– Puerperal eclampsia – its etiology and treatment (H. D. Bishop)
The time will probably come when puerperal eclampsia will no longer be called the “disease of theories,” as it was so aptly designated by Zweifel, but that time is not yet, as is shown by the endless array of methods of treatment which are constantly being brought forth.
The belief that renal disease is its chief, if not its only cause, which was first pointed out by Frierichs in 1851, had an almost general acceptance for many years, yet it has been as generally abandoned since conclusive data have been available showing that eclampsia occurred without albuminuria and that chronic cases of renal disease often existed in pregnant women, without the occurrence of eclampsia, or, if it did occur, it was only in exceptional cases.
Many other theories of the cause of the disease have been advanced: hepatic disease (Klebs); brain anaemia and oedema (Traube, Rosenstein, Munk); toxemia, arising from the genital tract, particularly the interior of the uterus (Müller); bacterial invasion (Délore, Rodet); auto-intoxication from maternal and fetal metabolism (Chamberlent, Tarnier, Fehling, Dienst, Schmorl and Knapp).
It is certain that all of these observers have based their conclusions upon careful clinical and experimental data and as such they are evidence of advance in the knowledge of the complex nature of the disease, yet the fact remains that up to the present time no conclusive evidence has been adduced in support of any one theory. The most tenable conclusion, to be derived from all investigations, is that puerperal eclampsia is due to some disturbance of metabolism during pregnancy, which produces an auto-intoxication of some sort, this auto-intoxication being caused either by defective elimination of the products of metabolism or by a failure to properly transform or destroy such products.
In connection with the probable cause of this auto-intoxication. I wish to speak somewhat in detail of the idea, advanced by Nicholson (Scottish Medical and Surgical Journal, June, 1901), and urged by others since that time. Nicholson suggested a possible causative relationship between puerperal eclampsia and an inadequacy of function of the thyroid and parathyroid glands. He based his conclusions upon the observations made by Lange (Zcits. f. Geb. u. Gynäk., Band 40, Heft I.), that the thyroid is frequently small in eclamptic cases.
Lange examined the condition of the thyroid in 133 women during the last twelve weeks of pregnancy. In 108 there existed the normal enlargement incident to pregnancy, in three cases its existence was doubtful and in 22 it was absent. Of the 12 cases in which the enlargement was manifestly absent, 20 showed evidences of the toxemia of pregnancy, 16 of the 20 having albumen and casts in the urine. In the 108 cases, which had normal thyroid enlargement, only two had an albuminuria and both of these presented a history of nephritis existing before pregnancy.
These observations certainly point to some positive relationship existing between the thyroid secretion and the disturbances of metabolism which are found in eclampsia. Sajous (The Internal Secretions and the Principles of Medicine, Vol. 1, 1903), by a most remarkable line of reasoning, which is based upon physiological and clinical observations, has formulated a principle regarding the function of the thyroid, which the above data of Lange confirm. If Sajous’ line of reasoning is correct, it would seem that he has explained the condition noted by Lange and has established a basis upon which the treatment of puerperal eclampsia, and in fact all intoxications, can be systematically studied.
Sajous’ line of reasoning can be summed up in the following conclusions:
The thyroid gland, the anterior pituitary body and the adrenals are functionally inter-dependent, and constitute a system, which has for its purpose, to sustain physiological oxidation and the metabolic activity of the tissues.
The physiological function of the internal secretion of the adrenals is loosely to combine with the atmospheric oxygen in the lungs, and to endow the blood-plasma with its oxidizing properties. To this oxidizing compound, thus formed, Sajous has given the name “adrenoxin.”
The anterior pituitary body governs the functional activity of the adrenals, and is directly connected with them through the cervico-thoracic ganglia, the splanchnic nerves and the semi-lunar ganglia of the sympathetic nervous system.
