Top

Critical Care

Published in:

Open Access 01-12-2019 | Central Nervous System Trauma | Review

A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury

Authors: Hanbing Chen, Fei Wu, Penglei Yang, Jun Shao, Qihong Chen, Ruiqiang Zheng

Published in: Critical Care | Issue 1/2019

Abstract

Purpose

Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury.

Methods

We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool.

Results

Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007).

Conclusions

Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

Available only for authorised users

Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Buki A, Chesnut RM, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987–1048. https://doi.org/10.1016/s1474-4422(17)30371-x.CrossRefPubMed

Andrews PJD, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JKJ, Murray GD. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2015;373(25):2403–12. https://doi.org/10.1056/NEJMoa1507581.CrossRefPubMed

Cooper DJ, Nichol A, Presneill J. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2016;374(14):1384. https://doi.org/10.1056/NEJMc1600339.CrossRefPubMed

Bergman KS, Beekmans V, Stromswold J. Considerations for neuroprotection in the traumatic brain injury population. Crit Care Nurs Clin North Am. 2015;27(2):225.CrossRefPubMed

Dietrich WD, Bramlett HM. The evidence for hypothermia as a Neuroprotectant in traumatic brain injury. Neurother. 2010;7(1):43–50.CrossRef

Zhao QJ, Zhang XG, Wang LX. 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. https://doi.org/10.1016/j.jcrc.2010.08.014.CrossRefPubMed

Gal R, Cundrle I, Zimova I, Smrcka M. Mild hypothermia therapy for patients with severe brain injury. Clin Neurol Neurosurg. 2002;104(4):318–21.CrossRefPubMed

Cooper DJ, Nichol AD, Bailey M, Bernard S, Cameron PA, Pili-Floury S, Forbes A, Gantner D, Higgins AM, Huet O, et al. 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. https://doi.org/10.1001/jama.2018.17075.CrossRefPubMedPubMedCentral

Andrews PJD, Rodriguez A, Suter P, Battison CG, Rhodes JKJ, 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. https://doi.org/10.1097/ccm.0000000000002376.CrossRefPubMedPubMedCentral

10.

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(2):R75. https://doi.org/10.1186/cc13835.CrossRefPubMedPubMedCentral

11.

Zhu Y, Yin H, Zhang R, Ye X, Wei J. Therapeutic hypothermia versus normothermia in adult patients with traumatic brain injury: a meta-analysis. SpringerPlus. 2016;5(1):801. https://doi.org/10.1186/s40064-016-2391-2.CrossRefPubMedPubMedCentral

12.

Crompton EM, Lubomirova I, Cotlarciuc I, Han TS, Sharma SD, Sharma P. Meta-analysis of therapeutic hypothermia for traumatic brain injury in adult and pediatric patients. Crit Care Med. 2017;45(4):575–83. https://doi.org/10.1097/ccm.0000000000002205.CrossRefPubMed

13.

Watson HI, Shepherd AA, Rhodes JKJ, Andrews PJD. Revisited: a systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Crit Care Med. 2018;46(6):972–9. https://doi.org/10.1097/ccm.0000000000003125.CrossRefPubMed

14.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. https://doi.org/10.1136/bmj.b2535.CrossRefPubMedPubMedCentral

15.

Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, Fletcher J, Hayes RL, Choi SC. A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma. 1993;10(3):263–71; discussion 273. https://doi.org/10.1089/neu.1993.10.263.CrossRefPubMed

16.

Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T. Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg. 1993;79(3):363–8. https://doi.org/10.3171/jns.1993.79.3.0363.CrossRefPubMed

17.

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(8):540–6. https://doi.org/10.1056/NEJM199702203360803.CrossRefPubMed

18.

Shiozaki T, Kato A, Taneda M, Hayakata T, Hashiguchi N, Tanaka H, Shimazu T, Sugimoto H. Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure. J Neurosurg. 1999;91(2):185–91. https://doi.org/10.3171/jns.1999.91.2.0185.CrossRefPubMed

19.

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.CrossRefPubMed

20.

Jiang JY, Yu MK, 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.CrossRefPubMed

21.

Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR Jr, Muizelaar JP, Wagner FC Jr, Marion DW, Luerssen TG, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001;344(8):556–63. https://doi.org/10.1056/nejm200102223440803.CrossRefPubMed

22.

Shiozaki T, Hayakata T, Taneda M, Nakajima Y, Hashiguchi N, Fujimi S, Nakamori Y, Tanaka H, Shimazu T, Sugimoto H. 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. https://doi.org/10.3171/jns.2001.94.1.0050.CrossRefPubMed

23.

