"On narcotism by the inhalation of vapours"

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By John Snow, M.D.

Detection of ether in the expired air after inhalation--Detection of alcohol in the expired air after it had been taken into the stomach--The effects of chloroform and ether prolonged by causing the exhaled vapour to be re-inspired.

In my last communication it was shown that the vapour of chloroform can be detected by chemical tests, as it exhales from the blood in the expired air. The strong odour of ether, which continues to be perceived for hours in the breath of persons who have inhaled it, is a pretty good indication that this medicine is exhaled from the blood in a similar manner. I thought it desirable, however, to have a more material proof of the fact, than that afforded by the odour, and therefore contrived and performed the following experiments:--

Exp. 58.--As a preliminary measure I passed the expired air for twenty minutes through strong sulphuric acid, inspiring by the nostrils, and expiring by the mouth, through a spiral tube immersed in cold water; a continuation of this tube afterwards dipping into half an ounce of sulphuric acid contained in a bottle. The acid was afterwards boiled in a small retort, the beak of which communicated with a gas receiver under water. No gas was obtained beyond the air expelled from the retort by the heat, and the acid was not changed in colour.

Exp. 59.--On the following day--August 1st, I inhaled three fluid drachms of ether gradually, in the course of four minutes, and was rendered almost unconscious. After waiting for a minute, in order that the lungs might be entirely emptied of the vapour remaining at the conclusion of the inhalation, I commenced to pass the expired air through sulphuric acid, the air first passing through a spiral tube immersed in iced water, to condense the watery vapour, as in the last experiment. This procedure was continued for twenty minutes. A [749/750] few hours afterwards the sulphuric acid was placed in a small retort, the beak of which communicated with a receiver under water, and was heated with the flame of a spirit lamp. It was gradually rendered quite black by the heat, and 11.3 cubic inches of gas were obtained in the jar. The jar being transferred to the mercurial trough, and solution of caustic potash being introduced, the contents, after standing for an hour or two, and being agitated occasionally, till no further reduction of bulk would take place, were diminished to 3.9 cubic inches, showing an absorption of 7.4 cubic inches of carbonic acid gas. The jar being reversed, and a lighted taper being applied to its mouth, its remaining contents took fire, and burnt with a bluish flame. As 2.6 cubic inches of air were contained in the retort at the commencement of the process, the quantity of inflammable gas was probably 1.8 cubic inch.

Exp. 60.--On August 2nd, I again inhaled three fluid drachms of ether, and proceeded exactly as in the last experiment. The sulphuric acid was rendered black as before, and 7.6 cubic inches of gas were collected in the receiver. Potash absorbed 3.2 cubic inches of this, and the jar being reversed and a lighted taper applied to its mouth, the remaining contents burnt with a flame which gradually descended in the jar to the surface of the mercury. Allowing for the air expelled from the retort, the quantity of combustible gas was 1.6 cubic inches.

Exp. 61.--In order to ascertain the nature of the inflammable gas produced, another experiment was performed, on a subsequent day. The same quantity of ether was inhaled, and the expired air was passed through sulphuric acid in the same manner. The acid was boiled in the retort until 7.1 cubic inches of gas were obtained in the receiver, when the process was stopped. Solution of potassa being agitated in the gas absorbed 3.5 cubic inches. Two cubic inches of oxygen gas were added to the remaining 3.6 cubic inches, and a portion of the mixed gases was transferred to Dr. Ure's eudiometer. As it did not explode with the spark from a small electric machine, a small quantity of pure hydrogen gas was added, when explosion took place with the following result. The quantities are in hundredths of a cubic inch:--

Hydrogen	........	3.0
Oxygen, [etc.]	........	21.0
Total	........	24.0
After explosion	........	16.5
Loss of volume	........	7.5

being a diminution of three parts more than the hydrogen would occasion. The remaining 16.5 parts were agitated with a little solution of potassa, when a further diminution of about six parts took place; a little more than ten parts being left. This result shows that the inflammable gas under examination was carbonic oxide, which, in becoming converted into an equal volume of carbonic acid, consumes half its own volume of oxygen. The beak and upper part of the small retort contained 1.9 cubic inch of air, which would be necessarily expelled into the gas receiver, and when this and the oxygen afterwards added are subtracted, the remainder is in the same proportion, very nearly, as the carbonic acid produced by the explosion; consequently the gases obtained by heating the sulphuric acid were carbonic acid gas, and carbonic oxide.

