Source: Snow, John. London Med. Gazette, vol. 46, Aug. 23, 1850, pp. 321-27
On narcotism by the inhalation of vapours
By John Snow, M.D.
Chloroform passes off unchanged from the blood, in the expired air--Its detection in the urine--in the dead body--in an amputated limb--Remarks on the process for its detection.
At the end of the last paper, reasons were given for concluding that the effects of narcotic vapours were not due, as some had supposed, to the hydrogen and carbon they contain, combining with the oxygen of the air dissolved in the blood; and evidence was adduced to show that if such combination do take place, this would not explain their narcotic action. It still remained desirable to determine by experiment, if possible, whether these bodies are decomposed in the system, or pass off unchanged in the breath, or in other ways. With this view the following experiment was performed:--
Exp. 54.--Ten minims of chloroform were put into a hydrogen balloon, holding 300 cubic inches. The balloon was filled up with air, which I breathed backwards and forwards, in the way in which nitrous oxide gas is taken, for probably about two minutes. The word probably is used, because, after observing the watch for a minute and a half, I lost the recollection of what I was doing, and on recovering so as to observe the watch again, I found that another minute had elapsed, and that I had carefully lain aside the balloon in the meantime. Half a minute after this, and three minute after beginning to inhale, I commenced to pass the expired air through a tube of hard glass, which was placed in readiness in a charcoal fire. To the further end of the tube were fitted other tubes connecting it with two Woolfe's bottles each containing a solution of nitrate of silver. The respired air was taken in by the nostrils and breathed out by the mouth, passing first through the red hot tube, and afterwards through the solutions of nitrate of silver. This process was continued for four minutes. [321/322] The solution was rendered turbid, more especially that in the first bottle; being at first white, but shortly afterwards of a dark violet colour. At the end of twenty-five minutes from the inhalation, and when scarcely any appreciable effect of the chloroform remained on the feelings, I again breathed the expired air through the red-hot tube, the Woolfe's bottles having been removed, and a small tube moistened inside with solution of nitrate of silver having been attached. A slight precipitate of chloride of silver immediately appeared in the tube. The precipitate in the Woolfe's bottles having been washed and dried on the filter, was found to weigh 1.2 grain.
I have on other occasions, after inhaling chloroform, made the expired air to pass at once through a solution of nitrate of silver without the intervention of the red-hot tube, when not the least precipitate was occasioned; consequently, the chlorine which combined with the silver in the above experiment was the result of the decomposition of chloroform in the hot tube, and not in the circulation. As upwards of half a minute was allowed to elapse, during which several inspirations were taken between the conclusion of the inhalation and commencing to breathe through the tube, the lungs must have been completely emptied of the air taken from the balloon, and the vapour of chloroform must consequently have been exhaled from the blood. The further part of the experiment, performed twenty minutes later, more strongly proves this, and also shows that chloroform continues to be exhaled as long as any appreciable effects of it remain.
If all the chlorine of the chloroform united with the silver, the quantity of chloride obtained in four minutes, in the above experiment--viz. 1.2 grain, would indicate only 0.476 grain of chloroform. But I have found that on passing the vapour of a known quantity of chloroform through a red-hot tube, only about one-third of the chlorine is liberated, chiefly in the form of hydrochloric acid gas, and combines with the silver, as will be more fully explained further on: consequently, the above quantity of chloride of silver may be taken to indicate 1.428, or nearly a grain and a half of chloroform. It would not be easy to continue to test for the whole of the vapour exhaled by the breath. Indeed, breathing through the tubes and liquids for four minutes, in the above experiment, was attended with some inconvenience. But when it is considered that part of the chloroform used must have remained in the balloon, that a further part must have been exhaled before beginning to breathe through the red-hot tube, and that the vapour was still being exhaled twenty-five minutes after the inhalation, the experiment must help to confirm the view that by far the greater part of the chloroform inhaled is exhaled again by the breath.
It is probable that a small portion of chloroform passes out by other channels than that of the expired air: the latter, however, offers such a ready and expeditious outlet, that the quantity excreted in any other way is, most likely, very minute. I have on four occasions examined urine passes after the inhalation of chloroform, by boiling it in a flask, and passing the vapour, first through a red-hot tube, and afterwards through a tube moistened inside with solution of nitrate of silver, and I only on one occasion obtained a very slight precipitate of chloride of silver.
