Barbiturates drugs have been the prototype for anaesthetic protection against cerebral ischaemia.
The primary mechanism of protection of barbiturates drugs in cerebral ischaemia has been attributed to its ability to decrease the cerebral metabolic rate of oxygen consumption (CMRO2), thereby increasing the ratio of oxygen supply to oxygen demand.
The decrease in CMRO2 is accompanied by a parallel decrease in CBF and cerebral blood volume (CBV), which is the mechanism by which the barbiturates decrease ICP. Both these mechanisms may contribute secondarily to the protective effect of barbiturates drugs in cerebral ischaemia
However, a well-designed randomized controlled human trial has documented the ineffectiveness of barbiturates in preventing or ameliorating cerebral ischaemic damage that occurred in the setting of complete ischaemia.
It has been argued that EEG becomes iso-electric within 1-2 minutes of cessation of CBF and therefore, drugs suppressing EEG activity will be ineffective in such situations.
Following up on this theory, it was proposed that Barbiturates drugs act only during incomplete ischaemia, i.e., when EEG activity is still present.
These variables are experimental model, species differences, the type of Barbiturates drugs , dose, timing and duration of administration, temporary or permanent nature of the focal ischaemic insult and cardiovascular and respiratory responses to barbiturates.
While post-ischaemic treatment with high dose pentobarbital was reported to protect baboons from ischaemic injury, certain other studies reported failure to protect them from neurologic injury.
The experimental evidence in laboratory animals on Barbiturates drugs in focal cerebral ischaemia is contradictory and confusing because of the variables that influence outcome besides the barbiturate administration.
Miller’s anesthesia, 7th edition says the following about Effect of barbiturates drugs in cerebral ischaemia
There have been numerous demonstrations of the protective efficacy of barbiturates in focal cerebral ischemia in animals and a single demonstration of effectiveness in a human. The effect has been attributed principally to suppression of CMR. However, the effects of CBF redistribution and free radical scavenging have been suggested to contribute, and there is evidence that CMR suppression is not the sole mechanism. Suppression of CMR might logically be expected to be of benefit to brain regions in which oxygen delivery is inadequate to meet normal demands but is sufficient to allow energy consumption by some on-going electrophysiologic activity (i.e., in which the EEG was abnormal but not flat). Such regions are likely to be limited in size in the setting of focal ischemia, yet several of the animal investigations suggest a very substantial protective effect. Review of these experiments reveals that the methods used to monitor and maintain temperature, though accepted at the time, were below the standards that have evolved from more recent understanding of the effects of both deliberate and inadvertent hypothermia. Unrecognized cerebral hypothermia may well have been a factor in some of the cited investigations, and it is therefore possible that the protective efficacy of barbiturates may have been overestimated. Although more recent publications involving suitable temperature control methods do in fact indicate a protective effect by barbiturates, the magnitude of that effect was modest when compared with the results of earlier studies. Barbiturate-induced EEG suppression in an already anesthetized patient may still be logical therapy when it can be applied before or early in the course of a period of temporary focal ischemia (e.g., temporary occlusion during aneurysm surgery). However, the decision to institute such therapy should be made only after consideration of the risk of the occlusive event, the patient’s cardiovascular status, and the physician’s willingness to accept the possible prolongation of arousal, together with an objective view of the probable magnitude of the protective effect.
Numerous investigations in animals and humans have failed to demonstrate any protective effect of barbiturates in the setting of global cerebral ischemia (e.g., cardiac arrest).