"Further remarks on amylene"

Medical Times and Gazette
(18 April 1857): 379-82
Part 3.

PDF of the original article is included with the PDF posted for part 1

The most exact way of administering any narcotic vapour is that which I have been in the habit of pursuing in experiments on animals, namely, to place them in an air-tight vessel so large, relatively to their size, as to represent a considerable apartment, and to introduce a known quantity of the narcotic agent in such a manner that the vapour should become uniformly diffused through the air. This method is evidently inapplicable to the human subject, but I tried a plan in a few cases in 1849, which very nearly approaches to it in point of accuracy; this was, to put a measured quantity of a volatile liquid into a balloon of known size, to fill it up with air by means of the bellows, and let the patient breathe from it. With so much chloroform as produced four per cent of vapour, in proportion to the air, the effects were extremely uniform, the patients becoming insensible in three or four minutes, according to the greater or less freedom of respiration, and the vapour being easily breathed, owing to its being so equally mixed with the air. I did not try, however, to introduce this plan into general use, as the balloon would sometimes have been in the way of the Surgeon, and filling it with the bellows would have occasioned a little trouble. It seemed necessary to sacrifice a little of absolute perfection to convenience, and I therefore continued the plan which I had already followed.

The great point to be observed in causing insensibility by any narcotic vapour, is to present to the patient such a mixture of vapour and air as will produce its effects gradually, and enable one to stop at the right moment. Insensibility is not caused so much by giving a dose as by performing a process. Nature supplies but one mixture of diluted oxygen, from which each creature draws as much as it requires, and so, in causing insensibility by inhalation, if a proper mixture of air and vapour is supplied, each patient will gradually inhale the requisite quantity of the latter to cause insensibility, according to his size and strength. It is indeed desirable to vary the proportions of vapour and air, but rather according to the purpose one has in view, whether medicinal, obstetric, or surgical, than on account of the age or strength of the patient; for the respiratory process bears such a relation to the latter circumstances, as to cause each patient to draw his own proper dose from a similar atmosphere in a suitable time.

When sulphuric ether was first introduced, it was often very slow in producing the desired effect, and not infrequently failed altogether, owing to the great cold produced by its own evaporation. The sponge, or whatever contained the ether, was often reduced much below the freezing point, and the patient went on breathing air of an arctic temperature with very little vapour in it. By using a metal inhaler, and placing it in a good quantity of cold water, which replaced the caloric carried off by the vapour, I was enabled to cause insensibility in four or five minutes, in every patient who was able and willing to breathe the vapour of the strength which was supplied. When the use of chloroform was introduced by Dr. Simpson, I retained a small water-bath with the inhaler I employed, as a regulating power, and quite as much to prevent the vapour from being in excess as to ensure its sufficient quantity.

In the use of amylene some kind of inhaler is required to prevent a great loss of the article, and to insure its producing its effects. I have supplied amylene on a hollow sponge several times, to keep up the effect, after insensibility had been produced by means of an inhaler, and in short operations, such as most of those on the eye, it has answered perfectly, but in the longer operations, not always so well. In applying amylene in this way the moisture of the breath is condensed on the sponge, and congealed, so as to produce the appearance of hoar-frost, and at the temperature of freezing water, the air does not take up enough of the vapour of amylene to cause insensibility. M. Tourdes, of Strasbourg, has, indeed, succeeded perfectly in making children insensible with amylene by means of a sponge placed in a hollow cone of waxed cloth, with a small aperture at the extremity. The waxed cloth, no doubt, causes the warm breath to counteract, in some measure, the cooling effect of the evaporation. In an operation on the adult, however, in which M. Rigaud, of Strasbourg, applied amylene in this manner, he used 100 grammes (between four and five fluid ounces) in causing insensibility.

In administering amylene, I have employed the same kind of inhaler which I have used for many years in the exhibition of chloroform. I have lately had one made a little deeper, to adapt it better to the larger quantity of the agent used, and to make the water-bath a little more capacious. It is figured in the adjoining wood-cut. The inhaler itself is on a scale of half the dimensions, but the artist has drawn the face-piece on a smaller scale. The temperature of the water-bath varies according to that of one's dwelling-rooms, at different times of the year, but I am in the habit of diminishing the depth of the coils of bibulous paper in the inhaler in warm weather. The quantity of vapour can also be diminished to any extent by turning the expiratory valve of the face-piece more or less to one side.

From experiments I have made with the inhaler, by passing a measured quantity of air through it, in the way in which it passes through during inhalation, and weighing it before and afterwards, I find that when the water-bath is at 56º Fahr. the air takes up 16 per cent of the vapour of amylene, and at 62º nearly 19 per cent. For instance, 625 cubic inches of air carried off 76 grains of amylene at the former temperature, and 90 grains at the latter.

