CHAPTER XII

CEREBRAL POISONS

The symptom most characteristic of these poisons is the marked anæsthesia which they produce when their vapours are inhaled. The hydrate of chloral, though placed under the above heading, is more closely allied in its action to opium than to ether or chloroform.

ETHER

Ether, when taken in its liquid form, produces symptoms and _post-mortem_ appearances not unlike those caused by alcohol.

_Fatal Dose._--No death having been recorded, the fatal dose of this substance is unknown.

=Ether Vapour.=--The vapour of ether has caused death. Entering the blood through the lungs, it acts with great rapidity, a state of lethargy being quickly induced.

The early symptoms are noticed in a modification of respiration, the breathing becoming slow, prolonged, and stertorous. The face is pale, the lips bluish, and the surface of the body cold and exsanguine. The pulse, at first quickened, becomes slower, as the inhalation of the vapour is continued. The pupils are dilated, and the eyes glassy and fixed. The voluntary muscles of the body become flabby and relaxed, the patient still, however, having the power to move the limbs. The involuntary muscles are not affected; as an instance, the uterus contracts and expels its contents with ease. If the inhalation of the vapour be pushed too far, the pulse sinks, and coma ensues, from which the patient can only with difficulty be aroused; but if in an early stage the ether be discontinued, the patient quickly regains consciousness, due to the rapid elimination of the ether by the lungs. A marked peculiarity in this form of poisoning is the complete anæsthesia or paralysis of the nerves of sensation.

_Post-mortem Appearances._--These are chiefly found in the brain and lungs, which in most cases are greatly congested. The cavities of the heart have been found full of dark-coloured liquid blood. A marked effect noticed in poisoning by ether is the congestion of the vessels of the upper portion of the spinal cord. The liver, kidneys, and spleen are sometimes congested.

_Chemical Analysis._--The contents of the stomach and tissues must be treated and distilled, as described under alcohol.

_Tests_:

1. The vapour passed into a solution of bichromate of potash, and sulphuric acid added, gives the reactions of alcohol. 2. The vapour burns with a smoky flame, depositing carbon on any cool surface placed above the flame. 3. It is but sparingly soluble in water, on which liquid it floats.

_Treatment._--When the pulse becomes weak, and the breathing laboured and stertorous, the inhalation should be discontinued, and cold water dashed in the face--free ventilation being also allowed. Galvanism and artificial respiration should also be tried.

CHLOROFORM

The effects produced by chloroform when swallowed are not unlike those occasioned by alcohol. Four ounces have been taken without causing death; it is, therefore, not an active poison in this form.

=Chloroform Vapour.=--The symptoms occasioned by chloroform when inhaled are not unlike those caused by ether, with this exception, that insensibility and general relaxation of the muscles are more rapidly produced.

_Symptoms._--The symptoms of poisoning when chloroform is taken by the mouth are similar to those following inhalation, with irritation of the mucous membrane of the stomach and intestines. Vomiting generally occurs, the person becomes unconscious and comatose, the face cyanosed and the skin moist. The pupils are dilated and insensitive to light. The breathing is slow and stertorous, the pulse small and feeble. Death is due to respiratory paralysis first, and paralysis of the heart in addition, or the latter, according to some observers, may be the primary cause. On recovery diarrhœa may follow, with occasionally enlargement of the liver and jaundice.

_Post-mortem Appearances._--Congestion of the vessels of the brain, and also of the lungs, is generally found. The cavities of the heart are usually empty; but, in some cases, the right side of the heart is found distended with dark-coloured fluid blood. Congestion of the spleen, liver, and kidneys is not of infrequent occurrence.

_Fatal Period and Dose._--In one or two cases where the vapour was inhaled, death took place in from one to two minutes. Thirty drops thus taken destroyed life in one minute, and even fifteen drops have proved speedily fatal. It has thus destroyed life in a smaller dose, and more rapidly, than any other known poison. When swallowed, one fluid drachm has proved fatal in a boy, about four fluid drachms in an adult. Recovery has taken place after four fluid ounces. Three hours is the shortest fatal period after swallowing chloroform.

_Chemical Analysis._--In searching for the presence of this substance in the blood or tissues, the examination should be made as speedily as possible, as chloroform is thought by some observers to have a great tendency to pass into formic acid, and thus to escape recognition.

