Presented to the meeting of SAMHS at the Calvary Hospital on 15 September 2005 by Dr. W.R. Fuller.

Introduction

Today, we naturally think of surgery and anaesthesia as being hand in glove. In the words of a popular song of some years ago, you can't have one without the other. But this hasn't always been the case. Next month, on October16, general anaesthesia will be 159 years old. In contrast, the beginnings of surgery are buried in the realms of antiquity. Surgeons, perhaps with tongue in cheek, will tell you surgery began in the Garden of Eden when God removed a rib from Adam. Mind you Genesis also informs us that God put Adam into a deep sleep first so perhaps anaesthesia can also claim such antiquity and God may thus have been the first "sole" anaesthetist / surgeon.

Seriously though, more substantive evidence exists as to the antiquity of surgery. In the National Museum of Copenhagen (1) there are skulls displayed with nice neat round holes bored in them. The edges of these holes do not consist of cancellous bone but smooth compact bone. This means bone healing had occurred indicating their owners were alive when the operations were performed and since healing doesn't occur overnight presumably survived them. These skulls are those of Neolithic man and date from something like 5000 years BC. The purpose of these operations, whether medical or magical, remains unknown. In the Peabody Museum at Harvard University (2), Cambridge , Massachusetts is an excavated mandible of an Egyptian mummy dating from 1000 to 2000 BC with two holes drilled in it. These appear to have been done to drain an abscess which had formed at the base of some carious teeth. Here we have surgery for medical reasons. Ancient writings from the Indian sub-continent dating from the 4th century AD describe a method of restoring a lost nose by rotating a skin flap from the forehead (3). Since cutting off the nose was an official punishment for such misdemeanours as theft, assault, fraud and adultery I would suggest the Indian surgeons of the time would have gained plenty of practice in performing such reconstructions.

In spite of its antiquity the progress of surgery through the centuries was slow, limited as it was by lack of effective pain control and devastating post operative infection. Many attempts were made to overcome the pain problem with use of such analgesic, soporific and narcotic agents as opiates, extracts from plants containing hyoscyamus, mandragora and alcohol. Concussion and hypnotism (mesmerism) were also tried but none of these measures were uniformly or completely successful. Surgery remained literally very superficial and very quick. The patients were simply held down by assistants and the surgeons got on with it. Those most in demand were the fastest. The shortest time recorded for a leg amputation is 13 to 15 seconds by Napoleon's chief surgeon, Dominique Larrey(4). Legend as opposed to historical fact has it that it is a record that is unlikely to be emulated as it also included the forefinger of the assistant and one of the patient's testicles.

Of the early anaesthetic agents, nitrous oxide, a gas, was discovered by Joseph Priestley in 1772 (5). Later it was used as a party drug and the basis of a stage act because of the sense of euphoria it produced when inhaled. It thus became known as laughing gas. In 1799, Sir Humphrey Davy of mining lamp fame, noticing a reduced sense of pain in such revellers, suggested it might be useful in surgery (6). The suggestion wasn't taken up. In 1844, Horace Wells, a Connecticut Dentist, heard of the properties of nitrous oxide and had one of his own teeth extracted under its influence. Pleased with the result, he tried it on several of his patients and then persuaded a Harvard surgeon, John C. Warren, to let him demonstrate its properties during one of the surgeon's classes. The patient cried out with pain during the procedure, Warren is said to have exclaimed "This is Humbug," and Wells was denigrated as a charlatan (7).

Ether was actually discovered as a chemical compound by Valerius Cordis in 1540. It wasn't until three centuries later that interest in ether as a possible preventer of surgical pain developed. Like nitrous oxide before it, it became a party drug. In 1842, an American general practitioner from the state of Georgia, Crawford W. Long, noting its party effects, became interested in its possible use as an adjunct to surgery. He used it successfully for several minor procedures. Unfortunately, for unknown reasons, he did not publish his results until several years after ether was rediscovered and developed properly. This rediscovery occurred when William T. G. Morton, a dental associate of Horace Wells, became interested in ether (8). He practised not only on himself but also on the family dog, cat, hens and rats and finally successfully extracted a tooth under ether. At this time in addition to continuing his dental practice, he had also become a student in the Harvard Medical School . Following his above success with a tooth extraction he persuaded a surgeon, again John C. Warren, to attempt surgery under its influence. This event took place on the 16th. October 1846 in the subsequently named and famous Ether Dome at the Massachusetts General Hospital in front of a very skeptical audience. The demonstration was a complete success. This time Warren exclaimed "This is no humbug."

