INDICATIONS FOR BLOOD TRANSFUSION
The indications for blood transfusion are gradually becoming more
numerous as experience of its effects accumulates, and there can be
no doubt that the value of transfusion as a therapeutic measure is
destined to become much more generally recognized than it is at the
present time. Lack of knowledge, together with an exaggerated idea of
the difficulties of the process, is the chief obstacle to its more
extended use. Time and the education of the rising generation will
provide the remedy for this.
The conditions for which blood transfusion may be used fall into four
well-defined groups. On the one hand are those characterized by an
acute anæmia, which demand the performance of a blood transfusion
as an emergency or life-saving operation; on the other hand are
those in which the anæmia is of slow onset, and is to be combated
by a single transfusion to tide the patient over an operation or a
critical period or by repeated transfusions in the hope of prolonging
the patient’s life if not of obtaining a cure. A third group includes
the hæmorrhagic diseases in which the transfusion is administered not
only to replace blood which has been lost, but also to bring about
cessation of the hæmorrhage. A fourth group includes cases of general
toxæmia, whether chemical or bacterial, in which the new blood is
given partly on account of its therapeutic properties, partly in
order to dilute the circulating toxins or to supply healthy red blood
cells to carry on the oxygenation of the tissues.
For the first and third of these groups blood transfusion is
now very firmly established as a method of treatment which is of
extraordinary value. For the second group it may be regarded as a
palliative to be given with circumspection. For the fourth group
administration of blood is still in the experimental stage.
In the present work each condition will be taken in turn and, as
far as possible, separately, though at the outset it has been found
undesirable to dissociate the two conditions, hæmorrhage and shock.
The present position of blood transfusion in relation to each
condition will be discussed; its limitations and the precautions to
be observed will be described.
HÆMORRHAGE AND SHOCK
Blood transfusion is pre-eminently the best form of treatment that
is known for the condition of acute anæmia following hæmorrhage to
whatever cause it may be due. Its good effects were seen by a number
of operators in many hundreds of exsanguinated patients during the
latter part of the war, and its value was then established upon
a secure foundation. It was unusual during the war to meet with
patients who were in danger of their lives from loss of blood alone
without the additional factor of traumatic shock, but such cases did
occur, and they are also to be met with in civil practice, as, for
instance, in attempted suicide by throat cutting, in gastric ulcer
with severe hæmatemesis, and in secondary hæmorrhage after operation.
The more typical condition following war wounds, hæmorrhage with
shock, will be faithfully reproduced in the victims of train or
street accidents, in patients who have undergone certain severe
operations, and in women suffering from post-partum hæmorrhage or a
ruptured ectopic gestation.
The signs and symptoms of acute anæmia will be familiar to most
readers. It is characterized by a peculiar greyness of the skin, by
extreme pallor of the mucous membranes, by a cold perspiration, by a
thready and rapid pulse which may exceed 140 beats to the minute,
and by extreme restlessness. The “amaurosis” of the text-books
is seldom met with, but in the last stages the patient becomes
semi-unconscious, the restlessness tends to disappear, the muscles
relax, and the respiration takes on a peculiar sighing character,
which is described as “air hunger,” and probably indicates exhaustion
of the respiratory centre. Meanwhile, if instruments are at hand,
additional signs may be recognized. The most important of these is a
fall in blood pressure. It has been stated that a systolic pressure
below 70 mm. of mercury is scarcely compatible with life, but this
is not in accordance with experience. It was common during the war
to meet with blood pressures below 45 mm., so low in fact that they
could not be measured with the ordinary apparatus that was available,
but many patients whose lives had reached even so low an ebb as
this were quickly restored by the administration of blood, provided
that the exsanguinated state had not lasted for too long a time.
If the medullary centres are damaged beyond recovery by inadequate
oxygenation lasting for several hours, then no treatment is of any
avail. But provided that it be given before this length of time
has elapsed, a blood transfusion may succeed in saving life at any
stage of the condition. Its efficacy is indeed only limited by the
actual cessation of the patient’s heart beats. I have successfully
treated a patient who before transfusion could only be described as
moribund. He was almost unconscious, absolutely blanched, and his
radial pulse imperceptible; his jaw was relaxed and his breathing had
become a series of fish-like gasps, such as are only associated with
imminent dissolution. His heart would certainly have ceased beating
within a few minutes, yet his condition improved so rapidly after
transfusion that an hour later it was possible, with the help of a
second transfusion, to amputate his leg above the knee. This patient
ultimately recovered, having been as near death as it is possible to
be and yet remain alive.
The results of a blood transfusion upon a patient suffering from
acute anæmia are, indeed, amongst the most dramatic effects to be
obtained in the whole range of surgery. Within a few minutes of its
commencement the whole aspect of the patient alters. His respiration
becomes deep and regular, his restlessness disappears, colour
returns to his face, his pulse rate falls, and he begins to take an
intelligent interest in his surroundings. These changes taking place
within a period of fifteen minutes may well strike an onlooker as
little short of miraculous. Shortly afterwards the patient may fall
into a natural sleep, a sure sign that the normal circulation has
been restored to the exhausted central nervous system.
