Source: Snow, John. London Med. Gazette 48 (19 December 1851): 1053-57.
On narcotism by the inhalation of vapours
By John Snow, M.D.
Action of oxygen in respiration--Nature of asphyxia--Comparison between asphyxia and narcotism--Between narcotism and apoplexy--Cause of the symptoms in apoplexy--Diminished production of carbonic acid, and reduction of temperature under the influence of narcotics--Narcotic effect of cold--Colour of the blood under the influence of chloroform and ether--Irritability of the muscles after death--Effect of chloroform, etc. on this irritability, and on the rigor mortis--Modus operandi of chloroform, etc.
For a length of time after the changes which are effected in the air by respiration were discovered, it was generally believed that the carbonic acid was formed in the lungs, by the union of the oxygen of the air with carbon contained in the blood; and the phenomena of asphyxia were thought to be occasioned by the direct action of some form or combination of carbon which ought to have been excreted. Experiments by Edwards, and others, on the respiration of animals in hydrogen gas, and especially the beautiful experiments of Professor Magnus on the blood, clearly proved, however, what many physiologists had believed from the first,--that the oxygen of the air is absorbed (along with some nitrogen) and circulates with the arterial blood, combining with carbon in the systemic capillary circulation; and thus forming the carbonic acid which is exhaled from the blood in its passage through the lungs. Asphyxia is simply due to the want of oxygen in the arterial blood: for, although there is a little carbonic acid gas present in this blood during the more ordinary forms of asphyxia, yet the same symptoms occur to animals placed in hydrogen or nitrogen gas, although the carbonic acid gas in the blood is then exhaled. The presence of oxygen in the blood seems absolutely necessary to the performance of the animal functions--so necessary that none of them can continue an instant without it. Animals live, it is true, for a short time after they are deprived of air, but a little consideration shows that they live only by virtue of the oxygen which is contained in their bodies, and that when this is consumed life no longer continues. The length of time which animals live after they are deprived of air is in the inverse ration of the activity of their functions, and Dr. W. F. Edwards has shown* that animals of cold blood, as reptiles and fishes, die of asphyxia nearly as quickly as animals of warm blood when they are placed in water deprived of air, and of a temperature of about 100° Fah. (*De l'Influence des Agens Physiques sur la Vie.) The increase of heat quickens the changes taking place in the body, as the same author has proved by distinct experiments: the oxygen dissolved in the fluids of the animal is soon appropriated, and life is then extinct. Animals of cold blood can also be quickly killed at the ordinary temperature by the rapid absorption of agents, such as the vapour of ether, which have the undoubted power of arresting oxidation out of the body, and when present in the blood in sufficient quantity, have the effect of preventing the oxygen it contains from any longer entering into combination. The experiments of Dr. Kay† show that venous blood has some power of supporting the functions of the brain, and the irritability of the muscles when injected into the arteries, but this depends on some free oxygen it contains; for the analyses of Magnus have proved that arterial blood is only deprived of part of its oxygen by passing once through the systemic capillaries (†The Physiology, Pathology, and Treatment of Asphyxia, p. 193).
The relation between asphyxia and narcotism is this--that in asphyxia there is an absence of oxygen, whilst in narcotism the oxygen is present, but is prevented from acting by the influence of the narcotic. With this close affinity between asphyxia and narcotism, as regards their intimate nature, there is, as might be expected a great similarity in the phenomena of the two conditions. The different parts of the nervous centres lose their power, under the influence of ether and chloroform, in the [1653/1654] same order as in asphyxia. The action of the heart continues in asphyxia after the muscles of respiration have ceased to contract, and this is the case under the effects of chloroform, alcohol, ether, and probably all narcotics, when they are absorbed in a gradual and uniform manner. For, as the muscular contractions of a peristaltic character, which are under the influence of the ganglionic system of nerves, can go on with a smaller amount of oxygen than those which are dependent on the cerebrospinal system, so it requires a larger quantity of the narcotic to arrest them. During sudden asphyxia of robust subjects by privation of air, there are generally convulsions after the loss of consciousness, and there is likewise usually an amount of muscular rigidity and contraction approaching to convulsions when insensibility is quickly induced by chloroform or ether, in muscular persons or robust animals. By gradually inducing narcotism these contractions can be avoided, and in like manner, when asphyxia is slowly induced by vitiation of a limited supply of air, convulsions are not induced. The impediment offered to the absorption of oxygen in the lungs during bronchitis is sometimes accompanied by delirium not unlike that caused by a narcotic, and occasionally coma is met with. The state of the fœtus in utero--just able to perform a few languid movements of its limbs--resembles very much the sleep caused by a narcotic. At this time it receives only a limited supply of oxygen at second hand through the placenta; but on being born, no sooner has it taken one or two free inspirations, than it exhibits an amount of activity and strength which would be fatal to the mother did it possess it whilst in the womb.
