shown in the first experiments which were made with this substance,
viz., those by Dr. R. M. Glover in 1842.[58] In animals which were
killed by injecting it into the jugular vein, the irritability of the
heart was found to be destroyed, whilst this organ retained its
irritability in those that were killed by the injection of chloroform
into the arteries, stomach, or peritoneum. I have frequently arrested
the action of the heart remaining in animals which were opened
immediately after death, by blowing the vapour of chloroform on it; and
I ascertained by some experiments on frogs, that the motion of the heart
can be arrested by an amount of chloroform somewhat greater than
suffices to suspend the respiration. As absorption of chloroform vapour
is continued by the skin of these animals after the respiratory
movements have ceased, they can be exposed to the vapour till the action
of the heart is suspended by its direct influence.
_Experiment 26._ Four and a half grains of chloroform were introduced
into a jar containing 600 cubic inches, being three-quarters of a grain
to each 100 cubic inches, and, the vapour having been equally diffused,
two frogs were put in. They tried to climb up the side of the jar, as if
wishing to make their escape, and one or the other occasionally ceased
to breathe for a minute or two, probably from disliking the vapour, but
commenced to breathe again. In about five minutes the efforts to escape
ceased, and they only moved to adjust their equilibrium when the jar was
disturbed. They were now breathing regularly, and continued to do so
till about ten minutes after their introduction, when all voluntary
power ceased, and the breathing began to be performed only at intervals.
They were allowed to remain till half an hour had elapsed, during the
last ten minutes of which time no respiratory movement was observed in
either of them. On taking them out, and laying them on their backs, the
pulsations of the heart were observed on each side of the sternum. These
pulsations were the more distinct, from the lungs being apparently
empty. I continued the experiment on these frogs, placing one of them
back again, in the course of two or three minutes, in the same jar, with
three grains of chloroform, and the other in a jar of 400 cubic inches
capacity, with five grains. They were laid on their backs, and the heart
of the former one, in air containing half a grain of chloroform to each
100 cubic inches, continued to beat distinctly and regularly, 45 times
in the minute, for four hours that it remained in the jar, and it was
not observed to breathe during the whole time, although it was watched
almost constantly. The respiration commenced again within half an hour
after its removal. In about an hour, it recovered its power of voluntary
motion, and it was not injured by the long narcotism.
The pulsations of the heart of the other frog, in air containing a grain
and a quarter of chloroform to each 100 cubic inches of air, became
slower and more feeble, and in a quarter of an hour could not be
observed. The frog was left in the jar a quarter of an hour longer, and
removed when it had been in half an hour. The under part of the thorax
was immediately opened sufficiently to expose the heart. It was
moderately full of blood, but not contracting at all, and it did not
evince the least irritability on being pricked, either at first or after
exposure to the air for some time. It is evident that the heart of this
last frog became paralysed by the absorption into the blood of more
vapour, in addition to the quantity that was sufficient to arrest the
respiration. The temperature of the room during this experiment was 65°
Fah.
The effect of chloroform on the heart of the frog is further shewn by
the next experiment.
