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Old 02-25-2011
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Question Aneshthetics and the arteriovenous gradient!

guys i am really confused about this one concept for anesthetics..there was a question on uworld asking if an anesthetic had a high arteriovenous gradient then how would it affect the anesthetic..
the answer was it will cause it to have a slower onset of action...
now the explanation confused me..it said that AV gradient signifies tissue solubility so when the anesthetic has a high solubility a large amount of anesthetic is taken from the arterial side and less is given off at the venous side..which i assume means a high AV gradient and also the drug having a low onset of action..Now if the tissue is getting more drug on the arterial side isn't that supposed to be good? so how will the onset of action be slow?
can someone plz explain this to me..i tried reading it up from lippincott too but I didn't understand that clearly either
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Old 02-25-2011
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I think I can clear your doubt:

The AV gradient they speak of is the difference between the pulmonary artery and pulmonary vein.

Does that clear it up? A high pulmonary AV gradient still means high solubility in the tissue (Fick's law) - only this time the tissue in question is the blood. Higher blood solubility means lower diffusion into the CNS, which means slower onset.

hope that helps...

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Old 02-25-2011
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Quote:
Originally Posted by Mondoshawan View Post
I think I can clear your doubt:

The AV gradient they speak of is the difference between the pulmonary artery and pulmonary vein.

Does that clear it up? A high pulmonary AV gradient still means high solubility in the tissue (Fick's law) - only this time the tissue in question is the blood. Higher blood solubility means lower diffusion into the CNS, which means slower onset.

hope that helps...

wow thanks a bunch..tht really does clear it up
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Old 02-25-2011
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Default Clarification

I am not very familiar with the concept of arteriovenous gradient so let me see if I have this straight:

High AV gradient always mean high solubility and low AV gradient always means low solubility

For inhaled drugs such as anesthetics, a high AV gradient means that it is very soluble in the blood and is taken up from the lungs quickly ("arterial side") but does not diffuse into tissues well ("venous side") thus a slow onset of action.

For other drugs (IV, oral, etc), a high AV gradient means that a lot of the drug is taken up at the arterial side and so less is taken up at the venous side. Thus a high AV gradient for these drugs means fast onset.

Is this sound reasoning or am I just making stuff up?
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Old 02-25-2011
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Quote:
Originally Posted by apx85 View Post
I am not very familiar with the concept of arteriovenous gradient so let me see if I have this straight:
High AV gradient always mean high solubility and low AV gradient always means low solubility
Yes - here is how I think of it:
  • I eat ten jelly beans. The next time I poop, there is one jelly bean in the toilet bowl. This represents a high in/out gradient. Jelly beans therefore have high solubility in my GI tract.
  • I eat ten marbles. When I poop, there are nine marbles in the toilet bowl. This is a low in/out gradient. Marbles therefore must have a low solubility in my GI tract.

Quote:
Originally Posted by apx85 View Post
For inhaled drugs such as anesthetics, a high AV gradient means ... a slow onset of action.
Yes, because the gradient is between the pulmonary artery (before the blood has been exposed to the drug-laden alveolar tissue) and the pulmonary vein (after exposure to the drug). I think of it in this very unscientific way:
An inhaled anesthetic with high AV gradient is absorbed into the tissue of the alveoli, but has a greater affinity for blood. When that anaesthetic+blood makes it to other tissues, the drug will still have the affinity for blood and not want to leave to go into the other tissues. This is the story I tell myself about it - I don't know how accurate it really is, but the metaphor works for me.

Quote:
Originally Posted by apx85 View Post
For other drugs (IV, oral, etc), a high AV gradient means that a lot of the drug is taken up ... Thus a high AV gradient for these drugs means fast onset.
Yes, because in this case the gradient is between blood on one side of a tissue (before the drug gets to choose between blood and the tissue) and blood on the other side of the tissue (after the blood has followed its affinity, as it were). The AV gradient in this case is totally different from that of the inhaled anesthetic, except that both are derived from a jellybean-vs-marbles sort of observation.

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Old 02-25-2011
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hahaha the pooping example made me laugh but it is something I will never forget now so thank you for that. If I have a similar question on the exam, I'd smile.
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My understanding of this concept was that a high AV gradient means the substance is very tissue soluble so it it quickly distributed in the tissues leading to not enough levels to cause anesthesia. So reaching sufficient levels takes longer as the the substance is constantly distributed in the body tissues like fat etc and thus slower onset. Now I am confused!
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Old 06-12-2011
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I guess there is a huge confusion here!

So, first:
The product of three factors determines anesthetic uptake: solubility (λ), cardiac output (Q), and alveolar-to-venous partial pressure difference (PA - PV).

Uptake = [(λ) (Q) (PA − PV)]/Barometric pressure

1.- Solubility (λ) : here we have the blood-gas partition coefficient (i.e., blood solubility [λ]), which describes the relative affinity of an anesthetic for two phases and therefore the partitioning of that anesthetic between the two phases at equilibrium.

For example, Isoflurane has a blood-gas partition coefficient of 1.4, indicating that at equilibrium, isoflurane's concentration in blood is 1.4 times its concentration in the gas (alveolar) phase.

A larger blood-gas partition coefficient produces a greater uptake and hence a lower alveolar gas concentration/inspired gas concentration or FA/FI ratio.

2.- Cardiac output : greater pulmonary blood flow removes more anesthetic and thereby lowers the FA/FI ratio.

3.- (PA − PV) : the alveolar-to-venous anesthetic partial pressure difference results from tissue uptake of anesthetic. Were there no tissue uptake, the venous blood returning to the lungs would contain as much anesthetic as the arterial blood that left the lungs. The alveolar (which equals arterial)-to-venous partial pressure difference would be zero.

So:

If solubility is small (as with N2O, Desfrurane or Sevoflurane = less potency = MAC increases) = Fa/Fi aproach one = rapid onset of anesthesia.
If cardiac output approaches zero (as in profound myocardial depression) = Fa/Fi aproach one = rapid onset of anesthesia (and complications...hipotension....)
If large AV diff = small Fa/Fi = slow onset of anesthesia
If the alveolar-to-venous difference becomes almost 0 (as can occur after an extraordinarily long anesthetic), uptake would be minimal, and FA/FI would equal 1.0.

Good luck!
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