SEPARATED BY DISTILLATION FROM NEUTRAL OR ACID LIQUIDS.
HYDROCARBONS--CAMPHOR--ALCOHOL--AMYL NITRITE--ETHER--CHLOROFORM AND
OTHER ANÆSTHETICS--CHLORAL--CARBON DISULPHIDE--CARBOLIC
ACID--NITRO-BENZENE--PRUSSIC ACID--PHOSPHORUS.
I.--Hydrocarbons.
1. PETROLEUM.
§ 137. Petroleum is a general term for a mixture of hydrocarbons of
the paraffin series, which are found naturally in certain parts of
the world, and are in commerce under liquid and solid forms of
various density. Crude petroleum is not imported into England, the
original substance having previously undergone more or less
rectification. The lighter and more volatile portions are known
under the name of cymogene, rhigolene, gasolene, and naphtha.
§ 138. =Cymogene= has a specific gravity of ·590, and boils at 0°.
It has been employed in refrigerating machines. It appears to
consist chiefly of butane (C₄H₁₀).
§ 139. =Rhigolene= is now used in medicine in the form of spray to
produce local anæsthesia. It boils at 18°, and has a density of
·650.
§ 140. =Gasolene= has a density of ·680-·688; it has received
technical applications in the “naphthalising” of air and gas.
§ 141. =Benzoline= (=mineral naphtha=, =petroleum naphtha=,
=petroleum spirit=, =petroleum ether=) is a mixture of the lighter
series of hydro-carbons; the greater part consists of heptane, and
there is also a considerable quantity of pentane (C₇H₁₆) present.
The specific gravity varies from ·69 to ·74. It is very inflammable,
and is used in sponge lamps, and also as a solvent for gutta-percha,
naphthalene, paraffin, wax, and many other bodies. By the practical
chemist it is much employed.
The similarity of the terms _benzoline_ and _benzene_ has caused
benzoline to be often confused with _benzol_ or _benzene_, the
leading constituent of coal-tar naphtha (C₆H₆). Mr Allen[132] gives
in the following table a summary of the chief points of distinction,
both between petroleum naphtha, shale naphtha, and coal-tar naphtha.
The table is founded upon the examination of particular samples, and
commercial samples may present a few minor deviations.
[132] _Commercial Organic Analysis_, vol. ii. p. 31.
TABLE OF THE VARIETIES OF NAPHTHA.
+---------------------+----------------------+----------------------+
| Petroleum Naphtha. | Shale Naphtha. | Coal-tar Naphtha. |
+---------------------+----------------------+----------------------+
|Contains at least 75 |Contains at least 60 |Consists almost wholly|
|per cent. of heptane,|to 70 per cent. of |of benzene, C₆H₆, and |
|C₇H₁₆, and other |heptylene, C₇H₁₄, and |other homologous |
|hydrocarbons of the |other hydrocarbons of |hydrocarbons, with a |
|marsh gas or paraffin|the olefin series; the|small percentage of |
|series; the remainder|remainder paraffins. |light hydrocarbons in |
|apparently olefins, |No trace of benzene or|some samples. |
|C_{n}H_{2n}, with |its homologues. | |
|distinct traces of | | |
|benzene and its | | |
|homologues. | | |
| | | |
|Specific gravity at |Specific gravity at |Specific gravity ·876.|
|15°, ·600. |15°, ·718. | |
| | | |
|Distils between 65° |Distils between 65° |Distils between 80° |
|and 100°. |and 100°. |and 120°. |
| | | |
|Dissolves coal-tar |Behaves similarly to |Readily dissolves |
|pitch, but slightly; |petroleum naphtha with|pitch, forming a deep |
|liquid, but little |regard to the solution|brown solution. |
|coloured even after |of pitch. | |
|prolonged contact. | | |
| | | |
|On shaking three |When treated with |The liquids form a |
|measures of the |fused carbolic acid |homogeneous mixture |
|sample with one |crystals, the liquids |when treated with |
|measure of fused |mix perfectly. |fused carbolic acid |
|crystals of absolute | |crystals. |
|carbolic acid, no | | |
|solution. Liquids not| | |
|miscible. | | |
| | | |
|Combines with 10 per |Combines with upwards |Combines slowly with |
|cent. of its weight |of 90 per cent. of its|30-40 per cent. of its|
|of bromine in the |weight of bromine. |weight of bromine. |
|cold. | | |
+---------------------+----------------------+----------------------+
§ 142. =Paraffin Oil= (or =kerosine, mineral oil, photogen=, &c.) is
the chief product resulting from the distillation of American
petroleum--the usual specific gravity is about ·802--it is a mixture
of hydrocarbons of the paraffin series. It should be free from the
more volatile constituents, and hence should not take fire when a
flame is applied near the surface of the cold liquid.
§ 143. =Effects of Petroleum.=--Since we have here to deal with a
commercial substance of such different degrees of purity, and
various samples of which are composed of such various proportions of
different hydrocarbons, its action can only be stated in very
general terms. Eulenberg[133] has experimented with the lighter
products obtained from the distillation of Canadian petroleum. This
contained sulphur products, and was extremely poisonous, the vapour
killing a rabbit in a short time, with previous insensibility and
convulsions. The autopsy showed a thin extravasation of blood on the
surface of each of the bulbi, much coagulated blood in the heart,
congested lungs, and a bloody mucus covering the tracheal mucous
membrane. An experiment made on a cat with the lighter petroleum
(which had no excess of sulphur) in the state of vapour, showed that
it was an anæsthetic, the anæsthesia being accompanied by
convulsions, which towards the end were tetanic and violent. The
evaporation of 1·5 grm. in a close chamber killed the animal in
three hours. The lungs were found congested, but little else was
remarkable. Much petroleum vapour is breathed in certain factories,
especially those in which petroleum is refined.[134] From this cause
there have been rather frequent toxic symptoms among the workmen.
