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Prophylactic and Therapeutic Hypothermia in Severe Traumatic Brain Injury

  • Traumatic Brain Injury (A Valadka, Section Editor)
  • Published:
Current Trauma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review aims to synthesize knowledge on the efficacy and safety of prophylactic hypothermia (PH—cooling started shortly after trauma) and therapeutic hypothermia (TH—cooling started to treat increased intracranial pressure (ICP)) in severe traumatic brain injury (TBI).

Recent Findings

Current evidence on the use of hypothermia in severe TBI is conflicting. Recent multicenter trials on the topic have demonstrated no improvement in functional outcome or mortality in patients treated with PH. Certain patient subgroups seem to benefit from this therapy, such as individuals undergoing craniotomy. TH appears to be ineffective as a stage 2 therapy, but evidence supports its use in stage 3 ICP management. Higher risks of complications occur with hypothermia, but they can be mitigated by using milder cooling, selective brain cooling, and gradual rewarming.

Summary

Short-term PH appears to be ineffective in improving outcome for severe TBI. However, PH may still be useful as a longer-duration therapy and in specific patient subgroups. In addition, optimal rate of rewarming and ideal target temperature need to be established. TH as a stage 3 ICP control therapy has only shown benefit in small trials. Higher-quality studies that shed light on these questions are required.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobsingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341–53.

    PubMed  Google Scholar 

  2. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21(5):375–8.

    Article  PubMed  Google Scholar 

  3. Scholten AC, Haagsma JA, Panneman MJM, Van Beeck EF, Polinder S. Traumatic brain injury in the Netherlands: incidence, costs and disability-adjusted life years. PLoS One. 2014;9(10):e110905.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Te Ao B, Brown P, Tobias M, Ameratunga S, Barker-collo S, Theadom A, et al. Cost of traumatic brain injury in New Zealand evidence from a population-based study. Neurology. 2014;83(18):1645–52.

    Article  Google Scholar 

  5. Chen A, Bushmeneva K, Zagorski B, Colantonio A, Parsons D. Direct cost associated with acquired brain injury in Ontario. BMC Neurol. 2012;12:76. https://doi.org/10.1186/1471-2377-12-76

  6. Maas AIR, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol [Internet]. 2008;7(8):728–41. Available from: http://www.sciencedirect.com/science/article/pii/S1474442208701649

    Article  Google Scholar 

  7. Stein SC, Georgoff P, Meghan S, Mizra K. 150 years of treating severe traumatic brain injury: a systematic review of progress in mortality. J Neurotrauma. 2010;27(7):1343–53.

    Article  PubMed  Google Scholar 

  8. Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC, Becker DP, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991 Nov;75(5):731–9.

    Article  PubMed  CAS  Google Scholar 

  9. Gerber L, Chiu Y, Carney N, Hartl R, Ghajar J. Marked reduction in mortality in patients with severe traumatic brain injury. J Neurosurg [Internet]. 2013;119(6):1583–90. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=medl&NEWS=N&AN=24098983

    Article  PubMed  Google Scholar 

  10. •• Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GWJ, Bell MJ, et al. Guidelines for the management of severe traumatic brain injury, Fourth Edition. Neurosurgery. 2017;80(1):6–15. Most recent guidelines, established using a systematic review with quality assessment approach, on the management of severe TBI.

    PubMed  Google Scholar 

  11. •• Andrews PJD, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JKJ, et al. Hypothermia for intracranial hypertension after traumatic brain. N Engl J Med. 2015;373(25):2403–12. Largest and most recent multicenter RCT on TH to treat severe TBI.

    Article  PubMed  CAS  Google Scholar 

  12. Hutchinson PJ, Kolias AG, Timofeev IS, Corteen EA, Czosnyka M, Timothy J, et al. Trial of decompressive craniectomy for traumatic intracranial hypertension. N Engl J Med. 2016;375(12):1119–30.

    Article  PubMed  Google Scholar 

  13. Li J, Jiang J. Chinese Head Trauma Data Bank: effect of hyperthermia on the outcome of acute head trauma patients. J Neurotrauma. 2012;29(1):96–100.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bao L, Chen D, Ding L, Ling W, Xu F. Fever burden is an independent predictor for prognosis of traumatic brain injury. 2014;9(3):3–7.

    Google Scholar 

  15. Rincon F, Ghosh S, Dey S, Maltenfort M, Vibbert M, Urtecho J, et al. Impact of acute lung injury and acute respiratory distress syndrome after traumatic brain injury in the United States. Neurosurgery [Internet]. 2012;71(4):795–803. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=medl&NEWS=N&AN=22855028

    Article  Google Scholar 

  16. Dietrich WD, Bramlett HM. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: clinical challenges for successful translation. Brain Res [Internet]. 2016;1640:94–103. https://doi.org/10.1016/j.brainres.2015.12.034.

