History of Anaesthesia1

Approximately 500,000 years ago, the early man, or the subman, Pithecanthropus erectus, struggled with nature, wild beasts, and his fellow submen for existence. Approximately, around 50,000 years ago the Neanderthal man, appeared on the scene. He first lived alone like his ancestors. Later he joined with other individuals to form groups for mutual help in hunting and in battling with other groups for their women (Wells 1921). These early men discovered that bruises and sprains felt better when the injured part was held in a cold stream or lake. Other painful wounds felt better when exposed to the sun's heat, and as a result, the radiant heat from fire and warm stones was probably used. If the injuries were severe, early man either suffered and died, or suffered and got well without help.

Approximately 25 to 40,000 years ago, the first true man developed. In each village, there evolved one person who developed greater skills in the treatment of injuries and diseases, the Cro-Magnon medicine man (Haggard 1934). This medicine man frightened away the evil spirits who were blamed for the unfortunate victim's plight, treated his suffering parts by building smoky fires in which his various “therapeutic agents” were burnt, at the same time moaning mysterious incantations. The patient, flat on his back where the heavy smoke was the thickest, became semi-asphyxiated. This might be termed the first form of “inhalation anaesthesia.”

St. Appolonia was persecuted because of her christian faith, and in punishment for her refusal to renounce her religion, her teeth were knocked out, one at a time (Bruck 1915). This is to indicate the severity of pain experienced while teeth are removed without anaesthesia, and hence the severity of punishment. Of course, later, she was pardoned and granted sainthood.

4Later the narcotic properties of certain plants were discovered. The benumbing or intoxication effect caused by juices of some plants were also utilised. Alcohol in an overdose, had been employed quite often as an agent to produce a state of unconsciousness in which pain of surgery was relieved. Hippocrates, about 450 BC, mentioned in his works that he produced perfect narcosis by having the patient inhale the vapour of bangue.

Galen, the Greek physician and philosopher, about 165 AD, used his anaesthetic agent for extraction of teeth, used the application of “pirethrin” root and strong vinegar, from the action of which, the remaining teeth were preserved by covering them with a layer of wax. The Peruvian Indians chewed cocoa leaves and allowed the saliva laden with extract to drop on the injured part. A modified technique was practised by natives in Africa. The patient chewed the bark of enklovidi tree, swallowing the saliva to deaden pain.

The Egyptians practised compression and many surgeons from time to time used this practice of long-continued “Mechanical Compression” to produce numbness in the part to be operated upon. Hugh of Luca, in about 1250 AD, who was the teacher of Theodoric, used the “spongia somnifera” or sleeping ball to prevent pain.

During the 14th, 15th, and 16th centuries, it was the custom of some of the jailors to give criminals about to undergo torture, a compound of narcotics, which deaden their pain. Guy de Chauliac and Brunus (1350 AD) are the only surgeons who have used narcotics, mostly opium, and “sleeping sponge” to relieve pain during surgical procedures.

Dominique Jean Larry, Surgeon-in-chief, Napolean's Army, at the battle of Eylan, noticed when operating on wounded soldiers who were half-frozen from the intense cold that they felt very little pain. From this discovery arose “Refrigeration anaesthesia”. In 1786, Frederick Anton Mesmer used what he believed to be “ magnetic emanations” to produce state of insensibility to surgical pain (Hollander 1932).

The first truly modern experimental work was done in 1799, when Sir Humphrey Davy, published an account of his researches and experiments with various vapours and gases. Davy observed that the pain caused by an erupting “wisdom tooth” was relieved when he inhaled nitrous oxide. (Davy 1799). Henry Hill Hickman, who follows Davy in the history of anaesthesia, seemed to have had a strong realisation of clinical potentialities of gases as anaesthetics. In 1824, he had performed many surgical operations on animals, which he had rendered unconscious with carbon dioxide (Hickman 1930) (Table 1.1).

Crawford W Long, a physician, removed a tumour from the neck while the patient was under the effect of sulphuric ether, in 1842 (Long 1849). A year subsequent to the discovery of ether, as an anaesthetic, Sir James Y. Simpson, an English Surgeon, demonstrated successfully the anaesthetic properties of chloroform. This new anaesthetic soon became popular in Europe and supplemented ether for a number of years.

