V.—Chloroform.
CHLOROFORM, TRICHLOROMETHANE OR METHENYL CHLORIDE (CHCl3).
§ 174. Chloroform appears to have been discovered independently by Soubeiran and Liebig, about 1830. It was first employed in medicine by Simpson, of Edinburgh, as an anæsthetic. Pure chloroform has a density of 1·491 at 17°, and boils at 60·8°; but commercial samples have gravities of from 1·47 to 1·491. It is a colourless liquid, strongly refracting light; it cannot be ignited by itself, but, when mixed with alcohol, burns with a smoky flame edged with green. Its odour is heavy, but rather pleasant; the taste is sweet and burning.
Chloroform sinks in water, and is only slightly soluble in that fluid (·44 in 100 c.c.), it is perfectly neutral in reaction, and very volatile. When rubbed on the skin, it should completely evaporate, leaving no odour. Pure absolute chloroform gives an opaline mixture if mixed with from 1 to 5 volumes of alcohol, but with any quantity above 5 volumes the mixture is clear; it mixes in all proportions with ether. Chloroform coagulates albumen, and is an excellent solvent for most organic bases—camphor, caoutchouc, amber, opal, and all common resins. It dissolves phosphorus and sulphur slightly—more freely iodine and bromine. It floats on hydric sulphate, which only attacks it at a boiling heat.
Chloroform is frequently impure from faulty manufacture or decomposition. The impurities to be sought are alcohol, methylated chloroform,[158] dichloride of ethylene (C2H4Cl2), chloride of ethyl (C2H5Cl), aldehyde, chlorine, hydrochloric, hypochlorous, and traces of sulphuric acid: there have also been found chlorinated oils. One of the best tests for contamination by alcohol, wood spirit, or ether, is that known as Roussin’s; dinitrosulphide of iron[159] is added to chloroform. If it contain any of these impurities, it acquires a dark colour, but if pure, remains bright and colourless.
[158] Methylated chloroform is that which is prepared from methylated spirit. It is liable to more impurities than that made from pure alcohol, but, of course, its composition is the same, and it has recently been manufactured from this source almost chemically pure.
[159] Made by slowly adding ferric sulphate to a boiling solution of ammonic sulphide and potassic nitrite, as long as the precipitate continues to redissolve, and then filtering the solution.
The presence of alcohol or ether, or both, may also be discovered by the bichromate test, which is best applied as follows:—A few milligrammes of potassic bichromate are placed at the bottom of a test-tube with four or five drops of sulphuric acid, which liberates the chromic acid; next, a very little water is added to dissolve the chromic acid; and lastly, the chloroform. The whole is now shaken, and allowed to separate. If the chloroform is pure, the mass is hardly tinged a greenish-yellow, and no layer separates. If, however, there is anything like 5 per cent. of alcohol or ether present, the deep green of chromium chloride appears, and there is a distinct layer at the bottom of the tube.
Another way to detect alcohol in chloroform, and also to make an approximate estimation of its quantity, is to place 20 c.c. of chloroform in a burette, and then add 80 c.c. of water. On shaking violently, pure chloroform will sink to the bottom in clear globules, and the measurement will be as nearly as possible the original quantity; but if anything like a percentage of alcohol be present, the chloroform is seen to be diminished in quantity, and its surface is opalescent, the diminution being caused by the water dissolving out the alcohol. The addition of a few drops of potash solution destroys the meniscus, and allows of a close reading of the volume. The supernatant water may be utilised for the detection of other impurities, and tested for sulphuric acid by baric chloride, for free chlorine and hypochlorous acid by starch and potassic iodide, and for hydrochloric acid by silver nitrate.[160] Fuchsine, proposed by Stœdeler, is also a delicate reagent for the presence of alcohol in chloroform, the sample becoming red in the presence of alcohol, and the tint being proportionate to the quantity present. The most delicate test for alcohol is, however, the iodoform test fully described in “Foods,” p. 375.[161] Dichloride of ethylene is detected by shaking up the chloroform with dry potassic carbonate, and then adding metallic potassium. This does not act on pure chloroform, but only in presence of ethylene dichloride, when the gaseous chlor-ethylene (C2H3Cl) is evolved. Ethyl-chloride is detected by distilling the chloroform and collecting the first portions of the distillate; it will have a distinct odour of ethyl-chloride should it be present. Methyl compounds and empyreumatic oils are roughly detected by allowing the chloroform to evaporate on a cloth. If present, the cloth, when the chloroform has evaporated, will have a peculiar disagreeable odour. Aldehyde is recognised by its reducing action on argentic nitrate; the mineral acids by the reddening of litmus paper, and the appropriate tests. Hypochlorous acid first reddens, and then bleaches, litmus-paper.