The presence of chloroform can be detected in portions of the body removed by the surgeon, when the patient is under its influence, and in the bodies of animals killed by it. And as this part of the subject is interesting in a medico-legal as well as in a physiological point of view, I shall enter a little more minutely into the account of it than I might otherwise have done. In the Journal de Chemie Médicale for March, 1849, a process for the detection of chloroform in the blood is described in the following terms:--"In order to recognize the presence of chloroform in the blood, we take advantage of the property which this body possesses of being decomposed at a red heat, in giving rise to chlorine and hydrochloric acid. In order to perform the operation, it is sufficient to boil an ounce of blood for some time in a glass flask over the water bath. The vapour must pass through a tube heated to redness at one part, and of which the extremity is smeared interiorly with a mixture of iodide of potassium and paste of starch. A strip of paper moistened with the same mixture may also be put into the tube. If any chlorine be produced by [322/323] the decomposition of chloroform, the strip of paper will be turned blue. In this way one part of chloroform in 10,000 of blood may be discovered." It is not stated in this article whether the chloroform detected had entered the blood during life, or had been added after its removal, though the former was probably meant.
In employing this process I substituted solution of nitrate of silver for the starch and iodine test, considering that to obtain some of the chlorine as chloride of silver would be more satisfactory, in a medico-legal point of view, than merely showing the presence of something which decomposes the iodide of potassium. I find, also, that the nitrate of silver possesses other decided advantages. In the first place, it is a much more certain and delicate test. The iodine test is not acted on by hydrochloric acid, but only by the free chlorine, very little of which is produced by passing the vapour of chloroform through a red-hot tube, and that not constantly. Again, if there be a trace of chlorine to set free a little of the iodine, a little warm vapour, which is very apt to rush through the tube, whilst it does not affect the chloride of silver, may either prevent the blue colour of iodide of starch being developed, or suddenly discharge it, as I have seen. And lastly, the nitrite of silver test allows of a quantitative analysis being made, whilst the other does not admit of it. Dr. Alfred Taylor has, however, suggested to me to combine the two tests with a third one, by introducing a slip of starch paper moistened with solution of iodide of potassium, and also a slip of blue litmus paper, into another part of the tube, where it is not wet with the nitrate of silver. Used in this way, these additional tests may tend to confirm the evidence, and to meet objections that might possibly be made to the nitrate of silver test when used alone.
Before relating the experiments in which the presence of chloroform was detected in the body, it will be preferable to give some account of the decomposition which takes place when the vapour of that substance is passed through a red-hot tube. Soubeiran, when treating, in 1831,* of the body afterwards named chloroform, said, that on passing it, in the form of vapour, through a tube of porcelain filled with small fragments of porcelain, and made red-hot, that a good deal of charcoal is deposited, and that a gas is produced formed almost entirely of hydrochloric acid; and that there is found besides a very small quantity of chloride and of an inflammable gas. He added, that, unless the pieces of porcelain are so arranged in the tube as to delay the passage of the vapour, without obstructing it too much, there is more chlorine liberated, and a substance left in the tube which strains paper like an oil. (*Annales de Chimie et de Physique, t. xlviii. o. 135.) Liebig* says of chloroform, "when its vapour is passed through a red-hot tube it is decomposed into carbon, hydrochloric acid, and a crystalline body which appears in long white needles." (*Turner's Chemistry, 8th edit. p. 1009.) On another occasion† he says that this crystalline body is probably the perchloride of carbon discovered by Mr. Faraday (†Annales de Chimie, t. xlix.).
I performed the following experiments with a view more particularly to ascertain whether any appreciable quantity of free chlorine is produced during the decomposition of chloroform at a red heat:--
a. Ten grains of chloroform were put into a dry retort, made out of a small green glass tube, and capable of holding only a drachm. The retort was heated gradually in the water bath. Its beak was kept red-hot by the flame of a spirit lamp, and communicated with two Woolfe's bottles, containing solution of nitrate of silver. Charcoal was deposited in the beak of the retort at the part where it was red-hot: half an inch from this part, on each side, there was a copious deposit of long white, needle-shaped crystals, and, after a time, a reddish-brown oily-looking liquid appeared. The precipitate of chloride of silver, which was found almost exclusively in the first bottle, weighed, after being washed and thoroughly dried, 12.5 grains.