In considering how much blood should ordinarily be given in the
treatment of acute anæmia, experience is a safer guide than any
theoretical considerations. Nevertheless, it is worth while to
inquire briefly into the experimental and theoretical basis upon
which the treatment of acute anæmia rests. It is difficult to
estimate accurately the total quantity of blood in the body of an
adult, but it has been variously stated by physiologists to be
from a twentieth to a tenth part of the body weight, or, in liquid
measure, from 3 to 6 litres (approximately 5 to 10 pints). This
has been estimated in several ways, the results of which show some
discrepancy. A figure approaching the higher one was obtained long
ago by the direct method of washing out the blood from the bodies
of executed criminals. Recently it has been claimed by Haldane that
these determinations were inaccurate; by means of his carbon monoxide
method, with the details of which we are not concerned here, he has
estimated that the blood volume is but one-twentieth of the body
weight, or in very stout persons is even as low as one-thirtieth.
Still more recently Haldane’s estimation has been challenged in
its turn by observers who have injected a dye into the circulation
and have then determined its degree of concentration in the blood
by means of colorimetric comparisons. It is evident that if the
dilution which occurs when a known quantity of dye is injected can
be accurately estimated, then the total volume of circulating fluid
can be calculated. This method could not be used until a non-toxic,
non-diffusable dye had been discovered, but it was found in 1915 that
“vital red” fulfilled these requirements (143). The results obtained
in this way show that those originally given by the direct method
were substantially correct. The blood volume was found to vary from
1/13 to 1/10·5 of the body weight; on the average it amounted to
5,350 cc., or 85 cc. per kilogram of body weight. These observations
have been in their turn criticized (114), but only to the extent
of reducing the amount by 1/10. It may therefore be assumed that,
according to the most recent work, the blood volume is from 5 to 6
litres, or, approximately, 8 to 10 pints.
It is a still more difficult matter for obvious reasons to estimate
how much blood a man can lose and yet remain alive. This will depend
partly on the power of physiological accommodation possessed by the
individual in his vaso-motor system and tissue fluids and partly
on the rapidity with which the bleeding takes place. Clinical
observations have shown that after a moderate hæmorrhage, such as
the withdrawal of 800 cc. of blood from a donor, the blood volume
may be restored to normal within an hour. If, on the other hand, the
hæmorrhage is excessive, a condition results in which the normal
process of rapid restoration of volume fails, and the circulation
remains in a dangerously depleted condition. The heart attempts to
keep the blood pressure at an adequate level by an increase in its
rate, but it is in effect attempting to circulate a small volume of
fluid in a vascular system which has become too big for it. Imperfect
oxygenation of the medullary and cerebral centres with exhaustion of
the heart results, and this is accompanied by all the symptoms of
anæmia which have been already described.
If the initial hæmorrhage be very rapid, death may result almost at
once, since the physiological processes may have no time to act. On
the other hand, a rapid hæmorrhage may under certain circumstances
save the patient’s life, for the immediate syncope which results
produces so great a fall in the blood pressure that hæmorrhage almost
ceases and a clot may form in the lumen of the divided vessel. If the
hæmorrhage be more gradual, the physiological compensation may at
first be adequate to maintain the blood volume, but finally a point
is reached at which this process fails and the patient then passes
into the condition of acute anæmia.
The actual amount of blood therefore that must be lost to be
fatal will vary according to circumstances. Experience shows that
hæmorrhage may take place into the peritoneal or pleural cavities
to the extent of two litres or even more, and it may be stated as a
rough guess that 2·5 litres, that is to say, even as much as almost
half the total blood volume, may be lost without immediate death
resulting. This degree of depletion could not, however, be endured
for long. A series of clinical observations made by Keith by the
vital-red method upon the blood volume in soldiers suffering from the
combined effects of hæmorrhage and wound shock showed that in the
most serious cases the volume was below 65 per cent. of the normal,
frequently even between 50 and 60 per cent. Serious symptoms followed
a reduction to between 65 and 75 per cent. In patients without
distressing symptoms the volume was never below 75 per cent. of the
normal. There is direct evidence, therefore, that those patients who
are most in need of treatment, such as a transfusion of blood, will
probably have lost from 25 to 50 per cent. of their blood volume,
that is to say, 1·5 to 3 litres in amount, and will need from 750 cc.
to 1·5 litres to restore them to, or near to, the 75 per cent. level
at which the compensatory processes can begin to regain their power.
