Defeating normal thermoregulatory defenses: induction of therapeutic hypothermia.

Therapeutic hypothermia may be useful in various circumstances including stroke. However, core body temperature is normally tightly regulated. Even mild hypothermia in conscious subjects thus provokes vigorous thermoregulatory defenses which are potentially harmful in fragile patients. Furthermore, thermoregulatory responses are effective, which reduces the rate at which hypothermia can be induced. Drugs are thus often given to blunt normal thermoregulatory defenses. General anesthetics profoundly impair thermoregulatory control, but prolonged general anesthesia is rarely practical or appropriate. A variety of other drugs have therefore been evaluated. Most opioids only slightly impair thermoregulatory defenses, but meperidine is considerably more effective than equipotent doses of other opioids. The central alpha-2 agonists clonidine and dexmedetomidine are also useful. However, the best overall approach to inducing thermal tolerance appears to be a combination of buspirone and meperidine, which reduces the core temperature triggering shivering to about 33.5 degrees C in doses that maintain adequate ventilation.