Going Under: What we don't know about anesthetics

The majority of people reading this sentence will, at some point in their lives, undergo a medical treatment that requires general anesthesia. Doctors will inject them with a drug, or have them breathe it in. For several hours, they will be unconscious. And almost all of them will wake up happy and healthy.

We know that the general anesthetics we use today are safe. But we know that because they've proven themselves to be safe, not because we understand the mechanisms behind how they work. The truth is, at that level, anesthetics are a big, fat question mark. And that leaves room for a lot of unknowns. What if, in the long term, our anesthetics aren't as safe for everyone as we think they are?

The only way to know for sure is to figure why anesthetics cause unconsciousness, and how one drug differs from another. Roderic G. Eckenhoff, MD, is a professor at the University of Pennsylvania's Perelman School of Medicine. He's one of the people trying to figure out what general anesthetics really do inside the human body, and how we can use that information to discover even safer drugs than the ones we already rely on today. How does he study that? By drugging tadpoles.

This week, Chemical and Engineering News published a profile of Eckenhoff and his work, written by journalist Carmen Drahl. That piece inspired me to call up Eckenhoff and find out more about what we think we know about anesthetics, why it's taking medical scientists so long to understand such a commonly used class of drugs, and why tadpoles make an ideal model animal.

Maggie Koerth-Baker: Describe for me, in your own words, the current basic theory of how anesthetics work. We're talking about chemicals binding to protein receptors, correct? But what does that mean? Why do proteins matter?

Roderic G. Eckenhoff, MD: The real simple answer is that we don't know. We don't even know what class of macromolecule, for certain, underlies the effects of general anesthetics. And anesthetics don't just do one thing. They produce a myriad of effects ranging from hypnosis, to amnesia, to pain relief and a range of other effects that are much less desirable, like hypothermia, nausea, and vomiting.

But most of us think about the primary effect, which would be unconsciousness, and the answer is still we don't know for sure. But there has been a gradual shift in the field to thinking that protein targets are the likely candidates for this interaction. The main reason is selectivity. Even though "unconsciousness is unconsciousness" the whole spectrum of what the unconsciousness looks like aren't always the same from drug to drug. Some patients are more dysphoric afterwards, for instance. There are components of the electroencephalogram that look different from one drug to the next. That leads us to believe that there's some selectivity.

That's a bit of a surprise, actually, that the drugs aren't all working the same. In the last 5 years or so that's come more to the forefront. A very, very small molecule like halothane, which isn’t used in the United States anymore, might act differently than a drug that's more popular today called isoflurane. There's surprising selectivity to these drugs and we're only now starting to appreciate. And when you talk about selectivity, you're talking about proteins because they have the most diversity in terms of structure.

Ion channels [A type of protein—MKB] are also important because they transduce most communication and signaling in the central nervous system. If we think the drugs affect synaptic transmission, for example, then there's a host of ion channels that could be candidates. They are prime targets simply because of what they do. The evidence to date looking at ion channels in vitro strongly supports that notion.

MKB: In the Chemical and Engineering News article, writer Carmen Drahl talks about some of the major discoveries behind how anesthetics work, and we find out that these discoveries happened in the 1980s. What took so long?

RE: That gives you some insight into how difficult the problem will be. A large group of people has been working on this for a long time and we barely know what class of macromolecule underlies the effects. That's remarkable at this stage, given the millions of dollars that have been poured into the problem. It’s taken so long because we've been searching for the single target or just a few ... but it's probably a bigger problem than that.

My bias, which is somewhat speculative, but evidence supported, is that we're talking about interactions with as many as 10, 20, or even 50 different protein targets. That constellation of small effects disrupts the extraordinarily well-timed signaling in the central nervous system to produce the final common pathway of unconsciousness.

What we’ve seen is that people have their favorite targets that they work on in vitro and when they work their way back up to an intact animal they find that this target has only a very small contribution to the overall effect, in contrast to in vitro work. That's been reproduced time and time again. The model that seems to work best is a small-effects-at-multiple-targets model. How does one achieve selectivity then? What you’re probably seeing is each drug affecting different but overlapping mix of targets.

MKB: We've been using anesthetics for more than a century without really understanding how they work. What does that mean for safety? Are there cases where we know, in retrospect, that an anesthetic was being used improperly because we thought it worked differently than it really did?

RE: The first question is about safety. We started with two principle drugs in 1850, chloroform and diethylether. Those two grew up together and the latter is a very safe anesthetic, but it’s explosive and flammable. So it doesn't mix well with today's electronics. Chloroform is unsafe, in the sense that it's metabolized into reactive products in the liver and causes liver toxicity. It also has bad cardiovascular effects. So both drugs have gone by the wayside and the safety profile of the drugs we do use has continuously improved. But it’s not because of us knowing how they work. It's all been empirical, trial and error stuff.

Today, we have drugs that are safe in the short term, but we’re worried about long lasting effects, especially cognitive effects in the vulnerable brain, for example the elderly and children. Effects could last well beyond duration of administration. That's gotten people worried. That's why we're trying to come up with other chemotypes that don't do these things.

MKB: I think this is one of those things that would sound quite scary to a lot of people — that their anesthesiologist doesn't really know exactly how anesthetics work. But we use these things every day, so it must be safer than it sounds. Why is that not actually as big of a problem as people might think?

RE: Because we get away with it. Worldwide, it's estimated that over 200 million general anesthetics are given each year. In this country alone it’s something like 40 or 50 million per year. Really, only 30-40% of people make it through life without experiencing a general anesthetic. Based on the safety profiles, the bad things that happen and are directly attributable to anesthetic are very rare. But that's just the tip of the iceberg. We don't know what else we're doing long term. We're just not set up to know that yet.

