Source: Snow, John. Med.
Times and Gazette, n. s. vol. 8, Feb. 25, 1854, pp. 180-182.
The principles on which the treatment of cholera should be based
Medical Times and Gazette
(25 February 1854): 180-82
By John Snow, M.D,
(Read at the Medical Society of London, January 21, 1854)
Without clear and definite ideas on pathology there can be no fixed principles of therapeutics; and the absence of any settled opinions respecting the nature of cholera is the cause of the various and contrary plans on which it is treated. It is, I believe, the more prevalent opinion, that the cholera poison acts on the whole system through the blood, and that the local symptoms are the effect of the general disease. In a paper I read to the Society, some time ago, on the mode of communication of cholera, I expressed my conviction that the cholera poison acts solely on the alimentary canal; but I did not enter on the consideration of the influence which this view of its pathology ought to have on the treatment of the disease.
In the greater number of epidemic, or what may be termed self-propagating diseases, the morbid poison appears to enter the blood in some way, and, after multiplying during a period of so-called incubation, it affects the whole system. Such is undoubtedly the case in small-pox, measles, scarlet-fever, and the various kinds of continued fever; but it must be remarked, that in all these diseases the illness always commences by general symptoms, as headache, rigors, fever, and lassitude; and the symptoms more particularly indicating the disease appear only afterwards. Cholera, on the other hand, commences with an effusion of fluid into the alimentary canal, without any previous illness whatever. Indeed, after this fluid has commenced to flow away as a copious diarrhœa, the patient often feels so little indisposed that he cannot persuade himself that anything serious is the matter. There are some cases, it is true, in which dizziness, singing in the ears, faintness, and a sense of sinking and uneasiness in the abdomen occur before any discharge makes its appearance from the alimentary canal; but this is just what happens in certain cases of hæmorrhage into the bowels, where all the symptoms of loss of blood are felt some hours, it may be, before that fluid makes its appearance in the stools. It is contrary to all analogy that a morbid poison, or indeed a poison of any kind, if present in the blood, should show its effects on a single tract of mucous membrane, without first producing any symptoms whatever of its presence.
The symptoms which follow the affection of the alimentary canal in cholera are exactly those which this affection is adequate, and, indeed, could not fail to produce. The analyses which have been made of the blood of cholera patients, show that the watery fluid effused into the stomach and bowels is not replaced by absorption, or is replaced only to a small extent. The experiments of Dr. O'Shaughnessy and others during the cholera of 1831-32, show that the amount of water in the blood was very much diminished in proportion to the solid constituents, and that the salts of the blood were also diminished. The experiments of Dr. Garrod and Dr. Parkes in the spring of 1849, were more numerous and exact.* (* See London Journal of Medicine, May, 1849) The amount of water in the blood of healthy persons is on the average 785 parts in 1000, whereas in the average of the analyses performed by Drs. Garrod and Parkes it was only 733 parts, while the amount of solid constituents of the blood relatively to the water was increased from 215--healthy standard--to 267. The globules, together with the albumen and other organic constituents of the serum, amount in the healthy state to 208 parts in 1000, while in the blood of cholera patients they amounted to 256 parts. The saline constituents in 1000 parts of blood are somewhat increased on account of the great diminution of water; but when estimated in relation to the other solid ingredients, or to the whole quantity existing in the healthy body, the amount is diminished. Dr. Garrod is of opinion that a chemical analysis will determine whether or not a specimen of blood has been derived from a cholera patient.
The stools and vomited matters in cholera consist of water containing a small quantity of the salts of the blood, and a very little albuminous substance. The change in the blood is precisely that which the loss by the alimentary canal ought to produce; and, indeed, it is physically impossible that the alteration in the blood can be caused in any other way. The sweating which takes place in an advanced stage of the disease may increase the density of the blood to a trifling extent; but it does not come on till the blood is already altered, and is only a consequence of the diminished force of the circulation, like the sweating met with in collapse from hæmorrhage or severe injuries, and in faintness from venesection.
