Source: Snow, John. London Med. Gazette, vol. 42,  Oct. 13, 1848, pp. 614-619 (part 6).

On narcotism by the inhalation of vapours

By John Snow, M.D.

Vice-President of the Westminster Medical Society.

[Part 6]

Phenomena attending death from Chloroform.--Post-mortem appearances.--The fatal cases of inhalation of Chloroform.

In my last communication it was shewn, that when an animal of warm blood is made to breathe the vapour of chloroform, well diluted with air, until death ensues, the heart continues to pulsate for some time after the respiration has ceased, the circulation being arrested, secondarily, by the failure of the breathing. It was also shewn, by some experiments on frogs, that chloroform has the effect of directly paralyzing the heart, when it is absorbed in a somewhat larger quantity than is required to stop the respiratory movements. It is possible, indeed, to narcotize the heart of warm-blooded animals by chloroform. When the vapour is exhibited to them in a concentrated form, the breathing and circulation appear to cease nearly together; probably, because the quantity of vapour in the lungs, at the time the breathing stops, is sufficient, when absorbed, and added to that already in the blood, to narcotise the heart. The two following experiments confirm this view.

Exp. 44.--120 grains of chloroform were put into a jar of the capacity of 600 cubic inches, which was kept accurately covered with a piece of plate-glass, and moved about to diffuse the chloroform over its sides. In a few minutes the chloroform was all converted into vapour. The temperature of the jar was 65?; the air in it was consequently nearly saturated with vapour, and contained 20 grains in each 100 cubic inches. A young rabbit was put into the jar. It was very quickly affected, and ceased to breathe in less than a minute. It was taken out immediately the respiration ceased, and the ear was applied to its chest, but no motion of the heart was audible. The thorax was opened as quickly as possible, and when the heart was first observed it was quite motionless; but it had not been exposed to the air for a minute, before it began to contract, the auricles beginning to move first, and shortly afterwards the ventricles,--and in three or four minutes it was contracting vigorously. This recommencement of the heart’s action no doubt resulted from the influence of the vapour. Soon after the chest had been opened, a drop of chloroform was allowed to fall on the heart, and its motion instantly ceased, but gradually commenced again in the course of a few minutes, and it continued to contract feebly for some time. The lungs, which collapsed as soon as the chest was opened, were, when first observed, of a vermilion tint. This colour of the lungs is an additional proof that the circulation had not continued after the respiration ceased. There was active vermicular motion of the intestines of the rabbit when they were exposed to the air, soon after death, and a drop of chloroform being put on the ileum at once stopped the contractions at the place of contact, whilst they continued as before in the rest of the intestine. The next morning the body of the rabbit was rigid, and the blood in the heart was coagulated. The right cavities were nearly full, and the left contained a small quantity of blood. The brain was quite healthy, its vessels not being congested.

Exp. 45.--Two fluid drachms of chloroform were put into the same jar, which was placed near the fire, and moved about till the liquid was all converted into vapour, when the air within was of the temperature of 75?, saturated with chloroform, and containing about 29 grains in each 100 cubic inches. A young rabbit was put in. It first attempted to escape, then gave a little cry, and sank down on its side, and was dead three quarters of a minute after its introduction. It was immediately removed, and the ear applied to its chest, but no sound could be heard. The thorax was opened directly, and the heart observed to be perfectly motionless; but it commenced to contract after its exposure, as in the former ex-[614/615] periment, and in a few minutes was contracting vigourously. The rabbit was placed back again in the jar, in which the vapour was still retained, except a little that escaped during the momentary removal of the cover, and the heart became quickly affected from the absorption of the vapour by its moist surface. Its contractions became more and more feeble, and at the end of four minutes had entirely ceased, and could not be excited by pricking; yet they commenced again spontaneously about ten minutes after the removal of the rabbit from the jar, but were not so strong as before. The lungs of this rabbit were of a vermilion colour when the chest was opened, and the appearances on examination of the body next day were precisely the same as in the former experiment.

It has appeared to me that the respiration and circulation cease nearly together in those instances, also, in which an animal is slowly killed by the inhalation of vapour of chloroform of moderate strength. One experiment will suffice to relate in illustration of this.

