[ MAC, Ideal agent, Physical properties, Classical vs Modern, ]
Great review from NEJM in 2003 here. Thanks to frca.co.uk.
Is the concentration of agent in volumes % at equilibrium, which prevents the response to surgical stimulation in 50% of subjects. It acts as a guide to the concentration of volatile required for anaesthesia. It is analogous to ED50 (Effective dose). The AD95 is the anaesthetic dose required to prevent response to surgical stimulus in 95% of subjects.
- MAC-awake. Is MAC to prevent voluntary responses to spoken commands
- MAC-immobility. Is MAC
- MAC-BAR (Blunt Autonomic Responses). Is MAC required to blunt autonomic responses to painful stimuli
Factors increasing MAC i.e. you need more volatile
Factors decreasing MAC i.e. use less
|Hyperthermia / pyrexia||Hypothermia|
|Catecholamines and other sympathomimetics||Alpha -2 - agonists (like clonidine)|
|Chronic opioid use||Acute Opioids|
|Chronic alcohol use||Acute Alcohol|
|Acute amphetamine use||Chronic amphetamine use|
To achieve equilibrium the gas must be be at the same concentration in the brain as in the delivered gas flow. The rate at which this occurs depends upon:
List of desirable physical and pharmacological properties:
Blood / Gas coefficient
Blood/gas coefficient is the ratio of the amount of anaesthetic in blood and gas when the two phases are of equal volume and pressure and in equilibrium at 37oC. In other words it is a reflection of the gas' solubility - a high b/g ratio = highly soluble.
You might think that the more of a substance in the blood - the greater it's effect. Oddly, that is not the case. The greater the partial pressure of a gas in the blood - the greater the effect.
Partial pressure = Total pressure x % by volume.
So a gas with a high solubility will exert a low partial pressure and will be slow to take effect and to offset.
A gas with a low solubility (like Sevoflurane) exerts a high partial pressure and therefore has a rapid onset and offset.
|Effect of the B/G partition coefficient and the partial
pressure exerted by halothane. 2% Halothane by volume of inspired gas will
exert 15.2mmHg (Atmospheric pressure = 760mmHg, 0.02 x 760 = 15.2)
Henry's law = the partial pressure will be equal in both
But the concentration in the blood will be the product of the concentration in the air and the B/G coefficient. 2 x 2.3 = 4.6%
|Rate of change of alveolar partial pressure against time.
The ratio of alveolar tension (Fa) to Inspired tension (Fi) is plotted
The numbers on the right are the B/G coefficients for each agent.
It is clear that the lower the B/G coefficient, less gets in the blood, therefore equilibrium is achieved more rapidly.
The more soluble the gas is, more molecules have to get into the gas to get to the same partial pressure.
It is the partial pressure of the agent in the blood and hence the brain that gives rise to anaesthesia. Therefore, agents with a low b:g coefficient exert a high partial pressure and therefore a more rapid onset/offset of action.
Oil / Gas coefficient
The oil:gas coefficient is an index of potency and is inversely related to MAC. The action of anaesthetic agents is suggested to be related to the lipid solubility (Meyer-Overton theory).
|SVP at 20oC||243||238||175||669||157|
|MAC in 100% O2||0.75||1.15||1.8||6||2.05|
|MAC in 70% N2O||0.29||0.56||0.57||2.5||0.66|
|20||0.2||2||<0.1||3 - 5|
|Blood / gas||2.2||1.36||1.91||0.45||0.6|
|Oil / gas||224||98||98.5||28||47|
Unitary hypothesis = All anaesthetics work via the same mechanism
Meyer-Overton rule = potency of anaesthetics correlates with their solubility in olive oil. Hypothesis: Do they act non specifically on the lipid components of cells.
Why has this been abandoned?
A general anaesthetic usually has many different effects and these are caused in different proportions by different agents. Therefore different agents act to differing degrees on separate sites in the CNS.
Some effects are spinal and some supra-spinal.
Ablation of movement in response to pain in mediated in the spinal cord.
Hypnosis and amnesia are supraspinal
In the brain there is globally depressed metabolism and blood flow and selective suppression of several centres.
Ion channels that are sensitive to volatiles - cysteine loop neurotransmitter receptors includes:
Working hypothesis is that they
enhance inhibitory postsynaptic channel activity
inhibit excitatory synaptic channel activity