b. Ten grains of chloroform were put into a similar retort and treated in the same way, except that the beak of the retort opened under a receiver in the mercurial trough. The deposits in the tube of the retort were the same as before, and 9.15 cubic inches of gaseous matter were obtained in the receiver. [323/324] The tenth of a cubic inch of water being passed through the mercury, 8.5 cubic inches of the gas were absorbed by it. Solution of potash absorbed one-tenth of a cubic inch more, and the remainder consisted almost, or entirely, of air expelled from the retort.
c. Ten grains of chloroform were treated in the same way as before, the beak of the small retort communicating with two Woolfe's bottles, the first of which contained only thirty minims of distilled water, and the second some solution of nitrate of silver. A very slight cloudiness was merely produced in this solution in the second bottle. The water in the first bottle being added, at the end of the process, to a solution of nitrate of silver, and the precipitate occasioned being boiled in nitric acid, washed, and thoroughly dried, was found to weigh 11.45 grains.
If one of the three atoms of chlorine which were contained in the chloroform were to combine with the single atom of hydrogen, the hydrochloric acid thus produced from ten grains would weigh 3.04 grains, and would suffice to form 12.08 grains of chloride of silver. In experiment a, the chloride of silver obtained exceeded this by a very little. In experiment b, any chlorine which might be developed would be absorbed by the mercury, and the 8.5 cubic inches of gas absorbed by the small quantity of water must have consisted of hydrochloric acid. The weight of it would be 3.24 grains--a very little more than ought by theory to result from the combination of one of the atoms of chlorine with the hydrogen of the formyle; and it would combine to form 12.7 grains of chloride of silver. In experiment c, the thirty minims of water, whilst they absorbed the hydrochloric acid gas, could absorb but a very minute quantity of chlorine, certainly less than the tenth of a grain, and consequently if a greater amount of chlorine than this had been evolved it must have passed on to the second bottle, and there caused a precipitate of chloride of silver. On precipitating with nitrate of silver, it will be observed that the quantity of chloride obtained was very nearly that which ought to be formed by the hydrochloric acid produced as suggested above. These experiments, then, tend to show, that if chlorine be produced by passing the vapour of chloroform through a red-hot tube, it must be in extremely small quantity, and that consequently the proper tests to employ are those which indicate the presence of hydrochloric acid.
The following is a brief account of the experiments for the detection of chloroform in the body:--
Exp. 55.--Two kittens about a fort-night old were placed in a glass jar holding 120 cubic inches. Twelve minims of chloroform were dropped on a piece of blotting paper in the jar, and it was closed. In two minutes the kittens were both insensible, and in two minutes more one of them had ceased to breathe; the other continued to breathe feebly and irregularly for six minutes longer. On the following day one of the kittens was opened: there was no odour of chloroform perceptible in this, any more than in the numerous other animals I have killed with it.
a. The lungs, liver, and kidneys of this kitten were placed in a wide-mouthed glass flask with two or three drachms of water. The flask was placed in the water bath, to which (common salt not being at hand) was added a little chloride of calcium, to increase the temperature somewhat. A tube passing through the cork of the flask was connected with one of hard glass, which was kept red-hot in the flame of a spirit lamp, and to the end of the latter tube was attached one wetted inside with solution of nitrate of silver. About the time that the contents of the flask began to boil, a white curdy precipitate appeared in the latter tube. This precipitate was rendered dark-coloured by the light. It was insoluble in nitric acid, and very soluble in ammonia.
b. Two days after the death of the kittens, the lungs, heart, liver, and kidneys of the other animal were treated in a similar manner. Soon after the water in the flask began to boil, a precipitate of chloride of silver appeared in the tube.
c. Three days after their death, the brains of both kittens were put into a flask without any water, and heated in the chloride of calcium bath, as the other parts had been. On this occasion the tube moistened with solution of nitrate of silver ended in a Woolfe's bottle containing a few minims of the same solution. By the time that the liquid which had exuded from the brains began to boil, a precipitate began to appear in the tube, and in a short time there was one also, to a slight extent, in the bottle. [324/325] The brains were kept boiling in their own serosity for an hour. On the following day heat was again applied to the flask containing the brains which had not been removed; the tube and Woolfe's bottle having, however, been cleaned and supplied with a fresh solution of nitrate of silver. Not the slightest precipitate was obtained on this occasion, although the brains were kept boiling for two hours.
