Source:  Snow, John. Med. Times and Gazette, n. s. vol. 14, Apr. 4, 1857, pp. 332-334 (Part 1); Apr. 11, 1857, pp. 357-359 (Part 2); Apr. 18, 1857, pp. 379-382 (Part 3).

Further remarks on amylene

By John Snow, M.D.

Part 1

In my former paper, which appeared on the 17th and 24th of January, I merely stated, with regard to the preparation of amylene, that it was made by distilling fusel oil with chloride of zinc; and I referred to the original paper of M. Balard, its discoverer, for further particulars.* (*Annales de Chimie et de Physique, t. lxxxvii. 1844.) As amylene is beginning to be somewhat extensively used, I think it is desirable that I should quote the process of its preparation more in detail. The crude fusel oil must be submitted to a careful distillation with a thermometer in the retort. It begins to boil at a comparatively low temperature, but that portion only is to be retained which comes over from 130º to 140º Centigrade. Caustic potash is added to decompose the œnanthic ether which the distilled liquid contains, and it is then redistilled, and that portion which boils steadily at 132º Cent. is collected as pure amylic alcohol. Amylene can be obtained from amylic alcohol in the same manner that olefiant gas, or ethylene, can be made from common alcohol, namely, by heating it with dishydrating agents, as sulphuric, phosphoric, fluoboric and fluosilic acids, and chloride of zinc; but most conveniently with the last substance, which is the one that M. Balard employed. The product which is obtained when amylic alcohol and chloride of zinc are distilled together contains at least three distinct hydro-carbons, amylene, paramylene, and metamylene; and the amylene which is the most volatile is separated from the others by successive distillations.

It is probable that the amylene hitherto produced is not entirely free from other hydro-carbons of a similar composition, for its boiling-point is not quite steady. M. Balard gives 39º Cent. (102º Fahr.) as its boiing-point; and I have found [332/333] this to be the average boiling-point of the amylene I have obtained from Mr. Bullock, but it usually begins to boil freely at about 35º Cent.; and as it evaporates the boiling-point gradually rises to about 43º Cent. There are some specimens which begin to boil at a still lower temperature than 35º Cent., and are put in a state of ebullition by the warmth of the hand, owing to gaseous hydro-carbons, which they hold in a state of solution. The greatest part of the odour of amylene is contained in that portion which distils over below 39º Cent. It is probable that the amylene, as hitherto prepared, contains a little butylene, for butylic alcohol is one of the constituents of crude fusel oil, and it is not likely that amylic alcohol can be obtained entirely free from it by fractional distillation, the only process at present known for its separation.

The fact of amylene not being an absolutely pure body in a chemical sense is no objection to its use, since it can be obtained uniform in all its properties and in its physiological effects. The numerous specimens of amylene with which Mr. Bullock has supplied me, have been uniform in their physical properties, and in their effects. Soon after my former paper was published some amylene was made by M. Berthé, of Paris, which was shown to M. Balard, the discoverer of the substance, and met with his approval. A portion of this was administered by Dr. Debout, to some patients operated on by M. Aran, in the Hospital Saint Antoine, and produced exactly the effects which I had described.* (*See Bulletin Général de Thérapeutique, 15 Février, p.127. Since the above passage was written Dr. Debout has kindly sent me, through Mr. De Metic, a specimen of the amylene prepared by M. Berthé. I found it to be just like that prepared in London, and I used it in an operation by Mr. Fergusson, in King's College Hospital, with the usual result.) Dr. Debout also examined some amylene made by Mr. Bullock, in London, and performed some experiments on animals with it, and he found it to possess the same properties as that prepared in Paris.† (†Ibid. 15 Mars, p. 215 and 223.)