    Article  CAS  Google Scholar 

  17. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.

    Article  Google Scholar 

  18. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.

    Article  PubMed  Google Scholar 

  19. Yokobori S, Yokota H. Targeted temperature management in traumatic brain injury. J Intensive Care. 2016;4:28.

    Article  PubMed  PubMed Central  Google Scholar 

  20. • Maekawa T, Yamashita S, Nagao S, Hayashi N, Ohashi Y. 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(7):422–9. Most recent multicenter trial assessing the impact of prolonged PH (72 hours) in severe TBI.

    Article  PubMed  PubMed Central  Google Scholar 

  21. •• Clifton GL, Valadka A, Zygun D, Coffey CS, Drever P, Fourwinds S, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011;10(2):131–9. Recent multicenter trial on the impact of PH on TBI outcomes.

    Article  PubMed  Google Scholar 

  22. Zhao Q-J, Zhang X-G, Wang L-X. Mild hypothermia therapy reduces blood glucose and lactate and improves neurologic outcomes in patients with severe traumatic brain injury. J Crit Care. 2011;26(3):311–5.

    Article  PubMed  CAS  Google Scholar 

  23. Yan Y, Tang W, Deng Z, Zhong D, Yang G. Cerebral oxygen metabolism and neuroelectrophysiology in a clinical study of severe brain injury and mild hypothermia. J Clin Neurosci Off J Neurosurg Soc Aust. 2010;17(2):196–200.

    CAS  Google Scholar 

  24. Zhi D, Zhang S, Lin X. Study on therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury. Surg Neurol. 2003;59(5):381–5.

    Article  PubMed  Google Scholar 

  25. Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KRJ, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001;344(8):556–63.

    Article  PubMed  CAS  Google Scholar 

  26. Shiozaki T, Hayakata T, Taneda M, Nakajima Y, Hashiguchi N, Fujimi S, et al. 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. 2001;94(1):50–4.

    Article  PubMed  CAS  Google Scholar 

  27. Aibiki M, Maekawa S, Yokono S. Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans. Crit Care Med. 2000;28(12):3902–6.

    Article  PubMed  CAS  Google Scholar 

  28. Jiang J, Yu M, Zhu C. Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases. J Neurosurg. 2000;93(4):546–9.

    Article  PubMed  CAS  Google Scholar 

  29. Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, et al. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997;336(8):540–6.

    Article  PubMed  CAS  Google Scholar 

  30. Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, et al. A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma. 1993;10(3):263–71. discussion 273

    Article  PubMed  CAS  Google Scholar 

  31. • Jiang J, Xu W, Li W, Gao G, Bao Y, Liang Y. 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. Trial comparing shorter duration to longer duration PH.

    Article  PubMed  Google Scholar 

  32. Beca J, McSharry B, Erickson S, Yung M, Schibler A, Slater A, et al. Hypothermia for traumatic brain injury in children—a phase II randomized controlled trial. Crit Care Med. 2015;43(7):1458–66.

    Article  PubMed  CAS  Google Scholar 

  33. Adelson PD, Wisniewski SR, Beca J, Brown SD, Bell M, Muizelaar JP, et al. 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 

  34. •• Hutchison JS, Ward RE, Lacroix J, Hebert PC, Barnes MA, Bohn DJ, et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med. 2008;358(23):2447–56. Largest trial on PH in pediatric patients with severe TBI.

    Article  PubMed  CAS  Google Scholar 

  35. Idris Z, Zenian MS, Muzaimi M, Hamid WZWA. Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: a prospective randomized study. Asian J Neurosurg. 2014;9(3):115–23.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Harris OA, Muh CR, Surles MC, Pan Y, Rozycki G, Macleod J, et al. Discrete cerebral hypothermia in the management of traumatic brain injury: a randomized controlled trial. J Neurosurg. 2009;110(6):1256–64.

    Article  PubMed  Google Scholar 

  37. Qiu W, Shen H, Zhang Y, Wang W, Liu W, Jiang Q, et al. Noninvasive selective brain cooling by head and neck cooling is protective in severe traumatic brain injury. J Clin Neurosci Off J Neurosurg Soc Aust. 2006;13(10):995–1000.

    Google Scholar 

  38. Lee H-C, Chuang H-C, Cho D-Y, Cheng K-F, Lin P-H, Chen C-C. Applying cerebral hypothermia and brain oxygen monitoring in treating severe traumatic brain injury. World Neurosurg. 2010;74(6):654–60.

