October 16th was World Ether Day (for those of you who might have missed it, intentionally or otherwise). The first public demonstration of general anesthesia was a medical miracle, but it wasn't without problems.
More than a century later, another medical miracle, also a general anesthetic agent, [1] was developed by researchers at Imperial Chemical Industries (ICI) in the United Kingdom. Its pharmaceutical business eventually became part of AstraZeneca. The compound is chemically known as 2,6-diisopropylphenol, but was marketed under the brand name Diprivan. You probably know it because of Michael Jackson's lethal overdose or by its generic name, propofol. Or maybe as "milk of amnesia," a nickname that is particularly well suited to describe the stuff.
Those of you who are colonoscopy enthusiasts may remember it because you don't remember it, hence the name. Once the anesthesiologist starts pushing that blissful elixir through your IV and asks you to count backward from 100 (good luck getting to 95), it's bye-bye, Mamacita! Then, you wake up asking when they're gonna start.
Going under and coming out of anesthesia can produce some spectacularly ridiculous conversations. We'll get to those shortly. But first, I need to justify my paltry salary with a little science. Deal with it.
Propofol: Discovery Was "Easy." Development? Not So Much.
I'll spare you a Dreaded Chemistry Lesson From Hell.™ What follows is actually pretty straightforward. Any moderately competent chemist looking at the structure of propofol is gonna say, "damn, that looks really insoluble." It is.
It takes about 1,300 mL (1.4 quarts) of water to dissolve a typical induction dose of 200 mg. That's more than a large IV bag. Good luck pumping that into a patient, especially one who may not find it funny to wake up and find that his eyeballs have popped out at the speed of sound. (By comparison, propofol prefers soybean oil to water by a factor of about 4,000.
What to do?
Propofol and water don't mix
The solution was to forget about dissolving propofol in water and find something else that would carry it into the bloodstream. The first attempt used something called Cremophor EL, a solubilizing agent made from castor oil. Unfortunately, there was a catch. Cremophor EL had already been implicated in serious allergic-type reactions, including potentially fatal anaphylaxis, when used with other anesthetics. Subsequent clinical experience with propofol reinforced those concerns. The drug worked beautifully, but the stuff used to dissolve it could be dangerous. Back to the snoring board.
Eventually, researchers developed a lipid emulsion containing soybean oil and egg phospholipids. Instead of dissolving propofol in water, they dissolved it in tiny oil droplets dispersed throughout water. Problem solved. It requires only 20 mL of emulsion to deliver the entire 200 mg dose in under a minute. No flying eyeballs should be anticipated.
A trip to the recovery room
What a difference! Propofol (in addition to its other wonderful qualities) has antiemetic properties, so nausea and vomiting are substantially less common than with many older anesthetics. But just because people wake up feeling better doesn't mean they wake up behaving better.
-
Dr. John
My long-time friend John is a highly respected obstetrician at a Pennsylvania hospital. Following a medical procedure, his wife, also a physician, reported that he emerged from anesthesia screaming, "I want a happy ending!" Sadly, no happy ending was offered.
-
Spider-Man (or Woman)
This is from a nursing discussion on Reddit. "Had a kid high off her ass from propofol tell me she was Spider-Man. When I took her vitals, she was yelling excitedly that her muscles were growing from the cuff. So I told her I knew the tooth fairy, because I remember vividly that once, when I came off anesthesia, I told everyone I met the tooth fairy. She asked me if I could connect her to the tooth fairy so they can collab. Whatever that would look like."
-
A woman with exquisite taste
Another Reddit story, this time an anesthesiologist discussion. A doctor described a woman in her forties who was about to undergo an appendectomy. As he administered propofol, she slurred, "I don't remember it tasting like that before." Puzzled, since propofol is given intravenously, he asked what it tasted like; she shouted, "DEEEZ NUTS!" And promptly passed out.
The source of the nuts in question was not disclosed.
-
A Large Pair Beats Three of a Kind
On the website Bored Panda, a nurse anesthetist described preparing a woman for surgery. As he administered propofol, he placed an oxygen mask over her face and instructed her to take "nice big breaths." Just before losing consciousness, she replied, "Thanks, I just had them done."
5. Sax, Drugs, and Rock ’n’ Roll
Finally, here's a short gem from the Thought Catalog. A woman regaining consciousness somehow said, "Wow, I’ve never been inside a saxophone before."
As if that's so special. Now, a piccolo, on the other hand...
NOTES:
[1] Propofol can be used for general anesthesia (complete unconsciousness) or, at lower doses, deep sedation, as during colonoscopies. It puts you to sleep but doesn't relieve pain, so other drugs, such as fentanyl, are often added during surgery. Otherwise, you might wake up, which would really suck.
Josh Bloom
Dr. Jonathan (Josh) Bloom, ACSH's Director of Chemical and Pharmaceutical Sciences, earned his Ph.D. at the University of Virginia and completed postdoctoral training at the University of Pennsylvania. During his 20-plus years in drug discovery at Wyeth, his research group discovered the antibiotic Tygacil®, approved in 2005. He holds 25 issued patents and has authored 35 academic papers. Since joining ACSH in 2010, he has written more than 2,000 articles and dozens of op-eds for major newspapers, including The Wall Street Journal and Chicago Tribune.
