SpringerLink
Log in

Temperature Control and the Role of Therapeutic Hypothermia in Traumatic Brain Injury

  • Chapter
  • First Online:
Traumatic Brain Injury

Part of the book series: Hot Topics in Acute Care Surgery and Trauma ((HTACST))

  • 173 Accesses

Abstract

Currently there are limited therapeutic interventions that have been reported to improve functional outcomes in patients with traumatic brain injury (TBI) in terms of successful Phase 3 randomized controlled clinical trials. Therapeutic hypothermia (controlled induced hypothermia) and targeted temperature management (32–36 °C) have been evaluated in a variety of experimental and clinical situations indicating that this is a potentially important strategy for limiting secondary injury mechanisms. Indeed, studies using clinically relevant animal models of acute CNS injury conducted by multiple laboratories have repeatedly shown that while therapeutic hypothermia is protective and improves functional outcomes, mild elevations in temperature can produce detrimental consequences. Based on these preclinical investigations, clinical studies have been initiated including both single institutional and multicenter TBI trials. Unfortunately, while some mild-to-moderate hypothermia TBI studies and trials have reported improvements in neurological outcomes in certain patient populations, larger randomized multicenter trials have failed to show significant improvements in severe TBI patients when comparing normothermic and hypothermic treatments. Various explanations for these failures have been discussed and include issues concerning patient heterogeneity, a limited therapeutic window for cooling effectiveness, and uncertainty regarding optimal cooling levels, duration as well as rewarming protocols. Nevertheless, there remains significant interest in determining better ways to apply hypothermia as well as determining which patients may be responsive or non-responsive to this powerful therapeutic intervention. This chapter summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms after TBI. Emphasis is also placed on recent studies that are hel** to clarify specific factors that may be critical in the successful use of this powerful treatment intervention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
GBP 19.95
Price includes VAT (United Kingdom)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
GBP 71.50
Price includes VAT (United Kingdom)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
GBP 89.99
Price includes VAT (United Kingdom)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Faul MXL, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.

    Google Scholar 

  2. Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018;130:1080–97. Advance online publication.

    Article  PubMed  Google Scholar 

  3. Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J Head Trauma Rehabil. 2010;25:72–80.

    Article  PubMed  Google Scholar 

  4. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21:375–8.

    Article  PubMed  Google Scholar 

  5. CDC. Traumatic Brain Injury in the United States, emergency department visits, hospitalizations, and deaths. 2016. http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf.

  6. Sarnaik A, Ferguson NM, O'Meara A, Agrawal S, Deep A, Buttram S, Bell MJ, Wisniewski SR, Luther JF, Hartman AL, Vavilala MS, Investigators of the ADAPT Trial. Age and mortality in pediatric severe traumatic Brain Injury: results from an international study. Neurocrit Care. 2018;28(3):302–13.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic Brain Injury: an overview of epidemiology, pathophysiology, and medical management. Med Clin North Am. 2020;104(2):213–38.

    Article  PubMed  Google Scholar 

  8. Tarvonen-Schröder S, Tenovuo O, Kaljonen A, Laimi K. Usability of World Health Organization disability assessment schedule in chronic traumatic brain injury. J Rehabil Med. 2018;50(6):514–8.

    Article  PubMed  Google Scholar 

  9. Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE. Traumatic brain injury in the United States: a public health perspective. J Head Trauma Rehabil. 1999;14:602–15.

    Article  CAS  PubMed  Google Scholar 

  10. Rosomoff HL, Safar P. Management of the comatose patient. Clin Anesth. 1965;1:244–58.

    CAS  PubMed  Google Scholar 

  11. Polderman KH, Tjong T** Joe R, Peerdeman SM, Vandertop WP, Girbes AR. Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury. Intensive Care Med. 2002;28:1563–73.

    Article  PubMed  Google Scholar 

  12. Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet (London, England). 2008;371(9628):1955–69.

    Article  PubMed  Google Scholar 

  13. Jackson TC, Kochanek PM. A new vision for therapeutic hypothermia in the era of targeted temperature management: a speculative synthesis. Ther Hypothermia Temp Manag. 2019;9(1):13–47.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fay T. Observations on generalized refrigeration in cases of severe cerebral trauma. Assoc Res Nerv Ment Dis Proc. 1943;24:611–9.

    Google Scholar 

  15. Williams GR Jr, Spencer FC. The clinical use of hypothermia following cardiac arrest. Ann Surg. 1958;148:462–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Benson DW, Williams GR, Spencer FC. The use of hypothermia following cardiac arrest. Anesth Analg. 1959;38:423–8.

    Article  CAS  PubMed  Google Scholar 

  17. Alzaga AG, Salazar GA, Varon J. Resuscitation great. Breaking the thermal barrier: Dr. Temple Fay. Resuscitation. 2006;69:359–64.

