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  3. Brownstein MJ. A brief history of opiates, opioid peptides, and opioid receptors. Proc Natl Acad Sci U S A. 1993;90:5391-5393.
  4. Norn S, Kruse PR, Kruse E. [History of opium poppy and morphine]. Dan Medicinhist Arbog. 2005;33:171-184.
  5. Conlay LA, Sim P. Acupuncture from East to West: Chinese medicine and therapeutics: early texts represented in the WLM collection. American Society of Anesthesiologists Newsletter. 2007;71:11-15.
  6. Bhattacharya S. Sushrutha—our proud heritage. Indian J Plast Surg. 2009;42:223-225.
  7. Loukas M, Lanteri A, Ferrauiola J, et al. Anatomy in ancient India: a focus on the Susruta Samhita. J Anat. 2010;217:646-650.
  8. Bushak L. A brief history of medical cannabis: from ancient anesthesia to the modern dispensary. Medical Daily. Accessed May 14, 2016.
  9. Carter AJ. Narcosis and nightshade. BMJ. 1996;313:1630-1632.
  10. Chidiac EJ, Kaddoum RN, Fuleihan SF. Special article: mandragora: anesthetic of the ancients. Anesth Analg. 2012;115:1437-1141.
  11. Carter AJ. Myths and mandrakes. J R Soc Med. 2003;96:144-147.
  12. Fairley HB. [Anesthesia in the Inca empire]. Rev Esp Anestesiol Reanim. 2007;54:556-562.
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Contributor Information

Bret S. Stetka, MD
Editorial Director
Medscape Anesthesiology

John Watson
Freelance writer
Brooklyn, New York

Disclosure: John Watson has disclosed no relevant financial relationships.


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Opium to the OR: A Visual History of Anesthesia

Bret S. Stetka, MD; John Watson  |  June 2, 2016

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Slide 1

Progress Against Pain

Humanity's millennia-long pursuit of defeating surgical pain has been waged in every corner of the earth, with nearly all documented societies seeking its relief in one form or another. As such, the history of anesthesia is as varied as the cultures that contributed to its progress. Little by little, their efforts helped surmount the brutal conditions that made even minor procedures a torturous proposition. This collection highlights some of the most important contributions that have brought us to the far less painful position surgical patients enjoy today.

Image courtesy of Wikimedia Commons

Slide 2

The Oldest Known Sedative: Booze

Alcohol may have been easing the pain of Neolithic humans as far back as 10,000 BCE. Stone jugs from that time contain the residue of a fermented liquid that in all likelihood was initially produced unintentionally from the effects of ambient yeast on honey or fruit. Intentional fermentation was probably applied around 1000 years later in Georgia, and then in 5000 BCE in the regions surrounding Mesopotamia. Records of alcohol fumes being used for anesthetic purposes appear in the 16th century, with direct intake of alcoholic beverages recommended by surgeons two centuries later to keep certain patients from struggling. Although the image of a taciturn Western hero taking a slug of whiskey before going under the knife is burnished in our minds, it's a prescription bound for failure. Alcohol's analgesic effects and ability to erase the vivid memories of surgical pain are much too blunt to make it an effective anesthetic.[1,2]

Image from Alamy

Slide 3

The Joy Plant

Archeological evidence indicates that the Sumerians (living in what is now Iraq) may have cultivated the opium poppy for anesthetic—and probably euphoric—purposes as early as 3400 BCE. A Sumerian clay tablet from approximately 2100 BCE, the oldest known pharmacopeia, is thought to refer specifically to the opium poppy, then known as hul gil, or "joy plant." Arab physicians applied it extensively, with traders from this region introducing it to India and China in the eighth century. Riding a wave of conquest and discovery, opium would make its way into the hands of medical practitioners in most major European cities by the late Middle Ages. The plant's singular analgesic qualities would ensure that it remained a mainstay of efforts to thwart pain until the present day.[3,4]

Image from Dreamstime

Slide 4

China's 4000-Year Pursuit

With a history stretching back roughly 4000 years, Chinese medicine has a very plausible claim to being the first to commonly use anesthesia. A written record of a painless surgery performed using a narcotic wine in 255 BCE is steeped in myth, involving as it does a successful double heart transplant. However, it indicates Chinese physicians of the time were actively trying to surmount the fundamental problem of surgical pain. Hua T'uo (approximately 190-265 CE) was the first Chinese physician to apply surgical anesthesia, in a formulation believed to include opium. The practice of acupuncture stretches even further back to the Nei Ching (Canon of Internal Medicine), the earliest known Chinese medical treatise, which was elaborated on by generations of later physicians. Acupuncture is perhaps the most influential technique for relieving illness-related pain in the ancient world, dominating such practices in China and Japan before finding its way to Europe in the late 17th century.[5]

