The Astonishingly Slow Progress Towards Surgical Anesthesia

Imagine...

...it is 1842 London, and you are suddenly awakened from a fevered and distressed state by several men summoned by your family to take you to one of London’s public operating room theatres. You suffered a fracture one day ago, and part of your lower femur is jutting through the skin above your knee. Amputation is the only way of saving you from a horrible death. However afraid you are of that kind of death, you are equally if not more fearful of what you know is to come.

You arrive to find yourself in the center of an amphitheater surrounded by as many as two hundred spectators there to see another of the night’s amputations done by the renowned surgeon Dr. Robert Liston. There is no anesthesia offered to avoid your inevitable suffering. As Liston enters the theatre dressed in his apron stiffened by other patients’ blood, the audience of medical students and the public remains hushed. While students have come to learn from the renowned fastest surgeon of his time, others come to see the gore as entertainment.

Think of the unimaginable horror you would experience when observing the blood-stained surgical instruments laid out, the audience there to be regaled in your torment, and the men there to hold you down. The terror you feel causes you to fight Liston’s assistants but to no avail. Liston’s men overpower you, and the surgery commences as you experience the most unfathomable pain as he speedily makes deep incisions to fashion large flaps of tissue to cover the stump below your knee. Liston stops the bleeding with forceps and ligature and rapidly saws through the bone proximal to the compound fracture. He finishes by skillfully sewing up the stump left behind with no hint of aseptic concern throughout the entire operation, of course.

This was the tragic experience of countless patients throughout history before the advent of dependable and safe anesthesia. It is upsetting to find out that there were compounds available for hundreds of years before 1842 (arguably the year of the first recorded general anesthetic) that an anesthesiologist of today could have used in combination to provide adequate and safe anesthesia.

The world needed a safe and dependable state of general anesthesia to end agony during surgery and allow surgical progress to begin. That definitive discovery came in 1842 (or 1846, depending on which historical version of events one believes.) What came after is a complicated tale of three gases (ether, nitrous oxide, and chloroform), a topic that others have extensively covered. It is incredible how long it took for humanity to employ sufficient anesthesia to avert the pain, shock, and mental anguish caused by surgery.

Robert Liston operating in a surgical theatre in London. Painting by Ernest Board of Bristol 1912.

In a paper published in 2010, Astyrakaki, Papaioannou, and Askitopoulou from the University of Crete examined the Hippocratic Collection in its original Greek and found evidence that the first physician to use the words “anesthesia” and “analgesia” in medical writing was Hippocrates himself. Incredibly, he not only defined pain’s characteristics and identified opium and other hypnotic (soporific) substances to relieve pain, but he also associated analgesia with the state of anesthesia when he asserted that the “unconscious patient is insensitive to pain.”¹ Hippocrates is the historical figure who liberated medicine from religion by redefining it as a science. Humanity then essentially ignored his teachings about analgesia and anesthesia for over two millennia, postponing the triumph over surgical pain.

Today, student physicians can go through their entire anesthesia residency and come away with little more than a cursory understanding of anesthesia’s foundational history. Most are ignorant of how truly horrible it was during most human history for patients to undergo surgery without the techniques and drugs skillfully used by modern anesthesiologists. The discovery of dependable and safe anesthesia was one of the most monumental breakthroughs in the history of medicine. And for the 179 years that followed, the application of reliable anesthesia allowed millions to avoid suffering and death caused by surgically treatable disease and injury. The ever-improving knowledge, pharmacopeia, and anesthesia technique have permitted medical and surgical innovation, leading to surgical advances like transplantation of organs and correction of once deadly congenital heart disease.

Any empathetic person would be disturbed by reading the rare accounts of surgery on the awake patient. Stories of amputations, bladder stone removals through incisions in the perineum, and tumor excisions carried out on fully conscious screaming patients, especially children, will send a chill up the spine and cause horror thinking of those poor patients. There are descriptions and drawings of patients with tumors nearly as heavy as they were, cystic masses that had to be carried along in carts, and facial deformities that caused persistent misery all because of the fear of being conscious of the pain during surgery. People endured infections until they had to choose between surgery or certain death. Countless people must have died rather than feel the pain of the surgeon’s cruel blade.

