Memory and Anesthesia

Proc Natl Acad Sci U S A. 2008 February 5; 105(5): 1722–1727.

Sevoflurane (shown to the right) is used in the induction or maintenance of general anesthesia. It boils at 58 degrees Celsius and is administered through an anesthetic vaporizer with a mixture of nitrous oxide and oxygen. The mechanism of action for sevoflurane is yet unknown. It is one molecule in a class of fluorinated methyl ethyl ethers and fluorinated methyl isopropyl ethers that are currently being used for anesthesia. These anesthesia compounds must have at max 4 carbons as their volatility (decreased with increased molecular weight) is necessary for action (Anesthesiology. 2008 Mar;108(3):531-3.) Interestingly, soda lime is used in anesthesiology to absorb exhaled carbon dioxide (reaction shown below) and the anesthetic agents need to be monitored for side reactions with soda lime.

1. CO2 + H2O --> H2CO3
2. H2CO3 + 2 NaOH (or KOH) --> Na2CO3 (or K2CO3) + 2 H2O + Energy
3. Na2CO3 (or K2CO3) + Ca(OH)2 --> CaCO3 + 2 NaOH (or KOH) (source)

Here are the components of soda lime: H2O (water), Ca(OH)2 (third reaction), NaOH (second reaciton- recycled in reaction), KOH (second reaction - recycle). Wet soda lime must be used - to force reaction 2. Otherwise Sevoflurane reacts with dry soda lime to form CF2=C(CF3)OCH2F. It seems this occurs through an elimination reaction with the hydrogen from the carbon neighbored by oxygen and the two fluorinated carbons. A fluorine is a good leaving group and what could abstract this hydrogen? Not H2O, Ca(OH)2 probably could and would form water. Perhaps, extra water would limit this side reaction (equilibrium). Well this is a side track.

I wanted to talk about memory, which is thought to be made through a neurobiological mechanism involving the amygdala. What was really cool about the study mentioned above is that they used no more than 0.25% sevoflurane doses in the study. To make this story short, subjects remembered less traumatic images with this low dose of anesthesia as compared to placebo. The article shows that the anesthesia lowered the metabolic rate of the thalamus (not amygdala) but the suppression was in areas of the brain that "interact with the amygdala and are known to play a role in mediating arousal and controlling the level of consciousness during anesthesia."

Furthermore, two doses 0.2% and 0.25% decreased memory of emotional slides while the o.10% enhanced this recollection. Further work is definitely going to be done to figure out whats going on. This has been mentioned as having the potential to relieve post traumatic stress disorder by breaking the connection of a certain image or thought with the amygdala. There is definitely more work to be done as the implications are very exciting!

A joke at every end:

A panda walks into a bar and orders spaghetti.
After the panda finishes he takes out a bow and arrow and shoots the bartender in the heart.
Next night, the panda walks into the same bar and orders lobster.
After the panda finishes he takes out a gun and pops the new bartender.
The next night, the panda walks in and orders pork chops.
The new bartender says "woh, I am not gonna serve you, you've injured the two previous bartenders, what's your problem panda."
"But I am a panda" says the panda.
"Hey, since when do pandas cause so much trouble! No panda I know" replies the bartender.
"Oh yea, look it up," says the panda "in that dictionary behind you"
The bartender pulls down the dictionary, opens to Panda and reads aloud.
"Panda: eats shoots and leaves."