Exp.46.--A cat, which it was requisite to destroy, was placed in a jar holding 800 cubic inches, and a fluid drachm and a half of chloroform was put in, and the jar covered. The cat made efforts to escape for the first minute; it then became insensible, and was affected with spasmodic movements for about half a minute, after which it was quite motionless, and relaxed, and the breathing ceased about two minutes after the commencement of the experiment. It was taken out, and the stethoscope applied to the chest, and the sounds of the heart’s action were distinctly heard. At this moment the breathing began again, and the cat was put back into the jar, from which, however, the greater part of the vapour had escaped. It remained insensible, and the breathing after a time became very feeble, except at intervals, when it was laborious. In little more than half an hour the animal died. It was taken out as soon as the respiration ceased, but no movement of the heart could be heard. Next day the body was very rigid, the right cavities of the heart and the two cavæ were full, but not greatly distended; the left cavities of the heart were nearly empty. All the blood was dark coloured and fluid. The lungs were collapsed and of a bright red colour. They were not congested.

Post-mortem appearances.

As might be expected from these investigations concerning the mode in which chloroform causes death, the post-mortem appearances resulting from it are neither constant nor striking. I have preserved brief notes of the examination of 14 animals killed by chloroform--3 cats, 3 rabbits, 2 guinea pigs, 4 small birds (chaffinches and larks), and 2 mice. In every instance the right cavities of the heart were more or less filled with blood, and in five cases out of the fourteen they were much distended. The left cavities of the heart contained a little blood in every instance in which their state is mentioned. The blood was fluid in one instance-–that of the cat, related above. In the other instances it was coagulated-–generally firmly, but in three or four cases only loosely. The lungs were quite free from congestion in ten of the animals, in the other four they were congested in patches. The head was examined in only eight instances, and in these the substance of the brain was free from congestion, and the sinuses were not particularly distended, except in two.

The fatal cases of inhalation of chloroform.

After seeing how rapidly the vapour of chloroform kills animals when it pervades to a certain extent the air they breathe, and when we recollect that it came all at once to be generally administered without any previous teaching on the subject in the schools, it ought not to surprise us, however much we are called on to deplore the circumstances, that a few cases have occurred, in different parts of the world, in which the exhibition of chloroform has been attended with fatal results; especially when we consider that the vapour has usually been so administered that its strength could not be controlled. Reflecting, indeed, on the mildness and uniformity of the action of the vapour on animals, when more diluted, as shown in some of the experiments related in the first part of these papers, we ought to feel confident that it is capable of being used with perfect safety, certainty, and precision; and this view of the subject agrees with my [615/616] experience, which has extended now over a great number of cases.

I offered some remarks at the time respecting the fatal case that occurred near Newcastle.* (*Med. Gaz. vol xli. p. 277.) The next case recorded is one at Cincinnati, U.S. in February last.† († See Med. Gaz. p. 79, present vol.)

The remarks I made on the Newcastle case apply in great measure to this. Although the chloroform was not administered on a handkerchief, the vapour seems to have been inhaled in too concentrated a form, as its effects were produced very rapidly. The patient inhaled from a glass globe, containing a sponge of considerable size saturated with chloroform. "Breathing at first slow; inhaled 12 or 15 times, occupying from a minute to 75 seconds," and some stumps of teeth were then immediately removed. Now, it takes three or four moderately deep inspirations, and as many expirations, to replace all the air contained at one time in the lungs. Consequently, the patient was made sufficiently insensible for the operation by the effect of about 8 to 12 inspirations, whilst the chloroform of 3 or 4 inspirations more was in the lungs, waiting to be absorbed and increase the effect. I am aware that part of this would be expired again unabsorbed as the patient continued to breathe, but that is equally true of what was inhaled at the previous inspirations; so the fact remains, that the patient must have had from one-third to one-half more chloroform than was necessary to produce what was deemed sufficient insensibility. And according to what I have observed, insensibility to pain cannot be obtained in a very rapid manner without considerable narcotism of the nervous centres-–the third or fourth degree: therefore, that the patient should be in a dying state a few moments after the inhalation was discontinued, was only what might have been expected. The female friends of the patient considered that she died about two minutes after the commencement of the inhalation; and although the dentists who administered the chloroform thought that the patient lived a few minutes longer, yet, even according to their account, she was during this time in a dying condition. According to Mrs. Pearson’s account, which is clear and precise, the pulse became feeble and then stopped, and the breathing ceased about the same time. This agrees with what is stated above respecting the phenomena of death when rapidly caused by chloroform, and with what was observed in the rabbits in experiments 44 and 45.

