Source: Snow, John. London Med.
Gazette 48 (26 December 1851): 1090-94.
On narcotism by the inhalation of vapours
By John Snow, M.D.
Antiseptic power of narcotics--Narcotic vapours and gases prevent ordinary combustion--They prevent the slow combustion of hydrogen by means of spongy plotinum--They prevent the oxidation of phosphorus--Nature of the power by which narcotics prevent oxidation in the living body and out of it--Recapitulation.
During the last two years, whilst the investigation which I have been making respecting chloroform and ether, and publishing from time to time in the Medical Gazette, have been directed more particularly to showing the modus operandi of these agents, M. Robin, of Paris, has been engaged in a like inquiry, and has arrived at similar conclusions, although his researches have been made in a different manner. His opinion was given at the Academy of Sciences to the following effect;--That the anæsthetic action of the vapour of ether or chloroform is the result of a state of asphyxia more or less complete; but that this kind of asphyxia is produced by these agents, when absorbed, protecting the blood in the capillary vessels against the action of the oxygen, in the same way that they protect a piece of flesh, or any other animal substance that is plunged into them, against the action of the same agent oxygen, and thus prevent putrefaction* (*See Comptes Rendus, t. xxx. p. 52). [1090/1091] M. Robin subsequently gave his views to the Academy in a more extended form. He stated that all substances which will preserve dead animal and vegetable matters against putrefaction are capable of acting as poisons to all organised beings, whether possessed of a nervous system or not; that the action is independent of their coagulating or not coagulating albumen; and that it consists in the power they have of protecting organised matters from slow combustion by moist oxygen. He stated that they diminish or completely interrupt the combustion according to the quantity; and that, in proportion to the dose, they are sedative medicines to animals, and asphyxiating poisons to all organised beings* (*Comptes Rendus, t. xxxi. p. 383; and Med. Gaz. vol. xlvi. p. 590).
The following are amongst the substances enumerated by M. Robin as having the properties in question:--Sulphuric ether, chloroform, benzin, Dutch liquid, hydriodic ether, acetic ether, naphtha, sulphuret of carbon, camphor, protochloride of carbon, carburet of nitrogen, hydrocyanic acid, and arsenic. The first seven of the above agents are amongst those whose narcotic effects I have described in the Medical Gazette.
The antiseptic power of these and other substances is probably in direct proportion to their narcotic strength; at all events, I have ascertained that such is the case as regards chloroform, ether, and alcohol. A few drops of chloroform, when put into a bottle, form enough vapour to prevent putrefaction in a piece of flesh suspended in it; but it requires a larger quantity of ether, which is a less powerful narcotic, to produce a like effect. One part of ether, when mixed with nine or ten parts of water, preserves animal matters; but a larger proportion of alcohol is required for a like effect; and alcohol, as is well known, requires to be taken in much larger quantity than ether to cause insensibility. I have often observed the antiseptic powers of chloroform, even in the small quantity which suffices to cause the death of an animal, especially when it has been inhaled slowly, so that the tissues were intimately impregnated with it. For instance, the cat which formed the subject of Experiment 73 in a former paper, and which was killed with chloroform, was kept for sixteen days in a temperature between 50° and 60° Fahr., and, at the end of that time, the rigor mortis was only beginning to subside, and putrefaction had scarcely commenced.* (*I am persuaded that the antiseptic properties of various substances are capable of producing greater advantages than they have hitherto, especially if applied by the method of injecting the arteries immediately after death, which was described in my last paper. Owing to the difficulty of curing meat by the ordinary methods in tropical climates, thousands of oxen and sheep are slaughtered in South America and Australia, for the tallow and hides, whilst the flesh is left to rot; when, by injecting the vessels, it could be immediately rendered as firm as in the coldest climate. There would probably be a prejudice against using a medicine such as chloroform for this purpose; but it fortunately happens that the essential oils, which exist in nearly all condiments, are both narcotic and antiseptic. I have frequently made insects insensible by exposing them in a covered vessel to the vapour of oil of peppermint; and, on one occasion, I rendered a linnet insensible by the inhalation of the vapour of oil of lemons: by injecting twenty minims only of the latter essential oil (shaken up with an ounce of water) into the arteries of a rabbit after death, it kept very well for seventeen days. I have found that injecting with a saturated solution of common salt very much hastens rigidity, although it does not produce it immediately. I hope that some one who has the opportunity will follow up this subject, as it promises to yield a kind of wealth more useful than the newly discovered treasures of California and Australia.)
