Pique the Geek 20110821: Anesthetics

Anesthetics are as essential to modern surgery as are sterile fields and antiseptics.  There are a couple of reasons for that, the most obvious being that the patient most likely could not survive the shock and pain of any but the least invasive procedure with out them.  Interestingly, the use of anesthetics in the modern sense is quite recent, dating only from the mid 1800s.

There are two major divisions of anesthetics, general anesthetics and local ones.  General ones cause a more or less complete loss of sensation and consciousness, whilst local ones cause a loss of sensation for only a relatively small part of the body and leave the patient conscious.  In addition, general anesthetics fall into two wide classes, inhalation ones and intravenous ones.  We shall discuss, in general terms, inhalation general anesthetics tonight.

The earliest use of a general anesthetic seems to have been performed by Dr. Crawford Long on 18420330.  He used diethyl ether, and it remained the anesthetic agent of choice for some time.  Ether is really a pretty good anesthetic, but has been supplanted in the developed world because newer agents are both more effective and easier to administer.  Ether has the disadvantages of being a liquid at room temperature, making it rather difficult to administer in carefully regulated doses like modern gaseous agents.  It is also quite flammable, making it a hazard in the old open breathing method of administration.  In that method, a cone of paper is placed over the nose and mouth of the patient and ether dripped onto it until the patient is rendered unconscious.  Additional ether is dripped onto the cone as needed to prevent the patient from awaking.

In 1847 a Scot, James Simpson, used chloroform as a general anesthetic for the first time.  It rapidly became popular because it is a powerful anesthetic and is not flammable, making it much safer from a fire standpoint.  It also sensitizes the myocardium, thus making ventricular fibrillation a possibility.  It is hardly ever used in medical practice these days.  It also has a much narrower therapeutic index than ether, meaning that the difference betwixt a therapeutic dose and a dangerously toxic one is smaller than for ether.  In addition, chloroform is now listed as reasonably anticipated to be a human carcinogen and is also a fairly potent hepatic toxin.

Probably the most commonly used inhalation anesthetic is nitrous oxide.  The brilliant British chemist Sir Humphrey Davy anticipated its use as an anesthetic as early as 1800, but almost a half century passed before it was actually used for that purpose.  However, nitrous oxide was extremely popular at parties at the time, and Sir Humphrey was a popular man, since he perfected the method of production in which large volumes of high purity gas could be made.  The great poet Samuel Taylor Coleridge is said to have this to say about nitrous oxide:

If there be a Heaven, it’s[sic] Atmosphere surely must be comprised of this wonderful Air.

Note that the possessive its was spelt with an apostrophe at the time, around the early 1800s.  In any event, nitrous oxide is very commonly used in dental settings and sometimes mixed with other inhalation agents for more invasive work.  Back in 1976 I had a summer job at a cylinder gas company and used to deliver all kinds of gas to welding shops, dentists, and other customers.  I HATED to deliver nitrous oxide because it, unlike most other common gasses other than carbon dioxide, exists as a liquid the the cylinders, and that makes them very heavy.  The empties were not any worse than others, but the full ones were horrible to handle.  I could roll two full oxygen cylinders upright at a time, but struggled with only one nitrous oxide one.

These are the “classic” inhalation anesthetics, and there are many newer and, in some senses, better ones.  As mentioned earlier, materials that are gases at room temperature are in general easier to administer because of simpler metering considerations.  However, some liquids are used because of their potency or relative lack of adverse effects.  With modern technology, handling volatile liquids is much easier than in the 1960s due to better sensor technology.  In the old days, gas flowmeters were used to control the amount of anesthetic agent, and obviously these work only for gases.  Now, it is rather easy to measure directly the concentration of the vapor of a liquid anesthetic and thus control the dose.

It is interesting that the mechanism of action of these agents is still not fully understood.  The classical theory, now disproven, was that these agents, being very fat soluble, concentrated in the cell membranes in the central nervous system and thus disrupted signal processing.  The best model that is currently available is that there is interaction with these agents and specific proteins in the membrane, changing the opening and closing of ion channels and thus signal propagation.  This is is supported somewhat by the fact that in some chiral inhalation anesthetics one enantiomer is much more active that the other.  Since the lipid bilayer in the cell membrane is relatively achiral and proteins are chiral, this makes some sense.  I expect that these questions will be resolved in the next few years as our technology for probing microbiochemistry improves.