1. The substance to be examined should be placed in a flask, to which is adapted a glass tube bent at right angles. A piece of blue litmus paper, and another portion of paper moistened with iodide of potassium and starch paste, are inserted into the end of the glass tube. The flask and its contents should now be placed in a water bath heated to a temperature of 161° F. (72° C.), and a portion of the glass tube just past the bend heated to redness. Any chloroform vapour evolved from the contents of the flask is decomposed during its passage through the heated glass tube into free chlorine and hydrochloric acid, the presence of the former being indicated by the starch paper becoming blue; while at the same time the reddening of the litmus paper reveals the presence of the acid. As a further corroboration, the exit tube may be made to dip into nitrate of silver solution, when a precipitate of the curdy-white chloride of silver will take place, insoluble in nitric acid, but dissolving on the addition of ammonia. Every 100 parts of chloride of silver formed, equals 27.758 of chloroform. By this process chloroform has been detected four weeks after death in putrid organs.

2. Chloroform may be separated from organic mixtures by distillation. If aniline and alcoholic solution of potash be added to chloroform and heated, the peculiar odour of phenyl-isocyanide is given off.

3. A solution of β-naphthol dissolved in caustic potash, when added to chloroform and heated, gives a blue colour.

4. Chloroform reduces Fehling‘s solution.

_Treatment._--The same as recommended with regard to ether. M. Nelaton recommends inversion of the body, and ascribes the recovery of one patient to his suddenly lifting him up and throwing him over his shoulder with his head hanging down.

CARBON BISULPHIDE

This substance is largely used in certain industries, as it dissolves oils, fats, caoutchouc, gutta percha, &c. It is very inflammable, burns with a blue flame, evolving sulphur dioxide. The odour, when this substance is impure, is very disagreeable. If taken internally, it produces an intense burning sensation in the throat, headache, and giddiness. In chronic poisoning from the vapour in manufactories where it is used, there appear to be two stages--one of excitement, and one of depression. In the former, there are more or less persistent headache, irritability of temper, tinnitus aurium, and even mania; in the latter, anæsthesia of the skin, even affecting the mucous membranes, patients complaining that their tongues feel as if tied in a cloth. Paralysis of the limbs has been noted in prolonged cases of chronic poisoning. The _post-mortem_ appearances do not differ much from those found after death from the inhalation of chloroform. Carbon bisulphide may be separated from organic liquids by distillation, and detected by its odour, and by a black precipitate of sulphide of lead when heated with nitrate of lead and potash.

CHLORAL HYDRATE

This substance is prepared by acting on alcohol by chlorine. It is used extensively as a hypnotic, and, owing to its indiscriminate use, many fatal cases have been recorded. Care should be taken when large doses are given not to repeat them too quickly, as there appears to be a tendency to accumulation, and sudden and dangerous action of the drug.

_Symptoms._--Chloral, in moderate doses, acts on the brain as a powerful hypnotic, the early symptoms being gradual drowsiness, followed by deep sleep. With a dose of about 30 grains, the patient can, however, by walking about, ward off sleep. In large doses the narcosis becomes completely uncontrollable, and the poison then acts as a depressant to the basal ganglia of the brain, and on the spinal cord; and, as a result, there is weakness of the heart‘s action, with ultimate diastolic arrest, slowing of the respiratory movements, and general muscular weakness, with some anæsthesia. Under these circumstances the patient has all the appearance of a drunken person, the face is flushed, and the deep sleep may pass imperceptibly into death without any marked change. In some cases delirium precedes the condition of sleep. The pulse in some cases is quickened, and the face flushed; but, in other cases, the pulse becomes slow and almost imperceptible, the heart being ultimately arrested in diastole. In these cases the face is pale, and the breathing performed at long intervals. The motor paralysis present, when a poisonous dose is taken, is due to the action of the drug on the spinal cord, and not on the nerves. During the sleep produced by chloral, the pupils are contracted, but dilate on the person awakening. In a case described by Dr. Levinstein, and reported in the _Lancet_, 21st February 1874, the patient took six drachms with intent to commit suicide. The face was at first flushed, the veins swollen, and the pulse 160 per minute; he then became livid, the pupils contracted, and at times the circulation appeared to be entirely arrested. The temperature varied from 32.9° C. to 38.7° C. (89.6° F. to 100.4° F.). This case recovered under treatment by the subcutaneous injections of strychnine (.03 to .04 grain), and the use of faradisation in thirty-two hours after the poison had been taken. Chronic chloral poisoning, “chloral-drinking,” has unfortunately become far too common of late years, in which the mental faculties suffer severely, so that in our asylums, cases of mania and melancholia are rightly (or wrongly) attributed to the habit. A peculiar eruption, not unlike that produced by shell-fish, and followed by desquamation, sometimes occurs when this substance has been given for some time in medicinal doses.

_Post-mortem Appearances._--These are not unlike those of asphyxia, the vessels of the brain being engorged, and the ventricles containing an abnormal quantity of fluid. The mucous membrane of the larynx may be injected, and in some cases œdematous. The right side of the heart is engorged and the left empty, together with congestion of the lungs. Chloral is very little decomposed into chloroform by the blood. W. H. Roberts has in several cases recovered it as chloral from the blood.