Eulenberg[135] describes the symptoms as follows:--A person, after
breathing an overdose of the vapour, becomes very pale, the lips are
livid, the respiration slow, the heart’s action weak and scarcely to
be felt. If he does not immediately go into the open air away from
the poisonous vapour, these symptoms may pass on to insensibility,
convulsions, and death. It often occasions a condition of the
voluntary muscles similar to that induced by drunkenness, and on
recovery the patient is troubled by singing in the ears and noises
in the head. The smell and taste of the poison may remain for a long
time.
[133] _Gewerbe-Hygiene._
[134] The vapour most likely to rise at the ordinary temperature, and
mix with the atmosphere, is that of the lighter series, from cymogene to
benzoline.
[135] _Op. cit._
§ 144. Poisoning by taking light petroleum into the stomach is not
common. In a case recorded by Taylor,[136] a woman, for the purpose
of suicide, swallowed a pint of petroleum, There followed a slight
pain in the stomach, and a little febrile disturbance, and a
powerful smell of petroleum remained about the body for six days;
but she completely recovered. In August 1870 a sea-captain drank a
quantity of paraffin, that is, lighting petroleum, and died in a few
hours in an unconscious state. A child, 2 years old, was brought to
King’s College Hospital within ten minutes after taking a
teaspoonful of paraffin. It was semi-comatose and pale, with
contracted pupils; there was no vomiting or purging. Emetics of
sulphate of zinc were administered, and the child recovered in
twenty-four hours. In another case treated at the same hospital, a
child had swallowed an unknown quantity of paraffin. It fell into a
comatose state, which simulated tubercular meningitis, and lasted
for nearly three weeks.[137] In a case recorded by Mr Robert
Smith,[138] a child, 4 years of age, had swallowed an unknown
quantity of paraffin. A few minutes afterwards, the symptoms
commenced; they were those of suffocation, with a constant cough;
there was no expectoration; the tongue, gums, and cheeks were
blanched and swollen where the fluid touched them; recovery
followed. A woman, aged 32, who had taken a quarter of a pint of
paraffin, was found unconscious and very cold; the stomach-pump was
used, and she recovered.[139] Hence it is tolerably certain, from
the above instances, that should a case of petroleum poisoning
occur, the expert will not have to deal with infinitesimal
quantities; but while the odour of the oil will probably be
distinctly perceptible, there will be also a sufficient amount
obtained either from matters vomited, or the contents of the
stomach, &c., so that no difficulty will be experienced in
identifying it.
[136] _Poisons_, p. 656
[137] _Brit. Med. Journ._, Sept. 16, 1876, p. 365.
[138] _Brit. Med. Journ._, Oct. 14, 1876.
[139] _Pharm. Journ._, Feb. 12, 1875; also for other cases see _Brit.
Med. Journ._, Nov. 4, 1876; and Köhler’s _Physiol. Therap._, p. 437.
§ 145. In order to separate petroleum from any liquid, the
substances under examination must be carefully distilled in the
manner recommended under “_Ether_.” The lighter petroleums will
distil by the aid of a water-bath; but the heavier require a
stronger heat; redistillation of the distillate may be necessary.
The odour of the liquid, its inflammable character, and its other
properties, will be sufficient for identification.
2. COAL-TAR-NAPHTHA--BENZENE.
§ 146. Coal-tar-naphtha in its crude state, is an extremely complex
liquid, of a most disagreeable smell. Much benzene (C₆H₆) is present
with higher homologues of the benzene series. Toluene (C₇H₈),
naphthalene (C₁₀H₈), hydrocarbons of the paraffin series,
especially hexane (C₆H₁₄), and hydrocarbons of the olefin series,
especially pentylene, hexylene, and heptylene (C₅H₁₀, C₆H₁₂ and
C₇H₁₄). Besides these, there are nitrogenised bases, such as
aniline, picoline, and pyridine; phenols, especially carbolic acid;
ammonia, ammonium sulphide, carbon disulphide, and probably other
sulphur compounds; acetylene and aceto-nitrile. By distillation and
fractional distillation are produced what are technically known
”_once run_” _naphtha_, _90 per cent. benzol_, _50 and 90 per cent.
benzol_,[140] _30 per cent. benzol_, _solvent naphtha_, and residue
known as “_last runnings_.”
[140] Or 50/90 benzol, this indicates that 50 per cent. distils over
below 100°; and 40, making in all 90, below 120°.
§ 147. Taylor[141] records a case in which a boy, aged 12, swallowed
about 3 ozs. of naphtha, the kind usually sold for burning in lamps,
and died with symptoms of narcotic poisoning. The child, after
taking it, ran about in wild delirium, he then sank into a state of
collapse, breathing stertorously, and the skin became cold and
clammy. On vomiting being excited, he rejected about two
tablespoonfuls of the naphtha, and recovered somewhat, but again
fell into collapse with great muscular relaxation. The breathing was
difficult; there were no convulsions; the eyes were fixed and
glassy, the pupils contracted; there was frothing at the mouth. In
spite of every effort to save him, he died in less than three hours
after taking the poison. The body, examined three days after death,
smelt strongly of naphtha, but the _post-mortem_ appearances were in
no way peculiar, save that the stomach contained a pint of
semi-fluid matter, from which a fluid, having the characteristics of
impure benzene, was separated.
[141] _Op. cit._, p. 657.
