"Further remarks on amylene"

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By John Snow, M.D.

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 appeared in the 11 April issue.]