Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: Indications and evidence

Abstract

Objective

Hypothermia has been used for medicinal purposes since ancient times. This paper reviews the current potential clinical applications for mild hypothermia (32–35°C).

Design and setting

Induced hypothermia is used mostly to prevent or attenuate neurological injury, and has been used to provide neuroprotection in traumatic brain injury, cardiopulmonary resuscitation, stroke, and various other disorders. The evidence for each of these applications is discussed, and the mechanisms underlying potential neuroprotective effects are reviewed. Some of this evidence comes from animal models, and a brief overview of these models and their limitations is included in this review.

Results

The duration of cooling and speed of re-warming appear to be key factors in determining whether hypothermia will be effective in preventing or mitigating neurological injury. Some other potential usages of hypothermia, such as its use in the peri-operative setting and its application to mitigate cardiac injury following ischemia and reperfusion, are also discussed.

Conclusions

Although induced hypothermia appears to be a highly promising treatment, it should be emphasized that it is associated with a number of potentially serious side effects, which may negate some or all of its potential benefits. Prevention and/or early treatment of these complications are the key to successful use of hypothermia in clinical practice. These side effects, as well as various physiological changes induced by cooling, are discussed in a separate review.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Hippocrates (460–375 BC). De Vetere Medicina. Translation: Jones WHS, Withington ET. Hippocrates. Loeb Classical Library

  2. 2.

    Celcus AC (1st century AD) De Medicina. Translation: Spencer WG. DE Medicina. Loeb Classical Library

  3. 3.

    Galaenus C (129–199 AD) Opera Omnia (Medicorum Graecorum Opera). Translation: Brock AJ. Galaenus: On the natural faculties

  4. 4.

    Larrey IJ (1814) Memoirs of military service and campaigns of the French armies, vol 2. Cushing, Baltimore, pp 156–164

  5. 5.

    Fay T (1945) Observations on generalized refrigeration in cases of severe cerebral trauma. Assoc Res Nerv Ment Dis Proc 24:611–619

    Google Scholar 

  6. 6.

    Botterell EH, Lougheed WM, Scott JW, Vandewater SL (1956) Hypothermia and interruption of carotid, or carotid and vertebral circulation, in the management of intracranial aneurysms. J Neurosurg 13:1–42

    PubMed  Google Scholar 

  7. 7.

    Botterell EH, Lougheed WM, Morley TP, Vandewater SL (1958) Hypothermia in the surgical treatment of ruptured intracranial aneurysms. J Neurosurg 15:4–18

    CAS  PubMed  Google Scholar 

  8. 8.

    Bigelow WG, Callaghan JC, Hopps JA (1950) General hypothermia for experimental intracardiac surgery. Ann Surg 132:531–537

    Google Scholar 

  9. 9.

    Bigelow WC (1959) Methods for inducing hypothermia and rewarming. Ann NY Acad Sci 80:522–532

    CAS  PubMed  Google Scholar 

  10. 10.

    Rosomoff HL (1959) Protective effects of hypothermia against pathologic processes of the nervous system. Ann NY Acad Sci 80:475–486

    CAS  PubMed  Google Scholar 

  11. 11.

    Rosomoff HL, Clasen RA, Hartstock R, Bebin J (1965) Brain reaction to experimental injury after hypothermia. Arch Neurol13:337–345

    Google Scholar 

  12. 12.

    Rosomoff HL, Safar P (1965) Management of the comatose patient. Clin Anesth 1:244–258

    CAS  PubMed  Google Scholar 

  13. 13.

    Lazorthes G, Campan L (1964) Moderate hypothermia in the treatment of head injuries. Clin Neurosurg 12:293–299

    CAS  PubMed  Google Scholar 

  14. 14.

    Hamby WB (1963) Intracranial surgery for aneurysm: effect of hypothermia upon survival. J Neurosurg 20:41–45

    CAS  PubMed  Google Scholar 

  15. 15.

    Auer RN (2001) Non-pharmacologic (physiologic) neuroprotection in the treatment of brain ischemia. Ann NY Acad Sci 939:271–282

    CAS  PubMed  Google Scholar 

  16. 16.

    Corbett D, Nurse S (1998) The problem of assessing effective neuroprotection in experimental cerebral ischemia. Prog Neurobiol 54:531–548

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Milde LN (1992) Clinical use of mild hypothermia for brain protection: a dream revisited. J Neurosurg Anesthesiol 4:211–215

    CAS  PubMed  Google Scholar 

  18. 18.

    Small DL, Morley P, Buchan AM (1999) Biology of ischemic cerebral cell death. Prog Cardiovasc Dis 42:185–207

    CAS  PubMed  Google Scholar 

  19. 19.

    Siesjo BK (1992) Pathophysiology and treatment of focal cerebral ischemia: I. Pathophysiology. J Neurosurg 77:169–184

    CAS  PubMed  Google Scholar 

  20. 20.

    Hall ED (1999) Free radicals in stroke. In: Miller LP (ed) Stroke therapy: basic, preclinical, and clinical directions, Wiley-Liss, New York, pp 245–270

  21. 21.

    Siesjo BK, Bengtsson F, Grampp W, Theander S (1989) Calcium, excitotoxins, and neuronal death in brain. Ann NY Acad Sci 568:234–251

    CAS  PubMed  Google Scholar 

  22. 22.

    Povlishock JT, Buki A, Koiziumi H, Stone J, Okonkwo DO (1999) Initiating mechanisms involved in the pathobiology of traumatically induced axonal injury and interventions targeted at blunting their progression. Acta Neurochir Suppl (Wien) 73:15–20

    Google Scholar 

  23. 23.

    Xu L, Yenari MA, Steinberg GK, Giffard RG (2002) Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 22:21–28

    Article  PubMed  Google Scholar 

  24. 24.

    Adachi M, Sohma O, Tsuneishi S, Takada S, Nakamura H (2001) Combination effect of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats. Pediatr Res 50:590–595

    CAS  PubMed  Google Scholar 

  25. 25.

    Ning XH, Chen SH, Xu CS, Li L, Yao LY, Qian K, Krueger JJ, Hyyti OM, Portman MA (2002) Hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis. J Appl Physiol 92:2200–2207

    CAS  PubMed  Google Scholar 

  26. 26.

    Auer RN (2001) Non-pharmacologic (physiologic) neuroprotection in the treatment of brain ischemia. Ann NY Acad Sci 939:271–282

    CAS  PubMed  Google Scholar 

  27. 27.

    Busto R, Dietrich WD, Globus MY, Valdes I, Scheinberg P, Ginsberg MD (1987) Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7:729–738

    PubMed  Google Scholar 

  28. 28.

    Winfree CJ, Baker CJ, Connolly ES Jr, Fiore AJ, Solomon RA (1996) Mild hypothermia reduces penumbral glutamate levels in the rat permanent focal cerebral ischemia model. Neurosurgery 38:1216–1222

    CAS  PubMed  Google Scholar 

  29. 29.

