250–1256PubMedCrossRefGoogle Scholar
  17. 17.
    Horiguchi T, Shimizu K, Ogino M et al (2003) Postischaemic hypothermia inhibits the generation of hydroxyl radical following transient forebrain ischaemia in rats. J Neurotrauma 20(5):511–520PubMedCrossRefGoogle Scholar
  18. 18.
    Maier CM, Sun GH, Cheng D et al (2002) Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischaemia. Neurobiol Dis 11(1):28–42PubMedCrossRefGoogle Scholar
  19. 19.
    Lei B, Tan X, Cai H et al (1994) Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation. Stroke 25(1):147–152PubMedCrossRefGoogle Scholar
  20. 20.
    Wang GJ, Deng HY, Maier CM et al (2002) Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke. Neuroscience 114(4):1081–1090PubMedGoogle Scholar
  21. 21.
    Akriotis V, Biggar WD (1985) The effects of hypothermia on neutrophil function in vitro. J Leukoc Biol 37(1):51–61PubMedGoogle Scholar
  22. 22.
    Dempsey RJ, Combs DJ, Maley ME et al (1987) Moderate hypothermia reduces postischaemic edema development and leukotriene production. Neurosurgery 21(2):177–181PubMedCrossRefGoogle Scholar
  23. 23.
    Xu L, Yenari MA, Steinberg GK et al (2002) Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 22(1):21–28PubMedCrossRefGoogle Scholar
  24. 24.
    Zhao H, Yenari MA, Cheng D et al (2005) Biphasic cytochrome c release after transient global ischaemia and its inhibition by hypothermia. J Cereb Blood Flow Metab 25(9):1119–1129PubMedCrossRefGoogle Scholar
  25. 25.
    Fukuda H, Tomimatsu T, Watanabe N et al (2001) Post-ischaemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia-ischaemia. Brain Res 910(1–2):187–191PubMedCrossRefGoogle Scholar
  26. 26.
    Eberspacher E, Werner C, Engelhard K et al (2005) Long-term effects of hypothermia on neuronal cell death and the concentration of apoptotic proteins after incomplete cerebral ischaemia and reperfusion in rats. Acta Anaesthesiol Scand 49(4):477–487PubMedCrossRefGoogle Scholar
  27. 27.
    Bernard SA, Jones BM, Horne MK (1997) Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 30(2):146–153PubMedCrossRefGoogle Scholar
  28. 28.
    Yanagawa Y, Ishihara S, Norio H et al (1998) Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest. Resuscitation 39(1–2):61–66PubMedCrossRefGoogle Scholar
  29. 29.
    Nagao K, Hayashi N, Kanmatsuse K et al (2000) Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital. J Am Coll Cardiol 36(3):776–783PubMedCrossRefGoogle Scholar
  30. 30.
    Zeiner A, Holzer M, Sterz F et al (2000) Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group. Stroke 31(1):86–94PubMedCrossRefGoogle Scholar
  31. 31.
    International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations (2005) Part 4: Advanced life support. Resuscitation 67 (2–3):213-247Google Scholar
  32. 32.
    Nolan J (2005) European Resuscitation Council Guidelines for Resuscitation 2005. Sect. 1. Introduction. Resuscitation 67(Suppl1):S3–S6PubMedCrossRefGoogle Scholar
  33. 33.
    Arrich J (2007) Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med 35(4):1041–1047PubMedCrossRefGoogle Scholar
  34. 34.
    Knafelj R, Radsel P, Ploj T et al (2007) Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation 74(2):227–234PubMedCrossRefGoogle Scholar
  35. 35.
    Wolfrum S, Pierau C, Radke PW et al (2008) Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention. Crit Care Med 36(6):1780–1786PubMedCrossRefGoogle Scholar
  36. 36.
    Holzer M, Mullner M, Sterz F et al (2006) Efficacy and safety of endovascular cooling after cardiac arrest: cohort study and Bayesian approach. Stroke 37(7):1792–1797PubMedCrossRefGoogle Scholar
  37. 37.
    Oddo M, Schaller MD, Feihl F et al (2006) From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 34(7):1865–1873PubMedGoogle Scholar
  38. 38.
    Holzer M, Bernard SA, Hachimi-Idrissi S et al (2005) Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis. Crit Care Med 33(2):414–418PubMedCrossRefGoogle Scholar
  39. 39.
    Watts DD, Trask A, Soeken K et al (1998) Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity. J Trauma 44(5):846–854PubMedCrossRefGoogle Scholar
  40. 40.
    Kettner SC, Sitzwohl C, Zimpfer M et al (2003) The effect of graded hypothermia (36 degrees C-32 degrees C) on hemostasis in anesthetized patients without surgical trauma. Anesth Analg 96(6):1772–1776PubMedCrossRefGoogle Scholar
  41. 41.
    Michelson AD, MacGregor H, Barnard MR et al (1994) Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro. Thromb Haemost 71(5):633–640PubMedGoogle Scholar
  42. 42.
    Högberg C, Erlinge D, Braun OO (2009) Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment. Thromb J 7:2PubMedCrossRefGoogle Scholar
  43. 43.
    Spiel AO, Frossard M, Mayr FB et al (2009) Pronounced platelet hyperfunction in patients with cardiac arrest achieving restoration of spontaneous circulation. Crit Care Med 37(3):975–979PubMedCrossRefGoogle Scholar
  44. 44.
    Tiainen M, Parikka HJ, Makijarvi MA et al (2009) Arrhythmias and heart rate variability during and after therapeutic hypothermia for cardiac arrest. Crit Care Med 37(2):403–409PubMedCrossRefGoogle Scholar
  45. 45.
    Skulec R, Kovarnik T, Dostalova G et al (2008) Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome. Acta Anaesthesiol Scand 52(2):188–194PubMedCrossRefGoogle Scholar
  46. 46.
    Hovdenes J, Laake JH, Aaberge L et al (2007) Therapeutic hypothermia after outof-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand 51(2):137–142PubMedCrossRefGoogle Scholar
  47. 47.
    Tortorici MA, Kochanek PM, Poloyac SM (2007) Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med 35(9):2196–2204PubMedCrossRefGoogle Scholar
  48. 48.
    Fukuoka N, Aibiki M, Tsukamoto T et al (2004) Biphasic concentration change during continuous midazolam administration in brain-injured patients undergoing therapeutic moderate hypothermia. Resuscitation 60(2):225–230PubMedCrossRefGoogle Scholar
  49. 49.
    Koren G, Goresky G, Crean P et al (1984) Pediatric fentanyl dosing based on pharmacokinetics during cardiac surgery. Anesth Analg 63(6):577–582PubMedCrossRefGoogle Scholar
  50. 50.
    Leslie K, Sessler DI, Bjorksten AR et al (1995) Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. Anesth Analg 80(5):1007–1014PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2011

Authors and Affiliations

  • T. Pellis
  • V. Mione
  • W. P. Mercante

There are no affiliations available

Personalised recommendations