Considering the fact that the only method of communication between the US and the rest of the western world was by ship the news spread rapidly. Some eight weeks later on Saturday the 19th December, a dentist, James Robinson extracted a tooth under ether in London . Two days later Robert Liston performed a leg amputation in what is now the University College Hospital (9).

The news took a little longer to reach Australia . In fact the first Newspaper reference to Anaesthesia appeared in the "South Australian" here in Adelaide on May 4, 1847 . This news had arrived the previous day in Port Adelaide courtesy of the good ship "Lightning". The ship carried much wanted news from "home” in the form of British newspapers which had travelled the overland route via England , Alexandria , Suez , Galle in Sri Lanka , and Singapore with the last leg to Port Adelaide being provided by the Lightning.

The news actually reached Sydney some 5 days before this being carried by a ship which had travelled via the Cape of Good Hope . Strangely, the use of ether for surgery was not published there until May 18. Shortly after this report, a Sydney dentist, Mr Bellisario, used it to carry out painless tooth extractions. This was the first use of ether in Australia and occurred around the end of May and the beginning of June 1847.

The first use of ether for a surgical procedure was by Dr. William Russ Pugh, a Launceston General Practitioner, on June 7, 1847 . The way in which the news reached him seems clear. Pugh himself recorded that he built his apparatus for administering ether from a sketch in the "Illustrated London News" of January 9, 1847 . This arrived in Hobart on the ship "Lady Howden" and was carried to Launceston by coach, arriving there on May 29 (10).

Adelaide may have been the first in Australia to publish news of anaesthesia but was the last of the settlements to actually use it. The first report of an anaesthetic being given in South Australia appeared in the local paper the "South Australian" on Friday, October 1, 1847 . It was stated that on the previous night an operation for the cutting off of a cancerous breast was performed by a Dr. Kent and a Dr. Bayer with Bayer performing the excision and Kent administering the ether (11).

It is interesting to note that in October when Morton first publicly demonstrated the effects of ether the term anaesthesia was not known. They used such names as etherisation, narcotism, and stupefaction, to name a few. It was in fact Oliver Wendel Holmes who suggested the terms anaesthesia, anaesthetic and anaesthetist. In his own words in a letter to Morton he writes "The state should, I think, be called "anaesthesia". This signifies insensibility, more particularly (as used by Linneas and Cullen) to objects of touch. The adjective will be anaesthetic" (12). Obviously his suggestion was adopted although the Yanks, having never been much into diphthongs, spelt them "anes" rather than using Holmes spelling of "anaes. " He obviously appreciated their classical origins. Anesthesiologist came later ostensibly to distinguish between those who administered anaesthesia without necessarily being medically trained and medical doctors who specialised in using it. I wonder though if a further reason may have been due to them having difficulties in pronouncing anaesthetist. Anesthesiologist rolls off the tongue much more easily.

Chloroform was prepared independently in 1831 in Germany by Justus von Liebig, a chemist and famous teacher of chemistry, in France by Eugene Soubeiran, a pharmacologist, and in America , by Samuel Guthrie, a physician and experimenter in practical chemistry. In 1835, a distinguished French chemist, Jean Baptiste Andre Dumas, described its physical and chemical properties and gave it the name of chloroform. Early in 1847, the French physiologist, Jean Pierre Flourens, found it had anesthetic properties in animals. In the same year in Edinburgh , Dr. James Young Simpson had become interested in looking for another substance with anaesthetic properties that was more pleasant to inhale than ether. He tried various volatile agents unsuccessfully but at the suggestion of a colleague, David Waldie, an Edinburgh surgeon and medical scientist, he tried chloroform. His trial consisted of inviting several friends around to dinner and before starting to eat, they all had a good sniff of chloroform. When they all woke up recumbent upon the dining room floor, Simpson reasoned that chloroform was the substance he was looking for. He then introduced it into clinical practice on November 4th. 1847 by successfully relieving the pains of labour and childbirth (13). This did meet with some opposition from the Calvinistic clergy who considered that child birth wasn't meant to be easy and quoted Genesis 3:16 in which Adam and Eve were instructed "In sorrow thou shalt bring forth children" . Simpson countered by quoting Genesis 2:21 which described Adam being placed into a deep sleep to have a rib removed. He argued that since the latter quote preceded the former relieving the pain of childbirth was acceptable. Nevertheless, it wasn't until 1853 when John Snow used chloroform during the birth of Queen Victoria's eighth child that it became generally accepted (13).