§ 148. The effects of the vapour of benzene have been studied by
Eulenberg in experiments on cats and rabbits, and there are also
available observations on men[142] who have been accidentally
exposed to its influence. From these sources of information, it is
evident that the vapour of benzene has a distinctly narcotic effect,
while influencing also in a marked degree the spinal cord. There
are, as symptoms, noises in the head, convulsive trembling and
twitchings of the muscles, with difficulty of breathing.
[142] Dr. Stone, _Med. Gaz._, 1848, vol. xii. p. 1077.
DETECTION AND SEPARATION OF BENZENE.
§ 149. Benzene is separated from liquids by distillation, and may be
recognised by its odour, and by the properties described at p. 130.
The best process of identification, perhaps, is to purify and
convert it into nitro-benzene, and then into aniline, in the
following manner:--
1. =Purification.=--The liquid is agitated with a solution of
caustic soda; this dissolves out of the benzene any bodies of an
acid character, such as phenol, &c. The purified liquid should again
be distilled, collecting that portion of the distillate which passes
over between 65° and 100°; directly the thermometer attains nearly
the 100°, the distillation should be stopped. The distillate, which
contains all the benzene present, is next shaken with concentrated
sulphuric acid in the cold; this will dissolve out all the
hydrocarbons of the ethylene and acetylene series. On removing the
layer of benzene from the acid, it must be again shaken up with
dilute soda, so as to remove any trace of acid. The benzene is, by
this rather complicated series of operations, obtained in a very
fair state of purity, and may be converted into nitro-benzene, as
follows:--
2. =Conversion into Nitro-Benzene.=--The oily liquid is placed in a
flask, and treated with four times its volume of fuming nitric acid.
The flask must be furnished with an upright condenser; a vigorous
action mostly takes place without the application of heat, but if
this does not occur, the flask may be warmed for a few minutes.
After the conversion is over, the liquid, while still warm, must be
transferred into a burette furnished with a glass tap, or to a
separating funnel, and all, except the top layer, run into cold
water; if benzene was originally present, either oily drops of
nitro-benzene will fall, or if the benzene was only in small
quantity, a fine precipitate will gradually settle down to the
bottom of the vessel, and a distinct bitter-almond smell be
observed; but, if there be no benzene in the original liquid, and,
consequently, no nitro-benzene formed, no such appearance will be
observed.
3. =Conversion into Aniline.=--The nitro-benzene may itself be
identified by collecting it on a wet filter, dissolving it off the
filter by alcohol, acidifying the alcoholic solution by hydrochloric
acid, and then boiling it for some time with metallic zinc. In this
way aniline is formed by reduction. On neutralising and diluting the
liquid, and cautiously adding a little clear solution of
bleaching-powder, a blue or purple colour passing to brown is in a
little time produced.
3. TERPENES--ESSENTIAL OILS--OIL OF TURPENTINE.
§ 150. The terpenes are hydrocarbons of the general formula
C_{n}H_{2n-4}. The natural terpenes are divided into three
classes:--
1. =The true terpenes=, _formula_ (C₁₀H₁₆)--a large number of
essential oils, such as those of turpentine, orange peel, nutmeg,
caraway, anise, thyme, &c., are mainly composed of terpenes.
2. =The cedrenes=, _formula_ (C₁₅H₂₄)--the essential oil of cloves,
rosewood, cubebs, calamus, cascarilla, and patchouli belong to this
class.
3. =The colophene hydrocarbons=, _formula_ (C₂₀H₃₂), represented by
colophony.
Of all these, oil of turpentine alone has any toxicological
significance; it is, however, true that all the essential oils, if
taken in considerable doses, are poisonous, and cause, for the most
part, vascular excitement and complex nervous phenomena, but their
action has not been very completely studied. They may all be
separated by distillation, but a more convenient process for
recovering an essential oil from a liquid is to shake it up with
petroleum ether, separating the petroleum and evaporating
spontaneously; by this means the oil is left in a fair state of
purity.
4. OIL OF TURPENTINE--SPIRIT OF TURPENTINE--“TURPS.”
§ 151. Various species of pine yield a crude turpentine, holding in
solution more or less resin. The turpentine may be obtained from
this exudation by distillation, and when the first portion of the
distillate is treated with alkali, and then redistilled, the final
product is known under the name of “rectified oil of turpentine,”
and is sometimes called “camphene.” It mainly consists of
terebenthene. Terebenthene obtained from French turpentine differs
in some respects from that obtained from English or American
turpentine. They are both mobile, colourless liquids, having the
well-known odour of turpentine and highly refractive; but the French
terebenthene turns a ray of polarised light to the left -40·3° for
the sodium ray, and the English to the right +21·5°; the latter
terebenthene is known scientifically as austra-terebenthene. This
action on polarised light is retained in the various compounds and
polymers of the two turpentine oils.
The specific gravity of turpentine oil is ·864; its boiling point,
when consisting of pure terebenthene, 156°, but impurities may raise
it up to 160°; it is combustible and burns with a smoky flame. Oil
of turpentine is very soluble in ether, petroleum ether, carbon
disulphide, chloroform, benzene, fixed and essential oils, and by
the use of these solvents it is conveniently separated from the
contents of the stomach. It is insoluble in water, glycerin, and
dilute alkaline and acid solutions; and very soluble in absolute
alcohol, from which it may be precipitated by the addition of water.
It is polymerised by the action of strong sulphuric acid, the
polymer, of course, boiling at a higher temperature than the
original oil. With water it forms a crystalline hydrate
(C₁₀H₂₀O₂,H₂O). On passing nitrosyl chloride gas into the oil,
either pure or diluted with chloroform or alcohol, the mixture being
cooled by ice, a white crystalline body is deposited, of the formula
C₁₀H₁₆(NOCl). By treating this compound with alcoholic potash, the
substitution product (C₁₀H₁₆NO) is obtained. By treating turpentine
with an equal bulk of warm water, and shaking it in a large bottle
with air, camphoric acid and peroxide of hydrogen are formed. When
turpentine oil is left in contact with concentrated hydrochloric
acid, there is formed terebenthene dihydrochloride (C₁₀H₁₆2HCl),
which forms rhombic plates, insoluble in water, and decomposable by
boiling alcoholic potash, with formation of terpinol, (C₁₀H₁₇)₂O.
