Source: Snow, John. London Med. Gazette, vol. 45,  April 12, 1850, pp. 622-27 (part 13).

On narcotism by the inhalation of vapours

By John Snow, M.D.

PART XIII.

Action of Alcohol compared with that of Chloroform and Ether.

Experiments on frogs with alcohol--On fishes, with alcohol, chloroform, and ether--Quantity of alcohol necessary to cause drunkenness--To cause death. Anæsthetic effects of alcohol--Liebig's views of the action of alcohol--their application to ether and chloroform--Objections to these views.

I feel that I ought to apologise to the readers of the Medical Gazette for the great length of time that has been allowed to elapse before the completion of these papers. The delay has not arisen from any want of anxiety on my part to bring the subject to a conclusion, but from finding, as I proceeded with it, that it was desirable to repeat many experiments and institute fresh ones, the performance of which occupied a great deal of time.

In order to enter on the investigation of the modus operandi of ether an chloroform with every advantage, it is desirable to ascertain whether or not alcohol, which, in its chemical constitution and general physiological properties, considerably resembles these medicines, is identical with them in its action. It was previously stated* that alcohol, pyroxilic spirit, and acetone, which are miscible with water in all proportions, confirm the general rule then laid down, that the power of volatile narcotic substances of the class we are considering is in the inverse ratio of their solubility, as a large quantity of the above three liquids requires to be taken to produce narcotism. (*Vol. xliii. p. 333.) It afterwards occurred to me that experiments might be instituted to ascertain whether alcohol and the other two liquids obey exactly the law which we found to apply to chloroform, ether, and a number of other bodies. Experiments to determine this point could not easily be made on animals that breathe air exclusively, on account of the length of time that the vapour would continue to be absorbed; but, by employing frogs and fishes, the end could be attained. In the experiments previously related, it was found that the second degree of narcotism was caused when the serum of the blood contained about a fifty-sixth part as much of the chloroform, ether, or other substance examined, as it would hold in solution. Now, if the rule apply to alcohol, the second degree of narcotism ought to be induced when the amount of spirit is equal to one fifty-sixth of the volume of the serum.

The following are some of the experiments undertaken to determine this point.

Exp. 47.--A frog was placed in a shallow glass jar, capable of holding a pint. Seven ounces of water, mixed with a fluid drachm and a quarter of rectified spirit of wine, were put into the jar. The spirit consisted of 80 per cent absolute alcohol, of which it consequently contained one drachm; and, as there are fifty-six drachms in seven ounces, the water contained one part of alcohol in fifty-six. It was the early part of March; and the frog, although quite sensible, was not very lively. When enclosed in the jar, it sat, with the head above the water, breathing the air at the rate of ninety respirations in the minute. As the jar was covered by a plate of glass, the air it contained would soon become charged with vapour of alcohol to the same relative extent as the water; that is to say, it would contain 1-56th part as much as if saturated at the same temperature, and the tendency of the absorption, by both the lungs and skin of the frog, would be to establish an equilibrium between the quantity of alcohol in the fluids of its body and that in the surrounding [622/623] water, when the blood of the frog would consist of about 1-56th part spirits. Two hours after the commencement of the experiment, the strength of the frog appeared to be diminished, and it had a difficulty in keeping its nostrils above the water. It was breathing irregularly, and much less frequently than before. At the end of four hours its head was under the surface, and it was not breathing. Being taken out for a minute or two, it moved its head and limbs feebly, but apparently in a voluntary manner, but did not attempt to breathe. It was replaced in the jar, and left for the night, with its head beneath the surface, the jar being covered as before. The next morning, twelve and a half hours from the beginning of the experiment, the frog was found with its nostrils slightly raised above the surface of the spirit and water, and breathing gently and slowly. Being taken out, it was found to flinch slightly on the skin being pinched, and was able to crawl slowly, chiefly by the use of the anterior extremities. It recovered perfectly in the course of the day. The temperature of the room during this experiment was 50 Fahr.

