ether for the prevention of pain on this side of the Atlantic, Dr.
Simpson of Edinburgh administered the vapour in a case of labour, and
ascertained that it was capable of removing the sufferings of the
patient without interfering with the process of parturition.
Etherization was soon afterwards employed in the reduction of
strangulated hernia and dislocations of the femur and humerus, some of
them of long standing. It was also used with advantage in neuralgia,
tetanus, and the convulsions of infants, and it became more and more
general in surgical operations.
No great improvement in the practice of medicine was probably ever
established so readily as the inhalation of ether for the prevention of
pain. Yet it met with stout opposition in certain quarters, and when a
serious operation in which ether had been used terminated unfavourably,
there were those who attributed the patient’s death to the new practice,
although numerous other patients had sunk in exactly the same manner
long before ether was used. In one of these cases a coroner’s inquest
was held, and the jury returned a verdict that the death of the deceased
was caused by the inhalation of ether, although the patient had not even
been made insensible by it, had felt all the pain of the operation,
which was retarded by her struggles, and did not die till the third day.
Notwithstanding a certain amount of opposition and mistrust, the
inhalation of ether was becoming more general in the course of the year
1847, and there is every reason to conclude that it would very soon have
obtained the complete confidence of the medical profession and the
public, had it not been for circumstances which must next be considered.
A medicine called chloric ether has been in use since 1831. It consists
of a solution of chloroform in spirits of wine. It is somewhat variable
in strength, but usually contains about twelve per cent. of its volume
of chloroform. Dr. Henry Jacob Bigelow of Boston tried this by
inhalation, as well as other substances, when Dr. Morton first used
sulphuric ether, but he did not succeed with it in causing insensibility
to pain. Mr. Jacob Bell of London tried the chloric ether in the
beginning of 1847, and succeeded in causing insensibility with it in
some cases.[34] After this time the chloric ether was exhibited
occasionally in St. Bartholomew’s and the Middlesex hospitals, and in
the private practice of Mr. Lawrence, but it did not come into general
use, owing to its expense, and its frequently failing to cause
insensibility.
The relation of chloroform to chloric ether is exactly the same as that
of opium to laudanum, and no one acquainted with this circumstance could
doubt for a moment that chloroform inhaled alone would produce the
effects which it did when inhaled from its solution in spirit; the only
uncertainty about the matter that could possibly exist would be whether
it might not be too strong for use in its undiluted state.
The true nature of the so-called chloric ether was, however, known to
very few persons. It did not enter into the pharmacopœias, and it was
mentioned in very few of the works on materia medica. I examined a
specimen of it, and found that its properties when inhaled were due to a
volatile body containing chlorine, which evaporated first, leaving a
great quantity of spirits of wine behind. I concluded that the volatile
body was hydrochloric ether, and as this article is so volatile that it
exists in the form of gas except in comparatively cold weather, and
consequently could not be conveniently used for inhalation, I did not
consider the matter any further. M. Flourens had indeed experimented on
animals with undiluted chloroform, but was so struck with its great and
dangerous power, that he was far from recommending its use in surgical
practice.
It was left for Dr. Simpson of Edinburgh, who had already the merit of
having discovered the use of inhalation in midwifery, to be the first to
administer chloroform in an undiluted state, and to recommend it
successfully for general use. Mr. Waldie, of the Apothecaries’ Hall of
Liverpool, first mentioned chloroform to Dr. Simpson, as the latter
states in a foot-note to his first pamphlet on the subject. Mr. Waldie
has given the following account of the circumstance in a pamphlet on
chloroform.[35]
“When in Scotland, in October last, Dr. Simpson introduced the subject
to me, inquiring if I knew anything likely to answer. Chloric ether was
mentioned during the conversation; and, being well acquainted with its
composition, and with the volatility, agreeable flavour, and medicinal
properties of the chloroform, I recommended him to try _it_, promising
to prepare some after my return to Liverpool, and to send it to him.
