"On narcotism by the inhalation of vapours"

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By John Snow, M.D.

Experiments to determine the amount of Carbonic Acid Gas excreted under the influence of Chloroform--of Ether.-- Diminution of Carbonic Acid caused by Alcohol.--Chloroform, Ether, etc., produce their effects by diminishing Oxidation in the system, without necessarily combining with oxygen themselves.--Proofs of this view.

In order to ascertain with accuracy the quantity of carbonic acid gas excreted by animals whilst under the influence of chloroform and ether, I employ some apparatus similar to part of that used by MM. V. Regnault and J. Reiset in their chemical researches on the respiration of animals* (*Annales de Chimie et de Physique, 1849).

The accompanying engraving will assist to give a correct idea of the apparatus. The animal to be experimented on having been placed in a large glass jar, the latter is covered with a lid, padded on its under surface with an India rubber cushion, to make it fit accurately. In this lid there are three apertures. One of them serves for introducing the chloroform or ether, and can be closed by a brass mount; the others are connected, by means of tubes of vulcanized India rubber, to a potash apparatus, consisting of two glass vessels with an opening at each end, connected together at the lower part by means of another elastic tube. The solution of potash employed is diluted with sufficient pure water to make it fill one of the vessels; and as these vessels are made to move up and down during the experiment, by means of a cord passing over pullies, the solution of potassa is moved alternately from one vessel to the other, its place being occupied by air from the jar, which is returned back again as the vessel descends and becomes again filled with the liquid. As the tube from one of the potash vessels is continuous with one which descends nearly to the bottom of the jar containing the animal subjected to experiment, air is alternately withdrawn and returned at its upper

[622/623] and lower part. A constant circulation of air thus takes place, and the carbonic acid gas becomes absorbed soon after it is given off from the lungs.

To determine the quantity of carbonic acid gas taken up by the solution of potassa, it is first put into a flask and boiled, to expel the chloroform or ether it may have absorbed. The flask is afterwards closed with a stopper, perforated for the admission of a safety tube, and a tube containing chloride of calcium* (*See figure at the left side of the engraving). The whole is then carefully weighed, together with a bottle containing rather more dilute sulphuric acid than is sufficient to saturate the solution of potassa. The acid is introduced gradually through the safety tube, and the contents of the flask heated to the boiling point, in order to expel the whole of the carbonic acid gas from the liquid. By making aspiration through the chloride of calcium tube, the whole of the carbonic acid is removed from the flask, its place becoming occupied by fresh atmospheric air, which enters through the other tube. When the contents of the flask have cooled to the temperature at which the previous weighing took place, the apparatus is again carefully weighed, and the loss of weight shows the quantity of carbonic acid known to have been contained in the solution of potassa employed, the remainder shows the quantity which has been absorbed by it during the experiment.

Exp. 70.--On December 18th, 1850, a rabbit, weighing four pounds, was placed in a jar holding 1,600 cubic inches, and allowed to remain for half an hour, the potash apparatus above described being kept in motion during this time. The rabbit was very quiet during this part of the experiment.

The potash vessels having been emptied and replenished, and the rabbit having been removed for a few minutes for the ventilation of the jar, it was put in again, and twenty-five grains of chloroform were introduced through the aperature in the cover. The vessels containing the solution of potassa were kept moving up and down, as before. The rabbit moved about briskly on the introduction of the chloroform, and continued to do so for six minutes, after which it lay apparently asleep, but started spontaneously, now and then, as if in a disturbed dream. On its removal it showed signs of sensibility when touched, but appeared quite unconscious.

After being put out of the jar for five minutes, and the jar having been well ventilated in the meantime, the rabbit was put in again, in much the same state as when removed. It remained for half an hour, sleeping the greater part of the time, but had almost recovered from the effects of the chloroform on its removal. The potash apparatus was in action as before.

The solution of potassa employed in the different parts of the experiment was analysed, with the precautions before described, and gave the following results:--

The quantity of carbonic acid gas absorbed in the first part of the experiment, before the exhibition of chloroform, was 0.80 grains. In the second part of the experiment, during the inhalation of chloroform, 2.78 grains were absorbed; and 2.85 grains after the inhalation, whilst the rabbit was gradually recovering.

