"On the vapour of amylene"

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By John Snow, M.D.

We are indebted for the agents which have hitherto been inhaled for the prevention of pain rather to a number of accidental circumstances, than to any systematic and well-regulated investigation. In the course of his experiments on nitrous oxide gas, Sir Humphrey Davy found that severe pain arising from inflammation of his gums was relieved by breathing it, and he published the following opinion in the first year of the present century:--"As nitrous oxide in its extensive operation seems capable of destroying physical pain, it may, probably, be used with advantage during surgical operations in which no great effusion of blood takes place."* (*Researches concerning Nitrous Oxide, p. 556.) This sentence was read by hundreds, and listened to at public lectures by thousands, for the period of forty-four years, without any result, when the late Mr. Horace Wells, a dentist of Hartford, Connecticut, being present at a lecture by a Mr. Colston, was induced to request the lecturer to accompany him to his office, and to exhibit the gas to him, while another dentist, named Dr. Riggs, extracted a tooth which was troublesome. The tooth was extracted without pain, and Mr. Wells, after the effect of the gas had subsided, exclaimed, "A new era in tooth-pulling!" Mr. Wells administered the nitrous oxide in thirteen or fourteen cases of tooth-drawing, in Hartford, with a success more or less complete; and before the end of the year he repaired to Boston, to introduce his discovery to the Professors at the Massachusetts General Hospital. For want of a more important operation, the gas was tried in a case of tooth-drawing. The patient felt some pain, and the application was considered to be a failure. Mr. Wells returned to Hartford in disappointment. He expressed his opinion to his friends that nitrous oxide gas was uncertain in its effects, and not to be relied on; and he altogether abandoned the use of it until some time after Dr. Morton's discovery of the effects of sulphuric ether in preventing pain.

Ever since 1818 the vapour of ether had been known to produce exhilarating effects, similar to those of the laughing gas. The circumstance was mentioned in nearly all the standard works on Chemistry; and it was the practice for the Medical Students in many of the Colleges, both in England and America, to inhale ether on the day of the lecture on that medicine. Dr. Morton, a dentist of Boston, had been formerly in partnership with Mr. Horace Wells, and had been [60/61] present at his unsuccessful attempt to apply the nitrous oxide in the Hospital. On September 30, 1846, Dr. Morton administered the vapour of sulphuric ether successfully in a case of tooth-drawing, and shortly afterwards he administered it with success in some Surgical operations in the Massachusetts General Hospital. He thus established the power of sulphuric ether to prevent pain in the very institution where Mr. Horace Wells had failed in his attempt to introduce the nitrous oxide. Dr. Morton had apparently received some information respecting ether from Dr. Charles Jackson, Professor of Chemistry, but to Morton the merit is entirely due of introducing the practice of preventing the pain of Surgical operations. This is certainly true of modern times, and, probably, of all times to which history extends; for I believe that the use of mandrake by the Greeks and Romans, and of Indian hemp by the Chinese, must have been attended only with slight success in Surgical operations. I need hardly remind the Society that the inhalation of ether was soon extended to the prevention of pain in obstetric cases and a number of diseases, as well as in Surgical operations.

A medicine called chloric ether has been in use since 1831. It was first applied by inhalation with success in preventing pain by Mr. Jacob Bell, of London, early in 1847; and it was exhibited afterwards with occasional success in St. Bartholomew's and the Middlesex Hospitals, and in the private practice of Mr. Lawrence. This miscalled chloric ether is a solution of chloroform in spirit, and the insensibility it occasions when inhaled is entirely due to the chloroform, of which it contains about twelve per cent. Mr. Waldic, of Liverpool, being in Edinburgh in the autumn of 1847, explained these circumstances to Dr. Simpson, who had been the first to apply inhalation in the practice of midwifery, and was at the time paying great attention to the subject of anæsthesia. Dr. Simpson procured the chloroform in its undiluted state, and was the first to exhibit it in this condition, and the public and the Profession are indebted to him for its introduction to general use. Chloroform was immediately adopted, to the almost entire exclusion of ether, and has continued to keep its place, with a few exceptions, to the present time. At the Massachusetts General Hospital the use of chloroform was prohibited by the governors three or four years ago, on account of two accidents; and sulphuric ether has since been used, to the entire exclusion of chloroform. Ether is the agent employed in private practice in the town of Boston; and I have been informed that this is the case at Philadelphia, and in Europe, at Naples and Lyons.