Mr. Bullock has succeeded in preparing amylene during the last few weeks with much less odour than before, and thus the strongest objection to this agent is already in a great measure removed. It is probable that the nearer the amylene approaches to a state of absolute purity, the less will be its odour. A substance was supplied as amylene to one of the large hospitals in London, which produced no effect when inhaled, and I found that it was brownish liquid, having no resemblance to amylene. At another placed the amylene failed to produce an effect, and I was informed that it was adulterated with twice its volume of spirit of wine. This kind of adulteration can easily be detected by shaking a portion of the amylene with water in a graduated tube or minim measure, when the spirit mixes with the water and the amylene rises to the surface. When the amylene is pure it is not diminished in volume by shaking with water; it is perfectly clear and colourless, and it evaporates quickly and entirely when dropped on the hand. Although it has a very distinct odour, somewhat resembling naphtha, it is almost without taste, and it is entirely without pungency, furnishing in this last respect a marked contrast to both chloroform and ether. It produces no irritation or effect of any kind on the sound skin, even when confined, and prevented from evaporating.

Amylene is inflammable, and in pouring it out by candlelight the same care is required as in dealing with sulphuric ether. A slight explosion may be obtained by applying a light to a mixture of a small quantity of its vapour with a large amount of air.

The paramylene, which is produced at the same time as amylene, does not possess sufficient volatility to be inhaled with a view to induce insensibility. It has been tried in Paris, and failed. It boils at 160º Cent. Metamylene, which does not boil till raised to 300º Cent., is still further out of the question. There are, however, other carbo-hydrogens produced in the process of making amylene, which boil at a temperature between the boiling point of amylene and that of paramylene, and, so far as their physical properties are concerned, I thought they might be eligible and convenient for inhalation; but, on making some experiments on guinea-pigs and mice, with a specimen boiling from 85º to 100º Cent., with which Mr. Bullock was good enough to furnish me, I found that the physiological effects were altogether undesirable. It produced illness, debility, and difficulty of breathing, but neither unconsciousness nor anæsthesia.

I have administered amylene in 110 additional cases since January 10, when my former paper was written; and this extended experience has confirmed the observations which I made on the earlier cases. The great ease with which it can be breathed owing to its entire want of pungency, is a decided advantage which it possesses over both ether and chloroform. It rarely causes the least cough, unless the vapour be inhaled too strong at the very beginning; and insensibility can always be induced in as short a time as is desirable, namely, in from three to four minutes in the adult, and about two minutes in young children. It is not desirable to cause insensibility in a shorter time than this with any agent. If narcotism is induced too quickly, the symptoms are not uniform or in regular order, owing, no doubt, to the circumstance that the narcotic vapour is not equally distributed through the blood, which must convey it to the nervous centres. Insensibility can, indeed, be generally induced with chloroform in the time above-mentioned, but there are many cases in which there is considerable delay at the commencement of inhalation, owing to the pungency of the vapour, especially in nervous and in sensitive patients, and in persons with irritability of the air-passages from chronic bronchitis, phthisis, or any other cause.