_Experiment 27._ A frog was placed in the jar containing 600 cubic
inches, with six grains of chloroform. In twenty minutes the respiration
had ceased, but the heart continued to pulsate strongly. At the end of
three-quarters of an hour, the pulsations were more feeble, and had
diminished from 40 to 30 in the minute. An hour and five minutes from
the commencement of the experiment, no movement of the heart could be
observed. The frog was taken out of the vapour, and a portion of the
sternum and integuments removed, so as partly to expose the heart, when
it was found to be still contracting, with a very feeble undulatory
motion. This motion increased in force, and, in a quarter of an hour
after its removal, the heart was pulsating regularly and strongly, the
ventricle apparently emptying itself perfectly. When the frog had been
out twenty minutes, it was placed again in the same jar, with the same
quantity of chloroform. In about ten minutes, the heart’s action began
to fail again; and in about twenty minutes, the slightest movement could
no longer be perceived in it. The frog was immediately taken out, and
the ventricle of the heart was pricked with a needle. In a few seconds,
a slight quivering was observed,—whether the result of the prick is not
certain,—and the action of the heart became gradually reestablished as
before. It was arrested a third time by exposure to the vapour; and
although, in its third removal, the anterior extremities of the frog had
become rigid, the heart resumed its action partially, and continued to
contract feebly for three or four hours after the rigidity of death had
invaded the body and limbs of the animal. The temperature of the room
was 62° during this experiment.[59]
In the human being and all other creatures of warm blood, any vapour
which is inhaled and absorbed in the lungs passes at once to the left
side of the heart, and as the coronary arteries are the first branches
given off from the aorta, the heart must, during the process of
inhalation, be always a very little in advance of the rest of the body,
as regards the amount of vapour to which it is subjected. This, however,
is no source of danger, as regards chloroform, if the inhalation takes
place in a gradual and uniform manner; for the heart being able, as
shown by the above experiments on frogs, to bear a greater amount of
this narcotic than the brain, its action continues even after
respiration has ceased, if the vapour is added only by a little at once
to the blood, as it passes through the lungs. But if the air which the
patient breathes be too highly charged with vapour, it is easy to
understand how the sensibility of the nerves of the heart may be
paralysed, notwithstanding their power to bear somewhat more of this
agent than the brain and nerves of respiration. I calculated (p. 74) the
quantity of chloroform which would suffice to arrest respiration in the
adult of average size to be thirty-six minims, provided it were equally
diffused through the circulation; but supposing a patient breathes, at
any time, air containing ten per cent. of vapour of chloroform, a
considerable part of this might enter the lungs at a very few
inspirations, for thirty-six minims of chloroform occupy only 37·5 cubic
inches, and would be contained in 375 cubic inches of air, and might be
breathed in less than a minute; but for the whole of the blood to pass
through the lungs occupies a considerable time—I believe about four
minutes in the adult—and therefore the portion of blood which is passing
through the lungs, at the time when vapour of the above strength is
inhaled, must become much overcharged with chloroform, making every
allowance for the portion of vapour which is expired again, without
being absorbed.
I have observed the manner in which the breathing and circulation ceased
in a great number of instances, with the stethoscope applied to the
chest of the animal, when the quantity of chloroform contained in the
air it breathed was known, and have notes of the result. The animals
were chiefly cats, which would otherwise have been killed by prussic
acid, or in some other way. In every instance in which the quantity of
vapour in the air breathed by the animals was from three to six per
cent., the respiration ceased whilst the sounds of the heart were still
very distinct, as in Experiment 23, related above; in many instances the
heart continued to beat from two to three minutes after the breathing
had ceased, and, in a great number of instances, there were one or more
gasping inspirations just at the moment when the sounds of the heart
ceased. In many cases these gasping inspirations caused the action of
the heart to return, as in Experiment 23, if the animal had been
withdrawn from the chloroform; but this was not always the case; and if
the chloroform was still breathed during these gasping efforts, all
signs of life immediately ceased in every instance.
When, on the other hand, the air breathed by the animals contained eight
or ten per cent., or upwards, of vapour of chloroform, the action of the
heart was always seriously affected and rendered extremely feeble, if it
did not actually cease, at the time the breathing was arrested. In
several instances, indeed, the sounds of the heart entirely ceased
before the breathing, as in Experiment 25; and although the chloroform
was withdrawn, in this and many other experiments, the moment the heart
ceased to beat, and fresh air was drawn in by inspiratory efforts, it
very rarely had the effect of restoring the heart’s action, although
this happened so frequently when that organ had gradually ceased to act
on account of suspension of the breathing, by the effect of more diluted
vapour.
