Source: Snow, John. London Med. Gazette, vol. 41,  June 23, 1848, pp. 1074-78 (part 3).

On narcotism by the inhalation of vapours

By John Snow, M.D.

[Part 3]

Experiments to determine the quantity in the blood, and illustrate the action of nitric ether, bisulphuret of carbon, and benzin.

Nitric ether, or nitrate of the oxide of ethyle, consists of nitric acid combined with ordinary or sulphuric ether. It is described as a colourless liquid of sp. gr. 1.112, with a sweet taste and pleasant smell, and boiling at 185° Fah. Two specimens of it which I have answer to this description. One was made and presented to me by Mr. Bullock; and the other, which was made by Mr. Joseph Spence, was given to me by Dr. Barnes. Dr. Chambert, of Paris, related some experiments that he had performed on dogs with the vapour of this substance, in a work on Ether, published in autumn last; and Dr. Simpson afterwards mentioned it in his pamphlet on Chloroform, as one of the things that he had tried.

The two following experiments will serve to determine the quantity of nitric ether in the blood, when insensibility is induced by it:--

Exp. 29.--Four grains were diffused through the air in a jar containing 800 cubic inches; and a common mouse was introduced in the same manner as in the preceding experiments. In ten minutes it became rather torpid, but could be disturbed by touching the jar. It was left in this condition when it had been in a quarter of an hour. On returning at the end of an hour from the commencement of the experiment, I found the mouse lying still. It was taken out, and it moved spontaneously, endeavouring to walk, but falling over; it was quite sensible to being pinched. In five minutes it had recovered power to walk, but was not yet conscious of danger, as it would have walked off the table if not prevented. In a few minutes longer it had recovered its usual state.

Exp. 30.--Another mouse was placed in the same jar with eight grs. of nitric ether. It became affected in ten minutes, and at the end of a quarter of [1074/1075] an hour had ceased to move, but lay breathing naturally 160 times in the minute. It remained in this state till removed half an hour after the commencement of the experiment, when it was found to be relaxed, and totally insensible. It began to move in ten minutes; it could walk at the end of a quarter of an hour, and in a little time longer was quite active.

We perceive from the above experiments that half a grain of nitric ether to each 100 cubic inches of air suffices to induce the second degree of narcotism, and one grain the fourth degree. I have not met with a statement of the specific gravity of the vapour of this ether in any work to which I have referred, and consequently I endeavoured to determine it myself--not with great nicety, but with sufficient accuracy to satisfy the purpose of this inquiry. I made it to be 5.67; and half a grain of vapour in 100 cubic inches of air saturated with it at 100° is 15.7 cubic inches, and 0.284÷15.7 will give 0.018, or rather less than one fifty-fifth, as the relative saturation of the blood with nitric ether in the second degree of narcotism. One grain produces 0.568 of a cubic inch of vapour: and this, divided by 15.7, gives 0.0361, or very nearly one twenty-eighth, as the relative saturation of the blood in the fourth degree of narcotism. So we find that the quantity of the vapour in the blood, viewed in relation to what it would dissolve, is the same as in the cases of chloroform and sulphuric ether. In some experiments on birds, a rather larger quantity of vapour was required; but when their higher temperature was taken into account the relative proportion to what the air would take up was found to be the same, and, consequently, their blood was saturated to just the same extent.

One part by measure of nitric ether requires 52 parts of serum at 100° to dissolve it, and 52 x 56 = 2912; consequently, one part in 2912 is the proportion in the blood in the second degree of narcotism; and considering the average quantity of serum in the body, as before, to be 410 fluidounces, we get by calculation 67 minims as the whole quantity in the blood in this degree; and twice as much, or 2 drachms and 14 minims, in the fourth degree. These quantities agree with the little experience I have had of its effects on the human subject.