The dihydrochloride gives a colour-reaction with ferric chloride.
This is an excellent test--not, it is true, confined to oil of
turpentine--but common to the dihydrochlorides of all the terpenes.
A few drops of the oil are stirred in a porcelain capsule with a
drop of hydrochloric acid, and one of ferric chloride solution; on
gently heating, there is produced first a rose colour, then a
violet-red, and lastly a blue.
§ 152. =Effects of the Administration of Turpentine.=--L. W.
Liersch[143] exposed animals to the vapour of turpentine, and found
that a cat and a rabbit died within half an hour. There was observed
uneasiness, reeling, want of power in the limbs (more especially in
the hinder extremities), convulsions partial, or general, difficulty
of respiration; and the heart’s action was quickened. Death took
place, in part, from asphyxia, and in part was attributable to a
direct action on the nervous centres. The autopsy showed congestion
of the lungs, ecchymoses of the kidney, and much blood in the liver
and spleen. Small doses of turpentine-vapour cause (according to Sir
B. W. Richardson)[144] giddiness, deficient appetite, and anæmia.
From half an ounce to an ounce is frequently prescribed in the
country as a remedy for tape-worm; in smaller quantities it is found
to be a useful medicine in a great variety of ailments. The larger
doses produce a kind of intoxication with giddiness, followed often
by purging and strangury, not unfrequently blood and albumen (or
both) is found in the urine. When in medical practice I have given
the oil, and seen it given by others, in large doses for tape-worm
to adults, in perhaps 40 cases, but in no one instance were the
symptoms severe; the slight intoxication subsided quickly, and in a
few hours the patients recovered completely. Nevertheless it has
been known to destroy the lives of children, and cause most serious
symptoms in adults. Two fatal cases are mentioned by Taylor; one was
that of a child who died fifteen hours after taking half an ounce of
the oil; in another an infant, five months old, died rapidly from a
teaspoonful. The symptoms in these fatal cases were profound coma
and slight convulsions; the pupils were contracted, and there was
slow and irregular breathing. Turpentine is eliminated in a changed
form by the kidneys, and imparts an odour of violet to the urine;
but the nature of the odoriferous principle has not yet been
investigated.
[143] Clarus in Schmidt’s _Jahrbücher_, Bd. cxvii., i. 1863; and
_Vierteljahrsschr. für ger. Med._, xxii., Oct. 1862.
[144] _Brit. and For. Med.-Chir. Review_, April 1863.
II.--Camphor.
§ 153. A great many essential oils deposit, after exposure to air,
camphors produced by oxidation of their terpenes. Ordinary camphor
is imported in the rough state from China and Japan, and is prepared
by distilling with water the wood of _Camphora officinarum_; it is
resublimed in England. The formula of camphor is C₁₀H₁₆O; it has a
density of ·986 to ·996; melts at 175°, and boils at 205°. It is
readily sublimed, especially in a vacuum, and is indeed so volatile
at all temperatures, that a lump of camphor exposed to the air
wastes away. It is somewhat insoluble in water (about 1 part in
1000), but this is enough to impart a distinct taste to the water;
it is insoluble in chloroform, ether, acetone, acetic acid, carbon
disulphide, and oils. It has a fragrant odour and a burning taste. A
10 per cent. solution in alcohol turns a ray of polarised light to
the right +42·8°. By distillation with zinc chloride, cymene and
other products are produced. By prolonged treatment with nitric
acid, camphor is oxidised to camphoric acid (C₁₀H₁₆O₄). Camphor
unites with bromine to form a crystalline, unstable dibromide, which
splits up on distillation into hydrobromic acid and monobrom-camphor
(C₁₀H₁₅BrO). The latter is used in medicine; it crystallises in
prisms fusible at 76°, and is readily soluble in alcohol.
§ 154. =Pharmaceutical Preparations.=--The preparations officinal in
the British Pharmacopœia are _camphor water_--water saturated with
camphor, containing about one part per thousand.
=Camphor Liniment.=--A solution of camphor in olive oil, strength 25
per cent.
=Compound Camphor Liniment.=--Composed of camphor, oil of lavender,
strong solution of ammonia and alcohol; strength in camphor about 11
per cent.
=Spirit of Camphor.=--A solution of camphor in spirit; strength, 10
per cent.
Camphor is also a constituent of the _compound tincture of camphor_;
but in this case it may be considered only a flavouring agent. There
is a homœopathic solution of camphor in spirit (Rubini’s Essence of
Camphor). The solution is made by saturating alcohol with camphor;
it is, therefore, very strong--about half the bulk consisting of
camphor. Camphor is used in veterinary medicine, both externally and
internally.
§ 155. =Symptoms.=--Camphor acts energetically on the brain and
nervous system, especially if it is given in strong alcoholic
solution, and thus placed under conditions favouring absorption.
Some years ago, Dr. G. Johnson[145] published a series of cases
arising from the injudicious use of “homœopathic solution of
camphor,” from 7 to 40 drops of Rubini’s homœopathic camphor taken
for colds, sore throat, &c., having produced coma, foaming at the
mouth, convulsions, and partial paralysis. All the patients
recovered, but their condition was for a little time alarming.
[145] _Brit. Med. Journ._, Feb. 27, 1878, p. 272; see also _ibid._, Feb.
