Being a brief but discursive history of some of the developments in general anaesthesia up to the twentieth century, mostly in Europe.

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The birth of true anaesthetics may be said to date from the day in about 1795 (dates are uncertain) on which Sir Humphry Davy (1778-1829) discovered the anaesthetic properties of nitrous oxide (N₂O). Davy reported his find in Researches, Chemical and Philosophical; Chiefly Concerning Nitrous Oxide, or Dephlogisticated Nitrous Air, and Its Respiration (1800). He had discovered that inhaling this compound caused unusual symptoms: at first, it produced a soaring euphoria, which soon passed into uncontrollable outbursts of laughter and sobbing, until it made him unconscious. Reasonably enough, he christened this discovery “laughing gas”.⁵

Davy himself appreciated the medical value of N₂O: “it may probably be used with advantage during surgical operations in which no great effusion of blood takes place”, but the mood-elevating and disinhibiting properties, as usual, were at first exploited in the cause of entertainment, rather like modern TV hypnotists. An American dentist, Horace Wells (1815-48), finally successfully used it while extracting a tooth in 1844, but a bungled attempt in front of the medical establishment at Massachusetts General Hospital in 1845 led to its, and his, loss of credit.

Meanwhile, Henry Hill Hickman (1800-30), a Shropshire-born country doctor, is recorded as experimenting with CO₂ anaesthesia in the 1820s. He promoted pain-free surgery, testing the efficacy of the gas by amputating the limbs of animals so sedated. He advocated what he called "suspended animation" ( ie general anaesthesia) for surgery on humans as well. He had the right idea about inhalation anaesthesia but picked the wrong agent. Carbon dioxide can indeed induce unconsciousness, but the gas also induces confusion and panic attacks because of the sense of suffocation. Worse, it can easily kill, or cause irreversible brain damage, if the administration is not carefully controlled. In 1824 Hickman published a pamphlet, A Letter on Suspended Animation, Containing Experiments Showing that it may be Safely Employed on Animals, with the View of Ascertaining its Probable Utility in Surgical Operations on the Human Subject, but in 1826, his work was savaged in an article entitled "Surgical Humbug", after which he emigrated to Paris, where he was no more successful.⁶

Mesmerism is hypnotism, known to the ancient Chinese and Indians, and still practised in China today as an alternative to pharmacological anaesthesia. Anton Mesmer (1734-1815) dressed it up with a lot of gobbledegook about “magnetic fluids” and “cosmic energy”, and it was occasionally tried out as an anaesthetic during the 19^th century in the West, not with much success apparently.

{mospagebreak title=Diethyl Ether}

Diethyl ether (then called sulfuric ether) was successfully used by the American dentist William E Clarke (1818-78) and a surgeon Crawford Williamson Long (1815-78), both in 1842. But the first public demonstration of ether anaesthesia in 1847, again at Massachusetts GH, administered by William Thomas Green Morton (1819-68) (he was another dentist, although the surgeon was operating on the patient's neck), was so successful that it became for a while the drug of choice. Morton, who had observed the Wells fiasco, carried out careful private experiments prior to this public demonstration; he anaesthetized himself, two assistants, his pet dog, and, intriguingly, his goldfish. (One assumes the dog and the goldfish survived, but history is unfeelingly silent on this point.)

This was a revolutionary development for surgery. Since records began, surgeons had been extremely limited in what they could attempt electively. “Meatball surgery” – battlefield patching-up operations – had been known since the year dot, but the surviving records from Greek, Egyptian, Chinese⁴, Indian and European sources indicate that elective “cold” surgery, even when the doctors thought they knew what needed to be done, was rarely if ever attempted. The brain, thorax, abdomen and pelvis were internal no-go areas; cancers had to wait until they fungated, ie became apparent on the surface. Amputations, external fracture reductions, manipulations of joints, cauterisations and excisions of superficial ulcers were performed to more-or-less frightening mortality rates. The one invasive exception, strangely, was a form of cystectomy known as “cutting for the stone” – the removal of bladder calculi. Ever since Hippocrates mentioned the practice specifically in his Oath, practitioners of this operation were a special caste, often peripatetic. Samuel Pepys underwent it in 1658 – successfully, but the things tend to recur. Its name survives in the lithotomy position (flat on back, feet up in stirrups).

