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Hypothermia in the management of traumatic brain injury

A systematic review and meta-analysis

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Abstract

Objective

Brain injury remains the leading cause of death in cases of trauma in North America and Europe. This article critically appraised and summarised all published and peer-reviewed, randomised, controlled trials of the use of hypothermia in traumatic brain injury.

Design

To be included, a study had to be a published, randomised, controlled trial of the use of hypothermia in the management of traumatic brain injury. Pooling of data and meta-analysis of results occurred.

Setting

Conducted at a tertiary level Canadian teaching hospital.

Patients and participants

Patients were combined from eight randomised, controlled trials to generate a population of 748 severely head-injured patients.

Measurements and results

Eight studies provided data on the efficacy of hypothermia in the management of traumatic brain injury. The pooled odds ratio of mortality in the hypothermic group was 0.81 (95%CI =0.59–1.13, p=0.22). The OR of a poor neurological outcome (GOS 1,2 or 3) was 0.75 (95% CI=0.56–1.01, p=0.06). The odds ratio for pneumonia in the normothermic group was 0.42 (95%CI =0.25–0.70, p=0.001).

Conclusions

Although meta-analysis suggests that iatrogenic hypothermia may confer a marginal benefit in neurological outcome, there does not appear to be clear evidence of lower mortality rates in unselected traumatic brain injury patients. Prolonged hypothermia may confer a benefit, particularly in patients with elevated intracranial pressure refractory to conventional manipulations. Conclusions regarding the use of hypothermia are controversial and not strongly supported by the available evidence.

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References

  1. Finfer SR, Cohen J (2001) Severe traumatic brain injury. Resuscitation 48(1), 77–90

    Article  CAS  PubMed  Google Scholar 

  2. Anonymous (2000) The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Critical pathway for the treatment of established intracranial hypertension. Journal of Neurotrauma 17(6–7), 537–538

    PubMed  Google Scholar 

  3. Jennett B, Snoek J, Bond MR, Brooks N (1981) Disability after severe head injury: observations on the use of the Glasgow Outcome Scale. Journal of Neurology, Neurosurgery & Psychiatry 44(4), 285–293

    CAS  PubMed  Google Scholar 

  4. Ishikura H YK, Akahori M, Shoji Y, Fukui H, Tanaka T (1998) Changes in blood platelet count and serum thrombopoietin (TPO) level under moderate hypothermic therapy in traumatic severe closed head injury. Crit Care Med Vol. 26, No.1 (Suppl.)

  5. Meissner WFH, Dohrn B, Specht M, Reinhart K (1998) Influence of hypothermia on cytokine concentrations in head injured patients. Crit Care Med Vol. 26, No.1 (Suppl.)

  6. 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 (2001) Lack of effect of induction of hypothermia after acute brain injury. New England Journal of Medicine 344(8), 556–563

    CAS  PubMed  Google Scholar 

  7. 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. Journal of Neurotrauma 10(3), 263–271; discussion 273

    CAS  PubMed  Google Scholar 

  8. 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. New England Journal of Medicine 336(8), 540–546

    CAS  PubMed  Google Scholar 

  9. Shiozaki T, Kato A, Taneda M, Hayakata T, Hashiguchi N, Tanaka H, Shimazu T, Sugimoto H (1999) Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure. Journal of Neurosurgery 91(2), 185–191

    CAS  PubMed  Google Scholar 

  10. 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. Journal of Neurosurgery 79(3), 363–368

    CAS  PubMed  Google Scholar 

  11. Clifton G (1991) Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab 11(1), 114–121

    CAS  PubMed  Google Scholar 

  12. Aibiki M (2000) Hypothermia and head injury. Journal of Neurosurgery 92(6), 1074–1076

    CAS  PubMed  Google Scholar 

  13. Clifton G (2000) Hypothermia and severe brain injury. Journal of Neurosurgery 93(4), 718–719

    CAS  PubMed  Google Scholar 

  14. 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. Journal of Neurosurgery 94(1), 50–54

    CAS  PubMed  Google Scholar 

  15. Aibiki M, Maekawa S, Yokono S (2000) Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans. Critical Care Medicine 28(12), 3902–3906