The loss of water from the blood causes it to assume the thick tarry appearance so well known to all who have opened a vein in cholera. The diminished volume of the blood causes many of the symptoms of a true haemorrhage, as debility, faintness, and coldness; while these effects are much increased by its thick and tenacious condition, which impedes its passage through the pulmonary capillaries, thereby reducing the contents of the arteries throughout the system to the smallest possible amount, as indicated by the thready pulse. The interruption to the pulmonary circulation occasioned by the want of fluidity of the blood, is the cause of the distressing feeling of want of breath. Proofs of the obstructed circulation through the lungs generally remain after death, in the distended state of the pulmonary arteries and right cavities of the heart. The deficient supply of blood to the various organs, and its unfitness to pass through the capillaries, are the cause of the suppression of the renal, biliary, and other secretions. The cramps appear to consist chiefly of reflex action caused by the irritation and probably the distension of the bowels.
If any further proof were wanted than those above stated, that all the symptoms attending cholera, except those connected with the alimentary canal, depend simply on the physical alteration of the blood, and not on any cholera poison circulating in the system, it would only be necessary to allude to the effects of a weak saline solution injected into the veins in the stage of collapse. The shrunken skin becomes filled out, and loses its coldness and lividity; the countenance assumes a natural aspect; the patient is able to sit up, and for a time seems well. If the symptoms were caused by a poison circulating in the blood, and depressing the action of the heart, it is impossible that they should thus be suspended by an injection of warm water, holding a little carbonate of soda in solution.
It has often been contended that the collapse of cholera cannot be the mere result of the purging and vomiting, because, in some of the most rapid and malignant cases, the amount of the stools and vomited fluid is less than in milder and more protracted ones, or even in some cases in which the patient recovers. But in the most rapid and malignant cases there is sufficient loss of aqueous fluid by the alimentary canal to alter the blood into the thick tenacious state peculiar to this disease; and the fact of more purging occurring in other cases which are more protracted only proves that, in these latter, absorption from the stomach and intestines has not been altogether arrested, or that the stools have been diluted with fluids drunk by the patient. The loss of fluid in every case of fully developed cholera must be sufficient [180/181] to cause the thickened state of the blood which is the cause of the algide symptoms, and the amount of malignancy of the case must depend chiefly on the extent to which the function of absorption is impaired. If absorption were altogether arrested in every case of cholera from the beginning, the amount of discharge from the alimentary canal would not equal that of a fatal hæmorrhage, for the thickened blood which remains behind is certainly not able to maintain life so well as the same quantity of healthy blood. Indeed, it is easy to calculate the amount of fluid separated from the blood, by means of the analyses previously quoted, and others which have been made of the cholera stools. In some analyses of these evacuations performed by Dr. Parkes* (* London Journal of Medicine, Loc. Cit.) the average composition in 1000 parts was found to be 982.4 water and 17.6 solids; consequently, the problem merely is to find how much of such a fluid requires to be subtracted from blood consisting of water 785 and solids 215, in 1000 parts, in order to reduce it to blood, consisting of water 733 and solids 267. The answer to this problem is, that 208.5 parts would require to be subtracted from 1000 parts of blood. M. Valentin has estimated the average amount of blood in the human adult at thirty pounds; and, therefore, the whole quantity of fluid that requires to be effused into the stomach and bowels, in order to reduce the blood of a healthy adult individual to the condition in which it is met with in the collapse of cholera is, on the average, 100 ounces, or five imperial pints. This calculation may be useful as indicating the amount of fluid, which ought not to be exceeded in the injection of the blood-vessels.
The evidence of the mode of propagation of cholera--which there is not time to discuss on the present occasion--confirms the above facts respecting the pathology of the disease, by showing that the cholera poison enters the alimentary canal by being accidentally swallowed, and there becomes multiplied. It is most probable that all morbid poisons having the property of propagating themselves are more or less organized; and if it be objected that the cholera poison cannot be recognized by the microscope in the feces or in the alimentary canal after death, it must be remembered, that the matter of small-pox cannot be distinguished from so much harmless pus; and it is only by their origin and effects that we can distinguish this and other morbid poisons.
It is pretty obvious, for the reasons stated above, that what we have to deal with in cholera is, a low form of organic action going on upon the interior surface of the stomach and intestines. The morbid poison so multiplying or reproducing itself probably acts as an irritant, and causes the great effusion of watery fluid and the arrest of absorption which produce all the mischief in this disease; or, what is still more probable, if the materies morbi have a cellular structure, is, that it withdraws the fluid from the blood circulating in the capillaries by a power analogous to that by which the epithelial cells of the various organs abstract the different secretions in the healthy body.