[160] Neither an alcoholic nor an aqueous solution of silver nitrate causes the slightest change in pure chloroform.
[161] An attempt has been made by Besnou to estimate the amount of alcohol by the specific gravity. He found that a chloroform of 1·4945 gravity, mixed with 5 per cent. of alcohol, gave a specific gravity of 1·4772; 10 per cent., 1·4602; 20 per cent., 1·4262; and 25 per cent., 1·4090. It would, therefore, seem that every percentage of alcohol lowers the gravity by ·0034.
Dr. Dott, Pharm. Journ., 1894, p. 629, gives the following tests:—Specific gravity, 1·490 to 1·495. On allowing 1⁄2 fluid drm. to evaporate from a clean surface, no foreign odour is perceptible at any stage of the evaporation. When 1 fluid drm. is agitated with an equal volume of solution of silver nitrate, no precipitate or turbidity is produced after standing for five minutes. On shaking up the chloroform with half its volume of distilled water, the water should not redden litmus-paper. When shaken with an equal volume of sulphuric acid, little or no colour should be imparted to the acid.
§ 175. The ordinary method of manufacturing chloroform is by distilling alcohol with chlorinated lime; but another mode is now much in use—viz., the decomposition of chloral hydrate. By distilling it with a weak alkali, this process yields such a pure chloroform, that, for medicinal purposes, it should supersede every other.
Poisonous Effects of Chloroform.
1. AS A LIQUID.
§ 176. Statistics.—Falck finds recorded in medical literature 27 cases of poisoning by chloroform having been swallowed—of these 15 were men, 9 were women, and 3 children. Eighteen of the cases were suicidal, and 10 of the 18 died; the remainder took the liquid by mistake.
§ 177. Local Action of Chloroform.—When applied to the skin or mucous membranes in such a way that the fluid cannot evaporate—as, for example, by means of a cloth steeped in chloroform laid on the bare skin, and covered over with some impervious material—there is a burning sensation, which soon ceases, and leaves the part anæsthetised, while the skin, at the same time, is reddened and sometimes even blistered.
§ 178. Chloroform added to blood, or passed through it in the state of vapour, causes it to assume a peculiar brownish colour owing to destruction of the red corpuscles and solution of the hæmoglobin in the plasma. The change does not require the presence of atmospheric air, but takes place equally in an atmosphere of hydrogen. It has been shown by Schmiedeberg that the chloroform enters in some way into a state of combination with the blood-corpuscles, for the entire quantity cannot be recovered by distillation; whereas the plasma, similarly treated, yields the entire quantity which has in the first place been added. Schmiedeberg also asserts that the oxygen is in firmer combination with the chloroformised blood than usual, as shown by its slow extraction by stannous oxide. Muscle, exposed to chloroform liquid by arterial injection, quickly loses excitability and becomes rigid. Nerves are first stimulated, and then their function for the time is annihilated; but on evaporation of the chloroform, the function is restored.
§ 179. General Effects of the Liquid.—However poisonous in a state of vapour, chloroform cannot be considered an extremely active poison when taken into the stomach as a liquid, for enormous quantities, relatively, have been drunk without fatal effect. Thus, there is the case recorded by Taylor, in which a man, who had swallowed 113·4 grms. (4 ozs.), walked a considerable distance after taking the dose. He subsequently fell into a state of coma, with dilated pupils, stertorous breathing, and imperceptible pulse. These symptoms were followed by convulsions, but the patient recovered in five days.
In a case related by Burkart,[162] a woman desired to kill herself with chloroform, and procured for that purpose 50 grms. (a little less than one ounce and a half); she drank some of it, but the burning taste and the sense of heat in the mouth, throat, and stomach, prevented her from taking the whole at once. After a few moments, the pain passing off, she essayed to drink the remainder, and did swallow the greater portion of it, but was again prevented by the suffering it caused. Finally, she poured what remained on a cloth, and placing it over her face, soon sank into a deep narcosis. She was found lying on the bed very pale, with blue lips, and foaming a little at the mouth; the head was rigidly bent backwards, the extremities were lax, the eyes were turned upwards and inwards, the pupils dilated and inactive, the face and extremities were cold, the body somewhat warmer, there was no pulse at the wrist, the carotids beat feebly, the breathing was deep and rattling, and after five or six inspirations ceased. By the aid of artificial respiration, &c., she recovered in an hour.
[162] Vierteljahrsschr. für ger. Med., 1876.
A still larger dose has been recovered from in the case of a young man, aged 23,[163] who had swallowed no less than 75 grms. (2·6 ozs.) of chloroform, but yet, in a few hours, awoke from the stupor. He complained of a burning pain in the stomach; on the following day he suffered from vomiting, and on the third day symptoms of jaundice appeared,—a feature which has been several times noticed as an effect of chloroform.
[163] Brit. Med. Journ., 1879.
On the other hand, even small doses have been known to destroy life. In a case related by Taylor, a boy, aged 4, swallowed 3·8 grms. (1 drm.) of chloroform and died in three hours, notwithstanding that every effort was used for his recovery.
§ 180. The smallest dose that has proved fatal to an adult is 15 grms. (a little over 4 drms.).
From twenty-two cases in which the quantity taken had been ascertained with some degree of accuracy, Falck draws the following conclusions:—In eight of the cases the dose was between 4 and 30 grms., and one death resulted from 15 grms. As for the other fourteen persons, the doses varied from 35 to 380 grms., and eight of these patients died—two after 40, two after 45, one after 60, 90, 120, and 180 grms. respectively. Hence, under conditions favouring the action of the poison, 15 grms. (4·3 drms.) may be fatal to an adult, while doses of 40 grms. (11·3 drms.) and upwards will almost certainly kill.
§ 181. Symptoms.—The symptoms can be well gathered from the cases quoted. They commence shortly after the taking of the poison; and, indeed, the local action of the liquid immediately causes first a burning sensation, followed by numbness.
Often after a few minutes, precisely as when the vapour is administered, a peculiar, excited condition supervenes, accompanied, it may be, by delirium. The next stage is narcosis, and the patient lies with pale face and livid lips, &c., as described at [p. 147]; the end of the scene is often preceded by convulsions. Sometimes, however, consciousness returns, and the irritation of the mucous membranes of the gastro-intestinal canal is shown by bloody vomiting and bloody stools, with considerable pain and general suffering. In this way, a person may linger several days after the ingestion of the poison. In a case observed by Pomeroy, the fatal malady was prolonged for eight days. Among those who recover, a common sequela, as before mentioned, is jaundice.
A third form of symptoms has been occasionally observed, viz.:—The person awakes from the coma, the breathing and pulse become again natural, and all danger seems to have passed, when suddenly, after a longer or shorter time, without warning, a state of general depression and collapse supervenes, and death occurs.
§ 182. Post-mortem Appearances.—The post-mortem appearances from a fatal dose of liquid chloroform mainly resolve themselves into redness of the mucous membrane of the stomach, though occasionally, as in Pomeroy’s case, there may be an ulceration. In a case recorded by Hoffman,[164] a woman, aged 30, drank 35 to 40 grms. of chloroform and died within the hour. Almost the whole of the chloroform taken was found in the stomach, as a heavy fluid, coloured green, through the bile. The epithelium of the pharynx, epiglottis, and gullet was of a dirty colour, partly detached, whitened, softened, and easily stripped off. The mucous membrane of the stomach was much altered in colour and consistence, and, with the duodenum, was covered with a tenacious grey slime. There was no ecchymosis.
[164] Lehrbuch der ger. Medicin, 2te Aufl.
2. THE VAPOUR OF CHLOROFORM.
§ 183. Statistics.—Accidents occur far more frequently in the use of chloroform vapour for anæsthetic purposes than in the use of the liquid.
Most of the cases of death through chloroform vapour, are those caused accidentally in surgical and medical practice. A smaller number are suicidal, while for criminal purposes, its use is extremely infrequent.
The percentage of deaths caused by chloroform administered during operations is unaccountably different in different years, times, and places. The diversity of opinion on the subject is partly (though not entirely) explicable, by the degrees of purity in the anæsthetic administered, the different modes of administration, the varying lengths of time of the anæsthesia, and the varying severity of the operations.
During the Crimean War, according to Baudens and Quesnoy, 30,000 operations were done under chloroform, but only one death occurred attributable to the anæsthetic. Sansom[165] puts the average mortality at ·75 per 10,000, Nussbaum at 1·3, Richardson at 2·8,[166] Morgan[167] at 3·4. In the American war of secession, in 11,000 operations, there were seven deaths—that is, 6·3 per 10,000, the highest number on a large scale which appears to be on record. In the ten years 1883-1892, 103 deaths are attributed to chloroform in England and Wales, viz., 88 deaths (57 males, 31 females) from accidents (no doubt in its use as a general anæsthetic), 14 (9 males, 5 females) from suicide, and a solitary case of murder.
[165] Chloroform: its Action, &c., London, 1865.
[166] Med. Times and Gazette, 1870.
[167] Med. Soc. of Virginia, 1872.
§ 184. Suicidal and Criminal Poisoning by Chloroform.—Suicidal poisoning by chloroform will generally be indicated by the surrounding circumstances; and in no case hitherto reported has there been any difficulty or obscurity as to whether the narcosis was self-induced or not. An interesting case is related by Schauenstein,[168] in which a physician resolved to commit suicide by chloroform, a commencing amaurosis having preyed upon his mind, and his choice having been determined by witnessing an accidental death by this agent. He accordingly plugged his nostrils, fitted on to the face an appropriate mask, and fastened it by strips of adhesive plaster. In such an instance, there could be no doubt of the suicidal intent, and the question of accident would be entirely out of the question.
[168] Maschka: Handbuch der gerichtlich. Medicin, p. 787, Tübingen, 1882.
A dentist in Potsdam,[169] in a state of great mental depression from embarrassed circumstances, killed his wife, himself, and two children by chloroform. Such crimes are fortunately very rare.
[169] Casper: Handbuch der ger. Med.
There is a vulgar idea that it is possible, by holding a cloth saturated with chloroform to the mouth of a sleeping person (or one, indeed, perfectly awake), to produce sudden insensibility; but such an occurrence is against all experimental and clinical evidence. It is true that a nervous person might, under such circumstances, faint and become insensible by mere nervous shock; but a true sudden narcosis is impossible.
Dolbeau has made some interesting experiments in order to ascertain whether, under any circumstances, a sleeping person might be anæsthetised. The main result appears to answer the question in the affirmative, at least with certain persons; but even with these, it can only be done by using the greatest skill and care, first allowing the sleeper to breathe very dilute chloroform vapour, and then gradually exhibiting stronger doses, and taking the cloth or inhaler away on the slightest symptom of approaching wakefulness. In 75 per cent. of the cases, however, the individuals awoke almost immediately on being exposed to the vapour. This cautious and scientific narcosis, then, is not likely to be used by the criminal class, or, if used, to be successful.
§ 185. Physiological Effects.—Chloroform is a protoplasmic poison. According to Jumelle, plants can even be narcotised, ceasing to assimilate and no longer being sensitive to the stimulus of light. Isolated animal cells, like leucocytes, lose through chloroform vapour their power of spontaneous movement, and many bacteria cease to multiply if in contact with chloroform water. According to Binx, chloroform narcosis in man is to be explained through its producing a weak coagulation of the cerebral ganglion cells. As already mentioned, chloroform has an affinity for the red blood-corpuscles. Chloroform stimulates the peripheral ends of the nerves of sensation, so that it causes irritation of the skin or mucous membranes when locally applied. Flourens considers that chloroform first affects the cerebrum, then the cerebellum, and finally the spinal cord; the action is at first stimulating, afterwards paralysing. Most anæsthetics diminish equally the excitability of the grey and the white nervous substance of the brain, and this is the case with chloroform, ether, and morphine; but apparently this is not the case with chloral hydrate, which only diminishes the conductivity of the cortical substance of the brain, and leaves the grey substance intact. Corresponding to the cerebral paralysis, the blood pressure sinks, and the heart beats slower and weaker.[170] The Hyderabad Commission made 735 researches on dogs and monkeys, and found that in fatal narcosis, so far as these animals are concerned, the respiration ceased before the heart, and this may be considered the normal mode of death; but it is probably going too far to say that it is the exclusive form of death in man, for there have been published cases in which the heart failed first.