On inspecting the body, the brain was found to be in a normal state, but the vessels and sinuses of the dura mater contained a larger quantity of blood than usual, which was liquid, and mixed with some bubbles of air. The lungs were considerably, but not intensely, congested. The heart was flaccid, and all its cavities entirely empty. It had been emptied, undoubtedly, after death. Artificial respiration was resorted to, and Mr. Sibson has remarked* that he has often known the heart to be emptied after death by artificial inflation of the lungs. (*Med. Gaz. p. 216, present vol.) Or if the head was first opened, as appears by the order in which the inspection is reported, part of the two or three ounces of fluid blood which flowed from the sinuses of the dura mater might have come from the right side of the heart, as I have seen the blood flow from the chest and out by the lateral sinuses in an inspection in which it was liquid. The blood in the case under consideration was as fluid as water in every part of the body, and the globules were thought to be altered in microscopic appearance. The cause which prevent the coagulation of the blood after death are not yet well understood, and although it is not correct, as was once supposed, that fluidity of the blood is a constant rule in certain kinds of sudden death, yet there are sufficient cases recorded where it was so, to show that it is not uncommon in the human subject when death takes place suddenly. The observations on animals, recorded above, as well as numerous others, show that it is not a characteristic property of chloroform to prevent the coagulation of the blood; and I think that the artificial respiration would assist, in more ways than one, to prevent its coagulation in this case, and one presently to be mentioned.

The next case that we have to notice occurred at Hyderabad.† († See Med. Gaz., present vol. p. 84.) The subject of it was a young woman, who required to have the distal phalanx of one of [616/617] her fingers amputated.

The surgeon who operated says, "I administered a drachm of chloroform in the usual way--namely, by sprinkling it on a pocket handkerchief, and causing her to inhale the vapour. She coughed a little, and then gave a few convulsive movements." When these subsided, the operation was performed, and endeavours were made to recover the patient, but in vain. Scarcely a drop of blood escaped during the operation, and the surgeon remarks, "I am inclined to think that death was almost instantaneous; for, after the convulsive movements above described, she never moved, or exhibited the smallest sign of life." There was no inspection of the body.

The case which occurred at Boulogne,* is so like to above, that we may consider the two together. (*See Med. Gaz., present vol. p. 76 and 211.) The patient was a female, about 30 years of age, and took chloroform, for the opening of an abscess. M. Gorré, the operator, says, "I placed over the nostrils of the patient, a handkerchief moistened with from fifteen to twenty drops at the most of chloroform. Scarcely had she taken several inspirations, when she put her hand on the handkerchief to withdraw it, and cried with a plaintive voice, 'I choak!' [sic] Immediately the face became pale; [a symptom recorded also of the Newcastle case; and the one at Cincinnati--inserted by JS] the countenance changed; the breathing embarrassed; and she foamed at the mouth. At the same instant, (and that certainly less than a minute after the beginning of the inhalation), the handkerchief moistened with chloroform was withdrawn." The operation was performed and then efforts were made to restore the patient, but she was dead; and M. Gorré remarks that the death was without doubt complete at the moment when he made the incision.