    Article  PubMed  Google Scholar 

  18. Brain Trauma F, American Association of Neurological, S., Congress of Neurological, S. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24(Suppl 1):S1–106.

    Google Scholar 

  19. Rosomoff HL, Holaday DA. Cerebral blood flow and cerebral oxygen consumption during hypothermia. Am J Phys. 1954;179:85–8.

    CAS  Google Scholar 

  20. Karnatovskaia LV, Wartenberg KE, Freeman WD. Therapeutic hypothermia for neuroprotection: history, mechanisms, risks, and clinical applications. Neurohospitalist. 2014;4:153–63.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Dietrich WD, Busto R, Globus MY, Ginsberg MD. Brain damage and temperature: cellular and molecular mechanisms. Adv Neurol. 1996;71:177–97.

    CAS  PubMed  Google Scholar 

  22. Polderman KH, Andrews PJ. Hypothermia in patients with brain injury: the way forward? Lancet Neurol. 2011;10:404–5. author reply 1180.0.

    Article  PubMed  Google Scholar 

  23. Berntman L, Welsh FA, Harp JR. Cerebral protective effect of low-grade hypothermia. Anesthesiology. 1981;55:495–8.

    Article  CAS  PubMed  Google Scholar 

  24. Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke. 1979;10:267–72.

    Article  CAS  PubMed  Google Scholar 

  25. Furlow TW Jr. Cerebral ischemia produced by four-vessel occlusion in the rat: a quantitative evaluation of cerebral blood flow. Stroke. 1982;13(6):852–5.

    Article  PubMed  Google Scholar 

  26. Blomgvist P, Mabe H, Ingvar M, Siesjo BK. Models for studying long-term recovery following forebrain ischemia in the rat.1. Circulatory and functional effects of 4-vessel occlusion. Acta Neurol Scand. 1984;69:376–84.

    Article  Google Scholar 

  27. Busto R, Dietrich WD, Globus MY, Valdes I, Scheinberg P, Ginsberg MD. Small differences in intra ischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab. 1987;7:729–38.

    Article  CAS  PubMed  Google Scholar 

  28. Dietrich WD, Bramlett HM. Therapeutic hypothermia and targeted temperature management for traumatic brain injury: experimental and clinical experience. Brain Circ. 2017;3(4):186–98.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Leonov Y, Sterz F, Safar P, Radovsky A, Oku K, Tisherman S, Stezoski SW. Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J Cereb Blood Flow Metab. 1990;10:57–70.

    Article  CAS  PubMed  Google Scholar 

  30. Welsh FA, Sims RE, Harris VA. Mild hypothermia prevents ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab. 1990;10(4):557–63.

    Article  CAS  PubMed  Google Scholar 

  31. Onesti ST, Baker CJ, Sun PP, Solomon RA. Transient hypothermia reduces focal ischemic brain injury in the rat. Neurosurgery. 1991;29(3):369–73.

    Article  CAS  PubMed  Google Scholar 

  32. Bramlett HM, Green EJ, Dietrich WD, Busto R, Globus MY, Ginsberg MD. Posttraumatic brain hypothermia provides protection from sensorimotor and cognitive behavioral deficits. J Neurotrauma. 1995;12:289–98.

    Article  CAS  PubMed  Google Scholar 

  33. Dietrich WD, Atkins CM, Bramlett HM. Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia. J Neurotrauma. 2009;26:301–12.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dietrich WD, Busto R, Alonso O, Globus MY, Ginsberg MD. Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats. J Cereb Blood Flow Metab. 1993;13(4):541–9.

    Article  CAS  PubMed  Google Scholar 

  35. Colbourne F, Li H, Buchan AM. Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. J Cereb Blood Flow Metab. 1999;19(7):742–9.

    Article  CAS  PubMed  Google Scholar 

  36. Corbett D, Hamilton M, Colbourne F. Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion. Exp Neurol. 2000;163(1):200–6.

    Article  CAS  PubMed  Google Scholar 

  37. Lu XC, Shear DA, Deng-Bryant Y, Leung LY, Wei G, Chen Z, Tortella FC. Comprehensive evaluation of neuroprotection achieved by extended selective brain cooling therapy in a rat model of penetrating ballistic-like brain injury. Ther Hypothermia Temp Manag. 2016;6(1):30–9.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Dietrich WD, Bramlett HM. Hyperthermia and central nervous system injury. Prog Brain Res. 2007;162:201–17.

    Article  CAS  PubMed  Google Scholar 

  39. Dietrich WD, Alonso O, Halley M, Busto R. Delayed posttraumatic brain hyperthermia worsens outcome after fluid percussion brain injury: a light and electron microscopic study in rats. Neurosurgery. 1996;38:533–41; discussion 541.

