CAUSE AND PREVENTION OF DEATH FROM CHLOROFORM.
All narcotics are capable of causing death, and the discovery of preventing pain by inhalation consists essentially in carrying the effects of a narcotic much further than had previously been the custom; there was, therefore, every reason to apprehend that accidents might occur in the new practice, unless the effects of the medicines employed could be very effectually controlled. There are certain circumstances connected with the physiological properties of chloroform, as ascertained in the experiments previously related, which indicate how accidents may very easily happen with this agent, if not carefully and systematically managed. It was calculated (p. 74) that 18 minims of chloroform is the average quantity in the system of an adult, when sufficiently insensible for a surgical operation, and that this amount might be absorbed by the use of 36 minims, allowing one-half of the quantity breathed to be exhaled again, without being absorbed; but 36 minims of chloroform make only 37·5 cubic inches of vapour, which, at the temperature of 60° Fah., may exist in combination with 257 cubic inches of air, making it expand to not quite 300 cubic inches; the whole of which might be breathed in twelve ordinary inspirations of 25 cubic inches each. If the inhalation of vapour of this strength were continued till insensibility was induced, the lungs would still contain a great quantity of unabsorbed vapour. The amount of air usually present in the lungs is about 250 cubic inches, and if saturated with chloroform at the temperature of 60° it would contain the vapour of 30 minims. About half of this might be absorbed, the remaining half passing off in the expired air; but the addition of 15 minims to the 18 minims already absorbed would almost double the quantity of chloroform in the system, and bring the patient necessarily to the brink of death. It is true that, in the ordinary methods of inhalation, the air seldom becomes quite saturated with vapour, and usually is not more than half saturated, or accidents might be of much more frequent occurrence; but the above considerations are sufficient to show that the amount of vapour contained in the air breathed by the patient should not be left to mere accident, such as the varying temperature of the handkerchief from which the chloroform is breathed, or the greater or less extent of wetted surface over which the air passes. It should be recollected also that the patient sometimes draws a deep and sudden inspiration by which he may inspire 100 cubic inches of air, which would contain, if strongly charged with vapour, ten or twelve minims of chloroform—a large quantity to be suddenly added to that already in the circulation, when the patient is insensible, or nearly so.
It is, however, only by a knowledge of the different modes in which chloroform is capable of causing death, that the exact nature of the accidents from this agent can be understood, together with the means of preventing them, and the reason why they are usually irremediable when they happen. If animals are kept for a very long time under the deep influence of chloroform, they become ultimately exhausted, the circulation and respiration are gradually weakened, and cease nearly together. Such a mode of death from this agent is never likely to occur to the human subject, and therefore need not engage our further attention. The following experiments illustrate the different modes of dying, when death is caused more suddenly by this agent.[[57]]
Experiment 23. A young but full grown cat was placed in a glass jar, of the capacity of 1,600 cubic inches, and a fluid drachm of chloroform was introduced, by a portion at a time, through a tube in the cover of the jar. As twenty-five minims of chloroform produce twenty-six cubic inches of vapour, the atmosphere which the cat had to breathe contained nearly four per cent. of vapour, and the jar was moved about, to ensure the uniform mixture of the vapour with the air. In five minutes, the cat became insensible, and lay breathing naturally. In about ten minutes more, the breathing became very feeble, and it ceased altogether in about another minute, or sixteen minutes after the cat commenced to breathe the chloroform. It was immediately taken out and laid on a table, and the stethoscope was applied to the chest. The heart could be heard beating distinctly at first, but the pulsations became slower and feebler, and in about a minute they could be no longer heard. Just at this time, however, the cat took a gasping inspiration, and immediately the heart was heard to beat in a most rapid manner. The gasps were repeated, and the action of the heart became less rapid, but stronger. In a little time, both the breathing and the action of the heart became natural, the cat remaining, however, insensible for some minutes.
