Intensive Care Medicine

, Volume 30, Issue 5, pp 757–769 | Cite as

Application of therapeutic hypothermia in the intensive care unit

Opportunities and pitfalls of a promising treatment modality—Part 2: Practical aspects and side effects
  • Kees H. PoldermanEmail author


Induced hypothermia can be used to protect the brain from post-ischemic and traumatic neurological injury. Potential clinical applications and the available evidence are discussed in a separate paper. This review focuses on the practical aspects of cooling and physiological changes induced by hypothermia, as well as the potential side effects that may develop. These side effects can be serious and, if not properly dealt with, may negate some or all of hypothermia’s potential benefits. However, many of these side effects can be prevented or modified by high-quality intensive care treatment, which should include careful monitoring of fluid balance, tight control of metabolic aspects such as glucose and electrolyte levels, prevention of infectious complications and various other interventions. The speed and duration of cooling and rate of re-warming are key factors in determining whether hypothermia will be effective; however, the risk of side effects also increases with longer duration. Realizing hypothermia’s full therapeutic potential will therefore require meticulous attention to the prevention and/or early treatment of side effects, as well as a basic knowledge and understanding of the underlying physiological and pathophysiological mechanisms. These and other, related issues are dealt with in this review.


Review Induced hypothermia Neurological injury Neuroprotection Side effects Physiological changes Cardiopulmonary resuscitation (CPR) Arrhythmias Coagulation Shivering Electrolyte disorders Intracranial pressure Ischemic brain injury Reperfusion injury 


  1. 1.
    Sessler DI (2000) Perioperative heat balance. Anesthesiology 92:578–594CrossRefPubMedGoogle Scholar
  2. 2.
    Tikuisis P, Bell DG, Jacobs I (1991) Shivering onset, metabolic response and convective heat transfer during cold air exposure. J Appl Physiol 70:1996–2002Google Scholar
  3. 3.
    English MJM (2001) Physical principles of heat transfer. Curr Anaesth Crit Care 12:66–71. DOI 10.1054/cacc.2001.0331CrossRefGoogle Scholar
  4. 4.
    Matsukawa T, Sessler DI, Sessler AM, Schroeder M, Ozaki M, Kurz A, Cheng C (1995) Heat flow and distribution during induction of general anesthesia. Anesthesiology 82:662–673CrossRefPubMedGoogle Scholar
  5. 5.
    Frank SM, Fleisher LA, Olson KF, Gorman RB, Higgins MS, Breslow MJ, Sitzmann JV, Beattie C (1995) Multivariate determinates of early postoperative oxygen consumption: the effects of shivering, core temperature and gender. Anesthesiology 83:241–249Google Scholar
  6. 6.
    Horvath SM, Spurr GB, Hutt BK, Hamilton LH (1956) Metabolic cost of shivering. J Appl Physiol 8:595–602PubMedGoogle Scholar
  7. 7.
    Milde LN (1992) Clinical use of mild hypothermia for brain protection: a dream revisited. J Neurosurg Anesthesiol 4:211–215PubMedGoogle Scholar
  8. 8.
    Small DL, Morley P, Buchan AM (1999). Biology of ischemic cerebral cell death. Prog Cardiovasc Dis 42:185–207PubMedGoogle Scholar
  9. 9.
    Schaller B, Graf R (2003) Hypothermia and stroke: the pathophysiological background. Pathophysiology 10:7–35CrossRefPubMedGoogle Scholar
  10. 10.
    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 74:135–144CrossRefPubMedGoogle Scholar
  11. 11.
    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 9:141–148PubMedGoogle Scholar
  12. 12.
    Kinoshita K, Chatzipanteli K, Alonso OF, Howard M, Dietrich WD (2002) The effect of brain temperature on hemoglobin extravasation after traumatic brain injury. J Neurosurg 97:945–953PubMedGoogle Scholar
  13. 13.