Further experience has entirely confirmed me in the conclusion that anæsthesia, or the absence of common sensibility, is obtained by the use of amylene with much less coma or stupor than occurs in the use of chloroform or ether. Indeed the greater number of operations under amylene have been performed whilst the patient was apparently awake, although not really conscious of surrounding objects. I am quite satisfied, from experiments which I have performed on animals, that amylene is capable of causing a state of deep coma, and that very quickly, by increasing the quantity of vapour in the inspired air; and I have in two or three instances observed this condition for half a minute or so in a patient; but since pain can be prevented by amylene without deep coma, one abstains from inducing it. The usual absence of come in the employment of amylene cannot be looked on otherwise than as an advantage. It must conduce to the safety of the agent. The reason why no accident is known to have happened from chloroform in the practice of midwifery when superintended by a Medical man, is, no doubt, due to the circumstance that it is only requisite to induce a slight effect, in comparison with the effect required in surgical operations. The best indication that the patient will quietly bear an operation under chloroform, is the more or less complete absence of sensibility of the ciliary edge of the eyelid; but during the inhalation of amylene the patient is often entirely regardless of the surgeon's knife, whilst the edges of the eyelids retain their full sensibility, and the slightest touch causes strong winking. In operations on the eye, however, and in all other cases where great steadiness on the part of the patient is required, I have though it best to continue the amylene till the sensibility of the margin of the eyelid was almost abolished; and to effect this it has usually been requisite to carry the influence of the vapour as far as the beginning of the third degree of narcotism, or that condition in which there is no longer voluntary motion of the eyes, or any other part, and in which the eyelids are usually closed, and the pupils inclined upwards. But even in these cases the patient has usually reverted to the second degree of narcotism before the end of the operation, and has shown signs of ideas by the voluntary motion of the eyes and eyelids, or in some cases by speaking. In several cases, however, the sensibility of the eyelid has been removed in the second degree of narcotism, and important operations have been commenced before the patient was "off," to use an expression familiar on these occasions. One instance of this kind was the operation of lithotomy by Mr. Fergusson on the 14th instant, in a young man, aged 17, in King's College Hospital. The sound was first introduced, and the stone being detected, the assistants were requested to tie the patient up; and finding his limbs somewhat rigid, they requested me to give him some more vapour; if I had been using chloroform, I should have done so without any request, in order to cause relaxation, but I allowed the effect of the amylene to partially subside, and in less than a minute the bandages could be easily applied. I then proceeded to give a little more amylene, but soon found that the margin of the eyelids was insensible, so the operation was performed whilst he was calmly looking about, as if awake, but he showed no signs of pain, and knew nothing of the operation. I never saw a capital operation performed on [333/334] the adult under the influence of chloroform or ether, whilst the patient was in this condition; but I once administered chloroform in St. George's Hospital to a child of three or four years old, which was cut for stone whilst lying calmly with its eyes open, and holding a toy in its hands, all the time of the operation, without letting it fall. In tenotomy, and many other minor operations, I have merely continued the amylene till an altered expression of countenance indicated that the patient was no longer conscious of his situation, or of surrounding objects, and the operations have always been completed without the patient's knowledge, although awaking often within a minute afterwards.

There is a tendency to laugh during the inhalation of amylene much more frequently than during the inhalation of chloroform. It occurs just after the patient has lost his consciousness, but it is soon subdued by the increasing effect of the vapour. The colour of the countenance is generally heightened more or less during the whole period of the inhalation. The expression generally remains calm and cheerful, but in a few instances there is a singular, and even unpleasant aspect of the countenance for a short time, arising apparently from a brief spasmodic action of the muscles. I have only met with strong mental excitement in three patients, all females; it subsided in half a minute in one case on leaving off the vapour, and was as quickly subdued in the others by continuing it. The excitement did not return in the first case, when the inhalation was resumed.

The pulse is almost always accelerated during the early part of the inhalation, and the breathing at the same time quickened. In many of the early cases in which I administered amylene the pupil was dilated for a short time, and I consider that this arose from giving the vapour rather stronger than is desirable. I have lately given the vapour more gently, and for several weeks I have not observed the pupils to be dilated; they have remained, as nearly as I could tell, of the natural size, and also sensible to light, in the cases where I have made an observation on that point.