Experiment 24. A cat, about the same size as the last, was put into the same jar, and the same quantity of chloroform was introduced. It was removed at the end of four minutes, when it was so far insensible as to offer no resistance. Being laid on the table, it was made to breathe air charged with ten per cent. of vapour of chloroform from a bladder. Twenty-five minims of chloroform were put into the bladder, which held 250 cubic inches, and it was filled up with the bellows. A portion of another bladder which was attached to the stop-cock, was made to surround the head of the cat, which consequently breathed to and from the bladder. In half a minute it was quite insensible: in about half a minute more the breathing became difficult, and the sounds of the heart less distinct. The breathing became gradually slower, and ceased altogether between three and four minutes after the respiration from the bladder commenced. The sounds of the heart were rather frequent, and scarcely audible, just before the breathing ceased, and they could not be heard afterwards. The chest was opened three-quarters of an hour after death. The lungs were of a pale red colour, everywhere permeated with air; and a small quantity of fluid blood flowed from them on making an incision. The right cavities of the heart were quite full of blood, and the left cavities contained a small quantity.
Experiment 25. A cat was made insensible in the same manner as the two previous ones. As it made strong efforts to get out of the jar, and consequently breathed more deeply, the chloroform took effect sooner; and it was removed and laid on the table, in a passive state, at the end of two minutes and a half. The respiration and sounds of the heart were quite natural. The nose of the animal was placed in the mouth of a metal vessel, lined with bibulous paper, and used as a chloroform inhaler. The inhaler contained chloroform, and was surrounded with water of the temperature of 110° Fahr. The stethoscope was kept applied to the chest whilst the chloroform was exhibited. After four or five inspirations from the inhaler, the heart suddenly ceased to beat, the breathing still going on. The inhaler was removed as soon as I was satisfied that the action of the heart had ceased, and there were two or three rather convulsive respirations afterwards, and then the breathing stopped; but, between one and two minutes later, there were two or three feeble inspirations, accompanied with motion of the nostrils, but no returning action of the heart could be heard. The chest was opened ten minutes after death. The lungs were quite pale throughout. There was a little clear serum in the pericardium. The heart appeared quite motionless when first observed; but, after exposure to the air for a short time, there were some slight contractions of a few fibres of the right ventricle. The right auricle and ventricle were filled with blood.
The air which this cat breathed must have contained much more than ten per cent. of vapour.
In experiment 23 the breathing was arrested by the influence of the chloroform on the nervous centres, but the action of the heart continued, until it was stopped, or very nearly so, for want of respiration, as in asphyxia from privation of air. In experiments 24 and 25 the action of the heart was arrested by the direct effect of the chloroform; in one instance at the same moment as the respiration, and in the other instance, even before it.
The paralysing effect on the heart of large doses of chloroform was shown in the first experiments which were made with this substance, viz., those by Dr. R. M. Glover in 1842.[[58]] In animals which were killed by injecting it into the jugular vein, the irritability of the heart was found to be destroyed, whilst this organ retained its irritability in those that were killed by the injection of chloroform into the arteries, stomach, or peritoneum. I have frequently arrested the action of the heart remaining in animals which were opened immediately after death, by blowing the vapour of chloroform on it; and I ascertained by some experiments on frogs, that the motion of the heart can be arrested by an amount of chloroform somewhat greater than suffices to suspend the respiration. As absorption of chloroform vapour is continued by the skin of these animals after the respiratory movements have ceased, they can be exposed to the vapour till the action of the heart is suspended by its direct influence.