Hashiguchi N, Shiozaki T, Ogura H, Tanaka H, Koh T, Noborio M, Fugita K, Akimau P, Kuwagata Y, Shimazu T, et al. Mild hypothermia reduces expression of heat shock protein 60 in leukocytes from severely head-injured patients. J Trauma. 2003;55(6):1054–60. https://doi.org/10.1097/01.ta.0000033252.43742.8b.CrossRefPubMed

24.

Meissner W, Krapp C, Kauf E, Dohrn B, Reinhart K. Thyroid hormone response to moderate hypothermia in severe brain injury. Intensive Care Med. 2003;29(1):44–8. https://doi.org/10.1007/s00134-002-1556-3.CrossRefPubMed

25.

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.CrossRefPubMed

26.

Qiu WS, Liu WG, Shen H, Wang WM, Hang ZL, Zhang Y, Jiang SJ, Yang XF. Therapeutic effect of mild hypothermia on severe traumatic head injury. Chinese J Traumatol. 2005;8(1):27–32.

27.

Smrcka M, Vidlak M, Maca K, Smrcka V, Gal R. The influence of mild hypothermia on ICP, CPP and outcome in patients with primary and secondary brain injury. Acta Neurochir Suppl. 2005;95:273–5.CrossRefPubMed

28.

Liu WG, Qiu WS, Zhang Y, Wang WM, Lu F, Yang XF. Effects of selective brain cooling in patients with severe traumatic brain injury: a preliminary study. J Int Med Res. 2006;34(1):58–64. https://doi.org/10.1177/147323000603400107.CrossRefPubMed

29.

Qiu W, Zhang Y, Sheng H, Zhang J, Wang W, Liu W, Chen K, Zhou J, Xu Z. Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy. J Crit Care. 2007;22(3):229–35. https://doi.org/10.1016/j.jcrc.2006.06.011.CrossRefPubMed

30.

Harris OA, Muh CR, Surles MC, Pan Y, Rozycki G, Macleod J, Easley K. Discrete cerebral hypothermia in the management of traumatic brain injury: a randomized controlled trial. J Neurosurg. 2009;110(6):1256–64. https://doi.org/10.3171/2009.1.jns081320.CrossRefPubMed

31.

Clifton GL, Valadka A, Zygun D, Coffey CS, Drever P, Fourwinds S, Janis LS, Wilde E, Taylor P, Harshman K, 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. https://doi.org/10.1016/s1474-4422(10)70300-8.CrossRefPubMed

32.

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. https://doi.org/10.1089/neu.2013.3197.CrossRefPubMedPubMedCentral

33.

Tang C, Bao Y, Qi M, Zhou L, Liu F, Mao J, Lei Q, Qi S, Qiu B. Mild induced hypothermia for patients with severe traumatic brain injury after decompressive craniectomy. J Crit Care. 2017;39:267–70. https://doi.org/10.1016/j.jcrc.2016.12.012.CrossRefPubMed

34.

Idris Z, Zenian MS, Muzaimi M, Hamid WZ. 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. https://doi.org/10.4103/1793-5482.142690.CrossRefPubMedPubMedCentral

35.

Peterson K, Carson S, Carney N. Hypothermia treatment for traumatic brain injury: a systematic review and meta-analysis. J Neurotrauma. 2008;25(1):62–71.CrossRefPubMed

36.

De Rosa S, De Cal M, Joannidis M, Villa G, Pacheco JLS, Virzi GM, Samoni S, D'Ippoliti F, Marcante S, Visconti F, et al. The effect of whole-body cooling on renal function in post-cardiac arrest patients. BMC Nephrol. 2017;18(1):376. https://doi.org/10.1186/s12882-017-0780-6.CrossRefPubMedPubMedCentral

37.

Jiang JY, Gao GY, Li WP, Yu MK, Zhu C. Early indicators of prognosis in 846 cases of severe traumatic brain injury. J Neurotrauma. 2002;19(7):869–74. https://doi.org/10.1089/08977150260190456.CrossRefPubMed

38.

Kelts EA. Traumatic brain injury and visual dysfunction: a limited overview. NeuroRehabilitation. 2010;27(3):223–9. https://doi.org/10.3233/nre-2010-0601.CrossRefPubMed

39.

Polderman KH. Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: indications and evidence. Intensive Care Med. 2004;30(4):556–75. https://doi.org/10.1007/s00134-003-2152-x.CrossRefPubMed

40.

