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There are a list of anesthetic gases, with a bewildering variety of molecular structures. Many or most are described as having a "sickly sweet" odor (once on Gilligan's Island, the Professor made sleep gas out of sweet fruits and flowers).
Does anyone have a clue as to how these disparate chemicals work? Does it have anything to do with the smell?
Order of Kilopi
I'm afraid I can't help with the serious answer (apart from a general comment that they presumably block certain receptors in the brain) but I am fascinated by the smell part.
"Well, professor what does that one smell like?"
* thump *
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As I understand it, the nature of the mechanism is not well known, and what little is know has only been discovered in recent years. There was an article about it in the May 21, 2011 issue of Science News, but it is only available to subscribers.
I did find this article from 2010. (Pharmaceuticals 2010, 3, 2178-2196; doi:10.3390/ph3072178)
Abstract: For over 160 years, general anesthetics have been given for the relief of pain and suffering. While many theories of anesthetic action have been purported, it has become increasingly apparent that a significant molecular focus of anesthetic action lies within the family of ligand-gated ion channels (LGIC’s). These protein channels have a transmembrane region that is composed of a pentamer of four helix bundles, symmetrically arranged around a central pore for ion passage. While initial and some current models suggest a possible cavity for binding within this four helix bundle, newer calculations postulate that the actual cavity for anesthetic binding may exist between four helix bundles.
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They're all relatively high molecular weight and lipid soluble. Xenon is an anaesthetic, and that is almost completrly inert chemically.
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I don't think the high molecular weight is a universal characteristic. Diethyl ether, the "ether" used as an anaesthetic, has a molecular weight of 74 grams/mole; I wouldn't call that highOriginally Posted by kzb
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This is my understanding as well. It's fairly interesting that the OP asked this question expecting to get an answer, while the real answer is that nobody knows very well. I think there are other drugs that even today are not so well understood, such as lithium.
As above, so below
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It's high compared to the major components of the atmosphere. I'm sure there is a relation between molecular mass and efficacy of anaesthesia. Basically, the higher the mass the lower the partial pressure needed for it to function as an anaesthetic.
Even dinitrogen has intoxication effects in deep-sea diving. If you replace the dinitrogen with helium (lighter than dinitrogen), you can dive a lot deeper without getting intoxicated. Both gases are chemically inert in this context. It is not chemistry per se that is governing this relationship.
Order of Kilopi
If Grant Hutchison were still active he might give us a few pointers about anaesthetics; he gave me some info on the anaesthetic properties of the theoretically inert gas Xenon that opened my eyes.
see, for example
http://en.wikipedia.org/wiki/Xenon#Anesthesia
Xenon is completely odourless, by the way, and is supposedly very safe, but also very expensive.
My nephew is an anaesthetist, but he's generally far too busy to natter on the interwebs these days.
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Isn't the displacement of oxygen a common factor? You cut down on their O2 intake, people get sleepy.
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No it's not. The oxygen concentration in anaesthetic gases is maintained at the standard level.
It seems to be a function of molecular mass, lipid solubility, chemical inertness in the body, and ability to be transported from the lungs to all parts of the body in sufficient concentration.
Xenon and krypton are both inert gases, but xenon functions as an anaesthetic at atmospheric pressure. You have to increase the pressure to be anaesthetised by krypton. Strange.
Order of Kilopi
Not all anesthetics are gases tho, I recall getting something through an IV, but is the mechanism of action be similar or different?
Et tu BAUT? Quantum mutatus ab illo.
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Cyclopropene doesn't have a particularly high molecular weight.
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Unfortunately, this is a true statement about most transmembrane proteins. Methods have been developed to accurately measure a chemical's effect on the potential across these channels, but the complex ionic environment around these proteins has made structural analysis of intact molecules notoriously difficult.
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The narcosis effect of simple "inert" gases at pressure (dissolution into lipid bilayer IIRC) seems to correlate roughly with molecular weight, but this is a different mechanism than the anesthetic effect from medical gases. Molecular weight is not the governing factor for structural interactions with ion channels; molecules with very similar molecular weights and empirical formulas can have drastically different effects as a drug.