The substances which have the property of limiting and preventing oxidation in the living body, have also the property of limiting and preventing that kind of oxidation which constitutes ordinary combustion. If, for instance, as much ether as will make not less than about eight cubic inches of vapour be diffused through the air of a bottle or jar holding one hundred cubic inches, and a lighted taper be lowered into the vessel, it will be extinguished. The vapour of ether will take fire at the mouth of the bottle; but the taper will go out as it descends into the air mixed with vapour not in a state of combustion. Flame is extinguished also by the vapour of chloroform when in sufficient quantity, and by many other vapours and gases. Sir Humphry Davy, whose investigations on flame resulted in the discovery of the safety lamp, thought at first that the power of preventing combustion in these instances depended on the cooling power of the gas employed as a diluent; but, on making experiments with various gases he found that some other cause or causes existed. Olefiant gas had a much greater effect in preventing the [1091/1092] explosion of oxygen and hydrogen by the electric spark than any of the other gases employed by Sir H. Davy, and this gas is a more powerful narcotic than carbonic acid, or any of the others he used, except sulphuretted hydrogen (which probably acts in a different manner from ordinary narcotics), for I have found that olefiant gas causes immediate insensibility in birds, when mixed with the air in the proportion of one part to ten.
Dr. Henry, and Professor Graham,* have ascertained that a number of gases have the effect of preventing the slow combination which takes place between oxygen and hydrogen with the aid of spongy platinum, and that the relative power of the various gases is nearly the same in this instance as when the electric spark is employed, olefiant gas being the most powerful. (*Quarterly Jour. of Sc., 1829, part ii, p. 354.)
Professor Graham discovered† that a number of vapours, as well as gases, have the property, when mixed with atmospheric air, of preventing the slow oxidation of phosphorus, which renders it luminous in the dark. He found that olefiant gas, and the vapour of oil of turpentine, and of other essential oils, possess this power, even when present in a very minute quantity. (†Op. Cit.) I expressed an opinion nearly five years ago,‡ that the action of ether on the human frame was of the same kind as that by which it prevented the oxidation of phosphorus (‡See Med. Gaz., vol. xxxix. p. 333); and this view is supported by the fact, that amongst substances of a similar constitution, whose narcotic power is known, this power bears a direct relation to the power of preventing the oxidation of phosphorus. For example, I find that the vapour of alcohol has but little influence in this respect, whilst Prof. Graham found that the vapour of ether, in the proportion of one part to 150 of air, prevents the oxidation of phosphorus at all temperatures up to 64° Fahr.; that one part of olefiant gas (which is a more powerful narcotic) has a like effect in 450 parts of air; and that one part of vapour of naphtha exerts this influence when diluted with 1820 parts of air. Now naptha consists chiefly of benzin, which, as was stated in a former paper, causes insensibility when less than a grain of it i[s] diffused in each hundred cubic inches of the respired air. Professor Graham ascertained that hydrochloric acid gas promotes the oxidation of phosphorus in the air; and I find that the vapour of chloroform does not prevent it: this is probably due to the chlorine it contains in such large quantity.
Professor Graham states that olefiant gas prevents phosphorus and hydrogen from uniting with oxygen without undergoing any change itself. This is exactly analogous to the action of ether and chloroform in the human body, which, as shown before, produce their effects, and pass off unchanged in the expired air.
Having traced the narcotic action of ether and other bodies to the more general law of their power of preventing oxidation under a great variety of circumstances, the mind naturally inquires by what kind of power oxidation is thus prevented. I feel considerable diffidence in offering a theory on a subject which falls as much within the domain of ordinary chemistry, as within that of physiology, when so eminent a chemist as Professor Graham has investigated a number of its details without suggesting any general explanation on the matter. However, as I have formed a theory in my own mind, I offer it for consideration: it is to the following effect:--That chemical attraction or affinity is a constantly acting force, by which each atom of matter exerts an influence on all other atoms within the sphere of its attraction, whether they are of the same or of a different kind, the force of the attraction varying with the respective nature of the substances, and the physical conditions in which they are placed. In this point of view, it will be seen that any two substances in a condition to unite together might be prevented from doing so by the intervention of a third body possessing a sufficient attraction for either of the others; and it would not be necessary that this third body should itself enter into chemical combination; for a balance of forces might be established, so that the three substances would remain exerting reciprocal attractions for each other, but unable to enter into more intimate union.
In the instances of prevented oxidation previously considered, the interfering substances no doubt owe their influence to their attraction for oxygen. [1092/1093] These substances, in fact, are known to possess a strong affinity for oxygen, being nearly all of them highly combustible. Those of them which have the greatest power in preventing oxidation--olefiant gas and benzin--contain no oxygen in their composition; whilst the oxide of ethyle, which contains rather more than one-fifth of its weight of oxygen, has less power; and alcohol, which consists of oxygen to the extent of rather more than one-third, has much less power than ether as a narcotic, as an antiseptic, and in preventing the oxidation of phosphorus. The salts of ethyle, without oxygen, produce narcotic effects also in much smaller doses than its oxygen salts. It was previously shown that the narcotic powers of the ethers and other allied agents was in the inverse ratio of their solubility in water,--a generalization which is in perfect accordance with what is now stated; for it so happens that the agents of this class which contain oxygen are more soluble than those which do not.