_Fatal Dose._--The fatal dose cannot be accurately stated, but children, as in the case of belladonna, are said to bear the drug better than adults. A child a year old died in ten hours from a dose of three grains. Ten grains proved fatal to an old lady seventy years of age. Twenty grains has caused death in an adult in half an hour, and in one case thirty grains. As a rule, any quantity over two drachms may be considered a dangerous, if not a fatal dose, although recovery has been stated to have occurred after one ounce. Dr. Richardson considers 120 grains, distributed over twenty-four hours, as a safe dose for an adult. Death may take place suddenly, or after the lapse of several hours.

_Fatal Period._--From fifteen minutes, which is the shortest time on record, to thirty-nine and a half hours, which is the longest period recorded.

_Chemical Analysis._--Chloral may be extracted from the stomach contents by digestion with absolute alcohol acidified by sulphuric acid. The alcoholic extract is filtered and evaporated. The residue is treated with petroleum ether to remove fatty substances, and finally shaken with pure ether to remove the chloral. On evaporating the ether the chloral hydrate is left. From urine it may be extracted by first acidifying with sulphuric acid and then treating it with petroleum ether and ether. Chloral hydrate in solution gives the following reactions:--

1. On agitation with solution of caustic potash, and gently warmed if necessary, chloroform is evolved, which can be detected by its odour. From a strong solution the chloroform may separate in the form of minute globules.

2. If one drop of ammonium sulphide be added to a solution of chloral hydrate and gently heated, a peculiar opalescent milky reddish-yellow precipitate forms. This test is extremely delicate, and differentiates chloral hydrate from chloroform.

3. Alcoholic solution of potash and aniline when added to chloral hydrate solution, shaken up and warmed, produces the peculiar odour of phenyl-isocyanide. This is due to the formation of chloroform on the addition of the caustic potash.

4. If β-naphthol dissolved in caustic potash solution be added to a solution of chloral hydrate and the mixture warmed, a blue colour is produced.

5. Chloral hydrate reduces Fehling‘s solution.

To separate chloroform in the stomach contents from chloral hydrate they should be acidified with tartaric acid and distilled, when the chloroform which was free in the stomach will pass over to the receiver. If the residue be now rendered alkaline with caustic potash and again distilled, any chloroform which then comes over must have been derived from chloral hydrate in the stomach contents.

_Treatment._--The treatment consists in washing out the stomach, the administration of emetics, or hypodermic injection of apomorphine, in the use of galvanism, friction, mustard-plasters to the calves of the legs, artificial respiration, and the hypodermic injection of a solution of nitrate of strychnia or injection of atropine. The warmth of the body must be carefully maintained in all cases by suitable external applications. Oxygen inhalations are said to be beneficial.

SULPHONAL

Sulphonal is a product of the oxidation of mercaptol, obtained from acetone and mercaptan; it occurs in tasteless, odourless, colourless crystals or powder, was introduced into medical practice in 1888, and has since caused many accidental deaths. The habit of taking it may be acquired. It has a tendency to accumulative action when taken for some time without interruption. A serious feature in most of the cases of poisoning is that usually those taking it have been apparently benefited by the drug up to the time of the appearance of toxic symptoms.

_Symptoms._--In medicinal doses (15-30 grains) it has an action similar to that of paraldehyde, it causes sleep with little depression of the circulation and respiration. Larger doses produce variable symptoms, mental confusion with nervous ataxic manifestations, stupor, and insensibility; less frequently excitement and convulsions. Skin eruptions may follow a large dose or from its long continued use. In severe cases there is marked cyanosis, feeble pulse, and stertorous and irregular breathing. Death usually results from failure of respiration, or the urine may be suppressed and fatal coma supervene. Albuminuria and hæmatoporphyrinuria are common features, especially in chronic cases. The deep pink colour of the urine was attributed to hæmatoporphyrin, and indicating extensive destruction of the red blood corpuscles. It is a grave symptom. That the colour of the urine is due to hæmatoporphyrin is questionable, for on removing the hæmatoporphyrin the colour remains the same. The cumulative action is due to slow elimination by the kidneys. A case published by Drs. Taylor and Sailer, and reported in the _Lancet_, February 1900, was that of a woman aged fifty-two years, unmarried, and presenting symptoms of hysteria. On inquiry it was discovered that she had been in the habit of taking sulphonal for some time, the dose being fifteen grains per diem. She was informed of the evil results likely to follow the continued use of the drug, and she discontinued its use for some weeks. After this she resumed taking the drug, and began speedily to exhibit all the symptoms of sulphonal poisoning: viz. mental confusion, marked insomnia, difficulty of speech, and a peculiar sighing dyspnœa. The urine was tinged a deep pink colour (hæmatoporphyrinuria), and a stiffness and paralysis of both legs soon developed. The control of the sphincters was lost. Cutaneous sensibility was not affected. The paralysis spread rapidly upwards, and death resulted from cardiac failure. Spectroscopic examination of both urine and blood disclosed the presence of hæmatoporphyrin. At the necropsy the following conditions were revealed: fatty degeneration was present in the heart, liver, and kidneys. The spleen was filled with a greenish pigment, both free and within the lymphoid corpuscles, the fibrous trabeculæ were greatly increased in size, and the lymphoid follicles were extremely well developed. Excessive pigmentation was found also in the lymphatic glands of the body and in the lungs. No morbid changes could be found in the spinal cord or brain.