In these experiments, the ether passing off in the expired air is in part absorbed by the sulphuric acid, and on the application of heat is decomposed into various products; the above gases being given off, and free carbon remaining in the acid, and rendering it black. Sulphurous acid gas is evolved, but is absorbed by the water. On adding a few minims of ether to half an ounce of sulphuric acid, and operating in the same way as in the above experiments, the same products were obtained. Alcohol, when heated with a large excess of sulphuric acid, yields the same products as ether; but as I had taken no kind of fermented liquor before inhaling the ether in the above experiments, these products must have resulted from the sulphuric ether.

From the general resemblance between the action of alcohol, ether, and chloroform, and from these substances being governed in their action by some of the same general laws, as previously shown in the experiments of frogs and fishes,* (*Med. Gaz., last vol., p. 622) it might be expected that since chloroform and ether can be shown to pass off in the expired air, alcohol would also [750/751] be exhaled in the same manner. Common experience, so far as the sense of smell is concerned, is in accordance with this view. Leibig [sic], however, says,* "according to all the observations hitherto made, neither the expired air, nor the urine, contains any trace of alcohol, after indulgence in spirituous liquors" (*Animal Chemistry, p. 239). This, so far as I know, was true as regards the human subject, but Dr. Percy† had obtained alcohol by distilling the urine of a dog, to which he had given a fatal dose of it (†Prize Thesis "On the Presence of Alcohol in the Brain," etc.).

Feeling a strong conviction that alcohol must pass off in the breath, I have made many experiments during the last twelve months, with a view to detect it. At first, I caused the expired air, after spirit had been drunk, to pass, for an hour or longer, through a spiral tube, immersed in ice and salt, but did not succeed in detecting alcohol in the condensed water. A little reflection, however, made it evident that alcohol could only exist there in extremely minute quantities; for the spirit which had been taken, being equivalent only to two ounces of absolute alcohol, the inspired air would only be able to take up about a two-hundredth part as much vapour of alcohol as would saturate it, at the heat of the body; and it would be in vain to attempt to reduce the air to such a low temperature as would cause it to deposit any part of so relatively small an amount of vapour; in other words, the alcoholic dew-point of the air must be lower than the temperature of the ice and salt, and , consequently, all the spirit that could be arrested would be that which might be attracted by the small quantity of condensed water. By collecting together the water condensed from the breath in six different experiments, I succeeded, however, in obtaining spirit in a pure state, as will be detailed further on.

In the following experiments the same method was employed, as detailed above, for the detection of ether.

Exp. 62.--August 6th, 1850. Two ounces and a half of rectified spirit of wine, of 80 per cent, were diluted with rather less than a pint of water, and taken, with bread and butter, at suppertime. A slight feeling of inebriation was occasioned by it, but not sufficient to interfere, in the least, with the proper performance of the experiment. The air was afterwards taken in by the nostrils and breathed out by the mouth, through a wide tube communicating with a metal box containing a spiral arrangement, by which the air was obliged to pass round several times. This box was surrounded with ice. The air was conducted next, by a glass tube half an inch wide to the bottom of a bottle containing half a fluid ounce of sulphuric acid. The object of condensing the moisture of the breath, in the metal box, was to prevent its diluting the sulphuric acid beyond the point at which it ceased to decompose alcohol when heated. The expired air was, in this manner, passed through the sulphuric acid for thirty-five minutes. Care was taken that no air coming from the stomach by eructation should pass into the apparatus. Two and a half fluid drachms of clear water were condensed in the metal box. The following morning, the sulphuric acid was put into a small retort, communicating with a gas receiver over water, and heated with the flame of a spirit lamp. The acid was rendered quite black, and 5.1 cubic inches of gas were obtained, of which 2.6 cubic inches consisted of air from the retort. The receiver being transferred to the mercurial trough, and a little solution of potassa introduced, 1.65 cubic inches were absorbed. The jar being inverted, and a light applied to its mouth, the remaining contents took fire, the flame gradually descending in the jar to the surface of the mercury. The quantity of inflammable gas was 0.85 cubic inch.

Exp. 63.--Another night the same quantity of rectified spirit was taken, in the same manner, and the expired air passed through the spiral box and the sulphuric acid as before. Six fluid drachms of acid were employed this time, and the process of breathing through it was continued for an hour. Two and a half drachms of water were again condensed in the metal box, and the acid was increased in bulk by rather more than half a drachm. The sulphuric acid was next morning placed in a retort and heated. It was turned black, and six cubic inches of gas were obtained, two of which consisted of air from the retort. Solution of potassa absorbed 3.45 cubic inches of carbonic acid gas, and the remaining contents of the receiver burnt with a slight explosion, on a light being [751/752] applied. The inflammable gas did not amount to more than 0.55 cubic inch.