There has been some amount of rigidity and spasm in a considerable number of cases in which I have employed amylene, but not to the extent which occurs sometimes in the employment of chloroform. The rigidity, moreover, is of a somewhat different kind, and occurs in patients in whom we should not expect it from chloroform. In the spasm and rigidity from the latter agent the head is more commonly bent forwards, or turned to one side, although occasionally it is thrown back; but under amylene the latter is the usual position it assumes when rigidity occurs, constituting a brief opisthotonus. The rigidity under the influence of chloroform is usually accompanied with struggling, while in that caused by amylene the patient is generally quieter. The person in whom rigidity and struggling are most violent from the effects of chloroform are lean, muscular men, who work at hard labour, or follow athletic sports, such as hunting, and especially boating; while those who lead a sedentary life, or are reduced by illness, seldom exhibit these phenomena. Women and children seldom exhibit any rigidity under chloroform, and fat persons least of all. Old people do sometimes, especially if thin. Under the use of amylene, on the other hand, I have most frequently met with some amount of rigidity in children and young persons, while many robust men, in whom it would be almost certain to occur under chloroform, have not shown any signs of it. The cause of this probably is, that the operation has generally been performed without carrying the narcotism beyond the second degree, while rigidity does not take place till the third degree is attained. In every case where rigidity and struggling have occurred in the employment of chloroform, however violent these symptoms might be, I have continued the vapour gently and steadily till they were subdued, either by removing the tendency to these symptoms, or by carrying the narcotism to the fourth degree, which is accompanied by relaxation of the voluntary muscular system, and usually with some tendency to stertor. When the struggling from chloroform is once subdued it rarely recurs during the operation, although there are a few patients, especially among hard drinkers, who have a tendency to struggle whenever the effect of the chloroform diminishes. In the use of amylene, on the contrary, I have not attempted to subdue the spasm by continuing the inhalation, but have, with the exception of a case of dislocation, to be mentioned further on, withdrawn the vapour when the rigidity appeared, and the operation has either been performed at once, or else, if it was of a nature that the spasm would interfere with, I have waited a short time, and exhibited a little more vapour very gently. I have every reason to conclude from experiments which I have made on animals, that the spasm caused by amylene could always be subdued by increasing the strength of the vapour; but I have not followed this plan, as it appears to be unnecessary. In fact, I have reason to believe that in some of the earlier cases in which I administered amylene, a certain amount of spasm, which might have been avoided, was induced by carrying the effects of the vapour a little further than was necessary, or by giving it a little more quickly than was desirable.

I stated in my former paper, that I had not met with sickness in any of the twenty-one cases in which I had exhibited amylene. I afterwards learnt, however, that vomiting had occurred in one of these cases two or three hours after the operation. In the subsequent 110 cases I have only been able to hear of sickness in seven instances, although I have been able to make inquiry respecting all but a few of the patients. What is remarkable is, that I have not seen vomiting take place in any instance in which I have administered amylene, although in the last hundred cases in which I have given chloroform twenty-two of the patients, or more than one-fifth, vomited before I left the room. This occurred, notwithstanding that directions had been given in the greater number of instances not to take a meal before the operation. Certainly, these directions were given in a greater proportion of the chloroform cases than in those where amylene had to be inhaled. I administered amylene on January 30 to a lady about 25, while Mr. Bowman operated for strabismus, and there was no vomiting or sickness, either at the time of the operation or afterwards; but the same patient had undergone a similar operation a week previously, when chloroform was administered, and on that occasion vomiting commenced before the operation was finished, and recurred every quarter of an hour, with violent retching, for twelve hours. The sickness caused by chloroform usually begins at the time of the operation, or within a quarter of an hour afterwards; the most usual time for it being, as consciousness is returning; and if there is no sickness after chloroform till some hours have elapsed, there has generally been a dose of opium in the mean time, or some other cause, which would account for it. The few instances of sickness which have happened after amylene, however, have chiefly occurred at the end of a few hours, although there was no intervening cause for it. The sickness has not been severe in any case; it was generally a single attack of vomiting, after which no feeling of sickness remained.