It is thus possible to arrive at a theoretical basis on which an idea
can be formed of the amount of blood that should be given in acute
anæmia. Practical experience is in agreement with the theory, and it
will now be easier to understand how it is that in treating acute
anæmia no attempt need be made to replace the whole amount of blood
that has been lost, or indeed anything approaching it. In an extreme
case 2 to 3 litres of blood will have been lost and 1 litre or more
will be needed to restore the blood volume to approximately 75 per
cent. of the normal. A case of this sort, however, is fortunately
not often to be met. One has already been described on page 21;
this patient received altogether nearly 1,600 cc. of blood in two
transfusions, and 1,000 cc. of normal saline were given in addition.
In most cases of severe hæmorrhage the patient has probably not lost
more than 1,400 to 1,800 cc. of blood, and 600 to 800 cc. will be
enough to restore the balance of the circulation. This is in practice
the amount of blood that is commonly administered, and it is well
within the limits of what a single blood donor can afford to lose.
If a more definite standard be required, it may be laid down that
in a single transfusion for acute anæmia 750 cc. of blood should
be given. If, in an exceptional case, more than this is needed, a
second transfusion should be performed with a similar amount taken
from another donor. Sometimes it may happen that a patient already
_in extremis_ from loss of blood, needs a severe operation; in such
a case a second transfusion may be given with great advantage at
the conclusion of the operation. The first transfusion will restore
the patient sufficiently to render the performance of an operation
possible; the second will combat the additional shock and hæmorrhage
which it has caused.
It has already been stated that it was uncommon during the war to
meet with patients who were suffering from anæmia uncomplicated by
traumatic shock. It was in fact the condition of shock which tended
to dominate the clinical picture, and it was towards the elucidation
of the facts concerning shock, its causation, prevention, and
treatment, that the investigations co-ordinated by the Medical
Research Committee were mainly directed. These investigations were
carried out both in the laboratory and in the military hospitals, and
considerable additions were made to the knowledge of the condition.
It is necessary to give some account of the conclusions which were
reached in order that the rôle of blood transfusion in the treatment
of shock may be fully understood.
Hæmorrhage and shock cannot be dissociated, and this is not only
because they so frequently occur together in the same patient, but
also because the manifestations of the two conditions are essentially
the same. In shock, as in hæmorrhage, are found the same pallor
of the face and mucous membranes, the same fall of blood pressure
and rapid pulse, the same perspiration, restlessness, and shallow
respiration. The symptoms following a severe hæmorrhage have
sometimes been referred to as constituting a “shock-like condition.”
As will be seen, however, it is more accurate to describe the
symptoms of shock as closely resembling those of hæmorrhage, and to
regard both conditions as a manifestation of deficient fluid content
in the circulation.
Numerous theories have been advanced to account for the symptoms
seen in shock. Until recent years it was customary to suppose
the vaso-motor centres had failed, being overcome by exhaustion
consequent upon excessive stimulation by a greatly increased number
of afferent impulses from the periphery of the body. It was suggested
that as a result there was a general dilatation of the vascular
system, especially in the abdominal veins, and therefore a general
impairment of the circulation. Various hypotheses were, in addition,
formulated, to account for the vaso-motor failure. These included
the ideas of deficient carbon dioxide in the blood, exhaustion
of the adrenal secretion, and exhaustion of nerve-cells in the
higher centres. All these theories found their supporters and much
experimental evidence was brought forward, but none was susceptible
of final proof. The whole theory of vaso-dilatation and the idea that
the patient “bleeds into his own abdominal veins” were eventually
disposed of by observation of the clinical facts. Many extensive
abdominal operations have been performed upon shocked patients, but
the accumulation of blood in the splanchnic area has never been
demonstrated. It has, on the other hand, been found that in the limbs
the arteries and arterioles are strongly contracted. It is also by
no means unusual to meet with the condition known as venospasm; the
veins are collapsed and their walls contracted, so that it becomes
necessary to use a considerable positive pressure before any fluid
can be induced to flow into them. It has, in addition, been shown
that the vaso-motor system is still active, and the heart, although
beating rapidly, still responds to reflex stimulation and to increase
of intracranial tension.
It becomes necessary, therefore, to find some other explanation of
the low blood pressure which is the essential feature of shock. Of
especial value in this connexion are the investigations by Keith,
already mentioned, into the changes in blood volume found in soldiers
suffering from shock and hæmorrhage. In very few of these cases
were the symptoms due to shock alone, but usually the loss of blood
volume was much greater than could be accounted for by the amount
of hæmorrhage which had taken place. Here, therefore, was evidence
strongly suggesting that the symptoms of shock are due to actual
loss of circulating fluid, and the problem now resolved itself into
a search for this fluid which has ceased to be part of the effective
blood volume. Enough has already been said to show that there is no
evidence that the larger vessels, whether arteries or veins, are
acting as reservoirs in which the blood is stagnating. It therefore
only remains to consider whether the capillary system is capable,
under abnormal conditions, of holding so large a proportion of the
blood as has been shown by Keith to have left the circulation. For
a discussion of this problem the reader may be referred to W. B.