d. Five days after its death one of the kittens was skinned, and the flesh of the limbs, together with the greater part of that of the body and neck, was stripped off and put into the flask and treated as before, with the exception that, instead of the solution of nitrate of silver, a slip of paper moistened with a mixture of starch and solution of iodide of potassium was placed in the farther end of the tube. After the flesh had been made to boil for a little time in its own juice, a small part of the paper was turned blue.
e. Six days after its death the skin of the other kitten was removed, and its flesh put into a flask and treated as above; on this occasion, solution of nitrate of silver being used as the test. The serosity of the flesh had scarcely began to boil, when a precipitate of chloride of silver began to appear, and was soon as copious as on any previous occasion, both in the tube and Woolfe's bottle. At this time the intestines of the kittens were beginning to be offensive, although the flesh used in the experiment was not all decomposed. The bodies had lain on a table since the time of death, at the beginning of last May, when the temperature was cool. From the size of the animals, the quantity of chloroform inhaled by each was considerably less than a grain.
To try the delicacy of the above process, a grain of chloroform was dissolved in a hundred drops of rectified spirit, and one drop of this solution was dropped into a flask containing a thousand grains of water. On treating this as above described, a distinct precipitate of chloride of silver was obtained in the tube, thus indicating the presence of the hundredth part of a grain of chloroform in a thousand grains of water.
Exp. 56.--On May 9, some portions of muscle, nearly sufficient to fill a three-ounce bottle, were taken from the calf of the leg of a little boy, about five years old, which had just been amputated by Mr. P. Hewett, under the influence of chloroform, in St. George's Hospital. About four hours afterwards the pieces of muscle were put into a flask, and treated as before described, solution of nitrate of silver being the test applied. When the liquid exuding from the muscle had been boiling for about ten minutes the precipitate began to appear, and was soon very distinct.
On July 2d, I assisted Dr. Taylor, in the Laboratory of Guy's Hospital, in applying this process to a little of the blood of a man whose death had been occasioned by chloroform, six days previously. The blood, which had been kept in a stoppered bottle, measured six and a half drachms, was of a dark red colour, fluid, but rather thick, and did not smell offensive. It was put into a clean Florence oil flask, from which a tube proceeded which was made red-hot, and a further tube moistened inside with solution of nitrate of silver. The flask was heated in the water bath, to which, after a time, common salt was added. The process was continued for twenty minutes or more, and although a slight cloudiness was observed in the tube, no distinct precipitate of chloride of silver was obtained. It should be remarked that this small quantity of blood must necessarily have been exposed to the air, before it was put into the bottle, by which means it would lose a part of its chloroform.
At the suggestion of Dr. Taylor, some chloroform (about 8 drops) was put into a flask with an ounce of water, and in the further tube were placed, first, a slip of starch paper moistened with solution of iodide of potassium; next, a slip of blue litmus paper, and the distal extremity of the tube was wetted inside with solution of nitrate of silver. The intermediate tube being made red-hot, as soon as heat was applied to the water bath, the two pieces of paper and the solution of nitrate of silver began to be affected, almost simultaneously: the starch paper being rapidly rendered very blue, the change of colour beginning at one end and traveling rapidly along it.
On the same occasion, in order to try the delicacy of these tests, a drop of chloroform, which is equal to the third of a grain, was agitated in a minim measure with fifty minims of alcohol. Five minims of this solution were added to an ounce of water in a flask, which [325/326] would consequently contain the thirtieth part of a grain of chloroform. A fresh tube being attached, containing the three tests before employed, and the flask being heated in the water bath, a decided effect was, in a little time, produced on all the tests. The starch paper was rendered blue; the litmus paper was turned red; and a very distinct precipitate was obtained in the solution of nitrate of silver.
Exp. 57.--July 13: Half a drachm of chloroform was diffused through a jar holding 670 cubic inches, and a kitten, weighing a little over thirteen ounces, was put in. In two minutes it was quite insensible, and at the end of ten minutes it died. On the 15th the kitten was opened, and the viscera of the chest, the liver, and the brain, weighing together nearly two ounces, were put into a flask and heated in the salt water bath. A tube coming from the flask was kept red-hot, and a further tube contained a slip of starch and iodide of potassium paper, and a slip of blue litmus, and terminated near the bottom of a Woolfe's bottle containing a few minims of solution of nitrate of silver. At the early part of the process, the edge of the starch paper seemed to be slightly changing colour, but after a little time no change of colour could again be observed in it. The blue litmus was very soon reddened, and the solution of nitrate of silver began to be turbid, and the turbidity increased for some time. The viscera were kept boiling in their serosity for half an hour.