The physiological function of the thyroid secretion is to sustain the functional activity of the anterior pituitary body. When the function of the thyroid is inhibited, the anterior pituitary body and the adrenals become correspondingly inefficient in their function, and all of the oxidation powers of the organism are reduced in proportion.
The above relationship between the anterior pituitary body, the thyroid, and the adrenals has been proven correct by animal experiments. Stimulation of the pituitary body produces all of the physiological effects secured by the administration of adrenal extract. Removal of the pituitary body produces death, preceded by symptoms resembling those of thyroidectomy. In diseases affecting metabolism, such as puerperal eclampsia, the pituitary body shows marked changes. L. Comte (Contribution à l’ étude de l’Hypophyse humaine, etc., Thése de doctorat, Lausanne, 1898) examined the pituitary body in a number of women who had died during pregnancy, and found not only that this organ was hypertrophied, but that the anterior lobe was alone the seat of the hypertrophy. P. E. Langlois and P. Mulon (Annales de Gynec, et d’Obstet., Jan., 1904) state that in the histological examination of the pituitary body in two eclamptic women, who died during eclamptic seizures, they found marked evidences of hyperactivity of this organ.
The normal enlargement of the thyroid during pregnancy corroborates this conception of the function of the adrenal system. This enlargement is not a hyperemia, but is a distinct hyperplasia which is characteristic of the normal physiological condition of pregnancy. If the assured relationship between the thyroid secretion and the anterior pituitary body is correct, this hyperplasia is simply a means of increasing the thyroid secretion in order that it may sufficiently stimulate the center of the oxidation processes of the body. Lange’s clinical observations (loc. cit.) sustain this conclusion, in that he found that where there was thyroid enlargement during pregnancy, the administration of thyroid extract reduced the size of the gland. This shows that during the time of thyroid medication less thyroid secretion was needed by the organism and therefore the thyroid hyperplasia diminished.
There is no doubt but that marked enlargement of the thyroid is comparatively rare during pregnancy, and the proportion noted by Lange is larger than is usually found, yet I believe that an unrecognized enlargement is present in many cases. Since the publication of Nicholson’s paper, I have noted thyroid enlargement of a greater or less degree in at least two-thirds of the cases I have examined.
It seems to me that this conception of the functions of the adrenals and their dependence upon the thyroid and anterior pituitary body explains the clinical facts noted in puerperal eclampsia. During pregnancy, there is an increase of toxic agents circulating in the blood stream, owing to the extra metabolism of the mother and fetus. Any condition which interferes with the elimination of these toxic products, predisposes to their producing the characteristic symptoms of poisoning, i. e., the lesions of the viscera and the nervous phenomena of puerperal eclampsia. Such predisposing conditions are pressure upon the ureters and kidneys, the kidney of pregnancy, nephritis and reflexly induced renal anemia, constipation, nervous and psychic excitability and irritability. These conditions do not produce toxic products of metabolism, they only favor their non-elimination. More important than non-elimination is the failure of the physiological function which, under ordinary circumstances, meets and conquers these toxic agents. We must admit that toxic agents are present in every case of pregnancy, the only difference being a variation of the amount. According to the views held by Sajous, failure to oxidize them into inert bodies is due to a partial or complete inactivity of the adrenal system. The adrenal system is primarily at fault, or it is overtaxed by the great amount of work it has to do.
“Adequate cellular metabolism,” says Sajous, “means life,” and proper functional activity of the thyroid, under normal conditions of metabolism, or stimulation of its activity in cases of increased metabolism, is necessary to such perfect cellular oxidation. All clinical and experimental data regarding the thyroid, bear out this principle. The effect of thyroid extractives upon metabolism, is that of oxidation, and when administered they “make the tissues, as it were, more inflammable, so that they burn away more rapidly.” (Hutchinson, British Medical Journal, July 16, 1898.)