Exp. 48. Another frog was placed in the same jar, with seven ounces of water containing two and a half fluid drachms of the same spirit, the strength being consequently one part of alcohol in twenty-eight parts. In about an hour and a half the frog seemed feeble, and had difficulty in keeping its nostrils above the surface. At the end of two hours, its head had sunk beneath the surface, but the respiratory movements were going on, though feebly, and it seemed to be swallowing the liquid. At the end of three hours the lower jaw had fallen, and the mouth was open, but there were slight respiratory movements of the hyoid bones. There were feeble muscular twitches (subsultus tendinum) observed occasionally. A support was at this time placed under the anterior extremities of the frog, to keep its head above the surface of the water. It was found to be totally insensible to pinching. Its mouth continued open, and the feeble respiratory movements went on. At the end of five hours it was breathing very gently, and very slight twitchings of the toes could be observed occasionally. Seven hours and a quarter from the commencement of the experiment, the respiration had ceased. The frog was taken out, and showed no signs of life at first; but, on closely observing it, slight quivering movements of the toes, and of different parts of the muscles just beneath the skin, could be seen. It was exposed to the air in a shallow dish containing a very little fresh water. In two hours after its removal, feeble respiratory movements could be occasionally observed. The breathing gradually became quite re-established, and seven hours after its removal it had recovered both sensibility and voluntary motion. The next day it seemed pretty well, and had resumed its colour, having been rendered nearly black whilst narcotized. The other frog also became much darker in colour, whilst under the influence of the spirit, in the previous experiment.

In the former of the above experiments the frog appeared to be in the second degree of narcotism, sensibility and voluntary power being impaired, but not abolished. In the last experiment the narcotism reached, and apparently rather exceeded, the fourth degree. The effect produced was nearly the same as that caused by one twenty-sixth part as much chloroform as the blood would dissolve, in one of the frogs, the subject of Experiment 15, formerly related; and rather more than the effect produced by one thirty-second part as much ether as the blood would dissolve, in a frog used in Exp. 28.

Exp. 49. The frog employed in Exp. 47, being in good health, was, four days afterwards, placed in the same jar with nine ounces of water, containing five fluid drachms of rectified spirit of 80 per cent, equivalent to half an ounce of absolute alcohol; the proportion of alcohol being, consequently, one in eighteen of the mixture. At first the frog made some attempts to get out. At the end of seven minutes it withdrew its head voluntarily beneath the surface and ceased to breathe; but two or three minutes afterwards it raised it again above the surface, and breathed the air. Twenty minutes from the commencement, it appeared to have a difficulty in keeping its nostrils above the surface, and now and then made an abortive attempt to leap up. The eyelids were half closed, and the cornea looked dim. At the end of half an hour it was lying on its belly without any sign of life. A support was placed under it to keep its head above the surface, and feeble [623/624] respiratory movements recommenced. Three quarters of an hour from the beginning of the experiment, the respiration had entirely ceased, and no external sign of life remained. It was left an hour longer in the jar, and was taken out after being exposed to the spirit and water, and the vapour given off from it, for an hour and three quarters. No pulsation of the heart could be observed externally, but on removing a portion of the integuments and sternum with the scissors, the heart was found to be pulsating feebly. The frog was placed again in the spirit and water, being laid on its back, so that the heart could be observed. It was noticed to continue pulsating feebly for half an hour. Being left for two hours, it was found at the end of that time that the action of the heart had entirely ceased. As only one or two drops of blood were lost in exposing the heart, and as frogs at the temperature at which this experiment was performed (52? Fah.) can live almost altogether without the pulmonary respiration, it is probable that the action of the heart was arrested by the narcotic effect of the alcohol; and it was found in experiment 42 and 43, formerly related, that one eighteenth part as much of the vapour of chloroform as the blood would dissolve, had the effect of arresting the action of the heart in frogs.

Exp. 50. Two fluid drachms and a half of rectified spirit, equivalent to a quarter of a fluid ounce of absolute alcohol, were mixed with sufficient water to make up fourteen ounces, which, consequently, contained one part of alcohol in fifty-six parts. This was put into the glass jar before used, and a small gold fish, weighing two drachms and a half, was put in. The jar was covered, to prevent loss of spirit by evaporation. After a few minutes the fish seemed rather more active than before it was put in. At the end of twenty minutes it no longer regarded, or was frightened by, any object touching the jar, and it began to oscillate from side to side when still. Half an hour from the beginning of the experiment it was swimming very much on its side. It did not become appreciably more narcotized, although it remained in the water and spirit until two hours had expired. It struggled whilst being removed into fresh water. In half an hour after its removal it had partially recovered, and when next observed, two or three hours later, it was in its usual state.

Exp. 51. Another small gold fish, weighing rather more than three drachms, was placed, in the same manner, in water containing one twenty-eighth part by measure of alcohol. In less than ten minutes the fish began to move about violently. Soon afterwards these movements became irregular and ill directed, the fish being unable to preserve the perpendicular position, and it no longer observed objects brought close to the jar. It continued, every now and then, to move about violently, and somewhat convulsively, till three quarters of an hour had expired, when it became quieter, floating on its side, and moving only occasionally. The opercula moved, but not regularly. At the end of an hour it had ceased to move its body and fins altogether, and a few minutes later it was found that the opercula did not move. It was placed in fresh water, and in a few minutes the opercula began to move, at first at long intervals, but in half an hour the respiration was regular, and the fish was beginning to move its body. The next morning it appeared quite well.