Maybe the common smell is because molecules that tend to interact with ion channels tend to also interact with the scent receptors that register "sickly sweet"?
Order of Kilopi
Or it's just plain false that they all smell sickly sweet, but it's generally experienced because it's common to use mixtures of different gases only some of which have the smell, but since people normally don't ask about the specific mix (which is varied during the procedure anyway) they get the impression it's always that smell.
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Reductionist and proud of it.
Being ignorant is not so much a shame, as being unwilling to learn. Benjamin Franklin
Chase after the truth like all hell and you'll free yourself, even though you never touch its coat tails. Clarence Darrow
A person who won't read has no advantage over one who can't read. Mark Twain
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No but it is potentially highly reactive. If you are telling me that it has anaesthetic effects, perhaps those effects are down to toxicity rather than true anaesthesia. So it's only an anaesthetic in the same sense that carbon monoxide is an anaesthetic ? Personally I wouldn't go inhaling cyclopropene without doing some careful checks first.
Ara Pacis wrote:
Not all anesthetics are gases tho, I recall getting something through an IV, but is the mechanism of action be similar or different?
They usually give you some serious drugs to make you really calm (or put you to sleep) before they gas you. But it's the gas that is classed as the anaesthetic.
Or it's just plain false that they all smell sickly sweet
Ether and chloroform could be described as sweet smells. With modern anaesthetic gases I am guessing the sweet smell comes either from an additive or from products used to clean the mask. If it smells nice it can't scare you can it?
Order of Kilopi
Halogenated ethers are still the main ingredient of anaesthetic gases, which will likely by itself account for the general impression of the smell.
__________________________________________________
Reductionist and proud of it.
Being ignorant is not so much a shame, as being unwilling to learn. Benjamin Franklin
Chase after the truth like all hell and you'll free yourself, even though you never touch its coat tails. Clarence Darrow
A person who won't read has no advantage over one who can't read. Mark Twain
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That makes sense.
I used to wonder why -- when they used to operate without anesthesia long ago -- they didn't just put a bag over the patient's head until he passed out from inhaling carbon dioxide. However, I guess he'd wake up as soon as they started cutting, so that wouldn't have helped for long.
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^ That's called suffocation not anaesthesia ! Have you tried re-breathing the same air by breathing in and out of a bag? It's pretty stressful. CO2 has special physiological effects, and stimulates you to breathe harder much more than simple lack of oxygen does. [note added in edit: Don't actually try it ! It could be dangerous, just take my word for it !]
In fact, in some cases, they add additional CO2 to oxygen, precisely to stimulate the breathing response.
Another interesting fact: if you walk into a room where most of the air has been displaced by nitrogen, you will black out and die almost instantly. Much quicker than being smothered or strangled. This is because you are actively expelling oxygen from your blood with every breath.
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In fact the respiratory drive in the vast majority of humans (i.e. the desire to breathe) is almost entirely the hypercapnic (high CO2) drive. In cases of very advanced COPD for extended periods of time where the person is persistently hypercapnic the respiratory drive effect due to Hypoxia (low oxygen) can appear and take over, which can cause a problem in emergency responder scenarios since for someone dependent on the hypoxic drive the administration of unmetred oxygen can in fact suppress the respiratory drive entirely...
this is generally considered a bad thing...
Order of Kilopi
Heh.
My neighbour (Hi, Hamilton) seems to make a habit of monitoring BAUT (as was) for non-physics-related threads he can mention to me in passing, to try to tempt me back into posting. It finally seems to have worked.
Here we go, first with some general stuff that I hope addresses various points raised in-thread, and then something more specific about the OP:
You can induce general anaesthesia using intravenous drugs and/or inhalational agents (various gases and vapours). Nowadays it's possible (indeed common) to undergo total intravenous anaesthesia, during which you are kept asleep entirely with intravenous drugs, while breathing air with a little supplementary oxygen. It's also common to receive an intravenous dose of general anaesthesia (to get you off to sleep quickly) followed by inhalational anaesthesia to keep you asleep. It's much less common to have anaesthesia induced by breathing a gas or vapour (that is, with no intravenous anaesthesia) but it still happens.
