Source: Snow, John. London Med. Gazette, vol. 41, May 26, 1848, pp. 893-95
On narcotism by the inhalation of vapours
By John Snow, M.D.
Experiments with Ether
We will now proceed to consider ether, and will begin with the brief relation of a few experiments, shewing the strength of its vapour required to produce narcotism to various degrees.
Exp. 17.--Two grains of ether were put into a jar holding 200 cubic inches, and the vapour diffused equally, when a tam mouse was introduced, and allowed to remain a quarter of an hour, but it was not appreciably affected.
Exp. 18.--Another mouse was placed in the same jar, with three grains of ether, being a grain and a half to each 100 cubic inches. In a minute and a half it was unable to stand, but continued to move its limbs occasionally. It remained eight minutes without becoming further affected. When taken out it was sensible to pinching, but fell over on its side in attempting to walk. In a minute and a half the effect of the ether appeared to have gone off entirely.
Exp. 19.--A white mouse in the same jar, with four grains of ether, was unable to stand at the end of a minute, and at the end of another minute ceased to move, but continued to breathe naturally, and was taken out at the end of five minutes. It moved on being pinched, began to attempt to walk at the end of a minute, and in two minutes more seemed quite recovered.
Exp. 20.--Five grains of ether, being two and a half grains to each 100 cubic inches, were diffused throughout the same jar, and a mouse put in. It became rather more quickly insensible than the one in the last experiment. It was allowed to remain eight minutes. It moved its foot a very little when pinched, and recovered in the course of four minutes.
Exp. 21.--A white mouse was placed in the same jar with six grains of ether. In a minute and a half it was lying insensible. At the end of three minutes the breathing became laborious, and accompanied by a kind of stertor. It continued in the state till taken out at the end of seven minutes, when it was found to be totally insensible to pinching. The breathing improved at the end of a minute; it began to move at the end of three minutes; and five minutes after its removal it had recovered.
Exp. 22.--The same mouse was put into this jar on the following day, with seven grains of ether, being 3.5 grs. to the 100 cubic inches. Stertorous breathing came on sooner than before; it seemed at the point of death when four minutes had elapsed; and being then taken out, was longer in recovering than after the last experiment.
Exp. 23.--Two or three days afterwards the same mouse was placed in the jar, with eight grains of ether, being four grains for each 100 cubic inches. It became insensible in half a minute. In two minutes and a half the breathing became difficult, and at a little more than three minutes it appeared that the breathing was about to cease, and the mouse was taken out. In a minute or two the breathing improved, and in the course of five minutes from its removal it had recovered.
The temperature of the mice employed in the above experiments was about 100°. That of the birds in the following experiments was higher, as is stated; and they differ widely from the mice in the strength of vapour required to produce a given effect, although I found but little difference between the mice and the birds, in this respect, in the former experiments on chloroform. And one of the linnets was employed in both sets of experiments. Having seen MM. Dumeril and Demarquay’s statement of the diminution of animal temperature from inhalation of ether and chloroform, before the following experiments were performed, the thermometer was applied at the beginning and conclusion of some of them. I have selected every fourth experiment from a larger series on birds.
Exp. 24.--18.4 grs. of ether were diffused through a jar holding 920 cubic inches, being two grains to each 100 cubic inches; and a green linnet was introduced. After two or three [893/894] minutes it staggered somewhat, and in a few minutes more appeared so drowsy, that it had a difficulty in holding up its head. It was taken out at the end of a quarter of an hour, quite sensible, and in a minute or two was able to get on its perch. The temperature under the wing was 110° before the experiment began, and the same at the conclusion.
Exp. 25.--Another linnet was placed in the same jar, with four grains of ether to each 100 cubic inches of air. In two minutes it was unable to stand, and in a minute more voluntary motion had ceased. It lay breathing quietly till taken out, at the end of a quarter of an hour. It moved its foot slightly when it was pinched. In three minutes it began to recover voluntary motion, and was soon well. The temperature was 110° under the wing, when put into the jar, and 105° when taken out.
Exp. 26.--A green linnet was put into the same jar with 55.2 grs of ether, being six grains to the 100 cubic inches. It was insensible in a minute and a half, and lay motionless, breathing naturally, till taken out at the end of a quarter of an hour. It moved its toes very slightly when they were pinched with the forceps, and it began to recover voluntary motion in two or three minutes. Temperature 110° before the experiment, and 102° at the end.
Exp. 27.--A linnet was placed in the same jar, containing eight grains of ether to each 100 cubic inches. Voluntary motion ceased at the end of a minute. The breathing was natural for some time, but afterwards became feeble, and at the end of four minutes appeared to have ceased; and the bird was taken out, when it was found to be breathing very gently. It was totally insensible to pinching. The breathing improved, and it recovered in four minutes.