In Exp. 50 the fish was in the second degree of narcotism, and in the last experiment there was complete insensibility, and the fish would soon have died, probably not from absorption of additional spirit, but because the utmost extent of narcotism cannot be long continued without extinguishing the vital powers.

In some experiments with pyroxilic spirit, or wood naphtha, the same effects were produced on fishes, when it was mixed with water in the same proportion as the alcohol in the two last experiments; but the fishes died several hours afterwards, through the poisonous action of the naphtha, having first, in a great measure, recovered their sensibility and voluntary power.

The two following experiments are introduced for the purpose of showing that chloroform and ether act on fishes in the same way as on other animals.

Exp. LII [52].--Six fluid drachms of water in a small evaporating dish was placed on a plate of glass, by the side of a small dish containing chloroform; the two dishes were covered by a bell-glass, ground at the edge, to fit air-tight [624/625] on the glass plate, and left till the next day, in order that the water might be saturated with chloroform, by absorbing it in the form of vapour. As soon as the bell-glass was removed, the small dish of water was put quickly into two pints of water, in which a gold fish was swimming, in a glass jar capable of holding three pints, and the jar was covered to prevent loss by evaporation. In ten minutes the fish began to oscillate a little in swimming. At the end of twenty minutes it was swimming frequently on its side, and then again recovering its balance. Half an hour from the beginning of the experiment the fish floated for a minute or two on its side, at the surface of the water, without moving its body or fins; then it began to swim about again for a time and it continued occasionally to move for a short time, and then again to appear lethargic, until it was removed and put into fresh water, three hours after the commencement of the experiment. It struggled a little whilst being lifted out of the water. In an hour it had in a great measure recovered, and next day was as well as before. The water saturated with chloroform composed a fifty-fourth of the whole, which consequently contained one fifty-fourth part as much chloroform as it would dissolve, and the fish was in the second degree of narcotism.

Exp. LIII [53].--A fluid drachm of ether was mixed with two pints of water, and a gold fish put into it, and the jar was covered, as in the former experiment. As water is capable of dissolving one-tenth of its volume of ether, the water in this experiment contained one thirty-second part as much as it would dissolve. The fish was but little affected during the first hour, but at the end of an hour and a half it inclined to one side in swimming. When two hours had elapsed it was floating completely on its side, and had ceased to move its fins. It was taken out and put into fresh water. It moved a little on being handled. In about ten minutes it began to swim, and the effects of the ether gradually and completely went off.

As the deeper degrees of narcotism cannot be long continued without dangerously depressing the vital actions, so, with an agent whose effects last so long as those of alcohol, a state of complete coma cannot be induced at all without risk, especially if the body be exposed to a low temperature. Ordinary drunkenness does not exceed the second degree of narcotism; the popular term of dead drunk being often applied to a state of sleep from which the individual is still capable of being roused to state of incoherent consciousness. In order to estimate the quantity of spirit that would be required to induce the second degree of narcotism in a man having the average amount of blood, 410 fluid ounces, which were taken as the amount of serum in the body in the earlier parts of this article, may be divided by 56, which will give seven ounces, or three-quarters of a pint of proof spirit. This is a quantity which, I believe, agrees pretty well with general experience. Less than twice this amount, if taken all at once, and on an empty stomach, so as to be quickly absorbed, ought, according to the above considerations, to prove fatal; and there have been many instances of such a result.

A few years ago a man drank a bottle of gin, in the Haymarket, for a wager. He was soon in a state of profound insensibility, and the late Mr. Read, the instrument maker, informed me that when he applied the stomach-pump at the police station, in the presence of medical gentleman, the stomach was found to be quite empty. The man shortly afterwards died. The quantity of absolute alcohol in a bottle (twenty-four ounces) of strong gin is about thirteen ounces. In the fifth case in Dr. Ogston's paper on intoxication,* a woman lost her life by drinking less that a bottle of whiskey (*Edin. Med. and Sur. Jour., vol.xl.); and I believe that it is only by dividing the dose, and thus distributing its effect over a longer time, that any person can, with impunity, take a quantity of spirit exceeding this. The two bottles of wine which, when drinking was less unfashionable than at present, some persons could take after dinner, without being rendered altogether incapable, would contain, according to Mr. Brande's table, from nine to twelve ounces of alcohol; but this quantity was consumed during a protracted sitting, and after eating food, which would further retard its absorption. The difference in susceptibility [625/626] to the influence of alcohol, though existing to some extent, is not so great as it appears to be. The real difference is more in the way in which the mind is affected by it. A person who is excited evinces the effects of a moderate quantity, which are not so apparent on one who is not excited; whilst to make both individuals quite insensible, the quantity, as in the case of ether or chloroform, would probably not differ more than the size of the individuals, or rather the quantity of blood they might contain. With respect to the large amount of wine and spirits that patients in a state of extreme debility sometimes take without being apparently intoxicated, the following remarks may be made. Such persons are usually incapable of showing excitement under the influence of narcotics; and, as the alcohol is given in divided doses, which are insufficient to cause insensibility or coma, the effects which are really produced pass unnoticed. Long habit has some effect in enabling a person to take a larger quantity of alcohol liquor: this, however, does not arise altogether from the diminished action of the spirit, but partly from experience of the muddled condition, which enables him to control his actions to some extent, and to go about his affairs with a sort of sober aspect when very unfit for business. The woman whose case is quoted above, and who was killed by less than a bottle of whiskey, was a drunkard; and, at all events, the habit of drinking alcohol has no power of enabling persons to increase the dose in the extraordinary manner in which that of opium can be increased.