    Google Scholar 

  16. Jiang J, Yu M, 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(4), 546–9

    CAS  PubMed  Google Scholar 

  17. Dietrich W (1996) Nonpharmacological strategies: Moderate hypothermia. Neurotrauma, 1491–1506

  18. Lyeth BG JJ, Liu S (1993) Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury. J Neurotrauma(10), 57–64

  19. Marion DW, Obrist WD, Carlier PM, Penrod LE, Darby JM (1993) The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neurosurg 79(3), 354–62

    CAS  PubMed  Google Scholar 

  20. Cappelleri JC, Ioannidis JP, Schmid CH, de Ferranti SD, Aubert M, Chalmers TC, Lau J (1996) Large trials vs meta-analysis of smaller trials: how do their results compare? [see comments]. Jama 276(16), 1332–1338

    Article  CAS  PubMed  Google Scholar 

  21. Ioannidis JP, Cappelleri JC, Lau J (1998) Issues in comparisons between meta-analyses and large trials. Journal of the American Medical Association. 279(14), 1089–109

    Article  CAS  PubMed  Google Scholar 

  22. Stocchetti N, Rossi S, Zanier ER, Zanier ER, Colombo A., Beretta L, Citerio G, Article CGL (2002) Pyrexia in head-injured patients admitted to intensive care. Intensive Care Med. 28(11): 1555–1562

    Article  Google Scholar 

  23. 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. Journal of Cerebral Blood Flow & Metabolism. 7(6), 729–378

    PubMed  Google Scholar 

  24. Minamisawa H, Smith ML, Siesjo BK (1990) The effect of mild hyperthermia and hypothermia on brain damage following 5, 10, and 15 minutes of forebrain ischemia. Annals of Neurology. 28(1), 26–33

    Google Scholar 

  25. Wass CT, Lanier WL, Hofer RE, Scheithauer BW, Andrews AG (1995) Temperature changes of > or = 1 degree C alter functional neurologic outcome and histopathology in a canine model of complete cerebral ischemia. Anesthesiology. 83(2), 325–333

    CAS  PubMed  Google Scholar 

  26. 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. Journal of Neurosurgery 94(1), 50–54

    CAS  PubMed  Google Scholar 

  27. Safar P, Kochanek PM (2001) Lack of effect of induction of hypothermia after acute brain injury.[comment]. New England Journal of Medicine. 345(1), 66

    Article  CAS  Google Scholar 

  28. Ioannidis JP, Lau J (1998) Heterogeneity of the baseline risk within patient populations of clinical trials: a proposed evaluation algorithm. American Journal of Epidemiology. 148(11), 1117–1126

    CAS  PubMed  Google Scholar 

  29. Agresti A, Hartzel J (2000) Strategies for comparing treatments on a binary response with multi-centre data. Statistics in Medicine. 19(8), 1115–1139

    Article  CAS  PubMed  Google Scholar 

  30. Anonymous (2000) The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Critical pathway for the treatment of established intracranial hypertension. Journal of Neurotrauma 17(6-7), 537–538

    PubMed  Google Scholar 

  31. Bernard SA, Jones BM, Horne MK (1997) Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Annals of Emergency Medicine 30(2), 146–153

    CAS  PubMed  Google Scholar 

  32. Clifton GL, Allen S, Berry J, Koch SM (1992) Systemic hypothermia in treatment of brain injury. Journal of Neurotrauma 9(Suppl 2), 487–495

    PubMed  Google Scholar 

  33. Clifton GL (1995) Systemic hypothermia in treatment of severe brain injury. Journal of Neurosurgical Anesthesiology 7(2), 152–156

    CAS  PubMed  Google Scholar 

  34. 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 Neurochirurgica-Supplementum 60, 541–543

    CAS  Google Scholar 

  35. 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. Journal of Neurosurgery 85(4), 533–541

    CAS  PubMed  Google Scholar 

  36. Polderman KH, Tjong Tjin Joe R, Peerdeman SM, Vandertop WP, Girbes ARJ (2002) Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury. Intensive Care Med. 28(11): 1563–1573

    Article  Google Scholar 

  37. Gadkary CS, Alderson P, Signorini DF (XXXX) Therapeutic Hypothermia for Head Injury, Cochrane Database Syst Rev, pp CD001048

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Correspondence to William R. Henderson.

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Henderson, W.R., Dhingra, V.K., Chittock, D.R. et al. Hypothermia in the management of traumatic brain injury. Intensive Care Med 29, 1637–1644 (2003). https://doi.org/10.1007/s00134-003-1848-2

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  • DOI: https://doi.org/10.1007/s00134-003-1848-2

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