Other engagements and various impediments prevented me from doing this
so soon as I should have wished; and in the meantime Dr. Simpson, having
procured some in Edinburgh, obtained the results which he communicated
to the Medico-Chirurgical Society of Edinburgh on the 10th of November,
and which he published in a pamphlet entitled—‘Notice of a New
Anæsthetic Agent as a Substitute for Sulphuric Ether in Surgery and
Midwifery.’”
Dr. Simpson’s first experiments with chloroform were made in the early
part of November 1847, and his pamphlet on the subject, which was
published on the 15th of that month, had a wide circulation, and created
great interest. Chloroform was immediately used everywhere to a greater
extent than ether had been. An impression became very prevalent that
chloroform was safer than ether. This impression arose rather from the
general tenour of Dr. Simpson’s essay than from any direct statement,
for he had not treated on this point.
The great strength of chloroform as compared with ether, and the extreme
care required in its use, were indeed soon pointed out;[36] these
precautions, however, attracted but little attention till the first
death from chloroform occurred near Newcastle on the 28th January, 1848.
Ether was exhibited by inhalation during eleven months in Europe, and
about sixteen months in America, before chloroform was introduced.
During all this time no death was occasioned by its use, if we except
one at Auxerre in France, which appeared to be occasioned by want of
air, owing to an imperfect inhaler, and not to the effect of ether.
Chloroform had only been employed between two and three months when the
above mentioned death occurred, and this was soon followed by others in
nearly all parts of the world. These accidents have prevented many
persons from inhaling chloroform, and they have prevented a still
greater number from enjoying that freedom from anxiety and apprehension
before an operation, which ought to be one of the greatest advantages of
any plan for preventing pain. As chloroform possesses advantages over
ether, in being more convenient and less disagreeable, it continues to
be used, to the exclusion of the latter agent, in most parts of the
world. In the Massachusetts General Hospital, however, where sulphuric
ether was first employed, it was resumed three or four years ago, and
the use of chloroform was prohibited by the governors, on account of two
accidents from it. Ether is also employed out of the hospital, both in
surgical and obstetric practice, in Boston and the neighbourhood; and I
have been informed that this is also the case in Philadelphia, whilst in
the state of New York both chloroform and ether are employed. I learned
last year that ether was the agent employed for causing insensibility at
Naples and at Lyons.
Several volatile substances have been tried in a few cases with the
effect of causing insensibility, since the introduction of chloroform,
but none of them came into use except amylene, which was first employed
by me in King’s College Hospital in November 1856, after I had made
several experiments on animals with it, and inhaled small quantities of
it myself. I have administered it in a great number of operations
already, and find it to possess certain advantages over chloroform in
the greater number of cases. Although it has not yet been generally
employed in this country, it has been used extensively in Paris,
Strasbourg, Lyons, and other places on the continent, with very
favourable results.
It is not improbable that, amongst the multitudes of new bodies which
chemistry makes known every year, some agent may be found superior to
those hitherto used; and besides the great practical advantages which
are directly derived from the discovery of inhalation for the prevention
of pain, the method of breathing medicinal substances in the gaseous
state offers great facilities for the investigation of their effects,
and cannot fail to hasten the time when the mode of action of medicines
will be a branch of exact knowledge.
ON THE
INHALATION OF CHLOROFORM, ETC.
GENERAL REMARKS ON INHALATION.
Inhalation is simply the act of breathing, or at least so much of it as
consists of inspiring, or drawing the air into the lungs. The term is
usually applied when any medicinal substance is added to the air which
the patient breathes, and the process is altogether different from that
called “smoking,” as practised by the nations of western Europe and of
America, where the fumes of tobacco are merely drawn into the mouth and
puffed out again. The eastern nations, however, always inhale when they
smoke, as was stated before (page 12). This process of inhaling smoke,
as I first witnessed it in a gentleman connected with one of the eastern
embassies to this metropolis, is very instructive, as showing that the
lungs become emptied of their contents by three rather full expirations
and inspirations. When this gentleman took the cigar from his mouth to
speak, the smoke could be seen issuing thickly with each word till there
was a momentary pause as he took a fresh inspiration, then the smoke
could be seen issuing with each word as before, only not so thick, and
after another inspiration, the smoke could be still perceived in the
expired air, but in a very diluted state; but after a third inspiration,
it could no longer be seen till he had resumed the cigar.
