Part 8

The next epoch-making event in the history of anæsthesia was the discovery of the anæsthetic properties of chloroform. The substance itself had been known for over a quarter of a century. Thomson, in his “System of Chemistry,” 1820, describes a liquid which is formed by the union of chlorine and olefiant gas, called “Dutch liquid,” or chloric ether. Early in the year 1831, Samuel Guthrie of Brimfield, Massachusetts, who was then residing in Sackett’s Harbour, New York State, in consequence of a statement that he had read that the alcoholic solution of this chloric ether was useful in medicine as a diffusible stimulant, devised an easy method of preparing it. This being done, he wrote an article which he entitled “A Spirituous Solution of Chloric Ether,” and forwarded it to the editor of the “American Journal of Science and Art,” in which it was published in October of the same year. In this article he fully describes his method of preparation. A few months later, in January, 1832, Soubeiran published a paper in a French journal, stating that he had discovered this method in 1831, and to the distilled fluid he produced he had given the name of “bichloric ether,” the formula being CHCl. Still a third claimant to the discovery came forward in the person of Liebig, who published his account in November, 1831, six months after Guthrie’s manuscript was in the publisher’s hands, and one month after its publication. The formula which Liebig deducted from his analysis was C{4}Cl{5}, and he called his product “chloride of carbon.” Although there may be some doubt as to which of these claimants was actually the first to manufacture the liquid, it is clear that Guthrie was the first to publish the account of the discovery. He was born in 1782, was a surgeon in the United States Army in 1812, and died in 1848.

From an account given by D. B. Smith, of Philadelphia, in the “Journal of the College of Pharmacy” in 1832, there can be little doubt that the liquid first made by Guthrie was a fairly pure chloroform. He describes it in the following words: “The action of this ether on the living system is interesting, and may hereafter render it an object of importance in commerce. Its flavour is delicious, and its intoxicating properties equal to or surpassing those of alcohol.” In 1834, Dumas examined the liquid as prepared by Soubeiran, and declared that he had not obtained it pure, and further, that Liebig had made an error in its composition. On further research, Dumas gave the liquid the name of “chloroform,” and first worked out the real formula, C{2}HCl{3} (or, using the present system of atomic weights, CHCl_{3}).

Now the “American Journal of Pharmacy”

Although its narcotising properties were known to some extent, no one who used it at that time seems to have conceived the idea of fully testing its properties. In 1831, Ives, of Newhaven, treated a case of difficult respiration by actual inhalation of the vapour, and published the facts in “Silliman’s Journal” in January, 1832. Four years later, Dr. Formby, of Liverpool, prescribed it in hysteria; and Tuson, of London, employed it in the treatment of cancer and neuralgia in 1844.

The fact that one or two deaths had been attributed to the use of ether about this time, caused many workers to make a search for other agents with similar properties. Foremost among these investigators was Dr. James Young Simpson, Professor of Midwifery in the University of Edinburgh, who personally experimented with several chemical liquids in the hope of finding something less disagreeable and persistent in smell than ether.

About this time, Jacob Bell, a chemist, and a founder of the Pharmaceutical Society, published a suggestion that chloric ether should be used for inhalation instead of sulphuric ether; but his suggestion was apparently never put into practice. In October, 1847, Waldie, a chemist of Liverpool, was visiting Edinburgh, and in conversation with Professor Simpson, suggested to the latter the use of chloroform. He recommended the Professor to try it as an anæsthetic, and promised to make and send him some on his return to his home in Liverpool.

It appears to have been in that city that the drug was first introduced and probably first used in England as a medicinal agent. Waldie states that about the year 1838 a prescription was brought to the Apothecaries’ Hall, Liverpool (where he held the position of manager), of which one of the ingredients was chloric ether. The preparation was at that timen apparently not known in this country, for Dr. Brett, the chemist of the Company, specially prepared some from the formula he found in the United States Dispensatory. Its properties pleased some of the medical men, particularly Dr. Formby, by whom it was introduced into local practice. Waldie, finding that the preparation was not uniform in strength, improved the process by separating and purifying the chloroform, and dissolving it in pure spirit, by which a product of sweet flavour was obtained.

There seems little doubt that Waldie was the first to suggest the use of chloroform, as an anæsthetic, to Professor Simpson, who at once resolved to try it by experimenting on himself and his assistants. He made the first experiment in his own house on November 4th, 1847, and in a letter written to Waldie thus describes the event: “I am sure you will be delighted to see part of the good results of our hasty conversation. I had the chloroform for several days in the house before trying it, as, after seeing it such a heavy, unvolatile-like liquid, I despaired of it, and went on dreaming about others. The first night we took it, Dr. Duncan, Dr. Keith and I all tried it simultaneously, and were all ‘under the table’ in a minute or two.” Professor Miller, who was a neighbour of Simpson’s, used to come every morning to see if the experimenters had survived! He describes how, “after a weary day’s labour, Simpson and his assistants sat down and inhaled various drugs out of tumblers, as was their custom. Chloroform was searched for and found beneath a heap of waste paper, and with each tumbler newly charged the inhalers resumed their occupation. . . . A moment more, then all was quiet; then a crash. On awakening, Simpson’s first perception was mental. ‘This is far stronger and better than ether,’ said he to himself. His second was to note that he was prostrate on the floor, and that among the friends about him there was both confusion and alarm. Of his assistants, Dr. Duncan he saw snoring heavily, and Dr. Keith kicking violently at the table above him. They made several more trials of it on that eventful evening, and were so satisfied with the results that the festivities did not terminate until a late hour.”

