Cerebral Protection

I've been monitoring EEG for almost 40 years, and have done many hundreds of carotid endarterectomies under GA with EEG moniutoring (quantitative spectral EEG analysis and upper limb evoked potential monitoring), supplemented with MCA doppler and pre/post clamp or continuouus I think that barbiturates predominantly act by inverse steal (flow redistribution), which minimises the severity of watershed region ischaemia under incomplete non-global ischaemia.

Barbiturates may additionally provide some benefits from inhibition of the effects of excitatory neurotransmitters during, rand perhaps after, ischaemia, whether global or regional

The suppression of metabolic rate per se is likely of no direct benefit at all. It's not enough to keep cells alive very long - adding one or two minutes of survival time under total ischaemia at most. In any case, metabolic rate suppression from barbiturates relates only to EEG suppression only. Any cell facing death becomes isoelectic before rupture, and once it no longer consumes energy to generate the EEG, the rate of fall of its energy stores under total ischaemia is likely the same whether or not barbiturate coma existed beforehand. This explains why there is no evidence of anything more than a transient (<1minute) benefit for thiopentone burst suppression under global total ischaemia or in single cell / cell culture models.

Methohexitone and propofol are just as likely to produce comparable flow redistirbution benefits as thiopemtone, without the slow offset of thiopemtone. They certainly appear to provide similar increases in stump pressures when the EEG is suppressed during ipsilateral carotid occlusion.

Hypothermia does provide strong metabolic suppression and prolongs cell survival by reducing metabolic rate whether or not the EEG is present. It also provides strong inhibition of excitatory neurotransmitters.

Modest hypothermia and EEG burst suppression, as part of an anaesthetic in whuch the arterial blood pressuere is reasonably maintained, the ICP not elevated (mild hypocapnoea, volatile agent avoidance), and the cerebral venous pressure is not high, is most likely to minimise watershed ischaemia and minimise cerebral injury due to global or regional partial ischaemia.

For even periods of global total ischaemia lasting more than two minutes, only cold is likely to provide meaningful benefit.