The thyroid theory, per se, as an explanation of puerperal eclampsia, has been opposed by many. Cases of myoedematous women have been reported, who have borne children and who did not have eclampsia, but, on the contrary, have improved in their general condition, the improvement, no doubt, being due to the action of the fetal thyroid. The thyroid has been removed from bitches while pregnant, without producing eclampsia. While these arguments might avail against the thyroid theory, alone, they do not hold as regard the so called adrenal theory. According to this, the fact that thyroidectomized animals did not develop eclampsia, simply shows that the adrenals, alone, were adequate to meet the extra call upon their function.
Treatment. In the light of the foregoing regarding etiology, the most important part of the treatment of puerperal eclampsia is its prophylaxis. This prophylaxis should consist of a prevention of the formation of toxic waste products of metabolism. This, alone, should be the basis of the treatment of toxemia of pregnancy as well as puerperal eclampsia.
The detection of the early signs of toxemia, therefore, becomes the most important part in the management of cases and in it lies the secret of the prevention of the more marked lesions of eclampsia.
At the present time, we have no knowledge as to the exact identity of the toxic waste products which accumulate in the blood stream as a result of fetal and maternal metabolism; neither have we positive means of determining their presence or the extent of their toxic action, by subjective and objective symptoms or methods of clinical diagnosis. “Animal protoplasm,” says Howell (American Text-Book of Physiology, 1900, p. 20), “is pre-eminently catabolic and the evidence of its catabolism is found in its waste products, CO2, H2O, and urea.” Urea, being the end product of nitrogenous metabolism, any lessening in the amount of its excretion, is an index either of a failure of its elimination or of the oxidation processes which produce it, yet we cannot assume that urea plays the chief role in the toxemia of pregnancy, because of the multiplicity of substances of indefinitely known identity, which are retained in the blood at the same time with urea. (Herter, N. Y. Medical Journal, May 21, 1898.)
Clinical experience, however, shows that the chief danger signal in puerperal toxemia is a constant and progressive lessening in the excretion of urea. It always means an auto-intoxication and is of much more importance than the evidence of renal disease. Whenever subjective symptoms of puerperal toxemia exist or there is evidence of a tendency towards it, as shown by a lessening in the normal amount of urea excretion, the rational method of treatment, based upon Sajous’ views of the physiology of the oxidation processes of the body, is along two lines.
(1) Hygienic. This includes restriction of the diet, particularly of nitrogenous foods; increase of the oxidizing powers of the body by attention to the improvement of the circulation and the oxygenation of the blood; increase of elimination by diuresis, diaphoresis and catharsis.
(2) Medical. This includes the stimulation of the adrenal function by known adrenal stimulants. Since the publication of Nicholson’s paper, I have given thyroid extract, syr. hydriodic acid, potassium iodide or arsenicum iodide in every case of pregnancy where there have been evidences of toxemia and especially where there has been a lessening in the amount of the excretion of urea. In the latter conditions, the increase in the elimination of urea has been marked in every case. In addition to this medication, the homeopathically indicated remedy has been prescribed for reasons to be referred to later. Upon this basis of treatment, I believe that most if not all cases of puerperal toxemia can be saved from the more serious and often fatal conditions incident to eclamptic convulsions.
If the toxemia has been overlooked and appropriate treatment has not been given, the condition is one in which the blood is surcharged with toxic products. The indications for treatment are renewal of the physiological functions whose inactivity permitted the formation of the toxic products, prevention for the time being, of the formation of these products, removal of the cause of the increased maternal and fetal metabolism, and rapid removal of the accumulated toxic products.
(1) The renewal of the physiological function whose inactivity permitted the formation of toxic products is accomplished by the re-establishment of the physiological function of the adrenals.
Puerperal eclampsia is due, according to the views previously expressed, to the inactivity and insufficiency of the adrenal system. Its function has failed on account of its inability to cope with the products of maternal and fetal metabolism. The first indication in treatment, then, is to so stimulate the adrenals that they will be raised from the depths to which they have been forced, in order that they may be able to resume their function.