    Globus MY-T, Alonso O, Dietrich WD, Busto R, Ginsberg MD (1995) Glutamate release and free radical production following brain injury: effects of post-traumatic hypothermia. J Neurochem 65:1704–1711

    CAS  PubMed  Google Scholar 

  30. 30.

    Baker AJ, Zornow MH, Grafe MR, Scheller MS, Skilling SR, Smullin DH, Larson AA (1991) Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations in rabbits. Stroke 22:666–673

    CAS  PubMed  Google Scholar 

  31. 31.

    Busto R, Globus MY, Dietrich WD, Martinez E, Valdés I, Ginsberg MD (1989) Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 20:904–910

    CAS  PubMed  Google Scholar 

  32. 32.

    Dempsey RJ, Combs DJ, Maley ME, Cowen DE, Roy MW, Donaldson DL (1987) Moderate hypothermia reduces postischemic edema development and leukotriene production. Neurosurgery 21:177–81

    CAS  PubMed  Google Scholar 

  33. 33.

    Kaibara T, Sutherland GR, Colbourne F, Tyson RL (1999) Hypothermia: depression of tricarboxylic acid cycle flux and evidence for pentose phosphate shunt upregulation. J Neurosurg 90:339–347

    CAS  PubMed  Google Scholar 

  34. 34.

    Dietrich WD, Busto R, Globus MY, Ginsberg MD (1996) Brain damage and temperature: cellular and molecular mechanisms. Adv Neurol 71:177–194

    CAS  PubMed  Google Scholar 

  35. 35.

    Globus MY-T, Busto R, Lin B, Schnippering H, Ginsberg MD (1995) Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J Neurochem 65:1250–1256

    PubMed  Google Scholar 

  36. 36.

    Negovsky VA (1988) Postresuscitation disease. Crit Care Med 16:942–946

    CAS  PubMed  Google Scholar 

  37. 37.

    Natale JA, D’Alecy LG (1989) Protection from cerebral ischemia by brain cooling without reduced lactate accumulation in dogs. Stroke 20:770–777

    PubMed  Google Scholar 

  38. 38.

    Kimura A, Sakurada S, Ohkuni H, Todome Y, Kurata K (2002) Moderate hypothermia delays proinflammatory cytokine production of human peripheral blood mononuclear cells. Crit Care Med 30:1499–1502

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Aibiki M, Maekawa S, Ogura S, Kinoshita Y, Kawai N, Yokono S (1999) Effect of moderate hypothermia on systemic and internal jugular plasma IL-6 levels after traumatic brain injury in humans. J Neurotraum 16:225–232

    CAS  Google Scholar 

  40. 40.

    Huang ZG, Xue D, Preston E, Karbalai H, Buchan AM (1999) Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia. Can J Neurol Sci 26:298–304

    CAS  PubMed  Google Scholar 

  41. 41.

    Chi OZ, Liu X, Weiss HR (2001) Effects of mild hypothermia on blood-brain barrier disruption during isoflurane or pentobarbital anesthesia. Anesthesiology 95:933–938

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Jurkovich GJ, Pitt RM, Curreri PW, Granger DN (1988) Hypothermia prevents increased capillary permeability following ischemia-reperfusion injury. J Surg Res 44:514–521

    CAS  PubMed  Google Scholar 

  43. 43.

    Kinoshita K, Chatzipanteli K, Alonso OF, Howard M, Dietrich WD (2002) The effect of brain temperature on hemoglobin extravasation after traumatic brain injry. J Neurosurg 97:945–953

    PubMed  Google Scholar 

  44. 44.

    Ghajar J (2000) Traumatic brain injury. Lancet 356:923–929

    CAS  PubMed  Google Scholar 

  45. 45.

    Reinert MM, Bullock R (1999) Clinical trials in head injury. Neurol Res 21:330–338

    CAS  PubMed  Google Scholar 

  46. 46.

    Morimoto Y, Kemmotsu O, Kitami K, Matsubara I, Tedo I (1993) Acute brain swelling after out-of-hospital cardiac arrest: pathogenesis and outcome. Crit Care Med 21:104–110

    CAS  PubMed  Google Scholar 

  47. 47.

    Fischer S, Renz D, Wiesnet M, Schaper W, Karliczek GF (1999) Hypothermia abolishes hypoxia-induced hyperpermeability in brain microvessel endothelial cells. Brain Res Mol Brain Res 74:135–144

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Ding D, Moskowitz SI, Li R, Lee SB, Esteban M, Tomaselli K, Chan J, Bergold PJ (2000) Acidosis induces necrosis and apoptosis of cultured hippocampal neurons. Exp Neurol 162:1–12

    Article  CAS  PubMed  Google Scholar 

  49. 49.

    Chopp M, Knight R, Tidwell CD, Helpern JA, Brown E, Welch KM (1989) The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia. J Cereb Blood Flow Metab 9:141–148

    PubMed  Google Scholar 

  50. 50.

    Hayashi N, Hirayama T, Udagawa A, Daimon W, Ohata M (1994) Systemic management of cerebral edema based on a new concept in severe head injury patients. Acta Neurochir Suppl (Wien) 60:541–543

    Google Scholar 

  51. 51.

    Mellergard P, Nordstrom CH (1991) Intracerebral temperature in neurosurgical patients. Neurosurgery 28:709–713

    CAS  PubMed  Google Scholar 

  52. 52.

    Schwab S, Spranger M, Aschhoff A, Steiner T, Hacke W (1997) Brain temperature monitoring and modulation in patients with severe MCA infarction. Neurology 48:762–767

    CAS  PubMed  Google Scholar 

  53. 53.

    Verlooy J, Heytens L, Veeckmans G, Selosse P (1995) Intracerebral temperature monitoring in severely head injured patients. Acta Neurochir (Wien) 134:76–8

    Google Scholar 

  54. 54.

    Kilpatrick MM, Lowry DW, Firlik AD, Yonas H, Marion DW (2000) Uncontrolled hyperthermia in the neurosurgical intensive care unit. Neurosurgery 47:850–855

    CAS  PubMed  Google Scholar 

  55. 55.

    Lanier WL (1995) Cerebral metabolic rate and hypothermia: their relationship with ischemic neurologic injury. J Neurosurg Anesthesiol 7:216–221

    CAS  PubMed  Google Scholar 

  56. 56.

    Soukup J, Zauner A, Doppenberg EM, Menzel M, Gilman C, Bullock R, Young HF (2002) Relationship between brain temperature, brain chemistry and oxygen delivery after severe human head injury: the effect of mild hypothermia. Neurol Res 24:161–168

    CAS  PubMed  Google Scholar 

  57. 57.