In speaking of the bisulphuret of carbon in 1848,* I said, "On account of the great volatility and very sparing solubility of this substance, the point of relative saturation of the blood by it is soon reached;" and further I said, "Indeed, I feel convinced that if a person were to draw a single deep inspiration of air, saturated with it at a summer temperature, instant death would be the result." (*London Medical Gazette, vol. i. 1848, p.1077.)

Last autumn, when I commence[d] my experiments on amylene, and ascertained its extremely sparing solubility, only one part to upwards of ten thousand of water, I was apprehensive that the above remark would apply to this agent; but on finding afterwards that the blood required to absorb about one-fifth as much of amylene as would saturate it, before a deep state of insensibility was [379/380] induced, instead of only one part in thirty-one, as in the case of sulphuret of carbon, the question was very much altered, and I came to the conclusion that it might be inhaled with at least comparative safety. I soon became aware, however, that it was capable of acting directly on the heart, if given too strong, or not well regulated. In one of the early experiments which I made to ascertain the effects of this substance, I placed a guinea pig in a jar holding 428 cubic inches with 25 grains of it. In two minutes and a half the animal was quite insensible. Soon afterwards the breathing became slower, and it ceased at the end of three minutes and a half from the beginning of the experiment. I immediately took the animal out, and in ten or fifteen seconds it gave a gasp, and in a few seconds more the breathing became quick and natural. There was, however, no action of the heart to be heard with the stethoscope, and, although the breathing continued for three minutes, the action of the heart did not return. The chest was opened immediately after the breathing ceased. The auricles were acting briskly, but the ventricles were not contracting. The right one was much distended with blood.

I concluded that the vapour was not properly mixed with the air in the above experiment, and that there had been an undue proportion of it at the bottom of the jar. I soon found that this must have been the case, for on introducing the amylene through an aperture contrived in the cover of the jar, and allowing it to evaporate gradually from a sheet of blotting paper suspended within, I found that twenty-five grains only produced a state of inebriation with staggering, however long the animal might breathe it, and that it was necessary to increase the quantity to forty-eight grains in order to induce a moderate state of insensibility. With the above quantity the air in the jar contains fifteen per cent of vapour. I found in several other experiments that the amount of vapour may be increased to twenty-five per cent, and that guinea pigs may breathe it for four minutes without danger. It was only by increasing the amount of vapour up to nearly forty per cent that I was able to arrest the action of the heart of a guinea pig by the direct effect of the amylene in such a way that the gasping respirations which followed did not restore its action. With a kitten six weeks old I did not succeed, even with vapour of this strength, for when the action of the heart seemed to have ceased, or to be on the point of ceasing, the respirations of the animal, when it was withdrawn from the vapour, always restored it.

Three cats, indeed, died with a less amount of vapour, but they died slowly. One of them was placed in a jar holding 3,000 cubic inches, and a fluid drachm of amylene was introduced on blotting paper every two minutes. The cat became gradually insensible after the sixth drachm had evaporated, and the breathing ceased as the eleventh drachm was evaporated, upwards of twenty minutes after the commencement of the experiment, and when the amount of vapour had reached between seventeen and eighteen per cent. The animal was immediately taken out and the stethoscope applied to the chest. The heart continued to beat for three minutes, quickly at first, more slowly afterwards, and it gradually ceased without any further respiration. I caused a cat to breathe air from a large bladder containing 20 per cent of the vapour of amylene, while the stethoscope was applied. The breathing became embarrassed, and the action of the heart rapid, but I did not succeed in stopping the latter. When mice are exposed for half a minute to air containing eight or ten per cent of vapour of chloroform, and taken out as the breathing gets embarrassed, I have always found them get worse and die; but if they are placed for half a minute in air containing 25 per cent of vapour of amylene, and taken out under the same circumstances, they recover.

Under all these circumstances I concluded that amylene might be employed with a greater prospect of safety, if care and caution were used; for it is only by the sudden action of a narcotic vapour on the heart that a patient would be allowed to die in the presence of a medical man.