Ever since the introduction of chloroform I have been of opinion that other agents would be met with more eligible for causing anæsthesia by inhalation. It seemed improbable that this one, which happened to be standing on the shelf of the Pharmaceutical Chemist for another purpose, should be better than all the very numerous volatile compounds which organic chemistry is daily bringing to light; and the continued use of chloroform is probably due to the circumstance, that hardly any one has made anæsthesia by inhalation a subject of constant and protracted investigation. I have from time to time made experiments on animals with a variety of substances, and I find that the agents which might be inhaled for the prevention of pain, in the absence of others which are more eligible, are extremely numerous. They include, among other things, carbonic acid and carbonic oxide gas, olefiant gas, the vapour of hydrocyanic acid and cyanogen gas, which last is contained, as I found, in the fumes of the puff-ball, which Dr. Richardson brought before the notice of this Society. The agents which I have exhibited as anæsthetics to the human subject, in addition to ether and chloroform, have as yet been but few. They are nitric ether, Dutch liquid, benzin or benzole, a bichloride of carbon, made by decomposing chloroform with chlorine gas, the monochlorinetted chloride of ethyle, and amylene, the subject of this paper. Nitric ether was exhibited also by Dr. Simpson, and Dutch liquid by him and Mr. Nenneley. These substances possess no advantage over chloroform, unless it be their slower action, while in other respects they are scarcely so agreeable. With regard to benzin, I discontinued the use it on account of convulsive tremors which it occasioned in a case of amputation in St. George's Hospital. I found that these tremors are a constant result when its effects reach a certain stage. I administered the chlorinetted muriatic ether in twenty surgical operations, in the summer of 1851, chiefly in King's College Hospital. Its sensible and physical properties and its effects are nearly the same as those of chloroform, but I thought that it might possess some advantage in the circumstance that, being less volatile, while its other properties are the same, it would be less liable to cause accident, even if incautiously used. I was, however, prevented from using it further, owing to the great difficulty of procuring it in a state of purity.

Amylene was discovered and described in 1844 by M. Balard, Professor of Chemistry to the Faculty of Science of Paris.* (*Annales de Chimie et de Physiqueem, 3me Serie, tom. xii. p. 320.) It is made by distilling fusel oil with chloride of zinc. M. Auguste Cahours had given this name five years previously to a product which is isomeric with amylene, and is made in nearly the same manner, but is now termed paramylene. Amylene itself is a colourless and very mobile liquid, of extremely low specific gravity. M. Balard has not stated the specific gravity in his essay, but I found that of the amylene made for me by Mr. Bullock,† (†[of] 15, Hanover-street, Hanover-square) and which is extremely pure, to be 0.659 at 56°. It is very volatile, boiling at 102º Fahr., and the specific gravity of its vapour is 2.45. It is composed of ten atoms carbon, and ten atoms hydrogen, and it bears the same relation to fusel oil, or amylic alcohol, that olefiant gas, or ethylene, bears to common alcohol. It burns with a brilliant white flame. It is soluble in alcohol and ether in all proportions, but is very sparingly soluble in water, being in fact a hundred times less soluble than many substances which are usually said to be insoluble in water. I have not yet been able to determine its solubility so exactly as I could wish, but as nearly as I can ascertain, 100 volumes of water dissolve two volumes of the vapour, at which rate one part of liquid amylene would require 10,220 parts of water for its solution. It has an odour somewhat resembling that of naphtha; some persons think the odour rather agreeable, and others think it somewhat unpleasant; the odour is not so strong or permanent as that of sulphuric ether, and does not remain long in the patients' breath. The vapour of amylene is much less pungent than those of ether and chloroform. It is therefore easier to breathe, and does not cause the choking feeling which sensitive and nervous patients often complain of in breathing chloroform. It has not caused any coughing to signify, except in two patients who were suffering from cattarrh, and in these cases the cough subsided in a minute or two.

I was not aware of the existence of amylene till a few months ago, or I should have tried it sooner; for I made inquiry in 1848 for a substance named eupion by Reichenbach, its discoverer, but was unable to obtain it. Eupion is a carbo-hydrogen, described as having all the physical characters which belong to amylene, though obtained in a different way; and I believe it is the same substance. Reichenbach obtained it from coal tar, but other chemists have not been able to make it.