In order to see more precisely the action of the vapour of chloroform on
the heart, when not sufficiently diluted, the chest and pericardium were
opened on four occasions, in cats and a rabbit, and chloroform was
exhibited by artificial respiration. I was assisted by Mr. Peter
Marshall in these experiments, and the following is the account of one
of them.[60]
_Experiment 28._ A young rabbit, rather more than half-grown, was made
insensible by breathing air charged with four per cent. of vapour of
chloroform in a large jar. The trachea was then opened, and a tube was
introduced and tied. The lungs and heart were then exposed, by making an
incision and removing the lower half of the sternum, with the adjoining
part of the cartilages of the ribs on each side. The front of the
pericardium was also cut away, to expose the heart. Whilst these
operations were performed, artificial respiration was kept up by means
of a bladder of air attached to the tube in the trachea. The heart
contracted vigorously and quickly, and the lungs were of a light red
colour. The rabbit was beginning to show signs of returning sensibility,
when the bladder of air was changed for one containing ten per cent. of
vapour of chloroform. The bladder contained 125 cubic inches, and twelve
minims of chloroform were put in before it was filled with the bellows.
Three or four inflations of the lungs only were made, when I perceived
that the heart was beginning to be affected, and I changed the
chloroform for a bladder containing only air. These three or four
inflations of the lungs with chloroform, had the effect of causing the
right cavities of the heart to become distended with blood, and its
pulsations to become much slower. In two or three minutes, however, the
action of the heart was quite reestablished by the artificial
respiration, the pulsations being vigorous and frequent, and the
ventricles being apparently emptied at each contraction. The bladder
charged with ten per cent. of chloroform was again attached, and
artificial respiration was made with it. The right ventricle began
almost immediately to become distended; and, by the time that eight or
ten inflations of the lungs had been made, the contractions of the heart
were very slow and feeble. Artificial respiration with air was resumed,
but without the effect of restoring the action of the heart. The lungs
were observed at the time when the right ventricle was becoming
distended, and it was noticed that their colour was unchanged. They
afterwards became paler, as the artificial respiration was continued
after the ventricle had ceased to empty itself. No contractions of the
diaphragm were observed after the first inflation of the lungs with
chloroform, and the rabbit did not gasp at any time; whilst the cats
were observed to make a few gasping efforts at the time when the heart’s
action was ceasing.
The circumstance of the lungs not changing in colour at the moment when
the right ventricle was becoming distended, which was observed in the
cats as well as in the rabbit, shows that the distension arose from the
failure of the contractile power of the heart, and not from impediment
to the pulmonary circulation; for, in the latter case, the lungs would
have become congested, and of a deeper colour. In one of the cats, it
appeared to me that the left, as well as the right ventricle, was
distended with blood; but this distension of the left ventricle did not
continue.
In the Experiments 24 and 25, related above, the animals were first made
insensible by vapour of moderate strength, in order to keep them quiet
for the application of the stethoscope whilst the stronger vapour was
inhaled, but when animals are made to breathe air containing ten per
cent. or so of vapour of chloroform from the first, death takes place in
the same manner, _i. e._ by the direct action of the chloroform on the
heart. Under these circumstances the creatures die suddenly, after a
brief interval of agitation and excitement, without previous
insensibility. This is what has happened in some of the accidents from
chloroform, to be related further on; whilst in many cases death has
happened after a longer or shorter period of insensibility.
In many of the fatal cases of inhalation of chloroform the alarming
symptoms commenced whilst the patient was still inhaling, but in a
considerable number there was no sign of danger until after the
inhalation had been left off; and this is a result which may be imitated
on animals. The two following experiments, which were made at Dr.
Sibson’s on December 27th, 1849, illustrate this point.
_Experiment 29._ The subject of this experiment was a young guineapig,
about half-grown. Ten or twelve drops of chloroform were put into a
short bent metal tube, lined with bibulous paper, which formed part of
an inhaler, and one end of the tube was applied to the animal’s nose,
which closed it. The guineapig consequently breathed backwards and
forwards through the tube, which was, moreover, warm from being held in
the hand. It struggled at first, endeavouring to get away from Dr.