_Fatal Dose._--This is very uncertain, depending upon idiosyncrasy. Thirty grains has caused death in a woman in forty hours, while a case is reported in the _Lancet_, January 1904, of recovery after the taking of 365 grains. In many cases death has followed the daily use of moderate doses (10-20 grains) for several months.

_Fatal Period._--May occur in a few hours, or days, or after months; also after the use of the drug has been discontinued.

_Chemical Analysis._--Sulphonal is very stable, and is unaffected by boiling alkalies or by concentrated nitric or sulphuric acids. From its solution in concentrated sulphuric acid it may be recovered by dilution. It is easily recovered from the body after death, as its stability prevents its decomposition. It is isolated from organic matter by treatment with alcohol, evaporation, and extraction of the residue with hot water, evaporation and final extraction with ether.

_Tests._--1. Heated in a test tube with powdered charcoal, sulphonal forms mercaptan, acetic acid, formic acid, and sulphur dioxide. The offensive odour of mercaptan may be noted, and the vapours will change blue litmus paper. Sulphur dioxide may be shown by its bleaching action on a piece of filter paper moistened with blue starch iodide and suspended in the mouth of the tube.

2. When melted with potassium cyanide, sulphonal develops a mercaptan odour, and potassium sulphocyanate is formed at the same time. A blood-red colour is therefore produced on the addition of ferric chloride to a solution of the residue in water. Great care must be exercised in the carrying out of this test, as it is somewhat dangerous to the experimenter.

_Treatment._--The stomach should be washed out in order to remove any drug unabsorbed. Diuretics, purgatives, and general stimulants given, such as strychnine, hot coffee, &c.

TRIONAL AND TETRONAL

These compounds are very similar in both their chemical and physiological properties to sulphonal, but both have a bitter taste. Both have caused fatal poisoning, the symptoms being very similar to those caused by sulphonal.

VERONAL

Veronal, a synthetic compound, is a white crystalline powder about four times as powerful as sulphonal, very slightly soluble in water, more soluble in hot water, and in alkaline solutions, and absorption takes place from the intestine.

_Symptoms._--In moderate doses it produces sleep without subsequent depression, and does not affect temperature or respiration. In larger doses it may cause erythema and constipation, with alternating semi-coma and delirium. During the last few years fatal cases of poisoning have become rather frequent.

Details of a fatal case by Dr. Durrant reported in Taylor, p. 616, are, briefly: A man aged thirty-three, a heavy drinker, to whom veronal had been prescribed, in fifteen-grain doses, with chloral hydrate and bromide of ammonium, had gradually increased the dose from 15 to 30 grains, or even 60 grains. Five weeks before death he had taken 100 grains, and had recovered in three days. Nine hours after taking 120 grains of veronal with 20 grains of chloral and 40 grains of ammonium bromide he was found deeply comatose, with surface warm, respirations 32, pulse 102, pupils dilated, corneæ insensitive, reflexes absent. Next day not so deeply comatose, he could be made to wince by slapping the face, the pupils were still dilated, temperature 102° F., pulse 110, reflexes still absent. Later he was still constipated, and the breathing impeded by mucus. On the third day he spoke when roused; the temperature, bowels, and pupils the same. With slight remission he became worse, and on the fourth day, in a comatose condition, with muscular flaccidity and absence of reflexes, temperature 104° F., respirations over 40, and the pulse 150, death took place. _Post-mortem._--Nothing was found except intense congestion of the lungs, liver, spleen, and brain, due, no doubt, to the asphyxial form of death. The mucous membrane of the alimentary canal was congested, but otherwise normal.

_Chemical Tests._--1. Heated dry with sodium carbonate, ammonia is evolved. If held in the mouth of the tube red litmus paper turns blue, turmeric paper brown.

2. A saturated solution acidified with nitric acid gives a white precipitate with Millon‘s reagent soluble in excess.

_Treatment._--As for sulphonal.

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