Hypothermia for brain protection and resuscitation

Clinicians are actively looking for an effective brain protection technique. With pharmacologic agents, several phase III trials in stroke, severe traumatic brain injury, and post-cardiac arrest survivors have failed. Hence there is renewed interest in mild to moderate hypothermia for brain protection. Phase III clinical trials with hypothermia have been successful only in post-cardiac arrest survivors and neonatal hypoxic encephalopathy. This review focuses on the possible reasons for our inability to translate into positive clinical trials what is observed consistently in laboratory models.

Several factors have been identified for the failure of successive hypothermia clinical trials. Patients with severe traumatic brain injury with Glasgow Coma Score of 4-7 on admission and those less than 45 years of age and neonates with hypoxic encephalopathy are more responsive to hypothermia. Similarly, early and effective cooling techniques and titration of hypothermia to a defined endpoint are likely to be more effective. New techniques such as local cooling of the brain and the combination of hypothermia with drugs are being evaluated.

Hypothermia can at present be recommended only for post-cardiac arrest survivors and in neonatal hypoxic encephalopathy.