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Anaesthetics

Most essays about the introduction of general anaesthesiaANCHOR refer to laughing gas parties or ether frolics in the 1840s, when these two anaesthetics were, apparently, used as social lubricants. However, this story is only partially true.

Laughing gas - the first anaesthetic
Searching for an anaesthetic to ease the pain of childbirth
The development of safer inhaled anaesthetics
Injected anaesthetics and local anaesthetics
References

Laughing gas - the first anaesthetic

Fifty years before an anaesthetic was used in patients, Humphrey Davy had demonstratedANCHOR that nitrous oxide produced a reversible state of unconsciousness in animals. These experiments led Davy to conclude that animals could survive for long periods in an atmosphere of nitrous oxide mingled with air, and he subsequently inhaled the gas himself, noting on one occasion that the gas relieved toothache. In his book Researches published in 1800 Davy concludes: "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."

In the early 1820s Dr Henry Hickman took the experiments a stage further by performing surgery on animals during a state of 'suspended animation' induced by carbon dioxide or nitrous oxide.ANCHOR Hickman then tried to interest the medical profession in the possibility of preventing pain during surgery by inhalation of these gases. However, he appears to have been ignored.

Over 20 years later the dentist Horace Wells, under nitrous oxide anaesthesia, had a wisdom tooth removed by partner Riggs. The nitrous oxide was administered by Quincy Colton, a one-time medical student who made his living by demonstrating the effects of laughing gas on members of the audience at his stage shows.

By 1846 major operations in both America and Britain were being performed under anaesthesia with ether, which Charles Jackson and William Morton (an ex partner of Wells) had found to be less erratic than the gas nitrous oxide.

During the dispute that followed the announcement by the USA of a substantial prize for the inventor of anaesthetics, Jackson gave credit to Humphrey Davy when he wroteANCHOR: "my attention was first awakened to this subject while a student of medicine, by reading Davy's researches."

Searching for an anaesthetic to ease the pain of childbirth

It is clear that animal experiments paved the way towards the development of general anaesthetics. However, it was not until the Victorian era that the desire to alleviate all suffering, even that of childbirth, came to the fore.

The desire to find the perfect anaesthetic for the pain of childbirth led James Simpson, the Professor of Midwifery at Edinburgh University, to search for an alternative to ether, which was not only an irritant but also highly inflammable - a risk when used in candlelight. Wemyss Reid had recently synthesised ethylene dibromide, but quite rightly insisted that the liquid should be tested on rabbits before being used in humans. The following day Simpson had intended to inhale ethylene dibromide himself but did not proceed when he discovered that the two rabbits used to assess the safety of the liquid had died overnight.ANCHOR

Simpson eventually obtained a sample of chloroform, which had been tested on animals by Flourens and shown to produce unconsciousness.ANCHOR Simpson used chloroform in midwifery and produced a paper describing its effects in 1847. As a result chloroform rapidly came into use in general surgery and for a while was believed to be absolutely safe. However,  the first death under chloroform anaesthesia occurred in 18487 and many deaths followed due to the toxicity of chloroform. In 1848, Thomas WakelyANCHOR tested chloroform and ether on a variety of animals of different species. Of those given ether, 34% died, of those given chloroform, 44% died.

The development of safer inhaled anaesthetics

The latter half of the nineteenth century and the early twentieth century saw improvements in equipment to deliver inhaled anaesthetics, the development of safer mixtures of gases and methods to measure their flow. Nitrous oxide was favoured from about 1868 when it became available in compressed form in cylinders.ANCHOR

A significant advance came in 1920, with the invention of the endotracheal tube. The development of further gaseous and volatile liquid anaesthetics followed. In 1929, Lucas and HendersonANCHOR showed that anaesthesia could be maintained in cats with 10 to 11 per cent cyclopropane in air. Ralph WatersANCHOR subsequently demonstrated its usefulness in humans. However, like the earlier anaesthetics, it was flammable.

The development from the 1950s of modern, non-flammable, safer, inhaled anaesthetics depended just as much on animal research. Experiments on rodents, rabbits, dogs, cats and monkeysANCHOR showed that the volatile liquid halothane, mixed with oxygen or air, was easy to use, produced rapid anaesthesia and recovery, had minimal side effects and the added advantage of some muscle relaxation. It rapidly became popular, and is still in use today, alongside related compounds.

Injected anaesthetics and local anaesthetics

Injected general anaesthetics are often used to induce anaesthesia before inhaled anaesthetics are administered, and are sometimes used alone for surgery of short duration. The most widely used modern intravenous anaesthetic is thiopentone sodium. Effective doses of this barbiturate were established by researchers at the University of WisconsinANCHOR, working with rats, rabbits and dogs. They first used it successfully in short surgical procedures in 45 patients between 1934 and 1936.

Local anaesthetics such as lignocaine are sufficient for some operations, and these are administered by injection or by application to the skin or mucous membranes. At about the same time that nitrous oxide in cylinders replaced the use of chloroform, KollerANCHOR demonstrated that cocaine applied to the eye of a rabbit could induce loss of sensation, thus paving the way for use of cocaine as a local anaesthetic in eye surgery. Later, James Corning demonstrated in dogs that cocaine injected into the dura, the membrane surrounding the spinal cord, caused anaesthesia of the hind legs14ANCHOR, paving the way for use of local anaesthetics for spinal anaesthesia. However, it soon became clear that cocaine was toxic, and around the turn of the centuryANCHOR the less toxic procaine was synthesised, widely used local anaesthetic until the development of lignocaine in 1948. In tests on rabbits corneasANCHOR, lignocaine was shown to be more effective with a shorter delay. Its low toxicity was established in rodents.


References

  1. Sharpe R (1988) The Cruel Deception, Thorsons Davy H (1800) Researches, Chemical and Philosophical, Chiefly Concerning Nitrous Oxide. Johnson, London
  2. Davy H (1800) Researches, Chemical and Philosophical, Chiefly Concerning Nitrous Oxide. Johnson, London
  3. Hewitt F (1912) Anaesthetics and their Administration, Macmillan
  4. Jackson CT (1861) A Manual of Etherisation, Mansfield
  5. Youngson AJ (1979) The Scientific Revolution in Victorian Medicine, Croom Helm
  6. Flourens M (1847) Comptes rendus 24, 342
  7. Wakely TH (1848) Lancet i, 19
  8. Livingston A (1983) in Discoveries in Pharmacology Vol 1 ed Parnham MJ & Bruinvels J, Elsevier
  9. Lucas GHW & Henderson VE (1929) Canadian Med Assn J 21, 173
  10. Stiles JA, Neff WB, Rovenstine EA et al (1934) Anesth Analg 13, 56
  11. Raventos, J (1956) Brit J Pharmacol 11, 394
  12. Pratt TW, Tatum AL, Hathaway HR, Waters RM (1936) Am J Surg 31, 464
  13. Koller C (1884) JAMA 24, 1592
  14. Corning JL (1885) NY Med J 42, 483
  15. Braun H (1905) deutsch Med Wochenschrift 42, 1667
  16. Wiedling S (1952) Acta Pharmacol et Toxicol 8, 117

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