Mild hypothermia cardiac arrest

The Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002 346 549-556. 

Recently, two landmark prospective randomized controlled studies were published demonstrating the benefit of mild hypothermia in improving neurologic outcome in patients suffering cardiac arrest from ventricular fibrillation (73,74). 

Weinrauch V., Safar P., Tisherman S., Kuboyama K., and Radovsky A. (1992) Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke 23,1454-1462. 

Leonov Y., Sterz F., Safar P., et al. (1990) Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J. Cereb. Blood Flow Metab. 10, 57-70. 

The aforementioned findings in rodents mirror results observed in dogs subjected to cardiac arrest with subsequent postischemic mild hypothermia of 1- to 12-h duration (38-44). For example, a 12-h period of 34°C hypothermia with hemodilution and elevated blood pressure reduced brain injury (e.g., hippocampus, neocortex, basal ganglia) and lessened functional deficits after cardiac arrest. However, in all of these studies the survival time was 4 d or less, and thus it has yet to be proven that postischemic hypothermia can permanently reduce ischemic brain injury in the dog. Based on the rodent literature, it would be useful to investigate more protracted bouts of mild hypothermia and assess longterm outcome in this intensive cardiac arrest model in the dog. 

Xiao F., Safar P., and Radovsky A. (1998) Mild protective and resuscitative hypothermia for asphyxial cardiac arrest in rats. Am. J. Emerg. Med. 16,17-25. 

Safar P., Xiao F., Radovsky A., et al. (1996) Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. Stroke 27, 105-113. 

These are the first clinical trials to demonstrate improved outcomes using hypothermia in this population of cardiac arrest patients. However, it s possible that some of the beneficial outcome in these studies was related to the prevention of hyperthermia. Experimental data have shown that even mild hyperthermia contributes to ischemic injury. 

Deliberate mild hypothermia has been shown to be an extremely effective means of neuroprotection during periods of ischemia in experimental models. Intraoperative mild hypothermia has become a standard of practice for many neurosurgeons performing complex intracranial procedures. Recent findings of neurologic benefit in prospective, randomized, controlled clinical studies of cardiac arrest patients are encouraging, but more research is required to confirm and extend these positive results to other patients with stroke and traumatic insults. Further investigation must be completed to establish the optimal time and duration when treatment should be instituted to offer the optimal protection for patients with acute ischemic and traumatic injuries. 

Restoration of blood flow following cardiac arrest can lead to several chemical cascades and destructive enzymatic reactions that can result in cerebral injury. These reactions include free-radical production, excitatory amino acid release, and calcium shifts, leading to mitochondrial damage and apoptosis (programmed cell death). Hypothermia can protect from cerebral injury by suppressing these chemical reactions, thereby reducing the production of free radicals. Various animal models have demonstrated improved functional recovery and reduced cerebral deflcits with the induction of mild therapeutic hypothermia. Recently, there have been two clinical trials in humans evaluating this technique. ... 

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