1875.
The cases of fatal poisoning by camphor are very rare. A woman, aged
46, pregnant four months, took 12 grms. (about 184 grains) in a
glass of brandy for the purpose of procuring abortion. In a very
short time the symptoms commenced; she had intolerable headache, the
face was flushed, and there was a sensation of burning in the
stomach. In eight hours after taking the dose, she had strangury and
vomiting, and the pain in the epigastrium was intense. These
symptoms continued with more or less severity until the third day,
when she became much worse. Her face was pale and livid, the eyes
hollow, the skin cold and insensible, pulse weak and thready,
breathing laboured. There were violent cramps in the stomach and
retention of urine for twenty-four hours, and then coma. The patient
lingered on yet another three days, aborted, and died.[146]
[146] _Journ. de Chim. Méd._, May 1860.
Dr. Schaaf[147] has recorded three cases of poisoning--one of which
was fatal. A woman gave about half a teaspoonful of a camphor
solution to each of her three children, the ages being respectively
five and three years and fifteen months. The symptoms noted were
pallor of the face, a burning pain in the throat, thirst, vomiting,
purging, convulsions, and afterwards coma. The youngest child died
in seven hours; the others recovered. The smallest dose known to
have produced violent symptoms in an adult is 1·3 grm. (20 grains);
the largest dose known to have been recovered from is 10·4 grms.
(160 grains).[148]
[147] _Journ. de Chim. Méd._, 1850, p. 507.
[148] Taylor on _Poisons_, 3rd ed., 661.
§ 156. =Post-mortem Appearances.=--The bodies of animals or persons
dying from poisoning by camphor, smell strongly of the substance.
The mucous membrane of the stomach has been found inflamed, but
there seem to be no characteristic lesions.
§ 157. =Separation of Camphor from the Contents of the
Stomach.=--The identification of camphor would probably in no case
present any difficulty. It may be readily dissolved out from organic
fluids by chloroform. If dissolved in fixed oils, enough for the
purposes of identification may be obtained by simple distillation.
It is precipitated from its alcoholic solution by the addition of
water.
III.--Alcohols.
1. ETHYLIC ALCOHOL.
§ 158. The chemical properties of ordinary alcohol are fully described,
with the appropriate tests, in “Foods,” pp. 369-384, and the reader is
also referred to the same volume for the composition and strength of the
various alcoholic drinks.
=Statistics.=--If we were to include in one list the deaths indirectly
due to chronic, as well as acute poisoning by alcohol, it would stand
first of all poisons in order of frequency, but the taking of doses so
large as to cause death in a few hours is rare. The deaths from alcohol
are included by the English registrar-general under two heads, viz.,
those returned as dying from _delirium tremens_, and those certified as
due directly to intemperance.
During the twenty-five years, from 1868 to 1892, 30,219 deaths have been
registered as due to intemperance, which gives an average of 1209 per
year. The rate per million has varied during the period from 29 to 71;
and the figures taken as a whole show that deaths from intemperance
appear to be increasing; the increase may be only apparent, not real,
for it is a significant circumstance that deaths registered under liver
diseases show a corresponding decrease; it is, therefore, not unlikely
that deaths which formerly would be ascribed to liver disease, are more
often now stated to be the effects of intemperance.
Deaths directly due to large doses of alcohol are not uncommon; during
the ten years ending 1892, 105 deaths (81 males and 24 females) were
ascribed under the head of “accident or negligence” directly to alcohol.
[Illustration: CHART SHEWING DEATHS PER MILLION PERSONS LIVING, FROM
INTEMPERANCE & FROM LIVER DISEASES.
THE MEDICAL “OFFICERS OF HEALTH” CHART.
ENT. AT STA. HALL.
Notes.
_Intemperance_ --------------
_Liver disease_ ..............
_The Scale for Intemperance is as printed._
_That for Liver diseases is 10 times larger._]
§ 159. =Criminal or Accidental Alcoholic Poisoning.=--Suicide by
alcohol, in the common acceptation of the term, is rare, and murder
still rarer, though not unknown. In the ten years ending 1892, only
three deaths from alcohol (1 male and 2 females) are recorded as
suicidal. Perhaps the most common cause of fatal acute poisoning by
alcohol is either a foolish wager, by which a man bets that he can drink
so many glasses of spirits without bad effect; or else the drugging of a
person already drunk by his companions in a sportive spirit.
§ 160. =Fatal Dose.=--It is difficult to say what would be likely to
prove a lethal dose of alcohol, for a great deal depends, without doubt,
on the dilution of the spirit, since the mere local action of strong
alcohol on the mucous membranes of the stomach, &c., is severe (one may
almost say corrosive), and would aid the more remote effects. In
Maschka’s case,[149] a boy of nine years and a girl of five, died from
about two and a half ounces of spirit of 67 per cent. strength, or 48·2
c.c. (1·7 oz.) of absolute alcohol.
[149] Recorded by Maschka (_Gutachten der Prager Facultät_, iv. 239; see
also Maschka’s _Handbuch der gericht. Medicin_, Band. ii. p. 384). The
following is a brief summary:--Franz. Z., nine years old, and Caroline
Z., eight years old, were poisoned by their stepfather with spirit of 67
per cent. strength taken in small quantities by each--at first by
persuasion, and the remainder administered by force. About one-eighth of
a pint is said to have been given to each child. Both vomited somewhat,
then lying down, stertorous breathing at once came on, and they quickly
died. The autopsy, three days after death, showed dilatation of the
pupils; _rigor mortis_ present in the boy, not in the girl; and the
membranes of the brain filled with dark fluid blood. The smell of
alcohol was perceptible on opening the chest; the mucous membrane of the
bronchial tubes and gullet was normal, both lungs œdematous, the fine
tubes gorged with a bloody frothy fluid, and the mucous membrane of the
whole intestinal canal was reddened. The stomach was not, unfortunately,
examined, being reserved for chemical analysis. The heart was healthy;
the pericardium contained some straw-coloured fluid. Chemical analysis
gave an entirely negative result, which must have been from insufficient
material having been submitted to the analyst, for I cannot see how the
vapours of alcohol could have been detected by the smell, and yet have
evaded chemical processes.