Ether had in fact been first discovered in the thirteenth century by Raymundus Lullius (1232-1315) and again synthesised in 1540, by the German botanist-apothecary Valerius Cordus (1514-54); he named it oleum dulci vitrioli – sweet oil of vitriol. In 1730 the chemist W G Frobenius renamed it Æther (Greek: of heaven). Paracelsus (Philippus Aureolus Theophrastus Bombastus von Hohenheim, 1490-1541) had already noted its hypnotic property; as usual, he went overboard: “quiets all suffering without any harm and relieves all pain and quenches all fevers and prevents complications in all disease.” Friedrich Hoffmann (1660-1742) marketed it under the name “Hoffman’s Anodyne”, compounded with ethyl alcohol, as a treatment for cramps, earache, dysmenorrhoea, cholecystitis, toothache....In England its use was extended to the notably recreational. James Graham (1745-94), proprietor of the Temple of Hymen and the Celestial Bed (a purported fertility aid), was a noted addict, habitually and publicly inhaling a couple of ounces several times a day. Students and others celebrated “ether frolics”: parties where everybody would sit round a table and get stoned and then fall under the table. But nobody seems to have seriously thought of it as an aid to surgery in all that time.

{mospagebreak title=Dangerous Speed}

Following the Massachusetts demonstration, its fame spread to Europe; when the eminent surgeon Robert Liston (1794-1847) saw his first operation under ether he remarked “Gentlemen, this Yankee dodge beats Mesmerism hollow.” Liston had previously concentrated on speed; people used to time him with stopwatches, a challenge he welcomed. But speed can have its dangers. Once, performing a leg amputation in under 2½ minutes by the clock, he accidentally amputated in addition the fingers of the surgeon assisting, who, together with the patient, died of septicaemia shortly afterwards; a spectator had his coat-tails slashed during the same operation and dropped dead from shock. This becoming, so far as I know, the only surgical operation to achieve 300% mortality.

Liston it was, also, who when in the middle of cutting for the stone, witnessed his patient break free from the restraining attendants and leg it out of the theatre to the nearest lavatory, where he locked himself in. Not to be gainsaid, Liston himself broke down the door, manhandled the patient back to the operating table, and completed the procedure. But riotous fun aside, the point about Liston is that he was a humane man. He deliberately developed speed in operating, not to show off, but to spare his patients what he knew was excruciating suffering, not least because most of them would die shortly afterwards of hospital-acquired septicaemia, a prognosis which surgeons were all too aware of but didn’t encourage their patients to dwell on overmuch.

Sir James Young Simpson (1811-70) received his M.D. from the University of Edinburgh, where he became Professor of Obstetrics. After news of the use of ether in surgery in Boston reached Scotland, he employed it to relieve labour pains (in 1847) and later substituted chloroform (CHCl₃) (discovered by von Liebig in 1832) , which he continued to use despite opposition from other obstetricians and the clergy. Queen Victoria settled all that by insisting on chloroform for the birth of her eighth child, Prince Leopold, in 1853. Legend hath it that, in reply to the fundamentalist cries of "in-sorrow-shalt-thou-labour" she replied "We are having the baby and we are having the chloroform.” Simpson himself smartly quoted back at his opponents Genesis 2, 21: “So the Lord God caused a deep sleep to fall upon the man, and while he slept took one of his ribs and closed up the place with flesh”, thus cannily endowing his practice with the same holy authority as their objections.

{mospagebreak title=Voluptuous Sensations}

Not least of Simpson’s problems at the time was that self-appointed moralists had latched on to the idea that general anaesthesia released sexual inhibitions, especially in women. Humphry Davy hadn’t helped matters by recording that inhaling N₂O could induce “voluptuous sensations”. A Dr Smith wrote indignantly “To a woman of this country the bare possibility of having feelings of such a kind excited and manifested in outward uncontrollable actions would be more shocking even to anticipate than the endurance of the last extremity of physical pain.” Although, perhaps not surprisingly, he did not give any figures for this bias. Simpson himself anticipated a well-worn medical foible when he started to administer chloroform to guests at his dinner-parties; when they fell unconscious, and if they were young, pretty, and female, he is reported to have “kissed” them.