In any event, just rendering the patient unconscious is not enough for many except the least invasive surgical procedures.  If much muscle has to be penetrated, that muscle tissue needs to be relaxed, not tense.  One of the advantages of ether was that it is pretty good at relaxing muscles.  However, many of the newer agents are not so good, and ether was not perfect.  Thus, additional agents are used to facilitate muscle relaxation.  Although not anesthetics themselves per se, they are essential in modern surgery to cause this muscle relaxation.

These agents are the paralytic agents, most of them derivatives of the South American native arrow poison curare.  The indigenous poeples there coat the tips of their arrows with this plant material and then shoot game.  The game animal, although perhaps not otherwise not seriously wounded, soon becomes immobile due to the paralysis caused by the poison.  Thus, more game can be had for less effort in chasing wounded animals.  Curare is not active orally, so the game can safely be eaten with no fear of paralysis in the consumer of the game.

Sounds perfect, right?  Well, not quite.  It turns out that all of these agents not only paralyze voluntary muscles, but also paralyze the diaphragm, making it impossible to breathe.  When these agents are used it is essential that the anesthesiologist provide positive ventilation of the patient or the patient will surely die.  In modern settings this is not difficult, and a good anesthesiologist can exercise very good control on all three factors:  the level of anesthesia (how “out” the patient is), the level of muscle relaxation, and the level of oxygenation of the blood.  However, there is still one catch.

It turns out that when paralytics are not being used, as the level of anesthesia becomes lower and lower, the patient will begin to feel pain, even if not fully conscious, and begin to move about somewhat.  That is a signal for the anesthesiologist to give additional anesthesia to regain the level necessary for the specific procedure.  When paralytics are used, this does not happen, and at the extreme a patient may be frankly alert and feeling the full pain of the procedure!

This actually happened to someone whom I know well.  She was having a surgical procedure performed and started to feel some pain.  Figuring that she is in postoperative recovery and not being fully conscious, that was that.  Then she became aware enough to realize that she was still in the operating room and that they were still working on her.  She never became fully conscious, but enough that, as she told me later, it was the most painful and terrifying experience of her life.  Fortunately, the anesthesiologist realized that she was not adequately anesthetized and increased the dosage of the agent and she became unconscious again.

This is not an isolated incident.  There have been enough reports of similar occurrences that some studies have been done, notably using the electroencephalograph (EEG), to determine that an adequate level of anesthesia is being maintained.  Like the difference betwixt waking and sleeping states, the EEG can distinguish betwixt an anesthetized and an emerging state.  Depending on the frequency of these occurrences, it may be that EEG monitoring becomes routine.

I think that it should be routine anyway, and here is why.  All general anesthetics are, when all is said and done, POISONS.  The trick is to poison you enough that you are essentially comatose, but not dead, for as long as a particular procedure requires.  It seems to me that by using the EEG to allow a tighter titration of the agent, adverse effects could be reduced significantly.  

The same person about whom I told you also almost always has bad emergence reactions from general anesthesia, including nausea and vomiting.  Not only is that unpleasant, but depending on the procedure it could be quite dangerous in that sutures could be damaged.  I strongly suspect that it is more common to receive too much anesthetic than too little, and I suspect that many of the adverse reactions could be minimized if only just enough agent were given.

Well, you have done it again!  You have wasted many einsteins of perfectly good photons reading this sleep inducing piece.  And even though Rick Perry decides that secession from the Union is a bad idea when he reads me say it, I always learn much more than I could possibly hope to teach by writing this series.  Thus, keep those comments, questions, corrections, and other feedback coming!  Tips and recs are also welcome.  I shall hang around this evening as long as comments warrant, and shall return tomorrow after Keith’s show for Review Time.  Bill Nye indeed!

Next week we shall discuss IV general anesthetics, and the next week shall conclude this series with a piece about local anesthetics.  Please be sure to visit.

Warmest regards,

Doc, aka Dr. David W. Smith

Crossposted at The Stars Hollow Gazette,

Docudharma,  and

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