Because induction of anaesthesia with chloroform was more pleasant, more rapid and easier than with ether it initially enjoyed a greater popularity all over the world. In the United states , this only lasted a year or two partly because they were worried about its safety but also for patriotic reasons. In The UK and Europe this popularity continued for a number of years. In hind sight, perhaps, more significance should have been given to the first recorded anaesthetic death. It occurred on the 28th. January, 1848 only a little under three months after the introduction of chloroform. The patient was a fifteen year old girl named Hannah Greener. She was given chloroform and collapsed and died before her operation commenced.(14) Argument as to its safety gradually increased. More and more reports of sudden death while under its administration started to appear in the Journals. Reports of post operative liver problems also raised concerns.

Eventually with its safety under question, two Commissions to look into its use and safety were convened, the first in 1888, the second in 1889 (15). Both of these took place in Hyderabad in India at the instigation of Surgeon Major Edward Lawrie. The majority of the attendees were in favour of chloroform and produced anecdotal accounts of the large numbers of anaesthetics which they had given without problems. The second commission, however, was attended by representatives of the Lancet. When this commission reported in favour of chloroform, the Lancet and many clinicians in England and Europe were particularly critical of this conclusion. Subsequently, the use of chloroform gradually waned and ether, although as an induction agent slower and more difficult to use, became once again the preferred agent. Chloroform continued to be used, however, well in to the 20th Century either straight or in the form of the famous azeotropic ACE mixture (ethyl alcohol 1 part, chloroform 2 parts and ether 3 parts). It was commonly believed (erroneously) that chloroform was safer when used for the relief of pain in obstetrics and here in Adelaide 1, as a medical student, witnessed the administration of chloroform to a woman in labour at the Queen Victoria Hospital in 1951.

It should also be noted that around 1800 a Japanese Surgeon, Seishu, developed a general anaesthetic which he called Tsusensan. In 1804 he was able to use it to successfully to perform a mastectomy. The anaesthetic technique involved oral administration, was dangerous and difficult to use. It tended to cause long lasting unconsciousness and here we're talking 24 hours plus. Seishu was well aware its toxicity and as a result refused to publish his technique. Thus only his students who received personal and painstaking tuition were able to learn the technique. Tsusensan was in fact aconite and therefore far too toxic to have ever achieved widespread use as an anaesthetic agent. (Ref. Professor Shizu Sakai: The introduction of western medicine in Japan . Paper presented at 9th Biennial Conference of the Australian Society of the History of Medicine in Auckland February, 2005.)

The elimination of pain alone was not enough to stimulate the successful expansion of surgery. In fact surgery went backwards in some respects because with the control of pain surgeons delved more deeply in to the human body with disastrous results because of severe post operative infection. It still needed the pioneering work in 1860 of Louis Pasteur (1822-1895) on bacteria, the resulting development of the germ theory of disease, and the insight of the British surgeon, Joseph Lister for this to happen. Having heard of Pasteur's work he recognised the possibility of bacteria being the cause of the inevitable post operative development of purulent broken down wounds. Where Pasteur had used heat to kill these microorganisms Lister used carbolic acid, spraying the body surface and subsequent layers with dilute solutions of it before incising them. He published his work in the Lancet in 1867 following which this antiseptic technique of achieving sterility became widely but not completely accepted throughout Europe (16). The surgeons of the United States were not so keen on the idea. They were against the concept of using carbolic and concentrated their arguments on this thus tending to miss the basic principles upon which its use was based. Other surgeons, such as Lawson Tait in the United Kingdom , while denigrating the use of carbolic and not believing the germ theory, used strict rules of cleanliness effectively. Thus the so called aseptic technique still in use today came to be developed.

The Lancet of February 17, 1912 in Lister's obituary stated intriguingly that Lister "raised English surgery to a pinnacle from which not even the presumptuous ignorance of politicians will be able to take it down "(17). It also commented on hospital surgical wards pre Lister saying that they were, "veritable pest houses, from which escape with life could hardly be regarded as probable. It seems scarcely credible today, but it is none the less true, that only half a century ago it was gravely proposed that surgical hospitals should be temporary buildings, which should be destroyed by fire, as dangerous nuisances, after the fulfillment of two or three years of existence, or as soon as gangrene became of common occurrence among their inmates."