    Chi OZ, Liu X, Weiss HR (2001) Effects of mild hypothermia on blood-brain barrier disruption during isoflurane or pentobarbital anesthesia. Anesthesiology 95:933–938CrossRefPubMedGoogle Scholar
  14. 14.
    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 26:298–304PubMedGoogle Scholar
  15. 15.
    Siesjo BK, Bengtsson F, Grampp W, Theander S (1989) Calcium, excitotoxins and neuronal death in brain. Ann NY Acad Sci 568:234–251PubMedGoogle Scholar
  16. 16.
    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 30:1499–1502CrossRefPubMedGoogle Scholar
  17. 17.
    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 16:225–232Google Scholar
  18. 18.
    Frank SM (2001) Consequences of hypothermia. Curr Anaesth Crit Care 12:79–86CrossRefGoogle Scholar
  19. 19.
    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 20:904–910PubMedGoogle Scholar
  20. 20.
    Dempsey RJ, Combs DJ, Maley ME, Cowen DE, Roy MW, Donaldson DL (1987) Moderate hypothermia reduces postischemic edema development and leukotriene production. Neurosurgery 21:177–181PubMedGoogle Scholar
  21. 21.
    Frank SM, Satitpunwaycha P, Bruce SR, Herscovitch P, Goldstein DS (2003) Increased myocardial perfusion and sympathoadrenal activation during mild core hypothermia in awake humans. Clin Sci (Lond) 104:503–508Google Scholar
  22. 22.
    Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP (1988) Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test. Circulation 77:43–52PubMedGoogle Scholar
  23. 23.
    Hale SL, Dae MW, Kloner RA (2003) Marked reduction in no-reflow with late initiation of hypothermia in a rabbit myocardial infarct model. J Am Coll Cardiol 41 (6 Suppl B):381–382CrossRefPubMedGoogle Scholar
  24. 24.
    Hale SL, Dae MW, Kloner RA (2003) Hypothermia during reperfusion limits ‘no-reflow’ injury in a rabbit model of acute myocardial infarction. Cardiovasc Res 59:715–722CrossRefPubMedGoogle Scholar
  25. 25.
    Hale SL, Kloner RA (2002) Elevated body temperature during myocardial ischemia/reperfusion exacerbates necrosis and worsens no-reflow. Coron Artery Dis 13:177–181CrossRefPubMedGoogle Scholar
  26. 26.
    Hale SL, Kloner RA (1998) Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits. Cardiovasc Res 40:502–507CrossRefPubMedGoogle Scholar
  27. 27.
    Miki T, Liu GS, Cohen MV, Downey JM (1998) Mild hypothermia reduces infarct size in the beating rabbit heart: a practical intervention for acute myocardial infarction? Basic Res Cardiol 93:372–383CrossRefPubMedGoogle Scholar
  28. 28.
    Hale SL, Dave RH, Kloner RA (1997) Regional hypothermia reduces myocardial necrosis even when instituted after the onset of ischemia. Basic Res Cardiol 92:351–357CrossRefPubMedGoogle Scholar
  29. 29.
    Hale SL, Kloner RA (1997) Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia. Am J Physiol 273(1 Pt 2):H220–227PubMedGoogle Scholar
  30. 30.
    Dae MW, Gao DW, Sessler DI, Chair K, Stillson CA (2002) Effect of endovascular cooling on myocardial temperature, infarct size and cardiac output in human-sized pigs. Am J Physiol Heart Circ Physiol 282:H1584–1591PubMedGoogle Scholar
  31. 31.
    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 40:1928–1934CrossRefPubMedGoogle Scholar
  32. 32.
    Valeri CR, Feingold H, Cassidy G, Ragno G, Khuri S, Altschule MD (1987) Hypothermia-induced reversible platelet dysfunction. Ann Surg 205:175–181PubMedGoogle Scholar
  33. 33.
    Michelson AD, MacGregor H, Barnard MR, Kestin AS, Rohrer MJ, Valeri CR (1994) Hypothermia-induced reversible platelet dysfunction. Thromb Haemost 71:633–640PubMedGoogle Scholar
  34. 34.