    CAS  PubMed  Google Scholar 

  40. Yu CG, Jagid J, Ruenes G, Dietrich WD, Marcillo AE, Yezierski RP. Detrimental effects of systemic hyperthermia on locomotor function and histopathological outcome after traumatic spinal cord injury in the rat. Neurosurgery. 2001;49:152–8; discussion 158-9.

    CAS  PubMed  Google Scholar 

  41. Kilpatrick MM, Lowry DW, Firlik AD, Yonas H, Marion DW. Hyperthermia in the neurosurgical intensive care unit. Neurosurgery. 2000;47:850–5; discussion 855-6.

    Article  CAS  PubMed  Google Scholar 

  42. Natale JE, Joseph JG, Helfaer MA, Shaffner DH. Early hyperthermia after traumatic brain injury in children: risk factors, influence on length of stay, and effect on short-term neurologic status. Crit Care Med. 2000;28:2608–15.

    Article  CAS  PubMed  Google Scholar 

  43. Thompson HJ, Pinto-Martin J, Bullock MR. Neurogenic fever after traumatic brain injury: an epidemiological study. J Neurol Neurosurg Psychiatry. 2003;74:614–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Diringer MN, Neurocritical Care Fever Reduction Trial, G. Treatment of fever in the neurologic intensive care unit with a catheter-based heat exchange system. Crit Care Med. 2004;32:559–64.

    Article  PubMed  Google Scholar 

  45. Todd MM, Hindman BJ, Clarke WR, Torner JC, Weeks JB, Bayman EO, Shi Q, Spofford CM, Investigators I. Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2009;64:897–908; discussion 908.

    Article  PubMed  Google Scholar 

  46. Li J, Jiang JY. Chinese head trauma data bank: effect of hyperthermia on the outcome of acute head trauma patients. J Neurotrauma. 2012;29:96–100.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Hifumi T, Kuroda Y, Kawakita K, Yamashita S, Oda Y, Dohi K, Maekawa T. Fever control management is preferable to mild therapeutic hypothermia in traumatic Brain Injury patients with abbreviated Injury scale 3-4: a multi-center, randomized controlled Trial. J Neurotrauma. 2016;33(11):1047–53.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Clifton GL, Jiang JY, Lyeth BG, Jenkins LW, Hamm RJ, Hayes RL. Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab. 1991;11:114–21.

    Article  CAS  PubMed  Google Scholar 

  49. Dietrich WD, Alonso O, Busto R, Globus MY, Ginsberg MD. Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. Acta Neuropathol. 1994;87:250–8.

    Article  CAS  PubMed  Google Scholar 

  50. Bramlett HM, Dietrich WD, Green EJ, Busto R. Chronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia. Acta Neuropathol (Berl). 1997;93:190–9.

    Article  CAS  PubMed  Google Scholar 

  51. Lyeth BG, Jiang JY, Liu S. Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury. J Neurotrauma. 1993;10:57–64.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  53. Dixon CE, Markgraf CG, Angileri F, Pike BR, Wolfson B, Newcomb JK, Bismar MM, Blanco AJ, Clifton GL, Hayes RL. Protective effects of moderate hypothermia on behavioral deficits but not necrotic cavitation following cortical impact injury in the rat. J Neurotrauma. 1998;15:95–103.

    Article  CAS  PubMed  Google Scholar 

  54. Matsushita Y, Bramlett HM, Alonso O, Dietrich WD. Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult. Crit Care Med. 2001;29:2060–6.

    Article  CAS  PubMed  Google Scholar 

  55. Ma M, Matthews BT, Lampe JW, Meaney DF, Shofer FS, Neumar RW. Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury. Exp Neurol. 2009;215:119–27.

    Article  PubMed  Google Scholar 

  56. Bramlett HM, Dietrich WD. The effects of posttraumatic hypothermia on diffuse axonal Injury following Parasagittal fluid percussion brain injury in rats. Ther Hypothermia Temp Manag. 2012;2:14–23.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Bramlett H, Dietrich WD. Long-term consequences of traumatic brain injury: current status of potential mechanisms of Injury and neurologic outcomes. J Neurotrauma. 2014;32:1834.

    Article  PubMed  Google Scholar 

  58. Markgraf CG, Clifton GL, Moody MR. Treatment window for hypothermia in brain injury. J Neurosurg. 2001;95:979–83.

    Article  CAS  PubMed  Google Scholar 

  59. Suzuki T, Bramlett HM, Dietrich WD. The importance of gender on the beneficial effects of posttraumatic hypothermia. Exp Neurol. 2003;184:1017–26.

    Article  PubMed  Google Scholar 

  60. Suzuki T, Bramlett HM, Ruenes G, Dietrich WD. The effects of early post-traumatic hyperthermia in female and ovariectomized rats. J Neurotrauma. 2004;21:842–53.