The specific effect sites for the intravenous drugs are pretty well defined - they bind to a variety of neurotransmitter receptors. A guy I work with was involved in the work that zeroed in on the exact site of action for propofol - there are mice alive today which are completely immune to propofol anaesthesia, because they've had their GABA-A receptors genetically tweaked to alter the propofol binding site.
Receptor sites for inhalational agents are less well-defined. The "Overton-Meyer relationship" between fat solubility and anaesthetic potency is pretty strong. It used to be thought that these agents worked simply by dissolving in the lipid bilayer of the cell membrane, thereby inducing changes in the shape of neurotransmitter receptors which float in the membrane. The most popular theory now is that relative fat solubility is just a reflection of the inhalational agent's willingness to bind to some specific hydrophobic site within a broad family of membrane receptors. It also seems likely that the simple anaesthetic gas molecules (nitrous oxide, xenon, etc) work at a different effect site from the larger molecules of the various halogenated hydrocarbons and ethers.
There's a very rough relationship between atomic weight and potency for the inert gases, but it's not linear: the five-fold increase in atomic weight between helium and neon buys you a 50% increase in potency, whereas the 50% increase in atomic weight from krypton to xenon is associated with a tenfold increase in potency. Non-monatomic gases sometimes buck the trend: hydrogen molecules are lighter than helium, but hydrogen is a more potent anaesthetic. And the vapours don't seem to show such a relationship, albeit within a fairly narrow range of molecular weights: enflurane and isoflurane, for instance, have the same molecular weight (they're isomers) but different potencies.
Carbon dioxide and low oxygen concentrations have both been used in anaesthesia in the past (I've seen it called "suffocation anaesthesia"!) but the physiological stress associated with that sort of thing can be life-threatening, so there are all sorts of alarm and safety systems in place nowadays specifically to ensure that anaesthetized patients aren't exposed to either reduced levels of oxygen or raised levels of carbon dioxide.
I've never encountered an anaesthetic gas or vapour I would describe as "sickly sweet" - I've always imagined that description was made up by novelists who didn't know any better, and who were trying to evoke something both appealing and threatening. The only other explanation I can think of is that Oil of Orange was used back in the early twentieth century to "mask" the smell of truly pungent inhalational agents like ethylene, so perhaps the high-intensity fruity smell became confused with the smell of the agent itself. Anyway: the vapour anaesthetics are all based on hydrocarbons or ethers, and so they tend to smell somewhere on that spectrum between petroleum products and stain-remover solvents. Some are described as "sweet" in the textbooks, but this is really just used as the opposite of "pungent" - the "sweet" agents are not as unpleasant to breathe as the pungent ones, and I'd tend to use the word "light" rather than "sweet"; I don't get the sense of smelling something that might be sweet-tasting, as I do with (say) the pear-drop smell of some ketones.
Here's my impression of the agents I've actually used:
Nitrous oxide: I find it odourless, but some people describe a vague mustiness.
(Diethyl) Ether: Light, solventy, but pungent at high concentrations..
Cyclopropane: Light, petrol. (It's said to taste of petrol, too, in high concentrations.)
Halothane: Light, somewhere in the petrol-to-solvent range.
Enflurane: Slightly pungent solvent, with a hint of the British throat lozenge "Victory-V".
Isoflurane: Very pungent solvent.
Sevoflurane: Light solvent, a little like a white-board marker pen.
Desflurane: Very pungent solvent, but distinctly different from isoflurane.
So we've got a bunch of gases (nitrous oxide, nitrogen, hydrogen, the inert gases) that don't smell of much and probably bind to one region of various neurotransmitter receptors, and a bunch of rather similar hydrocarbon/ether-based molecules that probably bind to another part of the receptors, and which all smell vaguely similar. So it may be that the receptor site selects for a family of similar molecules that also generate similar smells. But I also suspect we haven't explored much of "molecular space" in our search for anaesthetic vapours. The rule has always been to take a small hydrocarbon or ether, and to whack some halogens on to it - to a large extent, we're still looking under the same streetlight where we first chanced on inhalational anaesthesia. Maybe there are molecules out there that look different and smell different, but which can also do the trick at the right receptors.