With all these points of resemblance between narcotism and asphyxia, it might perhaps be asked why a limitation of the supply of air, or in other words a partial asphyxia, might not be resorted to instead of a narcotic to prevent the pain of operations. The answer must probably be sought in the circumstance remarked by all the observers of the phenomena of asphyxia, that the blood becomes arrested at the pulmonary capillaries, when oxygen is no longer admitted into the air cells of the lungs. On this account insensibility cannot be induced by means of asphyxia, without causing congestion of the lungs, and great distress of the respiration.
In a profound state of narcotism the symptoms often exactly resemble those of apoplexy. In both conditions there is a partial suspension of the process of oxidation on which the functions of the brain depend; but this impediment to the natural process of oxidation arises from a different cause in the two cases. In narcotism it is due to the presence of the narcotic substance in the blood, which retards oxidation, as we shall presently see, by a kind of counter affinity for the oxygen: in apoplexy it depends on more or less complete interruption to the circulation of the blood. For the constant action between the oxygen of the arterial blood and the brain, there is obviously required a never-ceasing current of blood; and when this is interrupted in any part of the brain, it matters not whether the circulation be interfered with by pressure arising from effusion, by the occlusion of one or more of the arteries which cuts off part of the supply, or by such an amount of congestion from any cause that the current of the circulation is interrupted. According to these views it ought not to signify whether there is increased or diminished pressure in the cranium, or whether the quantity of blood in the brain is more or less than natural; but if the circulation is interrupted or greatly impeded, there ought to be the symptoms which arise from impeded oxidation. Such indeed is the fact; we meet with the same symptoms in very different physical conditions of the contents of the cranium, and the question of bleeding and the application of other remedies cannot be decided by the cerebral symptoms alone, without the consideration of other particulars.
The circulation through the capillaries of the brain is undoubtedly sometimes retarded under the influence of narcotics; but this is the consequence and not the cause of the impeded functions of the brain. For, as was first pointed out by Professor Alison, the functions of the various organs of the body are accompanied by a force which aids the capillary circulation; and on the function of any organ being interrupted, the circulation through it is retarded, as is seen in the most striking manner in [1054/1055] the lungs during asphyxia. There is this further difference also between narcotism and apoplexy, that the narcotic acts directly on all parts of the body as well as on the brain, whilst in apoplexy the remainder of the nervous system and the other organs of the body are only effected in a secondary manner.
In my last communication,* several experiments were detailed which show that the quantity of carbonic acid evolved from the lungs is considerably diminished under the influence of ether and chloroform (* See last vol. p. 622 [part 16]). This circumstance indicates diminished oxidation, for carbonic acid is the chief product of that process in the animal frame, and it bears a pretty close relation to the amount of oxygen consumed. Dr. Prout formerly showed that the quantity of carbonic acid produced in respiration was diminished after drinking alcoholic liquors, and alcohol very much resembles ether and chloroform in chemical constitution and physiological effects. Under the influence of this agent, alcohol, Böcker ascertained, as was noticed before, that the amount of every one of the constituents of the urine is diminished, and phosphoric acid and urea are important products of oxidation.
In some experiments detailed in the first part of these papers,† the temperature of animals was seen to diminish under the continued influence of ether and chloroform (†Medical Gazette, vol. xli. p. 850). This circumstance is also illustrative of the diminished oxidation that is taking place, for the experiments of Dr. W. F. Edwards‡ (‡Op. cit.) on animals of various species, at different seasons of the year, show that the consumption of oxygen in respiration always bears a direct proportion to the evolution of animal heat.§ (§ The cooling of animals, in Sir B. Brodie's experiments, when the circulation was kept up by artificial respiration, after they were reduced to a state of suspended animation by narcotics, gives support to the above views; allowance being made for the artificial condition of the animals. The other experiments of this eminent physiologist, in which animals were found to cool rapidly under similar circumstances, after removal of the brain, are not at all opposed to the view that animal heat results from the process of respiration, if we reflect that respiration, or oxidation, is essential to all the animal functions, and that the formation of phosphoric acid and urea are probably as much accompanied by the evolution of caloric, as is the formation of carbonic acid.)