Part 2

Amylene differs widely from chloroform, and still more from sulphuric ether, in the promptitude with which patients generally recover from its effects. This is a character of amylene which might have been predicted from its physical properties. I have many times observed how quickly, and, indeed, almost instantaneously small animals recover from the stupor occasioned by certain permanent gases which are sparingly soluble in watery fluids, as olefiant gas, carbonic oxide and carbonic acid gases, nitrous oxide and the gaseous oxide of methyle. Now amylene is so volatile as to approach to a permanent gas; at a temperature a little above that of the human body it would be a gas, and the vapour is very sparingly soluble in water fluids, and consequently in the blood. Suphuric ether is, indeed, as volatile as amylene. I cannot remember any other two bodies whose volatility is so nearly alike; but sulphuric ether is very soluble in watery fluids, in comparison with amylene. Water dissolves a tenth of its volume of liquid ether, or 23 volumes of the vapour. Consequently a large quantity of ether is absorbed during inhalation, and the blood has to pass many times through the lungs before it is freed from it. The quantity of amylene which is absorbed is, on the contrary, extremely small, as I explained in my paper in January, and this, together with its volatility, is no doubt the reason why the patient recovers so promptly from its influence. In about a minute after the operation is concluded, and the inhalation left off, the patient usually awakes from the influence of amylene, and completely recovers his consciousness. The same quick recovery may take place after chloroform, but more frequently it is a few minutes before the patient is quite conscious. I have seen two or three instances in which a child has slept for twenty minutes or half an hour after amylene, but it must be remembered that children sometimes sleep for hours after chloroform in cases where the operation has not produced a painful wound. The quick recovery of the patient is a decided advantage in all minor operations. In great operations, where the patient is obliged to keep his bed afterwards, it is of less consequence whether he wakes promptly or not, although, even under [357/358] these circumstances, his friends are generally anxious to see him recover his consciousness. The smarting of the wound after an operations is often prevented longer when chloroform has been employed than after the use of amylene, and this may be considered as a slight advantage which chloroform possess in certain cases. In some instances, however, in which chloroform has been used, the patient begins to show symptoms of suffering pain in the wound before he has entirely recovered his consciousness, while after amylene I have not seen symptoms of pain in the wound till consciousness has completely returned. In any case where the pain after an operation, either from a wound or ligature or caustic, is very great, the inhalation of the agent which has been employed may be gently repeated at times until the pain has a tendency to subside, or till an opiate shall take effect.

The patient generally seems surprised or confused on first recovering from the effects of the amylene, but in a few seconds he becomes, in most cases, completely conscious of his position, and feels that his mind has been wandering. He often says he does not know where he has been in his dreams, or that he has been a long way. Sometimes he does not remember exactly what he has dreamed about; at other times he does. All this is common enough after chloroform, except that the process of recovery is generally much slower; but there is one condition of mind which is very common after chloroform, which I do not remember yet to have met with after amylene. If the patient, when he awakes from even a deep and prolonged insensibility, is in the same position as when he became unconscious, he often asserts that the vapour has not taken effect, he requests that the operation may not be commenced, and will not believe it is over till convinced by his own senses. It seems as if, in such cases, a piece has been snipped, as it were, out of the mental existence of the patient, and that not even dreams had occurred.

The patient has nearly always a very cheerful expression of countenance when he recovers from the amylene, and the state of his mind, as indicated by his conversation, corresponds to his look. Dr. Debout has noticed the same circumstances. Speaking of the patients operated on under amylene in Paris, he says, "A leur réveil et le premier moment de stupeur passé, leur physionomie est épanouie." The same state of countenance and mind is met with after chloroform only now and then, and is by no means the rule. I have met with hysterical laughing and crying in three females after operations under amylene, which I think is not oftener than the same symptoms might be met with after chloroform. In one case where Mr. Fergusson amputated the leg of a young woman, the hysteria lasted about an hour; in the other two cases it subsided in a much shorter time, although the patients were very subject to this affection.

Amylene appears to support the pulse under loss of blood at least as well as chloroform. I have not as yet found the pulse to fail, although there was rather free hæmorrhage in one or two operations.

There has been a little headache in a few cases as the effects of this agent were subsiding, but it has passed off in a few minutes.

I have already administered amylene in many of the chief operations of surgery. There have been five cases of lithotomy in the male, three of them by Mr. Fergusson, in King's College Hospital; the young man and the child already alluded to in my former papers, and another child; and two cases in St. George's Hospital, one by Mr. H. C. Johnson, and the other by Mr. Pollock, both children. All the five cases have done well. In addition to the amputation of the thigh by Mr. Henry Lee, mentioned in the paper in January, I administered amylene in a similar operation by Mr. Tatum, in St. George's Hospital, and also in an amputation of the forearm by the same gentleman, and an amputation below the knee by Mr. Fergusson, in King's College Hospital. I have administered amylene in the removal of the head of the femur by Mr. Bowman; in the removal of three large tumours near the groin, two of them by Mr. Bowman, and one by Mr. Fergusson; in the removal by Mr. H. C. Johnson of a tumour deeply seated behind the angle of the jaw, and in the removal of six tumours of the breast by different Surgeons. There have also been three operations for stricture by perineal section, two by Mr. Fergusson, and one by Mr. Curling. The amylene has answered perfectly well in all these cases, so there can be no doubt of its general applicability in the great operations of surgery.