Grant Hutchison
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That makes sense. I do recall that I must have had a tube in my mouth since my lower lip was numb for a few days because it was pinched between my teeth and something, so maybe it was for anesthesia. I'm not sure what the IV was, but I felt it moving through my system and told them where it was until it got to my neck, and then I told them goodnight, closed my eyes and was out like a light.
Et tu BAUT? Quantum mutatus ab illo.
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Until a few years ago, my only experience with anesthesia was quite long ago, but it made an indelible impression on me.
It must have been 1955 or 1956: I'm pretty sure that I was four or five years old, and it was at a dentist's office. I think that was a period where they did that routinely.
I remember having a rubbery mask slapped on my little face, then inhaling something very rarefied, and having the illusory sensation of first my mouth and then my entire head being distorted and turned inside out before I lost consciousness.
I have no memory of any tooth problems from that period (though I must have had something that required attention), but I vividly remember those sensations, after 50-odd years.
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Is anesthesia awareness well understood at all? That is, varying degrees of awareness (and sometimes feeling pain) while on the operating table during general anesthesia.
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That's a classic paediatric dental anaesthetic of the time. Done without monitoring, and the dentist was responsible both for administering the anaesthetic and getting the teeth out.
I had a similar anaesthetic in the 1960s, but without the benefit of oxygen. Nitrous oxide is a pretty poor anaesthetic agent, and even an 80:20 mix with oxygen doesn't reliably stop people moving around when someone yanks on a tooth. So there was a vogue for cranking the nitrous up to 100% briefly, to get a brief period of deeper anaesthesia, and then to quickly hoick the teeth.
They put the rubber mask on and at first I felt pretty mellow, then suddenly I felt like I couldn't breathe and I was out like a light. Couple of minutes later I woke up vomiting, with a pounding headache. Shame - I'm sure I could be putting some of those dead brain cells to good use now.
I have a textbook of dental anaesthesia from that time which (paraphrasing from memory) says: 100% nitrous oxide should be administered until the lips are blue and the pulse begins to fade. At that point a single breath of air should be administered, and extractions may commence.*
The footnote reads *If the child fails to breathe at this point, it is advisable to assist ventilation.
Grant Hutchison
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It's pretty well understood [we think, see below]. These people didn't get enough anaesthetic, and usually there's an obvious reason for that - the two broad categories are: 1) equipment failures and errors; 2) situations in which patients are so sick the anaesthetist deliberately throttles back on the anaesthesia in order to avoid killing the patient. In the latter situation (as with near-death situations generally), recall is usually patchy and pain is very rare.
Traditionally, avoiding anaesthetic awareness has relied on making sure we're delivering the right drugs in the right quantity to the right place, and on monitoring the patient's physiology for signs of light anaesthesia. Nowadays there are a number of modalities available that use analysed EEG to tell us if the patient's asleep or not, but in my experience they all have a similar short-coming: they're good at telling you if someone's unconscious, they're good at telling you if someone's conscious, but they're not good at telling you if someone is about to be conscious. Given that the final signal the anaesthetist looks at has been integrated over the previous minute or two, the horse could be well gone before you even started thinking about checking the stable door. So these are valuable monitors, but still very much second-line behind punctilious care with the basic checks.
Added: But watch this space. In the UK at present there's a national audit of anaesthetic awareness going on. We're making an extensive effort to pick up every possible story from a patient that even might reflect an episode of awareness or some sort of residual recall taking place during anaesthesia, and examining them all in detail. That's a rather different undertaking from just looking at barn-door cases of detailed recall which the patient immediately reports, so there's the potential for our understanding of the problem to change.
Grant Hutchison
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I find this subject very interesting, although I do not have much interest in medicine in general. I didn't become interested in this until I had surgery a few years ago.