    Kimura T, Sako K, Tanaka K, Kusakabe M, Tanaka T, Nakada T (2002) Effect of mild hypothermia on energy state recovery following transient forebrain ischemia in the gerbil. Exp Brain Res 145:83–90

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Eisenberg MS, Horwood BT, Cummins RO, Reynolds-Haertle R, Hearne TR (1990) Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 19:179–186

    CAS  PubMed  Google Scholar 

  59. 59.

    Bernard SA (1998) Outcome from prehospital cardiac arrest in Melbourne, Australia. Emerg Med 10:25–29

    Google Scholar 

  60. 60.

    Berger R, Kelley M (1994) Survival after in-hospital cardiopulmonary arrest of non critically ill patients: a prospective study. Chest 106:872–879

    CAS  PubMed  Google Scholar 

  61. 61.

    Edgren E, Hedstrand U, Kelsey S, Sutton-Tyrrell K, Safar P (1994) Assessment of neurological prognosis in comatose survivors of cardiac arrest. Lancet 343:1055–1059

    Article  CAS  PubMed  Google Scholar 

  62. 62.

    Oku K, Kuboyama K, Safar P, Obrist W, Sterz F, Leonov Y, Tisherman SA (1994) Cerebral and systemic arteriovenous oxygen monitoring after cardiac arrest: inadequate cerebral oxygen delivery. Resuscitation 27:141–152

    CAS  PubMed  Google Scholar 

  63. 63.

    Hickey RW, Ferimer H, Alexander HL, Garman RH, Callaway CW, Hicks S, Safar P, Graham SH, Kochanek PM (2000) Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats. Crit Care Med 28:3511–3516

    CAS  PubMed  Google Scholar 

  64. 64.

    Coimbra C, Wieloch T (1992) Hypothermia ameliorates neuronal survival when induced 2 hours after ischaemia in the rat. Acta Physiol Scand 146:543–544

    CAS  PubMed  Google Scholar 

  65. 65.

    Colbourne F, Li H, Buchan AM (1999) Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. J Cereb Blood Flow Metab 19:742–749

    Article  CAS  PubMed  Google Scholar 

  66. 66.

    Leonov Y, Sterz F, Safar P, Radovsky A (1990) Moderate hypothermia after cardiac arrest of 17 minutes in dogs Effect on cerebral and cardiac outcome: a preliminary study. Stroke 21:1600–1606

    CAS  PubMed  Google Scholar 

  67. 67.

    Sterz F, Safar P, Tisherman S, Radovsky A, Kuboyama K, Oku K (1991) Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med 19:379–389

    CAS  PubMed  Google Scholar 

  68. 68.

    Safar P, Xiao F, Radovsky A, Tanigawa K, Ebmeyer U, Bircher N, Alexander H, Stezoski SW (1996) Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. Stroke 27:105–113

    CAS  PubMed  Google Scholar 

  69. 69.

    Weinrauch V, Safar P, Tisherman S, Kuboyama K, Radovsky A (1992) Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke 23:1454–1462

    CAS  PubMed  Google Scholar 

  70. 70.

    Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H (1993) Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 21:1348–1358

    CAS  PubMed  Google Scholar 

  71. 71.

    Gisvold SE, Safar P, Rao G, Moossy J, Kelsey S, Alexander H (1984) Multifaceted therapy after global brain ischemia in monkeys. Stroke 15:803–812

    CAS  PubMed  Google Scholar 

  72. 72.

    Markarian GZ, Lee JH, Stein DJ, Hong SC (1996) Mild hypothermia: therapeutic window after experimental cerebral ischemia. Neurosurgery 38:542–550

    CAS  PubMed  Google Scholar 

  73. 73.

    Benson DW, Williams GR, Spencer FC (1958) The use of hypothermia after cardiac arrest. Anesth Analg 38:423–428

    Google Scholar 

  74. 74.

    Williams GR Jr, Spencer FC (1958) The clinical use of hypothermia following cardiac arrest. Ann Surg 148:462–468

    PubMed  Google Scholar 

  75. 75.

    Bohn DJ, Biggar WD, Smith CR, Conn AW, Barker GA (1986) Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning. Crit Care Med 14:529–534

    CAS  PubMed  Google Scholar 

  76. 76.

    Safar P, Abramson NS, Angelos M, Cantadore R, Leonov Y, Levine R, Pretto E, Reich H, Sterz F, Stezoski SW et al. (1990) Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest. Am J Emerg Med 8:55–67

    CAS  PubMed  Google Scholar 

  77. 77.

    Sterz F, Zeiner A, Kurkciyan I, Janata K, Mullner M, Domanovits H, Safar P (1996) Mild resuscitative hypothermia and outcome after cardiopulmonary resuscitation. J Neurosurg Anesthesiol 8:88–96

    CAS  PubMed  Google Scholar 

  78. 78.

    Bernard SA, Jones BM, Horne MK (1997) Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 30:146–153

    CAS  PubMed  Google Scholar 

  79. 79.

    Yanagawa Y, Ishihara S, Norio H, Takino M, Kawakami M, Takasu A, Okamoto K, Kaneko N, Terai C, Okada Y (1998) Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest. Resuscitation 39:61–66

    Article  CAS  PubMed  Google Scholar 

  80. 80.

    Nagao K, Hayashi N, Kanmatsuse K, Arima K, Ohtsuki J, Kikushima K, Watanabe I (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 36:776–783

    Article  CAS  PubMed  Google Scholar 

  81. 81.

    Zeiner A, Holzer M, Sterz F, Behringer W, Schorkhuber W, Mullner M, Frass M, Siostrzonek P, Ratheiser K, Kaff A, Laggner AN (2000) Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Stroke 31:86–94

    CAS  PubMed  Google Scholar 

  82. 82.

    Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–663

    PubMed  Google Scholar 

  83. 83.

    The Hypothermia After Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556

    PubMed  Google Scholar 

  84. 84.

    Polderman KH, Sterz F, van Zanten ARH, Uray T, Losert H, de Waal R, Girbes ARJ, Holzer M (2003) Induced hypothermia improves neurological outcome in asystolic patients with out-of hospital cardiac arrest. Circulation 108:IV-581 (Abstract 2646)

    Google Scholar 

  85. 85.

    Bernard S, Buist M, Monteiro O, Smith K. (2003) Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report. Resuscitation 56:9–13

    Article  PubMed  Google Scholar 

  86. 86.

    Sosin DM, Sniezek JE, Thurman DJ (1996) Incidence of mild and moderate brain injury in the United States 1991. Brain Injury 10:47–54

    Article  CAS  PubMed  Google Scholar 

  87. 87.

    Woringer E, Schneider J, Baumgartner J, Thomalske G (1954) Essai critique sur l’effet de l’hibernation artificielle sur 19 cas de souffrance du tronc cérébral après traumatisme sélectionnés pour leur gravité parmi 270 comas postcommotionels. Anesth Analg (Paris) 11:34–45

    Google Scholar 

  88. 88.