    Watts DD, Trask A, Soeken K, Perdue P, Dols S, Kaufmann C (1998) Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function and fibrinolytic activity. J Trauma 44:846–854PubMedGoogle Scholar
  35. 35.
    Valeri CR, MacGregor H, Cassidy G, Tinney R, Pompei F (1995) Effects of temperature on bleeding time and clotting time in normal male and female volunteers. Crit Care Med 23:698–704CrossRefPubMedGoogle Scholar
  36. 36.
    Patt A, McCroskey B, Moore E (1988) Hypothermia-induced coagulopathies in trauma (Review). Surg Clin North Am 68:775–785PubMedGoogle Scholar
  37. 37.
    Ferrara A, MacArthur JD, Wright HK, Modlin IM, McMillen MA (1990) Hypothermia and acidosis worsen coagulopathy in the patients requiring massive transfusion. Am J Surg 160:515–518PubMedGoogle Scholar
  38. 38.
    Reed RL, Bracey AW, Hudson JD, Miller TA, Fischer RP (1990) Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels. Circ Shock 32:141–152PubMedGoogle Scholar
  39. 39.
    Rohrer MJ, Natale AM (1992) Effect of hypothermia on the coagulation cascade. Crit Care Med 20:1402–1405PubMedGoogle Scholar
  40. 40.
    Resnick DK, Marion DW, Darby JM (1994) The effect of hypothermia on the incidence of delayed traumatic intracerebral hemorrhage. Neurosurgery 34:352–356Google Scholar
  41. 41.
    Jurkovich GJ, Greiser WB, Luterman A, Curreri PW (1987) Hypothermia in trauma victims: an ominous predictor of survival. J Trauma 27:1019–1024PubMedGoogle Scholar
  42. 42.
    Luna GK, Maier RV, Pavlin EG, Anardi D, Copass MK, Oreskovich MR (1987) Incidence and effect of hypothermia in seriously injured patients. J Trauma 27:1014–1018PubMedGoogle Scholar
  43. 43.
    Gentilello LM, Jurkovich GJ, Stark MS, Hassantash SA, O’Keefe GE (1997) Is hypothermia in the victim of major trauma protective or harmful? Ann Surg 226:439–447CrossRefPubMedGoogle Scholar
  44. 44.
    Tisherman SA, Rodriguez A, Safar P (1999) Trauma care in the new millennium. Therapeutic hypothermia in traumatology. Surg Clin North Am 79:1269–1289PubMedGoogle Scholar
  45. 45.
    Steinemann S, Shackford SR, Davis JW (1990) Implications of admission hypothermia in trauma patients. J Trauma 30:200–202PubMedGoogle Scholar
  46. 46.
    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 344:556–563PubMedGoogle Scholar
  47. 47.
    Salman H, Bergman M, Bessler H, Alexandrova S, Beilin B, Djaldetti M (2000) Hypothermia affects the phagocytic activity of rat peritoneal macrophages. Acta Physiol Scand 168:431–436CrossRefPubMedGoogle Scholar
  48. 48.
    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 94:50–54PubMedGoogle Scholar
  49. 49.
    Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA (2001) Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 32:2033–2035PubMedGoogle Scholar
  50. 50.
    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 336:540–546PubMedGoogle Scholar
  51. 51.
    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 28:1563-1567CrossRefGoogle Scholar
  52. 52.
    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 346:557–563PubMedGoogle Scholar
  53. 53.
    The Hypothermia after Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556PubMedGoogle Scholar
  54. 54.
    Kurz A, Sessler DI, Lenhardt R and the Study of Wound Infection and Temperature Group (1996) Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. New Engl J Med 334:1209–1215CrossRefPubMedGoogle Scholar
  55. 55.
    Sessler DI (2001) Complications and treatment of mild hypothermia. Anesthesiology 95:531–543CrossRefPubMedGoogle Scholar
  56. 56.