Horace Wells, who was a practicing Dental Surgeon, closely observed the sufferings caused to patients while extracting teeth. He had been looking for some agent to alleviate suffering during dental surgical work. Horace Wells gave a considerable thought to the subject of pain relief during extraction of teeth. In an attempt to constantly enlarge his knowledge, he attended a lecture on chemical phenomena by Gardener, D. Colton, a travelling chemist on December 10, 1844. Colton manufactured nitrous oxide, known as “laughing gas” Colton invited spectators from the audience to inhale the “laughing gas fumes”. Wells, in the audience, observed that no signs of pain exhibited when the volunteers under the influence of the gas stumbled around the stage. Soon the idea of inhalation anaesthesia was crystallised in the mind of Wells.

After the lecture, Wells talked to Colton and persuaded him to bring a bag of gas to his office next day. Wells had an aching tooth and intended to have his tooth removed painlessly by inhaling sufficient nitrous oxide. Wells, had the courage of his convictions, and persuaded Colton, despite objection from Colton, because of fear of fatal outcome, inhaled a bag of gas until he lost consciousness. Then his associate and former pupil, John Riggs, extracted the aching wisdom tooth painlessly. Colton administered the laughing gas to Wells. On regaining consciousness, Wells explained “a new era in tooth pulling.” Thus anaesthesia was born on 11th December, 1844. Later, Wells arranged a demonstration through a former pupil and partner, William TG Morton. Dr. Morton was actually a dental student with Wells in Boston who later became associated with him in practice. Unfortunately, for some reason, the demonstration was 6not successful. Later, Wells, continued to use nitrous oxide in his practice and taught others to use it.

Morton received the idea of inhalation anaesthesia from the demonstration given by Wells. He performed some experimental work with ether; and continued to use ether at the suggestion of Charles T. Jackson, physician and chemist of Boston, in place of nitrous oxide. Finally, on 30 Sept, 1846, he extracted a firmly rooted bicuspid tooth in a patient, under the influence of a disguised ether compound. The patient became unconscious almost immediately. He recovered in a minute and knew nothing of what had been done for him.

Nitrous oxide, at first was discredited, however, proved to be a boon to humanity later. It stimulated further experiments with other agents and that led to the final discovery of other anaesthetic agents.

Morton gave a public demonstration of practicability of anaesthesia in the Massachusetts General Hospital in Boston, on Oct 16, 1846. Amongst the several prominent surgeons and physicians present was the Surgeon-in-Charge, John C. Warren, to whom credit is due for giving Wells and Morton the opportunity to demonstrate publicly their anaesthetic agents. The operation involved was the removal of a tumour from the left side of the jaw bone of a young man, performed by Warren. The exhibition of the anaesthetic and the operation was a complete success. The patient after recovery from the slumber exclaimed, “I have felt no pain”. Warren deeply impressed, turned to the audience and said, “Gentlemen, you have witnessed a miracle, this is no humbug”(Rice 1858).

The American Dental Association (ADA), at its 4th annual meeting, in 1864, adopted a resolution wherein the credit and honour of introduction of anaesthesia in USA, was given to Horace Wells of Hartford, (then deceased) (ADA 1864). This resolution was reaffirmed in 1872. (ADA 1872). The American Medical Association in 1870, in its 21st annual meeting, approved the following resolution, “the honour of the discovery of practical anaesthesia is due to the late Dr. Horace Wells, of Connecticut”.

Charles G. Pravaz, a French physician, in 1851, discovered hypodermic syringe. Alexander Wood, a physician from Edinburgh, in 1853, discovered hollow hypodermic needle for subcutaneous injections to relieve neuralgic pains. Both Pravaz and Wood and their contemporaries used the syringe and the needle for injection of morphine, opium and other drugs to alleviate pain and for surgical analgesia.

From 1850-1890, chloroform was used for dental, as well as major surgical operations, as a local anaesthetic. In the mouth, cotton wool saturated with chloroform or ether was held to the buccal and lingual tissues with a small tray like device (Richardson 1860). Refrigeration for local anaesthesia was advocated by Fournier (Fournier 1861-2), who exposed the part to be operated upon to spray of acetic acid and chloroform. He called this process “chloracetisation”.