Experiment 26. Four and a half grains of chloroform were introduced into a jar containing 600 cubic inches, being three-quarters of a grain to each 100 cubic inches, and, the vapour having been equally diffused, two frogs were put in. They tried to climb up the side of the jar, as if wishing to make their escape, and one or the other occasionally ceased to breathe for a minute or two, probably from disliking the vapour, but commenced to breathe again. In about five minutes the efforts to escape ceased, and they only moved to adjust their equilibrium when the jar was disturbed. They were now breathing regularly, and continued to do so till about ten minutes after their introduction, when all voluntary power ceased, and the breathing began to be performed only at intervals. They were allowed to remain till half an hour had elapsed, during the last ten minutes of which time no respiratory movement was observed in either of them. On taking them out, and laying them on their backs, the pulsations of the heart were observed on each side of the sternum. These pulsations were the more distinct, from the lungs being apparently empty. I continued the experiment on these frogs, placing one of them back again, in the course of two or three minutes, in the same jar, with three grains of chloroform, and the other in a jar of 400 cubic inches capacity, with five grains. They were laid on their backs, and the heart of the former one, in air containing half a grain of chloroform to each 100 cubic inches, continued to beat distinctly and regularly, 45 times in the minute, for four hours that it remained in the jar, and it was not observed to breathe during the whole time, although it was watched almost constantly. The respiration commenced again within half an hour after its removal. In about an hour, it recovered its power of voluntary motion, and it was not injured by the long narcotism.
The pulsations of the heart of the other frog, in air containing a grain and a quarter of chloroform to each 100 cubic inches of air, became slower and more feeble, and in a quarter of an hour could not be observed. The frog was left in the jar a quarter of an hour longer, and removed when it had been in half an hour. The under part of the thorax was immediately opened sufficiently to expose the heart. It was moderately full of blood, but not contracting at all, and it did not evince the least irritability on being pricked, either at first or after exposure to the air for some time. It is evident that the heart of this last frog became paralysed by the absorption into the blood of more vapour, in addition to the quantity that was sufficient to arrest the respiration. The temperature of the room during this experiment was 65° Fah.
The effect of chloroform on the heart of the frog is further shewn by the next experiment.
Experiment 27. A frog was placed in the jar containing 600 cubic inches, with six grains of chloroform. In twenty minutes the respiration had ceased, but the heart continued to pulsate strongly. At the end of three-quarters of an hour, the pulsations were more feeble, and had diminished from 40 to 30 in the minute. An hour and five minutes from the commencement of the experiment, no movement of the heart could be observed. The frog was taken out of the vapour, and a portion of the sternum and integuments removed, so as partly to expose the heart, when it was found to be still contracting, with a very feeble undulatory motion. This motion increased in force, and, in a quarter of an hour after its removal, the heart was pulsating regularly and strongly, the ventricle apparently emptying itself perfectly. When the frog had been out twenty minutes, it was placed again in the same jar, with the same quantity of chloroform. In about ten minutes, the heart’s action began to fail again; and in about twenty minutes, the slightest movement could no longer be perceived in it. The frog was immediately taken out, and the ventricle of the heart was pricked with a needle. In a few seconds, a slight quivering was observed,—whether the result of the prick is not certain,—and the action of the heart became gradually reestablished as before. It was arrested a third time by exposure to the vapour; and although, in its third removal, the anterior extremities of the frog had become rigid, the heart resumed its action partially, and continued to contract feebly for three or four hours after the rigidity of death had invaded the body and limbs of the animal. The temperature of the room was 62° during this experiment.[[59]]
In the human being and all other creatures of warm blood, any vapour which is inhaled and absorbed in the lungs passes at once to the left side of the heart, and as the coronary arteries are the first branches given off from the aorta, the heart must, during the process of inhalation, be always a very little in advance of the rest of the body, as regards the amount of vapour to which it is subjected. This, however, is no source of danger, as regards chloroform, if the inhalation takes place in a gradual and uniform manner; for the heart being able, as shown by the above experiments on frogs, to bear a greater amount of this narcotic than the brain, its action continues even after respiration has ceased, if the vapour is added only by a little at once to the blood, as it passes through the lungs. But if the air which the patient breathes be too highly charged with vapour, it is easy to understand how the sensibility of the nerves of the heart may be paralysed, notwithstanding their power to bear somewhat more of this agent than the brain and nerves of respiration. I calculated (p. 74) the quantity of chloroform which would suffice to arrest respiration in the adult of average size to be thirty-six minims, provided it were equally diffused through the circulation; but supposing a patient breathes, at any time, air containing ten per cent. of vapour of chloroform, a considerable part of this might enter the lungs at a very few inspirations, for thirty-six minims of chloroform occupy only 37·5 cubic inches, and would be contained in 375 cubic inches of air, and might be breathed in less than a minute; but for the whole of the blood to pass through the lungs occupies a considerable time—I believe about four minutes in the adult—and therefore the portion of blood which is passing through the lungs, at the time when vapour of the above strength is inhaled, must become much overcharged with chloroform, making every allowance for the portion of vapour which is expired again, without being absorbed.