The following are the chief reasons for resorting to inhalation.
1. Certain agents, as nitrous oxide and oxygen, being permanently in the
gaseous form, cannot be administered in any other way.
2. By taking advantage of the immense surface of the air-cells of the
lungs for absorption, a more sudden and profound effect may be produced
by medicine than it would be safe, or, in some cases, even possible to
produce in any other way. It is to this circumstance, and to the
rapidity with which certain volatile medicines exhale in the breath, and
leave the patient free from their effects, that the power of preventing
the pain of surgical operations is due.
3. Many medicines which have a disagreeable taste—as turpentine,
creasote, and camphor—are not unpleasant when inhaled in the form of
vapour; and the process of digestion is less interfered with than by
taking them into the stomach.
4. Medicines, such as benzoic acid, and some of the gum-resins, which
are believed to exert a local action on the mucous membrane of the
air-passages, may be expected to have a greater effect when inhaled,
than when they are taken into the stomach in the same doses, and reach
the lungs only through the circulation.
5. Some agents, as chlorine and ammonia, have a local action when
inhaled, which they could not exert if exhibited in any other way.
In every kind of inhalation, the breathing should be allowed to go on
freely, and in the natural way.
Medicines may be inhaled either at the ordinary temperature, or with the
aid of artificial heat; and in the latter case they may be breathed with
the addition of vapour of water, or with only so much of it as is
naturally present in the atmosphere. The medicines in use for the
prevention of severe pain, are always inhaled at the ordinary
temperature.
CHLOROFORM.
_History and Composition._ Chloroform was first made in 1831 by two
chemists who operated independently of each other. The liquid, which is
formed by the union of equal volumes of chlorine and olefiant gas, and
which is usually called Dutch liquid, was named chloric ether by Dr.
Thos. Thomson (_System of Chemistry_, 6th ed., 1820). In consequence of
a statement in Silliman’s _Elements of Chemistry_, that the alcoholic
solution of this chloric ether was useful in medicine as a diffusible
stimulant, Mr. Guthrie, an American chemist, attempted an easy method of
obtaining it.[37] He distilled together chloride of lime and alcohol,
and he considered that the product he had obtained was an alcoholic
solution of the chloric ether of Dr. Thomson,[38] and it is still used
in medicine under that name. About the same time, M. Soubeiran distilled
together the above ingredients in France, and analysed the chloroform
which he obtained. His analysis, which was incorrect, led him to name
the liquid bichloric ether.[39] In 1832, Liebig examined the liquid
which has been since named chloroform, but as he failed to detect the
hydrogen which it contains, he called the liquid chloride of carbon,[40]
a name which its alcoholic solution occasionally bore afterwards when
used as a medicine. In 1831, Dumas examined this liquid. He proved that
Soubeiran and Liebig had not obtained it pure, or had been incorrect in
their analysis.[41] He showed that it consists of two atoms carbon, one
atom hydrogen, and three atoms chlorine.
Dumas gave the name of chloroform to the liquid, on account of the
relation it bears in composition to formic acid, which consists of two
atoms carbon, one hydrogen, and three oxygen.[42] Liebig, who, in common
with other chemists, admits the accuracy of Dumas’ analysis, has
proposed the name of perchloride of formyle.[43] He supposes that the
carbon and hydrogen which enter, in the same definite proportion, into
numerous compounds, form a base which he calls formyle; and although
this base has never been obtained in a separate form, its existence is
well supported by analogy, and the term formyle is useful in assisting
the memory to retain the composition of a number of substances. For all
practical purposes, however, the medicine we are considering is likely
to go by the name of chloroform. In the last edition of the London
Pharmacopœia, the article has received a name intermediate between the
other two. It is called chloroformyl, a name which departs from the
brevity of the word chloroform, without having the merit of expressing
the chemical constitution of the substance. I believe that no one uses
the word chloroformyl; not even the Fellows of the College of Physicians
in their individual capacity.