From its slight pungency, and the gradual way in which, owing to its sparing volatility, its effects are produced, nitric ether would be a very safe anaesthetic, suitable for minor surgical operations if its effects were agreeable, but such is apparently not always the case. M. Chambert met with vomiting in most of the dogs to which he gave it, and was deterred from inhaling it himself. Dr. Simpson states, in the Monthly Journal of April last, that he had found it to produce sensations of noise and fullness in the head before insensibility, and, usually, much headache and giddiness afterwards. I have inhaled a small quantity of it on two or three occasions, and it caused a disagreeable feeling of sickness each time. I have given it only to one patient, but in that instance it acted very favourably. A middle-aged man applied at St. George’s Hospital, on May 26, to have a tooth extracted. He inhaled from the apparatus I use for chloroform. Soon after he began his pulse became accelerated and increased in force, and his face rather flushed. He continued to inhale steadily for three minutes, when I found that the sensibility of the conjunctiva was considerably diminished, although voluntary motion continued in the eyes and eyelids, the expression of his countenance not being altered from that of complete consciousness and he held his head upright. The vapour was left off, and the tooth, which was firmly fixed, was taken out by Mr. Price, the dresser for the week, without any sign of the operation being felt; the man holding his mouth wide open in an accommodating manner. A minute afterwards he began to spit on the floor; and being questioned, he said that he had no knowledge of the removal of the tooth, and should have thought that he had never lost his senses, except for what he found had been done. His feelings were not unpleasant whilst inhaling, and he felt well, and walked away in a few minutes afterwards. A fluid-drachm and a half was employed, and it was not all used. There was perfect immunity from pain, whilst the narcotism of the nervous centres was not [1075/1076] carried further than the second degree: this, however, I do not look on as a peculiarity of nitric ether, for I have met with it occasionally from chloroform and sulphuric ether when the vapour was introduced slowly. The above case, I think, affords encouragement for further trials of this medicine.

Bisulphuret of Carbon.

This substance is well known to every one at all conversant with chemistry. It is a transparent colourless liquid, of sp. gr. 1.272, having a very fœtid odour, and boiling at about 113°. A paragraph copied from the Morgenblad went the round of the journals of this country about the end of February last, stating that M. Harald Thanlow, of Christiana, in Norway, had discovered a substitute for chloroform and ether, in a sulphate of carbon, a very cheap substance made from sulphur and charcoal. This, of course, could be nothing else than the bisulphuret of carbon. I immediately examined its effects of animals, and found that it causes convulsive tremors, but that the kind of narcotism such as ether produces may be recognized. 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.

The following experiments will shew both the action of the yapour [vapour] and the quantity of it in the blood.

Exp. 31.--Two grains of bisulphuret of carbon were diffused through the air in a jar holding 200 cubic inches, and a white mouse was introduced. In three minutes it was altered in its manner, and no longer regarded the approach of the hand towards it. In six minutes tremors came on, which soon became violent, and lasted till after the mouse was taken out at the end of ten minutes; but voluntary motion continued along with the tremors. When taken out, it flinched on being pinched; attempted to walk, but fell over on its side: it had no appreciation of danger at first, but it quickly recovered.

Exp. 32.--A common mouse was put into a jar holding 800 cubic inches, in which 12 grains of bisulphuret of carbon had been diffused, being a grain and a half to each 100 cubic inches. In a minute it began to have convulsive tremors whilst still walking. In half a minute more, voluntary motion ceased, but the tremors continued. It was removed at the end of ten minutes, was sensible to pricking and pinching, and in a minute or two began to recover voluntary motion, the trembling of the whole body continuing for a little time after it was able to walk.

Exp. 33.--A white mouse was placed in the jar of 200 cubic inches capacity, with four grains of this substance in the form of vapour. It became quickly affected, and was lying powerless in less than half a minute. Convulsive tremors came on immediately after it fell, and lasted till death. At the end of four minutes the breathing became difficult, being performed only by distant convulsive efforts. The mouse was immediately removed, but only gave one or two gasps afterwards.

In another experiment, in which there were two and a quarter grains to each 100 cubic inches of air, the mouse, after running about for a minute, fell down, and stretched itself violently out, and died.

There is no stage of muscular relaxation prior to death by this vapour, as by those we have previously considered, when their effects are gradually induced; but tremulous convulsions of the whole body continue till death, which seems to be threatened almost as soon as complete insensibility to external impressions is established.

In Exp. 31, narcotism to the second degree was occasioned by one grain to 100 cubic inches. The sp. gr. of the vapour of bisulphuret of carbon being 2.668, it will be found that one grain of the liquid must produce 1.209 cubic inches of vapour; and I find that air, when saturated with it at 100°, expands to four times it former volume, so that 100 cubic inches contain 75 of vapour. Therefore 1.209 ÷ 75 gives 0.0161, or one part in 62 of what the blood would dissolve, as the relative saturation of the blood in the second degree of narcotism; and, as Exp. 33 may be regarded as the nearest approach to the fourth degree that we can get with this vapour, twice as much, or one part in 31, is the relative amount for that degree. These proportions do not differ much from those arrived at in the inquiries concerning the vapours previously examined.

