CEREBRAL PROTECTION - ROLE OF INTRAVENOUS ANESTHETIC AGENTS

The administration of an intravenous anaesthetic agent before experime ntal cerebral ischaemia in animals improves the functional and histolo gical outcome. Cerebral ischaemia may be global or focal, complete or incomplete. Intravenous anaesthetic agents reduce the cerebral metabol ic demand for oxygen (CMRO(2)) and abolish electrophysiological activi ty. This reflects a discontinuation of the functionnal neuronal activi ty with maintenance of its basic metabolic activity. The oxygen spared by the decrease in consumption, while reducing the functional activit y, might be used by the neurons to sustain longer periods of ischaemia . This protective effect is also observed after pretreatment with eith er lidocaine or volatile agents, but their potentially deleterious vas odilating effect must be considered. Ketamine has recently been shown to antagonize NMDA receptors. The protective effect of barbiturates wa s experimentally demonstrated more than 30 years ago. They are still u sed as a reference. They reduce CMRO(2), optimise the ratio between ox ygen consumption and oxygen delivery and thus reduce cerebral blood fl ow and cerebral blood volume, as a result of the decrease of the metab olic demand. This might explain why a protective effect is seen in cas e of global or focal hypoxia with increased intracranial pressure, whi le no protection is documented in case of global cerebral ischaemia, s uch as after cardiac arrest, where EEG is immediately flat and ICP low . However, at doses required to obtain a protective effect, barbiturat es induce deleterious side effects such as severe arterial hypotension , which limits their use. Cerebrovascular and cardiac surgery or surge ry of the carotids are characterised by potentially ischaemic episodes which can be predicted. This allows proper application of protective measures, such as administration of intravenous anaesthetic agents. No t surprisingly, the only clinical documentation of a protective effect of barbiturates in man was achieved in patients undergoing cardiac su rgery under extracorporeal circulation. The concept of pharmacological cerebral protection in case of cerebral ischaemia was investigated wi th other agents than barbiturates, such as etomidate, gamma-OH and pro pofol. Anaesthetic agents with their properties of reducing CMRO(2) mi ght be of benefit if applied early, by <<buying time>> in the very fir st phase of the ischaemic insult.