    Sedzimir CB (1959) Therapeutic hypothermia in cases of head injury. J Neurosurg 16:407–414

    CAS  PubMed  Google Scholar 

  89. 89.

    Lazorthes G, Campan L (1958) Hypothermia in the treatment of craniocerebral traumatism. J Neurosurg 15:162–167

    CAS  PubMed  Google Scholar 

  90. 90.

    Hendrick EB (1959) The use of hypothermia in severe head injuries in childhood. Ann Surg 79:362–364

    CAS  Google Scholar 

  91. 91.

    Dietrich WD, Alonso O, Busto R, Globus MYT, Ginsberg MD (1994) Posttraumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. Acta Neuropathol 87:250–258

    CAS  PubMed  Google Scholar 

  92. 92.

    Buchan A, Pulsinelli WA (1990) Hypothermia but not the N-methyl-Daspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J Neurosci 10:311–316

    CAS  PubMed  Google Scholar 

  93. 93.

    Clifton GL, Jiang JY, Lyeth BG, Jenkins LW, Hamm RJ, Hayes RL (1991) Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab 11:114–121

    CAS  PubMed  Google Scholar 

  94. 94.

    Busto R, Dietrich WD, Globus MYT, Valdes I, Scheinberg P, Ginsberg MD (1987) Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7:729–738

    PubMed  Google Scholar 

  95. 95.

    Pomeranz S, Safar P, Radovsky A, Tisherman SA, Alexander H, Stezoski W (1993) The effect of resuscitative moderate hypothermia following epidural brain compression on cerebral damage in a canine outcome model. J Neurosurg 79:241–51.

    CAS  PubMed  Google Scholar 

  96. 96.

    Smith SL, Hall ED (1996) Mild pre- and posttraumatic hypothermia attenuates blood–brain barrier damage following controlled cortical impact injury in the rat. J Neurotrauma 13:1–9

    CAS  PubMed  Google Scholar 

  97. 97.

    McIntosh TK Vink R, Yamakami I, Faden AI (1989) Magnesium protects against neurological deficit after brain injury. Brain Res 482:252–260

    CAS  PubMed  Google Scholar 

  98. 98.

    Vink R (1988) Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. J Biol Chem 263:757–761

    CAS  PubMed  Google Scholar 

  99. 99.

    Vink R, Cernak I (2000) Regulation of intracellular free magnesium in central nervous system injury. Front Bioscience 5:656–665

    Google Scholar 

  100. 100.

    Clark RS, Kochanek PM, Marion DW, Schiding JK, White M, Palmer AM, DeKosky ST (1996) Mild posttraumatic hypothermia reduces mortality after severe controlled cortical impact in rats. J Cereb Blood Flow Metab 16:253–261

    Article  CAS  PubMed  Google Scholar 

  101. 101.

    Matsushita Y (2001) Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult. Crit Care Med 29:2060–2066

    Article  CAS  PubMed  Google Scholar 

  102. 102.

    Bernard OS (1996) Induced hypothermia in intensive care medicine. Anaesth Intensive Care 24:382–388

    CAS  PubMed  Google Scholar 

  103. 103.

    Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T (1993) Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:363–386

    CAS  PubMed  Google Scholar 

  104. 104.

    Tateishi A, Soejima Y, Taira Y Nakashima K, Fujisawa H, Tsuchida E, Maekawa T, Ito H (1998) Feasibility of the titration method of mild hypothermia in severely head-injured patients with intracranial hypertension. Neurosurgery 42:1065–1069

    Google Scholar 

  105. 105.

    Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, Fletcher J, Hayes RL, Choi SC (1993) A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma 10:263–271

    CAS  PubMed  Google Scholar 

  106. 106.

    Jiang J-Y, Yu M-K, Zhu C (2000) Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases. J Neurosurg 93:546–549

    CAS  PubMed  Google Scholar 

  107. 107.

    Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, DeKosky ST (1997) Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 336:540–546

    CAS  PubMed  Google Scholar 

  108. 108.

    Hayashi S, Inao S, Takayasu M, Kajita Y, Ishiyama J, Harada T, Yoshida J (2002) Effect of early induction of hypothermia on severe head injury. Acta Neurochir Suppl 81:83–84

    CAS  PubMed  Google Scholar 

  109. 109.

    Tokutomi T, Morimoto K, Miyagi T, Yamaguchi S, Ishikawa K, Shigemori M (2003) Optimal temperature for the management of severe traumatic brain injury: effect of hypothermia on intracranial pressure, systemic and intracranial hemodynamics, and metabolism. Neurosurgery 52:102–111

    PubMed  Google Scholar 

  110. 110.

    Metz C, Holzschuh M, Bein T, Woertgen C, Frey A, Frey I, Taeger K, Brawanski A (1996) Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. J Neurosurg 85:533–541

    CAS  PubMed  Google Scholar 

  111. 111.

    Polderman KH, Tjong Tjin Joe R, Peerdeman SM, Vandertop WP, Girbes ARJ (2002) Effects of artificially induced hypothermia on intracranial pressure and outcome in patients with severe traumatic head injury. Intensive Care Med 28:1563–1567

    Article  Google Scholar 

  112. 112.

    Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR, Muizelaar JP, Wagner FC, Marion DW, Luerssen TG, Chesnut RM, Schwartz M (2001) Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 344:556–563

    CAS  PubMed  Google Scholar 

  113. 113.

    Zhi D, Zhang S, Lin X (2003) Study on therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury. Surg Neurol 59:381–385

    Article  PubMed  Google Scholar 

  114. 114.

    Shiozaki T, Hayakata T, Taneda M, Nakajima Y, Hashiguchi N, Fujimi S, Nakamori Y, Tanaka H, Shimazu T, Sugimoto H (2001) A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan. J Neurosurg 94:50–54

    CAS  PubMed  Google Scholar 

  115. 115.

    McIntyre LA, Fergusson DA, Hebert PC, Moher D, Hutchison JS (2003) Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review. J Am Med Assoc 289:2992–2999

    Article  Google Scholar 

  116. 116.

    Clifton GL, Choi SC, Miller ER, Levin HS, Smith KR Jr, Muizelaar JP, Wagner FC, Marion DW, Luerssen TG (2001) Intercenter variance in clinical trials of head trauma. Experience of the national acute brain injury study: hypothermia. J Neurosurg 95:751–755

    CAS  PubMed  Google Scholar 

  117. 117.

    Polderman KH, Girbes ARJ, Peerdeman SM, Vandertop WP (2001) Hypothermia (review/comment). J Neurosurg 94:853–855

    CAS  Google Scholar 

  118. 118.

    Polderman KH, Peerdeman SM, Girbes ARJ (2001) Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. J Neurosurg 94:697–705

    CAS  PubMed  Google Scholar 

  119. 119.