Before considering the remedies to be used for this purpose, I wish to speak of a line of thought which I have been pursuing since the publication of Sajous’ views. I believe that a possible explanation of our homoeopathic law of cure is found in his investigations regarding the physiological action of the adrenal system.
The physiological action of a drug, upon which our materia medica rests, represents the disturbances produced by it upon the healthy body. The cardinal symptoms of the physiological action are in reality, the manifestations of overactivity or insufficiency of the adrenals, brought about by the efforts of the organism to dispose of the drug. These symptoms are induced by the primary action of the drug upon the center of the nervous elements that control the adrenal secretion. The opposite effects, so often noted in drug action, are due to the primary action of stimulation of the anterior pituitary body, by the drug and the secondary action of partial or complete arrest of its function.
Precisely as is the case with drugs, the toxins of disease produce similar conditions of overactivity and insufficiency of the adrenal system, acting directly upon the anterior pituitary body, either stimulating it, or if of sufficient amount, depressing its function. Each toxin acts upon the anterior pituitary body in its characteristic way, producing the characteristic symptoms of disease.
The conclusion seems evident that the manifestations of adrenal disturbance originate from similar causes, whether the cause be a poisonous drug, a pathogenic germ or its toxin. Assuming that this conclusion is correct, is it not reasonable to assume that for a symptom of disease which represents overactivity or depression of a function, a remedy should be chosen which produces a similar symptom.
It seems to me that if the above explanation of the physiology of the adrenal system is correct, the law of similia offers a means of close differentiation of remedies in choosing the adrenal stimulant required in a given case.
It is beyond the limit of this paper to further discuss this interesting question, but I believe that it is worthy of careful consideration and study by others more capable than I.
In considering the remedies to be used in the treatment of puerperal convulsions, mention is made only of those which are known to have a well-defined action upon the adrenal function. It is to be noted that the drugs most often used in the homoeopathic treatment of this disease, such as Aconite, Belladonna, Cuprum, Gelsemium, Iodine and Veratrum viride, correspond in their general pathogenesis, to the symptoms produced by the removal of the adrenals. Removal of these organs is followed by extreme muscular weakness, marked reduction in blood pressure, hypothermia, dyspnoea and blood changes. (Sajous, loc. cit., p. 39.)
(a) Iodine. This halogen is the chief constituent of the thyroid secretion and as such it is indicated in every condition in which there is evidence of insufficiency of the adrenal function. It is distinctively homoeopathic to the conditions manifested in puerperal eclampsia. “Through the organic nervous system, it acts upon the whole lymphatic and glandular system, especially centering upon the thyroid. At first it stimulates it to increased action and this hyperstimulation is soon followed by depression of the most marked character.” (Burt, physiological Materia Medica, 1881, p. 481. The internal use of iodine, in the form of thyroiodine, has been shown to be curative in puerperal eclampsia by Nicholson, (loc. cit.) He reports a case which had eclampsia and who was cured by the administration of thyroid extract, ultimately going on to term and giving birth to a healthy living child.
(b) Belladonna. In toxic doses, this remedy produces symptoms, identical with those of adrenal inactivity. Its pathogenesis corresponds to the eclamptic seizures and it occupies a high position in the homoeopathic treatment of puerperal eclampsia. “No remedy responds to this disorder as completely as Belladonna,” says Bachr (The Science of Therapeutics, p. 166).
(c.) Carbolic acid. The action of carbolic acid in toxic doses, corresponds to the symptoms produced by adrenal insufficiency. Its action as an adrenal stimulant, when given in small doses, is shown in the results secured by Baccelli in his treatment of tetanus. He states “that of 40 cases of tetanus treated with carbolic acid, sub-cutaneously, only one died.” (Packard and Wilson, American Journal, Medical Sciences, Dec. 1902.) The similarity between tetanus and puerperal eclampsia lies in the fact that both diseases are caused by the accumulation of toxins in the blood. This accumulation is dependent upon inhibited oxidation from adrenal insufficiency (Sajous, loc. cit., p. 769).
