Blood Transfusion

by Geoffrey Keynes

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.