In a case related by Taylor, a child, seven years old, died from some
quantity of brandy, probably about 113·4 c.c. (4 ozs.), which would be
equal to at least 56·7 c.c. (2 ozs.) of absolute alcohol. From other
cases in which the quantity of absolute alcohol can be, with some
approximation to the truth, valued, it is evident that, for any child
below ten or twelve, quantities of from 28·3 to 56·6 c.c. (1-2 ozs.) of
absolute alcohol contained in brandy, gin, &c., would be a highly
dangerous and probably fatal dose; while the toxic dose for adults is
somewhere between 71·8-141·7 c.c. (2·5-5 ozs.).
§ 161. =Symptoms.=--In the cases of rapid poisoning by a large dose of
alcohol, which alone concern us, the preliminary, and too familiar
excitement of the drunkard, may be hardly observable; but the second
stage, that of depression, rapidly sets in; the unhappy victim sinks
down to the ground helpless, the face pale, the eyes injected and
staring, the pupils dilated, acting sluggishly to light, and the skin
remarkably cold. Fräntzel[150] found, in a case in which the patient
survived, a temperature of only 24·6° in the rectum, and in that of
another person who died, a temperature of 23·8°. The mucous membranes
are of a peculiar dusky blue; the pulse, which at first is quick, soon
becomes slow and small; the respiration is also slowed, intermittent,
and stertorous; there is complete loss of consciousness and motion; the
breath smells strongly of the alcoholic drink, and if the coma continues
there may be vomiting and involuntary passing of excreta. Death
ultimately occurs through paralysis of the respiratory centres.
Convulsions in adults are rare, in children frequent. Death has more
than once been immediately caused, not by the poison, but by accidents
dependent upon loss of consciousness. Thus food has been sucked into the
air-tubes, or the person has fallen, so that the face was buried in
water, ordure, or mud; here suffocation has been induced by mechanical
causes.
[150] _Temperaturerniedrigung durch Alcoholintoxication, Charité
Annalen_, i. 371.
A remarkable course not known with any other narcotic is that in which
the symptoms remit, the person wakes up, as it were, moves about and
does one or more rational acts, and then suddenly dies. In this case
also, the death is not directly due to alcohol, but indirectly--the
alcohol having developed œdema, pneumonia, or other affection of the
lungs, which causes the sudden termination when the first effect of the
poison has gone off. The time that may elapse from the commencement of
coma till death varies from a few minutes to days; death has occurred
after a quarter of an hour, half an hour, and an hour. It has also been
prolonged to three, four, and six days, during the whole of which the
coma has continued. The average period may, however, be put at from six
to ten hours.
§ 162. =Post-mortem Appearances.=--Cadaveric rigidity lasts tolerably
long. Casper has seen it still existing nine days after death, and
Seidel[151] seven days (in February). Putrefaction is retarded in those
cases in which a very large dose has been taken, but this is not a very
noticeable or constant characteristic. The pupils are mostly dilated.
The smell of alcohol should be watched for; sometimes it is only present
in cases where but a short time has elapsed between the taking of the
poison and death; putrefaction may also conceal it, but under favourable
circumstances, especially if the weather is cold, the alcoholic smell
may remain a long time. Alcohol may cause the most intense redness and
congestion of the stomach. The most inflamed stomach I ever saw, short
of inflammation by the corrosive poisons, was that of a sailor, who died
suddenly after a twenty-four hours’ drinking bout: all the organs of the
body were fairly healthy, the man had suffered from no disease; analysis
could detect no poison but alcohol; and the history of the case,
moreover, proved clearly that it was a pure case of alcoholic poisoning.
[151] Seidel, Maschka’s _Handbuch_, Bd. ii. p. 380.
In a case related by Taylor, in which a child drank 4 ozs. of brandy and
died, the mucous membrane of the stomach presented patches of intense
redness, and in several places was thickened and softened, some portions
being actually detached and hanging loose, and there were evident signs
of extravasations of blood. The effect may not be confined to the
stomach, but extend to the duodenum and even to the whole intestinal
canal. The blood is generally dark and fluid, and usually the contents
of the skull are markedly hyperæmic, the pia very full of blood, the
sinuses and plexus gorged; occasionally, the brain-substance shows signs
of unusual congestion; serum is often found in the ventricles. The great
veins of the neck, the lungs, and the right side of the heart, are very
often found full of blood, and the left side empty. Œdema of the lungs
also occurs with tolerable frequency. The great veins of the abdomen are
also filled with blood, and if the coma has been prolonged, the bladder
will be distended with urine. A rare phenomenon has also been
noticed--namely, the occurrence of blebs on the extremities, &c., just
as if the part affected had been burnt or scalded. Lastly, with the
changes directly due to the fatal dose may be included all those
degenerations met with in the chronic drinker, provided the case had a
history of previous intemperance.
§ 163. =Excretion of Alcohol.=--Alcohol, in the diluted form, is quickly
absorbed by the blood-vessels of the stomach, &c., and circulates in the
blood; but what becomes of it afterwards is by no means settled. I think
there can be little doubt that the lungs are the main channels through
which it is eliminated; with persons given up to habits of intemperance,
the breath has constantly a very peculiar ethereal odour, probably
dependent upon some highly volatile oxidised product of alcohol.