    Aibiki M, Kawaguchi S, Maekawa N (2001) Reversible hypophosphatemia during moderate hypothermia therapy for brain-injured patients. Crit Care Med 29:1726–1730

    CAS  PubMed  Google Scholar 

  120. 120.

    Polderman KH, Girbes ARJ (2002) Induced hypothermia: a highly promising treatment, but beware of preventable side effects [letter]. N Engl J Med 347:64

    Google Scholar 

  121. 121.

    The Brain Trauma Foundation. The American Association of Neurological Surgeons (2000) The joint section on neurotrauma and critical care. Guidelines for cerebral perfusion pressure. J Neurotrauma 17:507–511

    PubMed  Google Scholar 

  122. 122.

    Fearnside MR, Cook RJ, McDougall P, McNeil RJ (1993) The Westmead Head Injury Project outcome in severe head injury. A comparative analysis of pre-hospital, clinical and CT variables. Br J Neurosurg 7:267–279

    CAS  PubMed  Google Scholar 

  123. 123.

    Chesnut RM, Marshall SB, Piek J, Blunt BA, Klauber MR, Marshall LF (1993) Early and late systemic hypotension as a frequent and fundamental source of cerebral ischemia following severe brain injury in the Traumatic Coma Data Bank. Acta Neurochir Suppl (Wien) 59:121–125

    Google Scholar 

  124. 124.

    Polderman KH, Zanten ARH van, Girbes ARJ (2003) The importance of magnesium in critically ill patients: a role in mitigating neurological injury and in the prevention of vasospasms. Intensive Care Med 29:1202–1203

    Article  PubMed  Google Scholar 

  125. 125.

    Polderman KH, Bloemers F, Peerdeman SM, Girbes ARJ (2000) Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury. Critical Care Med 28:2022–2025

    Article  CAS  Google Scholar 

  126. 126.

    van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367

    PubMed  Google Scholar 

  127. 127.

    Van Den Berghe G, Wouters PJ, Bouillon R, Weekers F, Verwaest C, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P (2003) Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med 31:359–366

    PubMed  Google Scholar 

  128. 128.

    Schwab S, Schwarz S, Aschoff A, Keller E, Hacke W (1998) Moderate hypothermia and brain temperature in patients with severe middle cerebral artery infarction. Acta Neurochir Suppl (Wien) 71:131–134

    Google Scholar 

  129. 129.

    Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W (1998) Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 29:2461–2466

    CAS  PubMed  Google Scholar 

  130. 130.

    Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA (2001) Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 32:2033–2035

    CAS  PubMed  Google Scholar 

  131. 131.

    Park CK, Jun SS, Kim MC, Kang JK (1998) Effects of systemic hypothermia and selective brain cooling on ischemic brain damage and swelling. Acta Neurochir Suppl (Wien) 71:225–228

    Google Scholar 

  132. 132.

    Berrouschot J, Sterker M, Bettin S, Koster J, Schneider D (1998) Mortality of space-occupying (“malignant”) middle cerebral artery infarction under conservative intensive care. Intensive Care Med 24:620–623

    Article  CAS  PubMed  Google Scholar 

  133. 133.

    Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, Mayberg MR, Furlan AJ (2001) Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 32:1847–1854

    CAS  PubMed  Google Scholar 

  134. 134.

    Steiner T, Friede T, Aschoff A, Schellinger PD, Schwab S, Hacke W (2001) Effect and feasibility of controlled rewarming after moderate hypothermia in stroke patients with malignant infarction of the middle cerebral artery. Stroke 32:2833–2835

    CAS  PubMed  Google Scholar 

  135. 135.

    Castillo J, Davalos A, Marrugat J, Noya M (1998) Timing for fever-related brain damage in acute ischemic stroke. Stroke 29:2455–2460

    CAS  PubMed  Google Scholar 

  136. 136.

    Georgilis K, Plomaritoglou A, Dafni U, Bassiakos Y, Vemmos K (1999) Aetiology of fever in patients with acute stroke. J Intern Med 246:203–209

    Google Scholar 

  137. 137.

    Schwarz S, Hafner K, Aschoff A, Schwab S (2000) Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 54:354–361

    CAS  PubMed  Google Scholar 

  138. 138.

    Albrecht RF, Wass CT, Lanier WL (1998) Occurrence of potentially detrimental temperature alterations in hospitalized patients at risk for brain injury. Mayo Clin Proc 73:629–635

    PubMed  Google Scholar 

  139. 139.

    Castillo J, Dávalos A, Noya M (1997) Progression of ischaemic stroke and excitotoxic amino acids. Lancet 349:79–83

    Article  CAS  PubMed  Google Scholar 

  140. 140.

    Ginsberg MD, Busto R (1998) Combating hyperthermia in acute stroke: a significant clinical concern. Stroke 29:529–534

    CAS  PubMed  Google Scholar 

  141. 141.

    Dávalos A, Castillo J, Pumar JM, Noya M (1997) Body temperature and fibrinogen are related to early neurological deterioration in acute ischemic stroke. Cerebrovasc Dis 7:64–69

    Google Scholar 

  142. 142.

    Azzimondi G, Bassein L, Nonino F, Fiorani L, Vignatelli L, Re G, D’Alessandro R (1995) Fever in acute stroke worsens prognosis: a prospective study. Stroke 26:2040–2043

    CAS  PubMed  Google Scholar 

  143. 143.

    Reith J, Jørgensen HS, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, Olsen TS (1996) Body temperature in acute stroke: relations to stroke severity, infarct size, mortality, and outcome. Lancet 347:422–425

    CAS  PubMed  Google Scholar 

  144. 144.

    Wang Y, Lim LL, Levi C, Heller RF, Fisher J (2000) Influence of admission body temperature on stroke mortality. Stroke 31:404–409

    CAS  PubMed  Google Scholar 

  145. 145.

    Hajat C, Hajat S, Sharma P (2000) Effects of post-stroke pyrexia on stroke outcome: meta-analysis of studies on patients. Stroke 31:410–414

    CAS  PubMed  Google Scholar 

  146. 146.

    Castillo J, Davalos A, Marrugat J, Noya M (1998) Timing for fever-related brain damage in acute ischemic stroke. Stroke 29:2455–2460

    CAS  PubMed  Google Scholar 

  147. 147.

    Kammersgaard LP, Jorgensen HS, Rungby JA, Reith J, Nakayama H, Weber UJ, Houth J, Olsen TS (2002) Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen stroke study. Stroke 33:1759–1762

    Article  CAS  PubMed  Google Scholar 

  148. 148.

    Reith J, Jørgensen HS, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, Olsen TS (1996) Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet 347:422–425

    CAS  PubMed  Google Scholar 

  149. 149.