Exp. 71.--On December 21st, 1850, a young dog, weighing eight pounds, was placed in the jar holding 1,600 cubic inches, and allowed to remain half an hour, the potash apparatus being kept moving, as in the previous experiment. The dog whined and turned round occasionally, but did not make much muscular effort.

The dog having been removed for a few minutes in order to ventilate the jar, was put in again, and twenty-five minims (thirty six grains) of chloroform were introduced. The potash apparatus, which had been replenished, was moved up and down as before. On the introduction of the chloroform the dog made violent efforts to escape, and his muscular exertions continued, when they were no longer directed by consciousness, till he sank down apparently insensible at the end of about eight minutes. The head and limbs, however, continued to be moved occasionally during the remainder of the half hour. On his removal from the jar the dog yelped, but his muscles were quite flaccid, and he lay for a time where he was placed, and afterwards recovered gradually.

The solution of potassa employed in the half hour just before the chloroform, was found to have absorbed 10.1 grains of carbonic acid, whilst that employed for the same period with the chloroform had absorbed only 4.8 grains. [623/624]

Exp. 72.--On January 19, 1851, a cat about half-grown was placed in a jar holding 920 cubic inches, and allowed to remain for half an hour whilst the potash apparatus was in operation, as in the other experiments. The cat made occasional efforts to get out of the jar.

A few minutes after its removal from the jar, the cat was put in again, and twenty grains of chloroform were introduced through the aperture in the cover. The potash apparatus, having been replenished, was kept in motion, as before. On the introduction of the chloroform the cat made violent efforts to get out. In two or three minutes it became unconscious; but it continued to move involuntarily until five minutes had elapsed, when it sank down in a state of insensibility. During the remaining twenty-five minutes of the experiment the breathing was quick, and much deeper than natural. The cat was quite insensible to pricking and pinching on its removal.

The solution of potassa employed just before the chloroform was given absorbed 5.7 grains of carbonic acid gas; whilst that used during the time that the chloroform was exhibited, absorbed but 2.0 grains.

Exp. 73.--On Feb. 17, 1851, a cat weighing four pounds and a half was placed in the jar holding 1600 cubic inches, and kept there for half an hour. It sat very quietly the whole time. A few minutes afterwards it was put into the same jar again, and eighteen grains of chloroform were introduced by the aperture in the lid. The cat moved about somewhat during the first seven or eight minutes, but it lay sleeping the remainder of the half-hour: it was not insensible on its removal, but inclined to sleep when not disturbed. The cat, having been removed for a few minutes to ventilate the jar, was put in again, and twenty-seven grains of chloroform were introduced. The cat had in a great measure recovered from the effects of the former dose of chloroform during its removal: it attempted to escape on the fresh chloroform being introduced, but soon became quiet and apparently insensible. At the end of half an hour the solution of potassa was changed, without removing the animal from the jar. Chloroform was now added by ten minims at a time, about every ten minutes, till the cat was killed. It died very gradually at the end of three-quarters of an hour. The breathing became very feeble, and intermitted, for long intervals before death took place, and there were no gaspings.

The potash apparatus was in operation during the experiment, and the analysis of the solution of potass gave the following results:--

Carbonic acid gas excreted in half an hour, just before the chloroform, 7.7 grains.

In half an hour, with eighteen grains of chloroform in the jar, 5.7 grains.

In the same time, with twenty-seven grains of chloroform, 4.9 grains.

During the last three-quarters of an hour, 7.1 grains, which is at the rate of 4.7 grains for half an hour.

It will be observed that the quantity of carbonic acid gas excreted under the influence of chloroform was considerably less in all the above experiments than it had been just before; and in the last experiment, it will be remarked that the excretion of carbonic acid kept diminishing as the narcotism increased; whilst in Exp. 70 it increased somewhat during the last stage of the experiment, whilst the effects of the chloroform were subsiding.

It would not be easy to make correct experiments for ascertaining the amount of carbonic acid gas excreted by patients whilst under the influence of chloroform; and my inquiries on this point in the human subject have been confined to such experiments as I could conduct on myself whilst slightly affected by the vapour.