Gradual exposure to a lower temperature, as happens in the change of season from summer to winter, alters the constitution of many animals, causing them to consume more oxygen and thus to develop more heat, and bear up against a colder season; but other species, including some mammalia, as well as nearly all reptiles are narcotised by the cold, and fall into a state of torpor in the winter, when the consumption of oxygen is reduced to a minimum. Cold air, or whatever abstracts the heat of the body, so as to make a considerable reduction in its temperature, is a true narcotic, and acts like other narcotics, by diminishing oxidation. Travelers in the arctic regions inform us that the symptoms produced by intense cold are sometimes not to be distinguished from intoxication by alcohol, except by the circumstance that no spirituous liquor can have been obtained. As regards its local effects, cold is probably the narcotic which has been longest known to the human species; for its benumbing effects (??????, I benumb) make themselves felt, in the fingers at least, in most parts of the earth, at some season of the year. The local application of cold closely resembles that of chloroform and many other narcotics, in causing a slight amount of pain before sensibility is altogether abolished. Dr. James Arnott, who has given great attention to the local effects of graduated temperature in the treatment of various affections, has relieved neuralgic pains by the application of a mixture of salt and pounded ice, and has also rendered the surface of the body so insensible, that the introduction of setons, and other operations of a superficial nature, have been performed without pain. Dr. Arnott calls the process congelation; but the hardness which is produced in the part must depend on the solidification of the adipose substance; for if the water which enters into the composition of the tissues were frozen, then intimate structure would be destroyed, and a slough would be the result.
The effects of ether and chloroform on the appearance of the blood agree perfectly with the view above given of their modus operandi. There is generally no alteration in the complexion of the patient, or in the colour of the mixed venous and arterial blood as it [1055/1056] flows from the wound, so long as the inhalation is not pushed to the extent of embarrassing the respiration, and provided the patient is not holding his breath, on account of the pungency of the vapour, or a general state of rigidity which sometimes occurs for a minute or two; but when the blood which flows from the arteries and veins can be separately observed, whilst the patient is well under the influence of the narcotic, it is seen that the arterial blood is somewhat less florid, and the venous blood less dark than under ordinary circumstances. The lighter colour of the venous blood, which has been spoken of by Dr. Gull, as well as by myself, points particularly to a diminution of oxidation in the systemic capillaries.
The phenomena attending the irritability which remains in the muscles for a longer or shorter time after death, and particularly the effect of narcotics on this irritability, accord exactly with the views above expressed. It can be shown, by the following amongst other reasons, that the muscular irritability depends on a little oxygen still remaining in the blood contained in the muscular tissue. Nysten* found that the injection of oxygen gas into the cavities of the heart increased the vigour and duration of the contractions (*Recherches Physiologiques, p. 335). Sir B. Brodie states that, in dogs in which the circulation was kept up after death by artificial respiration, "there seemed to be actually an increased irritability of the voluntary muscles, continued not for a short time, but even for an hour and a half."† (†Physiological Researches, 1851, p. 108.) Nysten informs us‡ that the general result of his observations on the duration of the muscular irritability in animals of different classes, and of different orders of the same class, was in the inverse ratio of the muscular energy developed during life (‡Opus cit. p. 355); and we previously saw, on the authority of Edwards, that this was just the ratio of duration of life under privation of air or asphyxia.
Chloroform ether, alcohol, and probably all narcotics, have the power of suspending the muscular irritability. In a former paper of this series§ some experiments were related in which the irritability of the heart in frogs and rabbits was removed by the vapour of chloroform; and in two of the experiments the irritability was alternately allowed to recover by letting the chloroform evaporate, and then suspended again by a fresh exposure to the vapour (§ Vol. xlii. p. 415 [part 5], 614 [part 6]). In one of these experiments the peristaltic action of the small intestine of a rabbit was arrested by the local action of chloroform. I have frequently stopped the quivering motion of the intercostal muscles, which is seen on opening the chest of an animal immediately after death, by blowing a little vapour of chloroform on them through a tube. On one of these occasions Dr. Sibson was present.