Exp. 64.--The same quantity of rectified spirit was taken at night on another occasion, and the expired air passed for an hour through sulphuric acid in the same way as before. The quantity of acid employed this time was a fluid ounce. On the following morning six drachms of the acid were heated in a small retort: they were rendered quite black, and somewhat viscid. 4.85 cubic inches of gas were obtained in the receiver, of which 1.8 cubic inch consisted of air from the retort; potash absorbed 0.6 cubic inch; 0.85 cubic inch of the remainder was transferred into a small jar, to the mouth of which a taper was applied, when the contents burnt for a little time with a bluish flame. To the residue in the receiver 3.8 cubic inches of oxygen were added, and a portion of the mixture was introduced into the eudiometer. As it did not explode with the electric spark, a small quantity of pure hydrogen gas was added, when an explosion was effected with the following result:-

Hydrogen	........	3.0
Oxygen, etc.	........	32.0
Total	........	35.0
After explosion	........	27.0
Diminution	........	8.0

being a loss of 3.5 more than occasioned by the hydrogen.

Solution of potassa being agitated in the remaining 27 parts, they were diminished to 19; showing an absorption of 8 parts of carbonic acid. The loss of volume was consequently very nearly half as great as the quantity of carbonic acid gas produced by the explosion; and therefore the inflammable gas under examination was carbonic oxide, the amount of which was just one-fourth of the mixed gas introduced into the eudiometer. It is evident on calculation that nearly 1.8 cubic inch of carbonic oxide must have been expelled from the retort, and that this and the carbonic acid were the only gases evolved by the sulphuric acid.

The decomposition which the alcohol, absorbed from the expired air, undergoes in the sulphuric acid is the same as that undergone by the ether in the experiments previously detailed.

Exp. 65.--The water condensed in the metal box, surrounded with ice in the above three experiments, and in three others not related, amounted together to two ounces. It was placed in a retort, and about three drachms were distilled. This product was placed in a smaller retort, and about twenty minims were distilled into a small test tube. Dry carbonate of potassa was added to this till it would dissolve no more. In a little time a layer of clear spirit, about the tenth of an inch in thickness, floated on the top of the solution of potash. A piece of asbestos being dipped in this, it burnt with a blue flame. A very little powdered camphor was dropped into a small tube, drawn at one end to a capillary point. This point being brought in contact with the liquid floating on the solution of potash, a little of it rose by capillary attraction, and was observed to dissolve the camphor within. On blowing at the other end of the tube, a minute drop of solution of camphor was forced out, and received on a piece of glass, when the spirit immediately evaporated, leaving a coating of camphor. These tests leave no doubt of the presence of alcohol. The process used in this experiment is similar to that employed by Dr. Percy for the detection of alcohol in the brain and other organs.

Exp. 66.--Two and a half fluid ounces of rectified spirit, of 80 per cent, were diluted with water, and taken at suppertime. The air was afterwards inspired for fifty minutes by the nostrils, and expired by the mouth, through a glass tube which dipped into three ounces of water contained in a bottle. Next morning the water was put into a retort, and about three drachms were distilled, which were put into a smaller retort, and about twenty minims were distilled into a small test tube. On carbonate of potassa being added in excess, a thin layer of clear liquid floated on the surface. This was proved to be alcohol; for a little bit of asbestos being moistened in it, burnt with a blue flame, and it dissolved camphor in the way described in the former experiment.

Whilst the above experiments show that alcohol is exhaled in the breath after it has been taken into the stomach, a little consideration will prove that only a small part of it can be excreted in this manner. When there are two ounces of alcohol in the blood, the air which reaches the lungs can only take [752/753] up, as stated before, about a two-hundredth part as much as would saturate it at the temperature of the blood. At this rate, a person breathing the usual amount of air would only exhale about twelve minims of alcohol in an hour; consequently, if it had to pass off entirely in the expired air, its effects would continue for a very much longer period than they do; and, since alcohol can hardly be detected in the other excretions, it must be decomposed in the system into fresh products.