_Mode of Preparation._ Chloroform can be obtained in various ways, but
the most convenient process, and the one which yields it in greatest
purity, is that alluded to above, by which it was first procured. The
following are the directions in the London Pharmacopœia for making it.
“Take of chlorinated lime, lb. iv; rectified spirit, Oss; water, Ox;
chloride of calcium, broken in pieces, ʒj. Put the lime first mixed with
the water into a retort, and add the spirit to them, so that the mixture
may fill only the third part of the retort. Then heat them in a
sand-bath, and as soon as ebullition begins, withdraw the heat as
quickly as possible, lest the retort should be broken by the sudden
increase of heat. Let the liquid distil into the receiver so long that
there may be nothing which subsides, the heat being reapplied if
necessary. To the distilled liquid add a quarter of the water, and shake
them all well together. Carefully separate the heavier portion which
subsides, and add the chloride to it, and frequently shake them for an
hour. Lastly, let the liquid distil again from a glass retort into a
glass receiver.”[44]
Some manufacturers of chloroform prefer to rectify it from dry carbonate
of potassa, since they consider that it is liable to get an acid
reaction from decomposition of the chloride of calcium, when it is
distilled from that substance. The truth is, however, that there is very
little occasion to use either of these substances; for the small
quantity of water which chloroform can hold in solution is of no
consequence.
_Chemical and Physical Properties._ Chloroform is a clear colourless
liquid, having a hot and intensely sweet taste. It is not inflammable,
but when paper moistened with it is introduced into the flame of a
candle, it is destroyed with the evolution of smoke and chlorine gas. It
is just half as heavy again as distilled water. Its specific gravity was
formerly stated to be 1·483, but the liquid used for inhalation of late
years has been heavier than this. I find that pure chloroform, when
saturated with water, has a specific gravity of 1·500 at 60° Fah.; and
after agitating it with sulphuric acid, to deprive it of the water, the
specific gravity is 1·503. The amount of water that chloroform can hold
in solution is only one part in from 200 to 300; and when this is
separated by oil of vitriol, the chloroform is liable to undergo
spontaneous decomposition.[45]
Chloroform is soluble in alcohol and ether in all proportions, but it is
very sparingly soluble in water. It has been said to require 2000 parts
of water for its solution, but this is an error. As the solubility of
this and similar medicines in watery fluids has a very important
connexion with their physiological action, I took great pains to
ascertain the solubility of chloroform correctly. By admitting small
quantities of water into graduated jars containing chloroform vapour, I
was able to ascertain that chloroform is soluble in about 288 times its
volume of water. Chloroform is itself an active solvent of many bodies;
dissolving camphor, caoutchouc, gutta percha, wax, resin, iodine, and
some other substances very readily. It is a very mobile liquid, and when
dropped from the lip of a small phial, the drops are very small. There
are three drops to a grain of the liquid, and as a minim of it weighs a
grain and a half, there are nine drops in two minims. Consequently
persons should not speak indiscriminately of drops and minims, as they
sometimes do, when talking of chloroform.
_Adulterations._ The odour of chloroform is by no means disagreeable.
The only liquids that resemble it in smell are Dutch liquid and the
chlorinated products of hydrochloric ether, but as they are much more
difficult to prepare than chloroform, they are not likely to be
substituted for it, or used for its adulteration. The smell of
chloroform is therefore a good criterion of its purity and identity.
When dropped on the hand, it should quickly evaporate, leaving not the
least moisture or smell behind. If a disagreeable odour remains on the
hand after the evaporation of the chloroform, it has probably been made
from impure spirit, or even from wood spirit or acetone, and is unfit
for medicinal use.[46] When chloroform becomes decomposed from any
cause, it acquires a greenish-yellow colour, and gives off chlorine and
hydrochloric acid, so that the alteration is at once apparent. When
chloroform is pure it has no reaction on test-paper, but is quite
neutral. The best way to detect a small quantity of hydrochloric acid in
it, is to moisten a slip of blue litmus paper with distilled water, and
hold it just within the neck of the bottle exposed to the vapour. If
sulphuric acid should be present, it may be discovered by agitating the
chloroform with distilled water, and adding nitrate of baryta.