Cannon’s summary of the arguments (45), from which it becomes clear
that the capillary system may be regarded as a potential reservoir
large enough to contain the lost blood in shock. The question is,
however, further complicated by the fact that the capillary blood in
shock differs from the circulating blood in containing an abnormal
concentration of corpuscles. Extensive observations made on wounded
soldiers have shown that the number of red blood cells may rise even
to 8,000,000 per cmm. in the capillary blood, while the number in
the venous blood remains at 5,500,000 or less. This concentration of
the red cells is gradual and progressive, and will by itself account
for a large part of the loss of volume, since normally the bulk of
the blood is made up of corpuscles and plasma in approximately equal
parts. The stagnation is, moreover, accentuated by the increased
viscosity of the blood resulting from the concentration, and by the
chilling of the surface of the body, which is always a feature of
the state of shock. A vicious circle is thus established, and the
symptoms of shock become severe as the capillary stagnation becomes
more pronounced.
A second factor which may also play its part in the loss of blood
volume in the general circulation is the exudation of some of
the plasma into the surrounding tissue spaces. As the stagnation
increases, oxygenation decreases, and the walls and the capillaries
become more permeable, so that some fluid is probably lost in this
way. This permeability may also be accentuated by the increased
hydrogen-ion concentration in the blood, which often accompanies
shock, but it seems to be clear that this is a secondary phenomenon
resulting from imperfect oxygenation in the tissues, and it will
therefore not be regarded as one of the factors responsible for
shock. Further fluid is lost by the copious perspiration commonly
seen in shock. There seems, therefore, to be a conspiracy between a
whole set of different factors all tending to deprive the patient
of his circulating fluid. The net result is a condition so closely
resembling hæmorrhage that it may be impossible to distinguish the
two, this difficulty being increased by the fact that they so often
occur together.
In the foregoing account of the production of shock the fate of
the lost blood has been discussed, but nothing has been said of
the factors initiating the capillary stagnation. This is a subject
which is of great interest and some obscurity, and is of evident
importance in considering how shock may be avoided. The present
treatise, however, is primarily concerned with the treatment of
shock when already established, and it is therefore not proposed to
follow out the other question in detail. An injury may be followed
immediately by a condition of “primary wound shock,” in which the
patient becomes suddenly pale and pulseless. This is a physiological
reaction, which may be transient, and it is to be distinguished
from the much more serious condition of “secondary wound shock”
which appears some time later. It is this secondary shock alone
which has been under consideration in the preceding pages. The chief
importance of the primary shock lies in the fact that it may initiate
the conditions which predispose to secondary shock, so that under
certain circumstances the one may become merged in the other. These
predisposing conditions are increased evaporation from the skin, a
general fall in the temperature of the body, mental anxiety, and the
continued stimulation of the higher centres by afferent impulses as
is manifested by pain. The condition of secondary wound shock was
shown in a striking degree, during the earlier years of the war,
by the men suffering from fracture of the femur. In the later part
of the war warmth was supplied more systematically than before to
the seriously wounded, and all fractured femurs were treated at an
early stage with Thomas’s splints. Two of the factors predisposing
to shock, namely cold and pain, were in this way to some extent
eliminated, and it was very striking how much better than before was
the general condition of the patients on arrival at the hospitals.
Nevertheless, the elimination of these factors, which is a simpler
matter in civil life than it was under conditions of war, will not
avert all shock in a large proportion of cases. It is necessary,
therefore, to find some additional factor which will initiate shock
in addition to the predisposing causes. It is thought that this
may have been identified in a substance of obscure nature which is
derived from the damaged tissues themselves, and which, circulating
in the blood, is able directly to affect the capillary system. Just
as the shock following severe burns is believed to be due to the
circulation of a toxic substance formed by the burning of the skin
and other tissues, so the shock following severe trauma is believed
to be of toxic origin, the toxin being derived from damaged tissues,
muscle being particularly active in this respect. The condition
may, therefore, be one of “traumatic toxæmia,” in which there is a
general loss of capillary tone throughout the body, so that “the
blood percolates into the network of channels as into a sponge.”
The circulating blood is thus rapidly depleted, and the symptoms
of shock become established. The investigation of this source of
shock was carried out chiefly by Dale, Bayliss and Cannon (65), who
were able to reproduce the condition of shock in animals by the
injection into their circulation of a substance obtained from damaged
muscles. To this substance the name histamine was given. It would be
a mistake, however, to suppose that because a substance producing
shock experimentally has been obtained from muscles, that therefore
this is the identical substance which is responsible for every case
of traumatic toxæmia. Extreme shock may be produced when but little
damage has been done to muscles. Probably damage to any tissue of
the body if extensive enough will produce a substance or substances
which will give rise to the symptoms, and it may be a long time
before these are isolated and identified. That the last word on the
production of shock is still far from being uttered is shown by the
fact that profound shock may be induced without doing any appreciable
damage to tissue, namely, by handling and exposing the abdominal
viscera.
It may be this traumatic toxæmia which will account for many cases of
post-operative shock, but it has been shown that some anæsthetics,
such as chloroform or ether, will of themselves greatly accentuate
shock initiated by other causes.
