General Question

Arglebargle_IV's avatar

What happens to consciousness during anesthesia?

Asked by Arglebargle_IV (68points) May 31st, 2008

somewhere I came across the idea that a measure of the effectiveness of an anesthesia (drug) could be predicted by how well the compound dissolved in olive oil.
olive oil supposedly like our nerve cells (in some manner I don’t get) and the better the drug dissolves the more effective it can be.
there was some speculation about how anesthesia drug interacted at the molecular/quantum (??) level that explained how anesthesia could stop the mind without killing the nervous system.
am I dreaming this up? know more?

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8 Answers

osakarob's avatar

I hope you get a comprehensive answer to this. Sounds fascinating.
I’m not sure if this will help, however it might be worth looking at.

More than 100 years ago. Ham Meyer in Marburg (1) and Charles Ernest Overton in Zurich (2) independently found that the action of general anesthetics is related to their partition coefficient between water and olive oil. Overton performed experiments on tadpoles and recorded the critical drug concentration, ED^sub 50^, at which they stopped swimming. Assuming that the solubility of these anesthetics in olive oil is proportional to that in biomembranes, he suggested that this critical concentration corresponded to a fixed concentration in biomembranes. The Meyer-Overton rule can be expressed as [ED^sub 50^] × P = const, where P is the partition coefficient of the anesthetic drug between membranes and water. Small molecules, as different as nitrous oxide, chloroform, octanol, diethylether, procaine, and even the noble gas xenon, all act as anesthetics. Overton noted that this action is completely unspecific, i.e., dependent only on the solubility of the anesthetic in oil and independent of its chemical nature. Surprisingly, this finding is still valid for general and local anesthetics (2–5) but remains unexplained. Overton concluded that this nonspecific! Iy requires a single mechanism based on physical chemistry and not on the molecular structure of the drugs. Although the close relation between anesthetic effect and solubility in lipids led many scientists to believe that anesthetic action is lipid-related, no model was proposed by Meyer and Overton or by later research. It is known, however, that lipid-melting transitions are lowered in the presence of anesthetics. This has been related to the anesthetic function (6,7).

In the absence of a satisfactory physiological membrane mechanism, many others prefer to view the action of anesthetics as due to specific effects on proteins, e.g., sodium channels or luciferase (8–10). Since anesthetics act on nerves and the Hodgkin-Huxley theory for the action potential is based on the opening and closing of ion channels, it seems natural to attribute the action of anesthetics to interactions with these channels. Some anesthetics show a stereospecificity indicating that the effective anesthetic concentration (ED^sub 50^) is different for the two chiral forms even though the partition coefficient is not affected to the same degree ( 11 ). In this regard, however, we note that lipid molecules are also chiral. While it is widely believed that local anesthetics are sodium channel blockers, a satisfactory general model of how anesthetics act on proteins is again lacking. The action of anesthetics is still mysterious. Some lipid and protein theories on anesthesia are reviewed in the literature (8,12).

The general absence of specificity and the strong correlation between solubility in lipid membranes and anesthetic action seems to speak against specific binding and a protein mechanism. On the other hand, there is clear evidence that the action of some proteins is influenced by anesthetics. Data on the influence of anesthetics on luciferase and on Na- and K-channels are summarized in Firestone et al. (13) and suggest that the action of lipids and that of proteins are coupled in some simple manner. Cantor has thus proposed that all membrane-soluble substances alter the lateral pressure in the hydrocarbon region and thereby influence the structure of proteins (14–16). Lee proposed a coupling of protein function to the transition temperature of a lipid annulus at the protein interface ( 17). While such mechanisms may provide a control of protein function, it is nevertheless remarkable that all animals are affected to the same degree by anesthetics, suggesting that anesthetic action is largely independent of the specific protein composition of membranes. (see (2), foreword to the English edition.) In addition to their effect on nerves, anesthetics also change membrane properties such as permeability and/or the hemolysis of erythrocytes (5,13). This indicates the need for a more general view of anesthetic action.

