(9 pm. – promoted by ek hornbeck)
Last week we started this three part series with inhalation anesthetics, and here is a link. This week we shall discuss injected anesthetics, and finally shall finish up the series next week with local ones.
We should once again stress the difference betwixt anesthetics and analgesics. In general (this rule is not 100%, but darned close), anesthetics render the patient unconscious so that surgical procedures can be performed with no physical pain during the procedure. In addition, many anesthetics cause muscle relaxation which makes surgical procedures less traumatic.
Analgesics, on the other hand, are not designed to render the patient unconscious, but rater to moderate the sensation of pain caused by many reasons. A few analgesics can be used as anesthetics, but in general depress the medulla such that respiratory difficulties often result.
There are lots of different injectable anesthetics, way too many to cover here. Almost all of them are given intravenously because it is easy to control the dosage by that route. Intramuscular and subcutaneous routes are almost never used because of variable uptake. Often more than one anesthetic agent is given both to reduce the total dosage because of synergistic effects, and also because often no single agent has all of the properties desired.
As is the case with inhalation anesthetics, paralytic agents often have to be given to provide adequate muscle relaxation when deep procedures are performed. Those were discussed last week at the link in the introduction.
Since there are so many different IV anesthetics, we shall limit the discussion to only three or four. I chose the ones because I have personal experience with one of them (Alfentenil), another was much in the news recently (Propofil), and a combination of fentanyl and Versed was mentioned by more than one commenter last week. If time permits we might take on another one or two.
Alfentanil is a synthetic opiate, often used for short and simple procedures. Like other opiates, it is a strong agonist of the mu opiate receptor. I was given alfentanil back around 1990 when I had outpatient surgery to open my sinuses. I had carried a sinus staph infection for years, and repeated regimens of Augmentin would knock it down for a while, only for it to return. I just about lived on pseudoephedrine and diphenhydramine betwixt antibiotic courses. My primary care physician finally referred me to an otolaryngologist for evaluation and he recommended with so called “windowing” procedure to provide enough drainage area so that my sinuses could drain and thus become less apt for infection.
The surgery was not really remarkable. Of course I had to forgo food overnight, but when I got to the office they prepped me and started an IV. They induced me with what probably was some sort of benzodiazapine, then the next thing that I knew I was in a recovery bed with my nostrils stuffed with gauze and a surgical glove fill of ice on my brow. After a couple of hours I was allowed to go home. I was off of work for a few days, until they could unpack my nostrils. They gave me some hydrocodone for pain, but it was not that bad. Ibuprofen was good enough, and the glove with the cracked ice really helped.
It gets a little funny now. When I returned the surgeon had me sit in the chair. He told me that my septum was a bit crooked so he repaired it at the same time. He had splinted it with what appeared to by X-ray film, and he clipped the couple of sutures, put a hemostat on it, and yanked it out of my nose. I about came out of the chair! It did not really hurt that much, but it took me quite by surprise. Then he told me to relax and started unpacking my nostrils.
He took the hemostats and latched onto the end of the gauze and commenced pulling, then used his hands. It did not really hurt too badly, but I could feel the gauze pull away from the nostril, and of course clotted blood made it tend to stick. The sound was incredible, as every time a clot would let go, the crackle was bone conducted to my ears, making it sound very loud indeed. He kept pulling, and it started reminding me of the old magician trick where they take a handkerchief from their sleeve and dozens just keep on coming. I had no idea that it was possible to get that much gauze in your head! He finally got finished, and I realized that we still had the other side to go!
They sent me home with instructions to irrigate my sinuses with warm saline, and gave me a rubber bulb with a tube one it (like the ones that you use to remove mucus from kid’s nose) to use three times daily for a week to two. I disliked that very much, as it was like waterboarding yourself. I realized that it was not really the water that bothered me, but the mixture of water and air that did. I got a 30 mL plastic syringe (without the needle) and used it instead and the solid stream of water was much less unpleasant than the air and water mixture.
The surgery was successful, and in the 20 years of so since, I have had maybe three infections, always associated with a cold or some such, and they were easily cured with a short course of antibiotics. For those of you with chronic sinus infections, I would urge you to consult a specialist about this procedure. I have heard rumors that they now use lasers and that the recovery is now much faster, but I do not know that for sure.
Alfentanil is really good for these short procedures because it clears fast, has an extraordinarily rapid onset of action, and has less cardiac affect than many IV anesthetics. However, it does tend to depress breathing more than some agents, so careful patient monitoring is necessary. However, a simple squeeze bag is enough to tide the patient over because the procedures that it is used for rarely last more than 10 or 20 minutes. It is not a very good muscle relaxant (its mode of action that depresses breathing is completely different than that for the true paralytic agents), but 10 to 20 minute procedures are rarely deep enough to require muscle relaxation.
Just a s a footnote, the place that I worked at the time required random drug testing. I anticipated that I might need the information, so I asked my physician to give me a copy of the records regarding the medications that I was given during the surgery and the hydrocodone the he prescribed for me to take at home. Sure enough, about the second day after I returned to work, my number came up and I had to report for drug testing. I had memorized the list, and when the tech asked me if I had been on any drugs, I rattled off, “Well, Valium, alfentanil, hydrocodone, and cocaine”. He looked at me oddly, and I explained that I had just had the surgery. He said, “We’ll not even bother with this test, since we know it is going to come back hot.” He waived it for medical reasons, and I got tested the next time I was randomly chosen. By the way, the cocaine was used to control bleeding whilst the surgery was progressing. We shall talk more about that drug next week.