Carbolic acid has never been used, to my knowledge, in the treatment of puerperal eclampsia, yet it should have the same result when given in small doses, as in the Baccelli treatment of tetanus. It not only counteracts the insufficiency of the adrenal system, but it raises the activity beyond the normal.
(2) Prevention, for the time being, of the formation of toxic products.
The favorable action produced by the administration of comparatively large doses of morphine during eclamptic seizures, cannot be entirely explained by the fact that opium is an adrenal stimulant. One of the most pronounced actions of opium is the inhibition of metabolism and it seems reasonable to assume that a part, at least, of its favorable action is eclampsia, as the cutting off for the time being of the source of the toxins. I believe that unless it is contraindicated, morphine should always be given in full doses, during the eclamptic convulsions.
(3) The removal of the cause of increased maternal and fetal metabolism.
In the majority of cases, at least, the existence of a living child in the uterus, is the chief factor in the production of the increased metabolism. Duhrssen, Ilshausen, and Zweifel noted a cessation of the eclamptic convulsions, either immediately, or some time after delivery in 93.75%, 85%, and 66% of their cases, respectively (Williams, Obstetrics, 1903, p. 707). The belief that labor should be induced immediately upon the advent of eclamptic convulsions is based upon such statistics as these.
In the light of the views previously expressed, regarding the etiology of puerperal convulsions, operative treatment by the induction of premature labor, should not be resorted to until it is found that the treatment based upon these views, is futile. A toxemia, which has reached a point of intensity, sufficient to produce convulsions, will usually precipitate labor. If it does not do so, I do not believe that we are warranted in immediately inducing it. Instead, we should resort to every known means of stimulation of the adrenal function and only after failure in this should we resort to operative treatment.
The most satisfactory method of inducing labor, in my experience, is to dilate the cervix with a small dilator sufficient to admit a small Champetier de Ribes bag. This is filled with sterile salt solution and the internal is dilated until manual dilatation can be carried out by the Harris’ method. Instrumental delivery can be made, if necessary, after full dilatation.
Caesarean section is indicated in severe cases where the life of the mother is in danger and where there is a possibility of preserving the life of the child by its prompt removal from the uterus.
(3) Rapid removal of the accumulated toxic products.
(a) Saline infusion. Whatever the role of action of saline infusion, it is clearly demonstrated by animal experiments and clinical tests, that by its use, toxic products in the blood stream are rendered less toxic or absolutely inert. It seems unnecessary, in the light of the extensive use of saline infusions in all forms of toxemia, to give clinical data bearing upon this assertion. A most convincing test of the hypothesis is given by the experiments reported by Mathews (Yale Medical Journal, June, 1903). “Rabbits were injected with fatal doses of tetanus toxin and 48-60 hours after the injection, when the symptoms of the disease were just appearing, saline infusion was given. In nearly all cases, if taken early, the animals survived while the control animals died. In well advanced cases, the saline infusion was found to be useless.”
From the latter observation, it seems to me that an important point is to be deduced, namely, that saline infusion, if given at all in toxemias, should be given early. My experience with its use in all forms of toxemia, is that the best results are obtained when it is given early, given continuously, and given slowly, no more than the tissues will absorb without producing distension.
(b) Catharsis. I do not use the hydragogue cathartics in the treatment of puerperal eclampsia unless there has been a history of constipation and a quick acting cathartic is indicated.
(c) Diaphoresis. The hot pack offers a valuable means of elimination of toxic products and I usually use it at the same time with the saline infusion.