    Oliveira-Filho J, Ezzeddine MA, Segal AZ, Buonanno FS, Chang Y, Ogilvy CS, Rordorf G, Schwamm LH, Koroshetz WJ, McDonald CT (2001) Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome. Neurology 56:1299–1304

    CAS  PubMed  Google Scholar 

  150. 150.

    Weir B, Disney L, Grace M, Roberts P (1989) Daily trends in white blood cell count and temperature after subarachnoid hemorrhage from aneurysm. Neurosurgery 25:161–165

    CAS  PubMed  Google Scholar 

  151. 151.

    Schwarz S, Hafner K, Aschoff A, Schwab S (2000) Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 54:354–361

    CAS  PubMed  Google Scholar 

  152. 152.

    Takino M, Okada Y (1991) Hyperthermia following cardiopulmonary resuscitation. Intensive Care Med 17:419–420

    CAS  PubMed  Google Scholar 

  153. 153.

    Baena RC, Busto R, Dietrich WD, Globus MY, Ginsberg MD (1997) Hyperthermia delayed by 24 hours aggravates neuronal damage in rat hippocampus following global ischemia. Neurology 48:768–773

    CAS  PubMed  Google Scholar 

  154. 154.

    Kim Y, Busto R, Dietrich WD, Kraydieh S, Ginsberg MD (1996) Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia. Stroke 27:2274–2281

    CAS  PubMed  Google Scholar 

  155. 155.

    Minamisawa H, Smith M-L, Siesjö BK (1990) The effect of mild hyperthermia and hypothermia on brain damage following 5, 10, and 15 minutes of forebrain ischemia. Ann Neurol 28:26–33

    Google Scholar 

  156. 156.

    Ginsberg MD, Sternau LL, Globus MY-T, Dietrich WD, Busto R (1992) Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev 4:189–225

    CAS  PubMed  Google Scholar 

  157. 157.

    Chen H, Chopp M, Welch KMA (1991) Effect of mild hyperthermia on the ischemic infarct volume after middle cerebral artery occlusion in the rat. Neurology 41:1133–1135

    CAS  PubMed  Google Scholar 

  158. 158.

    Coimbra C, Boris-Moller F, Drake M, Wieloch T (1996) Diminished neuronal damage in the rat brain by late treatment with the antipyretic drug dipyrone or cooling following cerebral ischemia. Acta Neuropathol (Berl) 92:447–453

    Google Scholar 

  159. 159.

    Coimbra C, Drake M, Boris-Moller F, Wieloch T (1996) Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug: evidence for chronic encephalopathic processes following ischemia. Stroke 27:1578–1585

    CAS  PubMed  Google Scholar 

  160. 160.

    Hickey RW, Kochanek PM, Ferimer H, Alexander HL, Garman RH, Graham SH (2003) Induced hyperthermia exacerbates neurologic neuronal histologic damage after asphyxial cardiac arrest in rats. Crit Care Med 31:531–535

    Article  PubMed  Google Scholar 

  161. 161.

    Commichau C, Scarmeas N, Mayer SA (2003) Risk factors for fever in the neurologic intensive care unit. Neurology 60:837–841

    PubMed  Google Scholar 

  162. 162.

    Mayer SA, Commichau C, Scarmeas N, Presciutti M, Bates J, Copeland D (2000) Clinical trial of an air-circulating cooling blanket for fever control in critically ill neurologic patients. Neurology 56:292–298

    Google Scholar 

  163. 163.

    Kammersgaard LP, Rasmussen BH, Jørgensen HS, Reith J, Weber U, Olsen TS (2000) Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: a case-control study: the Copenhagen Stroke Study. Stroke 31:2251–2256

    CAS  PubMed  Google Scholar 

  164. 164.

    Thome C, Schubert G, Piepgras A, Elste V, Schilling L, Schmiedek P (2001) Hypothermia reduces acute vasospasm following SAH in rats. Acta Neurochir Suppl 77:255–258

    CAS  PubMed  Google Scholar 

  165. 165.

    Piepgras A, Elste V, Frietsch T, Schmiedek P, Reith W, Schilling L (2001) Effect of moderate hypothermia on experimental severe subarachnoid hemorrhage, as evaluated by apparent diffusion coefficient changes. Neurosurgery 48:1128–1135

    CAS  PubMed  Google Scholar 

  166. 166.

    Nagao S, Irie K, Kawai N, Kunishio K, Ogawa T, Nakamura T, Okauchi M, Nagao S, Irie K, Kawai N, Kunishio K, Ogawa T, Nakamura T, Okauchi M (2000) Protective effect of mild hypothermia on symptomatic vasospasm: a preliminary report. Acta Neurochir Suppl 76:547–550

    CAS  PubMed  Google Scholar 

  167. 167.

    Keller E, Fortunati M, Muroi C, Gandjour J, Yonekawa Y (2003) Hypothermia in the treatment of patients with intractable cerebral vasospasm after aneurysmal subarachnoid haemorrhage. In: Bacher A, Schwab S, Spiss CK, Sterz F, Zimpfer M (eds) Proc 3rd International Symposium on Therapeutic Hypothermia. P 84 [S8] (Abstract)

  168. 168.

    Nagao S, Irie K, Kawai N, Nakamura T, Kunishio K, Matsumoto Y (2003) The use of mild hypothermia for patients with severe vasospasm: a preliminary report. J Clin Neurosci 10:208–212

    Article  CAS  PubMed  Google Scholar 

  169. 169.

    Gasser S, Khan N, Yonekawa Y, Imhof HG, Keller E (2003) Long-term hypothermia in patients with severe brain edema after poor-grade subarachnoid hemorrhage: feasibility and intensive care complications. J Neurosurg Anesthesiol 15:240–248

    Article  PubMed  Google Scholar 

  170. 170.

    Hindman BJ, Todd MM, Gelb AW, Loftus CM, Craen RA, Schubert A, Mahla ME, Torner JC (1999) Mild hypothermia as a protective therapy during intracranial aneurysm surgery: a randomized prospective pilot trial. Neurosurgery 44:23–33

    CAS  PubMed  Google Scholar 

  171. 171.

    Karibe H, Sato K, Shimizu H, Tominaga T, Koshu K, Yoshimoto T (2000) Intraoperative mild hypothermia ameliorates postoperative cerebral blood flow impairment in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 47:594–601

    CAS  PubMed  Google Scholar 

  172. 172.

    Massad MG, Charbel FT, Chaer R, Geha AS, Ausman JI (2001) Closed chest hypothermic circulatory arrest for complex intracranial aneurysms. Ann Thorac Surg 71:1900–1904

    Article  CAS  PubMed  Google Scholar 

  173. 173.

    Young WL, Lawton MT, Gupta DK, Hashimoto T (2002) Anesthetic management of deep hypothermic circulatory arrest for cerebral aneurysm clipping. Anesthesiology 96:497–503

    Article  PubMed  Google Scholar 

  174. 174.