    Article  PubMed  Google Scholar 

  61. Hirst TC, Klasen MG, Rhodes JK, Macleod MR, Andrews P. A systematic review and meta-analysis of hypothermia in experimental traumatic brain injury: why have promising animal studies not been replicated in pragmatic clinical trials? J Neurotrauma. 2020;37(19):2057–68.

    Article  PubMed  Google Scholar 

  62. Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, Jane JA, Marmarou A, Foulkes MA. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993a;34:216–22.

    Article  CAS  PubMed  Google Scholar 

  63. Robertson CS, Valadka AB, Hannay HJ, Contant CF, Gopinath SP, Cormio M, Uzura M, Grossman RG. Prevention of secondary ischemic insults after severe head injury. Crit Care Med. 1999;27:2086–95.

    Article  CAS  PubMed  Google Scholar 

  64. Dietrich WD. The importance of brain temperature in cerebral injury. J Neurotrauma. 1992;9(Suppl 2):S475–85.

    PubMed  Google Scholar 

  65. Globus MY, Alonso O, Dietrich WD, Busto R, Ginsberg MD. Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem. 1995;65:1704–11.

    Article  CAS  PubMed  Google Scholar 

  66. Kinoshita K, Chatzipanteli IK, Vitarbo E, Truettner JS, Alonso OF, Dietrich WD. Interleukin-1beta messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats: importance of injury severity and brain temperature. Neurosurgery. 2002a;51:195–203. discussion 203.

    Article  PubMed  Google Scholar 

  67. Truettner JS, Suzuki T, Dietrich WD. The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat. Brain Res Mol Brain Res. 2005;138:124–34.

    Article  CAS  PubMed  Google Scholar 

  68. Lotocki G, de Rivero Vaccari JP, Perez ER, Sanchez-Molano J, Furones-Alonso O, Bramlett HM, Dietrich WD. Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia. J Neurotrauma. 2009;26:1123–34.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Dietrich WD, Bramlett HM. The evidence for hypothermia as a neuroprotectant in traumatic brain injury. Neurotherapeutics. 2010;7:43–50.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Lotocki G, de Rivero Vaccari JP, Alonso O, Molano JS, Nixon R, Safavi P, Dietrich WD, Bramlett HM. Oligodendrocyte vulnerability following traumatic brain injury in rats. Neurosci Lett. 2011;499:143–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yenari MA, Han HS. Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat Rev Neurosci. 2012;13:267–78.

    Article  CAS  PubMed  Google Scholar 

  72. Yenari MA, Han HS. Influence of therapeutic hypothermia on regeneration after cerebral ischemia. Front Neurol Neurosci. 2013;32:122–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Han Z, Liu X, Luo Y, Ji X. Therapeutic hypothermia for stroke: where to go? Exp Neurol. 2015;272:67.

    Article  PubMed  Google Scholar 

  74. Li YH, Zhang CL, Zhang XY, Zhou HX, Meng LL. Effects of mild induced hypothermia on hippocampal connexin 43 and glutamate transporter 1 expression following traumatic brain injury in rats. Mol Med Rep. 2015;11:1991–6.

    Article  CAS  PubMed  Google Scholar 

  75. Jiang JY, Lyeth BG, Kapasi MZ, Jenkins LW, Povlishock JT. Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat. Acta Neuropathol. 1992;84:495–500.

    Article  CAS  PubMed  Google Scholar 

  76. Dietrich WD, Bramlett HM. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: clinical challenges for successful translation. Brain Res. 2016;1640(Pt A):94–103.

    Article  CAS  PubMed  Google Scholar 

  77. Chatzipanteli K, Wada K, Busto R, Dietrich WD. Effects of moderate hypothermia on constitutive and inducible nitric oxide synthase activities after traumatic brain injury in the rat. J Neurochem. 1999;72:2047–52.

    Article  CAS  PubMed  Google Scholar 

  78. Chatzipanteli K, Alonso OF, Kraydieh S, Dietrich WD. Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: biochemical and immunocytochemical studies. J Cereb Blood Flow Metab. 2000;20:531–42.

    Article  CAS  PubMed  Google Scholar 

  79. Kinoshita K, Chatzipanteli K, Alonso OF, Howard M, Dietrich WD. The effect of brain temperature on hemoglobin extravasation after traumatic brain injury. J Neurosurg. 2002b;97:945–53.

    Article  PubMed  Google Scholar 

  80. Vitarbo EA, Chatzipanteli K, Kinoshita K, Truettner JS, Alonso OF, Dietrich WD. Tumor necrosis factor alpha expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature. Neurosurgery. 2004;55:416–24; discussion 424-5.

    Article  PubMed  Google Scholar 

  81. Truettner JS, Bramlett HM, Dietrich WD. Posttraumatic therapeutic hypothermia alters microglial and macrophage polarization toward a beneficial phenotype. J Cereb Blood Flow Metab. 2017;37(8):2952–62.