I have assumed from the first that the speedy subsidence of the narcotism caused by chloroform and ether, in comparison with that from alcohol and other narcotics, depends on the volatility of the former substances, which allows of their ready exit by the expired air. Indeed, the effects of these medicines usually subside in the period which a calculation founded on this view would assign to them. It was previously estimated, for instance, that twenty-four minims of chloroform are contained in the blood of an adult of average size in a state of very complete insensibility; this being about one twenty-eighth part as much as the blood would dissolve. The inhalation being now discontinued, the fresh air which reaches the air cells will abstract from the blood nearly one-twenty-eighth part as much as it can hold in suspension at the temperature of 100°; and as each hundred cubic inches of air, when saturated at 100°, contains 43.3 cubic inches of vapour of chloroform, 43.3 ÷ 28 = 1.54 cubic inches, or 1.48 minims, will be the quantity removed by the first hundred cubic inches of air which reaches the air-cells. It has been shown that about half the inspired air gets as far as the air-cells; and, supposing the patient to be breathing 400 cubic inches in the minute, 200 cubic inches would act in the removal of the vapour. In this manner it would take two minutes and a half to reduce the quantity of chloroform from 24 to 18 minims, and the narcotism from the fourth to the third degree; after which the effects would diminish more slowly, and in three and a half minutes longer the narcotism would have diminished to the second degree. Then, as the air would only take up about one-fifty-sixth part as much as it would hold, in about five minutes longer we might expect the return of consciousness; and the slight dizziness or confusion which might remain would subside still more gradually. The above statement expresses pretty well what usually occurs when the inhalation has been kept up for a little time. Children recover from the effects of chloroform more rapidly, on account of their quicker circulation and respiration. Old people, on the other hand, more slowly, for the opposite reason. When insensibility is produced in the course of two minutes for a short operation, and the inhalation is not repeated, the effects of the vapour subside more quickly than stated above; because, at the same time that the chloroform is passing off by the lungs, it is also escaping from the main current of the circulation, by permeating the coats of the small vessels, and diffusing itself in the tissues, and thus allowing the brain to resume its functions.

Ether is more volatile than chloroform; but being also much more soluble, the relative quantity absorbed into the system is so much greater, as to more than compensate for the superior volatility; and consequently the effects of ether subside somewhat more slowly than those of chloroform, the ether taking rather longer to pass off in the expired air.

It follows as a necessary consequence of this mode of excretion of a vapour, that, if its exhalation by the breath could in any way be stopped, its narcotic effects ought to be much prolonged. The following experiments show that such is the case:--

Exp. 67.--About 750 cubic inches of oxygen gas were introduced into a balloon of thin membrane varnished with solution of Indian rubber in turpentine. The balloon was attached to one of the apertures of the spiral box which forms part of the ether inhaler I employ, and which was used for condensing the moisture in the experiments on alcohol previously detailed. Four ounces of solution of potassa were put into the inhaler, and to its other opening was attached a tube, connected with a face-piece without valves.* (*I used the same arrangement in giving oxygen gas last year, at the request of Dr. Wilson, to a cholera patient in St. George's Hospital. The patient, who was in a state of collapse, was not saved or relieved by it.) After inhaling as much chloroform as I could without [753/754] being rendered unconscious, I immediately began to breathe the oxygen from and to the balloon, and over the solution of potassa. In this way the vapour exhaled in the breath had, the greater part of it, to be re-inspired. This process was continued for ten minutes, during which time the feeling of narcotism subsided very little, and it passed off very slowly afterwards, about half an hour elapsing before it was quite gone.

The oxygen was used, in this and the following experiments, to allow of respiration being continued for some time from the balloon without employing such an amount of air as would take up a great deal of the vapour. As there was air both in the lungs and inhaler at the beginning of the experiment, the oxygen was not breathed unmixed with nitrogen. The solution of caustic potash was employed for the purpose of absorbing the carbonic acid gas generated by respiration as the air passed to and fro over a large extent of its surface.

Exp. 68.--On another day the same quantity of oxygen and solution of potassa were employed, and fifteen minims of chloroform were placed in the spiral inhaler, in a small glass vessel, which prevented its mixing with the solution of potassa. I then began to breathe as in the former experiment, and continued to do so for fifteen minutes. The effects of the chloroform were gradually induced during the first three minutes, causing a considerable feeling of narcotism, but not producing unconsciousness. After the end of three minutes, the feeling of narcotism remained stationary till twelve minutes had elapsed, and during the last three minutes it very slightly diminished. The experiment was discontinued on account of a feeling of want of breath. It was half an hour longer before the effects of the chloroform were altogether removed.

Exp. 69.--The oxygen and solution of potassa were employed as before, and two and a half fluid drachms of ether were put into the inhaler, with the potash. The oxygen was breathed to and fro over the potash for twenty minutes. The effects of the ether were rapidly developed during the first three minutes, but not amounting to loss of consciousness. From this time, the influence of the ether remained nearly the same to the end of the experiment, and afterwards subsided very gradually.

The effects of the small quantity of chloroform and ether inhaled in these experiments would have passed off in three or four minutes, if the exhaled vapour had been allowed to diffuse itself in the air in the usual way.

The amount of carbonic acid absorbed by the potassa was determined, and will be given in the next communication, as it forms a separate branch of the inquiry into the action of narcotic vapours.