In two experiments related in the last part of this series of papers,* in which oxygen gas was breathed to and fro over solution of potassa, whilst under the partial influence of chloroform, the amount of carbonic acid absorbed by the potash was determined in the manner described above, for comparison with that absorbed in experiments conducted in a similar manner a little time before the chloroform was inhaled (*[part 15]; Medical Gazette, last vol. p. 753). The quantity of carbonic acid as is shown in the following table:--In Exp. 67, for instance, 42 grains of carbonic acid gas were absorbed by the potash whilst breathing oxygen for ten minutes before the chloroform had been inhaled, and only 33 grains during the same period, just after the inhalation of chloroform. [624/625] A similar diminution of the amount of carbonic acid took place in Exp. 68.

In the subsequent experiments enumerated in the table, the air was inspired by the nostrils and expired by the mouth, through a glass tube which conveyed it through a solution of potassa placed in two Woulfe's bottles. The experiments were made at ten or eleven o'clock in the evening, after sitting quietly for two or three hours. The breath was passed through the solution of potassa before inhaling, and then through a similar solution, after inhaling as much chloroform, for three or four minutes, as could be taken without causing unconsciousness. An inspiration of chloroform was also taken, now and then, during the remainder of the experiment, to prevent the effects of the vapour from altogether subsiding.

Soon after the introduction of the introduction of the inhalation of ether, I made some observations on the amount of carbonic acid gas exhaled from the lungs under its influence, by passing the expired air through lime water, when I found the quantity to be diminished* (*See Report of Westminster Med. Soc. in Med. Gaz., Feb. 26, 1847}. The following more recent experiments on animals have been attended with a similar result.

Exp. 78.--On Dec. 15, 1850, a rabbit, weighing four pounds, was kept in a jar, of the capacity of 1600 cubic inches, for forty minutes, the potash apparatus, before described being in motion all the time. The rabbit was perfectly quiet. Soon afterwards, the rabbit was put into the jar again, and forty grains of ether were introduced, which did not cause insensibility, but only inebriation. The rabbit remained in a position between sitting and lying, being able to hold its head up. It was removed at the end of forty minutes.

Twenty minutes after its removal, when the effects of the ether had almost altogether gone off, the rabbit was a third time placed in the jar, for the space of forty minutes.

The analysis of the potash employed in the first part of the experiment, before the ether, yielded 12.6 grains of carbonic acid. The carbonic acid given off during the inhalation of ether was not correctly determined, owing to an accident; but that employed in the third part of the experiments yielded 10.8 grains, showing a notable diminution, although the effects of the ether on the animal had almost ceased to be perceptible.

Exp. 79.--In March, 1851, two pigeons were placed for twenty minutes in a jar holding 670 cubic inches. They stood still the whole time. A few minutes after their removal they were put into the jar again, and sixty grains of ether were introduced, at short intervals, by a few grains at a time. The pigeons became gradually insensible, and at the end of eight minutes were lying on the side. They showed no signs of sensibility when removed at the end of twenty minutes, but lay where they were placed. After being out for three minutes, they were put into the jar again, as they were beginning to evince signs of returning sensibility. In ten minutes more they were able to stand, but they were not fully recovered, when they were removed, at the end of twenty minutes.

The potash apparatus was in action, [625/626] as in the previous experiments. The solution of potassa employed in the first part of the experiment absorbed 6.1 grains of carbonic acid; that employed in the second part absorbed 3.6 grains; and that employed in the last part of the experiment, whilst the effects of the ether was subsiding, absorbed 4.4 grains.

The late Dr. Prout discovered, nearly forty years ago, that fermented and spirituous liquors diminish the amount of carbonic acid given off from the lungs. He summed up the result of his experiments on this point in the following words:--"Alcohol, in every state, and in every quantity, uniformly lessens, in a greater or less degree, the quantity of carbonic acid gas elicited, according to the quantity and circumstances under which it is taken."* Dr. Prout's experiments were confined to the proportion of carbonic acid gas in the expired air (*Ann. Phil. vol. ii. p.336). A recent German author has extended his inquiries to the quantity exhaled in a given time, and he finds that both the proportions in the expired air and the quantity excreted per minute are diminished during the action of alcohol. He also finds that the total amount of every one of the constituents of the urine is lessened, under the same circumstances.† (†Beiträge zur Heilkunde nach eigenen Untersuchungen von Friedr. Wilh. Böcker. Crefeld, 1849. I am indebted to the kindness of Dr. Bence Jones for the knowledge of this work).