On November 10th, 1847, Simpson communicated his discovery to the Medico-Chirurgical Society of Edinburgh, in a paper entitled, “Notice of a new anæsthetic agent as a substitute for sulphuric ether.” A day or two afterwards an arrangement was made with Simpson to administer the new anæsthetic to a patient who was about to be operated upon, but, owing to some cause, he was unable to be present. The operation went on without him, and the patient died on the first incision of the knife. Simpson’s absence was providential indeed, for it saved the reputation of chloroform at the outset. On November 15th, chloroform was used for the first time in a surgical operation in the Edinburgh Royal Infirmary. Three patients were operated on successfully under its influence. One, who was a soldier, was so delighted with the effect that, on awaking after the operation, he is said to have seized the sponge with which administration had been made, and, thrusting it into his mouth, again resumed inhalation more vigorously than before.

To Simpson, there is no doubt, belongs the merit of having made anæsthesia triumph over all the opposition, which was at first, actively, offered to its use. For this he well deserved the rewards which fell upon him in the evening of his life.

Among those who aided in the establishment of the use of anæsthetics, mention must be made of the work of John Snow, who by his researches placed the practice on a scientific basis.

The advent of chloroform gave an impetus to other investigators in the field of anæsthesia, and during the last fifty years many other bodies have been introduced and tried with more or less success for the same purpose. Methyl chloride, which was discovered by Dumas and Peligot, was introduced by Deboe in 1887, who used it extensively in local affections. In 1867, Sir B. W. Richardson introduced methyl bichloride or methylene [methylene dichloride]. He formed a very high estimate of its properties as a good general anæsthetic, and said he preferred it for many reasons to chloroform, as he found that the anæsthetic sleep was produced more quickly and was more prolonged.

Sir T. Spencer Wells also advocated its use, and stated, in 1872, that it had fewer drawbacks than any then known anæsthetic. Tetra-chloride of methyn [carbon tetrachloride], which much resembles chloroform, was discovered by Regnault in 1839, and its anæsthetic properties were first made known by Sansom and Harley in 1864. Simpson was of the opinion that it had a more depressing effect upon the heart than chloroform, and was more dangerous generally as an anæsthetic.

Nunneley, of Leeds, also contributed work of value in this department of research, and introduced ethyl bromide and chloride of carbon. He dispelled the idea, long prevalent, that anæsthetics could be found only in a limited class of chemical compounds.

Among other substances which have been introduced during the last twenty-five years, but which, owing to one defect or another, have since been practically abandoned, mention should be made of butylic hydride [butane], ethylene, amylene, ethyl nitrate, aldehyde (introduced by Poggiale), carbon bisulphide, ethidene dichloride [ethylene dichloride] (discovered by Regnault and first used as an anæsthetic by Snow), and ethyl bromide, first prepared by Serullus in 1827.

LOCAL ANÆSTHETICS

Local anæsthesia, already alluded to as probably the earliest form of numbing sensibility to pain, was practised in antient times by the inunction of various narcotics, but after the seventeenth century the practice seems to have almost entirely gone out of use. The latter end of the nineteenth century, however, marks a new era in this department.

On September 15th, 1884, considerable interest was aroused by a communication made at the Ophthalmological Congress at Heidelberg, by Karl Koller, of Vienna, in which he demonstrated the effects of cocaine as a local anæsthetic.

The alkaloid now known as cocaine was isolated by Gädeke, from the leaves of the Erythroxylon Coca as far back as 1855. He called it ethroxylene. Four years later a further investigation of the plant was made by Nieman, who noticed that the leaves produced a numbness of the tongue; and in 1874 Hughes Bennett demonstrated that cocaine possessed anæsthetic properties. In 1880, Von Anrep, who made a careful investigation of the drug, hinted that the alkaloid might be of use in general surgery as a local anæsthetic, and Koller undertook a series of experiments on animals in the laboratory of Professor Stricker, in which he found that complete anæsthesia of the eye, lasting, on an average, ten minutes, followed the introduction of a two per cent. solution of the alkaloid.