Narcotic spray was used for local anaesthesia in 1867. However, the pain during and after the production of local anaesthesia was greater than that due to extraction of tooth. Cases of marked sloughing of tissue were also observed.

Claude Bernard, In 1869, injected morphine as a preliminary narcotic before administration of ether or chloroform, the two general anaesthetic agents which became popular at that time.

Castle, in 1872, claimed to have extracted teeth painlessly by “obtunding or benumbing the extremities of temporal nerves”, for a period of 32 years. He used ice to the temples or had his “assistant press for one minute with persistent firmness into the fossa or hollow behind the ridge of temporal bone that forms the external bone circle orbit of the eye (Castle 1872). This was reintroduction of so-called compression anaesthesia practised centuries ago by the Egyptians.

Local anodynes had been in use to reduce the pain of drilling carious teeth.

Subsequently, a new anaesthetic destined to be of major significance—cocaine was discovered. The local anaesthetic effect of cocaine hydrochloride was discovered by Schraff in 1862, when he noted the local analgesic properties of this substance when it was placed on the tongue. Carl Koller, later, in 1884, discovered the local anaesthetic properties of cocaine, and instilled the agent into the eye of frog and guinea pig.

In 1884, William S. Halsted and Hall R.J. utilised this knowledge to block inferior alveolar nerve to remove mandibular teeth. They showed that the injection of nerve trunk with a 4% cocaine solution in any part of its course is followed by loss of sensation in its entire peripheral distribution. Halsted made the injection and Hall was the patient. The first mandibular injection was made at Bellevue Hospital, in New York 8City, in November, 1884, exactly forty years after nitrous oxide was used for the same purpose on Horace Wells by John M. Riggs. Thus, Halsted was the first to have introduced nerve block injections. The nerve he first “blocked” was the inferior alveolar nerve (mandibular nerve). In 1922, the Maryland State Dental Association honoured Dr. Halsted with a gold medal for his original researches and discoveries in local and neuro-regional anaesthesia. Later, Halsted transferred his activities to John Hopkins Hospital.

In 1894, Carlson, and in 1896, Thiesing, both Dental Surgeons, when producing local anaesthesia by spraying ethyl chloride on the gums, observed that several patients became unconscious (Thiesing 1896). This observation prompted Thiesing to make experiments to employ ethyl chloride as a general anaesthetic. In 1896, it passed from dentist's chair to operation theatre in the hospitals.

In 1890, “Pressure Anaesthesia” was introduced into dentistry, by Edwards C. Briggs (Briggs 1891). Many high pressure obtunding syringes charged with 4% cocaine, were advocated for desensitising teeth for cavity preparation and pulpal anaesthesia.

Cataphoresis, a method of anaesthesia, which was discarded 40 years earlier, was reintroduced. The technique was to saturate a piece of cotton with cocaine and the cotton containing electrode is applied to the part to be influenced. A weak current being turned on in the meantime. The part was supposed to become” obtunded “ or “benumbed” (Anon 1896). In some cases the electrode was connected to forceps.

In 1900, Legrand (Legrand 1900) used a mixture of gelatin with his cocaine solution. Gelatin acted as a haemostatic. For the first time the chemical method was employed for achieving haemostasis. The other methods used earlier were application of physical aids such as (i) cold; for its vasoconstriction action and (ii) Pressure; in the form of a tourniquet, around an extremity, effectively limited circulation; thereby definitely retarding absorption of cocaine. However, a great advancement took place when the action of epinephrine was demonstrated by Elsberg, Barber and Braun, when mixed with solution of cocaine.

In 1897, eucaine was used in place of cocaine. In 1901, George B Haycock, used betaeucaine, produced his “Bucaine compound” in tablet form. It was claimed to be superior to cocaine. It was non-toxic; could be sterilised by boiling and solutions could be stored indefinitely.

The intraosseous injections were introduced in England, using procaine hydrochloride as the anaesthetic agent (Masselink 1910). A high-pressure syringe, such as Gunthorpe's, was necessary for this procedure.

