Lipid Solubility is the first of these and due to the fact that most anaesthetics are lipid soluble this supports the theory that it is the displacement or expansion of the cell membranes that causes the anaesthetic effect. Diethyl ether, halothane, nitrous oxide and isoflurane all have this property but they do not seem to have anything else in common. General anaesthetics are not widely understood. However, though lipid solubility seems to be vital for this (or at least very important) the very long chain lipids do not seem to have an anaesthetic effect. This can be explained by the follow-up theory.The protein theory is that there is a protein binding site, but lipid solubility is needed to access the domain. This can be seen on the image! Chain length does improve lipid solubility but there is this 'cut-off' seen as lipids get to a certain size, suggesting that they have a specific space they must fit in. Another way the protein theory is demonstrated is by the fact that if you use a stereoisomer of an anaesthetic though it has the same lipid solubility it does not have the same anaesthetic effect.
Another important point about anaesthesia is that the dose required easily causes memory loss and loss of consciousness, but the difference in dose between loss of movement and CVS suppression is relatively small, thus there is a small therapeutic window.
Anaesthesia also happens in stages as the dose within the cells rises. These stages are:
I Analgesia
II Delerium
III Surgical Anaesthesia
IV Medullary Paralysis
Clearly we want to avoid getting medullary paralysis as this leads to death, but we need to keep within the surgical anaesthesia bracket.
Delerium is a very dangerous stage and must be passed through quickly both in and out of anaesthesia to prevent a person vomiting and choking. Adjuncts can help with this process. Adjuncts are medications given along side anaesthesia. For example, benzodiazepine is often given to aid anxiety and to relax the muscles so there is no need for a deeper anaesthesia. Metoclopramide is particularly useful in limiting nausea.
The concentration of anaesthetic given needs to be sufficient to distribute through inspiration into the alveoli and to the brain where it has its effect.
The minimal alveolar concentration is the amount that needs to be given in order to produce immobility in 50% of patients when exposed to a painful stimulus. Each anaesthetic has a different MAC, which is inversely proportional to the lipid solubility meaning that the higher the lipid solubility, the lower the concentration needed.
Transfer to the alveoli depends on the rate of breathing and the depth. If breathing is fast and deep this will lead to quicker induction. The transfer to the blood relies on the solubility. If it is highly soluble the blood has a larger capacity for it and it will take longer to saturate the blood. Finally, the transfer to the blood relies on the gas being given up by the blood. The blood:gas partition coefficient is the main factor in speed of conduction. The speed of induction is not related to the potency.
Commonly used anaesthetics include halothane, isoflurane, sevoflurane and nitrous oxide (gas and air).