The immense value of such an anæsthetic in ophthalmic operations was universally recognised, and it at once came into general use. In painful conditions of mucous surfaces, and for minor operations, cocaine has been found of great service, and as a local anæsthetic it has a large field of usefulness. Since the introduction of cocaine, other substances have been brought forward, which, after extensive trials, have proved to be of real clinical value. Of these may be mentioned eucaine, a synthetic product (benzoyl-vinyl-diaceton-alkamine) discovered by Merling, and first studied by Vinci in Liebreich’s laboratory. Of the two forms of this drug used, which are known as A and B, the latter was soon found to be the only one suitable for producing local anæsthesia. Its properties are similar to those of cocaine, with the exception that it produces no vaso-constriction, and it is claimed that it is equal in anæsthetic power, whilst its toxicity is very much less.

Stovaine, or benzoyl-ethyl-dimethylaminopropanol hydrochloride, more recently introduced, is a synthetic product elaborated by Fourneau, and derived from tertiary amyl alcohol. It is much less toxic than cocaine, but its comparative value still remains to be proved by further trial. Tropa-cocaine, a drug closely allied to cocaine, and derived from the leaves of the Java coca plant, has recently been much used in Germany, but it does not appear to possess any advantages over cocaine or eucaine.

Novocaine, or para-amido-benzoyl-diethylamino-ethenol hydrochloride, has lately been found to possess satisfactory properties as a local anæsthetic in dental operations. It is said to be free from the toxic and local irritant action common to other local anæsthetics.

THE NECESSITY FOR ABSOLUTE PURITY IN CHLOROFORM

Considerable attention has been directed to different methods of administering chloroform, and various forms of apparatus have been devised which claim to reduce to a minimum the dangers of anæsthesia. Assuming a most skilled and competent administrator, an ideal method of administration, and a suitable patient, an unsatisfactory result can only be attributed to the chloroform employed. Purity of chloroform is a most important factor in contributing to safe anæsthesia. The physician claims that absolute purity shall characterise all medicinal agents, and the justice of the claim is acknowledged by the trend of recent legislation. Purity is a prime essential of any anæsthetic. The presence of impurities largely increases the risk inseparable from the use of chloroform. The train of symptoms observed during the normal process of anæsthesia may be masked and altered, and dangerous results may supervene under the most competent, careful and observant administrator.

That some of the chloroform offered to the profession may reasonably be regarded with suspicion is evidenced by the words of a prominent obstetrician, based on the experience of 40 years in the use of chloroform; this authority expresses himself as follows: “I may say I fear the chloroform in common use is often far from being as pure as it should be, and is sometimes very defective in this respect.”

Impurities may result from the process of manufacture, or from decomposition. Conspicuous amongst these undesirable elements are chlorine, hydrochloric acid and carbonyl chloride (phosgene), which irritate the lining membrane of the respiratory tract and interfere with the normal process of respiration. Such irritation may result in arrest of cardiac action or may produce a severe form of bronchitis. It is obviously of great importance that chloroform should be free from irritating properties, that the respiratory passages should not be obstructed, and that during anæsthesia the breathing and the circulation should approximate the normal. Superadded to these results, produced by local irritation, is the effect of other impurities which exert their action after absorption. These latter markedly increase the cardiac depression which has been shown to follow the administration of pure chloroform. Such an action is difficult of detection, and is, probably, in large degree responsible for a considerable number of the accidents reported.

Of recent years increased knowledge has elaborated exact tests, which ensure the absence of these impurities. Nevertheless, anæsthetists of wide experience have obtained results which could not be reconciled with the use of pure chloroform. It has been observed that different chloroforms, all of which answer the official tests for purity, give effects which are difficult to harmonise, and the interpretation of which only appears satisfactory on the assumption that the chloroforms differ in composition. Whilst one chloroform acts most satisfactorily, another produces, during the early stages of administration, a marked excitement and an irregularity of breathing, which prolongs the period of induction. Further investigation has therefore been deemed necessary, and a comprehensive and careful research has elucidated the cause of these hitherto unexplained phenomena (Wade and Finnemore, “Journal of the Chemical Society,” 1904, 85, 938). In the chloroforms which produced anæsthesia in a satisfactory manner, has been demonstrated the presence of ethyl chloride in minute and varying quantities. When the undesirable effects were noted, no ethyl chloride was detected in the anæsthetic. A physiological test conclusively proved that ethyl chloride was the factor which determined these differences.

A chloroform which had previously given undesirable effects, and in which the presence of ethyl chloride could not be demonstrated, was modified so as to contain a small proportion of the latter. The chloroform then proved a most satisfactory anæsthetic, and there was entire absence of the excitement and respiratory irregularity previously observed. The results of this research are of the utmost value. In the initial stages of the induction of chloroform anæsthesia, the presence of a small quantity of ethyl chloride has a beneficial effect, leading to the absence of mental excitement, and steadies the breathing. The respiration is stimulated and becomes regular and deep. In these circumstances, satisfactory anæsthesia is induced with rapidity and ease.