In this article, we focus on a thermodynamic description of general anesthesia based on lipid properties. We recognize that this can seem heretical given the dominance of the ion channel picture. Nevertheless, there are a variety of reasons for considering a macroscopic thermodynamic view. The striking fact that noble gases can act as general anesthetics speaks against specific binding to macromolecules. In particular, the Meyer-Overton rule would require all anesthetics to have exactly the same partition coefficient between lipid membrane and protein binding sites for all relevant proteins. It is difficult to imagine that nature provides binding sites for such a variety of molecules on the same protein in precisely such a manner that binding affinity is independent of chemical nature. (It is unlikely that one protein provides binding sites for all anesthetics. Therefore, if a protein picture was to be maintained one has to abandon a unique mechanism for anesthesia (Keith Miller, Harvard Medical School, private communication, 2006.)) An acceptable description should account for this evident lack of specificity, and this suggests the utility of thermodynamic arguments. Moreover, it is to be emphasized that thermodynamics is not inimical to microscopic (e.g., ion-channel) descriptions of the same phenomena. No one would claim, for example, that the manifest successes of thermodynamics in describing the properties of real gases in any way contradict the tact that they are composed of interacting atoms. Thermodynamics rather recognizes that many macroscopic phenomena are independent of such microscopic details and that a large number of microscopic systems can display features, which are bolh qualitatively and quantitatively susceptible to more generic methods. Precisely the absence of detail means that thermodynamic approaches are often capable of making testable quantitative predictions, which are often inaccessible to or obscured by more microscopic models. Thus, we wish to propose a simple thermodynamic explanation of the MeyerOverton rule based on the well-known physical chemical phenomenon of freezing-point depression. We will show that this picture has the benefit of providing an immediate and intuitive picture for the pressure reversal of anesthesia as a consequence of the pressure-induced elevation of the melting point in lipid membranes and can explain the effects of inflammation and divalent cations on anesthetic action.

source: The Biophysical Journal; Thermodynamics of General Anesthesia.

PupnTaco's avatar

I was under general anesthesia for the first time last year and I can tell you my consciousness went bye-bye for many many hours.

Overall, it wasn’t a horrible experience – apart from feeling like I was drowning or suffocating for about ten seconds before I went under.

shilolo's avatar

What you are describing is the fact that most volatile anaesthetics are hydrophobic (meaning that they do not mix well with water) and in general, are very lipophilic (meaning they like to mix with oily substances, i.e. olive oil).

You are correct to state that despite being used for over 150 years, the precise mechanism(s) of the volatile (inhaled) anesthetics remain unknown. However, most people believe that the drugs work by regulating ion channels in the brain, either directly or indirectly (via manipulation of intracellular calcium levels, which then regulate the ion channels).

I hope that answered your question. Feel free to follow up if you want to know more.

Arglebargle_IV's avatar

ion channels, yes, that was part of it! something about the possible ‘connections’ of ion channels surpassing the connections of dendrites/synapses….
then the idea that consciousness could be beyond (could never be explain in term of) the electro-chemical mechanism of synapses and instead reside in realm of these more complex connections.
you have all been very helpful.
is this making more sense?

shilolo's avatar

Sorry I didn’t address the concept of consciousness and anaesthesia. That is a far more complex discussion. I thought you simply wanted to know the mechanism of action of anaesthetic drugs.

Arglebargle_IV's avatar

@shilolo No need to apologize, you perfectly anticipate where I wanted to go.
I wanted to try to relate the mechanism of anesthesia to the question of the origins of consciousness.
I would appreciate it dearly if you would address the concept consciousness and anesthesia.
I’m vaguely familiar with the role calcium plays in ion channels. Regulating cellular membranes by triggering selective permeability. (Maybe I am way off, here.)
I’m curious for a ‘mechanism’ explanation of consciousness.

osakarob's avatar

Thanks for asking this question Arglebargle! This is the kind of discussion that I really love to see on fluther!!!!! ( as compared to some of the less substantial questions. )

Shilolo, thanks for your “layperson-friendly” response. I’d like to know more. I hope you will follow up!

SourIntel's avatar

Anesthesia is interesting. It just so happens we spoke about it during my philosophy class. We were discussing various solutions to the identity problem (sort of “how do i know i am the same person today than 15 years ago”) when we came upon memory.

Locke argues that it is our memories and experiences-that continuation-make us who we are. A type of anesthesia was mentioned by the professor just at that moment. It just so happened that some experimental anesthesia was being used in the 80’s-don’t quote me-that actually did not make you unconscious. You lost all motor functions, you couldn’t talk , etc, but you could feel. Imagine the excruciating pain patients would feel.

The funny thing is that the drug wiped your memory after the operation so you had no recollection of the pain. That would mean that upon waking, you felt fine, granted you just had an operation and must feel a bit crabby, but generally you thought everything went swell.

Maybe anesthesia doesn’t wipe our consciousness. Perhaps like this drug, which we don’t use anymore (the professor claimed), it is our recollection of the event that is gone.
What does that mean?

What i am saying argle, is that i don’t believe (i don’t have much scientific fact anyway) that anesthesia really “stops the mind” at all. I refuse to believe that our minds can just be switched on and off like a computer.

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