MKB: Besides the fluorescence which makes it easier to track through a tadpole's body, what makes 1-aminoanthracene, the anesthetic you're working with, a better drug? What could it do for humans that existing anesthetics don't already do?

RE: I wouldn't give that to any human. Aminoanthracene is strictly a lab anesthetic that helps us to understand what the microscopic and molecular targets might be. It's only advantage is that it’s fluorescent. If you do reading on 1-aminoanthracene you know they aren't good molecules to have in you for any length of time. Probably carcinogenic.

We have two arms to our research, finding the targets and trying out new drugs. Aminoanthracene has helped in both arms. One arm of the project is discovering new drugs — we've done a large screen of half a million compounds and are now sorting through the hits to find a new class of general anesthetic. The other arm tries to identify what the molecular targets might be. Finding the targets helps us to direct drug development a bit more.

MKB: How is this different from localized anesthetics? Do we understand those better?

RE: The mechanism of local anesthetics for things like epidurals, spinals, local anesthesia, we think we understand that a lot better. They're bigger molecules and there’s a good relationship between selectivity of the molecule and its size — local anesthetics are more selective about what they affect. And part of the safety also comes from the fact that we only give a little bit in a very selective place, to begin with. By the time it disseminates into the rest of the body the concentrations are so low that it does nothing. Dose matters. For example, if you give enough local anesthetic intravenously, they can cause seizures and cardiovascular collapse. But in small doses it’s safe.

MKB: I think a lot of people will be interested in the fact that you work with tadpoles, and not a model that's more familiar to the general public, like mice. Carmen Drahl writes that this is because tadpoles are cheap, and that they are an excellent mimic for human responses to anesthetic. When we say "excellent mimic" what are we really talking about? How does a tadpole on anesthesia resemble a human?

RE: Basically, this sounds kind of primitive, but the basic endpoint used in anesthesia is that when a surgeon cuts the patient, they don't move. I'm serious. It's very, very crude, but it's the coin of the realm. The bottom line is that when you do something that ought to hurt the animal, it doesn't respond. In a tadpole that means trying to elicit a startle reflex by tapping their dish, or tapping the tadpole itself. If it doesn’t do anything, it’s considered anesthetized.

That behavior, loss of movement, we see in animals going all the way down to the fruit fly or the nematode. Any animal that can move can be an anesthetic model. But what I really mean by “mimic” is that concentrations required to produce that endpoint are almost the same, within 10 or 20% or so, of those required to achieve the endpoint in humans. And that’s right across a large number of common anesthetics.

The ability to be anesthetized is a very conserved response. I wrote a paper a few years back on “Why can all of biology be anesthetized?” The response even extends to plants!

MKB: So why can all of biology be anesthetized?

RE: I have a theoretical, protein-based argument — that proteins have small hydrophobic cavities that are essential to their movements and function. If you fill those holes with a small hydrophobic molecule, like anesthetics, you're going to inhibit or change the function of the protein in some way. It may be such a small change that it doesn't matter, or it can matter a lot. But all proteins have these cavities, so all of biology should be affected.

Thanks to Aaron Rowe!

Image: P1110844CrvHC, a Creative Commons Attribution Share-Alike (2.0) image from thirteenofclubs's photostream


  1. I’ve been put-under twice in my life. It’s just the oddest, slightly disturbing thing to close your eyes for a mere second and have four hours pass in that blink.

    1. Absolutley, I was under once for joint surgery, and it really feels like the removing of a link between moments in time. One moment I’m being introduced to the anestheologist and counting backwards, the next being rolled down a hallway asking when we will begin, and being told that the surgery had been done. Freaky as hell. No dreams, no sense of time passing, just a jump, b ut no awareness of a jump. You have to accept there was one because of the clocks and the expieriences of others.

      1. And the counting backwards trick is dirty.  You never make it all the way to zero.  The other mean one is to ask if the anesthetic feels hot or cold going in to distract you.  To this day I’m still not sure if it felt like either.

        1. “if the anesthetic feels hot or cold…  To this day I’m still not sure if it felt like either.”

          Definitely not ether – they don’t use that anymore.  Too flammable.

        2. I really liked that trick… but then, the first time I needed general anaesthesia, I was 1) terrified, 2) a young teenager and 3) suffering from congenitally poor circulation which makes it hard to get a needle into my adult arms.  In hindsight, I really admire the anaesthesiologist – coaxing a scared child into talking calmly while he changed arms for the fifth time in an attempt to get a needle in.

    2. same here, and both times I try like HELL to fight it and just never works! Not that I thought I could stave off the effects, but it sounded fun to try it :)

        1. Wisdom teeth removal is not usually done under actual general anaesthesia. Usually, a local or regional anaesthetic combined with sedation is used (this is called monitored anaesthesia care, MAC). Same drugs that are used for general anaesthesia can be used for sedation, but the dosage is lower. That’s why the surgeon was talking to you.

          1. Ah! Thank you! It really wasn’t explained properly to me – as I mentioned, the guy wasn’t actually an oral surgeon. His incompetence is already proven, so I’m not surprised he didn’t properly explain. The only reason I know *anything* about the anesthetic used is because I read “Sodium Pentothal” off of the IV and looked it up. It’s listed as a drug used for general anesthesia. Anyway, all in all, that surgery wasn’t a great experience. I *highly* recommend having an oral surgeon do any oral surgery that you may need.

          2. Hmm, I had the option of being put under for my teeth, which I took. I was a little scared, but it went just fine. They were removing all 4 of my wisdom teeth, 2 which had broken through the gums and 2 which hadn’t, in case that makes a difference.