Propofol is unlike any other anesthetic. As IV anesthetics go, it is a tiny little molecule, and contains only carbon, oxygen, and hydrogen (most IV anesthetics contain nitrogen, and many contain sulfur). It is the di-isopropyl derivative of phenol, and phenol is used as a local anesthetic in OTC preparations like Chloraseptic. Its mechanism of action is very different than most IV anesthetics, not affecting the opioid receptors nor the benzodiazapine ones, but rather acting as an agonist for the GABAA receptor, a sodium channel blocker, and perhaps also as cannabinoid receptor agonist.
Propofol is a strong respiratory depressant, and it is only used in full OR settings where all of the necessary resuscitation equipment is readily available and ample staff are present to take action quickly. In addition, this respiratory action is synergistic with that of benzodiazapines, making concomitant administration risky. As we will learn in a bit, benzodiazapines are often used to induce anesthesia.
Propofol has been in the news lately, being blamed at least in part for the death of the pop singer Michael Jackson. It turns out that it was apparently administered along with a benzodiapine in that case, by a lone person, and without the proper resuscitation equipment. Since this case is not yet resolved, I have no comment on the culpability of anyone involved. Propofol, when administered properly, can be used for both short and relatively long surgical procedures, but is a poor muscle relaxant. As a matter of fact, a rare adverse reaction is dystonia, where the muscles actually become more rigid than normal. For deep procedures, a paralytic is almost always used with it.
Since it has a very rapid onset, it is a desirable drug. And because it rarely causes postoperative nausea, it is even more desirable. It may be that the lack of nausea is at least in part due to the suspected cannabinoid receptor agonist properties, consistent with using THC as an antinausea agent. It is also very easy to awaken a patient after surgery is over, as it drops to subtherapeutic levels almost immediately after the IV is stopped. Unlike phenol itself, propofol, the because of the two isopropyl groups ortho to the hydroxy group hindering hydrogen bonding due to steric effects. Thus, it is marketed as a water suspension of it, some soy oil, and an emulsifying agent. This give it the appearance of a milky liquid, and that, coupled with its strong amnesia producing effect, had some wag give the moniker of “milk of amnesia”. All in all, it is an excellent agent when used properly, but that may not be possible for very long. As of 2010 only two firms manufactured it, and in June of that year the largest manufacturer, Teva, announced it no longer make it, leaving only Hospira as the sole source. I strongly suspect that a big factor in Teva’s decision was the Jackson death.
After the piece last week, several commentators mentioned the combination of fentanyl and Versed, aka midazolam for procedures that they had. This is a very commonly used combination, but the readers were not very pleased with the results. In many respects, midazolam is the perfect anesthetic coagent. It is rapid in onset, rapid in recovery, causes significant muscle relaxation, and is quite amnesic, all positive attributes. It does cause some respiratory depression, but not like propofol. In a few patients, a paradoxical reaction occurs so that instead of being sedated, they become agitated and experience dystonia, things that are right out for an anesthetic.
Like propofol, midazolam activates GABAA receptors, but not directly, seemingly making the receptors more sensitive to GABA. This increases the level of chloride channel opening, thus tending to depolarize the neuron. Propofol blocks sodium channel opening, so it has a different mechanism.
Fentanyl is an extremely potent synthetic opoid. Coming in at 100 times the potency of morphine, it is like heroin on steroids, but causes less respiratory depression than morphine, making it one of the relatively rare agents that can be used both as an anesthetic and and analgesic. It also is less apt to cause nausea than many other anesthetics, but its use alone requires a full OR with staff and equipment. Combined with midazolam, it is widely used for endoscopic procedures. Although it is extremely potent, it has a very wide therapeutic index, the difference betwixt a clinically useful dose and a toxic one, so in the proper hands is quite safe. Once again, this seems to be an ideal anesthetic.
I have an hypothesis about why some readers were not pleased with the results of this combination. For many procedures, like endoscopy, the goal is not to anesthetize completely the patient, but rather just to sedate the patient. I strongly suspect that not enough of the agents were administered and so that sedation was not deep enough. I strongly suspect that if enough midazolam in particular had been administered, even though the discomfort might still have occurred, the amnesic effects of this drug would have disrupted the memory of the discomfort. One reader used a term like “did not do a thing for me”, and I daresay that this reader would have not remembered whether or not it did if enough had been given. And remember, a small percentage of patients have that paradoxical reaction, although in most of even those cases they do not remember it.
A very good alternative to this combination is propofol. It can be used in low enough doses to produce sedation rather than frank anesthesia, and its memory blocking properties are much greater than midazolam. In doses needed for sedation, respirator depression is hardly ever at all an issue, and because of the fast clearance of propofol, simple bagging would be enough to tide a patient over if such an unlikely event happened. That is dependent of an adequate supply of propofol being manufactured.
Well, you have done it again! You have wasted many more einsteins of perfectly good photons reading this sleepy piece. And even though Eric Cantor decides to give FEMA the funding that it needs after an earthquake and a hurricane blasted the east coast when he reads me say it, I always learn much more than I could possibly hope to teach in writing this series, so please keep those comments, questions, corrections, and other feedback coming! Tips and recs are always welcome as well. I shall stay around this evening as long as comment traffic warrants, and shall return tomorrow evening after Keith’s show for Review Time. He still needs to call me!
Doc, aka Dr. David W. Smith
Crossposted at The Stars Hollow Gazette,
If all goes well, I shall begin crossposting at ninkasi23’s new site next week.