    Nathan HJ, Wells GA, Munson JL, Wozny D (2001) Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: a randomized trial. Circulation 104:185–91

    Google Scholar 

  175. 175.

    Mora CT, Henson MB, Weintraub WS, Murkin JM, Martin TD, Craver JM, Gott JP, Guyton RA (1996) The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization. J Thorac Cardiovasc Surg 112:514–522

    CAS  PubMed  Google Scholar 

  176. 176.

    Veeragandham RS, Hamilton IN Jr, O’Connor C, Rizzo V, Najafi H (1998) Experience with antegrade bihemispheric cerebral perfusion in aortic arch operations. Ann Thorac Surg 66:493–499

    CAS  PubMed  Google Scholar 

  177. 177.

    Jacobs MJ, de Mol BA, Veldman DJ (2001) Aortic arch and proximal supraaortic arterial repair under continuous antegrade cerebral perfusion and moderate hypothermia. Cardiovasc Surg 9:396–402

    Article  CAS  PubMed  Google Scholar 

  178. 178.

    Frank SM, Parker SD, Rock P, Gorman RB, Kelly S, Beattie C, Williams GM (1994) Moderate hypothermia with partial bypass and sequential repair for thoracoabdominal aortic aneurysm. J Vasc Surg 19:687–697

    CAS  PubMed  Google Scholar 

  179. 179.

    Cambria RP, Davison JK, Zannetti S, L’Italien G, Brewster DC, Gertler JP, Moncure AC, LaMuraglia GM, Abbott WM (1997) Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair. J Vasc Surg 25:234–241

    CAS  PubMed  Google Scholar 

  180. 180.

    Svensson LG, Hess KR, D’Agostino RS, Entrup MH, Hreib K, Kimmel WA, Nadolny E, Shahian DM (1998) Reduction of neurologic injury after high-risk thoracoabdominal aortic operation. Ann Thorac Surg 66:132–138

    Article  CAS  PubMed  Google Scholar 

  181. 181.

    Barone FC, Feuerstein GZ, White RF (1997) Brain cooling during transient focal ischemia provides complete neuroprotection. Neurosci Biobehav Rev 21:31–44

    Article  CAS  PubMed  Google Scholar 

  182. 182.

    Hindman BJ, Todd MM, Gelb AW, Loftus CM, Craen RA, Schubert A, Mahla ME, Torner JC (2002) Intraoperative hypothermia and rewarming during aneurysm surgery: Progress of IHAST2. J Neurosurg Anesth 14:344 (Abstract)

    Article  Google Scholar 

  183. 183.

    Vacanti FX, Ames AA (1983) Mild hypothermia and Mg++ protect against irreversible damage during CNS ischemia. Stroke 15:695–698

    Google Scholar 

  184. 184.

    Robertson CS, Foltz R, Grossman RG, Goodman JC (1986) Protection against experimental ischemic spinal cord injury. J Neurosurg 64:633–642

    CAS  PubMed  Google Scholar 

  185. 185.

    Brown WR, Moody DM, Challa VR, Stump DA, Hammon JW (2000) Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke 31:707–713

    CAS  PubMed  Google Scholar 

  186. 186.

    Arrowsmith J, Grocott HP, Reves JG, Newman MF (2000) Central nervous system complications of cardiac surgery. Br J Anaesth 84:378–393

    CAS  PubMed  Google Scholar 

  187. 187.

    Grigore AM, Mathew J, Grocott HP, Reves JG, Blumenthal JA, White WD, Smith PK, Jones RH, Kirchner JL, Mark DB, Newman MF; Neurological Outcome Research Group (2001) Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery. Anesthesiology 95:1110–1119

    Article  CAS  PubMed  Google Scholar 

  188. 188.

    Plourde G, Leduc AS, Morin JE, DeVarennes B, Latter D, Symes J, Robbins R, Fosset N, Couture L, Ptito A (1997) Temperature during cardiopulmonary bypass for coronary artery operations does not influence postoperative cognitive function: a prospective, randomized trial. J Thorac Cardiovasc Surg 114:123–128

    CAS  PubMed  Google Scholar 

  189. 189.

    Martin TD, Craver JM, Gott JP, Weintraub WS, Ramsay J, Mora CT, Guyton RA (1994) Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. Ann Thorac Surg 57:298–302

    CAS  PubMed  Google Scholar 

  190. 190.

    The Warm Heart Investigators (1994) Randomised trial of normothermic versus hypothermic coronary bypass surgery. Lancet 343:559–563

    Article  PubMed  Google Scholar 

  191. 191.

    Bissonnette B, Holtby HM, Davis AJ, Pua H, Gilder FJ, Black M (2000) Cerebral hyperthermia in children after cardiopulmonary bypass. Anesthesiology 93:611–618

    Article  CAS  PubMed  Google Scholar 

  192. 192.

    Gunn AJ, Gluckman PD, Gunn TR (1988) Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 102:885–892

    Google Scholar 

  193. 193.

    Battin MR, Dezoete JA, Gunn TR, Gluckman PD, Gunn AJ (2001) Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 107:480–484

    CAS  PubMed  Google Scholar 

  194. 194.

    Battin MR, Penrice J, Gunn TR, Gunn AJ (2003) Treatment of term infants with head cooling and mild systemic hypothermia (35.0°C and 34.5°C) after perinatal asphyxia. Pediatrics 111:244–251

    PubMed  Google Scholar 

  195. 195.

    Shankaran S, Laptook A, Wright LL, Ehrenkranz RA, Donovan EF, Fanaroff AA, Stark AR, Tyson JE, Poole K, Carlo WA, Lemons JA, Oh W, Stoll BJ, Papile LA, Bauer CR, Stevenson DK, Korones SB, McDonald S (2002) Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics 110:377–385

    PubMed  Google Scholar 

  196. 196.

    Simbruner G, Haberl C, Harrison V, Linley L, Willeitner AE (1999) Induced brain hypothermia in asphyxiated human newborn infants: a retrospective chart analysis of physiological and adverse effects. Intensive Care Med 25:1111-1117

    CAS  PubMed  Google Scholar 

  197. 197.

    Azzopardi D, Robertson NJ, Cowan FM, Rutherford MA, Rampling M, Edwards AD (2000) Pilot study of treatment with whole body hypothermia for neonatal encephalopathy. Pediatrics 106:684–694

    CAS  PubMed  Google Scholar 

  198. 198.

    Thoresen M, Whitelaw A (2000) Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 106:92–99

    CAS  PubMed  Google Scholar 

  199. 199.

    Debillon T, Daoud P, Durand P, Cantagrel S, Jouvet P, Saizou C, Zupan V (2003) Whole-body cooling after perinatal asphyxia: a pilot study in term neonates. Dev Med Child Neurol 45:17–23

    PubMed  Google Scholar 

  200. 200.