Another motive behind the opposition to effective anaesthetics was rather more rational; in the absence of continuous cardiac monitoring, pulse oximeters, sphygmomanometers, or any metered method of administering the gases, surgeons were reasonably worried about their inability to judge accurately the patient’s state under anaesthesia. And at this time, administration was a hit-and-miss affair, usually left to medical students, nurses, or even relatives or strangers off the street who wandered into the operating theatre to kibitz. The existence of a wide-awake, yelling subject was at least assurance that s/he was not over-anaesthetized and heading for cardiac or respiratory arrest. “Pain in surgical operations is in a majority of cases even desirable, and its prevention or annihalation is for the most part hazardous to the patient,” noted one Dr James Pickford.

Chloroform was less irritating and thus easier to administer than ether, induction with which tends to make the patient fighting mad; however, the former had two rather serious disadvantages: it is pretty hepatotoxic and it induces ventricular fibrillation, frequently leading to irreversible cardiac arrests. Indeed the first such took place as early as 1848; the patient a fifteen-year-old girl. However, compared to ether, chloroform was effective in smaller quantities, and quicker-acting, so despite many fatalities it was still employed well into the 20^th century.

Both ether and chloroform were originally administered by a method that had not changed, basically, since the days of the soporific sponge. Ether was dripped on to a sponge in a glass inhaler from which the patient then breathed until unconscious; chloroform was dripped onto a pad or handkerchief which was then held over the face. (In A Pattern of Islands Grimble gives a vivid description of the technique of self-anaesthesia with chloroform during childbirth.)

Sir Benjamin Ward Richardson (1828-96) was a pioneer in experimental anaesthetics (as well as a fervent advocate of bicycling); he brought into use no less than fourteen agents, of which methylene bichloride (dichloromethane) was the most used; as an inhalation agent it is narcotic in high concentrations. It is now used only as a solvent in manufacturing and food technology. One of his less likely candidates was the spore dust of the puffball mushroom Lycoperdon giganteum, which he had noted was used by beekeepers to sedate their swarms. Whether he tried it on humans I don’t know; I cannot conceive its mode of action on mammals, short of suffocation; but he definitely did use it for humane euthanasia of unwanted animals, another cause he espoused.

{mospagebreak title=Nineteenth-Century Attempts}

Other nineteenth-century attempts at developing general anaesthetics included oral potassium bromide (KBr), first tried in 1853, chloral hydrate (C₂HCl₃O · H₂O), and paraldehyde (2,4,6-trimethyl-1,3,5-trioxane).

And while all this was going on, the Japanese had beaten the West to it; in 1804 the surgeon Hanaoka Seishū used an oral compound he called Tsusensan, based on the plants Datura metel, Aconitum spp. and others, to perform the first attested operation – a partial mastectomy - under general anaesthesia.

Induction of anaesthesia nowadays (except in the case of small children and babies) is almost invariably carried out by intravenous injection, as that is much more pleasant for the patient than gas induction, which produces a suffocating sensation; but that obviously had to wait until the invention of a syringe, needle and drugs capable or achieving this. Nevertheless, be it noted that Sir Christopher Wren is credited with giving a dog an IV injection of tincture of opium, via a bladder attached to a bird’s quill stem. This was in 1665; a hollow needle capable of piercing the skin was not invented until 1845, by the Irish surgeon Francis Rynd (1811-61), although credit is often given to Alexander Wood and Charles Pravaz, who both independently developed practicable syringes in 1853.