    3. It’s just the oddest, slightly disturbing thing to close your eyes for a mere second and have four hours pass in that blink.

      You’re obviously not going to the right cocktail parties.

  2. Good article and interesting point.  Part of the issue is that we barely understand what consciousness is, so we still don’t quite have a grip on why things go wobbly. 

  3. I’ll admit, my irrational fear about general anesthesia (I’ve never experienced it myself) is that maybe you feel all the pain in the moment, but the drugs just make you forget everything as soon as its over. I know this isn’t totally reasonable. But it’s my heebie-jeebie nightmare. 

    1. Midazolam works like that.
      General anaesthetics seem to stop you from creating the memories in the first place as well as reduce your conciousness of the things around you.

      1. Midazolam works like that.

        It can also make you lose a week of memories, which happened to me. Early UK studies of Midazolam showed that it permanently decreased cognitive functioning and memory, but those studies seem to have disappeared several decades ago. I’ve declared myself allergic to benzodiazepines. It’s the only way to keep them from giving them to you when you have a procedure.

        1. Yikes about the Midazolam! thats is tres freaky. that was what they gave me first, then followed by that milk of amnesia stuff the MJ loved almost as much as Ferris Wheels.

        2. ‘I’ve declared myself allergic to benzodiazepines.  It’s the only way to keep them from giving them to you when you have a procedure.’

          If only that worked for me when I tell them I’m allergic to opiates.  Their attitude seems to be that if the drug won’t kill you, the possibility of using it is still on the table.  The patient frantically scratching and unable to sleep isn’t on their radar.  If it’s not a problem for them – it’s not a problem.  They are equally confident an antihistamine will deal sufficiently with the symptoms.  It never does.

          1. I usually find that the threat of liability inherent in giving a patient something that their chart says they’re allergic to is a sufficient deterrent.

    2. Actually, it is totally reasonable.   Some anesthetics (midazolam, for example) induce amnesia, and there have been cases of folks who return to partial consciousness during a procedure but have been paralyzed by the drugs.

       And yes, it totally creeps me out as well.

    3. I have that very same fear. After harboring this fear for some time, I saw a segment on some news magazine show of people who had been put under for surgery and then claimed afterward they were conscious throughout the surgery but paralyzed from the anesthesia and so, couldn’t alert anyone. That didn’t do anything to ease my fear! That fear is partly what prompted me to read this post.

      1. As I recall, there’s a device that they can attach to you while you’re under to make sure that you actually *are* well and truly under. If you need surgery, ask your doctor about it.

        1. there are a few devices actually, not to mention the blood pressure monitor, it you are experiencing intense pain or panic, trust me, your blood pressure will instantly reflect this.

    4. That’s not an irrational fear at all. I actually *have* woken up in the
      middle of a surgery. It was only a quadruple wisdom tooth removal, but
      still… They had injected a local anesthetic (and the needles in the
      mouth were the most painful part of the whole experience) and put me
      under light general anesthetic – sodium thiopental. I woke up for about
      ten seconds, heard the surgeon say “Okay, you’re going to feel a little
      pressure, now,” and felt one of my wisdom teeth *being crushed* so it
      could be removed from my jaw in small sections. It didn’t hurt, but it
      wasn’t pleasant. I also wonder why the surgeon was talking to me at all
      if I was supposed to be entirely unconscious. I assume the nurse pushed a
       little more thiopental when I started squirming.

      There’s also the little matter of the surgery being done by someone who
      wasn’t actually an oral surgeon, but that’s a different matter

      1. Wisdom teeth removal is not usually done under actual general
        anaesthesia. Usually, a local or regional anaesthetic combined with
        sedation is used (this is called monitored anaesthesia care, MAC). Same
        drugs that are used for general anaesthesia can be used for sedation,
        but the dosage is lower. That’s why the surgeon was talking to you.

      2. Wisdom teeth removal is not usually done under actual general
        anaesthesia. Usually, a local or regional anaesthetic combined with
        sedation is used (this is called monitored anaesthesia care, MAC). Same
        drugs that are used for general anaesthesia can be used for sedation,
        but the dosage is lower. That’s why the surgeon was talking to you.

    5. I don’t believe that you feel the pain when you’re under (having been under several times myself), because pain causes chemical reactions which should be detectable after you come out of it, no? If you had your teeth and gums hacked away at without anesthetic, I think you’d feel different at the same amount of time afterwards than if you’d been under.

      1. Pain is perceived as pain in the brain, and the adrenaline and other reactions that occur as a result of pain sensations are triggered by the brain. (Painful stimuli can be ignored or interpreted as non-painful, given the right person and under the right conditions)

        The only thing that isn’t handled in the brain is the spinal reflex, and being part of the voluntary nervous system, anesthesia stops that too. (The muscles of the diaphragm needed for breathing are also part of that, which is why some anesthesia requires a ventilator.)

          1. Technically, true general anaesthesia does stop pain. As the word’s greek roots indicate, it is the loss of all perception; the loss of consciousness, including conscious perception of pain. Thus the concept of a MAC – the Minimum Alveolar Concentration of an inhalant anesthetic needed to avoid a response to surgical pain in 50% of patients.

            You are correct that a balanced anesthetic protocol for surgery should include analgesia, amnesia, and skeletal muscle relaxation.

            Analgesics can and should be used in most cases to provide additional analgesia, which lowers the MAC of the inhalant anesthetic, allowing a safer protocol by using less gas.Less gas is always good because it does other nasty things like slow breathing and heart rate, lower blood pressure (possibly to the point of poor renal perfusion), and lower body temperature. Eventually, you stop breathing and go into cardiac arrest at high enough doses (Stage 4)

            Not to mention that if you didn’t give any analgesics, you’d be in a world of hurt as soon as you wake up, as anesthetics have no inherent analgesic effects (unless you include cyclohexamines like ketamine in animals but that only gets you to Stage 2 unless you combine it with other drugs).

