NeuroRounds: Therapeutic Hypothermia for Prevention of Neurological Injury

Therapeutic Hypothermia for Prevention of Neurological Injury

Hypothermia is the extreme cooling of the body’s temperature. In an uncontrolled setting, prolonged exposure to extreme cold can result in hypothermic body temperature and may result in loss of life.  However, advancements in the ability to induce and maintain stable body temperature and manage secondary side-effects have led to resurgence in the use of Ttherapeutic Hypothermia, or Controlled Thermoregulation, for the treatment of a number of acute neuropathological conditions.

Therapeutic hypothermia has a long tradition, emerging in the medical record as early as 1812 for preservation of limbs and treating fevers.  In the 1950s, it was used in medical practice, however, during this time, induction of hypothermia involved significant risks, including buildup of gases in the blood, coagulation, arrhythmia , etc and was therefore largely abandoned as a method of treatment(1).

In more recent years, this therapy has come back into the spotlight with numerous studies demonstrating its efficacy in reducing mortality and improving neurological recovery outcomes following cardiac arrest as compared to the typical course of treatment(2). In the last decade, this therapy has also been extended to many other pathologies including anoxic/hypoxic brain injury, traumatic brain injury, stroke or other ischemic events, encephalopathies, meningitis, tachycardia, respiratory distress, and spinal cord injury(3).


Why is it hypothermia neuroprotective?

In conditions where hemorrhage or edema occurs (hemorrhagic stroke, TBI, SCI, or hematoma) induced hypothermia results in vasoconstriction, i.e. narrowing of the blood vessels, to slow blood flow to the brain thereby reducing inflammation and intracranial or spinal column pressure(4-7). This reduction in pressure and inflammation preserves cells that might otherwise be damaged. See Figure 1.

Reduction in body temperature also results in a drop in cellular metabolism, meaning that cells slow down production of ATP and have a reduced need for oxygen and glucose. As body temperature drops, cellular metabolism decreases at a rate of 5-7% per 1.8 degrees farienhight or 1 degree celcius(4). In conditions where hypoxic/anoxic events occur (cardiac arrest, respiratory distress, ischemic stroke), poor oxygenation or blood perfusion will result in neuronal cell death after approximately 3-4 minutes with no intervention, because these cells are not being supplied with the valuable resources they need to create energy(8). By cooling the body and slowing cellular metabolism, brain cells take much longer to deplete the available resources allowing more time for medical intervention to restart the heart, intubate, or administer clot-breaking drugs. 


Given the reduction in cellular processes, it is possible that treatment during the acute phase of trauma injuries such as TBI may provide neuroprotection for the metabolic cascade that results in cell death due to excitotoxicity. However studies have not presently been able to demonstrate a consistent benefit of this treatment. Trials are underway to assess this further. In the meantime, therapeutic hypothermia is approved as a treatment for edema in TBI and SCI(9) and is generally gaining popularity in a number of different neurological conditions. See the links and references below for videos and links to articles.

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Learn More:

• Therapeutic Hypothermia in the news
• Intervention in Infant Hypoxia
• Therapeutic Hypothermia in Brain Injury  

Reference:

1. Varon, J. and P. Acosta (2008). "Therapeutic hypothermia*: Past, present, and future." CHEST Journal 133(5): 1267-1274.
2.  Friberg, H., Rundgren, M., Westhall, E., Nielsen, N., & Cronberg, T. (2013). Continuous evaluation of neurological prognosis after cardiac arrest. Acta Anaesthesiologica Scandinavica, 57(1), 6-15.
3. Polderman, K. H., & Herold, I. (2009). Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods*. Critical care medicine, 37(3), 1101-1120.
4. Kammersgaard LP, Jorgensen HS, Rungby JA, et al. (2002). Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study. Stroke, 33 (7), 1759-1762.
5. Kollmar, R., Staykov, D., Dörfler, A., Schellinger, P. D., Schwab, S., & Bardutzky, J. (2010). Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke, 41(8), 1684-1689.
6. Unterberg, A. W., Stover, J., Kress, B., & Kiening, K. L. (2004). Edema and brain trauma. Neuroscience, 129(4), 1019-1027.
7. A. Maybhate, C. Hu, F. A. Bazley, Q. Yu, N. V. Thakor, C. Kerr, and A. All, (2011). Potential Long Term Benefits of Acute Hypothermia after Spinal Cord Injury: Assessments with Somatosensory Evoked Potentials. Critical Care Medicine, 40 (2), 573-579.
8. CEN, C., Rolma Buruschkin, B. S. N., Kenyon, D. M., Stenton, K., & Susan Treseder, B. S. N. (2012). Improving outcomes with therapeutic hypothermia. Diabetes.
9. Urbano, L. A., & Oddo, M. (2012). Therapeutic hypothermia for traumatic brain injury. Current neurology and neuroscience reports, 12(5), 580-591.