Image from iStock

Slide 5

India's Father of Surgery

There is ongoing debate as to who first practiced surgical anesthesia. One of the most likely non-Chinese candidates is Sushruta, the father of Indian surgery. Estimates place Sushruta as having lived between 600-1000 BCE. He is best known for having written the Sushruta Samhita, one of the foundational pieces of Indian medicine and perhaps the oldest surgical textbook in world history. Amidst pages of detailed anatomical descriptions and surgical techniques, Sushruta also advocates using cannabis vapors with wine to sedate patients. The timing of the description may make it the first written record of anesthesiology. Whether it is or isn't, what is clear is that Sushruta was representative of India's early embrace of cannabis as an anesthetic. The plant was considered holy among certain Hindu cultures of the era and remained a key component of Indian medicine for millennia. Its use as an anesthetic was noted in several crucial medical textbooks that followed in the wake of Sushruta's pivotal work.[6-8]

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Slide 6

Taking Root in the Imagination

The overpowering dream-like qualities of early anesthetics often led to their confusion with agents of mysticism. This overlap is perhaps best personified by Mandragora officinarum, or mandrake, a plant indigenous to the Mediterranean whose sometimes eerily human-looking roots burnished its reputation as an ingredient for witchcraft. A process for extracting its potency using wine was described by Pediacus Dioscorides, a Greek physician employed in Nero's Roman army, who advised its use to "cause the insensibility of those who are to be cut or cauterized." In later years, mandrake was applied to a sponge in combination with opium to augment its sedative powers. The plant has had an outsized role in the cultural imagination. It's mentioned in the Bible as a fertility enhancer; in Shakespeare's Othello as an agent of desperately needed amnesia ("Not poppy, nor mandragora/Nor all the drowsy syrups of the world/Shall ever medicine thee to that sweet sleep); and, coming full circle, as an ingredient for sorcery in Harry Potter and the Chamber of Secrets.[9-11]

Image from iStock

Slide 7

Andean Anesthetics

Although the Incas lacked an alphabetic writing system, reports by Spanish conquistadors suggest that the empire may have made use of the local flora to induce anesthesia. Surgeons would chew coca leaves, common to the Andes, and drip their saliva into the wounds or incisions of patients, probably providing some degree of local analgesia. The Incas are also thought to have prepared a maize-based alcoholic beverage called chichi, which they used to render patients unconscious during minor surgical procedures. Several other plants native to Incan terrain have centralized effects and may have been exploited for their anesthetic properties; these include datura, espingo, tobacco, and San Pedro cactus.[12]

Image from Alamy

Slide 8

Wren's Quill: A Missed Opportunity

The first episode of intravenous anesthesia being successfully administered is also one of the great "what ifs" in medical history. The breakthrough was the product of Christopher Wren, perhaps the greatest English architect of his time, and Robert Boyle, an aristocratic chemist and physicist. In 1656 in Oxford, Wren used a goose quill to inject Boyle's preparation of opium mixed with alcohol into the vein of a dog, resulting in a brief period of anesthesia followed by full recovery. So why did it take until the design of an effective syringe in 1853 for similar procedures to be performed in humans? The authors of a 2013 paper on this topic posited several theories, including difficulties in titrating doses and the momentum-halting impact of a patient death after an attempted blood transfusion in France in 1667. The restless curiosity emblematic of Europe's so-called Age of Discovery was also often unconcerned with seeing such discoveries through to practical applications. A monumental path untaken, it consigned patients to roughly 200 more years of painful surgeries.[13]

Image courtesy of Wikimedia Commons

Slide 9

Anesthesia's Eureka Moment

"Gentlemen, this is no humbug!" With those words spoken to the awed spectators at a surgical amphitheater in Boston's Massachusetts General Hospital on October 16, 1846, Dr John Collins Warren declared the first successful surgical procedure performed with anesthesia. Collins, the chief of surgery at Harvard, had just removed a vascular tumor from a patient's neck. Yet the breakthrough is attributed to a more modest source, William T.G. Morton, a 27-year-old dentist who had been searching for more efficient analgesic than nitrous oxide. Eventually settling on a purified vapor of sulfuric ether, which he administered with a glass breathing apparatus designed to ensure rapid reversibility of the anesthetic state, Morton extracted teeth from patients who reported no pain or memory of the procedure upon recovery. After Collins validated Morton's technique under more rigorous conditions, thousands of years of striving had finally been realized, and the modern age of anesthesia was officially underway.[14]