    Article  CAS  PubMed  Google Scholar 

  82. Atkins CM, Oliva AA Jr, Alonso OF, Chen S, Bramlett HM, Hu BR, Dietrich WD. Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury. Eur J Neurosci. 2007;26:810–9.

    Article  PubMed  Google Scholar 

  83. Atkins CM, Truettner JS, Lotocki G, Sanchez-Molano J, Kang Y, Alonso OF, Sick TJ, Dietrich WD, Bramlett HM. Post-traumatic seizure susceptibility is attenuated by hypothermia therapy. Eur J Neurosci. 2010;32:1912–20.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yan C, Mao J, Yao C, Liu Y, Yan H, ** W. Neuroprotective effects of mild hypothermia against traumatic brain injury by the involvement of the Nrf2/ARE pathway. Brain Behav. 2022;12(8):e2686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Bregy A, Nixon R, Lotocki G, Alonso OF, Atkins CM, Tsoulfas P, Bramlett HM, Dietrich WD. Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat. Exp Neurol. 2012;233:821–8.

    Article  CAS  PubMed  Google Scholar 

  86. Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, DeKosky ST. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997;336:540–6.

    Article  CAS  PubMed  Google Scholar 

  87. Callaway CW, Donnino MW, Fink EL, Geocadin RG, Golan E, Kern KB, Leary M, Meurer WJ, Peberdy MA, Thompson TM, Zimmerman JL. Part 8: post-cardiac arrest care: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S465–82.

    PubMed  PubMed Central  Google Scholar 

  88. Suehiro E, Koizumi H, Fujisawa H, Fujita M, Kaneko T, Oda Y, Yamashita S, Tsuruta R, Maekawa T, Suzuki M. Diverse effects of hypothermia therapy in patients with severe traumatic brain injury based on the computed tomography classification of the traumatic coma data bank. J Neurotrauma. 2015;32:353–8.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Martinello K, Hart AR, Yap S, Mitra S, Robertson NJ. Management and investigation of neonatal encephalopathy: 2017 update. Arch Dis Child Fetal Neonatal Ed. 2017;102(4):F346–58.

    Article  PubMed  Google Scholar 

  90. Adelson PD, Wisniewski SR, Beca J, Brown SD, Bell M, Muizelaar JP, Okada P, Beers SR, Balasubramani GK, Hirtz D, Paediatric Traumatic Brain Injury C. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (cool kids): a phase 3, randomised controlled trial. Lancet Neurol. 2013;12:546–53.

    Article  PubMed  Google Scholar 

  91. Nielsen N, Wettersley J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, AlSubaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. TTM Trial Investigators. Targeted temperature management at 33 degrees c versus 36 degrees c after cardia arrest. N Engl J Med. 2013;369:2197–206.

    Article  CAS  PubMed  Google Scholar 

  92. Maekawa T, Yamashita S, Nagao S, Hayashi N, Ohashi Y, Brain-Hypothermia Study G. Prolonged mild therapeutic hypothermia versus fever control with tight hemodynamic monitoring and slow rewarming in patients with severe traumatic brain injury: a randomized controlled trial. J Neurotrauma. 2015;32:422–9.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Moler FW, Silverstein FS, Holubkov R, Slomine BS, Christensen JR, Nadkarni VM, Meert KL, Clark AE, Browning B, Pemberton VL, Page K, Shankaran S, Hutchison JS, Newth CJ, Bennett KS, Berger JT, Topjian A, Pineda JA, Koch JD, Schleien CL, Dalton HJ, Ofori-Amanfo G, Goodman DM, Fink EL, McQuillen P, Zimmerman JJ, Thomas NJ, van der Jagt EW, Porter MB, Meyer MT, Harrison R, Pham N, Schwarz AJ, Nowak JE, Alten J, Wheeler DS, Bhalala US, Lidsky K, Lloyd E, Mathur M, Shah S, Wu T, Theodorou AA, Sanders RC Jr, Dean JM. THAPCA Trial Investigators. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med. 2015;372:1898–908.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Moler FW, Silverstein FS, Holubkov R, Slomine BS, Christensen JR, Nadkarni VM, Meert KL, Browning B, Pemberton VL, Page K, Gildea MR, Scholefield BR, Shankaran S, Hutchison JS, Berger JT, Ofori-Amanfo G, Newth CJ, Topjian A, Bennett KS, Koch JD, Pham N, Chanani NK, Pineda JA, Harrison R, Dalton HJ, Alten J, Schleien CL, Goodman DM, Zimmerman JJ, Bhalala US, Schwarz AJ, Porter MB, Shah S, Fink EL, McQuillen P, Wu T, Skellett S, Thomas NJ, Nowak JE, Baines PB, Pappachan J, Mathur M, Lloyd E, Vander Jagt EW, Dobyns EL, Meyer MT, Sanders RC Jr, Clark AE, Dean JM. THAPCA Trial Investigators. Therapeutic hypothermia after in hospital cardiac arrest in children. N Engl J Med. 2017;376:318–29.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Cooper DJ, Nichol AD, Bailey M, Bernard S, Cameron PA, Pili-Floury S, Forbes A, Gantner D, Higgins AM, Huet O, Kasza J, Murray L, Newby L, Presneill JJ, Rashford S, Rosenfeld JV, Stephenson M, Vallance S, Varma D, Webb S, POLAR Trial Investigators and the ANZICS Clinical Trials Group. Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic Brain Injury: the POLAR randomized clinical Trial. JAMA. 2018;320(21):2211–20.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Adelson PD, Wisniewski SR, Beca J, Brown SD, Bell M, Muizelaar JP, Okada P, Beers SR, Balasubramani GK, Hirtz D, Paediatric Traumatic Brain Injury Consortium. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (cool kids): a phase 3, randomised controlled trial. Lancet Neurol. 2013;12(6):546–53.

