Current Treatment Options in Neurology

, Volume 14, Issue 2, pp 188–196

Hypothermia and Ischemic Stroke

Critical Care Neurology (K Sheth, Section Editor)

Opinion statement

The use of tissue plasminogen activator (tPA) is the major treatment method for acute ischemic stroke, but it reaches only a very limited number of stroke patients. Although neuroprotectants may be useful in stroke patients in principle, promising animal data have not yet been successfully transferred to stroke patients. However, many arguments favor the successful translation of therapeutic hypothermia (TH) to stroke patients: it is a multimodal method, there is a strong correlation between fever and outcome in stroke patients, and TH has been shown to be beneficial in other kinds of acute brain injury (resuscitation, perinatal asphyxia). In addition, it is useful in controlling intracranial pressure caused by brain edema. So far, available data from clinical studies are not sufficient to recommend TH for the routine treatment of acute ischemic stroke. The quality of trials and the number of stroke patients treated by TH are far too low to prove efficacy or futility, but multicenter randomized controlled clinical trials are on their way. Studies in awake stroke patients will use TH very early in the clinical setting, which implies certain problems. The use of TH in awake individuals requires methods to suppress cold-induced vegetative responses such as shivering and sympathic activation, clinically relevant side effects that need to be monitored and treated carefully. In mass-occupying ischemic stroke, randomized trials will evaluate the neuroprotective effects of controlling edema and intracranial pressure. Because the optimal depth, duration, and methods of cooling are not clear, only large randomized controlled trials will set the baseline from which TH as a neuroprotective therapy can be optimized and brought successfully to stroke patients.


Therapeutic hypothermia Acute ischemic stroke Treatment Intracranial pressure Brain edema Neuroprotection Space-occupying ischemic stroke Duration Timing 

References and Recommended Reading

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

  1. 1.••
    Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375:1695–1703. PubMedCrossRefGoogle Scholar
  2. 2.••
    Den Hertog HM, van der Worp HB, Tseng MC, Dippel DW. Cooling therapy for acute stroke. Cochrane Database Syst Rev. 2009;(1):CD001247. Meta-analysis of available stroke trials testing therapeutic hypothermia. No beneficial or harmful effects could be observed, potentially according to the overall small patient numbers.Google Scholar
  3. 3.
    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(Pt 12):3063–74.PubMedCrossRefGoogle Scholar
  4. 4.•
    van der Worp HB, Macleod MR, Kollmar R; European Stroke Research Network for Hypothermia (EuroHYP). Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? J Cereb Blood Flow Metab. 2010;30(6):1079–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Greer DM, Funk SE, Reaven NL, Ouzounelli M, Uman GC. Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke. 2008;39(11):3029–35.PubMedCrossRefGoogle Scholar
  6. 6.
    Reith J, Jørgensen HS, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996;347(8999):422–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Arrich J, Holzer M, Herkner H, Müllner M. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev. 2009;(4):CD004128.Google Scholar
  8. 8.
    Shankaran S. Neonatal encephalopathy: treatment with hypothermia. J Neurotrauma. 2009;26(3):437–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomized trial. Lancet. 2005;365:663–70.PubMedGoogle Scholar
  10. 10.
    Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–84.PubMedCrossRefGoogle Scholar
  11. 11.
    Azzopardi D, Strohm B, Edwards AD, et al. TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.PubMedCrossRefGoogle Scholar
  12. 12.
    Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke. 1998;29(12):2461–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA. Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke. 2001;32(9):2033–5.PubMedCrossRefGoogle Scholar
  14. 14.
    De Georgia MA, Krieger DW, Abou-Chebl A, et al. Cooling for acute ischemic brain damage (COOL AID): a feasibility trial of endovascular cooling. Neurology. 2004;63:312–7.PubMedGoogle Scholar
  15. 15.
    Sinclair HL, Andrews PJ. Bench-to-bedside review: hypothermia in traumatic brain injury. Crit Care. 2010;14(1):204.PubMedCrossRefGoogle Scholar
  16. 16.
    Testori C, Sterz F, Behringer W, Spiel A, Firbas C, Jilma B. Surface cooling for induction of mild hypothermia in conscious healthy volunteers—a feasibility trial. Crit Care. 2011;15(5):R248.PubMedCrossRefGoogle Scholar
  17. 17.
    Castrén M, Nordberg P, Svensson L, Taccone F, Vincent JL, Desruelles D, et al. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation. 2010;122(7):729–36.PubMedCrossRefGoogle Scholar
  18. 18.
    Kollmar R, Schellinger PD, Steigleder T, Köhrmann M, Schwab S. Ice-cold saline for the induction of mild hypothermia in patients with acute ischemic stroke: a pilot study. Stroke. 2009;40(5):1907–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Kim F, Olsufka M, Carlbom D, Deem S, Longstreth Jr WT, Hanrahan M, et al. Pilot study of rapid infusion of 2 L of 4 degrees C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest. Circulation. 2005;112:715–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Georgiadis D, Schwarz S, Kollmar R, Schwab S. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke. 2001;32(11):2550–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Georgiadis D, Schwarz S, Aschoff A, Schwab S. Hemicraniectomy and moderate hypothermia in patients with severe ischemic stroke. Stroke. 2002;33(6):1584–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Kammersgaard LP, Rasmussen BH, Jørgensen HS, Reith J, Weber U, Olsen TS. 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. 2000;31(9):2251–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, et al. Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke. 2001;32(8):1847–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Lyden PD, Allgren RL, Ng K, et al. Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis. 2005;14(3):107–14.PubMedCrossRefGoogle Scholar
  25. 25.
    Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, et al. ICTuS-L Investigators. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010;41(10):2265–70.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Erlangen-NuernbergErlangenGermany

Personalised recommendations