    Biswas AK, Bruce DA, Sklar FH, Bokovoy JL, Sommerauer JF (2002)Treatment of acute traumatic brain injury in children with moderate hypothermia improves intracranial hypertension. Crit Care Med 30:2742–2751

    Article  PubMed  Google Scholar 

  201. 201.

    Rose C, Michalak A, Pannunzio M, Chatauret N, Rambaldi A, Butterworth RF (2000) Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure. Hepatology 31:872–877

    CAS  PubMed  Google Scholar 

  202. 202.

    Jalan R, Damink SW, Deutz NE, Lee A, Hayes PC (1990) Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet 354:1164–1168

    Article  Google Scholar 

  203. 203.

    Jalan R, Olde Damink SW, Deutz NE, Davies NA, Garden OJ, Madhavan KK, Hayes PC, Lee A (2003) Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver transplantation for acute liver failure. Transplantation 75:2034–2039

    Article  PubMed  Google Scholar 

  204. 204.

    Maeda T, Hashizume K, Tanaka T (1999) Effect of hypothermia on kainic acid-induced limbic seizures: an electroencephalographic and 14C-deoxyglucose autoradiographic study. Brain Res 818:228–235

    Article  CAS  PubMed  Google Scholar 

  205. 205.

    Karkar KM, Garcia PA, Bateman LM, Smyth MD, Barbaro NM, Berger M (2002) Focal cooling suppresses spontaneous epileptiform activity without changing the cortical motor threshold. Epilepsia 43:932–935

    Article  PubMed  Google Scholar 

  206. 206.

    Silfvast T, Tiainen M, Poutiainen E, Roine RO (2003) Therapeutic hypothermia after prolonged cardiac arrest due to non-coronary causes. Resuscitation 57:109–112

    Article  CAS  PubMed  Google Scholar 

  207. 207.

    Takata T, Hirakawa M, Sakurai M, Kanazawa I (1999) Fulminant form of acute disseminated encephalomyelitis: successful treatment with hypothermia. J Neurol Sci 165:94–97

    Article  CAS  PubMed  Google Scholar 

  208. 208.

    Yokota S, Imagawa T, Miyamae T, Ito S, Nakajima S, Nezu A, Mori M (2000) Hypothetical pathophysiology of acute encephalopathy and encephalitis related to influenza virus infection and hypothermia therapy. Pediatr Int 42:197–203

    Article  CAS  PubMed  Google Scholar 

  209. 209.

    Munakata M, Kato R, Yokoyama H, Haginoya K, Tanaka Y, Kayaba J, Kato T, Takayanagi R, Endo H, Hasegawa R, Ejima Y, Hoshi K, Iinuma K (2000) Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy. Brain Dev 22:373–377

    Article  CAS  PubMed  Google Scholar 

  210. 210.

    Dalrymple-Hay MJ, Deakin CD, Knight H, Edwards JC, Keeton B, Salmon AP, Monro JL (1999) Induced hypothermia as salvage treatment for refractory cardiac failure following paediatric cardiac surgery. Eur J Cardiothorac Surg 15:515–518

    Article  CAS  PubMed  Google Scholar 

  211. 211.

    Yahagi N, Kumon K, Watanabe Y, Tanigami H, Haruna M, Hayashi H, Imanaka H, Takeuchi M, Ohashi Y, Takamoto S (1998) Value of mild hypothermia in patients who have severe circulatory insufficiency even after intra-aortic balloon pump. J Clin Anesth 10:120–125

    Article  CAS  PubMed  Google Scholar 

  212. 212.

    Villar J, Slutsky AS (1993) Effects of induced hypothermia in patients with septic adult respiratory distress syndrome. Resuscitation 26:183–192

    CAS  PubMed  Google Scholar 

  213. 213.

    Irazuzta JE, Pretzlaff R, Rowin M, Milam K, Zemlan FP, Zingarelli B (2000) Hypothermia as an adjunctive treatment for severe bacterial meningitis. Brain Res 881:88–97

    CAS  PubMed  Google Scholar 

  214. 214.

    Angstwurm K, Reuss S, Freyer D, Arnold G, Dirnagl U, Schumann RR, Weber JR (2000) Induced hypothermia in experimental pneumococcal meningitis. J Cereb Blood Flow Metab 20:834–838

    CAS  PubMed  Google Scholar 

  215. 215.

    Yu CG, Jimenez O, Marcillo AE, Weider B, Bangerter K, Dietrich WD, Castro S, Yezierski RP (2000) Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats. J Neurosurg 93 (Suppl 1):85–93

    CAS  PubMed  Google Scholar 

  216. 216.

    Hale SL, Dave RH, Kloner RA (1997) Regional hypothermia reduces myocardial necrosis even when instituted after the onset of ischemia. Basic Res Cardiol 92:351–357

    Article  CAS  PubMed  Google Scholar 

  217. 217.

    Hale SL, Kloner RA (1998) Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits. Cardiovasc Res 40:502–507

    Article  CAS  PubMed  Google Scholar 

  218. 218.

    Hale SL, Kloner RA (1997) Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia. Am J Physiol 273:H220–H227

    CAS  PubMed  Google Scholar 

  219. 219.

    Hale SL, Kloner RA (1999) Ischemic preconditioning and myocardial hypothermia in rabbits with prolonged coronary artery occlusion. Am J Physiol 276:H2029–H2034

    CAS  PubMed  Google Scholar 

  220. 220.

    Hale SL, Kloner RA (2002) Elevated body temperature during myocardial ischemia/reperfusion exacerbates necrosis and worsens no-reflow. Coron Artery Dis 13:177–181

    Article  PubMed  Google Scholar 

  221. 221.

    Safar P, Tisherman SA, Behringer W, Capone A, Prueckner S, Radovsky A, Stezoski WS, Woods RJ (2000) Suspended animation for delayed resuscitation from prolonged cardiac arrest that is unresuscitable by standard cardiopulmonary-cerebral resuscitation. Crit Care Med 28 (Suppl):N214–N218

    Article  CAS  PubMed  Google Scholar 

  222. 222.

    Dixon SR, Whitbourn RJ, Dae MW, Grube E, Sherman W, Schaer GL, Jenkins JS, Baim DS, Gibbons RJ, Kuntz RE, Popma JJ, Nguyen TT, O’Neill WW (2002) Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol 40:1928–1934

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

The author thanks E.W. Ely and A.B.J. Groeneveld for their critical appraisal of the manuscript.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Kees H. Polderman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Polderman, K.H. Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: Indications and evidence. Intensive Care Med 30, 556–575 (2004). https://doi.org/10.1007/s00134-003-2152-x

Download citation

Keywords

  • Therapeutic hypothermia
  • Induced hypothermia
  • Neurological injury
  • Resuscitation
  • Severe head injury
  • Artificial cooling
  • Review
  • Stroke
  • Ischemic injury
  • Reperfusion injury
  • Intracranial pressure