9The research and development continued for a better local anaesthetic agent; as cocaine had toxic and irritating properties, which resulted in extensive sloughing of tissues in many cases. A search was made to find synthetic substitute to cocaine, which would possess the anaesthetic properties of cocaine, but without its disadvantages. The contributors were Liebermann, Willstaetter, and particularly Einhorn. It was found that the anaesthetic property of cocaine depended upon the esterification of a basic alcohol with benzoic acid. Einhorn stated the definite principle that all esters of aromatic acids produced a greater or lesser degree of local anaesthesia.

The first attempt to prepare cocaine synthetically was made and resulted in the eucaines, which were synthetically prepared by Merling. Two types, α and β eutacaine; were introduced. Eucaines were subsequently discarded on account of their irritation action, increased toxicity, and less intense anaesthetic action. A more simple class of synthetic local anaesthetic, stovaine, was prepared by Fourneau in1904. Another drug, Elypin, which was prepared by Hoffmann, is chemically closely related to stovaine. These substances, because of their toxicity and irritating action on the tissues were not suitable for local anaesthesia.

Novocaine (procaine hydrochloride) (Procaine is the American name for Novocaine), one of the most popular substitutes was discovered in Germany, by Alfred Einhorn in 1905. However, it was introduced in the practice of medicine by Braun in 1905 (Braun 1905). The first paper in English on the use of novocaine in local anaesthesia was that of Shepley Part (Part 1906), in 1906. Since then, procaine rapidly replaced cocaine as a local anaesthetic. Initially, the drug was supplied commercially in powder or tablet form. The dental practitioner mixed his solution as per his needs. That was a cumbersome, time-consuming and inaccurate method. The idea of using anaesthetic solutions and drugs in cartridges, was first developed by Harvey, S. Cook, a physician in 1940.

In 1933, Cobefrin, an ischaemic agent, for use in local anaesthetic solutions, was introduced in the dental profession by Leo Winter (Winter 1933). Corbasil, the original name for Cobefrin, which is the American name, was first prepared by W. Gruettefien and was first reported in the application for German patent in 1911. Tiffeneau (Tiffeneau 1915) published the first pharmacological report on Cobefrin. However, the most complete study was carried out much earlier by Schaumann, but the results were reported in 1930. The first clinical tests with Corbasil, or Cobefrin, alone and in combination with Novocaine and other local anaesthetics, were carried out by Schaumann in 1933.

11Monocaine was introduced to dental profession by American chemists, Goldberg and Whitmore, who performed a research on PABA esters of monoalkylamino alcohols. Monocaine hydrochloride was introduced at the Dental Clinic of the Ocean Hill Memorial Hospital in 1936, by Mendel Nevin. (Goldberg and Whitmore 1937).

Later, in the middle of 20th century a number of newer local anaesthetic agents were introduced which are popular and commonly used today (Table 1.2). Lidocaine was prepared by Nils Lofgren in 1943 but was introduced in 1948. Propoxycaine was prepared by Clinton and Laskowski in 1952. Mepivacaine was prepared by Ekenstam in 1957 but was introduced into dentistry in 1960 as a 2% solution containing the synthetic vasopressor levonordefrin; and in 1961 as a 3% solution without a vasoconstrictor. Prilocaine was prepared by Lofgren and Tegner in 1953 but was reported in 1960. Articaine was prepared by Rusching, et al in 1969 but was introduced in 1978 in the Netherlands, in 1980 in Austria and Spain, and in 1983 in Canada. Bupivacaine was prepared by Ekenstam in 1957. Etidocaine was prepared by Takman in 1971.

As Nevin has pointed out that it is a matter of great pride to the dental profession that Horace Wells first discovered, demonstrated, and proclaimed the blessings of surgical anaesthesia and William TG Morton two years later successfully introduced ether anaesthesia. While Nevin and Nevin have pointed out that it is paradoxical that two dental practitioners, Horace Wells and William Morton discovered inhalation anaesthesia, which is mainly used by physicians; while a physician Koller, to whom belongs the honour of discovery of anaesthetic properties of cocaine and another physician, Halsted, who was 12 the first one to introduce block anaesthesia, which is universally used by dental practitioners.