In speaking of amylene in my paper published in January,* I said, "Whilst I cannot venture to predict for it the absolute safety which seems to attend sulphuric ether under all circumstances, I confidently trust that it will be perfectly safe with careful management;" and, further, "It is my opinion that the cold produced during its evaporation would, in all the ordinary methods of inhalation, prevent the air taking up a quantity of vapour which would be dangerous." (*Medical Times and Gazette, p. 84.) Mr. Clarke, of Bristol, in a paper published in the British Medical Journal (March 28), says of amylene, "It seemed impossible to get too much into the system, and with this I have been greatly impressed; it is this fact that appears to me to promise an immunity from danger. . . . It requires to be given almost unintermittingly, and requires the same amount of attention to keep up its effects as chloroform does to keep the patient safe. The direction of the attention, however, is one less calculated to give anxiety." Dr. Debout stated, as the result of some experiments on animals, in which he was assisted by M. Duroy, that if it sufficed to double the quantity of chloroform in order to transform the anæsthetic dose of that agent into a poisonous dose, it was necessary to quadruple that of ether, and to quintuple that of amylene, in order to arrive at the same result, and that, therefore, the innocuousness of the new agent was still greater than that of sulphuric ether.† (†Bulletin Général de Thérapeutique, 15 Mars, p. 223.) In a paper which Professor Tourdes, of [380/381] Strasbourg, read before the Academy of Medicine of Paris, he came to the conclusion, from a series of experiments and observations, that "amylene was evidently much less dangerous than chloroform, perhaps even than ether."* (*Gazette Hebdomadaire, 6 Mars, p.164.) In a subsequent paper, M. Tourdes says that the innocuousness of amylene is indicated theoretically by the insolubility and volatility of that substance; but this is a mistake; the insolubility and volatility which are a cause of the prompt recovery of the patient, as I have explained, are also a cause of its quicker action, and demand greater care in its administration; so that whatever safety amylene possesses is not a consequence of these properties, but rather exists notwithstanding they are present.

These sanguine expectations of the French investigators, and my own more moderate hopes, have been greatly disappointed by an accident which has happened in my own hands, since the last part of my paper was in print. Mr. Fergusson requested me to assist him on the 7th instant, in the case of a gentleman on whom he was about to operate for fistula in ano. The patient was 33 years of age and was in good health, with the exception of the local complaint, although he had lived somewhat freely. Mr. Fergusson examined the patient's chest the day before the operation, and found the sounds of the heart to be normal. I felt his pulse just before he began to inhale. It was natural, but somewhat accelerated, as usually happens just before an operation. He was lying on his side in bed. About six fluid drachms of amylene were put into the inhaler, (I never intentionally use all I put in, but add more before the paper become dry,) and he breathed steadily and gently. The valve was gradually advanced over the opening in the face-piece till it about three-quarters covered it, and the patient appeared to become quietly unconscious in about two minutes. He breathed quickly for a few inspirations just as he appeared to become unconscious. Just after this Mr. Fergusson came and felt the patient's pulse, and he says it was very good. I felt it also. I looked at my watch at this time, and it was two minutes and a-half or two and three-quarters from the beginning of the inhalation. Mr. Fergusson commenced to use the probe, and, finding the patient did not flinch, he began to use the bistoury. Mr. P. C. Price assisted at the operation. I held the patient's thigh with one hand, as I often do in such an operation, lest he should flinch. He did not flinch, however, but kept his limbs tense, without moving them. Just at this moment I observed that the valve of the face-piece, which I had left three-quarters covering the opening, had moved so as to cover it entirely, but I cannot say whether or not the patient had taken an inspiration a little stronger than I intended, and thought nothing of the matter, as I have frequently had to close the valve completely in giving amylene. It could not, however, have been many seconds in that position, for I paid no attention to the operation, except so much as was requisite to guide me in what I was doing. The inhalation was discontinued at the moment I have mentioned, and on looking round directly after I found that the operation, which had apparently been but one incision, was finished. I now began to feel for the pulse, more out of constant habit, and from a scientific curiosity, than from any supposed necessity of doing so. Although it had been good only half a minute before, I could not find it in the left wrist, and only a slight flutter in the right one. His breathing was, however, good, indeed quite natural, and he did not seem even to be very insensible, for there was some motion both of his features and limbs as if he were about to awake. I watched the patient with great anxiety, thinking that surely his good and natural breathing would restore the pulse, and feeling that at all events this superseded any other measure at the moment. In two or three minutes, however, he seemed to be getting more insensible; he did not wink on the edge of the eyelids being touched, and the breathing was getting slower and deeper. I called Mr. Fergusson's attention to the patient, and both he, who was preparing to go away, and Mr. Price, who had all the time been standing by the patient, were surprised to find that anything could be wrong, as they has seen the patient going on apparently so well, not only during the inhalation, but after it was discontinued. They dashed cold water in his face, which did not seem to have any effect. His countenance was now livid, and his breathing of a gasping character. It soon began to leave off, with the exception of deep, distant, gasping inspirations, and we therefore began to perform artificial respiration, by Dr. Marshall Hall's method, placing him in the prone position, and bringing him partly round, while Mr. Price kept the mouth open. The air could be distinctly heard passing through the larynx during this motion. We also tried pressing on the chest with the head on one side and the mouth open, which answered very well as regarded the ingress and egress of air. Inflation from mouth to mouth was tried, but did not seem to answer so well. Although deep gasping inspirations were made by the patient till fully ten minutes had elapsed from the failure of the pulse, the measures used had no effect; I believe that I heard a feeble motion of the heart even after this period; and, as Mr. Fergusson perceived a slight pulsation at the same time in the right wrist, I was probably not mistaken. There were no further signs of life after this, although the artificial respiration was continued for a long time. I am quite sure as to the length of time respiration continued after the failure of the heart's action. The pulse ceased to be distinctly perceptible at ten minutes before five, and the patient was still breathing at five o'clock. He had not taken food for some hours, but drank a pint bottle of ale a little while before the operation. A good portion of amylene remained in the inhaler after it had been uncovered for an hour and a half.