    Sheffield CW, Sessler DI, Hunt TK (1994) Mild hypothermia during isoflurane anesthesia decreases resistance to E. Coli dermal infection in guinea pigs. Acta Anesthesiol Scand 38:201–205Google Scholar
  57. 57.
    Sheffield CW, Sessler DI, Hunt TK, Scheuenstuhl H (1994) Mild hypothermia during halothane anesthesia decreases resistance to S. Aureus dermal infection in guinea pigs. Wound Rep Reg 2:48–56CrossRefGoogle Scholar
  58. 58.
    Polderman KH, Girbes ARJ, Peerdeman SM, Vandertop WP (2001) Hypothermia (review/comment). J Neurosurgery 94:853–855Google Scholar
  59. 59.
    Polderman KH, Peerdeman SM, Girbes ARJ (2001) Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. Journal of Neurosurg 94:697–705Google Scholar
  60. 60.
    Kaufman HH, Timberlake G, Voelker J, Pait TG (1993) Medical complications of head injury. Med Clin North Am 77:43–60PubMedGoogle Scholar
  61. 61.
    Weinberg AD (1993) Hypothermia. Ann Emerg Med 22:370–377PubMedGoogle Scholar
  62. 62.
    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 17:507–511PubMedGoogle Scholar
  63. 63.
    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 7:267–279PubMedGoogle Scholar
  64. 64.
    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) 59:121–125Google Scholar
  65. 65.
    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 (abstract). Circulation 108:IV-581 [abstract 2646]Google Scholar
  66. 66.
    Aibiki M, Kawaguchi S, Maekawa N (2001) Reversible hypophosphatemia during moderate hypothermia therapy for brain-injured patients. Crit Care Med 29:1726–1730PubMedGoogle Scholar
  67. 67.
    McIntosh TK Vink R, Yamakami I, Faden AI (1989) Magnesium protects against neurological deficit after brain injury. Brain Res 482:252–260PubMedGoogle Scholar
  68. 68.
    Vink R (1988) Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. J Biol Chem 263:757–761PubMedGoogle Scholar
  69. 69.
    Vink R, Cernak I (2000) Regulation of intracellular free magnesium in central nervous system injury. Front Biosci 5:656–665Google Scholar
  70. 70.
    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 29:1202–1203CrossRefPubMedGoogle Scholar
  71. 71.
    Polderman KH, Bloemers F, Peerdeman SM, Girbes ARJ (2000) Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury. Crit Care Med 28:2022–2025Google Scholar
  72. 72.
    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 87:250–258PubMedGoogle Scholar
  73. 73.
    Vacanti FX, Ames AA (1983) Mild hypothermia and Mg++ protect against irreversible damage during CNS ischemia. Stroke 15:695–698Google Scholar
  74. 74.
    Saatman KE, Bareyre FM, Grady MS, McIntosh TK (2001) Acute cytoskeletal alterations and cell death induced by experimental brain injury are attenuated by magnesium treatment and exacerbated by magnesium deficiency. J Neuropathol Exp Neurol 60:183–194Google Scholar
  75. 75.
    Bareyre FM, Saatman KE, Raghupathi R, McIntosh TH (2000) Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J. Neurotrauma 17:1029–1039PubMedGoogle Scholar
  76. 76.
    Garcia LA, Dejong SC, Martin SM, Smith RS, Buettner GR, Kerber RE (1998) Magnesium reduces free radicals in an in vivo coronary occlusion-reperfusion model. J Am Coll Cardiol 32:536–539CrossRefPubMedGoogle Scholar
  77. 77.
    Pyne GJ, Cadoux-Hudson TA, Clark JF (2001) Magnesium protection against in vitro cerebral vasospasm after subarachnoid haemorrhage. Br J Neurosurg 15:409–415CrossRefPubMedGoogle Scholar
  78. 78.
    Teragawa H, Kato M, Yamagata T, Matsuura H, Kajiyama G (2000)The preventive effect of magnesium on coronary spasm in patients with vasospastic angina. Chest 118:1690–1695PubMedGoogle Scholar
  79. 79.