Alcohol is eliminated in small proportion only by the kidneys.
Thudichum, in an experiment[152] by which 4000 grms. of absolute alcohol
were consumed by thirty-three men, could only find in the collected
urine 10 grms. of alcohol. The numerous experiments by Dupré also
establish the same truth, that but a fraction of the total alcohol
absorbed is excreted by the kidneys. According to Lallemand, Perrin, and
Duroy the content of the brain in alcohol is more than that of the
other organs. I have found also that the brain after death has a
wonderful attraction for alcohol, and yields it up at a water-heat very
slowly and with difficulty. In one experiment, in which a finely-divided
portion of brain, which had been soaking in alcohol for many weeks, was
submitted to a steam heat of 100°, twenty-four hours’ consecutive
heating failed to expel every trace of spirit.
[152] See Thudichum’s _Pathology of the Urine_, London, 1877, in which
both his own and Dr. Dupré’s experiments are summarised.
It is probable that true alcoholates of the chemical constituents of the
brain are formed. In the case of vegetable colloidal bodies, such, for
example, as the pulp of cherries, a similar attraction has been
observed, the fruit condensing, as it were, the alcohol in its own
tissues, and the outer liquid being of less alcoholic strength than that
which can be expressed from the steeped cherries. Alcohol is also
excreted by the sweat, and minute fractions have been found in the
fæces.
§ 164. =Toxicological Detection of Alcohol= (see “Foods,” pp.
406-419).--The living cells of the body produce minute quantities of
alcohol, as also some of the bacteria normally inhabiting the small
intestine produce small quantities of alcohol, and it is often found in
traces in putrefying fluids. Hence, mere qualitative proofs of the
presence of alcohol are insufficient on which to base an opinion as to
whether alcohol had been taken during life or not, and it will be
necessary to estimate the quantity accurately by some of the processes
detailed in “Foods,” p. 409, _et seq._ In those cases in which alcohol
is found in quantity in the stomach, there can, of course, be no
difficulty; in others, the whole of the alcohol may have been absorbed,
and chemical evidence, unless extremely definite, must be supplemented
by other facts.
2. AMYLIC ALCOHOL.
§ 165. =Amylic Alcohol=--_Formula_, C₅H₁₁HO.--There is more than one
amylic alcohol according to theory; eight isomers are possible, and
seven are known. The amylic alcohols are identical in their chemical
composition, but differ in certain physical properties, primary
amylic alcohol boiling at 137°, and iso-amyl alcohol at 131·6°. The
latter has a specific gravity of ·8148, and is the variety produced
by fermentation and present in fusel oil.
§ 166. The experiments of Eulenberg[153] on rabbits, Cross[154] on
pigeons, Rabuteau[155] on frogs, and Furst on rabbits, with those of
Sir B. W. Richardson[156] on various animals, have shown it to be a
powerful poison, more especially if breathed in a state of vapour.
[153] _Gewerbe Hygiene_, 1876, p. 440.
[154] _De l’Alcohol Amylique et Méthyl sur l’Organisme (Thèse)_,
Strasburg, 1863.
[155] “Ueber die Wirkung des Aethyl, Butyl u. Amyl Alcohols,” _L’Union_,
Nos. 90, 91, 1870. Schmidt’s _Jahrb._, Bd. 149, p. 263.
[156] _Trans. Brit. Association_, 1864, 1865, and 1866. Also, _Brit. and
Foreign Med. Chir. Rev._, Jan. 7, 1867, p. 247.
Richardson, as the result of his investigations, considers that amyl
alcohol when breathed sets up quite a peculiar class of symptoms
which last for many hours, and are of such a character, that it
might be thought impossible for the animal to recover, although they
have not been known to prove fatal. There is muscular paralysis with
paroxysms of tremulous convulsions; the spasms are excited by
touching the animal, breathing upon it, or otherwise subjecting it
to trifling excitation.
§ 167. Hitherto, neither the impure fusel oil, nor the purer
chemical preparation, has had any toxicological importance. Should
it be necessary at any time to recover small quantities from organic
liquids, the easiest way is to shake the liquid up with chloroform,
which readily dissolves amylic alcohol, and on evaporation leaves it
in a state pure enough to be identified. Amyl alcohol is identified
by the following tests:--(1) Its physical properties; (2) if warmed
with twice its volume of strong sulphuric acid, a rose or red colour
is produced; (3) heated with an acetate and strong sulphuric acid,
_amyl acetate_, which has the odour of the jargonelle pear, is
formed; (4) heated with sulphuric acid and potassic dichromate,
valeric aldehyde is first produced, and then valeric acid is formed;
the latter has a most peculiar and strong odour.
§ 168. =Amyl Nitrite, Iso-amyl Ester Nitrite= (C₅H₁₁NO₂).--Boiling
point 97° to 99°, specific gravity ·877. Amyl nitrite is a limpid,
and, generally, slightly yellow liquid; it has a peculiar and
characteristic odour. On heating with alcoholic potash, the products
are nitrite of potash and amylic alcohol; the amylic alcohol may be
distilled off and identified. The presence of a nitrite in the
alkaline solution is readily shown by the colour produced, by adding
a few drops of a solution of meta-phenylenediamine.
Sir B. W. Richardson and others have investigated the action of amyl
nitrite, as well as that of the acetate and iodide; they all act in
a similar manner, the nitrite being most potent. After absorption,
the effects of amyl nitrite are especially seen on the heart and
circulation: the heart acts violently, there is first dilatation of
the capillaries, then this is followed by diminished action of the
heart and contraction of the capillaries.
