MILD-TO-MODERATE HYPOTHERMIA AND BRAIN PROTECTION

To define the part played by mild-to-moderate hypothermia in neuroprotection, it is necessary to take into account the thermoregulatory responses that occur in the normal human as the change in central temperature exceeds 0.2 degrees C. The mechanisms induced by cold are cutaneous vasoconstriction and shivering. They must be suppressed before starting controlled hypothermia. In these conditions, controlled moderate hypothermia between 32 and 35 degrees C does not seem to have deleterious side-effects, especially on coagulation. Caution is needed with the analysis of the numerous papers reporting experiments concerning the effects of moderate hypothermia in animals with induced cerebral ischaemia because of significant differences in the study designs. These differences concern mainly the time of onset of hypothermia, viz before or after ischaemia, the fact that the ischaemia is either global or focal, that it is caused by vascular occlusion posttraumatic or initiated by hypo or hyperglycemia. Some differences are also existing in the criteria used to appreciate the neuronal damage, as well as in the level of temperature and the site where it is measured. The mechanism of neuroprotectionfrom moderate hypothermia seems to be not only a decrease in cerebral metabolism, but also involves a specific action on some intra cellular events such as the blocking of the release of glutamate and of lipid peroxydation in brain tissue. An indirect proof of the neuroprotective effect of moderate hypothermia is the increase in the neuronal damage induced by moderate hyperthermia. It is conceivable that moderate hypothermia could erect a better neuroprotective effect than the drugs having this reputation, such as barbiturates, isoflurane and propofol. The possible induction of hypothermia into experiments concerning barbiturate or isoflurane protection could even explain the protection observed, as this has been proven for anti NMDA, MK-801. The few clinical studies already published do not show obvious differences allowing to recommend moderate hypothermia as a standard technique among the therapeutic modalities used for cerebral protection for intracerebral vascular surgery or cerebral resuscitation after severe head trauma. However, the experimental results are strong enough to justify futur controlled clinical studies. The prevention of brain hyperthermia may also emerge as a major objective of resuscitative intervention.