    Weisinger JR, Bellorín-Font E (1998) Magnesium and phosphorus. Lancet 352:391–396CrossRefPubMedGoogle Scholar
  80. 80.
    Rubeiz GJ, Thill-Baharozian M, Hardie D, Carlson RW (1993) Association of hypomagnesemia and mortality in acutely ill medical patients. Crit Care Med 21:203–209PubMedGoogle Scholar
  81. 81.
    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 critically ill patients. New Engl J Med 345:1359–1367PubMedGoogle Scholar
  82. 82.
    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 31:359–366PubMedGoogle Scholar
  83. 83.
    Finney SJ, Zekveld C, Elia A, Evans TW (2003) Glucose control and mortality in critically ill patients. JAMA 290:2041–2047CrossRefPubMedGoogle Scholar
  84. 84.
    Connolly J, Boyd R, Calvin J (1962) The protective effect of hypothermia in cerebral ischemia: experimental and clinical application by selective brain cooling in the human. Surgery 52:15–24PubMedGoogle Scholar
  85. 85.
    Schwartz AE, Stone JG, Finck AD, Sandhu AA, Mongero LB, Adams DC, Jonassen AE, Young WL, Michler RE (1996) Isolated cerebral hypothermia by single carotid artery perfusion of extracorporeally cooled blood in baboons. Neurosurgery 39:577–581PubMedGoogle Scholar
  86. 86.
    Gelman B, Schleien CL, Lohe A, Kuluz JW (1996) Selective brain cooling in infant piglets after cardiac arrest and resuscitation. Crit Care Med 24:1009–1017CrossRefPubMedGoogle Scholar
  87. 87.
    Natale JA, D’Alecy LG (1989) Protection from cerebral ischemia by brain cooling without reduced lactate accumulation in dogs. Stroke 20:770–777PubMedGoogle Scholar
  88. 88.
    Xiao F, Safar P, Alexander H (1995) Peritoneal cooling for mild cerebral hypothermia after cardiac arrest in dogs. Resuscitation 30:51–59CrossRefPubMedGoogle Scholar
  89. 89.
    O’Donnel J, Axelrod P, Fisher C, Lorber B (1997) Use and effectiveness of hypothermia blankets for febrile patients in the intensive care unit. Clin Infect Dis 24:1208–1213PubMedGoogle Scholar
  90. 90.
    Georgiadis D, Schwarz S, Kollmar R, Schwab S (2001) Endovascular cooling for moderate hypothermia in patients with acute stroke. Stroke 32:2550–2553PubMedGoogle Scholar
  91. 91.
    Doufas AG, Akca O, Barry A, petrusca DA, Suleman MI, Morioka N, Guarnaschelli JJ, Sessler DI (2002) Initial experience with a novel heat-exchanging catheter in neurosurgical patients. Anesth Analg 95:1752–1756PubMedGoogle Scholar
  92. 92.
    Schmutzhard E, Engelhardt K, Beer R, Brössner G, Pfausler B, Spiss H, Unterberger I, Kampfl A (2002) Safety and efficacy of a novel intravascular cooling device to control body temperature in neurologic intensive care patients: a prospective pilot study. Crit Care Med 30:2481–2488CrossRefPubMedGoogle Scholar
  93. 93.
    Andrews PJD, Harris BA (2002) The rationale for selective brain cooling. Year book of intensive care and emergency medicine. Vincent JL (ed) Springer Verlag, Berlin Heidelbrg New York, pp 738–747Google Scholar
  94. 94.
    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 56:292–298Google Scholar
  95. 95.
    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 31:2251–2256PubMedGoogle Scholar
  96. 96.
    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 56:9–13CrossRefPubMedGoogle Scholar
  97. 97.
    Tarnow-Mordi WO, Hau C, Warden A, Shearer AJ (2000) Hospital mortality in relation to staff workload: a 4-year study in an adult intensive-care unit. Lancet 356:185–189PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Intensive CareVU University Medical CenterAmsterdamThe Netherlands

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