    Article  PubMed  Google Scholar 

  97. Beca J, McSharry B, Erickson S, Yung M, Schibler A, Slater A, Wilkins B, Singhal A, Williams G, Sherring C, Butt W, Pediatric Study Group of the Australia and New Zealand Intensive Care Society Clinical Trials Group. Hypothermia for traumatic brain injury in children-a phase II randomized controlled Trial. Crit Care Med. 2015;43(7):1458–66.

    Article  CAS  PubMed  Google Scholar 

  98. Clifton GL, Valadka A, Zygun D, Coffey CS, Drever P, Fourwinds S, Janis LS, Wilde E, Taylor P, Harshman K, Conley A, Puccio A, Levin HS, McCauley SR, Bucholz RD, Smith KR, Schmidt JH, Scott JN, Yonas H, Okonkwo DO. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: hypothermia II): a randomized trial. Lancet Neurol. 2011;10:131–9.

    Article  PubMed  Google Scholar 

  99. Clifton GL, Choi SC, Miller ER, Levin HS, Smith KR Jr, Muizelaar JP, Wagner FC Jr, Marion DW, Luerssen TG. Intercenter variance in clinical trials of head trauma—experience of the National Acute Brain Injury Study: hypothermia. J Neurosurg. 2001a;95:751–5.

    Article  CAS  PubMed  Google Scholar 

  100. Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR Jr, Muizelaar JP, Wagner FC Jr, Marion DW, Luerssen TG, Chesnut RM, Schwartz M. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001b;344:556–63.

    Article  CAS  PubMed  Google Scholar 

  101. Hifumi T, Kuroda Y, Kawakita K, Yamashita S, Oda Y, Dohi K, Maekawa T. Fever control management is preferable to mild therapeutic hypothermia in traumatic brain injury patients with abbreviated Injury scale 3–4: a multi-center, randomized controlled TRIAL. J Neurotrauma. 2015;33:1047.

    Article  PubMed  Google Scholar 

  102. Madden LK, DeVon HA. A systematic review of the effects of body temperature on outcome after adult traumatic Brain Injury. J Neurosci Nurs. 2015;47:190–203.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Kaneko T, Fujita M, Yamashita S, Oda Y, Suehiro E, Dohi K, Kasaoka S, Kuroda Y, Kobata H, Maekawa T. Slow rewarming improved the neurological outcomes of prolonged mild therapeutic hypothermia in patients with severe traumatic brain injury and an evacuated hematoma. Sci Rep. 2018;8(1):11630.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Kobata H, Kuroda Y, Suehiro E, Kaneko T, Fujita M, Bunya N, Miyata K, Inoue A, Hifumi T, Oda Y, Dohi K, Yamashita S, Maekawa T. Benefits of hypothermia for young patients with acute subdural hematoma: a computed tomography analysis of the brain hypothermia study. Neurotrauma Rep. 2022;3(1):250–60.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Andrews PJ, Sinclair HL, Battison CG, Polderman KH, Citerio G, Mascia L, Harris BA, Murray GD, Stocchetti N, Menon DK, Shakur H, De Backer D, Eurotherm Trial, c. European society of intensive care medicine study of therapeutic hypothermia (32-35 degrees C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial). Trials. 2011;12:8.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JK, Murray GD, Eurotherm3235 Trial Collaborators. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2015;373(25):2403–12.

    Article  CAS  PubMed  Google Scholar 

  107. Andrews P, Rodriguez A, Suter P, Battison CG, Rhodes J, Puddu I, Harris BA. Mortality risk stratification after traumatic Brain Injury and Hazard of death with titrated hypothermia in the Eurotherm3235Trial. Crit Care Med. 2017;45(5):883–90.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Jiang JY, Xu W, Li WP, Gao GY, Bao YH, Liang YM, Luo QZ. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J Cereb Blood Flow Metab. 2006;26(6):771–6.