From experiments related in former parts of these papers, the conclusion was arrived at, that to produce a degree of narcotism that would arrest the respiration, the blood must contain about one twenty-second part as much chloroform as it would dissolve; and that to narcotise the heart so as to stop its contractility, the blood must contain about one-eighteenth part as much as it would dissolve. By a calculation similar to that made before,* I find that half a fluid drachm is the quantity that there should be in the whole of the blood of a person of average size, to stop the respiration, and 37 minims to arrest the heart’s action. (*Med. Gaz. vol. xli. p. 894.) In the case which occurred in India, a drachm of chloroform was placed on the handkerchief. We cannot easily suppose that more than half of this entered the patient’s lungs, since the expired air carries away a portion as it passes over the handkerchief. And since, as was estimated before, only about half of what enters the lungs becomes absorbed, the remainder being expired again, there could only be about fifteen minims in the blood. This quantity, supposing the young Hindoo female was but half the average size of the adult, and this is not improbable, would only be just sufficient to cause death by arresting the respiration, without immediately stopping the heart’s action, providing the chloroform were equally diffused through the whole of the blood. There is every reason, however, from the symptoms, to believe that the action of the heart was suddenly arrested; and the quantity used in the case at Boulogne would not have sufficed to cause death in any way, if it had been equally mixed with the blood. But it was not equally diffused through the circulation in either case,--there was not time for it to be so. Mr. Sibson, in treating the subject of death from chloroform,† makes some remarks in which I entirely agree. He says, "the poison penetrates to the heart from the lungs in a single pulsation, and at the beginning of the next systole the blood is sent through the coronary artery to the whole muscular tissue of the heart. The blood passing into the coronary artery is less diluted-–is more strongly impregnated with chloroform-–than is the blood in any other part of the system, except the lungs." († Med. Gaz., present vol., p. 109.) By experiments 42 to 45 on frogs and rabbits, it had been shewn that chloroform will act locally on the heart; consequently, if the blood passing from the lungs to the left side of the heart should happen to contain one-eighteenth part as much vapour as it would dissolve, the patient might be suddenly killed before [617/618] the nervous system in general were brought under the influence of the narcotic. A small quantity of chloroform might suffice to produce this result, if the vapour were mixed with only a limited portion of air.

The difficulty of inhaling the vapour in a concentrated form, on account of its pungency, and the further dilution of it when inhaled with the air already in the lungs, no doubt would usually prevent this kind of accident, and are in fact the reasons why it has not more often occurred. Still I believe that the patient is not safe unless the vapour is systematically mixed with so much air that no great quantity of it can be in the lungs at one time. I am of the opinion that ether is incapable of causing this kind of accident; for the blood may imbibe with safety so considerable a volume of its vapour, that the quantity which the lungs can contain at once, adds but little to the effect. And I consider that a patient could only lose his life by ether, from its careless continuance for several inspirations after well-marked symptoms of danger had set in.

M. Gorré says that he poured on the handkerchief not more than fifteen to twenty drops. The drops of chloroform are very small. When dropped from an ordinary phial, nine of them are equal to about two minims, and twenty drops would be less than five minims-–a very small quantity. But, as the chloroform was poured, he probably means as much as would be equal to fifteen or twenty drops of water-–in fact, about as many minims; and, indeed, as it was not measured, we have no means of being certain that there was not more-–say, half a fluid-drachm. However, fifteen minims might be amply sufficient to cause death in the way indicated above, even if but half of it entered the lungs; and the sudden paleness, and almost instantaneous death, clearly indicate that the circulation must have ceased suddenly.

The post-mortem appearances in the case at Boulogne were very nearly the same as in the case which occurred at Cincinnati, previously alluded to. Artificial respiration had been resorted to, and carried to the extent of permanently dilating the pulmonary vesicles. Air was met with in the sinuses of the dura mater in the American case, and in this case a good deal of air was mixed with the blood in the veins of almost all parts of the body. There can be but little doubt that this was a result of the artificial respiration, although one cannot tell precisely in what way the result was produced. The peculiar state of the blood, which was very fluid and dark-coloured, as in the American case, must have depended rather on the suddenness of the death, and the artificial respiration, than on any immediate action of the small quantity of chloroform--a quantity much less than is usually inhaled in a surgical operation.