As regards their application to the substances when acting as narcotics, the views just explained may be thus briefly stated. When absorbed into the blood, they have attraction for the oxygen dissolved in it; and though unable to combine with the oxygen under the circumstances, the attraction is sufficient to counteract that existing between the oxygen, on the one hand, and the certain constituents of the blood and tissues of the organs, on the other; and thus the combination between the respired oxygen and the materials of the body--those changes which are, in a manner, the essence of all the animal functions--are prevented more or less completely, according to the dose of the narcotic.
There is a curious circumstance connected with the oxidation of phosphorus, to which it is necessary to allude. Professor Graham found that pure oxygen has no action on phosphorus under the atmospheric pressure, at temperatures below 64°; but that a slight expansion of the gas, by diminishing the pressure two or three inches, or diluting the oxygen with nitrogen, hydrogen, or certain other gases, enables it to act on the phosphorus, which then becomes luminous in the dark. The explanation I would offer of this circumstance is, that the attraction or affinity of the atoms of oxygen for each other is sufficient to prevent their combining with the phosphorus until that attraction is weakened by their separation to a greater distance by the diminution of the pressure of the intervention of the atoms of another gas.
In dismissing this part of the subject I should like to remark, that whatever may be thought of the above explanation of the power by which certain narcotics retard or arrest oxidation in the animal frame, will not affect the fact of these narcotics acting in this way, for it rests on distinct evidence previously stated.
I have said nothing of the stimulant or irritant properties which chloroform, ether, alcohol, and probably all narcotics, possess in a greater or less degree, and I have not space to enter on that subject; but I expect to be able to show on another occasion, that the irritation caused by narcotics is not opposed to the view of their acting in the way explained in the previous pages.
These papers on narcotism by the inhalation of vapours have extended over a very much longer time than I expected, and I have done after all much less than I intended. In now brining them to a close, however, it may be well to give a brief recapitulation of the more prominent points which I have endeavoured to establish.
Several experiments with chloroform and ether were described, the object of which was to determine the quantity of these agents which exists in the blood in a state of insensibility. The method employed was that of placing a small animal in a large vessel, containing a known quantity of vapour mixed with the air, and allowing it to remain till the effects of the vapour no longer increased, but became stationary; when, the solubility of the vapour in the serum of the blood being known, the quantity absorbed could be calculated from the relative saturation of the air. It was found that, with both chloroform and ether, the proportion, in a state of complete insensibility, was about one twenty-eighth part as much as the blood would dissolve. Similar experiments were made with several other substances, including some salts of ethyle, benzin, bromoform, Dutch liquid, and sulphuret of carbon, and it was found that the proportion absorbed into the blood, in causing insensibility, [1093/1094] was nearly the same as in the case of ether or chloroform. Hence the rule was deduced, that the narcotic strength of these substances was in the inverse ratio of their solubility. The agents to which this rule applies resemble chloroform and ether in containing carbon, and not containing any nitrogen as a radical element, and some of them were used as was described with success, in preventing the pain of surgical operations.
A description of the influence of chloroform was given, in which the effects it produces, if continued until respiration is suspended, were divided into five degrees. It was stated that when chloroform is given to animals neither very quickly or slowly, and continued till the breathing is arrested, the heart continues to beat; but some experiments were detailed which show that chloroform is capable of arresting the action of the heart, if absorbed in sufficient quantity.
The cases of accident from inhalation of chloroform, which had happened up to the time of writing, were next considered, when it appeared that the fatal event in these cases was due to the vapour of chloroform being given in too concentrated a form, by which not only was the breathing suddenly arrested, but the action of the heart was also paralysed by the effect of the vapour.* (*The fatal cases which have since happened, together with some that narrowly escaped being fatal, entirely confirm the opinion then expressed. The alarming symptoms always came on in the most sudden manner, the action of the heart being suspended without previous warning, although in some of the cases there had been at first an apparent difficulty in rendering the patient insensible. No means were used in any of these cases to insure a proper dilution of the vapour with air, a handkerchief being merely employed for administering chloroform, except I believe in one case, where it was not administered by a medical man.)
The opinion was expressed that chloroform, if given gradually and with due care, may be safely employed in every case in which a surgical operation has to be performed; an opinion in which I have been altogether confirmed by further experience.
Directions were next given for the administration of chloroform in various kinds of operations; the conditions and diatheses which influence its action were considered, and a numerical result of the larger operations in which I had administered chloroform or ether at that time was given, by which it was shown that the result had been favourable.
After some remarks on the use of Dutch liquid in operations and midwifery, some experiments with alcohol were detailed, by which it was shown to resemble ether and chloroform in its effects and mode of action. Experiments were related showing that chloroform passes off unchanged in the expired air; that it can be detected in limbs amputated whilst patients are inhaling, and also in the dead bodies of animals killed by it. It was next shown that ether and alcohol can be detected in the expired air, and that the quantity of carbonic acid excreted by the lungs is diminished under the influence of chloroform and ether. For these and other reasons the conclusion was arrived at, that the class of narcotics we have been considering, and probably other narcotics also, produce their effects by virtue of a power they possess of retarding the action of the respired oxygen on the blood and tissues of the body.
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