            Also, the best analgesic protocols are multimodal anyway, meaning that there are different places to interrupt the pain pathway – stimulus>transduction>transmission>modulation>perception.

    6. Sadly that’s not entirely unreasonable.  But to me, general anaesthesia feels a lot like waking up with a hangover, or after intense flu, or something – I know you did some stuff last night; I can’t remember exactly what. And then I throw up.

      Your nightmare is slightly chilling, but fortunately unlikely – under an amnetic effect you’d not forget the pain afterwards, but rather during – making it all fresh. (A stubbed toe hurts a lot, but we think of it as minor because it’s over in a fraction of a second.  Without the memory of pain, pain is fairly harmless.) What makes pain unbearable is it’s prolonged nature, and the lack of control.

      The – fortunately very rare – cases where the sedative/paralytic effects work and the amnetic doesn’t are the most nightmare-inducing things I’ve ever read.

    7. Actually, from what I’ve heard, conscious sedation is pretty much what you described – you’re awake but not very functional, and one of the drugs that’s administered causes amnesia, so you don’t remember what was done. That’s what they generally use for colonoscopies, and the aliens use that for nocturnal probing.

    8. I’ve been told that’s kind of exactly how Versed works. So either treat that as nightmare fuel, or take solace that since someone pointed it out about one particular drug the others don’t do that. 

  4. I was just put under last thursday for surgery, and the anesthetic burned at the insertion point (back of my hand), and I felt it going up my arm. It wasn’t a burn like heat was being applied, it felt more like horseradish was being pumped into my veins. When the sensation hit my neck, I fell into darkness. 

    I intended on trying to fight the effect, but by the time I started feeling anything I didn’t really care anymore about that contest of will. That was odd, as I think about it. I just stopped caring.

  5. Some people find propofol painful, others cold or hot.
    Occasionally it makes their mouth taste of garlic.
    If you use it for a long time it can make your hair go green.

    1. FWIW it’s not actually propofol that tastes like garlic, it’s the vehicle DMSO (dimethyl sulfoxide).

  6. Unconsciousness in general is interesting stuff. 

    Having been a diabetic for 25 years, I’ve experienced many “forms” of hypoglycemia. Apparently it’s no fun for anyone around me.. I can be really grumpy, or violent, or entirely comatose. But I come out of it with zero memory of what happened. There’s been a couple incidents where I have a hazy recollection of what happened, but usually, my memory completely blacks out at one point, and slowly returns a little while later. 

    If I ever get to choose how I die, it’ll be on the other side of injecting a full vial of insulin. I imagine it’ll seem painful to anyone who watches it happen, but whatever it is that makes me “me” won’t care one bit.

  7. Very interesting article.  I have required general anesthesia 3 times, once when I was an infant and don’t remember.  It was a disturbing experience for me both times.  Waking up was a bit like sleep paralysis, where my mind was druggy but active.  Afterwards I ended up with pretty bad nausea and vomitting.  It bothers me that we don’t understand more of how it affects humans, and botched anestesia is one of my greatest irrational fears.  Maggie, Keep up the good reporting.

  8. Does it really matter?  Most surgeries are done when there is no alternative. Death or a life of pain is usually the reasons. I am 40, I have had 11 surgeries in my life so far. I have never had anything go wrong. The alternatives for me in all cases except for 3 would have been death!  So I really don’t care what the so called long term effects are, LOL!

    1. It’s not about, “Should we stop using anesthetics?” Obviously, they’re better than the alternative in most cases and they’re safe enough that they’re worth it compared to the alternative. Instead, this is more about, “Hey, maybe we can do this better and avoid some long-term side effects for people who need to use these drugs.” 

      I think that does really matter. 

    2. “Most surgeries are done when there is no alternative.”

      Actually, no. Most surgeries are ‘elective’ to at least some degree. Also, except for emergency surgeries undertaken without consent, everyone has the right to refuse any surgery (and an advance medical directive can often prevent even emergency surgeries where verbal consent can’t be obtained). Many folks will opt for the possibility of dying from a condition rather than undergoing surgery.

      Also, various forms of non-allopathic medicine are able to resolve or control a huge range of conditions (most heart conditions, gallstones, many cancers, etc.) for which standard allopathic practice currently promotes surgery.

      1. From my work where I daily meet patients to discuss surgery and anaesthesia, my experience is that very  few “opt for the possibility of dying from a condition rather than undergoing surgery”. When the risk associated with surgery and/or general anaesthesia is considered too high for the benefits from undergoing it, the decision to refrain from doing surgery is in the most cases taken by the patient, surgeon and anaesthesiologist in agreement.

        Also, i second the request from the author of the article to see some evidence for alternative treatment for conditions (especially cancers and heart conditions) usually treated by surgery.

    3. Does it really matter? … The alternatives for me in all cases except for 3 would have been death!  So I really don’t care what the so called long term effects are, LOL!

      Maggie already answered you, but I’d like to add that we should all be shooting for more than just escaping death.

      Think about it.  The search for human understanding is what enabled those surgeries to save your life in the first place.

      Personally, I’m thankful that Maggie is delving into this subject.  It can only help raise more awareness of the need for more study.  That may very well prod more research that saves lives and stems suffering for people in the future.  Maybe even for you.

  9. The next time I undergo general anesthesia (and who knows when that is), I’m going to tell the anesthesiologist that I want to count off the powers of two.