I have observed the manner in which the breathing and circulation ceased in a great number of instances, with the stethoscope applied to the chest of the animal, when the quantity of chloroform contained in the air it breathed was known, and have notes of the result. The animals were chiefly cats, which would otherwise have been killed by prussic acid, or in some other way. In every instance in which the quantity of vapour in the air breathed by the animals was from three to six per cent., the respiration ceased whilst the sounds of the heart were still very distinct, as in Experiment 23, related above; in many instances the heart continued to beat from two to three minutes after the breathing had ceased, and, in a great number of instances, there were one or more gasping inspirations just at the moment when the sounds of the heart ceased. In many cases these gasping inspirations caused the action of the heart to return, as in Experiment 23, if the animal had been withdrawn from the chloroform; but this was not always the case; and if the chloroform was still breathed during these gasping efforts, all signs of life immediately ceased in every instance.
When, on the other hand, the air breathed by the animals contained eight or ten per cent., or upwards, of vapour of chloroform, the action of the heart was always seriously affected and rendered extremely feeble, if it did not actually cease, at the time the breathing was arrested. In several instances, indeed, the sounds of the heart entirely ceased before the breathing, as in Experiment 25; and although the chloroform was withdrawn, in this and many other experiments, the moment the heart ceased to beat, and fresh air was drawn in by inspiratory efforts, it very rarely had the effect of restoring the heart’s action, although this happened so frequently when that organ had gradually ceased to act on account of suspension of the breathing, by the effect of more diluted vapour.
In order to see more precisely the action of the vapour of chloroform on the heart, when not sufficiently diluted, the chest and pericardium were opened on four occasions, in cats and a rabbit, and chloroform was exhibited by artificial respiration. I was assisted by Mr. Peter Marshall in these experiments, and the following is the account of one of them.[[60]]
Experiment 28. A young rabbit, rather more than half-grown, was made insensible by breathing air charged with four per cent. of vapour of chloroform in a large jar. The trachea was then opened, and a tube was introduced and tied. The lungs and heart were then exposed, by making an incision and removing the lower half of the sternum, with the adjoining part of the cartilages of the ribs on each side. The front of the pericardium was also cut away, to expose the heart. Whilst these operations were performed, artificial respiration was kept up by means of a bladder of air attached to the tube in the trachea. The heart contracted vigorously and quickly, and the lungs were of a light red colour. The rabbit was beginning to show signs of returning sensibility, when the bladder of air was changed for one containing ten per cent. of vapour of chloroform. The bladder contained 125 cubic inches, and twelve minims of chloroform were put in before it was filled with the bellows. Three or four inflations of the lungs only were made, when I perceived that the heart was beginning to be affected, and I changed the chloroform for a bladder containing only air. These three or four inflations of the lungs with chloroform, had the effect of causing the right cavities of the heart to become distended with blood, and its pulsations to become much slower. In two or three minutes, however, the action of the heart was quite reestablished by the artificial respiration, the pulsations being vigorous and frequent, and the ventricles being apparently emptied at each contraction. The bladder charged with ten per cent. of chloroform was again attached, and artificial respiration was made with it. The right ventricle began almost immediately to become distended; and, by the time that eight or ten inflations of the lungs had been made, the contractions of the heart were very slow and feeble. Artificial respiration with air was resumed, but without the effect of restoring the action of the heart. The lungs were observed at the time when the right ventricle was becoming distended, and it was noticed that their colour was unchanged. They afterwards became paler, as the artificial respiration was continued after the ventricle had ceased to empty itself. No contractions of the diaphragm were observed after the first inflation of the lungs with chloroform, and the rabbit did not gasp at any time; whilst the cats were observed to make a few gasping efforts at the time when the heart’s action was ceasing.