    Article  PubMed  Google Scholar 

  39. Qiu W, Zhang Y, Sheng H, Zhang J, Wang W, Liu W, et al. Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy. J Crit Care. 2007;22(3):229–35.

    Article  PubMed  Google Scholar 

  40. • Polderman KH, Tjong Tjin Joe R, Peerdeman SM, Vandertop WP, Girbes ARJ. Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury. Intensive Care Med. 2002;28(11):1563–73. Non-randomized clinical trial assessing the impact of TH as a Stage 3 therapy in severe TBI.

    Article  PubMed  Google Scholar 

  41. • Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, et al. Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg. 1993;79(3):363–8. RCT assessing the impact of TH as a Stage 3 therapy in severe TBI.

    Article  PubMed  CAS  Google Scholar 

  42. Shiozaki T, Kato A, Taneda M, Hayakata T, Hashiguchi N, Tanaka H, et al. Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure. J Neurosurg. 1999;91(2):185–91.

    Article  PubMed  CAS  Google Scholar 

  43. Clifton GL, Christensen ML. Use of moderate hypothermia during elective craniotomy. Tex Med. 1992;88(12):66–9.

    PubMed  CAS  Google Scholar 

  44. To Study the Effect of Early Cooling in Acute Subdural Hematoma Patients (HOPES) [Internet]. [cited 2017 Nov 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT02064959.

  45. Povlishock JT, Wei EP. Posthypothermic rewarming considerations following traumatic brain injury. J Neurotrauma. 2009;26(3):333–40.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 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(11):2060–6.

    Article  PubMed  CAS  Google Scholar 

  47. Nichol A, Gantner D, Presneill J, Murray L, Trapani T, Bernard S, et al. 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(2):92–100.

    PubMed  Google Scholar 

  48. Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, et al. Guidelines for the management of severe traumatic brain injury. III. Prophylactic hypothermia. J Neurotrauma. 2007;24(Suppl 1):S21–5.

    Article  PubMed  Google Scholar 

  49. Georgiou AP, Manara AR. Role of therapeutic hypothermia in improving outcome after traumatic brain injury: a systematic review. Br J Anaesth. 2017;110(3):357–67.

    Article  Google Scholar 

  50. Sadaka F, Veremakis C. Therapeutic hypothermia for the management of intracranial hypertension in severe traumatic brain injury: a systematic review. Brain Inj. 2012;26(7–8):899–908.

    Article  PubMed  Google Scholar 

  51. Farahvar A, Gerber LM, Chiu Y-L, Carney N, Hartl R, Ghajar J, et al. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Neurosurg [Internet]. 2012;117(4):729–34. Available from: http://thejns.org/doi/pdf/10.3171/2012.7.JNS111816

    Article  Google Scholar 

  52. Lazaridis C. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2016;374:1384.

  53. O’Leary R, Hutchinson PJA, Menon D. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2016;374:1383–4.

  54. Shaefi S, Mittel AM, Hyam JA, Boone MD, Chen CC, Kasper EM. Hypothermia for severe traumatic brain injury in adults: Recent lessons from randomized controlled trials. Surg Neurol Int. 2016;7:103.

    PubMed  PubMed Central  Google Scholar 

  55. Cooper DJ, Nichol A, Presneill J. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2016;374:1384.

  56. Chesnut RM. What is wrong with the tenets underpinning current management of severe traumatic brain injury? Ann N Y Acad Sci. 2015;1345:74–82.

    Article  PubMed  Google Scholar 

  57. Chesnut RM. A conceptual approach to managing severe traumatic brain injury in a time of uncertainty. Ann N Y Acad Sci. 2015;1345:99–107.

    Article  PubMed  Google Scholar 

  58. Yuan Q, Wu X, Sun Y, Yu J, Li Z, Du Z, et al. Impact of intracranial pressure monitoring on mortality in patients with traumatic brain injury: a systematic review and meta-analysis. J Neurosurg. 2015;122(3):574–87.

    Article  PubMed  Google Scholar 

  59. Chesnut RM, Temkin N, Carney N, Dikmen S, Rondina C, Videtta W, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med. 2012;367(26):2471–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, McGill University/McGill University Health Centre, Montreal, Quebec, Canada

    Oliver Lasry & Solon Schur

  2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

    Oliver Lasry

  3. Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA

    Gregory W. Hawryluk

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  1. Oliver Lasry
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  2. Solon Schur
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Correspondence to Oliver Lasry.

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This article is part of the Topical Collection on Traumatic Brain Injury

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Lasry, O., Schur, S. & Hawryluk, G.W. Prophylactic and Therapeutic Hypothermia in Severe Traumatic Brain Injury. Curr Trauma Rep 4, 109–120 (2018). https://doi.org/10.1007/s40719-018-0121-7

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