  10. The last time I went under, it was for pretty invasive surgery. The IV anesthetic definitely stung, but it worked quite well. I remember being lifted onto the surgical table from the gurney, looking over at the wall, and murmuring something about not wanting to go to sleep until I looked at all the neat electronics over there. I went under to the sound of the anesthesiologist chuckling…

    Came to pretty quickly afterwards, but fighting the fog out of my brain took a while. It’s like getting very drunk quickly, and then having it go away very quickly. With no hangover – just the surgical pain.

  11. The aftereffects of the last general anesthesia I had were interesting- the pitch was ‘off’ on everything- the sound of the telephone was actually lower than I remember. My vision was strobey, and I saw rainbow trails coming from moving things. Rising smoke made slow motion letters in the air. And every drink of water I had for about 3 days resulted in a near-instant nap. I finally washed it all out of my system, but those were interesting days. I have no idea what I was given, and I was down for two hours.

  12. My mom went under for surgery once, early 80’s, and could hear the nurses and surgeons talking the whole time.  They were talking about baseball and then got on a big conversation about one of them buying a house and they were cracking jokes for awhile.  My mom was upset when she woke up and asked the nurse why they didn’t take the surgery seriously and were making jokes.  The nurse said, no, we weren’t making jokes at all, all our attention was on you.  My mom then asked the nurse about her favorite player and when the doc was closing on his house.  The nurse closed her mouth and left the room. 

  13. Also, various forms of non-allopathic medicine are able to resolve or control a huge range of conditions (most heart conditions, gallstones, many cancers, etc.)

    Citations (and, by that, I mean evidence not anecdote) very much needed. 

    1. “non-allopathic” is a phrase which tends to be used only by promoters of woo. Osteopathy is an alternate track to being a doctor which is fairly well accepted, but the others are like Chiropractic and ‘it’s the water’ Homeopathy. 

  14. I’ve only ever had valium administered by IV  while I was having my wisdom teeth removed. I was aware, and it seemed to hurt for a moment, and I tried to say ow. Then I distinctly remember thinking “well f**k this anyway” and daydreaming while they did the other three teeth

  15. I’m going under tomorrow morning, for the second time. The first was about 10 years ago, to have 8 teeth taken out (4 impacted wisdom teeth, and 4 poorly-cared-for molars). Tomorrow just one.

    That time I counted backwards from 100, and may have gotten to 97. The powers of 2 sounds like a good idea, or I could just say “Number 9” a few times until I float downstream.

    In the last few years, at times when I was falling asleep at the computer, fighting to stay awake, I’ve had the brief sensation of things bumping against my teeth, and a vague impression of foreign things and activity in my mouth. These are always extremely fleeting feelings, and seem to be a dim memory of that first surgery. There is never any memory of pain.

    I’d be interested to know why automatic functions like heart and lungs don’t also stop. The obvious answer is “we don’t use the ones that make those stop”, but it suggests that some parts of the nervous system stop responding while others keep going.

    1. The automatic functions are governed by deeper, more primitive parts of the brain which are more difficult to anaesthetise. Plus the heart and other organs pretty much regulate themselves with a bit of oversight from the brain, rather than there being direct control of every aspect of their function. Your body is a collection of complementary, parallel, homeostatic auto-egulatory mechanisms with the consciousness you think of as the essential “you” merely being the icing on the cake. And it’s remarkably easy to mess with the icing… That said, most anaesthetic drugs will affect basic functions if enough is given. The older, frailer and/or sicker you are the more likely that is to be a problem and that’s where the real skill and art comes in my job as an Anaesthesiologist.

      Nice article BTW. The article linked by @facebook-608971135:disqus above is worth reading too.

    2. Actually, lung function does stop with certain general anaesthetics. The anaesthesiologist has to intubate you and take over your breathing until the drugs wear off.  That’s why people often wake up from surgery with sore throats even though the operation had nothing to do with the throat…

  16. Jeez, how many surgeries, let me count them.  Maybe not.

    Anaesthetics, as shown in the article, work.  How they work is currently difficult to pinpoint with any certainty.  Having said that, we no longer do things like blow smoke up peoples asses (yet it really did happen) to resuscitate drowning victims.  We try something new, assess the data, make appropriate changes and move on.

    That’s how science works.  And it’s wonderful.

    I’d be very interested to see those citations when they turn up Maggie.  Will they be published here, do you think?

  17. I have been put under twice in my adult life. The first time, I was given a slight under dosage. Nothing traumatic for me, but I REALLY pissed off my doctor. Surgery was done, but not the cleanup. As I was coming out of it, I would wake up & try to get off the table. The doc would calm me down, get me to lay down, and I would fall under-kinda asleep. 10 seconds later I would wake up again & try to get up again, with no memory of the previous try. After some 15-20 loops where he, the nurses, and every one around me kept getting more and more agitated, he finally said lay back, but stay awake until we get you to the recovery area. The nurse explained what was going on, and said it is probably better for you to NOT fall asleep as you get in a loop!  I was in for sinus surgery, so below the neck, I had my full strength, and would physically wrestle with everyone trying to get up, and at 300lbs I have the mass and strength to use!  The 2nd time I explained the 1st time with my anesthesiologist, woke up 2 hrs after being wheeled into the recovery area. That was a much better subjective experience, but I wonder if I had a little too much the 2nd time.

    1. I was wondering about that too. My boyfriend after being in a serious accident had to be operated twice in a few days. The first time, he came out of it very relaxed (relatively), the second time they almost had to strap him to the bed because he attacked the surgeon and the nurses because after he woke up he desperately wanted to go home and didn’t understand why he couldn’t. So maybe they gave him to little? (For me the only time when I woke up after surgery I just couldn’t stay awake for more than one hour at the time for three days.)