At all events, whatever be the intimate nature of the morbid action we have to combat in treating cholera, it is situated on the inner surface of the alimentary canal, and our remedies should be directed to act on that part rather than to be absorbed; and should be so contrived as to come in contact, if possible, with every part of the mucous membrane of the whole alimentary canal. The medicines should be such as have the property of destroying low forms of organised beings, and of arresting fermentation, putrefaction, and other kinds of molecular change in organic matter.
A line of practice which seems to fulfil the indications just mentioned is related to have been followed in Spain with great success in 1833. Don Pedro Vazquez--its originator--published a pamphlet on the subject at Seville, in 1833, and another in the following year. The treatment consisted in giving about a quarter of a pint of olive oil, and repeating the dose two or three times at short intervals, with the intention, as the author says, of varnishing the interior of the stomach and intestines, to defend them against the action of a bad bile, by which he supposed the disease to be occasioned. It is not surprising that, with such an erroneous pathology for its basis, this treatment made no progress in countries where medicine is better cultivated than in Spain; but I consider it well deserving of a further trial on different grounds from those on which it was introduced. Prepared animal charcoal is an agent which I think deserves a more extended trial than it has yet received. Its antiseptic properties, and its power of preventing the rusting of iron and other forms of oxidation render it probable that it might counteract the effects of the cholera poison.
Sulphur, which has been recommended as a remedy for cholera by Mr. Grove, is very likely to be of service, judging of it from the power it possesses of destroying the lower forms of organized beings belonging both to the vegetable and animal kingdoms. The three agents just mentioned have the advantages that they may be given in large doses without fear of injury to the patient; and, from their physical condition, would be likely to be diffused over every part of the alimentary canal. Sulphurous acid, and the hyposulphite of soda, which have been recommended in cholera, would be likely to be beneficial for the same reasons that sulphur is advisable; but they would be less likely to pass along the whole tract of the intestines, on account of their solubility, except in cases where the function of absorption is quite in abeyance.
Some of the essential oils, and more particularly oil of cajeput, have had a considerable reputation in the treatment of cholera, as also have camphor and creosote. Now, all these agents are highly antiseptic, and also possess the property of preventing mouldiness and other low forms of organisation; and it is, no doubt, by a similar power that they are useful in cholera. Creosote has the additional recommendation, that it acts as an astringent in ordinary diarrhæa. If the view I take of the pathology of cholera be correct, these remedies should be intimately diffused in an emulsion, to insure, if possible, their application to the whole surface of the stomach and bowels. Chloroform resembles creosote, camphor, and the essential oils, in its antiseptic and medicinal properties; and it has gained some reputation as a remedy for cholera, when introduced into the stomach. Administered in the way of inhalation, it is merely useful in relieving the cramps, and has no effect on the progress of the malady; while, if cholera were a blood disease, it would be by inhalation that this and every other volatile medicine ought to be exhibited.
The benefit which has been observed in many cases from calomel, no doubt, arises from its direct action on the cholera poison in the alimentary canal, and not from its being absorbed. It has often been matter of regret to Medical men, that calomel and other medicines are not absorbed in cholera; but this regret is needless, as they do not require to be absorbed. If calomel be given in cholera, it should obviously not be in pills, but as a powder, in order that it may be diffused as extensively as possible over the mucous membrane. There are two plans of treatment having a considerable number of advocates, although they appear of an opposite nature. I allude to the saline treatment, consisting chiefly of draughts containing carbonate of soda; and the treatment of sulphuric acid. It is quite possible, however, that either of those plans, when commenced in time, may have the effect of destroying the cholera poison, or neutralising its action. There are many kinds of molecular changes in organic matter--low organic processes, as they may be called, which can be checked either by an alkali or a mineral acid. I feel great pleasure in being able to explain how cholera may probably be treated beneficially on very different plans; for, if this were not the case, the character of the Medical Profession for correct and trustworthy observation would be very much in danger. Making every allowance for the difficulty of the subject, unless cholera patients can be benefited by medicines which hold very different places in the classification of materia medica, it must be admitted that the literature on the treatment of this disease would be little creditable to us as scientific observers.