The gate for the surgeon had now been opened. The limits it seemed were endless. On the other hand general anaesthesia, relatively speaking, remained rather more static for nigh on a hundred years. After the initial introduction of ether and then in quick succession chloroform, other agents with anaesthetic properties were also introduced with varying success but were never able to take over from ether as the preferred agent for maintenance of general anaesthesia. At least not until the advent of halothane in 1956. New volatile agents with anaesthetic properties included ethyl chloride (1894) (18), divinyl ether (1933) (19), and trichloroethylene (1934) (20). Gases with anaesthetic properties were also introduced. Apart from rediscovering a role for nitrous oxide (1844) (21), the gas ethylene (1923) (22) and cyclopropane (1933) (23) also surfaced. Nitrous oxide achieved success in dental surgeries although its initial effect when given in high concentration of producing rapid loss of consciousness was more due to the production of acute anoxia than the effects of the gas. Nevertheless, the quick gas for the tooth extraction continued into the 1950's. It also became widely used (and still is) as an analgesic for pain relief in labour. It was too weak an anaesthetic agent to be successful in its own right but, since the 1940's, has achieved universal use as a carrier for more potent agents. The desirability of this practice is only now being seriously questioned. Ethyl chloride achieved popularity as an agent for the induction of anaesthesia with the anaesthetic then being continued with ether. This technique remained popular particularly with children right up to the 1960's. The others enjoyed limited success only and with the possible exception of trichlorethylene and cyclopropane never achieved widespread use. Cyclopropane although having some advantages particularly in patients requiring rapid induction with high inspired levels of oxygen and maintenance of normal blood pressure during surgery never overcame the fact that it is flammable and explosive.

Hexobarbitone was successfully introduced in 1932 (24) as an intravenous anaesthetic agent but the subsequent introduction in 1935 (25) of thiopentone led to its gradual demise. Thiopentone had early problems which came to light particularly during the Japanese attack on Pearl Harbour . It has been said with some justification that more American service personnel died from the effects of pentothal than from the direct effects of the bombs and bullets. Why? In 1941 anaesthesia tended to be one drug does all. That is induction and maintenance. Pentothal was marketed as 1G of powder to be dissolved in 20 ml of water. That is a 5% solution rather than the current 2.5 %. And it was common for most if not all of the 20 mls to be given during induction. Fit young troops would normally handle this without much difficulty. Anaesthetising them in a situation where significant blood loss has been compensated for by a reflex peripheral vaso constriction is a disaster waiting to happen. With lessons learnt pentothal became the standard drug for induction of anaesthesia and remained the flavour of the month almost to the end of the 20th century; a popularity which has now been significantly challenged by another agent, propofol.

Other achievements in the first hundred years of anaesthesia included the development of the forerunners of the modern anaesthetic machine with flow meters and vaporizers. These led to the more accurate administration of oxygen and anaesthetic agents. The introduction to clinical anaesthesia of CO2 absorption and the rebreathing circuit by Ralph Waters in 1924 (26) enabled economies to be made and facilitated the use of artificial ventilation during anaesthesia . Nevertheless, ether still remained the main general anaesthetic agent in use, the patients still by and large were expected to breath spontaneously and surgical relaxation such as it was depended on producing deep levels of unconsciousness. Although over the years many ether vaporisers were developed and successfully used the original technique such as dropping ether from a bottle on to a gauze cloth spread over a wire frame placed over the mouth and nose were still commonplace here in South Australia right up to the 1960's. I in fact I gave my last open ether anaesthetic using this technique in1965. So although of value, the introduction of the newer agents and advances in technology and understanding should probably be considered to be more a matter of smoothing out the wrinkles and rounding off the edges rather than representing highly significant advances in general anaesthesia.

In fact, the next major advance in anaesthesia occurred in 1942 with the introduction of the muscle relaxant, d-Tubocurarine (curare) by Dr. Harold Griffiths in Montreal . (27) For surgeons to operate successfully and achieve the best results consistently they require a still, quiet field of operation with relaxed muscles that do not resist their need to spread or stretch them in order to expose the diseased site. Before muscle relaxants the achievement of anything approaching this situation required deep levels of anaesthesia. The deeper the anaesthetic and the longer the operation the longer to wake up, the greater the length of time before self protective laryngeal reflexes returned to full capacity and the greater the chance of complications developing post operatively. Muscle relaxants achieve the desired relaxed operating field quickly, simply and without the need for deep anaesthesia. Thus patients need only be lightly anaesthetised. They wake up more quickly and more safely and with less of a hangover effect. To handle the respiratory muscle paralysis the relaxants also enabled the machines and circuits developed over the 1920's and 30's to now came into their own. The greater accuracy with which agents could be administered and the greater ease with which artificial ventilation could be established helped deliver the improved surgical conditions safely.

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