It has already been mentioned that the increased hydrogen-ion
concentration in the blood, which results from imperfect oxygenation
in the tissues, is not itself a cause of shock, but it will aggravate
shock due to other factors. A discussion of this will be found in the
paper by W. B. Cannon already referred to.
The present state of knowledge concerning the causation of shock
having been thus briefly reviewed, the question of the treatment
of the condition may be discussed. In this connexion the value of
blood transfusion will be considered. It will have become clear
that essentially the condition to be combated in treating shock is
one of lowered blood pressure following upon a diminution of the
volume of blood in the circulation. All the factors which have been
mentioned in considering the causation of shock must be combated.
Warmth must be supplied, morphia administered, fractures efficiently
immobilized, damaged tissues excised: but clearly all these measures
are prophylactic rather than curative. None of them will remove
a state of profound shock once established, for they will not of
themselves restore the blood volume depleted by capillary stasis.
It is necessary, therefore, to attack this condition directly. It
may with justice be compared to a state of acute anæmia following
hæmorrhage, but with this difference, that the blood is still present
in the body and will return to the circulation when the capillary
stasis has been abolished and the circulating balance has been
restored. The possibility of recovery from shock depends upon how
long the condition has existed. After a certain time the toxæmia,
whether the primary traumatic toxæmia or the secondary increase in
hydrogen-ion concentration, appears to have a damaging effect upon
the capillary walls, so that an increased loss of fluid takes place
into the tissues and this cannot be remedied. It is essential,
therefore, to use the means which will most rapidly restore the
circulation and bring about a rise in blood pressure which will be
permanent. It is reasonable to infer that the most hopeful means of
bringing this about is by a blood transfusion, which will actually
replace the blood temporarily lost. This is the physiological remedy,
and its value has been proved by the results obtained in many cases
of my own as well as in those recorded by others. The efficiency of
the treatment is accentuated by the fact that so large a proportion
of cases of shock are associated with, and aggravated by, some degree
of hæmorrhage. Apart from this, Keith’s observations have shown
that the diminution of blood volume in shock is comparable with
that which attends severe hæmorrhage. The state of shock in fact so
closely resembles hæmorrhage that most of the same remarks concerning
blood volume and the amounts that should be given by transfusion
may be applied, and it is unnecessary to repeat them here. It must
be remembered, however, that in pure shock the amount of hæmoglobin
in the body is not reduced though there is less in the circulation.
It is restored to the circulation when the capillary stagnation is
overcome. This will be referred to again later on.
During the war the value of blood transfusion in shock was amply
demonstrated. In civilian practice I have found it to be of value
when given after operations such as removal of the rectum, whether
by the perineal or abdomino-perineal route, amputation of the leg
through the hip joint, or removal of a sarcoma from the nasopharynx.
Transfusion should be given towards the close of the operation
before the evidences of shock have reached their maximum. The
depletion of the blood volume is then actually remedied as it takes
place, and transfusion becomes almost as much a prophylactic measure
as warmth and the administration of morphia.
It is probable that the mortality following very severe operations
such as those mentioned above would be considerably reduced if blood
transfusion were to be given as a routine measure. Reference has
already been made to the bad effect of the ordinary anæsthetics, and
the best effects are obtained by a blood transfusion in conjunction
with gas and oxygen or with spinal anæsthesia. It is necessary,
however, to draw attention to the fact that a blood transfusion if
given to a patient under the influence of a spinal anæsthetic must
not be performed until the operation is very nearly completed, for it
will very often produce a much more rapid return of sensation than
would otherwise occur.
In advocating the use of blood transfusion to combat the effects
of shock and hæmorrhage, it would be misleading to imply that this
is necessarily the only treatment that is available. Something
must be said of the substitutes for blood that have been used, and
in particular the value of gum acacia must be considered. In the
days before the war it was customary to treat post-operative shock
or hæmorrhage with large quantities of normal salt solution given
intravenously or subcutaneously. During the earlier part of the war
also this was used, and there can be no doubt that for the less
severe cases this treatment is often beneficial. Occasionally even
the lives of patients who were desperately ill have been saved by
it; I have seen a saline infusion cause the recovery of a man who
had a dozen perforations of the small intestine and who had, in
addition, lost several pints of blood intraperitoneally from a wound
of a large mesenteric vessel. Such cases are, however, exceptional.
In the presence of severe shock or hæmorrhage a saline infusion may
cause an immediate rise in blood pressure, but the fluid exudes so
rapidly into the tissues that the effect is usually very transient.