In 2005, I had an ATV accident and I shattered three of the bones in my right hand. About an hour before I was to go into surgery, the anesthesiologist came to speak to me and explain what he would be doing during my surgery. My wife asked most of the questions because I was doped up on morphine and I really didn't care what he was saying. When it was time for my surgery he walked up to my bed and put a syringe in my IV line. He said to me, "Here's one for the road" as he was pushing the plunger. I distinctly remember laughing and starting to say something to him, and then it seemed like immediately after I was waking up from the surgery.
I did a little research afterwards, and it turns out that they gave me some Versed-type of drug before the general anesthetic. That drug blocks the formation of memories, so it was possible that what I remember starting to say I actually did say. I just have no memory of it. The way I understand it, they do that so that if someone does regain any consciousness during the procedure they won't remember it. I guess being cut open and paralyzed while conscious, even if you can't feel the pain, is pretty traumatic and I can understand why.
In 2010, I took a pretty good bump on that hand and a tendon in my hand began to be irritated by some of the hardware that was in there. I had to have a second surgery to have the hardware removed. That was a fairly short procedure, about 45 minutes compared to the 3 hours the initial procedure required. I was offered a local anasthetic, but I chose to be out for the procedure. In that case, they just put the mask over my face and I remember becoming unconscious. I'm not sure why they did it differently, but I was able to go home the same day so I didn't complain about it.
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That's a hard act to follow. (Post #25.)
I've only been knocked out once, at age 15 to have my
appendix removed. It was in 1968. The anaesthesiologist
used a neat pen-sized Star Trek device to numb the back
of my hand slightly before sticking the IV needle in.
I recall that he immediately said that he thought the
first little tap with the device might not have been
enough, and gave me a second one. I wonder now,
for the first time, whether that might have been purely
psychological. Maybe it was just a pen! He had no
reason to think I was anxious about getting poked,
but it might have been something they always did at
least with kids to make them less concerned about
pain from the needle. After the IV was in, he told me
to count backward from 100. I counted "99, 98, 97"
and woke up back in my hospital room. I told the
nurse who was there about what I thought was the
rather interesting way that rectangular pieces of the
room were sliding and shifting around, but she didn't
find it as interesting as I did. I went back to sleep.
If they ever put a mask on me or anything in my mouth,
I didn't know about it.
The description "sickly-sweet smell" sounds very much
like how roses smelled to me for a very long time. The
fragrance was too strong to be attractive. Same with
any kind of perfume. Similarly, a patch of quackgrass
(I think it was) in my yard felt very uncomfortably rough
when I rolled over it. Years later I tried rolling over that
same patch of grass to see if it still felt uncomfortable,
and it didn't. I think kids are more sensitive to some
sensations than adults are. The sickly-sweet odor might
be something kids notice very readily, but not adults.
-- Jeff, in Minneapolis
http://www.FreeMars.org/jeff/
"I find astronomy very interesting, but I wouldn't if I thought we
were just going to sit here and look." -- "Van Rijn"
"The other planets? Well, they just happen to be there, but the
point of rockets is to explore them!" -- Kai Yeves
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Yep, it was a pen.
The technical term for this technique is "lying" - your anaesthesiologist just plain patronized the hell out of you.
Grant Hutchison
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I just read primummobile's post immediately before
mine. When he said that the anesthesiologist walked up
to his *bed* (rather than the operating table) it reminded
me that I had been given something before I was taken to
the operating room. Some sort of preliminary anaesthetic.
But I don't remember how it was administered or by whom,
or that it had a noticeable effect. It makes me wonder
how many different steps there were. First this preliminary
anaesthetic, given to me in the room I would spend the
next two days in, then the taps from the penlike thing,
then the IV, and possibly gas after that?
-- Jeff, in Minneapolis
http://www.FreeMars.org/jeff/
"I find astronomy very interesting, but I wouldn't if I thought we
were just going to sit here and look." -- "Van Rijn"
"The other planets? Well, they just happen to be there, but the
point of rockets is to explore them!" -- Kai Yeves
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