According to Richardson, it suspends the animation of frogs. No
other substance known will thus suspend a frog’s animation for so
long a time without killing it. Under favourable circumstances, the
animal will remain apparently dead for many days, and yet recover.
Warm-blooded animals may be thrown by amyl nitrite into a cataleptic
condition. It is not an anæsthetic, and by its use consciousness is
not destroyed, unless a condition approaching death be first
produced. When this occurs there is rarely recovery, the animal
passes into actual death.
=Post-Mortem Appearances.=--If administered quickly, the lungs and
all the other organs are found blanched and free from blood, the
right side of the heart gorged with blood, the left empty, the brain
being free from congestion. If administered slowly, the brain is
found congested, and there is blood both on the left and right sides
of the heart.
IV.--Ether.
§ 169. =Ether, Ethylic Ether, Ethyl Oxide,= (C₂H₅)₂O.--Ethylic ether is
a highly mobile liquid of peculiar penetrating odour and sweetish
pungent taste. It is perfectly colourless, and evaporates so rapidly,
that when applied in the form of spray to the skin, the latter becomes
frozen, and is thus deprived of sensibility.
Pure ether has a density of ·713, its boiling-point is 35°, but
commercial samples, which often contain water (1 part of water is
soluble in 35 of ether), may have a higher gravity, and also a higher
boiling-point. The readiest way to know whether an ether is anhydrous or
not, is to shake it up with a little carbon disulphide. If it is
hydrous, the mixture is milky. Methylated ether is largely used in
commerce; its disagreeable odour is due to contamination by methylated
compounds; otherwise the ether made from methylated spirit is ethylic
ether, for methylic ether is a gas which escapes during the process.
Hence the term “methylated” ether is misleading, for it contains no
methylic ether, but is essentially a somewhat impure ethylic ether.
§ 170. =Ether as a Poison.=--Ether has but little toxicological
importance. There are a few cases of death from its use as an
anæsthetic, and a few cases of suicide. Ether is used by some people as
a stimulant, but ether drinkers are uncommon. It causes an intoxication
very similar to that of alcohol, but of brief duration. In a case of
chronic ether-taking recorded by Martin,[157] in which a woman took
daily doses of ether for the purpose of allaying a gastric trouble, the
patient suffered from shivering or trembling of the hands and feet,
muscular weakness, cramp in the calves of the legs, pain in the breast
and back, intermittent headaches, palpitation, singing in the ears,
vomitings, and wakefulness; the ether being discontinued, the patient
recovered. In one of Orfila’s experiments, half an ounce of ether was
administered to a dog. The animal died insensible in three hours. The
mucous membrane of the stomach was found highly inflamed, the
inflammation extending somewhat into the duodenum; the rest of the canal
was healthy. The lungs were gorged with fluid blood.
[157] Virchow’s _Jahresber._, 1870.
§ 171. =Fatal Dose.=--The fatal dose of ether, when taken as a liquid,
is not known. 4 grms. (1·28 drms.) cause toxic symptoms, but the effect
soon passes. Buchanan has seen a brandy-drinker consume 25 grms. (7
drms.) and yet survive. It is probable that most adults would be killed
by a fluid ounce (28·4 c.c.).
§ 172. =Ether as an Anæsthetic.=--Ether is now much used as an
anæsthetic, and generally in conjunction with chloroform. Anæsthesia by
ether is said to compare favourably with that produced by chloroform. In
92,000 cases of operations performed under ether, the proportion dying
from the effects of the anæsthetic was only ·3 per 10,000 (Morgan),
while chloroform gives a higher number (see p. 149). The mortality in
America, again, from a mixture of chloroform and ether in 11,000 cases
is reckoned at 1·7 per 10,000; but this proportion is rather above some
of the calculations relative to the mortality from pure chloroform, so
that the question can hardly be considered settled. The symptoms of
ether narcosis are very similar to those produced by chloroform. The
chief point of difference appears to be its action on the heart. Ether,
when first breathed, stimulates the heart’s action, and the
after-depression that follows never reaches so high a grade as with
chloroform. Ether is said to kill by paralysing the respiration, and in
cases which end fatally the breathing is seen to stop suddenly:
convulsions have not been noticed. The _post-mortem_ appearances, as in
the case of chloroform, are not characteristic.
§ 173. =Separation of Ether from Organic Fluids, &c.=--Despite the low
boiling-point of ether, it is by no means easy to separate it from
organic substances _so as to recover the whole of the ether present_.
The best way is to place the matters in a flask connected with an
ordinary Liebig’s condenser, the tube of the latter at its farther end
fitting closely into the doubly perforated cork of a flask. Into the
second perforation is adapted an upright tube about 2 feet long, which
may be of small diameter, and must be surrounded by a freezing mixture
of ice and salt. The upper end of this tube is closed by a thistle-head
funnel with syphon, and in the bend of the syphon a little mercury
serves as a valve. Heat is now applied to the flask by means of a
water-bath, and continued for several hours; the liquid which has
distilled over is then treated with dry calcic chloride and redistilled
exactly in the same way. To this distillate again a similar process may
be used, substituting dry potassic carbonate for the calcic chloride. It
is only by operating on these principles that the expert can recover in
an approximate state of anhydrous purity such a volatile liquid. Having
thus obtained it pure, it may be identified (1) by its smell, (2) by its
boiling-point, (3) by its inflammability, and (4) by its reducing
chromic acid. The latter test may be applied to the vapour. An asbestos
fibre is soaked in a mixture of strong sulphuric acid and potassic
dichromate, and then placed in the tube connected with the flask--the
ethereal (or alcoholic) vapour passing over the fibre, immediately
reduces the chromic acid to chromic oxide, with the production of a
green colour.
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 ½ 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.
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.
[Illustration]
[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.