This fact is universally admitted to be true and need not be further
emphasized. Saline solution administered by the rectum is likely to
have a more lasting effect, but the process of absorption is slow,
and the patient may be dead before it has had time to act. The
same applies to water given by the mouth. A patient suffering from
severe shock is unable to tolerate more than a very small quantity
of fluid in his stomach without vomiting. Some success was attained
by Oswald Robertson in treating cases of hæmorrhage by the method of
“forced fluids,” large quantities being given by the mouth and by
the rectum (245). In many serious cases, however, this treatment is
inapplicable, and it is clear that transfusion is more rapid and more
certain in its effect. Isotonic saline having been found ineffectual,
it was suggested that a hypertonic solution (2 per cent. sodium
chloride) might be of more value. This was tested clinically and in
the laboratory, and was found to have no advantage over the isotonic
solution (11).
When the association of increased hydrogen-ion concentration with
shock was demonstrated, it was at first supposed to be one of the
factors producing the condition. It was therefore natural that the
effect of a solution of sodium bicarbonate (4 per cent.) should
be tried. The effect upon certain cases suffering from extreme
“acidosis” and air hunger was very striking, but in general the
alkaline solution was no more effective than the ordinary isotonic
saline. I soon abandoned its use for intravenous infusion, but it was
of service in serious cases when given by the rectum.
During the war the necessity for the conservation of time--and
of blood--was evident. The search for a satisfactory substitute
for blood was therefore prosecuted with great energy, most of the
research being done by, or under the direction of, Professor W. M.
Bayliss. The object of the research was to discover a non-toxic
solution which possessed the same “viscosity” as the blood, and the
same osmotic pressure due to contained colloid. It was believed that
such a solution would not tend to exude so rapidly into the tissues
and would therefore augment the blood volume more effectively than
the fluids previously used. After many experiments it was claimed
in 1916 that a blood substitute had been found in a 6 per cent.
solution of gum acacia with ·9 per cent. sodium chloride. It was
even stated on the evidence of laboratory experiments that the gum
solution was as effective as blood in the treatment of shock and
hæmorrhage. It was therefore used very extensively among the wounded,
and favourable reports upon its value were made by various workers.
It is difficult, however, to control the results in giving treatment
of this kind. If a patient dies after being given a gum infusion,
no one can state definitely that he would have lived had he been
given a blood transfusion instead. If a patient lived after having a
blood transfusion, it would be equally rash to state that he would
have died had he been given gum. Nevertheless, after giving the gum
solution a number of trials, I formed the opinion that the results
were inferior to those obtained with blood. Patients did not recover
whom from previous experience with blood transfusion I should have
expected to do so. I accordingly continued to use blood in preference
to gum whenever it was available, although justice must be done to
those who so strongly advocated gum by saying that there can be
no doubt that it is very much more effective than other solutions
previously used. The same opinion was formed by many other surgeons,
although it was natural to feel a bias in favour of gum which could
be given with much greater economy of time and effort than blood. Up
to the present time I have seen no reason for altering this opinion,
and should always prefer to treat hæmorrhage and shock with a blood
transfusion if possible.
Recently the relative values of a number of intravenous infusions
for shock have been put to an extensive experimental test by F. C.
Mann. The shock was produced by handling the abdominal contents,
and the effect on the blood pressure of the various fluids was
mechanically registered. The conclusion was reached that far the best
results were obtained by a transfusion of blood or blood serum, the
effect of these being more permanent than that of any other substance
used. The use of gum acacia was found to give results which were
“variable and sometimes disastrous,” but this may have been due to
some extent to errors in the technique of preparing the solution.
This draws attention to a possible objection to the use of gum,
namely, that some samples of the solution have been found to be
actually toxic; but it is said that this can be avoided if proper
care be exercised in its preparation. Full instructions for this are
given in a paper by S. V. Telfer.
Into the discussion of the relative merits of blood and gum solutions
may be profitably introduced the further question as to which is the
more valuable constituent of transfused blood, the corpuscles or the
plasma. It has been seen that the essential factor in producing the
symptoms of shock and hæmorrhage is a reduction of blood volume,
and treatment is therefore directed in the first place towards the
restoration of this volume, with a fluid of the same viscosity and
osmotic pressure as blood. This might be done with plasma or, some
may say, equally well with gum. From the point of view only of
volume, the corpuscles and plasma are of equal value, since each
forms approximately half the total volume of a given quantity of
blood. There is, however, another aspect to be considered. One of
the results of loss of blood volume is imperfect oxygenation in the
tissues. When the volume is increased by the addition of plasma or
gum, the corpuscles in the circulation are diluted, and this by
itself would tend further to impair oxygenation. The dilution is,
however, compensated for by the improvement in circulation which
in its turn improves the supply of oxygen to the tissues, and it is
still further counteracted by the restoration to the circulation of
the blood corpuscles which were stagnating in the capillary system.
It seems clear that these successive processes will be accelerated
by the use of a fluid which itself contains corpuscles, and this may
afford a theoretical explanation of the clinical observation that
blood is more effective than gum. Its use will tend to establish
more quickly the “virtuous circle” following increased volume, and
so undo the “vicious circle” due to insufficient volume. It has
been questioned whether the corpuscles of transfused blood really
do play an active part in the economy of their new host, or whether
their new environment may not quickly render them effete. This has
been answered by the exceedingly interesting and ingenious series of
experiments carried out by Winifred Ashby. She has transfused blood
of a known group (see Chapter IV) into an individual of a different,
but compatible group, and then shown that it is possible by selective
agglutination with a suitable serum to demonstrate the presence in
the blood of the two kinds of corpuscles side by side. In this way
she has shown that transfused corpuscles are still present in the
circulation and of normal appearance thirty days after they were
introduced.