Sibson, who held it; but in twenty or thirty seconds it became quiet;
and observing that the conjunctiva was insensible, I withdrew the
chloroform, and the guineapig was laid on the table. We remarked that
the breathing was very slow; and scarcely had this remark been made,
when it ceased altogether, three or four inspirations only having been
made since the inhalation was left off. Dr. Sibson proceeded immediately
to open the body; but as soon as he had divided the integuments of the
chest the animal began to make some convulsive gasping inspirations,
during which the mouth was widely opened, and we observed that the
diaphragm acted alone, the ribs being pressed inwards by the atmosphere.
The heart was not contracting at all when the pericardium was first
opened; but in a few moments the auricles began to contract
rhythmically. The lungs were of a light red colour.
_Experiment 30._ Another guineapig of the same age was treated in the
same manner, except that I removed the tube from the nose for a short
time between every two or three inspirations, in order to see if I could
not make it insensible in this way without a fatal result. In half a
minute or so the animal no longer required to be held, but lay on the
table without making any resistance, the conjunctiva being still
sensible, and some motion of the limbs, apparently voluntary, remaining.
It only inhaled once after Dr. Sibson ceased to hold it, and whilst in
the state just described, and then only for two or three inspirations.
After this it appeared quite insensible, and no more chloroform was
given. It breathed at first naturally, except more slowly and gently
than before the inhalation; but the breathing became slower, and ceased
altogether about a quarter of a minute after the inhalation had been
left off. The body was opened immediately. When the pericardium was
opened, the auricles were observed to contract slightly, and the
contractions increased after their exposure to the air.
The amount of vapour in the air breathed by these two guineapigs is not
known, but there is no doubt that it was upwards of eight per cent.
FATAL CASES OF INHALATION OF CHLOROFORM.
If it were possible for a medical man to mistake or disregard the
symptoms of approaching danger, and to go on exhibiting vapour of
chloroform, diluted to a proper strength, till the death of the patient,
this event would take place slowly and gradually, as in Experiment 23,
related above, and every other experiment in which the air did not
contain more than five per cent. of vapour. The action of the heart
would survive the respiration; there would be a great tendency to
spontaneous recovery, and the patient would be easily restored by
artificial respiration, if it were performed whilst the heart was still
acting; as I have always found it to be successful in animals under
these circumstances.
In examining the recorded cases of fatal inhalation of chloroform, we
shall find, however, that they have none of them taken place in this
gradual manner; but that in all cases the fatal symptoms, if not the
actual death, have come on very suddenly. Dr. Sibson was, I believe, the
first to point out that, in the fatal cases of inhalation of chloroform,
death was caused by its paralysing the heart; but he was not at that
time aware of the physical conditions under which this agent may act
directly on the heart. In commenting on the first four deaths from
chloroform, he says:[61] “In all the four cases it is manifest that the
immediate cause of the instantaneous death lay in the heart. The heart,
influenced by the poison, ceased to contract, not from the cessation of
respiration, for the heart in asphyxia will beat from one to three
minutes after respiration has ceased, but from immediate death of the
heart. There is no doubt a combination of causes operating to destroy
the heart’s contractile power: the mental influence, the congestion in
the systemic, and that in the pulmonary capillaries, will all have a
material influence.” And further on he says: “We are obliged, then, from
the experience of these cases, to conclude, that in man the death is
usually instantaneous, and due, as every instantaneous death is, to
paralysis of the heart. In animals the death is usually due to paralysis
of the muscles of respiration. It is chiefly owing to the superior
control of the mind over the body in man, that in him the poison acts on
the heart more than in dogs.”
I had been long aware that chloroform was capable of paralysing the
heart in animals; and, indeed, that sulphuric ether would do so when it
could reach the heart in sufficient quantity;[62] and soon after Dr.