There was a long way to go, however, as making the subject unconscious is only part of the story. None of the drugs so far mentioned causes paralysis. The patients had to be very deeply anaesthetized, in order to achieve maximum relaxation, and so operations on the throat, thorax, abdomen and pelvis, where the aforesaid muscles react to the stimulus of the scalpel by instant spasm, were necessarily extremely dangerous because of the respiratory and cardiac depression which accompanies deep anaesthesia; until the advent of curare (1942) and its allies in the 20^th century allowed a much lighter level of anaesthesia. Moreover, without the option of paralysis, and the possibility of endotracheal intubation, operations involving the head, face and throat were next to impossible without this extremely deep anaesthesia, because the method of delivery of the gases necessarily required some form of face mask.⁷

{mospagebreak title=Carbolic Acid Antisepsis}

Fortunately for the patients, Lister’s invention of carbolic acid antisepsis arrived in 1865 (Semmelweiss’s work having been largely ignored by the profession), thus considerably reducing the incidence of morbidity even before the introduction of antibiotics in the 1940s. Autoclaving was invented by von Bergmann in 1880, eventually leading to aseptic surgery. Nevertheless, if Shaw is to be relied upon, patients needn’t be uniformly grateful for anaesthetics. As he said in the Preface to The Doctor’s Dilemma:

“When doctors write or speak to the public about operations, they imply, and often say in so many words, that chloroform has made surgery painless. People who have been operated on know better. The patient does not feel the knife, and the operation is therefore enormously facilitated for the surgeon; but the patient pays for the anesthesia with hours of wretched sickness; and when that is over there is the pain of the wound made by the surgeon, which has to heal like any other wound. This is why operating surgeons, who are usually out of the house with their fee in their pockets before the patient has recovered consciousness, and who therefore see nothing of the suffering witnessed by the general practitioner and the nurse, occasionally talk of operations very much as the hangman in Barnaby Rudge talked of executions, as if being operated on were a luxury in sensation as well as in price.”

Patients had to wait well into the 20^th century for the speciality of effective pain control to be recognised, and very many of them will tell you that they are still waiting for its principles to be implemented.

{mospagebreak title=Notes}

¹Reputedly the words of the US Confederate General “Stonewall” Jackson (1824-63) on receiving chloroform anaesthesia before a left arm amputation.

²I have tried to chase this claim up with no success. The predominant stone is the Memphis area is limestone, which if mixed with vinegar would certainly give off some CO₂, but without an apparatus to collect and deliver the gas it is difficult to see how administration could be effected. There is an old nursing trick for calming down an hysterical overbreathing patient by getting him/her to breathe in and out of a paper bag for some minutes; perhaps some such method was used by the Egyptians, although any sedation would necessarily be of short duration.

³It has been claimed claimed that he said also that they used it as an anaesthetic but I have been unable to trace any such statement in the Histories. All he actually says is: “The Scythians then take the seeds of this hemp and, creeping under the mats, they throw them on the red hot stones; and, being thrown thus, they smoulder and send forth so much steam that no Greek steam bath could surpass it. The Scythians howl in their joy at their vapour-bath. This serves them instead of bathing, for they never wash their bodies with water.” (Book IV Cap. 75)

⁴There are fragmentary records of a Chinese surgeon Hua Tuo (c.110-207 CE) who reputedly used hemp boiled with wine as a general anaesthetic allowing him (allegedly) to perform complex abdominal operations.

⁵Nowadays affectionately known as "gas-and-air", a mixture of, roughly, 66% N₂O to 24% O₂, is still used in obstetrics and in A&E for reducing dislocations, as, inhaled, it has a rapid onset and offset, although full anaesthesia, ie unconsciousness, needs a considerably higher concentration and this limits N₂O’s use as it is a weak analgesic.

⁶CO₂ anaesthesia is still used, in the humane anaesthesia of animals prior to slaughter.

⁷In fact, the first description of endotracheal intubation and subsequent artificial respiration of animals was apparently made by Andreas Vesalius in 1543. He is said to have pointed out in De Humani Corporis Fabrici that such a measure could sometimes be life-saving; however, there are no records of this being acted upon by his successors. It was not until 1869, in the West at least, that the German surgeon Friedrich Trendelenberg accomplished the first intubation of a human being for the purpose of anaesthesia: he intubated the patient via a temporary tracheotomy. The first successful intubation via the oropharynx was in 1878.

{mospagebreak title=References}

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