Before anesthesia, a careful selection of patients who would likely tolerate a surgical procedure, keeping a patient conscious, and the surgeon’s speed were what made surgery relatively successful for that time in history. Bleeding was the surgeon’s enemy, and they thought anything that intoxicated a patient increased blood loss. Amputations were done at lightning speed to lessen blood loss and to reduce the risk of shock caused by extreme pain. Dr. Robert Liston was so fast that he once cut off an assistant’s fingers while amputating a patient’s leg. Both the assistant and the patient died of sepsis following the surgery. His rivals in London’s medical community were delighted to advertise that he had killed two people with one surgery, a two hundred percent mortality rate.²

Fanny Burney at age 32. Painted by her cousin Edward Francesco Burney, 1784–85 and excerpt from Francis Burney’s letter to her sister about her “terrible operation.”

Source: https://www.bl.uk/restoration-18th-century-literature/articles/frances-burneys-account-of-herterrible-operation

Witnessing surgery on the awake patient veered many potentially gifted people away from the practice of medicine altogether. As a medical student, Charles Darwin was witness to surgery without anesthesia. In 1827, he wrote in his diary: “I ... attended on two occasions the operating theatre in the hospital at Edinburgh, and saw two very bad operations, one on a child, but I rushed away before they were completed. Nor did I ever attend again ... The two cases fairly haunted me for many a long year.”³ Darwin promptly resigned from studying medicine because of what he experienced and began his education in mathematics, the classics, and theology.

There is a surprising lack of detailed descriptions of surgery’s psychological impact on patients without anesthesia, especially when equated with the total number that must have suffered through history. There are even fewer descriptions of how surgeons were affected by operating on awake patients. So gruesome was surgery before dependable anesthesia that surgeons felt like they were “going to a hanging” and would often shed tears and vomit after their patients’ forced torment.⁴ Patients expecting surgery were like criminals awaiting their execution, counting the days, hours, and minutes before the dreaded procedure. These nightmarish experiences of patients who survived surgery and the surgeons who operated on them probably precluded any desire to record their story.

From the patient’s perspective, Frances Burney (a 19th Century novelist, playwright, and diarist) authored one rare account of being awake during surgery. She wrote a letter to her sister describing the “profound evil” of her four-hour mastectomy for a painful tumor in 1811. Burney had put off the surgery she feared for years until her condition left her no choice.

She wrote: “When the wound was made, & the instrument was withdrawn, the pain seemed undiminished, for the air that suddenly rushed into those delicate parts felt like a mass of minute but sharp & forked poniards (small dagger), that were tearing the edges of the wound — but when again I felt the instrument — describing a curve — cutting against the grain, if I may so say, while the flesh resisted in a manner so forcible as to oppose & tire the hand of the operator...” “Yet—when the dreadful steel was plunged into the breast—cutting through veins, arteries—flesh—nerves—I needed no injunctions not to restrain my cries. I began a scream that lasted unremittingly during the whole time of the incision—and I almost marvel that it rings not in my Ears still! so excruciating was the agony.”⁵

After the operation, she could not think or speak of the incident for nearly nine months; she felt so utterly sick at what had happened to her that she battled incessant headaches. Burney also wrote powerfully about the operation’s terrible effect on her famous, experienced, and remarkably empathetic surgeons.

Before safe anesthesia, it is not surprising that surgeons tended to avoid intracranial, intrathoracic, and abdominal surgery for fear of profound shock, risk of death, and the unavoidable agony caused by these more complex prolonged operations. On average, only one major surgery was performed at Massachusetts General Hospital each week before the demonstration of ether in 1846.⁶ Even the fastest of surgeons like Liston only did a few significant operations each week.

Western and Religious Beliefs

There was an erroneous yet pervasive Western view for hundreds of years before 1842 that the awake patient’s stress and anguish during surgery primarily kept them alive. Surgeons felt more secure operating on conscious patients because their screams were a positive sign that they were still living. The thinking against having an unconscious surgical patient may also have come from anecdotal experience in administering too much opium or alcohol to surgical patients. Some unfortunate patients may have died secondary to respiratory arrest caused by excessive intoxication.

Religion was responsible for the false belief that surgical patients must be awake during their procedure because suffering was an Old Testament virtue. The religious doctrine of the time taught that if God meant us to suffer when injured (or operated on), we must not interfere with His plan, even if this led to excruciating and needless agony.⁷ Religious doctrine significantly impacted medicine from the Middle Ages to the mid 19^th century by steering thinking away from pain relief until the mid-1800s, when views changed in the West.