Amylene has succeeded perfectly well in operations of the eye. In the extraction of cataract it will probably have an additional advantage, in the almost entire absence of sickness after its use. I have exhibited it in two cases of extraction of cataract, performed by Mr. Bowman, and one operation for cataract by drilling. Also in six cases of excision of the eyeball for various diseases, by Mr. Bowman; one of these cases occurred in King's College Hospital, one in the Ophthalmic Hospital at Moorfields, and the others in private practice. There have been also twelve operations for strabismus, and a number of other operations on the eye and the eyelids, in which I have administered amylene chiefly for Mr. Bowman. I have given it in three cases of the forcible rupture of the adhesions in anchylosed joints, and it has answered perfectly in preventing the pain. Two of the cases were in King's College Hospital, and one in the Orthopædic Hospital, under Mr. Lonsdale.

I have employed amylene in two cases of dislocation of the humerus, both patients of Mr. French in the St. James's Parochial Infirmary. The first case was a dislocation downwards in a woman aged 68. She inhaled for three minutes, when extension being made, the bone slipped into its place with the utmost ease, although Mr. French had found a good deal of resistance in an attempt he made just before sending to me--not any serious resistance or pain, but so much of both as led him to think it would be a good opportunity for trying the amylene. In two minutes after the reduction of the dislocation, and five minutes after beginning to inhale, the patient was awake again, and said that she had felt nothing. The other case was a dislocation forwards in a man aged 72. No attempt to reduce it was made till the amylene was administered. The case was under the care of Mr. Buzzard. After inhaling two or three minutes, the old man got into a state of muscular rigidity, and did not get beyond this state, although I continued the inhalation nearly ten minutes until about two ounces of amylene were used. He was quite insensible, but the rigidity prevented the reduction of the dislocation. So I discontinued it, and sent for some chloroform, which I administered a few minutes afterwards. It produced muscular rigidity rather stronger than that which the amylene had caused, but by continuing the inhalation steadily for about two minutes, the limbs became relaxed, and the humerus slipped easily into place. This is the only case in which the amylene has not effected the purpose for which I have exhibited it; and I have no doubt, for reason which I stated before, that I could have produced relaxation of the voluntary muscles by increasing the strength of the vapour the patient was breathing; but there were one or two circumstances which at the moment stood in the way of this. The patient's face was so hollow from his loss of teeth that the face piece fitted badly, and as it was early in a frosty morning the water bath of the inhaler was colder than usual. These defects could have been remedied if necessary, but I thought it as well to use chloroform; and I am inclined to think that chloroform is the better agent to employ in those rare instances where relaxation of the voluntary muscular system is required. I remain also of the opinion, which I expressed years ago, and which I occasionally act on, that sulphuric ether is preferable to chloroform in the reduction of old dislocations, as it seems to produce complete relaxation of the muscles more readily and constantly than chloroform.

Amongst the minor operations in which I have administered amylene, have been eighteen operations of tenotomy, chiefly by Mr. Williams Adams and Mr. Lonsdale, in the Royal Orthopædic Hospital, and mostly in children and young people. An inhalation of about two minutes generally sufficed to prevent the pain entirely. I find that some surgeons have entertained an objection to use chloroform in tenotomy, lest it should cause a relaxation of the muscles, which would interfere with the operation. I have, however, been in the habit of exhibiting it for eight or nine years, both in King's College Hospital and in the private practice of Mr. Fergusson and some other surgeons. I never carried the effect of the chloroform so far as to cause relaxation of the muscles, and I have generally heard the tendons give way with a snap. With a small dose of amylene the tensions of the muscles not only remain, but is usually somewhat increased.

