Neurotoxicity of Anesthetics

Abstract

It is clear that the major and most obvious manifestation of a toxic effect of either a local or a general anesthetic is CNS irritability. When this progresses to frank seizures, a marked increase in the rate of cerebral metabolism is known to occur. Thus, delivery of adequate oxygen to the brain by an increase in blood flow becomes critical, and is the usual compensatory response. Assuming such a response is possible and ventilation is adequate, there is, to the authors' knowledge, no evidence of neurologic damage resulting from seizures. With repeated seizures and inadequate ventilation, brain damage will occur. Seizures produced by local anesthetics are perhaps more life-threatening, in part because the patient may not be as closely monitored and loss of airway is more likely. In addition, when seizures are produced by general anesthetics, treatment usually consists of simply decreasing the inspired concentration and correcting any hypocapnia. With local anethestic, an abrupt decrease in brain concentration is not possible, and some kind of pharmacologic CNS depression is necessary. In this regard, prevention and treatment have been improved by the use of diazepam. Other toxic effects of local anesthetics on neural tissue are difficult to demonstrate and, assuming use of proper concentrations, must be very rare. CNS toxicity of general anesthetics other than seizures is also difficult to demonstrate, and is largely speculative. Clearly, general anesthesia produced by inhalational agents cannot be equated with that produced by intravenous administration of barbiturates. Despite the clinical syndrome of 'barbiturate intoxication', it seems clear that CNS 'toxicity' secondary to an overdose of barbiturates consists of only an exaggerated pharmacologic depression, which is totally reversible by adequate supportive measures. By contrast, there is evidence that gross overdoses of volatile anesthetics can produce, in addition to pharmacologic CNS depression, a direct toxic effect on cerebral metabolic pathways. 196 references are cited.