For thousands of years, man has known that substances like opium, the root of the mandrake (mandragora), leaves of hemlock, and certain parts of the henbane (Hyoscyamus) plant can relieve pain and cause a degree of unconsciousness. In ancient times and through the Middle Ages, physicians boiled botanicals such as those listed above into a soporific (hypnotic) sponge used as a device for inhaling its vapor. The vapor inhaled or liquid that dripped from them supposedly caused such a deep pain-free sleep to render a patient motionless during even the most painful procedures. However, historical writings provide clues that this type of anesthesia was unreliable and that the patient still had to be tied or held down for surgery. Before the development of pharmacology as a science, it was impossible to administer precise amounts of hypnotic and analgesic substances. Giving too much could kill their patients, and giving too little would lead to suffering.

It was not until 1842 that one physician made the crucial mental leap that provided a safe and dependable general anesthetic to a surgical patient. For hundreds of years before the 1840s, people knew how to synthesize ether and knew its hypnotic qualities. There was common knowledge that opium was a potent pain reliever. How did surgeons not use these substances on their surgical patients during the centuries preceding the momentous discovery starting in the 1840s? The answer to this question is complicated and enormously infuriating when one thinks of the millions that have suffered surgery without the benefit of anesthesia.

Ancient Asian medical texts contain evidence that physicians in that part of the world used herbal concoctions to relieve suffering during surgery. The individual identified with bringing surgery to China in the early third century was the legendary physician Hua T’o (c.141–208.) Before T’o’s time, the Confucian doctrine that the human form was too sacred to mutilate in any way, even to save a life, prevented the development of surgery. Hua T’o was such a skilled physician that people constructed temples to honor him, and his fame and skill as a surgeon made surgery an accepted form of treatment in China for the first time. Chinese medical history also credits T’o with developing a powder that, when mixed with wine, made patients insensible to even the most ambitious surgical procedures. According to folklore, “Hua noted a wounded deer staggering to a pasture. After grazing at certain herbs, the animal seemed relieved of its discomfort. Out of curiosity Hua personally tasted several herbs and found a few that made his mouth numb.” This is how he thought to have produced his pain-relieving powder. Hua T’o was not able to leave behind his formula for the herbal anesthetic that he called mafeisan. Unfortunately, he was executed for escaping the captivity of King Ts’ao Ts’ao, whom he had been treating for chronic headache.⁸ It is impossible to verify that his concoction worked or that it was dependably safe. It was unlikely that mafeisan perform like a genuine general anesthetic considering what compounds were available during T’o’s time and location. His legendary skill as a surgeon survived through history, but the recipe for his miraculous powder did not.

Yuanmen Maijue Neizhao Tu (元門脈訣內照圖), a chart of the internal viscera and organs. Attributed to Hua Tuo, ancient Chinese Father of Surgery. Imprint of the Qing dynasty.

Source: wikipedia

Sweet Oil of Vitriol

It is a misconception that ether miraculously appeared when physician Crawford Long used it in the first general anesthetic recorded in 1842. For all its historical significance in medicine, ether is an easy compound to produce and was made for over five hundred years. In the thirteenth century, a Spanish mystic and philosopher named Raymond Lully was the first to make ether and describe it (Sweet Oil of Vitriol). He, in all probability, discovered it after spilling sulfuric acid into wine with high alcohol content. However, he did not recognize its anesthetic effects.⁹

Valerius Cordus (1515–1544) and Paracelsus (1493–1541) are the two figures that historians give simultaneous credit for studying ether as a chemical compound with medicinal value.

The Nuremberg physician and botanist Valerius Cordus was the first to record a precise method of preparing ether in his book written in 1561, “De Artificiosis Extractionibus.” His recipe was to combine sulfuric acid, called sour vitriol, with “strong, very biting thrice purified wine” (wine with very high alcohol content).¹⁰ Cordus wrote about the physiological effects of ether and proposed some possible medical uses, such as an expectorant of mucus. Curiously, he also did not uncover ether’s anesthetic qualities. He is, however, the first to describe using ether as a recreational drug.

The Swiss alchemist, physician, and the first real toxicologist Philippus Aureolus Theophrastus Bombastus von Hohenheim, known as Paracelsus, documented his method of distilling ether and his use of it on animals at around the same time as Cordus. His writings show that he realized some of its anesthetic and pain-relieving qualities.¹¹ Paracelsus documented that he succeeded in anesthetizing chickens by mixing ether with their feed. He is given credit for being the first known person to identify the anesthetic properties of ether. Frustratingly, he had no triumphant moment where he understood the benefit that ether could have for surgical patients.

Ether (or Aether) was given its name in 1730 by August Sigmund Frobenius, a German chemist. He demonstrated its various properties to the Royal Society in 1730.¹² Eighteenth-century chemists used ether in many ways, such as extracting essential oils from plants and separating gold from copper. Frobenius’s method of ether production was supposedly the same recipe used by Isaac Newton. It seems that even the renowned intellect of Sir Isaac Newton, who dabbled a bit in chemistry, could not make the mental leap that would have linked ether’s anesthetic effects to use on patients during surgery.