On the following day other six ounces of the same kitten were put into the same flask; the intestines, skin, and larger bones being only left. Fresh starch paper was put into the tube which terminated in the bottle containing the same solution of nitrate of silver. After a little time the starch paper was decidedly darkened, at the corner nearest the flask, but only to a limited extent, which did not increase. The parts were kept boiling in their serosity for two hours, when the process was ended by the breaking of the tube at the part where it was red-hot, owing to a little condensed steam being projected against it. At the same moment the limited blueness of the starch paper was discharged. The tube being left lying on the table, it was found the next day that the starch paper was very blue throughout its entire extent, from what cause I do not know. The precipitate of chloride of silver was separated by filtration, and but for an accident would have been dried and weighed. There appeared to be not less than the twentieth part of a grain of it.
There is no deposit of carbon in the red-hot part of the tube in this process, as the apparatus always contains sufficient air for the formation of the carbon into carbonic acid. The white needle-formed crystals previously mentioned are deposited, but not in sufficient quantity to be of service as a test. It is desirable to make the tubes proceeding from the flask incline a little upwards, so that the vapour which is condensed before reaching the red-hot part may flow back again. I consider that the solid organs of the body should be taken for analysis, in preference to the blood in a separate state, as that contained in the minute vessels is protected from the action of the air. The parts should be cut in pieces, and put into the flask, without any addition. The stomach should not be selected for examination by the above process, as the gastric juice contains a minute quantity of free hydrochloric acid, and hence the evidence would be liable to objection. The intestines also do not seem suitable parts for examination, as the sulphuretted hydrogen they might contain would interfere, more or less, with the tests. In other respects it matters little what part of the body be used, further than that the most vascular parts are the best. As regards a quantitative analysis, it results from some of the experiments, detailed in an early part of these papers,* that, in a case of death from chloroform, a quarter of a pound of any organ of average vascularity would contain about the twelfth part of a grain, which, if the whole of it were separated and decomposed, would produce about the tenth of a grain of chloride of silver. (*[part 5, in]Med. Gaz., vol. xlii. p. 415.)
The process above described does not prove the presence of chloroform itself, but only that of a volatile compound containing chlorine. In this respect it resembles the processes for the detection of arsenious acid and corrosive sublimate in the tissues, which prove only the presence of a compound of arsenic, or of mercury. The only compounds containing chloride which are volatile at [326/327] the heat of boiling water, are substances such as chloride of ethyle, Dutch liquid, and some others, which resemble chloroform in their effects, but are none of them in common use. In order to be quite certain that the precipitate is no other salt of silver than the chloride, besides the tests of ammonia and nitric acid, solution of potash might be added to another portion of it, as recommended by Dr. Taylor, in treating of hydrochloric acid.* (*Medical Jurisprudence, p. 91.) Potash does not change the chloride of silver without heat.
With these limitations and precautions the process is, I believe, liable to no fallacy. There are chlorides in the body, but they cannot be decomposed, except at a high temperature, and not till the part under examination should become dry, which, in the method here described, could not take place in the most protracted examination. Besides, I have made several examinations of parts not containing chloroform without meeting with anything that produced the slightest effect on the nitrate of silver, or on the starch or litmus test. The bodies of two kittens killed with the vapour of ether were submitted to the process, by portions at a time, which were made to boil in their own serosity for an hour or two, but not the least effect was produced on any of these tests. Hearing, in the beginning of May last, that chloroform was suspected, by some of the coroner's jury, to have been used in the case of a woman who was found dead, under mysterious circumstance, in the Wandsworth Road, I applied to Mr. John Parrott, who was polite enough to send me some portions of the body, including part of the brain and liver. They had been kept in a covered jar from the time they were removed from the body. The chemical examination commenced four days after death, whilst the parts were fresh, and although very carefully conducted, not the least effect was produced, either on the nitrate of silver or starch and iodine test.
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