Sibson’s remarks I was able to ascertain and point out the strength of
the vapour which will produce this effect, and how one may avoid the
risk of it, by having the vapour sufficiently diluted.[63] The greater
number of experimenters who have killed animals with chloroform have
found that the action of the heart continued after the breathing ceased;
but they did not either control or ascertain the proportion which the
vapours of chloroform bore to the inspired air. In Mr. Thomas Wakley’s
experiments the action of the heart continued after the breathing had
ceased; and this was the case in a great number of experiments performed
by a Commission which reported to the Society of Emulation of Paris, in
1855.[64]
This Commission came to the conclusion that, in all instances in which
animals are killed by chloroform, the action of the heart survives the
respiration; but they might have administered chloroform to an equal
number of human patients without any one of them being cut off by sudden
paralysis of the heart. If animals were usually to die suddenly of
paralysis of the heart, when the chloroform is given in a manner similar
to what may be called its ordinary administration to patients, we should
be at a loss to know how this agent could be used at all. It is only
reasonable to suppose that, in experiments so conducted, that mode of
death should usually be met with which would occur to the human subject,
if the chloroform were continued, in the disregard of dangerous
symptoms, till death should ensue. I have, indeed, been informed of
several instances in which animals died in a sudden, and what was
thought an unaccountable manner, whilst chloroform was given to prevent
the pain and struggles which would be occasioned by physiological
experiments. In these cases there is no doubt the heart was paralysed;
but the experimenters were often too intent on other matters to observe
the circumstance. By a proper arrangement of circumstances, however, one
may produce at will the event in animals which occurs, in fact, so very
rarely to a patient, although it may at any time happen if great
caution, guided also by right principle, is not used.
Air, when saturated only at 60° Fah., contains 12 per cent. of vapour of
chloroform, and at 70° 19 per cent. (p. 33); and 8 or 10 per cent. in
the inspired air is capable, as we have seen, of causing sudden death by
paralysing the heart; but in practice the air is usually far from being
saturated, in passing over a handkerchief or similar material, even at
the temperature at which it is inhaled; and this is generally lowered
considerably by the absorption of caloric by the chloroform, as it
changes its condition from a liquid to a vapour. Moreover, air strongly
charged with vapour of chloroform is not easy to breathe, owing to its
pungency; and the physiological knowledge and close attention of every
medical man who administers this medicine causes him to withdraw it
immediately on the least appearance of danger.
_Case 1._ The first death from chloroform was that of Hannah Greener,
which occurred at Winlaton, near Newcastle, on the 28th of January,
1848. The patient was a girl of 15, who required to have the nail of the
great toe removed. A similar operation had been performed on the other
foot, in the previous November, in the Newcastle Infirmary, when ether
was administered with a satisfactory result. The following is the
account of the accident by Dr. Meggison, who administered the
chloroform: “She appeared to dread the operation, and fretted a good
deal: in fact, she commenced sobbing on our entering the house, and
continued so until seated in the operating chair, and commencing the
inhalation, which was done from a handkerchief on which a teaspoonful of
chloroform had been poured. After drawing her breath twice, she pulled
my hand from her mouth. I told her to put her hands on her knees, and
breathe quietly, which she did. In about half a minute, seeing no change
in breathing, or alteration of pulse, I lifted her arm, which I found
rigid. I looked at the pupil and pinched her cheek, and, finding her
insensible, requested Mr. Lloyd to begin the operation. At the
termination of the semilunar incision she gave a kick or twitch, which
caused me to think the chloroform had not sufficient effect. I was
proceeding to apply more to the handkerchief, when her lips, which had
been previously of a good colour, became suddenly blanched, and she
spluttered at the mouth, as if in epilepsy. I threw down the
handkerchief, dashed cold water in her face, and gave her some
internally, followed by brandy, without, however, the least effect, not
the slightest attempt at a rally being made. We laid her on the floor,
opened a vein in her arm, and the jugular vein, but no blood flowed. The
whole process of inhalation, operation, venesection, and death, could
not, I should say, have occupied more than two minutes.”[65]