    Article  PubMed  Google Scholar 

  109. Lei J, Gao G, Mao Q, Feng J, Wang L, You W, Jiang J, Collaborators, L.T.H.t. Rationale, methodology, and implementation of a nationwide multicenter randomized controlled trial of long-term mild hypothermia for severe traumatic brain injury (the LTH-1 trial). Contemp Clin Trials. 2015;40:9–14.

    Article  PubMed  Google Scholar 

  110. Crossley S, Reid J, McLatchie R, Hayton J, Clark C, MacDougall M, Andrews PJ. A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Crit Care. 2014;18:R75.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Li P, Yang C. Moderate hypothermia treatment in adult patients with severe traumatic brain injury: a meta-analysis. Brain Inj. 2014;28:1036–41.

    Article  PubMed  Google Scholar 

  112. Zhang BF, Wang J, Liu ZW, Zhao YL, Li DD, Huang TQ, Gu H, Song JN. Meta-analysis of the efficacy and safety of therapeutic hypothermia in children with acute traumatic brain injury. World Neurosurg. 2015;83:567–73.

    Article  PubMed  Google Scholar 

  113. Thakur K, Kaur H, Dhandapani M, Xavier T, Srinivasan G, Gopichandran L, Dhandapani S. Systematic review exploring the effect of therapeutic hypothermia on patients with intracranial hypertension. Surg Neurol Int. 2022;13:237.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Marion DW, Regasa LE. Revisiting therapeutic hypothermia for severe traumatic brain injury again. Crit Care (London, England). 2014;18(3):160.

    Article  Google Scholar 

  115. Abu-Arafeh A, Rodriguez A, Paterson RL, Andrews P. Temperature variability in a modern targeted temperature management Trial. Crit Care Med. 2018;46(2):223–8.

    Article  PubMed  Google Scholar 

  116. Nichol A, Gantner D, Presneill J, Murray L, Trapani T, Bernard S, Cameron P, Capellier G, Forbes A, McArthur C, Newby L, Rashford S, Rosenfeld JV, Smith T, Stephenson M, Varma D, Walker T, Webb S, Cooper DJ. Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury. Crit Care Resusc. 2015;17:92–100.

    PubMed  Google Scholar 

  117. Olah E, Poto L, Rumbus Z, Pakai E, Romanovsky AA, Hegyi P, Garami A. POLAR study revisited: therapeutic hypothermia in severe Brain Trauma should not be abandoned. J Neurotrauma. 2021;38(19):2772–6.

    Article  PubMed  Google Scholar 

  118. Hui J, Feng J, Tu Y, Zhang W, Zhong C, Liu M, Wang Y, Long L, Chen L, Liu J, Mou C, Qiu B, Huang X, Huang Q, Zhang N, Yang X, Yang C, Li L, Ma R, Wu X, LTH-1 Trial collaborators. Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): a multicenter randomized controlled trial. EClinicalMedicine. 2021;32:100732.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Wu X, Tao Y, Marsons L, Dee P, Yu D, Guan Y, Zhou X. The effectiveness of early prophylactic hypothermia in adult patients with traumatic brain injury: a systematic review and meta-analysis. Aust Crit Care. 2021;34(1):83–91.

    Article  PubMed  Google Scholar 

  120. Hergenroeder GW, Yokobori S, Choi HA, Schmitt K, Detry MA, Schmitt LH, McGlothlin A, Puccio AM, Jagid J, Kuroda Y, Nakamura Y, Suehiro E, Ahmad F, Viele K, Wilde EA, McCauley SR, Kitagawa RS, Temkin NR, Timmons SD, Diringer MN, Kim DH. Hypothermia for patients requiring evacuation of subdural hematoma: a multicenter randomized clinical Trial. Neurocrit Care. 2022;36(2):560–72.

    Article  CAS  PubMed  Google Scholar 

  121. Inoue A, Hifumi T, Kuroda Y, Nishimoto N, Kawakita K, Yamashita S, Oda Y, Dohi K, Kobata H, Suehiro E, Maekawa T, Brain Hypothermia (B-HYPO) Study Group in Japan. Mild decrease in heart rate during early phase of targeted temperature management following tachycardia on admission is associated with unfavorable neurological outcomes after severe traumatic brain injury: a post hoc analysis of a multicenter randomized controlled trial. Crit Care. 2018;22(1):352.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Hutchison, J.S., Ward, R.E., Lacroix, J., Hebert, P.C., Barnes, M.A., Bohn, D.J., Dirks, P.B., Doucette, S., Fergusson, D., Gottesman, R., Joffe, A.R., Kirpalani, H.M., Meyer, P.G., Morris, K.P., Moher, D., Singh, R.N., Skippen, P.W., (2008) Hypothermia pediatric head injury trial I. the Canadian critical Care Trials, G. hypothermia therapy after traumatic brain injury in children. N Engl J Med 358, 2447–2456.