Before 1842, physicians used ether in many ways other than for anesthesia. Ether became a treatment for various maladies, including arthritic and rheumatological diseases, digestive disorders, and respiratory ailments. Some physicians advised patients to ingest two teaspoons of liquid ether per day to calm “nervous” conditions. Others treated headaches by having liquid ether rubbed into patients’ temples, and other physicians wanted their patients to inhale ether.¹⁰

In 1821, during a lecture by Benjamin Collins Brodie for the Royal College of Surgeons of England, he placed a jar containing ether over a guinea pig. For twelve minutes, it appeared dead, not moving. He then lifted the jar and revived the animal with artificial respiration to the astonishment of the audience.¹³ Not one physician that observed this demonstration is known to have grasped ether’s potential value for patients having surgery.

Dr. Crawford Long, a physician in Jefferson, Georgia, utilized ether as an anesthetic for the first recorded time and excised a tumorous growth off his patient James M. Venable’s neck.¹⁴ Mr. Venable, who felt nothing during the successful operation, was already accustomed to ether because of his experience inhaling it at parties with others who wanted to feel its stimulating effects. They called these gatherings the “ether frolics,” a common form of amusement in the mid-1800s. As detailed in a dental journal about that time: “There was hardly ever a gathering of young people that did not wind up with an ether frolic…. Some would laugh, some cry, some fight, and some dance, just as when nitrous oxide is inhaled.” ¹⁵

Dr. Long noticed that when he and his acquaintances emerged from their intoxication, they would often have evidence on their bodies of injuries from falling that they had not felt and did not remember. He and his patient Venable must have determined that because it seemed safe enough to use as a form of entertainment and appeared to have the ability to cause a pain-free and unconscious state, they should make use of ether while Dr. Long operated on him. Long did not seem to appreciate the significance of his accomplishment. Despite using it successfully a few other times before 1846, he did not announce his discovery to the medical community until 1849. Four years after Long used ether on his first anesthetized patient, other famous physician-scientists took credit for its first use. It is even more tragic because ether was available in apparent abundance at the time. For four years after ether’s successful use as a general anesthetic in 1842, patients had to suffer through surgery conscious because of Long’s lack of insight into his discovery’s impact on medicine.

Caricature of nitrous oxide (ether) frolics. 1808.

Source: http://susanbuckmorss.info/text/aesthetics-and-anaesthetics-part-ii/

Laughing Gas

The history of nitrous oxide “laughing gas” is also a story of a missed opportunity given the length of time people knew of its anesthetic characteristics before its demonstration as a potential anesthetic. It, like ether, was used as a form of entertainment long before the discovery of its medical utility. Joseph Priestley, a minister with no scientific education but thought of as the father of the modern scientific study of gases, described nitrous oxide gas in 1772 and isolated oxygen in 1774.¹⁶ Humphrey Davy, a 20-year-old Superintendent of Experiments at the prestigious Pneumatic Institution in England and former surgeon’s assistant, was the first to experiment with nitrous oxide in 1795. He realized its intoxicating and pain-relieving qualities in his experiments and when he used it on himself for dental pain. He stated that “as nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place.” ¹⁷ For some inexplicable reason, even though expertly published by one of England’s most outstanding minds at the time, Davy’s words on nitrous oxide were ignored by the medical community that denied a necessary treatment for surgical suffering for decades. Although not sufficient as a general anesthetic by itself as we understand today, it certainly would have offered safe and considerable respite from surgery’s pain.

Amputation of the Thigh. Sir Charles Bell, 1820.

Source: https://dirtysexyhistory.com/2016/07/17/the-age-of-agony-surgery-in-the-19th-century/

Other delayed great discoveries in science and medicine throughout human history resulted from cultural prejudice, religious doctrine, or the pure lack of the development of scientific analysis. However, only a small number of them had as many opportunities laid out for great minds to connect discovery with advancement for humanity, as seen with the development of safe and dependable general anesthesia. Even fewer delayed discoveries led to such an unfortunate impact on so many lives throughout history.

Going back to the imagined amputation Liston was performing on you, think of the relief you would feel if there was an anesthesiologist present. This physician was to administer ether plus nitrous oxide to you for the procedure. You knew it was safe and effective at preventing agony from amputation. Now you need only be concerned about postoperative pain and infection, other complications requiring medical breakthroughs.