The diminution of the amount of carbonic acid formed in the system under the influence of chloroform, ether, and alcohol, taken in conjunction with a circumstance shown in a former paper, that the chloroform and ether are exhaled unchanged from the blood, assist to prove a view of their modus operandi which I suggested with respect to ether, early in 1847.‡ (‡See Med. Gaz. vol. xxxix. p. 383). That view may be stated as follows.

Chloroform, ether, and similar substances, when present in the blood in certain quantities, have the effect of limiting those combinations between the oxygen of the arterial blood and the tissues of the body which are essential to sensation, volition, and, in short, all the animal functions. The substances modify, and in larger quantities arrest, the animal functions, in the same way, and by the same power, that they modify and arrest combustion, the slow oxidation of phosphorus, and other kinds of oxidation unconnected with the living body, when they are mixed in certain quantities with the atmospheric air.

This explanation is probably applicable to the action of all narcotics whatever, but is here applied only to the class considered in these papers, namely, the volatile narcotic substances not containing nitrogen, or those substances whose power was found to be in the inverse ratio of their solubility in water and the serum of the blood.

The circumstances which appear to my mind fully to establish the above stated theory of the operation of chloroform and similar bodies, are enumerated in the following propositions:--

1. Sensation, motion, thought, and indeed all the strictly animal functions, are as closely connected with certain processes of oxidation going on in the body, as the light and heat of flame are connected with the oxidation of the burning materials.

2. The diminution of the amount of carbonic acid gas excreted by the lungs under the influence of chloroform, ether, and alcohol, shows that the processes of oxidation going on in the body are lessened, for the amount of carbonic acid given off has a pretty close relation to the quantity of oxygen consumed.

3. The diminution of temperature in animals under the influence of chloroform and ether, alluded to in an early part of these papers, also shows that the processes of oxidation which take place in the body are diminished, since the development of animal heat has been shown, by Edwards and others, to have a constant relation to the quantity of oxygen which is consumed in respiration.

4. The venous blood in patients under the influence of chloroform or ether is less dark in colour than in the normal state; indicating that those changes in the blood which take place in the systemic capillary circulation are diminished.

5. The lessened quantity of all the constituents of the urine, observed by Böcker, from the effects of alcohol, also shows that oxidation is diminished.

6. The diminished oxidation is not owing to the combination of the narcotic substance with the oxygen of the arterial blood; for in the first place, the chloroform and ether, as well as part of the alcohol, have been shown to escape unaltered in the breath; in the second place, the quantity of material, in the case of chloroform, capable of combining with oxygen, is altogether insufficient so to appropriate the oxygen; and in the third place, to increase the amount of oxygen in the respired air does not prevent the action of the narcotics.

7. The different parts of the nervous system lose their power under the influence of the narcotics we are considering, in the same order as in asphyxia--the privation of oxygen, as was observed by M. Flourens with respect to ether, in 1847* (*Gazette des Hôpitaux, 20 Mars, 1847).

8. The muscular irritability, which continues for a short time after death, depends on the action of a little oxygen still remaining in the system; and this irritability can be at once extinguished by chloroform, ether, or alcohol, in proportion rather larger than is necessary to cause death. When the muscular irritability is thus extinguished, post-mortem rigidity comes on almost immediately, and lasts for an unusually long time, if the narcotic employed is prevented from evaporating.

9. The vapours of volatile narcotic substances have the property, when mixed with the air, of retarding, and, in larger quantity, of arresting, that form of oxidation which constitutes ordinary combustion; and their power in preventing combustion generally bears a direct relation to their narcotic strength.

10. Many of these same vapours have the property of preventing the slow oxidation of phosphorus, which renders it luminous in the dark, as was discovered by Prof. Graham; and their effects, in this respect, have a general relation to their narcotic power.

11. The putrefaction of animal substances consists, on its commencement at least, of a process of oxidation; and the numerous class of substances we are considering all have the property of preventing putrefaction, their antiseptic power having generally a direct relation to their narcotic properties.

12. The reduction of the temperature of the body, by exposure to cold, diminishes the consumption of oxygen, and causes symptoms very nearly resembling the effects of a narcotic.

The second and sixth of the above propositions have already been fully considered, and the remainder will receive further consideration in my next paper.