  18. I’ve never had a general anesthetic but I have been slipped a mickey in a bar with what I presume was a date rape drug meant for my much more attractive wife, supposedly I was conscious throughout and quite good fun in a detached ditzy kind of way and of course I was totally malleable to any suggestion made. Luckily my wife and buddies took care of me and saw me home safe, sadly I missed a very good Barcelona v Madrid Derby.

    To get to the point I am quite certain I could have been hit by a bus during this episode and never felt a jot because I have undergone some very strong voluntary self-medication much stronger and more illegal than booze that never had quite the on/off effect of what I presume was rohypnol or something close. Plus the next day I had no ill effects largely due to the fact that I was slipped aforementioned mickey after I’d only had two pints. I know I got off light but I’d still love to to have a chat with the guy that robbed me of my night out, and that wonderful football game.

    Plus I’ve always wanted to use the phrase “slipped a mickey”

    1. It really does work like that.  I had the same meds for the ‘magic eye’ down the throat.  I asked the anaesthetist beforehand if I’d remember, but I could watch on TV.  Sweet.  But if I couldn’t remember…..???!!   So I now have a lovely photograph of… probably my bile duct opening.  Very nice it is too.  Seriously though, that shit really works.

    2. Its weird because I got totally high once from a CT scan and nobody has been able to explain why. Two nurses (or medical technicians?) hooked up an IV for contrast and I remember they spent most of the time chatting about personal stuff. One of them arrived late and sounded a bit hung over.

      Going home on the bus I was incredibly happy. I thought I was the king of the world. I rushed home because I had just realized all this stuff which I absolutely had to write down. It wore off after a couple of hours and I still wonder if those techs accidentally gave me the wrong stuff.

  19. I heard a very interesting radio piece on WHYY in Philadelphia a few years ago.  The reporter went in for a colonoscopy, and left his audio recorder running during the procedure.  He clearly moaned several times in apparent discomfort during the procedure, but afterward had no recollection of any pain or unpleasantness.  So it appears that at least some of the time, the process of anesthesia involves induced amnesia rather than complete pain blocking. 

  20. What I want to know is not so much how an anesthetic shuts off consciousness but how consciousness comes back after having been utterly disrupted: why don’t you come out a vegetable?

  21. I only wish i was given a general when I had my wisdom teeth removed. Even sedation would have been great, but since I had no one to drive me home, I was just given half a dozen syringes full of Novocaine in each quadrant. I didn’t feel any pain, but I did get to hear and feel (via bone conduction) my teeth being cracked, twisted, crushed, and excavated. At one point I was expecting the dentist to pull out tiny amounts of high explosive and start blasting.

    The only time I’ve been completely under was when I had my tonsils out. For all I know back then they gave me ether. There is nothing in the world more helpless and irresponsible and depraved than a man in the depths of an ether binge…

  22. Kinda off topic but this seems like as good a time/place as any to ask something thats been bothering me:

    Does anyone have an issue with topical and local anesthetics not working for them. Like at all? What happens for me is that it makes the area slightly puffy and tingly but full pain and touch/pressure sensitivity remains. 

    It’s made some medical situations pretty horrifying. Doctors either seem to not believe me until its too late, question me about heavy drug/ alcohol use (don’t do drugs, weekend only kind of drinker), or they’re just plain befuddled. 

    Anyone else? It makes me pretty worried about actually having to be put out completely should I ever need surgery. 

      1. a) Thanks for looking into it!
        b) The symptoms shown in that link don’t seem to apply to me (phew!) – Especially the flexibility part.
        c) ED – means something very different where I’m from. Thankfully I don’t have that kind either…

    1. I have issues with local anesthetics not working. So far the doctors have always been dicks about it. I’ve had them refuse to give me more, and of course the whole “you must be a junkie” bullshit. The thing is I do get numbed, just not much and it seems like it takes a few hours for the effect to really come on. Just thinking about this brings back horrible memories of teenage dentistry. I actually had a dentist accidentally knock a tooth out once, which is pretty fucked even if you can’t feel the pain and I could.

      1. I asked my doctor a few years back if he thought that I have Marfan’s. He then asked me if, when I go to the dentist, it takes forever for the Novocain to work. I then asked him if he was psychic, but it turns out to be a classic symptom of Ehlers-Danlos, which otherwise can look like Marfan’s.

        I get shot up 45 minutes before the procedure and then again when the dentist is ready to start. That seems to work.

      2. I have to show up for my dentists appointments two hours early. You’re half right; the dentists has to inject you in the right spot, which is not in the same spot for everyone. 

    2. Does anyone have an issue with topical and local anesthetics not working for them. Like at all? What happens for me is that it makes the area slightly puffy and tingly but full pain and touch/pressure sensitivity remains.

      Novocaine at the dentist works very slowly for me. My dentist has this on file so they schedule extra time to let it soak in.

    3. Topical works poorly for me, and wears off very quickly. A local needs to be injected into my jaw bone(under the root, directly into the blood feeding that specific tooth), after drilling a hole in my jaw for any kind of dental work. Only doing this bone drill & then inject will it work, starts in 3 min, and lasts 15 min or so.
      See my other reply for my experience with 2 sessions of general anesthesia.

  23. Been under GA twice for elective shoulder surgery. No problems at all.

    For the second surgery my friend preformed it. I have yet to ask what happened in the OR.  Will make for a nice story next we have a beer together.

  24. Had major surgery about 2 months ago – over 10 hours on the table with another 2 in the recovery room. All I remember was the nurse pumping a syringe of “vein champange” into my IV and then nothing – absolutely nothing at all until I woke up in my hospital room and it was dark outside.  