A patient died whilst taking chloroform during an amputation at the hip-joint, a the Hôpital Beaujon, in Paris. But the death in this instance was probably not entirely due to the chloroform; for although the patient apparently got an overdose of the vapour when it was repeated during the operation, yet, as the pulse was occasionally appreciable for three-quarters of an hour afterwards, he would most likely have recovered, had it not been for the lesion occasioned by the operation, which it seems was never finished. So the four cases previously alluded to, and which happened at Newcastle, Cincinnati, Hyderabad, and Boulogne respectively, comprise the whole of the instances in which it appears to me that death has clearly and undoubtedly resulted from the inhalation of chloroform. There was a death at Aberdeen, but not from the professional administration of the agent. There is another case, however, in which the death is generally attributed to the chloroform; and occurring, as it did, in the practice of Mr. Robinson, who has had great experience, and deservedly earned a high reputation, connected with the administration of ether and chloroform, it has made a great impression both on medical men and the public. My reasons for doubting that death was caused by chloroform in this instance are these:--Mr. Robinson’s servant states, in her evidence, that the inhaler was not applied to the patient's face, but held at a little distance from it; and, with the kind of inhaler Mr. Robinson uses, it is impossible that the air the patient breathed could become strongly charged with vapour in this way; for it would pass into the mouth and nostrils by the side of the [618/619] face-piece, and very little of it would pass over or through the sponge. Again, the patient was remarking that the vapour was not strong enough, just when the inhaler was removed, and the moment before he suddenly expired.* (*I do not understand why Mr. Robinson was proceeding to add more chloroform, having previously put a drachm and a half on the sponge, as applying the inhaler closer to the face would have made the vapour stonger.)

I consider that he would have made no such remark if there had been a quantity of vapour in his lungs capable of suddenly paralysing the heart. This condition of the patient is totally unlike the coughing and convulsions in the case in India, or the exclamation "I choke," in that at Boulogne. I am not inclined, however, to attribute the sudden death at that moment to a mere coincidence, as it might be occasioned by mental emotion. Fainting is not altogether peculiar to the female sex; and, supposing syncope to occur in a patient who has fatty degeneration of the substance of the heart, and an enlarged liver greatly encroaching on the space of the thorax, one can easily understand why he should not recover. In some of the reports it was stated that the patient did not appear alarmed, for he was laughing and talking the moment before he died; but I do not know why a patient should laugh in a dentist’s operating chair, unless to disguise or try to banish his apprehension. He had been led by his medical attendant in the country to believe that the chloroform would be attended with danger in his case; and again, just the moment before he died, Mr. Robinson was asking him to have his teeth taken out without proceeding further with the vapour. The post-mortem appearances are quite consistent with this cause of death; and, according to this view of the subject, the disease of the internal organs assists to explain the fatal occurrence; but I do not see how it can assist in explaining it, if it be attributed to chloroform, although I am aware that it is usually thought to do so.

If the heart were so thinned that it were in danger of being ruptured by the least distension, or if some of its orifices were so contracted that it could not maintain the circulation under increased exertion or excitement, I could understand how the inhalation might be attended with danger, if excitement and struggling were produced by it, as sometimes happens. And on these grounds I always looked on extensive disease of the heart as a contra-indication, to a certain extent, of inhalation, and have expressed opinions to that effect; but I cannot conceive how a moderate and gradual inhalation of chloroform should cause any person’s heart, however diseased, suddenly to cease beating. There are neither facts nor analogies in support of such an occurrence. Mr. Thomas Wakley, having met with great congestion of the heart and lungs in certain of the animals that he killed with chloroform, and mistaking, in my opinion, the consequence of the mode of dying for the cause of death, had expressed an opinion that this agent would be particularly dangerous in diseases of the heart and lungs; but this case, the only one of those where death was attributed to chloroform, in which any previous disease of these organs was found, cannot be considered to support an opinion founded on these grounds; for here there was no congestion of the heart, and but very little of the lungs. I am happy to find views similar to my own, respecting chloroform in disease of the heart, entertained by one whose opinion, both on account of the attention he has paid to this subject, and his great merit as a physiologist, is entitled to so much respect as that of Mr. Sibson. He says* that "persons the subject of heart disease, when the dread of a severe operation is great, may sometimes be peculiarly benefited by the careful and short production of anæsthesia during the cutting part of an operation." (*Loc. cit.)

(To be continued)

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