Exp. 28.--0.2 grs. of ether, being one grain to each 100 cubic inches of air, were diffused through the jar holding 920 cubic inches of air, and a frog was introduced. At the end of a quarter of an hour it had ceased to move spontaneously, but could be made to move its limbs, by inclining the jar so as to turn it over. At the end of half an hour voluntary motion could no longer be excited, and the breathing was slow. It was removed at the end of three-quarters of an hour, quite insensible, and the respiratory movements being performed only at long intervals, but the heart beating naturally; and it recovered in the course of half an hour. The temperature of the room was 55° at the time of this experiment.
We find from the 18th experiment, that a grain and a half of ether for each 100 cubic inches of air, is sufficient to induce the second degree of narcotism in the mouse; and a grain a half of ether make 1.9 cubic inches of vapour, of sp. gr. [specific gravity] 2.586. Now the ether I employed boiled at 96°. At this temperature, consequently, its vapour would exclude the air entirely; and ether vapour in contact with the liquid giving it off, could only be raised to 100° by such a pressure as would cause the boiling point of the ether to rise to that temperature. That pressure would be equal to 32.4 inches of mercury, or 2.4 inches above the usual barometrical pressure; and the vapour would be condensed somewhat, so that the space of 100 cubic inches would contain what would be equivalent to 108 cubic inches at the usual pressure. This is the quantity, then, with which we have to compare 1.9 cubic inches, in order to ascertain the degree of saturation of the space in the air-cells of the lungs, and also of the blood; and by calculation, as when treating of chloroform,
1.9 is to 108 as 0.0175 is to 1.
So that we find 0.0175, or 1-57th, to be the amount of saturation of the blood by ether necessary to produce the second degree of narcotism; and as by Exp. 21, three grains in 100 cubic inches produced the fourth degree of narcotism, we get 0.035, or 1-28th, as the amount of saturation of the blood in this degree. Now this is within the smallest fraction of what was found to be the extent of saturation of the blood by chloroform, requisite to produce narcotism to the same degree. But the respective amount of the two medicines in the blood differs widely; for whilst chloroform required about 288 parts of serum to dissolve it, I find that 100 parts of serum dissolve 5 parts of ether at 100°; consequently 0.05 x 0.0175 gives 0.000875, or one part in 1142, as the proportion in the blood in the second degree of narco- [894/895] tism, and 0.05 x 0.035 gives 0.00175, or one part in 572, as the proportion in the fourth degree.
In Exp. 28, the frog was rendered completely insensible by vapour of a strength which was not sufficient to produce any appreciable effect on the mouse in Exp. 17. This is in accordance with what was met with in the experiments with chloroform. Air, when saturated with ether at 55°, contains 32 grains; so that the blood of the frog might contain 1-32d part as much as it would dissolve, which, although not quite so great a proportion as was considered the average for the fourth degree in the mice, yet was more than sufficient to render insensible the mouse in Exp. 20.
There is a remarkable difference between the birds and the mice in respect to the proportions of ether and air required to render them insensible, a difference that was not observed with respect to chloroform. In some experiments with ether on Guinea pigs, which are not adduced, they were found to agree with mice in the effects of various quantities.
The birds were found to require nearly twice as much: five grains to 100 cubic inches, the quantity used in an experiment between the 25th and 26th, which is not related, may be taken as the average for the fourth degree of narcotism in these birds, with a temperature of 110°. By the kind of calculation made before, we should get a higher amount of saturation of the blood than for the same degree in the mice. But as serum at 110° dissolves much less ether than at 100°, the quantity of this medicine in the blood of birds is not greater than in that of other animals; and considered in relation to what the blood would dissolve at 100°, the degree of saturation is the same.
By Expts. 22, 23, and 27, we find that with ether as with chloroform, a quantity of vapour in the air somewhat greater than suffices to induce complete narcotism has the effect of arresting the respiratory movements. The exact amount which has this effect might be determined if necessary.
Before proceeding to consider some other vapours, and the general conclusions to be drawn from these inquires, it may be as well to consider how far the above results coincide with experience as to the quantities of chloroform and ether required to produce insensibility in the human subject.
The blood in the human adult is calculated by M. Valentin to average about 30 pounds. This quantity would contain 26 pounds five ounces of serum, which, allowing for its specific gravity, would measure 410 fluid ounces. This being reduced to minims, and multiplied by 0.0000614, the proportion of chloroform in the blood required to produce narcotism to the second degree, gives 12 minims as the whole quantity in the blood. And to produce narcotism to the fourth degree we should have twice as much, or 24 minims. More than this is used in practice, because a considerable portion is not absorbed, being thrown out again when it has proceeded no further than the trachea, the mouth and nostrils, or even the face-piece. But I find that if I put twelve minims into a bladder containing a little air, and breathe it over and over again, in the manner of taking nitrous oxide, it suffices to remove consciousness, producing the second degree of its effects.
In order to find the whole quantity of ether in the blood, we may multiply 410, the number of fluid ounces of serum, by 0.000875 for the second degree, and by 0.00175 for the fourth degree, when we shall obtain 0.358 and 0.71 of an ounce, i.e. f?ij. ?l. in the first instance, and f?v. ?xl. in the second,--quantities which agree very well with experience when we allow for what is expired without being absorbed.
(To be continued)
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