    While I was very groggy, I instantly remembered precisely why I was there and all the details leading up to pre-op.  It was as if somebody simply turned off the power switch on my brain for 12 hours.  It was not an altogether unpleasant feeling.

  25. I was just watching an episode of Star Trek Enterprise last night, the bad guy put some kind of drug soaked cloth in the face of someone to knock them unconscious. I see those kind of scenes all the time.

    When I do, I always suggest the bad guy use the same line. “Does this smell like ether to you?”

    I crack myself up.

  26. I had five hours of facial surgery done with just Demerol and some local blocks.  I chatted with the doctors, got to see everything that came out or went in and even had a med student hold up a mirror so that I could watch part of the surgery.  And I didn’t feel like crap for a week like I did when I had a general.

    1. Great point. What about the medical science involved in patients who have to be awake? I received a corneal transplant; weird being awake the entire time. 

      Also, there are parts of the body that has very little nerve activity. Believe it or not, the chest cavity can be open and the heart exposed under local anesthesia. But remove a severe hangnail, put me under!

      And isn’t some anesthesia meant to just keep the patient quiet and still? What if the patient could do that on their own?

      1. The Chinese have performed truly amazing feats of surgery under acupuncture alone. Like your own corneal transplant, we do lots of surgeries under local or regional (limb) anesthesia. Some peeps just want the nap, though.

        1. Citations please.  Acupuncture is not on my list of accepted medical practices, especially when it comes to verifiable pain relief.  ie greater effect than placebo.

  27. So Maggie is finally admitting that scientists don’t really know what causes unconsciousness. They want us to believe it’s anestetics that cause this. But everyone knows that humans have been afflicted by unconsciousness for millenia. It’s just part of the natural cycle and anesthetically generated wastedness (AGW) is just a bogus theory that these researchers dreamed up so that they could keep raking in big bucks for their research.


  28. It is weird to be cut off mid-sentence in one’s consciousness, and restored what seems like 5 mins (but closer to an hour) later with a clean bill of health, no dreams, and zero pain from a procedure, despite a temporary loss of motor skills.  I imagine a future where severing the body/mind connection then restoring it at will is explored in depth, and what we do today may even be  considered barbaric.  

  29. I was aware throughout my cesarian section back in 1978. No pain thank goodness, but they must have used a muscle relaxant as I couldn’t move. I could hear the surgical team talking, and the scalpel felt like someone drawing a pencil down my tummy. I heard them saying, “It’s a boy!” while I was supposed to be unconscious, so when I finally came round properly, back in the ward, I was able to ask them how my son was before they told me his sex. Suffered nightmares and all sorts of stuff for ages. They didn’t offer counselling in those days. In fact they were less than interested when I tried to tell them what happened.

    But, hey, life goes on, and I got over it, and the baby grew up to be a fine healthy young man, so I guess it could have been a lot worse. But I’m still fascinated by the workings of anaesthetics.

    1. In all likelihood, you had a spinal anesthetic (performed awake) for your C-section and not a general anesthetic (“asleep”). As you describe it, there’s a decent chance that the local anesthetic in your spinal fluid rose high enough to make it difficult for you to move. I’m sorry no one apparently had the presence of mind to reassure you or explain this…

  30. General anesthesia is when the patient is unconscious and paralyzed.  You cannot breathe under general anesthesia – a machine does the breathing for you through a tube that is introduced into your throat.  All of the reports about regaining consciousness during an operation – those people were not under general anesthesia.  That’s the result of bad medicine.

    1. General anaesthesia means unconsciousness and lack of movement to painful stimuli. It doesn’t require paralysis and mechanical ventilation.

  31. Well, since everyone’s sharing, I had general anaesthetic for major abdominal surgery (hysterectomy for cancer) several years ago. The surgeon was late and everyone was getting antsy, so when he walked in, they put me under immediately, no counting backwards. (I’ve always wondered whether he had a liquid lunch – my scar definitely wanders a bit, and he ended up taking out 48 lymph nodes, none of which were cancerous. Oh well). It is quite freaky to “wake up” with the previous moment having actually occurred hours before. The surgeon also didn’t believe in using an epidural, with the result being that I was in intense pain both immediately after the surgery and for about another 8 hours. I was pushing that button on the morphine pump continuously. My friend finally convinced the nurse to release a bolus of extra morphine, which gave me enough relief that I could actually start to sleep and recover.

    What I think is really weird, though, is that I remember the events, what I said, what happened, etc. But I don’t remember the actual pain. I think your brain erases that – – I know I was IN pain, but I don’t remember the actual feeling…

  32. Remember, kids: anesthesia is administered to people by people. “They gave it to me” shouldn’t be part of your story. Any anesthetic should take place (unless absolute emergency) AFTER a thoughtful conversation between you and your anesthesiologist. Don’t let anything happen until you as a patient understand the RISKS, BENEFITS, and ALTERNATIVES to any proposed procedure and anesthetic. Informed consent is the only way to go… under.

  33. /receives pre-admission call from Hospital for throat surgery on Monday
    /logs on to BB
    /drinks tadpole blood

    Excellent and interesting article. I guess it shouldn’t be a surprise that GA is not well understood, when even basic sleep functions are not fully explained (and we trust the internal re-boot on that one every night). Nstzlogst: although there should be a “long and thoughtful conversation” between you and your anesthesiologist, (s)he is clearly the expert, and beyond recounting any problems you have faced in the past, you aren’t going to be making any meaningful choices except Yes or Abandon the Surgery.