The circumstance of the lungs not changing in colour at the moment when the right ventricle was becoming distended, which was observed in the cats as well as in the rabbit, shows that the distension arose from the failure of the contractile power of the heart, and not from impediment to the pulmonary circulation; for, in the latter case, the lungs would have become congested, and of a deeper colour. In one of the cats, it appeared to me that the left, as well as the right ventricle, was distended with blood; but this distension of the left ventricle did not continue.
In the Experiments 24 and 25, related above, the animals were first made insensible by vapour of moderate strength, in order to keep them quiet for the application of the stethoscope whilst the stronger vapour was inhaled, but when animals are made to breathe air containing ten per cent. or so of vapour of chloroform from the first, death takes place in the same manner, i. e. by the direct action of the chloroform on the heart. Under these circumstances the creatures die suddenly, after a brief interval of agitation and excitement, without previous insensibility. This is what has happened in some of the accidents from chloroform, to be related further on; whilst in many cases death has happened after a longer or shorter period of insensibility.
In many of the fatal cases of inhalation of chloroform the alarming symptoms commenced whilst the patient was still inhaling, but in a considerable number there was no sign of danger until after the inhalation had been left off; and this is a result which may be imitated on animals. The two following experiments, which were made at Dr. Sibson’s on December 27th, 1849, illustrate this point.
Experiment 29. The subject of this experiment was a young guineapig, about half-grown. Ten or twelve drops of chloroform were put into a short bent metal tube, lined with bibulous paper, which formed part of an inhaler, and one end of the tube was applied to the animal’s nose, which closed it. The guineapig consequently breathed backwards and forwards through the tube, which was, moreover, warm from being held in the hand. It struggled at first, endeavouring to get away from Dr. Sibson, who held it; but in twenty or thirty seconds it became quiet; and observing that the conjunctiva was insensible, I withdrew the chloroform, and the guineapig was laid on the table. We remarked that the breathing was very slow; and scarcely had this remark been made, when it ceased altogether, three or four inspirations only having been made since the inhalation was left off. Dr. Sibson proceeded immediately to open the body; but as soon as he had divided the integuments of the chest the animal began to make some convulsive gasping inspirations, during which the mouth was widely opened, and we observed that the diaphragm acted alone, the ribs being pressed inwards by the atmosphere. The heart was not contracting at all when the pericardium was first opened; but in a few moments the auricles began to contract rhythmically. The lungs were of a light red colour.
Experiment 30. Another guineapig of the same age was treated in the same manner, except that I removed the tube from the nose for a short time between every two or three inspirations, in order to see if I could not make it insensible in this way without a fatal result. In half a minute or so the animal no longer required to be held, but lay on the table without making any resistance, the conjunctiva being still sensible, and some motion of the limbs, apparently voluntary, remaining. It only inhaled once after Dr. Sibson ceased to hold it, and whilst in the state just described, and then only for two or three inspirations. After this it appeared quite insensible, and no more chloroform was given. It breathed at first naturally, except more slowly and gently than before the inhalation; but the breathing became slower, and ceased altogether about a quarter of a minute after the inhalation had been left off. The body was opened immediately. When the pericardium was opened, the auricles were observed to contract slightly, and the contractions increased after their exposure to the air.
The amount of vapour in the air breathed by these two guineapigs is not known, but there is no doubt that it was upwards of eight per cent.