Judging from experiments which I had made on analogous substances, there could be no doubt of amylene causing insensibility when inhaled; but I could not tell, without actual trial, whether it might not be too powerful, or otherwise unpleasant in its action. I made a number of experiments in 1848,‡ from which it appeared that each definite degree of narcotism was occasioned by an amount of the narcotic agent, bearing a certain relation to the whole amount which the blood is capable of dissolving, and that this relation was nearly the same in regard to ether, chloroform, and several allied substances. For instance, a very complete state of insensibility, which I named the fourth degree of narcotism, was caused by the presence in the blood of 1-28th part as much chloroform as it was capable of dissolving; and that the same state of insensibility was also occasioned by 1-28th part as much ether as the serum of the blood was capable of dissolving. The same relative amount of nitric ether produced the same degree of narcotism. In the case of bromoform and of bromide of ethyle, it was 1-27th part, with Dutch liquid it was 1-25th part, and with bisulphuret of carbon it required one part in 31 of what the blood was capable of dissolving, to induce the fourth degree of narcotism. Benzin was the only agent among those which I examined at that time which offered any great deviation from the others in the relative amount of its vapour which was required to be absorbed, in order to induce a definite degree of narcotism. To [61/62] induce the fourth degree of narcotism by benzin it required 1-17th part as much as the blood is capable of dissolving. Now, benzin bears a great resemblance to amylene, being, like it, a carbo-hydrogen, the composition, however, being different. (‡See Medical Gazette, Vol. II., 1848, "On Narcotism by the Inhalation of Vapours.")

The amount of amylene which requires to be absorbed is far greater in relation to the quantity which the blood would dissolve than in the case of benzin. I found, from some experiments which I made on guinea-pigs, mice, and linnets, that to cause the fourth degree of narcotism requires about 1-5th part as much amylene as the blood would absorb, to cause the second degree 1-10th part as much, and to cause the third degree, which is as far as I have carried its effect in the human subject, it requires an intermediate portion, or about 15 per cent. I found, for instance, that to induce the fourth degree of narcotism in a guinea-pig, it required that the air in the jar in which it was enclosed must contain 20 per cent, or a fifth part of its volume of the vapour of amylene. The temperature of the guinea-pig is, however, just that of the boiling point of amylene, when the tension of its vapour balances the weight of the atmosphere; and, consequently, the blood passing through the lungs could not take up, in the above experiment, more than 1-5th as much as the whole quantity which it could dissolve. This is a point capable of direct proof. The entire quantity of amylene which is absorbed during inhalation must, however, be extremely small, owing to its very sparing solubility. Taking the solubility of amylene in watery fluids to be what I have state above, viz., 1 part in 10,220, and taking the quantity of serum of the blood in the human adult to average 410 fluid ounces, as estimated by Valentin, then the amount of amylene circulating in the body in the third degree of narcotism would be not quite 3 minims. The above calculation of the small quantity absorbed into the blood is confirmed by some other experiments which I made. I introduced 14 minims of it into a bladder with 200 cubic inches of air, and after breathing it backward and forward a few times I became very nearly unconscious, and experienced, in fact, more effect from these 14 minims than from 45 minims breathed to and from a large bladder, holding 670 cubic inches.

Viewed in the light of the small quantity which requires to be absorbed into the system to cause insensibility, amylene is a very powerful agent; but when considered in relation to the quantity which is consumed during inhalation in the ordinary way, it is far from being powerful. This arises from the great tension and the small solubility of the vapour, in consequence of which it is, with the exception of a small fraction, expelled from the lungs again without being absorbed. In this respect it resembles, to a great extent, the nitrogen gas of the atmosphere, with which the lungs are always four-fifths filled, while the blood contains but a few cubic inches. It takes from three to four fluid drachms of amylene to cause insensibility in the adult, while less than a drachm of chloroform is usually sufficient. The quantity of sulphuric ether required to cause insensibility in the adult is eight to ten fluid drachms, one-half of which is absorbed into the blood. In a protracted operation of half-an-hour or upwards, the quantity of amylene used is greater even than that of sulphuric ether; the small quantity of the former which is absorbed is quickly exhaled again from the lungs, and has to be constantly replaced; while the large amount of sulphuric ether, when once absorbed, takes a much longer time to exhale in the breath. This constitutes some objection to the use of amylene in protracted operations, as it adds to the expense.

[Part 2 appeared in the issue of 24 January.]