  34. I woke up during relatively minor surgery to my nuts. I remember having a tube in my mouth and a sensation that the surgical team were a bit worried. I don’t recall any pain at the time. I’m quite solid and heavier than I look and I reckon the anaesthetist just guestimated how much to give me. Obviously guessed too little.

    After I came round I was told not to go to sleep afterwards which was really hard. I had people putting cold flannels on me and I had to literally hold my eyelids open. Horrible sensation.

    I was fine the next day.

  35. one thing you should definitely explore more Maggie, is the fact that gaseous anesthetics mess with brains in so many ways we dont understand that most anesthesiologist say that children under 4 shouldn’t have elective surgery because of the plasticity of the brain at that age. You said we dont know enough about long-term effects, but i think this nugget opens a whole new medical ( and legal) can of worms

  36. I required general anesthetic several years ago, and the most unsettling thing about it was waking up, after the operation, in the middle of a conversation with my surgeon (concerning technical aspects of the surgery).  My conscious mind was startled to discover some *other* part of my mind not only awake and functioning, but functioning at a high level.  It still gives me the chills to reflect on that moment, as I became aware of the fact that the brain/consciousness/thought operates in dimensions as yet unknown to us.

    1. I’ve actually done this under deep sleep. My mother will talk about conversations I don’t remember having with her which I’ve had in my sleep. Only remember the mid-convo thing once —  it’s my earliest memory: I’m asking my dad how old he is. 

  37. I have gone under many, many times for schock treatments. I’m not sure of how many, somewhere around 70 times. I am scared to know that not only did I lose a lot of memory, but that maybe there’s a timebomb inside me…

  38. Some kinds of anesthesia, as Maggie worried, do not make you unconscious, but rather make you forget the event. Typically, they give you Fentanyl (a very powerful opiate pain suppression drug) and Versed (which makes you forget the event). 

    I know some of you are screaming “WHY DEAR GOD?” — The reason for this is actually very reasonable — it’s much less risky to have you semi-conscious, breathing on your own, than to fully sedate you and use a breathing tube and a mechanical respirator.Perhaps the most likely case that people here WILL run into is when you have a colonoscopy. I haven’t had a colonoscopy yet, myself, but my wife has, and she assures me that the worst part of the procedure is the preparation — they give you powerful laxatives, and you poop a LOT. She said that once they got the IV started, she didn’t remember a thing until she woke up.I myself had a procedure kinda like that, which is called a sigmoidoscopy. (Same idea, but less far up the butt.) This involved no anesthesia. The one saving grace is that the entire procedure is very very quick — like 2 minutes, tops.
    I had an ulcer “blow out” so I had an emergency endoscopy — same idea, other end. After administering the above drugs, they stick a tube down your throat, and then use a fiber-optic viewer tube with some tools attached to look around, and cauterize the ulcers. That went perfectly. I had no memory of the surgery, and recovered nicely. (The scariest part of the whole ordeal was waking up on the floor, after having passed out, and then having the excellent emergency medical techs trying many, many times to start an IV to get fluids into me.)

    Then, six weeks later, I had another endoscopy, to make sure everything was healed up, no new problems etc. This time, the Versed was not 100% effective, so I had a distinct memory of the surgery. After explaining what I remembered, the doctor concurred that I probably was conscious for some of the time.

    You’re probably screaming, Maggie, but let me reassure you — the doctors HAD administered PLENTY of Fentanyl — I was feeling NO pain. I was just aware of the doctors talking, and the sound of my own throat, somewhere between coughing and gagging.

    I was not scared or upset at the time, and I am not today. It was just this dream-like memory.

    Obviously, if I were in pain, or if I were screaming, I’d feel very different about this. But I figure that if I were screaming, the doctors would have given me more pain meds and more forgetting meds, and I probably would not remember the event at all.Anyway, my main point: Most drugs, we don’t precisely know how they work. We have a pretty good understanding, but we don’t have all the details. But that’s far less important than two other things that we typically DO know:
    1) We are very confident that when you take the drug, it is very likely to do the job it is supposed to,.

    2) We are also very confident that when YOU take the drug, it is VERY unlikely that you will have a terrible side effect.

    3) We are also confident (a little less), that if YOU take the drug along with 10 other drugs, some wine, some pot, and maybe you forget once in a while, or you accidentally take 3 pills instead of 1, it is still very unlikely that you will have a terrible problem.

    To me, this is much more important than knowing, for example, exactly all of the chemical reactions that are involved.

  39. I’ve been under three times now, and I hate it. I wake up more slowly than most people and have more post-anesthesia side effects. But I had one surgery where they gave me an amensiac (sp?) and a muscle relaxant instead, and in that case I really did experience the ‘hole in time’ the other commenters mentioned. From fully awake to fully awake, with no memory of how I got to where I was.

    Interesting article. I am surprised anesthesia isn’t better understood.

  40. The early history of anesthesia is covered in this In Our Time podcast from 2007: http://www.bbc.co.uk/programmes/b00775zv

    The original “research” was all hit-or-miss discoveries typical of the 18th and 19th Centuries. A great boon to mankind, but I’m glad it’s finally being looked into with a modern eye.

  41. Maggie, you may want to investigate Nitrous Oxide, which I’ve always wondered WHY it works so well for me.  Since Novacaine(s) are slow-acting for me, I found a dentist who will use laughing gas.  I’m told I have a textbook reaction to it — pain is diminished, and what’s left my conscious mind deals with in a detached, mildly =interested= manner.  Even fairly violent maneuvers, like tugging at a tooth, seem like interesting events, intense but fleeting.
    The best aspect of Nitrous may be that it’s fast-acting AND fast-ending.  Five minutes after it’s stopped, I’m good to go, though typically they make you wait just to be sure.

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