The following experiments show the action of chloroform, etc., on all the muscles of the body:--
Exp. 80.--A half-grown guinea-pig was made to inhale chloroform in a glass jar till it ceased to breathe. The chest was then opened, and a tube armed with a stop-cock was introduced into the aorta and tied. The heart was still contracting, and the muscles were very sensible to the shocks of an electromagnetic apparatus. Fifteen minims of chloroform, and two drachms of tepid water, which had been agitated together till the chloroform was suspended in minutes globules, were now injected. At the moment of injection the right anterior extremity and the two posterior extremities were stretched out, and the toes quivered. These limbs became quite rigid at the moment of the injection, as did also the neck and trunk of the animal. The left anterior extremity remained flexible. The wires of the battery were applied to the muscles of various parts of the body immediately after the injection, but no contractions could be excited, except in the left anterior extremity, and the muscles of the chest on the same side, which remained as irritable as before; the reason of this being that the injection had not entered the left subclavian artery. The heart ceased to act at the moment of the injection, and was afterwards quite insensible to the shocks of the battery.
Exp. 81.--A similar guinea-pig to the last was killed by the inhalation of ether, and was opened immediately after it ceased to breathe, whilst the heart was still acting. The tube was secured in the descending aorta, and two fluid drachms of sulphuric ether were injected. The posterior extremities were stretched [1056/1057] out at the time of the injection, and there was a quivering motion of the toes. These extremities, together with the posterior half of the trunk, became instantly affected with post-mortem rigidity, and were totally insensible to the shocks of the electro-magnetic battery. The anterior extremities, and, indeed, all the anterior part of the body which had not been injected with ether, remained sensible to the shocks of the battery, and only became rigid between two and three hours after death. The heart ceased to act at the moment of the injection, some ether having been dropped on it from the syringe.
Exp. 82.--An ounce of rectified spirit of wine was injected into the aorta of a cat immediately after death from chloroform. There were muscular contractions at the moment of injection, but no contractions could be excited afterwards by mechanical irritation, although the muscles were very irritable just before, and were quivering when not touched. The heart, which was previously beating, also ceased to act. Post-mortem rigidity began to take place five minutes after the injection, and it still existed eight days afterwards.
Exp. 83.--A cat was killed by inhalation of chloroform, and three minutes after death three drachms of rectified spirit of wine, of 80 per cent, were mixed with three drachms of water, and injected into the descending aorta. The posterior extremities were stretched out at the moment of the injection, and almost immediately began to be rigid; and in less than ten minutes after the injection, the whole of the posterior half of the body was very rigid, whilst the anterior parts were quite flexible. An hour after death rigidity was commencing in the anterior extremities, and in half an hour more they and the neck were quite rigid. This cat was killed on Dec. 1st, 1850, and was kept in a room with a fire. The rigidity of the anterior half of the body began to subside at the end of a week, but that of the posterior extremities not till a fortnight had elapsed; and they were still quite fresh, although putrefaction was commencing in the chest and neck.
As absorption of vapour continues in the frog by its skin after the respiratory movements have ceased, it is not necessary to resort either to dissection or injection in them, as in mammalia, in order to cause the extinction of irritability, and bring on the post-mortem rigidity. It can be induced in a very few minutes by exposure to the vapour of ether or chloroform, although, under ordinary circumstances, the muscles remain long irritable and flexible in these animals. In some interesting experiments lately detailed in the Medical Gazette by Mr. W. F. Barlow,* that gentleman produced rigidity in a single limb of living frogs without much affecting the rest of the animal (*Page 713); he also observed what I had previously remarked,† that the setting in of rigidity in these animals is sometimes accompanied by a movement of the body (†[part 5] Med. Gaz., vol xlii. p. 415).
The state which is called post-mortem rigidity appears to be the natural condition of muscle when no kind of change in its composition is taking place. As long as the feeble oxidation continues, which enables it to be irritable after death, it remains flaccid; but when this ceases, from want of oxygen from reduction of temperature, from the counter affinity of a narcotic, or from exhaustion of the nutrient materials, the muscle becomes rigid, and remains so till a new kind of oxidation--that of putrefaction--commences, when it again becomes flaccid. Although the muscles, when affected with this kind of rigidity, are in a state of completely suspended animation, they are not always incapable of again living; for M. Brown-Seqnard has restored the irritability of the muscles of a dead guinea pig after they had been rigid from ten to twenty minutes, by making the blood of a living animal of the same species circulate in its vessels. Although reducing the temperature hastens rigidity, it is not essential to it; for I have seen a fœtus at the full term born in a state of complete rigor mortis.
In a former paper,‡ several proofs were given that chloroform and ether do not prevent oxidation in the system by themselves combining with the oxygen of the blood (‡[part 13] Vol. xlv. p. 626). Among these proofs were some experiments showing that the chloroform and ether are exhaled again unchanged from the blood as it circulate through the lungs. The paper of next week will contain an inquiry into the manner in which these narcotics act in limiting and preventing oxidation in the living frame.
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