    Google Scholar 

  123. Newmyer R, Mendelson J, Pang D, Fink EL. Targeted temperature management in pediatric central nervous system disease. Curr Treat Options Pediatr. 2015;1:38–47.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Lewis SR, Baker PE, Andrews PJ, Cheng A, Deol K, Hammond N, Saxena M. Interventions to reduce body temperature to 35 °C to 37 °C in adults and children with traumatic brain injury. Cochrane Database Syst Rev. 2020;10(10):CD006811.

    PubMed  Google Scholar 

  125. Du Q, Liu Y, Chen X, Li K. Effect of hypothermia therapy on children with traumatic Brain Injury: a meta-analysis of randomized controlled trials. Brain Sci. 2022;12(8):1009.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Rosario BL, Horvat CM, Wisniewski SR, Bell MJ, Panigrahy A, Zuccoli G, Narayanan S, Balasubramani GK, Beers SR, Adelson PD, Investigators of the Cool Kids Trial. Presenting characteristics associated with outcome in children with severe traumatic Brain Injury: a secondary analysis from a randomized, controlled Trial of therapeutic hypothermia. Pediatric Crit Care Med. 2018;19(10):957–64.

    Article  Google Scholar 

  127. Zusman BE, Kochanek PM, Bell MJ, Adelson PD, Wisniewski SR, Au AK, Clark R, Bayır H, Janesko-Feldman K, Jha RM. Cerebrospinal fluid sulfonylurea Receptor-1 is associated with intracranial pressure and outcome after pediatric TBI: an exploratory analysis of the cool kids Trial. J Neurotrauma. 2021;38(12):1615–9.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Bhatti F, Naiman M, Tsarev A, Kulstad E. Esophageal temperature management in patients suffering from traumatic brain injury. Ther Hypothermia Temp Manag. 2019;9(4):238–42.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Ferreira R, de Paiva B, de Freitas F, Machado FR, Silva GS, Raposo RM, Silveira CF, Centeno RS. Efficacy and safety of a nasopharyngeal catheter for selective Brain cooling in patients with traumatic brain injury: a prospective, non-randomized pilot study. Neurocrit Care. 2021;34(2):581–92.

    Article  CAS  PubMed  Google Scholar 

  130. van der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR. Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain. 2007;130:3063–74.

    Article  PubMed  Google Scholar 

  131. Callaway CW, Coppler PJ, Faro J, Puyana JS, Solanki P, Dezfulian C, Doshi AA, Elmer J, Frisch A, Guyette FX, Okubo M, Rittenberger JC, Weissman A. Association of initial illness severity and outcomes after cardiac arrest with targeted temperature management at 36 °C or 33 °C. JAMA Netw Open. 2020;3(7):e208215.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Geocadin RG. Moving beyond one-size-fits-all treatment for patients after cardiac arrest. JAMA Netw Open. 2020;3(7):e208809.

    Article  PubMed  Google Scholar 

  133. Elmer J, He Z, May T, Osborn E, Moberg R, Kemp S, Stover J, Moyer E, Geocadin RG, Hirsch KG, PRECICECAP Study Team. Precision care in cardiac arrest: ICECAP (PRECICECAP) study protocol and informatics approach. Neurocrit Care. 2022;37(Suppl 2):237–47.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Yokobori S, Gajavelli S, Mondello S, Mo-Seaney J, Bramlett HM, Dietrich WD, Bullock MR. Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model. J Neurosurg. 2013b;118:370–80.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA

    W. Dalton Dietrich & Helen M. Bramlett

  2. Bruce W. Carter Department of Veterans, Affairs Medical Center, Miami, FL, USA

    Helen M. Bramlett

Authors
  1. W. Dalton Dietrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helen M. Bramlett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W. Dalton Dietrich .

Editor information

Editors and Affiliations

  1. Dept. Anesthesia & Intensive Care, Pisa University Hospital, Pisa, Italy

    Etrusca Brogi

  2. General, Emergency and Trauma Surgery Deptartment, Pisa University Hospital, PISA, Pisa, Italy

    Federico Coccolini

  3. Surgical Intensive Care Unit, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Eric J. Ley

  4. Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Alex Valadka

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dietrich, W.D., Bramlett, H.M. (2024). Temperature Control and the Role of Therapeutic Hypothermia in Traumatic Brain Injury. In: Brogi, E., Coccolini, F., Ley, E.J., Valadka, A. (eds) Traumatic Brain Injury. Hot Topics in Acute Care Surgery and Trauma. Springer, Cham. https://doi.org/10.1007/978-3-031-50117-3_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-50117-3_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-50116-6

  • Online ISBN: 978-3-031-50117-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation