Chapter XXII: Part V: More or Less Volatile Poisonous Substances Capable of Being (2)

§ 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.

VI.--Other Anæsthetics.

§ 191. When chlorine acts upon marsh-gas, the hydrogen can be
displaced atom by atom; and from the original methane (CH₄) can be
successively obtained chloromethane or methyl chloride (CH₃Cl),
dichloromethane, or methene dichloride, methylene dichloride
(CH₂Cl₂), trichloromethane, or chloroform (CHCl₃), already
described, and carbon tetrachloride (CCl₄). All these are, more or
less, capable of producing anæsthesia; but none of them, save
chloroform, are of any toxicological importance.

Methene dichloride, recommended by Sir B. W. Richardson as an
anæsthetic, has come somewhat into use. It is a colourless, very
volatile liquid, of specific gravity 1·360, and boiling at 41°. It
burns with a smoky flame, and dissolves iodine with a brown colour.

§ 192. =Pentane= (C₅H₁₂).--There are three isomers of pentane; that
which is used as an anæsthetic is normal pentane,
CH₃-CH₂-CH₂-CH₂-CH₃; its boiling-point is 37-38°. It is one of the
constituents of petroleum ether.

Under the name of “Pental” it is used in certain hospitals
extensively, for instance, at the Kaiser Friederich’s Children’s
Hospital, Berlin.[179] It is stated to have no action on the heart.

[179] _Zeit. f. Kinderheilk._, Bd. iii.-iv., 1893.

One death[180] has been recorded from its use:--A lad, aged 14, was
put under pental for the purpose of having two molars painlessly
extracted. He was only a minute or two insensible, and 4-5 grms. of
pental was the quantity stated to have been inhaled. The boy spat
out after the operation, then suddenly fainted and died. The
_post-mortem_ showed œdema of the lungs; the right side of the heart
was empty. The organs of the body smelled strongly of pental.

[180] Dr. Bremme, _Vierteljahrsschr. f. gerichtliche Medicin_, Bd. v., 1893.

§ 193. =Aldehyde= (Acetaldehyde), C₂H₄O =

O
//
CH₃-C ,
\
H

a fluid obtained by the careful oxidation of alcohol (boiling-point,
20·8°), is in large doses toxic; in smaller, it acts as a narcotic.

=Metaldehyde= (C₂H₄O₂)₂, obtained by treating acetaldehyde at a low
temperature with hydrochloric acid. It occurs in the form of prisms,
which sublime at about 112°; it is also poisonous.

§ 194. =Paraldehyde= (C₆H₁₂O₃) is a colourless fluid, boiling at
124°; specific gravity ·998 at 15°. By the action of cold it may be
obtained in crystals, the melting point of which is 10·5°. It is
soluble in eight parts of water at 13°; in warm water it is less
soluble; hence, on warming a solution, it becomes turbid.
Paraldehyde acts very similarly to chloral; it causes a deep sleep,
and (judging by experiments on animals) produces no convulsive
movements.

VII.--Chloral.

§ 195. =Chloral Hydrate= (C₂H₃Cl₃O₂) is made by mixing equivalent quantities of anhydrous chloral[181] and water. The purest chloral is in the form of small, granular, sugar-like crystals. When less pure, the crystals are larger. These melt into a clear fluid at from 48° to 49°, and the melted mass solidifies again at 48·9°. Chloral boils at 97·5°; it is not very soluble in cold chloroform, requiring four times its weight. The only substance with which chloral hydrate may well be confused is chloral alcoholate (C₄H₇Cl₃O₂), but chloral alcoholate melts at a lower temperature (45°), and boils at a higher (113·5°); it is easily soluble in cold chloroform, and inflames readily, whereas chloral scarcely burns.

[181] Anhydrous chloral (C₂HCl₃O) is an oily liquid, of specific gravity 1·502 at 18°; it boils at 97·7°. It is obtained by the prolonged action of chlorine on absolute alcohol.

Chloral hydrate completely volatilises, and can be distilled in a vacuum without change. If, however, boiled in air, it undergoes slow decomposition, the first portions of the distillate being overhydrated, the last underhydrated; the boiling-point, therefore, undergoes a continuous rise. The amount of hydration of a commercial sample is of practical importance; if too much water is present, the chloral deliquesces, especially in warm weather; if too little, it may become acid, and in part insoluble from the formation of meta-chloral (C₆H₃Cl₉O₃). Chloral hydrate, by the action of the volatile or fixed alkalies, is decomposed, an alkaline formiate and chloroform resulting thus--

C₂HCl₃O,H₂O + NaHO = NaCHO₂ + H₂O + CHCl₃.

Trichlor-acetic acid is decomposed in a similar manner.

=Statistics.=--Chloral caused, during the ten years 1883-1892 in England and Wales, 127 deaths--viz., 111 (89 males, 22 females) accidentally, 15 (14 males, 1 female) from suicide, and a case in which chloral was the agent of murder.

§ 196. =Detection.=--It is, of course, obvious that after splitting up chloral into chloroform, the latter can be detected by distillation and applying the tests given at p. 152 and _seq._ Chloral hydrate is soluble in one and a half times its weight of water; the solution should be perfectly neutral to litmus. It is also soluble in ether, in alcohol, and in carbon disulphide. It may be extracted from its solution by shaking out with ether. There should be no cloudiness when a solution is tested with silver nitrate in the cold; if, however, to a boiling solution nitrate of silver and a little ammonia are added, there is a mirror of reduced silver.

§ 197. The assay of chloral hydrate in solutions is best effected by distilling the solution with slaked lime; the distillate is received in water contained in a graduated tube kept at a low temperature. The chloroform sinks to the bottom, and is directly read off; the number of c.c. multiplied by 2·064 equals the weight of the chloral hydrate present.

Another method, accurate but only applicable to the fairly pure substance, is to dissolve 1 to 2 grms. in water, remove any free acid by baric carbonate, and then treat the liquid thus purified by a known volume of standard soda. The soda is now titrated back, using litmus as an indicator, each c.c. of normal alkali neutralised by the sample corresponds to 0·1655 grm. of chloral hydrate. Small quantities of chloral hydrate may be conveniently recovered from complex liquids by shaking them up with ether, and removing the ethereal layer, in the tube represented in the figure.[182] The ether must be allowed to evaporate spontaneously; but there is in this way much loss of chloral. The best method of estimating minute quantities is to alkalise the liquid, and slowly distil the vapour through a red-hot combustion-tube charged with pure lime, as in the process described at p. 153. A dilute solution of chloral may also be treated with a zinc-copper couple, the nascent hydrogen breaks the molecule up, and the resulting chloride may be titrated, as in water analyses, by silver nitrate and potassic chromate.

[182] The figure is from “Foods”; the description may be here repeated:--A is a tube of any dimensions most convenient to the analyst. Ordinary burette size will perhaps be the most suitable for routine work; the tube is furnished with a stopcock and is bent at B, the tube at K having a very small but not quite capillary bore. The lower end is attached to a length of pressure-tubing, and is connected with a small reservoir of mercury, moving up and down by means of a pulley. To use the apparatus: Fill the tube with mercury by opening the clamp at H, and the stopcock at B, and raising the reservoir until the mercury, if allowed, would flow out of the beak. Now, the beak is dipped into the liquid to be extracted with the solvent, and by lowering the reservoir, a strong vacuum is created, which draws the liquid into the tube; in the same way the ether is made to follow. Should the liquid be so thick that it is not possible to get it in by means of suction, the lower end of the tube is disconnected, and the syrupy mass worked in through the wide end. When the ether has been sucked into the apparatus, it is emptied of mercury by lowering the reservoir, and then firmly clamped at H, and the stopcock also closed. The tube may now be shaken, and then allowed to stand for the liquids to separate. When there is a good line of demarcation, by raising the reservoir after opening the clamp and stopcock, the whole of the light solvent can be run out of the tube into a flask or beaker, and recovered by distillation. For heavy solvents (such as chloroform), which sink to the bottom, a simple burette, with a fine exit tube is preferable; but for petroleum ether, ordinary ether, &c., the apparatus figured is extremely useful.

§ 198. =Effects of Chloral Hydrate on Animals.=--Experiments on animals have taught us all that is known of the physiological action of chloral. It has been shown that the drug influences very considerably the circulation, at first exciting the heart’s action, and then paralysing the automatic centre. The heart, as in animals poisoned by atropine, stops in diastole, and the blood-pressure sinks in proportion to the progressive paralysis of the cardiac centre. At the same time, the respiration is slowed and finally ceases, while the heart continues to beat. The body temperature of the warm-blooded animals is very remarkably depressed, according to Falck, even to 7·6°. Vomiting has been rather frequently observed with dogs and cats, even when the drug has been taken into the system by subcutaneous injection.

The secretion of milk, according to Röhrig, is also diminished. Reflex actions through small doses are intensified; through large, much diminished. ·025-·05 grm. (·4-·7 grain), injected subcutaneously into frogs, causes a slowing of the respiration, a diminution of reflex excitability, and lastly, its complete cessation; this condition lasts several hours; at length the animal returns to its normal state. If the dose is raised to ·1 grm. (1·5 grain) after the cessation of reflex movements, the heart is paralysed--and a paralysis not due to any central action of the vagus, but to a direct action on the cardiac ganglia. Rabbits of the ordinary weight of 2 kilos. are fully narcotised by the subcutaneous injection of 1 grm.; the sleep is very profound, and lasts several hours; the animal wakes up spontaneously, and is apparently none the worse. If 2 grms. are administered, the narcotic effects, rapidly developed, are much prolonged. There is a remarkable diminution of temperature, and the animal dies, the respiration ceasing without convulsion or other sign. Moderate-sized dogs require 6 grms. for a full narcosis, and the symptoms are similar; they also wake after many hours, in apparent good health.[183]

[183] C. Ph. Falck has divided the symptoms into (1) Preliminary hypnotic; (2) an adynamic state; and (3) a comatose condition.

§ 199. Liebreich considered that the action of chloral was due to its being broken up by the alkali of the blood, and the system being thus brought into a state precisely similar to its condition when anæsthetised by chloroform vapour. This view has, however, been proved to be erroneous. Chloral hydrate can, it is true, be decomposed in some degree by the blood at 40°; but the action must be prolonged for several hours. A 1 per cent. solution of alkali does not decompose chloral at a blood-heat in the time within which chloral acts in the body; and since narcotic effects are commonly observed when, in the fatty group, hydrogen has been displaced by chlorine, it is more probable that chloral hydrate is absorbed and circulates in the blood as such, and is not broken up into chloroform and an alkaline formiate.

§ 200. =Effects of Chloral Hydrate on Man.=--Since the year 1869, in which chloral was first introduced to medicine, it has been the cause of a number of accidental and other cases of poisoning. I find, up to the year 1884, recorded in medical literature, thirty-one cases of poisoning by chloral hydrate. This number is a small proportion only of the actual number dying from this cause. In nearly all the cases the poison was taken by the mouth, but in one instance the patient died in three hours, after having injected into the rectum 5·86 grms. of chloral hydrate. There is also on record a case in which, for the purpose of producing surgical anæsthesia, 6 grms. of chloral were injected into the veins; the man died in as many minutes.[184]

[184] This dangerous practice was introduced by M. Ore. In a case of traumatic tetanus, in which M. Ore injected into the veins 9 grms. of chloral in 10 grms. of water, there was profound insensibility, lasting eleven hours, during which time a painful operation on the thumb was performed. The next day 10 grms. were injected, when the insensibility lasted eight hours; and 9 grms. were injected on each of the two following days. The man recovered. In another case, Ore anæsthetised immediately a patient by plunging the subcutaneous needle of his syringe into the radial vein, and injected 10 grms. of chloral hydrate with 30 of water. The patient became insensible before the whole quantity was injected with “_une immobilité rappellant celle du cadavre_.” On finishing the operation, the patient was roused immediately by the application of an electric current, one pole on the left side of the neck, the other on the epigastrium. _Journ. de Pharm. et de Chimie._, t. 19, p. 314.

§ 201. =Fatal Dose.=--It is impossible to state with any exactness the precise quantity of chloral which may cause death. Children bear it better, in proportion, than adults, while old persons (especially those with weak hearts, and those inclined to apoplexy) are likely to be strongly affected by very small doses. A dose of ·19 grm. (3 grains) has been fatal to a child a year old in ten hours. On the other hand, according to Bouchut’s observations on 10,000 children, he considers that the full therapeutic effect of chloral can be obtained safely with them in the following ratio:--

Children of 1 to 3 years, dose 1 to 1·5 grm. (15·4 to 23·1 grains)
„ 3 „ 5 „ „ 2 „ 3 „ (30·8 „ 46·3 „ )
„ 5 „ 7 „ „ 3 „ 4 „ (46·3 „ 61·7 „ )

These quantities being dissolved in 100 c.c. of water.

These doses are certainly too high, and it would be dangerous to take them as a guide, since death has occurred in a child, aged 5, from a dose of 3 grms. (46·3 grains). Medical men in England consider 20 grains a very full dose for a child of four years old, and 50 for an adult, while a case is recorded in which a dose of 1·9 grm. (30 grains) proved fatal in thirty-five hours to a young lady aged 20. On the other hand, we find a case[185] in which, to a patient suffering from epileptic mania, a dose of 31·1 grms. (1·1 oz.) of chloral hydrate was administered; she sank into a deep sleep in five minutes. Subcutaneous injections of strychnine were applied, and after sleeping for forty-eight hours, there was recovery. On the third day a vivid scarlatinal rash appeared, followed by desquamation. The examples quoted--the fatal dose of 1·9 grm., and recovery from 31 grms.--are the two extremes for adults. From other cases, it appears tolerably plain that most people would recover, especially with appropriate treatment, from a single dose under 8 grms., but anything above that quantity taken at one time would be very dangerous, and doses of 10 grms. and above, almost always fatal. If, however, 8 grms. were taken in divided doses during the twenty-four hours, it could (according to Sir B. W. Richardson) be done with safety. The time from the taking of the poison till death varies considerably, and is in part dependent on the dose.

[185] _Chicago Medical Review_, 1882.

In seven cases of lethal poisoning, three persons who took the small doses of 1·25, 2·5, and 1·95 grms. respectively, lived from eight to ten hours; two, taking 4 and 5 grms. respectively, died very shortly after the administration of the chloral. In a sixth case, related by Brown, in which 3·12 grms. had been taken, the patient lived an hour; and in another, after a dose of 5 grms., recorded by Jolly, death took place within a quarter of an hour.

§ 202. =Symptoms.=--With moderate doses there are practically no symptoms, save a drowsiness coming on imperceptibly, and followed by heavy sleep. With doses up to 2 grms. (30·8 grains), the hypnotic state is perfectly under the command of the will, and if the person chooses to walk about or engage in any occupation, he can ward off sleep; but with those doses which lead to danger, the narcosis is completely uncontrollable, the appearance of the sleeper is often strikingly like that of a drunken person. There is great diminution of temperature commencing in from five to twenty minutes after taking the dose--occasionally sleep is preceded by a delirious state. During the deep slumber the face is much flushed, and in a few cases the sleep passes directly into death without any marked change. In others, symptoms of collapse appear, and the patient sinks through exhaustion.

§ 203. With some persons doses, which, in themselves, are insufficient to cause death, yet have a peculiar effect on the mental faculties. A case of great medico-legal interest is described by the patient himself, Dr. Manjot.[186] He took in three doses, hourly, 12 grms. of chloral hydrate. After the first dose the pain, for which he had recourse to chloral, vanished; but Manjot, although he had all the appearance of being perfectly conscious, yet had not the slightest knowledge of what he was doing or speaking. He took the other two doses, and sank into a deep sleep which lasted twelve hours. He then awoke and answered questions with difficulty, but could not move; he lay for the next twelve hours in a half slumber, and the following night slept soundly--to wake up recovered.

[186] _Gaz. des Hôp._, 1875.

§ 204. The treatment of acute chloral poisoning which has been most successful is that by strychnine injections, and the application of warmth to counteract the loss of temperature which is so constant a phenomenon. As an illustration of the treatment by strychnine, an interesting case recorded by Levinstein[187] may be quoted.

[187] _Vierteljahrsschr. f. ger. Med._, Bd. xx., 1874.

A man, thirty-five years old, took at one dose, for the purpose of suicide, 24 grms. of chloral hydrate. In half an hour afterwards he was found in a deep sleep, with flushed face, swollen veins, and a pulse 160 in the minute. After a further half hour, the congestion of the head was still more striking; the temperature was 39·5°; the pulse hard and bounding 92; the breathing laboured, at times intermittent.

Artificial respiration was at once commenced, but in spite of this, in about another half hour, the face became deadly pale, the temperature sank to 32·9°. The pupils contracted, and the pulse was scarcely to be felt; 3 mgrms. (·04 grain) of strychnine were now injected subcutaneously; this caused tetanic convulsions in the upper part of the body and trismus. The heart’s action again became somewhat stronger, the temperature rose to 33·3°, and the pupils dilated; but soon followed, again, depression of the heart’s action, and the respiration could only be kept going by faradisation. Two mgrms. (·03 grain) of strychnine were once more injected, and the heart’s action improved. During the succeeding six hours the respiration had to be assisted by faradisation. The temperature gradually rose to 36·5°; ten hours after taking the dose the patient lay in a deep sleep, breathing spontaneously and reacting to external stimuli with a temperature of 38·5°. Eighteen hours from the commencement, the respiration again became irregular, and the galvanic current was anew applied. The last application aroused the sleeper, he took some milk and again slept; after twenty-seven hours he could be awakened by calling, &c., but had not full consciousness; he again took some milk and sank to sleep. It was not until thirty-two hours had elapsed from the ingestion of the poison that he awoke spontaneously; there were no after effects.

§ 205. =Chronic Poisoning by Chloral Hydrate.=--An enormous number of people habitually take chloral hydrate. The history of the habit is usually that some physician has given them a chloral prescription for neuralgia, for loss of sleep, or other cause, and finding that they can conjure sleep, oblivion, and loss (it may be) of suffering whenever they choose, they go on repeating it from day to day until it becomes a necessity of their existence. A dangerous facility to chloral-drinking is the existence of patent medicines, advertised as sleep-producers, and containing chloral as the active ingredient. A lady, aged 35, died in 1876, at Exeter, from an overdose of “Hunter’s solution of chloral, or sedative draught and sleep producer.” Its strength was stated at the inquest to be 25 grains to the drachm (41·6 per cent.).[188]

[188] _Exeter and Plymouth Gazette_, Jan. 12, 1876.

The evil results of this chloral-drinking are especially to be looked for in the mental faculties, and the alienists have had since 1869 a new insanity-producing factor. In the asylums may usually be found several cases of melancholia and mania referred rightly (or wrongly) to chloral-drinking. Symptoms other than cerebral are chilliness of the body, inclination to fainting, clonic convulsions, and a want of co-ordination of the muscles of the lower extremities. In a case recorded by Husband,[189] a lady, after twelve days’ treatment by chloral hydrate, in doses of from 1 to 2 grms. (15·4 to 30·8 grains), suffered from a scarlatina-like rash, which was followed by desquamation. Among the insane, it has also been noticed that its use has been followed by nettle-rash and petechiæ (Reimer and others).

[189] _Lancet_, 1871.

§ 206. =Excretion of Chloral.=--Chloral hydrate is separated in the urine partly as urochloral acid (C₈H₁₁Cl₃O₇). Butylchloral is separated as butyl urochloral acid (C₁₀H₁₅Cl₂O₇). Urochloral acid is crystalline, soluble in water, in alcohol, and in ether, reduces copper from Fehling’s solution, and rotates a ray of polarised light to the left. Urochloral acid, on boiling with either dilute sulphuric or hydrochloric acid, splits up into trichlorethyl alcohol and glycuronic acid--

C₈H₁₁Cl₃O₇ + H₂O = C₂H₃Cl₃O + C₆H₁₀O₇.

Trichloralcohol is an oily fluid (boiling-point 150°-152°); it yields by oxidation trichloracetic acid.

Urobutyl chloral acid gives on treatment with mineral acids trichlorbutyl alcohol and glycuronic acid.

To separate urochloral acid from the urine the following process has been found successful:--

The urine is evaporated to a syrup at the heat of the water-bath, and then strongly acidulated with sulphuric acid and repeatedly shaken out in a separating tube with a mixture of 3 vols. of ether and 1 vol. of alcohol. The ether-alcohol is separated and distilled off, the acid residue is neutralised with KHO, or potassic carbonate, and evaporated; the dry mass is then taken up with 90 per cent. alcohol, the filtrate precipitated with ether, and the precipitate washed with ether and absolute alcohol.

Next the precipitate is boiled with absolute alcohol and filtered hot. On cooling, the potassium salt of urochloral acid separates out in tufts of silky needles. The crystals are dried over sulphuric acid and again washed several times with absolute alcohol and ether to remove impurities.

To obtain the free acid, the potassium salt is dissolved in a little water and acidulated with hydrochloric acid; the liquid is then shaken out in a separating tube, with a mixture of 8 vols. of ether and 1 of alcohol. The ether-alcohol is distilled off, the residue treated with moist silver oxide until no farther separation of silver chloride occurs, the silver chloride is separated by filtration, the soluble silver salt decomposed by SH₂, and the filtrate carefully evaporated to a syrup; after a few hours, the acid crystallises in stars of needles.

Urobutylchloral acid can be obtained in quite a similar way.[190]

[190] V. Mering u. Musculus, _Ber._, viii. 662; v. Mering, _ibid._, xv. 1019; E. Kulz, _Ber._, xv., 1538.

§ 207. =Separation of Chloral from Organic Matters.=--It will be most convenient to place the organic fluid or pulped-up solid, mixed with water, in a retort, to acidify with tartaric acid, and to distil.

Chloral hydrate distils over from a liquid acidified with tartaric acid; to obtain the whole of the chloral requires distillation in a vacuum almost to dryness.

The distillation will, unless there is also some partly decomposed chloral, not smell of chloroform, and yet give chloroform reactions.

To identify it, to the distillate should be added a little burnt magnesia, and the distillate thus treated boiled for half an hour in a flask connected with an inverted condenser; in this way the chloral hydrate is changed into chloroform and magnesium formate--

2CCl₃CH(OH)₂ + MgO = 2CHCl₃ + (HCOO)₂Mg + H₂O.

The fluid may now be tested for formic acid: it will give a black precipitate with solution of silver nitrate--

(HCOO)₂Mg + 4AgNO₃ = 4Ag + Mg(NO₃)₂ + 2CO₂ + 2HNO₃.

It will give a white precipitate of calomel when treated with mercuric chloride solution--

(HCOO)₂Mg + 4HgCl₂ = 2Hg₂Cl₂ + MgCl₂ + 2HCl + 2CO₂.

Chloral (or chloroform), when boiled with resorcinol and the liquid made strongly alkaline with NaHO, gives a red colour, which disappears on acidifying and is restored by alkalies. If, on the other hand, there is an excess of resorcinol and only a very small quantity of NaHO used, the product shows a yellowish-green fluorescence; 1/10 of a milligramme of chloral hydrate gives this reaction distinctly when boiled with 50 mgrms. of resorcinol and 5 drops of a normal solution of sodium hydrate.[191]

[191] C. Schwarz, _Pharm. Zeit._, xxxiii. 419.

Dr. Frank Ogston[192] has recommended sulphide of ammonium to be added to any liquid as a test for chloral. The contents of the stomach are filtered or submitted to dialysis, and the test applied direct. If chloral is present, there is first an orange-yellow colour; on standing, the fluid becomes more and more brown, then troubled, an amorphous precipitate falls to the bottom, and a peculiar odour is developed. With 10 mgrms. of chloral in 1 c.c. of water, there is an evident precipitate, and the odour can readily be perceived; with 1 mgrm. dissolved in 1 c.c. of water, there is an orange-yellow colour, and also the odour, but no precipitate; with ·1 mgrm. in 1 c.c. of water, there is a weak, pale, straw-yellow colour, which can scarcely be called characteristic. The only substance giving in neutral solutions the same reactions is antimony; but, on the addition of a few drops of acid, the antimony falls as an orange-yellow precipitate, while, if chloral alone is present, there is a light white precipitate of sulphur.

[192] _Vierteljahrsschrift f. gerichtl. Medicin_, 1879, Bd. xxx. Hft. 1, S. 268.

VIII.--Bisulphide of Carbon.

§ 208. Bisulphide of carbon--_carbon disulphide_, _carbon sulphide_ (CS₂)--is a colourless, volatile fluid, strongly refracting light. Commercial samples have a most repulsive and penetrating odour, but chemically pure carbon sulphide has a smell which is not disagreeable. The boiling-point is 47°; the specific gravity at 0° is 1·293. It is very inflammable, burning with a blue flame, and evolving sulphur dioxide; is little soluble in water, but mixes easily with alcohol or ether. Bisulphide of carbon, on account of its solvent powers for sulphur, phosphorus, oils, resins, caoutchouc, gutta-percha, &c., is in great request in certain industries. It is also utilised for disinfecting purposes, the liquid being burnt in a lamp.

§ 209. =Poisoning by Carbon Bisulphide.=--In spite of the cheapness and numerous applications of this liquid, poisoning is very rare. There appears to be a case on record of attempted self-destruction by this agent, in which a man took 2 ozs. (56·7 c.c.) of the liquid, but without a fatal result. The symptoms in this case were pallor of the face, wide pupils, frequent and weak pulse, lessened bodily temperature, and spasmodic convulsions. Carbon disulphide was detected in the breath by leading the expired air through an alcoholic solution of triethyl-phosphin, with which it struck a red colour. It could also be found in the urine in the same way. An intense burning in the throat, giddiness, and headache lasted for several days.

§ 210. Experiments on animals have been frequent, and it is found to be fatal to all forms of animal life. There is, indeed, no more convenient agent for the destruction of various noxious insects, such as moths, the weevils in biscuits, the common bug, &c., than bisulphide of carbon. It has also been recommended for use in exterminating mice and rats.[193] Different animals show various degrees of sensitiveness to the vapour; frogs and cats being less affected by it than birds, rabbits, and guinea-pigs. It is a blood poison; methæmoglobin is formed, and there is disintegration of the red blood corpuscles. There is complete anæsthesia of the whole body, and death occurs through paralysis of the respiratory centre, but artificial respiration fails to restore life.

[193] Cloëz, _Compt. Rend._, t. 63, 85.

§ 211. =Chronic Poisoning.=--Of some importance is the chronic poisoning by carbon disulphide, occasionally met with in manufactures necessitating the daily use of large quantities for dissolving caoutchouc, &c. When taken thus in the form of vapour daily for some time, it gives rise to a complex series of symptoms which may be divided into two principal stages--viz., a stage of excitement and one of depression. In the first phase, there is more or less permanent headache, with considerable indigestion, and its attendant loss of appetite, nausea, &c. The sensitiveness of the skin is also heightened, and there are curious sensations of creeping, &c. The mind at the same time in some degree suffers, the temper becomes irritable, and singing in the ears and noises in the head have been noticed. In one factory a workman suffered from an acute mania, which subsided in two days upon removing him from the noxious vapour (_Eulenberg_). The sleep is disturbed by dreams, and, according to Delpech,[194] there is considerable sexual excitement, but this statement has in no way been confirmed. Pains in the limbs are a constant phenomenon, and the French observers have noticed spasmodic contractions of certain groups of muscles.

[194] _Mémoire sur les Accidents que développe chez les ouvrières en caoutchouc du sulfure de carb. en vapeur_, Paris, 1856.

The stage of depression begins with a more or less pronounced anæsthesia of the skin. This is not confined to the outer skin, but also affects the mucous membranes; patients complain that they feel as if the tongue were covered with a cloth. The anæsthesia is very general. In a case recorded by Bernhardt,[195] a girl, twenty-two years old, who had worked six weeks in a caoutchouc factory, suffered from mental weakness and digestive troubles; there was anæsthesia and algesis of the whole skin. In these advanced cases the mental debility is very pronounced, and there is also weakness of the muscular system. Paralysis of the lower limbs has been noted, and in one instance a man had his right hand paralysed for two months. It seems uncertain how long a person is likely to suffer from the effects of the vapour after he is removed from its influence. If the first stage of poisoning only is experienced, then recovery is generally rapid; but if mental and muscular weakness and anæsthesia of the skin have been developed, a year has been known to elapse without any considerable improvement, and permanent injury to the health may be feared.

[195] _Ber. klin. Wochenschrift_, No. 32, 1866.

§ 212. =Post-mortem Appearances.=--The pathological appearances found after sudden death from disulphide of carbon are but little different to those found after fatal chloroform breathing.

§ 213. =Detection and Separation of Carbon Disulphide.=--The extreme volatility of the liquid renders it easy to separate it from organic liquids by distillation with reduced pressure in a stream of CO₂. Carbon disulphide is best identified by (1) Hofman’s test, viz., passing the vapour into an ethereal solution of triethyl-phosphin, (C₂H₅)₃P. Carbon disulphide forms with triethyl-phosphin a compound which crystallises in red scales. The crystals melt at 95° C., and have the following formula--P(C₂H₅)₃CS₂. This will detect 0·54 mgrm. Should the quantity of bisulphide be small, no crystals may be obtained, but the liquid will become of a red colour. (2) CS₂ gives, with an alcoholic solution of potash, a precipitate of potassic xanthate, CS₂C₂H₅OK.

§ 214. =Xanthogenic acid or ethyloxide-sulphocarbonate= (CS₂C₂H₅OH)
is prepared by decomposing potassic xanthogenate by diluted
hydrochloric or sulphuric acid. It is a colourless fluid, having an
unpleasant odour, and a weakly acid and rather bitter taste. It
burns with a blue colour, and is easily decomposed at 24°, splitting
up into ethylic alcohol and hydric sulphide. It is very poisonous,
and has an anæsthetic action similar to bisulphide of carbon. Its
properties are probably due to CS₂ being liberated within the body.