It is therefore justifiable to make the inference that transfused
corpuscles can for some little time carry out their normal function.
If it be true that their presence is an advantage in the treatment
of deficient blood volume, it may also be conjectured that their
presence is likely to be of greater importance in treating hæmorrhage
than it is in the treatment of pure shock, for in the latter
condition all the original corpuscles are still present in the body,
while in the former they are not.
I should sum up the discussion of the relative merits of blood
and gum by saying that on the grounds of experiment and clinical
experience I believe blood to be the more efficient of the two,
particularly in the most serious cases. Every patient who needs it
should therefore have the advantages conferred by blood transfusion
if it can be done. If it cannot, then gum and saline is much the most
satisfactory substitute that is at present known.
Some of the concluding remarks in the foregoing pages will have
suggested that the use of gum infusion may be considered of more
value in treating pure shock than in treating hæmorrhage. For this
reason, apart from other diagnostic considerations, it may be of
importance to be able to distinguish clinically between shock and
hæmorrhage. Attention has already been drawn to the fact that the
symptoms and appearance seen in a patient suffering from severe shock
very closely resemble those seen in hæmorrhage. It may, in fact, be
impossible to say from purely clinical evidence whether a patient is
suffering from shock, or hæmorrhage, or both. A case which recently
came under my own observation well illustrates this point. A very
stout, elderly man had fallen down a lift-shaft and was brought into
St. Bartholomew’s Hospital soon after the accident. He appeared
to have fallen on his feet, and the lower ends of both tibiæ had
been driven through the inner sides of his soles, but there were no
other signs of injury. His general condition on arrival at hospital
was fairly good, but all the usual measures were taken to minimize
shock. An hour or two later he had passed into a condition of extreme
collapse, and exhibited all the symptoms which have already been
described. Not much hæmorrhage had taken place from the wounds in
his feet, and the question arose as to whether his present condition
was due to internal hæmorrhage from visceral injury, or whether it
was due chiefly to shock. His abdomen contained so much fat that no
evidence could be obtained from an examination of it, and it was in
fact impossible to arrive at any conclusion. There could, however,
be no question of performing any operation, and the patient made
no response to other treatment. At the autopsy it was found that
there were fractures of the ribs, spinal column, and symphysis
pubis in addition to the injuries to the legs. There was very little
hæmorrhage in connexion with any of the fractures, and it appeared
that death was to be attributed almost entirely to shock. This was
perhaps a somewhat unusual case, in which no help could be derived
from an examination of the patient, but similar difficulties will
sometimes be met.
It might be expected that a criterion would be supplied by an
examination of the blood. The results from this, however, have proved
to be disappointing. The facts have been investigated by Cannon and
others (47) and may be summarized as follows. The number of red
corpuscles in the blood from the capillaries of the ear or finger has
been found to be invariably raised in patients suffering from shock.
A blood count may show an increase up to seven million red cells per
cmm. or even more. The blood in the venous circulation, however, of
the same patient is more dilute, the count being less by one to two
million red cells. When the shock is complicated by hæmorrhage, the
blood count in the venous system will again be lower than that in
the capillaries, but in both the counts will be less than if there
were no hæmorrhage. The differences are, however, not so great or
so constant that any principle can be laid down by which the two
conditions may be distinguished. In patients in whom hæmorrhage is
the outstanding feature the blood counts will be still lower, but
the capillary and venous difference will still be present. It was
found that in hæmorrhage the hæmoglobin percentage, and therefore the
colour index, tended to be lower than in shock, but this was most
obvious when the hæmorrhage had been very severe, and in such cases
the diagnosis is usually clear from other evidences. The clinical
difficulty lies in the distinction between cases of pure shock and
of shock complicated by considerable hæmorrhage. It seems that
little help is to be derived from an examination of the blood. This
difficulty in diagnosis can only influence treatment in the direction
of giving blood rather than gum-saline, though the latter would
probably be effective for many of the cases of shock if they could be
distinguished.
The effects of transfusion for hæmorrhage and shock are to be
judged best by the clinical results. The abnormal distribution
of the corpuscles is altered by the treatment with a consequent
redistribution in the circulation. No constant changes, therefore, in
the blood count follow transfusion, and no exact mathematical effect
can be demonstrated. It has been shown by Huck that sometimes the
immediate rise in the blood count is greater than can be accounted
for by the amount of blood given. This is often followed by a fall,
which is succeeded in its turn by a second rise. These results are
to be explained by alterations in the amount of destruction and
formation of red cells going on in the body. That is to say, they are
biological rather than mechanical, and are at present but imperfectly
understood.