There was an examination of the body forty-eight hours after death. The body was rigid. There was a good amount of fat beneath the integuments. The cartilage of the ribs were ossified. The lungs were large, and did not collapse; they completely filled the cavity of the chest, and seemed by their texture to be emphysematous, although there were no large cells on the surface. There was a little congestion at the posterior surface of the left one, otherwise they were not very vascular. There was a little clear fluid in the pericardium. There was a good deal of fat on the surface of the heart, which was somewhat larger than natural. It was removed by cutting the great vessels before it was opened, and in removing it three or four ounces of dark-coloured fluid blood escaped. The right ventricle was somewhat dilated, otherwise the heart was healthy; the walls of the left ventricle seemed very thick, but it was contracted, so as almost to obliterate the cavity. The liver was vascular, dark coloured, and friable. The stomach was healthy, and contained only a little mucus. The organs were not examined. There was no odour of amylene in the body.

Although I used every care and attention in this case which seemed to be possible, I cannot attribute the patient's death to any other cause than the amylene. The failure of the pulse took place at the moment when the operation was performed; but, as the patient was unconscious, I can hardly connect the two events,† (†there are, however, some authorities who would still do so) or I might illustrate the case by one which I witnessed two or three years ago. In that case the Surgeon performed an operation for fistula, before the patient was unconscious, in mistake, and immediately afterwards the patient, a youngish man, went through the process of apparently dying; but, fortunately, gave a gasp and recovered. He then told us what I very well knew, the he had felt the pain of the operation. He said that he did not complain, as he expected to feel it; for he could not believe what had been told him about chloroform.

I believe the patient had emphysema of the lungs. There was no such force used in the artificial respiration as could permanently dilate the air-cells, and the dilation of the right ventricle indicates some chronic obstruction to the pulmonary circulation. In commenting on a case of death from chloroform, which occurred at the Mauritius, I made the following remarks:‡--"The reporter considered that the emphysema was the cause of death, by interfering with expiration, and thus detaining the vapour; and it must be admitted that, if the vapour were not sufficiently diluted with air, the emphysema would increase the danger. At the same time I have had practical experience to show, that when it is sufficiently diluted, it may be safely inhaled, even in extreme cases of emphysema." (‡London Journal of Medicine, May, 1852.)

The continuance of respiration so long after the heart is paralysed, in the case I have related above, and in some deaths which have happened from chloroform, is an extremely curious event. It proves that some little circulation must be still going on through the brain, and, in fact, the slight fluttering pulse and feeble sounds of the heart once or twice heard indicate this; but, under these circumstances, why does not the [381/382] heart recover itself? If the circulation were going on in the coronary arteries, it might be expected that the blood from the lungs, which has been aerated by respiration and freed from the narcotic vapour, would restore the action of the heart. Dr. Cockle has expressed the opinion, which is very probable, that the blood enters the coronary arteries in a retrograde manner, during the diastole of the ventricles, when the aorta and such great arteries are contracting on their contents; if so, with a very feeble circulation, the elasticity of the aorta, perhaps, cannot sufficiently act to cause a backward current, and perhaps, also, the over-narcotism of the heart is itself an obstacle to the coronary circulation, by the congestion in the capillary system which always attends on narcotism.

The above accident happened in the 144th case in which I have administered amylene. It is impossible to form an average from a single case. I do not know any reason why an accident like the above might not have occurred in one of the early cases in which I was giving chloroform, or, on the other hand, why I might not have been able to go on for four of five years at a time administering amylene, without any approach to an accident. The investigation of this agent has been actively taken up on the Continent, and the extent to which it will ultimately be used will probably not be much influenced by the occurrence I have had to relate.

18, Sackville-street, April, 1857.