The only article that can be mixed with chloroform without altering its
appearance and smell is alcohol. This can be detected by the reduction
it occasions in the specific gravity of the chloroform; or, if it be
present in any considerable quantity, it may be discovered by adding
water to a little of the chloroform in a graduated tube or measure, when
a diminution of its volume takes place, owing to the water abstracting
the alcohol. The chloroform also acquires a milky opacity under these
circumstances. M. Miahle[47] speaks of the milky opacity of the
chloroform on the addition of water as a very delicate test of the
presence of alcohol; but I find that it requires upwards of two per
cent. of alcohol to cause this appearance on the addition of water.
It has been asserted, and often repeated, that the presence of alcohol
in chloroform causes it to have caustic properties, and makes its vapour
unusually irritating. I have never seen any evidence of this, although I
have had hundreds of opportunities of witnessing the action of
chloroform mixed with spirit. Under certain circumstances, it is
advisable to dilute chloroform with alcohol previous to its
administration, as will be explained hereafter.
The chloroform I have met with in London has always been sufficiently
pure for inhalation, except in a few cases where a small quantity had
become decomposed, probably from having been left a long time exposed to
strong daylight. In these instances, its altered appearance generally
prevented its being used. I am not aware of serious consequences having
arisen anywhere from the impurity or adulteration of chloroform. A case
occurred in the London Hospital, where cough and a feeling of
suffocation were caused by hydrochloric acid with which the chloroform
was contaminated, but the inhalation was discontinued, and no ill
consequences resulted.[48]
Chloroform should be kept in well-stoppered bottles, and protected from
the light. It boils at 140 Fah. under the ordinary pressure of the
atmosphere. It is consequently one of the most volatile liquids employed
in medicine, with the exception of sulphuric ether and amylene.
_The Vapour of Chloroform_ is more than four times as heavy as
atmospheric air. It has a specific gravity of 4·2 at 60° Fah. Under
ordinary circumstances, the vapour of chloroform has of course no
separate existence, but is always mixed with air. It can exist in a pure
state only when the temperature is raised to 140° or upwards; or when
the pressure of the atmosphere is in a great measure removed by the
air-pump. The quantity of vapour of chloroform that the air will hold in
solution at different temperatures, under the ordinary pressure of the
atmosphere, depends on the elastic force of the vapour at these
temperatures. It is governed by a law precisely analogous to that which
determines the amount of watery vapour which air will hold in solution.
The following table shows the result of experiments I made to determine
the quantity of vapour of chloroform that 100 cubic inches of air will
take up, and retain in solution, at various temperatures.
Temp. Fah. Cubic inches.
40° 7
45 8
50 9
55 11
60 14
65 19
70 24
75 29
80 36
85 44
90 55
In the above table, the air is a constant quantity of 100 cubic inches
which becomes expanded to 107, and so on; but it may be convenient to be
able to view at a glance the quantity of vapour in 100 cubic inches of
the saturated mixture of vapour and air, at different temperatures, and
in the table which follows the figures are so arranged as to show this.
Temp. Fah. Air. Vapour.
40° 94 6
45 93 7
50 92 8
55 90 10
60 88 12
65 85 15
70 81 19
75 78 22
80 74 26
85 70 30
90 65 35
As the effects of chloroform when inhaled depend entirely on the
quantity of vapour present in the air which the patient breathes, the
effect of temperature on its volatility is of great practical
importance. The air, it is true, does not become fully saturated with
vapour during the process of inhalation, but the effects of temperature
are relatively as great. If, for instance, a person inhales chloroform
from a handkerchief or an inhaler, in such a way that the air he
breathes shall be half saturated with the vapour, then supposing the
temperature of the apartment, the handkerchief, etc., to be 50°, the air
he breathes will contain 4 per cent.; but if the temperature be 70°, the
air will contain 9·5 per cent. of the vapour.