In the foregoing discussion hæmorrhage and shock have been considered
in a general way. Something must now be said of the particular
conditions for which transfusion may be given. Concerning traumatic
hæmorrhage and shock there is little to be added, for these
conditions present the general features of the problem in its least
complicated form. No clear-cut rule can be laid down as to the point
at which transfusion becomes necessary. The blood pressure is perhaps
the best single indication, and if this has fallen below 80 mm.
(systolic), then a transfusion is certainly indicated. Apart from
this, the patient’s general condition is the safest guide. As soon as
it becomes evident that his life is in danger, a transfusion should
be given. Better save a few lives by many transfusions than lose them
by reserving transfusion for those who are actually moribund.
Secondary hæmorrhage following an operation is fundamentally similar
to primary hæmorrhage, but may present a few additional points. In
recent years by far the largest number of transfusions for secondary
hæmorrhage have been given for bleeding from septic amputation
stumps. In many cases of this sort it is no easy matter to stop the
bleeding by ligaturing a bleeding vessel; sometimes it is impossible.
Nevertheless, transfusion should not be withheld owing to a risk of
increased hæmorrhage supposed to follow a rise in blood pressure.
Usually the patient is debilitated by prolonged suppuration, and
often his blood is deficient in its power of coagulation. It has
been found that a transfusion, in addition to replacing some of the
blood that has been lost, tends to improve the patient’s resistance
to micro-organisms, and to shorten the coagulation time of the blood.
Recurrence of the hæmorrhage is therefore discouraged on the whole,
and in many cases a series of transfusions for recurrent hæmorrhages
has saved a patient’s life when the prognosis had seemed to be almost
hopeless.
Post-operative hæmorrhage associated with chronic jaundice is another
condition which demands special consideration; this will be dealt
with later under the heading of hæmorrhagic diseases.
The proper treatment of severe hæmorrhage from a gastric or duodenal
ulcer has always puzzled physicians and surgeons alike. It is
probably true that patients very seldom die as the result of a
single rapid hæmorrhage, even if severe. There can, however, be no
doubt that death due actually to acute anæmia may follow repeated or
prolonged hæmorrhage. Hitherto treatment has been conducted mainly
on medical lines. Opinion is now, however, tending to favour earlier
and more frequent surgical interference, and this can be made a
less dangerous procedure by giving a preliminary blood transfusion
to improve the patient’s general condition. When the patient’s life
is threatened by hæmorrhage repeated or prolonged, transfusion is
undoubtedly the best means of saving him. Here again the fear of
restarting the hæmorrhage by raising the blood pressure has acted as
a deterrent, so that transfusion is apt to be withheld until too
late. Nevertheless, it is clear from the numerous cases recorded in
the literature that this fear is groundless (130, 215, etc.). The
effect of a transfusion on the coagulating power of the patient’s
blood more than compensates for the risk attending a rise in blood
pressure. Now only is lost blood replaced, but also the clot plugging
the damaged vessel is made more secure. The patient is tided over
the immediate danger to his life, and surgical treatment is made
possible. This view will doubtless meet with much adverse criticism,
but its justice will eventually be recognized.
As in the early days of transfusion, so at the present time, a
considerable proportion of the patients that need transfusion will
be met with in the course of obstetrical practice. It has often
been remarked how much blood can be lost by a woman following the
delivery of her child without any serious result; nevertheless,
many deaths are occasioned every year by post-partum hæmorrhage,
placenta prævia, and rupture of an ectopic gestation. Sometimes the
bleeding is so rapid that there is no margin of time available for
a transfusion unless all the facilities be immediately at hand.
Short of this, transfusion is the ideal treatment, and the problem
is a simple one, the relief of acute anæmia being the only object
in view. One interesting modification of the procedure has been
recently recommended by German writers, namely, the reinfusion of the
patient’s own blood. This is applicable only when the hæmorrhage has
taken place into the peritoneal cavity, and is therefore limited to
the treatment of a ruptured liver or spleen, a ruptured uterus, or
a tubal abortion. With a ruptured uterus the sterility of the blood
is not assured, and this condition were better not included. For the
other conditions Lichtenstein recommends that the blood should be
ladled out of the peritoneal cavity into Ringer’s solution and then
strained to remove clots. The resulting fluid is infused into a vein.
Judging from my own experience of intraperitoneal hæmorrhage, not
much blood would actually be recovered in this way, since usually
so much of it has clotted. In any case, the whole procedure is to be
looked upon with suspicion owing to the unknown and probably profound
changes that have taken place in partially clotted blood. Eberle
records that in one case reinfusion was followed by hæmolysis, and
among twenty-one cases reported by Schweitzer in 1921, one death
was attributed to the reinfusion, which, as in Eberle’s case, was
followed by hæmoglobinuria. Transfusion has also been used for the
toxæmias of pregnancy, but this will be dealt with under another
heading.