In this episode, we tell the incredible tale of Dr. Scott Smith, an anesthesiologist who in 1946 purposefully paralyzed himself in a controlled setting. This experiment endeavored to answer a scientific question about which there was some equipoise at the time: do neuromuscular paralytics sedate and paralyze patients, or do they simply paralyze? Of course, we now know with certainty that neuromuscular do not cause sedation. But at the time in the 1940s, when paralytics were just starting to be used clinically, it wasn’t so clear.
Curare has long been used as a neuromuscular blocker for hunting purposes by indigenous peoples in Central and South America. It blocks the nicotinic acetylcholine receptor in the neuromuscular junction, leading to paralysis. In the 1930s, anesthesiologists started using curare as part of the induction of general anesthesia but this crucial question arose: if someone is chemically paralyzed, they look unconscious, but are they actually unconscious, OR do they just seem so. Put another way, does curare have sedating effects on its own or not?
Although we now take for granted that neuromuscular blockers do not sedate, this was not at all certain back in the 1930s and 40s. As a result, terrifyingly, some anesthesiologists were giving these agents to patients for surgery but not sedating them. Some clinicians strongly believed that curare caused sedation, and either used no or only local anesthesia when paralyzing patients. The majority of clinicians were not using curare alone, even when there was some uncertainty, but enough were foregoing sedation to raise alarm among anesthesiologists like Scott Smith.
Smith was a pioneer in the field of anesthesiology, and not just for this particular story. His main contributions centered around innovations in residency education and over a long and prominent academic career he became a leading light in the field. It’s worth remembering that anesthesiology is a relatively young specialty, compared to medicine or surgery, with the first procedural anesthesia occurring in the Ether Dome at MGH in 1846. Which, ironically, was exactly 100 years before Smith experimentally paralyzed himself. And he was understandably very uncomfortable with the idea of patients being paralyzed for procedures without sedation.
Smith essentially made himself the subject of his own experiment. And so at 2:11 pm on January 10, 1946, Smith submitted to awake paralysis by d-tubocaririne, which is a purified extract of curare, administered by his anesthesia colleagues. This was a monitored setting and they were fully prepared to intubate him once he became fully paralyzed. They even had him connected to an EEG to confirm wakefulness. They eventually published this story in 1947 in the journal Anesthesia, with the title “The lack of cerebral effects of d-tubocurarine”. And when you read the article, Smith gives a time-stamped play by play of what happened after he started receiving the paralytic.
They started by administering 200 units of d-tubocurarine over a 15 minute period. Smith and his colleagues had worked out a communication scheme for when he began to lose muscle tone and function. He would speak as long as he was able, then voluntary muscle contraction when he could no longer speak, and then of course he would be totally unable to communicate when paralyzed. Soon after the first infusion began at 2:11 pm, Smith reported feeling a bit dizzy and having quite a glow. But he was wide awake. He then began to have difficulty closing his eyes and mouth. By 2:20 pm Smith could no longer speak, though he could still nod his head and twitch his fingers.
At this point, his work of breathing began to visibly increase. The paper describes his breathing pattern as “diaphragmatic”. Smith’s colleagues continued asking if he was awake and with purposeful limb movements he indicated that he was. They even asked him if he needed to be intubated and he said no. Because he wasn’t fully paralyzed yet, they gave him another dose of d-tubocurarine. By 2:26 pm he was still indicating correct answers to questions and clearly not sedated. They tested pain response and he could feel pain. But he could no longer breath spontaneously or clear glottic secretions or open his eyelids. And when they manually lifted his eyelids he had marked double vision, because his eyes couldn’t move. This painful, frightening process went on for another 20 minutes with Smith progressively losing all voluntary movement and the ability to breath spontaneously. Finally, mercifully, at 2:45 pm Smith’s colleagues intubated him.
Thirty years later Smith was interviewed about the experiment and he recalled a profound sense of dyspnea and choking that he felt prior to his colleagues finally intubating him. He said that he felt like he was drowning, writing “I felt that I would give anything to be able to take one deep breath. The period of a few seconds taken for the tracheal intubation seemed unusually long”. In that interview, which was decades after the event itself, he still vividly remembered a sense of anxiety and panic that were so profound that he recalled feeling almost psychotic.
At 2:51 pm, or about 40 minutes after the experiment began, Smith received neostigmine for paralysis reversal. Over the next two hours they gave him more doses of neostigmine. Slowly he recovered respiratory and swallowing capabilities, as well as limb strength. By 6 pm he reported feeling weak but at this point essentially normal.
Thankfully, after Smith published his account, it was recognized that paralytics do not sedate. They gained wider use by anesthesiologists by the 1950s and pharmaceutical companies developed improved paralytic options such as pancurionium and succinylcholine.
Smith was not the first, nor the last, to perform self-experimentation. One of the most well-known examples was Werner Forssmann, a surgical resident in Germany in the late 1920s. He read research reports of right heart catheterization in animals and decided to try it on himself. So he inserted a foley catheter into his left arm and advanced it into his right atrium. He then convinced an x-ray technician to take a chest radiograph, proving that he had successfully performed right heart catheterization. He was promptly fired from residency but eventually won the Nobel Prize in Physiology or Medicine in 1956.
Another example is Barry Marshall, an Australian physician who along with his research collaborator Robin Warren, believed that infection with the bacteria helicobacter pylori was the primary cause of gastric ulcers. In 1984, Marshall drank a concentrated broth of helicobacter pylori and promptly developed severe gastritis and gastric ulcers, proving his theory. In 2005, they shared the Nobel Prize for their discovery.
Take Home Point
- Neuromuscular paralytics does not cause sedation!
CME/MOC
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Credits & Citation
◾️Episode written by Avi Cooper
◾️Show notes written by Avi Cooper and Tony Breu
◾️Audio edited by Clair Morgan of nodderly.com
Breu AC, Cooper AZ, Abrams HR. The Man Who Purposefully Paralyzed Himself. The Curious Clinicians Podcast. March 30, 2022
Image credit: https://wellcomecollection.org/works/mtctkh4b
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