The amount of anæsthesia from alcohol is apparently as great, in proportion to the narcotism, of the previous centres attending it, as from chloroform and ether. A case occurred in King's College Hospital illustrating this. On Thursday night, the 21st of December, 1848, Mr. Fergusson performed amputation of the leg on an elderly man who had just before sustained a bad compound fracture. The man was very drunk, and Mr. Fergusson informed me that he evinced but little feeling, and did not seem aware of what was being done. He called out once during the operation that he had the cramp in his leg. When I questioned the patient a day or two afterwards, he said that he did not remember anything of the operation, and he supposed that chloroform had been administered to him. This, however, was not the case. Alcohol does not yield sufficient vapour, at ordinary temperatures, to cause insensibility by inhalation in a reasonable time; but, if no better means had been discovered, there can be no doubt that it would have been both practicable and allowable to prevent the pain of severe operations by getting the patient to swallow a large quantity of spirit and water. The end would have justified the means, and, in fact, rendered it as praiseworthy as it is disgraceful when resorted to for the purpose of supposed enjoyment, or to satisfy a craving which has resulted from a pernicious habit.

The general tendency of physiological researches had for some time been to prove that all the strictly animal functions resulted from the combination of the oxygen of the air with the constituents of the body, when Liebig* stated the position more fully and clearly than, as I believe, had previously been done (*Animal Chemistry). His attempted explanation of the physiological action of alcohol, which many persons were inclined to extend to that of ether, on its introduction for inhalation, is in accordance with these views, and is to the following effect†.--That, according to all the observations hitherto made, neither the expired air, nor the perspiration, nor the urine, contains any trace of alcohol after indulgence in spirituous liquors‡ (‡This we shall afterwards find to be incorrect); that the elements of alcohol combine with oxygen in the body, and that its carbon and hydrogen are given off as carbonic acid and water; that the elements of alcohol appropriate the oxygen of the arterial blood, which would otherwise have combined with the matter of the tissues, or with that formed by the metamorphosis of the tissues: and that thus the change of the tissues, and the muscular and other forces which would result from that change, are diminished (†Ibid. p. 239.). Whilst it may be admitted that alcohol diminishes the change of tissues and the functions connected with these changes, and will, indeed, be shown further on that this is true with regard also to the narcotic vapours treated of in this article, it can readily be proved that it is not by appropriating the oxygen in the blood that [626/627] this diminution or suspension of the molecular change of tissues is effected. The following, amongst other considerations, show this:--First, the carbon and hydrogen of fat, starch, sugar, and gum, as Baron Liebig had the merit of showing, combine with oxygen in the blood, and are given off as carbonic acid gas and water; yet these substances are in no degree narcotic. Second, the carbon and hydrogen of chloroform, which in the laws of its action is almost, if not quite, identical with alcohol, could not possibly combine with oxygen sufficient to act in the way supposed. The amount of carbon and hydrogen in twenty-four minims of chloroform--the quantity which, as it was estimated on a previous occasion, exists in the blood of the adult in complete insensibility,--is only about four grains: an amount totally insignificant when compared to the oxygen which is continually absorbed in the lungs. And, third, if alcohol and the agents allied to it acted by appropriating the oxygen in the arterial blood, breathing air richer than usual in oxygen ought to prevent or arrest their narcotic action. But such is not the case: breathing even pure oxygen does not remove intoxication, or prevent or remove the effects of narcotic vapours. The latter point I have ascertained as regards both the human subject and inferior animals, and have seen insensibility kept up in an animal by the ordinary amount of ether vapour, whilst its skin was of a bright vermilion colour from the excess of oxygen in the blood.

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