Questions about Pharm of General Anesthetics

[Joe Joe on da Radio]

we had a dense 1 hour lecture on general anesthesia and i'm thoroughly confused.

can somebody please make sense of these statments to me...

"because a poorly soluble agent such as nitrous oxide has limited uptake into blood, the rate of increase in the partial pressure in arterial blood is rapid regardless of alveolar ventilation"

and

"because the rate of rise of the partial pressure in arterial blood toward the inhalational pressure is inversely related to the solubility of the anesthetic in blood, anesthetic induction is faster with less soluble agents"

i can understand that the potency of insoluble inhaled anesthetics are lower when compared to more soluble agents, but why is induction faster and the effect of ventilation minimal?

thanks!

-joe joe

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[UTSouthwestern]

When I first read about general anesthetics, I had the same problem grasping the concept as well.

The way I now visualize the concept is that a more soluble agent will stay in the blood to a greater degree when it is circulated to the brain whereas the less soluble agent will quickly leave the blood and cross the BBB into the brain. The trade off is as you have heard - the less soluble, quicker acting agents (Desflurane, nitrous, etc.) are not as potent as the more soluble, slower acting agents (Isoflurane, etc.), as penetration of neuronal membranes and disruption/alteration of neural conduction is functionally proportional to lipid solubility and agents with lower solubility will thus not be as potent.

 

[Joe Joe on da Radio]

thanks much UTSW

 

[beezar]

I had trouble initially with this concept too, but it becomes much easier (well sorta) if you go back to chemistry concepts.

For solubility of a gas in a liquid: The relationship between partial pressure of a gas created by dissolving it in a liquid and the actual amount of gas dissolved in a liquid is given by the solubility coefficient... before panicking let's look at an example--the solubility coefficient for O2 in blood is 0.003 ml O2/L blood/mmHg... in other words, if we dissolve 0.003 ml of O2 in each liter of blood, it will create a partial pressure of 1mmHg exerted by the O2. If we dissolve 0.006ml of O2 in each liter of blood, the partial pressure is 2mmHg etc.

So you can see that for a lower solubility gas much less gas is required to be dissolved into the blood to create the same partial pressure as for a higher solubility gas.

Example:
To create a partial pressure of 5mmHg,
-A low solubility gas (A) with solubility coefficient of 0.001 will require 5 x 0.001 = 0.005 ml of gas (A) per L of blood to be dissolved
-A higher solubility gas (B) with solubility coefficient of 1 will require 5 x 1 = 5ml of gas (B) per L of blood to be dissolved.

Thus much less of gas (A) is required to be dissolve in the blood vs. gas (B) to create the same partial pressure.

The key concept here is that it is the PARTIAL PRESSURE of gas in the blood that drives movement of the gas in and out of blood, NOT directly the number of ml of a gas per L dissolved in the blood.

So if a low solubility gas requires less ml of gas to be dissolved into the blood from the alveoli to create the same partial pressure, it will naturally cause quicker induction (b/c the partial pressure in alveoli can rise quicker because the blood is saturated quicker).

Hopes this makes sense.