[170] Kobert’s Lehrbuch der Intoxicationen.
§ 186. Symptoms.—There is but little outward difference between man and animals, in regard to the symptoms caused by breathing chloroform; in the former we have the advantage that the sensations preceding narcosis can be described by the individual.
The action of chloroform is usually divided into three more or less distinct stages. In the first there is a “drunken” condition, changes in the sense of smell and taste, and it may be hallucinations of vision and hearing; there are also often curious creeping sensations about the skin, and sometimes excessive muscular action, causing violent struggles. I have also seen epileptiform convulsions, and delirium is almost always present. The face during this stage is generally flushed, covered with perspiration, and the pupils contracted. The first stage may last from one minute to several, and passes into the second stage, or that of depression. Spontaneous movements cease, sensibility to all external stimuli vanishes, the patient falls into a deep sleep, the consciousness is entirely lost, and reflex movements are more and more annihilated. The temperature is less than normal, the respirations are slow, and the pulse is full and slow. The pupils in this stage are usually dilated, all the muscles are relaxed, and the limbs can be bent about in any direction. If now the inhalation of chloroform is intermitted, the patient wakes within a period which is usually from twenty to forty minutes, but may be several hours, after the last inhalation.
The third stage is that of paralysis; the pulse becomes irregular, the respirations superficial, there is a cyanotic colouring of the lips and skin, while the pupils become widely dilated. Death follows quickly through paralysis of the respiratory centre, the respirations first ceasing, then the pulse; in a few cases, the heart ceases first to beat.
According to Sansom’s facts,[171] in 100 cases of death by chloroform, 44·6 per cent. occurred before the full narcosis had been attained, that is in the first stage, 34·7 during the second stage, and 20·6 shortly after. So, also, Kappeler has recorded that in 101 cases of death from chloroform, 47·7 per cent. occurred before the full effect, and 52·2 during the full effect. This confirms the dictum of Billroth, that in all stages of anæsthesia by chloroform, death may occur. The quantity of chloroform, which, when inhaled in a given time, will produce death, is unknown; for all depends upon the greater or less admixture of air, and probably on other conditions. It has been laid down, that the inhalation of chloroform should be so managed as to insure that the air breathed shall never contain more than 3·9 per cent. of chloroform. Fifteen drops have caused death, but Taylor, on the other hand, records a case of tetanus, treated at Guy’s Hospital, in which no less a quantity than 700 grms. (22·5 ozs.) was inhaled in twenty-four hours. Frequent breathing of chloroform in no way renders the individual safe from fatal accident. A lady[172] having repeatedly taken chloroform, was anæsthetised by the same agent merely for the purpose of having a tooth extracted. About 6 grms. (1·5 drm.) were poured on a cloth, and after nine to ten inspirations, dangerous symptoms began—rattling breathing and convulsive movements—and, despite all remedies, she died.
[171] Op. cit.
[172] Edin. Med. Journ., 1855.
§ 187. Chronic chloroform poisoning is not unknown. It leads to various ailments, and seems to have been in one or two instances the cause of insanity.
Buchner records the case of an opium-eater, who afterwards took to chloroform; he suffered from periodic mania. In a remarkable case related by Meric, the patient, who had also first been a morphine-eater, took 350 grms. of chloroform in five days by inhalation; as often as he woke he would chloroform himself again to sleep. In this case, there was also mental disturbance, and instances in which chloroform produced marked mental aberration are recorded by Böhm[173] and by Vigla.[174]
[173] Ziemssen’s Handbuch, Bd. 15.
[174] Med. Times, 1855.
§ 188. Post-mortem Appearances.—The lesions found on section are neither peculiar to, nor characteristic of, chloroform poisoning. It has been noted that bubbles of gas are, from time to time, to be observed after death in the blood of those poisoned by chloroform, but it is doubtful whether the bubbles are not merely those to be found in any other corpse—in 189 cases, only eighteen times were these gas-bubbles observed,[175] so that, even if they are characteristic, the chances in a given case that they will not be seen are greater than the reverse. The smell of chloroform may be present, but has been noticed very seldom.