Serum at 100° dissolves, as nearly as I can determine, just its own volume [1076/1077] of the vapour of bisulphuret of carbon; and, as the liquid is 408 times as heavy as its own vapour at the temperature of 100°, it will be found, by a similar calculation to that made with respect to the vapours treated of previously, that about 7½ minims is the average quantity that there should be in the whole blood of the human subject in the second degree, and 15 minims in the fourth degree of narcotism. When the great volatility of this substance is also taken into account, it will be perceived that its effects, when inhaled, must be most powerful. Indeed, I feel convinced, that, if a person were to draw a single deep inspiration of air saturated with its vapour at a summer temperature, instant death would be the result. Although its odour is offensive, it is not difficult to inhale; and Dr. Simpson has given it in a surgical operation and an obstetric case; he also informs us (op. cit.) that its effects were so powerful and so transient, that it was very unmanageable, and that it also cause some unpleasant symptoms, and he does not recommend its use.

Benzin or Benzole.

This substance was first discovered by Dr. Faraday, as a product of the distillation of compressed oil-gas, and named bicarburet of hydrogen; it was afterwards obtained by Mitscherlich, by distilling a mixture of benzoic acid and slaked lime; latterly Mr. Blatchford Mansfield has obtained it by the distillation of coal-tar. It consists of carbon and hydrogen, as its first name implied, the proportions being C12H6. It is a clear, colourless, and very mobile liquid, of sp. gr. 0.85, and having an aromatic odour. It has been described as boiling at 180°; and a portion with which Mr. Mansfield favoured me, boils, as he always found it to do, about 178°. There is no difference either in sensible properties or physiological effects between the benzin made from benzoic acid, and that obtained from coal-tar. Like the substance last treated of, it causes convulsive tremors in addition to the other symptoms of narcotism; they usually begin in animals before voluntary motion ceases, and continue as long as the vapour is applied, and during part of the recovery, and until death when animals are killed by it. The tremors are usually violent, affecting the whole body, and accompanied in birds with flapping of the wings.

One experiment will suffice to shew the effects of this vapour.

Exp. 34.--Six grains of benzin were diffused through the air in a jar holding 800 cubic inches, being three-quarters of a grain for each 100 cubic inches; and a half-grown white mouse was introduced. In less than a minute it began to shake and tremble, and ceased to move voluntarily, but every now and then gave a sudden start; this start could also be occasioned at any time by striking the jar so as to make a noise. This mouse continued in the same state till removed at the end of a quarter of an hour; it was totally insensible to pricking and pinching, which produced not the slightest effect on it, whilst at the same time a sharp noise near it cause it to start. Five minutes after its removal it began to recover voluntary motion, but the tremors continued a little longer. The mouse was soon as well as before the experiment. Less than half a grain of benzin to each 100 cubic inches of air, suffices to impair the voluntary motion, and alter the manner of an animal; rather more than half a grain causes convulsive tremors, and three-quarters of a grain and upwards produces complete insensibility, whilst two grains will take away life. In the experiment related above, the fourth degree of narcotism appeared to be induced by three-quarters of a grain, but one grain to the 100 cubic inches of air is the average quantity for that state in several experiments. The specific gravity of the vapour of benzin being 2.738, one grain of the liquid makes 1.179 cubic inch of vapour; and I find that air saturated with it at 100°, contains 20 per cent of it by measure: so 1.179 ÷ 20 will give the relative saturation of the blood. It is 0.058, or one-seventeenth part of what it would dissolve. This is a greater proportion than we arrived at in examining the vapours treated of above.

Benzin requires 270 parts of serum for its solution; consequently, by the kind of calculation made before, 42 minims is obtained as the average quantity that there would be in the human body, if narcotism were [1077/1078] carried to the fourth degree by this vapour. It follows from this that benzin must be powerful in its effects, and such I have found to be the case, but they are not so rapidly produced as the effects of chloroform, on account of its lesser volatility. I employed it in some cases of tooth-drawing, and in one amputation, in St. George’s Hospital, at the latter part of last year. Its action in the minor operations was very nearly the same as that of nitric ether, in the case related above; but in the amputation, where its effects were carried further, the patient had violent convulsive tremors for about a minute, which, although not followed by any ill consequences, were sufficiently disagreeable to deter me from using it again, or recommending it in the larger operations.

(To be continued)

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