Marion DW, Obrist WD, Carlier PM, Penrod LE, Darby JM. The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neurosurg. 1993;79(3):354–62. https://doi.org/10.3171/jns.1993.79.3.0354.CrossRefPubMed

41.

Lyeth BG, Jiang JY, Liu S. Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury. J Neurotrauma. 1993;10(1):57–64. https://doi.org/10.1089/neu.1993.10.57.CrossRefPubMed

42.

Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, et al. Guidelines for the management of severe traumatic brain injury, Fourth Edition. Neurosurgery. 2017;80(1):6–15. https://doi.org/10.1227/neu.0000000000001432.CrossRefPubMed

43.

Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009;37(7 Suppl):S186–202. https://doi.org/10.1097/CCM.0b013e3181aa5241.CrossRefPubMed

44.

Sahuquillo J, Vilalta A. Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury. Curr Pharm Des. 2007;13(22):2310–22.CrossRefPubMed

45.

Geurts M, Macleod MR, Kollmar R, Kremer PHC, van der Worp HB. Therapeutic hypothermia and the risk of infection: a systematic review and meta-analysis. Crit Care Med. 2014;42(2):231–42.CrossRefPubMed

46.

Dengler B, Garvin R, Seifi A. Can therapeutic hypothermia trigger propofol-related infusion syndrome? J Crit Care. 2015;30(4):823–4. https://doi.org/10.1016/j.jcrc.2015.03.027.CrossRefPubMed

47.

Heier T, Caldwell JE. Impact of hypothermia on the response to neuromuscular blocking drugs. Anesthesiology. 2006;104(5):1070–80. https://doi.org/10.1097/00000542-200605000-00025.CrossRefPubMed

48.

Roberts I, Yates D, Sandercock P, Farrell B, Wasserberg J, Lomas G, Cottingham R, Svoboda P, Brayley N, Mazairac G, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364(9442):1321–8. https://doi.org/10.1016/s0140-6736(04)17188-2.CrossRefPubMed

49.

Kim Y, Busto R, Dietrich WD, Kraydieh S, Ginsberg MD. Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia. Stroke. 1996;27(12):2274–80; discussion 2281. https://doi.org/10.1161/01.str.27.12.2274.CrossRefPubMed

50.

Baena RC, Busto R, Dietrich WD, Globus MY, Ginsberg MD. Hyperthermia delayed by 24 hours aggravates neuronal damage in rat hippocampus following global ischemia. Neurology. 1997;48(3):768–73. https://doi.org/10.1212/wnl.48.3.768.CrossRefPubMed

51.

Lotocki G, de Rivero Vaccari JP, Perez ER, Alonso OF, Curbelo K, Keane RW, Dietrich WD. Therapeutic hypothermia modulates TNFR1 signaling in the traumatized brain via early transient activation of the JNK pathway and suppression of XIAP cleavage. Eur J Neurosci. 2006;24(8):2283–90. https://doi.org/10.1111/j.1460-9568.2006.05123.x.CrossRefPubMed

52.

Scerrati A, De Rosa S, Mongardi L, Cavallo MA, Trapella G, De Bonis P. Standard of care, controversies, and innovations in the medical treatment of severe traumatic brain injury. J Neurosurg Sci. 2018;62(5):574–83. https://doi.org/10.23736/s0390-5616.18.04462-4.CrossRefPubMed

53.

Burger R, Bendszus M, Vince GH, Solymosi L, Roosen K. Neurophysiological monitoring, magnetic resonance imaging, and histological assays confirm the beneficial effects of moderate hypothermia after epidural focal mass lesion development in rodents. Neurosurgery. 2004;54(3):701–11; discussion 711-702. https://doi.org/10.1227/01.neu.0000108784.80585.ee.CrossRefPubMed

Title: A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury
Authors: Hanbing Chen
Fei Wu
Penglei Yang
Jun Shao
Qihong Chen
Ruiqiang Zheng
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Central Nervous System Trauma
Intracranial Hypertension
Published in: Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/s13054-019-2667-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2019

Response

Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study

ECCCOing the call for emergency and critical care training in low middle-income countries

Detailed measurements of oesophageal pressure during mechanical ventilation with an advanced high-resolution manometry catheter

Intact cerebrovascular autoregulation in patients with refractory status epilepticus due to sufficient anesthetic treatment on a neurointensive care unit: a prospective cohort study

Obituary Brian P. Kavanagh, MD