Remembering the classics: A history of nitrous oxide, ether, chloroform, and the discovery of vapor anesthesia
Mark Schreiner MD and Myron Yaster MD
It’s summer time…hot dogs, baseball, ice cold beer and BBQ, California dreaming and the Beach Boys, and if you are an educator, the arrival of new anesthesia residents, fellows, and student CRNAs and AAs. When I saw today’s PAAD, an article by Mark Miodownik in the Guardian newspaper,1 I thought this would be a great one for the “newbies”, their teachers, and really for all of us. We have several members of the PAAD and SPA communities who are medical historians like Drs. Mark Schreiner, Mark Rockoff, and Christine Mai (running for a SPA Board member position), and are frequent contributors to the PAAD. I asked Dr. Schreiner to review this newspaper article as a “remembering the classics” Myron Yaster MD
Original article
Miodownik M. Revolution in the air: how laughing gas changed the world. The Guardian 07/04/2024 https://www.theguardian.com/society/article/2024/jul/04/revolution-in-the-air-how-laughing-gas-changed-the-world. (Edited extract from It's a Gas: The Sublime and Elusive Elements that Expand Our World. Mark Miodownik Mariner Books. Sept 2024 (Slightly different title and different publisher in the UK)
In an article published recently in The Guardian, and extracted from his upcoming book, Miodownik provides a history of the discovery and use of nitrous oxide, ether and chloroform for the intended purpose of producing general anesthesia. The stimulus for examining nitrous oxide was the author’s own experience with it. He dislocated a finger playing rugby. After a failed but very painful attempt to reduce the dislocated finger, he was then sedated using nitrous oxide. “It felt good, very good. I took another deep breath and soon found myself out of my mind and on a golf course, unable to find my ball.” “Returning to consciousness a few seconds (or minutes?) later, I saw the doctor standing in front of me, but there was no sign of his golf clubs. Instead, my finger was back where it should be. I had felt no pain this time. The doctor looked pleased.”
How did anyone get interested in the use of a gas as medical therapy? Miasma – bad air – was a dominant theory of disease transmission up until the latter quarter of the 19th century. Miasma explained the infection after childbirth and high death rates for wounded soldiers. Thomas Beddoes hoped to cure miasma by identifying gases that could be circulated in the environment that would cure rather than cause disease. To that end, he hired a chemist, Humphrey Davy (later to become Sir Humphrey Davy) to do the research. Nitrous oxide resulted from his efforts.
It quickly became apparent that inhalation of nitrous oxide caused fits of laughter and exhilaration. Laughing gas parties and public demonstrations of nitrous oxide became the rage. A part of the story I was unfamiliar with involves the role of Samuel Colt. Colt needed financing to produce his new gun and manufacturing methods and laughing gas demonstrations proved a profitable means for doing that. In 1844 a dentist Horace Wells attended a laughing gas demonstration and noticed that a man who fell and injured himself appeared unaware that he had done so.
While nitrous oxide proved effective in Wells dental practice, his attempted demonstration for a surgical procedure failed when the patient moved. William Morton, a student of Wells, successfully demonstrated the anesthetic effectiveness of ether in 1846. Morton called his preparation of ether Letheon and colored it to disguise it. However, Dr. John Collins Warren wouldn’t let Morton demonstrate the use without knowing what it was so the “secret” emerged. Morton sought a patent and became embroiled in litigation with Charles Jackson, a Harvard chemist who had suggested the use of ether to Morton. Eventually, Morton did obtain his patent which was the first one issued for a drug in the US.
The British were initially underwhelmed by ether, not because it was ineffective but because Morton was not a trained scientist. James Simpson spent months experimenting by inhaling the vapors of organic liquids after dinner with friends. When he and his friends tried chloroform in 1847, they found themselves waking up on the floor to the amusement of their female companions. Despite the obvious benefits, surgeons believed that the pain of surgery was in some way laudatory and objected to its use on “moral” grounds. Only after John Snow administered chloroform to Queen Victoria for the birth of Leopold in 1853 did anesthesia gain general acceptance.
The Brits favored chloroform over ether since it was discovered by one of their own. It proved fairly difficult to administer which likely resulted in an early tradition of physician anesthesia. Ether was far easier to use and nurses (e.g. Edith Graham and Alice Madaw at Mayo Clinic) were frequently trained to administer it. Only after the safety of ether compared to chloroform was established did the use of chloroform dissipate.
Within 3 years, 3 general anesthetic agents had been discovered and it wasn’t until the discovery of cyclopropane in the 1930s that there would be another. The most recent new anesthetic gases – desflurane and sevoflurane – have been around for 30 years. Ether and cyclopropane were abandoned in the 1960s-70s and replaced by halothane and enflurane because they were so explosive.
In addition to covering the early history of anesthetic gases and his own experience, Miodownik reports on a disturbing recent trend. “Young people, in their endless quest for different ways to inhabit their own minds, have rediscovered laughing gas. They buy boxes of whippets online and use them to blow up balloons of nitrous oxide. They then inhale the gas through the necks of the balloons as a recreational drug.” Not so very different than the laughing gas parties 2 centuries ago. By the way, the nitrous oxide whippets are used for making whipped cream.
For many reasons, the use of nitrous oxide in anesthesia practice is declining primarily because it is an ozone depleting green house gas.2 Some of the environmental concerns may be becoming less of a concern with the discovery that most medical nitrous oxide waste is the result of leaky hospital pipelines rather than during administration in the ORs.3 Switching to E cylinder tanked nitrous may significantly limit waste. Nevertheless, it is worth remembering that most (> 95%) nitrous oxide in the atmosphere come from agricultural and not medical sources.
Send your thoughts and comments to Myron who will post in a Friday reader response.
References
1. Miodownik M. Revolution in the air: how laughing gas changed the world. The Guardian2024.
2. Ravishankara AR, Daniel JS, Portmann RW. Nitrous oxide (N2O): the dominant ozone-depleting substance emitted in the 21st century. Science 2009;326(5949):123-5. (In eng). DOI: 10.1126/science.1176985.
3. Hansen EE, Chiem JL, Righter-Foss K, et al. Project SPRUCE: Saving Our Planet by Reducing Carbon Emissions, a Pediatric Anesthesia Sustainability Quality Improvement Initiative. Anesthesia and analgesia 2023;137(1):98-107. (In eng). DOI: 10.1213/ane.0000000000006421.
Dr. Schreiner and Dr. Yaster, thank you for your succinct and accurate history of the medical use of Nitrous Oxide and Ether. I appreciate the omission of He Who Must Not Be Named: Craw***d L**g. While Morton’s behavior was certainly less than, magnanimous, it was at least true, and not “Ah, um, yes, well I have been using that for years but didn’t tell anyone.” I think it’s important that younger anesthesia providers know about the advent of a pioneering discovery in Medicine.
Robert Nassif, DMD, MS