[175] Schauenstein (Op. cit.).
§ 189. The detection and estimation of chloroform from organic substances is not difficult, its low boiling-point causing it to distil readily. Accordingly (whatever may be the ultimate modifications, as suggested by different experimenters), the first step is to bring the substances, unless fluid, into a pulp with water, and submit this pulp to distillation by the heat of a water-bath. If the liquid operated upon possesses no particular odour, the chloroform may in this way be recognised in the distillate, which, if necessary, may be redistilled in the same manner, so as to concentrate the volatile matters in a small compass.
There are four chief tests for the identification of chloroform:—
(1.) The final distillate is tested with a little aniline, and an alcoholic solution of soda or potash lye; either immediately, or upon gently warming the liquid, there is a peculiar and penetrating odour of phenylcarbylamine, C6H5NC; it is produced by the following reaction:—
CHCl3 + 3KOH + C6H5NH2 = C6H5NC + 3KCl + 3H2O.
Chloral, trichloracetic acid, bromoform and iodoform also give the same reaction; on the other hand, ethylidene chloride does not yield under these circumstances any carbylamine (isonitrile).
(2.) Chloroform reduces Fehling’s alkaline copper solution, when applied to a distillate, thus excluding a host of more fixed bodies which have the same reaction; it is a very excellent test, and may be made quantitative. The reaction is as follows:—
CHCl3 + 5KHO + 2CuO = Cu2O + K2CO3 + 3KCl + 3H2O;
thus, every 100 parts of cuprous oxide equals 83·75 of chloroform.
(3.) The fluid to be tested (which, if acid, should be neutralised), is distilled in a slow current of hydrogen, and the vapour conducted through a short bit of red-hot combustion-tube containing platinum gauze. Under these circumstances, the chloroform is decomposed and hydrochloric acid formed; hence, the issuing vapour has an acid reaction to test-paper, and if led into a solution of silver nitrate, gives the usual precipitate of argentic chloride. Every 100 parts of silver chloride equal 27·758 of chloroform.
(4.) The fluid is mixed with a little thymol and potash; if chloroform be present, a reddish-violet colour is developed, becoming more distinct on the application of heat.[176]
[176] S. Vidali in Deutsch-Amerikan. Apoth.-Zeitung, vol. iij., Aug. 15, 1882.
§ 190. For the quantitative estimation of chloroform the method recommended by Schmiedeberg[177] is, however, the best. A combustion-tube of 24 to 26 cm. long, and 10 to 12 mm. in diameter, open at both ends, is furnished at the one end with a plug of asbestos, while the middle part, to within 5-6 cm. of the other end, is filled with pieces of caustic lime, from the size of a lentil to that of half a pea. The lime must be pure, and is made by heating a carbonate which has been precipitated from calcic nitrate. The other end of the tube is closed by a cork, carrying a silver tube, 16-18 cm. long, and 4 mm. thick. The end containing the asbestos plug is fitted by a cork to a glass tube. The combustion-tube thus prepared is placed in the ordinary combustion-furnace; the flask containing the chloroform is adapted, and the distillation slowly proceeded with. It is best to add a tube, bent at right angles and going to the bottom of the flask, to draw air continuously through the apparatus. During the whole process, the tube containing the lime is kept at a red heat. The chloroform is decomposed, and the chlorine combines with the lime. The resulting calcic chloride, mixed with much unchanged lime, is, at the end of the operation, cooled, dissolved in dilute nitric acid, and precipitated with silver nitrate. Any silver chloride is collected and weighed and calculated into chloroform.[178]
[177] Ueber die quantitative Bestimmung des Chloroforms im Blute. Inaug. Dissert., Dorpat, 1866.
[178] S. Vidali has made the ingenious suggestion of developing hydrogen in the usual way, by means of zinc and sulphuric acid, in the liquid supposed to contain chloroform, to ignite the hydrogen, as in Marsh’s test, when it issues from the tube, and then to hold in the flame a clean copper wire. Since any chloroform is burnt up in the hydrogen flame to hydrochloric acid, the chloride of copper immediately volatilises and colours the flame green.