Amongst the more important and painful operations in which I have given amylene, and where it has answered perfectly, [358/359] I ought to have mentioned several cases of necrosis affecting various bones,--as the femur, lower jaw, tibia, etc. I administered it to an infant about six months old, in King's College Hospital on January 17th, previous to Mr. Fergusson operating for hare-lip. The child was insensible to the knife at the beginning of the operation, but began to cry before the incisions were finished, and cried very lustily as the hare-lip pins were introduced. The property, previously alluded to, which amylene possesses, of allowing the patient to awake so quickly, although an advantage in most operations, is not desirable in operations about the mouth, where the inhalation cannot very well be continued or resumed. This is more especially the case in young children, who awake, even from chloroform, more quickly than we wish in such operations. There have been four or five operations on infants for hare-lip since the one above mentioned, but I have given either chloroform or sulphuric ether. In all the other operations in this Hospital, when I have been present to administer any narcotic vapour, since the 13th of December last, I have exhibited amylene, in order to give it a fair trial. There have been several plastic operations on the face in patients of adult age, or nearly so. The amylene has always prevented the pain at the beginning of the operation, and has been continued on a hollow sponge afterwards for some little time. On two or three occasions it was so continued with success to the end of the operation; but two or three times the sponge became so cold by the continued evaporations of the amylene, as to make my fingers ache, and to limit the evaporation so much that the patient seemed about to awake. I therefore put a little chloroform on the sponge, and it answered the purpose desired. Chloroform absorbs much less caloric than amylene during its evaporation, as the patient inhales, on account both of the quantity which evaporate being less, and of the specific gravity of the vapour being greater.

In tooth-drawing, amylene has both its advantages and disadvantages as compared with chloroform. The prompt recovery from its effects, and the almost constant absence of sickness, are decided advantages, as also is the greater ease with which it is inhaled; but in cases where eight or ten teeth require to be extracted at once, as often happens, where my assistance is required, or where several stumps are in the alveolus, the effect of amylene does not last long enough to complete the operation, without one or more repetitions of the inhalation. A difficulty in getting the mouth open occurs about as often, I think, with one agent as the other.

I have only as yet had leisure to administer amylene in two cases of labour. One was under the care of Mr. Buzzard in the St. James's Infirmary, on January 20th. It was the patient's second labour, and was a lingering one, having lasted 35 hours. I administered the amylene only during the last 20 minutes preceding the birth of the child, the head being advanced so as to rest on the perinæum. The vapour was given well diluted at the beginning of each pain. The patient breathed very deeply, and got relief very quickly from each pain; the mind was quite clear between the pains, and I could not tell whether or not the consciousness was removed for half a minute or so, during each pain. Half a fluid ounce of amylene was used. The other case occurred in an out-patient of King's College Hospital under the care of Mr. Meadows, Dr. Farre's assistant. It was the patient's third confinement. I arrived three hours after the commencement of labour, and two hours before the birth of the child. The os uteri was almost dilated on my arrival, and the pains were very strong, recurring every three minutes or so. They continued to increase in strength to the last. The patient was probably unconscious for a brief period during the uterine contractions, while the amylene was administered, but between the pains she was quite conscious. Under the use of chloroform, in a labour with brisk and frequently recurring pains, as in this case, the patient usually sleeps on from one pain to another, but I offer no opinion at present as to which state of circumstance is preferable. The amount of amylene inhaled in this case was three fluid ounces. The quantity used in each of these cases must have been about half a fluid drachm in each pain, and this is the quantity I had previously recommended Dr. Tylor Smith to employ, when he did me the honour to ask me some questions about amylene before he employed it in a case of labour. The results arrived at by Dr. Tylor Smith, in the case in which he employed amylene, were similar to my own, viz.[,] relief of suffering during the uterine contraction, consciousness between pains, and no interference with the progress of labour. I look forward with some interest to a more extended experience of amylene in midwifery. Chloroform answers so extremely well that there does not seem much room for improvement; there are cases, however, in which chloroform has a tendency to retard the progress of labour, by diminishing the force, duration, and frequency of the uterine contractions, even when administered very moderately; and it remains to be ascertained, by observing a number of cases, whether amylene may not be free from this disadvantage.

In the concluding part of this paper I shall make some remarks on the mechanical means of administering amylene in the most efficient way, and on its relative safety as compared with chloroform and ether.

Part 3

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.

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