When we consider that the materies morbi of cholera finds its proper seat and sustenance only in the alimentary canal of the human being, and produces no effect apparently on the domestic animals, by which it must often be accidentally swallowed, it is probable that very slight causes often prevent its action in the first instance; and there is very good evidence that medicines of no great power will generally arrest its effects if given early, in such cases as commence gradually. Without assuming either that all the cases of diarrhæa which accompany an epidemic of cholera would pass into the developed malady if unchecked, or that every case of cholera commences with what seems an ordinary diarrhæa, when we reflect how generally the history of cholera cases begins with an ordinary an ordinary looseness, and how seldom the cases of simple diarrhæa which come under treatment during an epidemic pass into cholera, it is pretty evident that the ordinary remedies for diarrhæa have the effect of curing many cases of cholera in the early stage. As it cannot for a moment be supposed that such medicines as the pulvis cretæ compositus cum opio can have the effect of arresting a disease caused by a morbid poison circulating in the blood, all the evidence of the benefits of house-to-house visitation among the poor during an epidemic confirms the view of the pathology of cholera with which I commenced this paper, viz., that the disease consists [181/182] primarily and essentially of a morbid action in the alimentary canal. The great difficulty in ascertaining the effect of treatment in cholera consists in the circumstance, that the disease cannot be distinguished with certainty, except in a very advanced stage. If we could not recognise typhus fever till the patient had lapsed into the state of stupor from which the disease is named, we should be able to show fewer recoveries from that complaint than from cholera. One effect of not perceiving that the real seat of cholera is the alimentary canal, is to cause the treatment directed to the bowels to be left off too soon, and the attention of the practitioner to be engrossed by what are only the secondary effects of the disease. When called to a patient in a state of collapse from hæmorrhage, the first consideration of the Medical man is to prevent any further loss of blood; and, in the collapse of cholera, the chief effort should still be, to prevent any more of that effusion which has brought the patient to the condition in which we find him. It has appeared to me, that the cases which prove fatal in the stage of collapse are generally lost through the continuance of the purging; and I have seen several patients, who appeared about to recover, suffer a relapse, and sink from a return of this symptom.
Unless it is determined to inject the veins, or, as Mr. Henry Lee has suggested, the arteries, with a very weak saline solution, it is clear that the patient cannot recover from the state of collapse, except by the absorption of watery fluids from the alimentary canal. To allow the drinking of cold water, for which there is a great desire, is in accordance both with reason and experience. The greater part of it is generally vomited, but that is of no consequence. On the other hand, reason and experience are just as much opposed to hot air-baths and other attempts to raise the heat of the surface, which can only have the effect of increasing the symptoms of asphyxia, so long as the blood remains so thick and tenacious, that it can hardly circulate either through the pulmonary or systemic capillaries. The results obtained, by injecting the blood-vessels in 1832, were so far encouraging, that it is somewhat surprising that this practice was hardly resorted to in 1849. The cause of its failing in most cases was, that the liquid injected flowed away almost immediately by the alimentary canal; in future, it would therefore be desirable to continue the treatment directed against the affection of the stomach and bowels, at the same time that the blood-vessels are injected. As regards the nature of the injected fluid, Dr. Garrod has very properly suggested, that a solution should be employed which resembles as much as possible the portion of the blood which has been lost; and he recommends that the phosphate of soda should be used, rather than the carbonate, which has generally been employed.
The so-called consecutive fever, which comes on after certain cases of cholera, is caused by the retention of excrementitious matters in the blood, owing to the kidneys not resuming their functions. It must be looked on rather as a sequela than an essential part of the disease, and I have nothing to offer to the Society respecting its treatment.
In bringing this short paper to a conclusion, it will be perceived that I have no plan of treatment to offer which promises any great results in the more severe and fully-developed cases of cholera, and, indeed, that I have suggested nothing in the way of treatment that is new. The view of the pathology, however, which I have endeavoured to establish, has a tendency to circumscribe and define the objects of treatment. I have endeavoured to prove that the seat and action of the materies morbi of cholera is the interior of the alimentary canal, and the principles of treatment resulting from this view of the disease may be briefly recapitulated as follows:--
1st. Medicines should be chosen which have the effect of preventing the various kinds of molecular change in organic matter.
2nd. They should be administered with a view to their action in the stomach and bowels, and not to their being absorbed.
3rd. The medicines should be given in such quantities and in such form as to insure as much as possible their application to the whole surface of the alimentary tube.
4th. These remedies should be continued until there is no danger of a relapse.
5th. It is useless and injurious to attempt to bring the patient out of the state of collapse by stimulants and the application of heat, and we should give watery drinks, and be content to wait till they are absorbed, unless in desperate cases, when it might be desirable to inject into the blood-vessels a weak saline solution resembling "the portion of the blood which has been lost."
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