Image courtesy of National Institutes of Health

Slide 10

The Rise of Chloroform

Although Morton's technique was justly greeted as a nearly miraculous discovery, ether's inherent limitations as a surgical anesthesia agent (eg, nausea and vomiting, prolonged induction) led to an immediate search for something better. Various researchers in this fledgling field, most notably the Scottish obstetrician James Y. Simpson, quickly settled upon chloroform as an ideal replacement. Chloroform offered several advantages over ether, including increased potency, faster onset of action, less associated costs, and the ability to be administered easily using a handkerchief or sponge. The treatment was popularized by Dr John Snow, the first physician to specialize in anesthesia, who administered it to Queen Victoria in the 1850s. Enthusiasm for chloroform dampened, however, when cases of treatment-related hepatotoxicity and several high-profile patient fatalities were reported.[14]

Image courtesy of Wikimedia Commons

Slide 11

Intubation's Innovators

At the turn of the century, methods for performing endotracheal intubation began to develop in tandem with the growing field of anesthesiology. The Scottish surgeon Sir William Macewen performed the first elective oral intubation to administer a chloroform-air anesthetic in 1878. The dangers of intubation were reduced considerably with the 1895 invention of the first direct-vision laryngoscope, the model on which all such contemporary devices are based, and the widespread availability of muscle relaxants beginning in the 1940s.[2,14]

Image courtesy of Wikimedia Commons

Slide 12

Potent Poisons

Although muscle relaxants were not commercially available in Western medicine until nearly a century after the foundation of surgical anesthesia, they had been known for ages to the indigenous tribes of South America in the form of curare, alkaloids derived from otherwise benign plant sap that turned poisonous upon injection. They were dramatically introduced to invading Spanish conquistadors in the form what they called "flying death," or curare-dipped blow darts. The explorer Charles Waterton later obtained curare samples from a native tribe, returning to England in 1814 to test their use on donkeys with the physician Benjamin Brodie. After much trial and error, they were eventually able to revive one of their subjects. Later experiments showed that curare prevented muscle contraction, and it was taken up in the 1940s by the neuropsychiatrist A.E. Bennet to combat spinal fractures in patients undergoing electroconvulsive shock therapy. The applicability of curare in anesthesiology was quickly evident, and it formed the basis of several neuromuscular blocking drugs to come.[15]

Image from Alamy

Slide 13

Recommendations of Dr Freud

Local/regional anesthesia can credit Sigmund Freud as an unlikely foundational figure. As a young physician in Vienna, Freud recommended cocaine to a younger colleague, Karl Koller, who then harnessed its analgesic qualities in cases of ophthalmic surgeries for which the current, facially obstructive methods of anesthesia were ill suited. After Koller demonstrated cocaine's formidable power in a patient with glaucoma, it was quickly adopted in the key surgical centers of the day. Two of its biggest adopters were the renowned New York City surgeons Alfred Hall and William Halsted, both of whom succumbed to crippling addictions in the years to come. As such cases became more common, public pressure led to the development of more sustainable alternatives, most prominently the anesthetic lidocaine.[2,14]

Image courtesy of National Institutes of Health

Slide 14

The Modern Era

In the years after World War II, progress in anesthesiology came rapidly in comparison with earlier eras. Supportive anesthetic agents, such as ketamine and etomidate, were developed in the 1960s and 1970s, replacing earlier barbiturates whose cardiovascular depressant effects had proven deadly in some patients. In the 1990s, the antiemetic qualities of propofol advanced the field even further by making it possible to avoid volatile agents entirely. Novel inhaled agents, such as sevoflurane, together with enhanced methods for objectively measuring the amount of anesthetic a patient was receiving, greatly reduced postsurgical complications. As the century came to a close, increasingly sophisticated technological imaging practices allowed tracheal intubation to be performed via video laryngoscope. Although the 21st century has yet to produce any breakthroughs on par with those of preceding decades, we will continue to discover safer, more predictable, easily reversible treatments for surgical patients.[2,16]

Image from Alamy

Slide 15

In Summary

For a few moments in October 1846, surgical pain was rendered temporarily, benevolently silent by William T.G. Morton and colleagues. The number of physiologic discoveries and medical breakthroughs that have followed from that point, and our newly acquired ability to halt pain and elongate surgical times, is so vast that it defies measurement. From the perspective of 170 years later, when more than 230 million surgical procedures are performed using general anesthesia worldwide annually,[16] it can be easy to take for granted this most common element of contemporary medicine. Yet, perhaps more so than for any other field, the disappearance of anesthesia would truly send mankind back to the drawing board, searching for any possible solution to one of life's most fundamental problems.

Image courtesy of National Institutes of Health

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