J. L. Moffat, M. D.: After reading Sajous’ book I felt that it will become more and more of an epoch-making work. I think it is going to make us understand how some of our homoeopathic remedies act, although I do not believe we will use our remedy according to Dr. Sajous’ theory. We still have our homoeopathic indications for remedies for eclampsia. I doubt if all diseases are due to excess or deficiency of adrenal secretion. They may all be due to over-action or under-action of the adrenal or the pituitary body. Some remedies will stimulate the pituitary body directly and some not. I think we may find that Stramonium, Belladonna, etc., will act on the pituitary body.
B. H. Ogden, M. D.: In the line of experience I can say that during the last year I have had cases not of eclampsia where elimination of urea was greatly deficient, and in two of these instances, one of which was based upon nervous disorder and seemed to be on the verge of paresis, Potassium-iodide was given in one- to five-grain doses. The excretion of urea was marvelous after giving this remedy; before using it there was 11/2 per cent of urea; afterward it jumped up to 4 per cent. With the excretion of urea there was remarkable improvement in the symptoms. Experience with these cases would make it seem to me that the administration of Potassium-iodide would be a useful procedure in eclampsia or any case characterized by deficient excretion of urea. I have not found diminished urea in all my cases of eclampsia. Possibly such cases are more of the neurotic than the toxemic type.
Jno. L. Moffat, M. D.: My attention was called last year to the danger of penetration of blood-vessels in giving saline infusions. The suggestion was made that we add sugar to the solution, and there was a fear expressed that the sugar might afford too much of a culture-medium.
The last speaker was talking about increased urea, and then he used the word “percentage.” To me that word is misleading. If we know the total quantity of urine for 24 hours, and the percentage of urea in that, why, very good; or if the total quantity at the end of a certain number of hours is a little more or a little less, then we can tell the quantity of urea. We may or may not have a higher percentage of urea in the urine when it is plentiful. I recall a case in our hospital some years ago where the patient was excreting 5 grams of urea in 24 hours, and she weighed 150 pounds. She was just about to be delivered. I think the boiling test for albumen made the albumen look solid. The percentage of albumen was not given in that case, but it was very high. The woman went through all right.
B. H. Ogden, M. D.: In the case I referred to the amount of urea which was eliminated after giving the Potassium-iodide was surprisingly great for two or three days, and then gradually came down to normal. I mentioned it simply to confirm Dr. Bishop’s observations upon the effects of the administration of Potassium-iodide when diminished secretion of urea is a symptom.
Geo. R. Southwick, M. D.: I think it is very difficult to know when to interfere in eclampsia. I have seen cases where I thought conservatism was carried on too long. We should watch our patient carefully, and if we find on examination of the urine that there is a diminution of urine and an increase in the solids, if we find epigastric pain and interference with vision, it is time to act. I do not believe it is right, if a patient has a slight convulsion, to wait to see what is going to happen. I think we better interfere early, as the mother’s life cannot be replaced. Another child may come, but the mother’s life is of supreme importance. It is possible, in the excitement of the moment, to do too much. I am confident that when we interfere too quickly we leave the patient in a condition where eclampsia is very apt to occur.
I am not quite sure that I believe entirely in the theory of the physiology of the glands. I would like to know whether post-mortem would show whether those glands have anything to do with the etiology of eclampsia. I think the practical point in eclampsia is not to wait too long before interfering – then interfere carefully, interfere slowly.
L. L. Danforth, M. D.: With reference to disturbance of the functions of the glands which has been mentioned as causative of eclampsia, I know very little. It seems to me that the subject is at present very theoretical. At the same time I believe that eclampsia is due to a poisoning of the system. We do not know the origin or the nature of the poison. The cause of the condition itself is extremely complex and difficult to understand.
With reference to the significance of the diminution of urea in these cases, I have been astonished to observe to what degree the urea may be diminished, and yet, very little toxemia. I have been in the habit of having my patients bring the 24 hour amount of urine, and I estimate the amount of urea for this time, but when it reaches 1 per cent they do not by any means always have bad symptoms. I regulate the diet, and I always take into consideration the amount of fat the patient is taking in estimating the significance of the amount of urea. It is important to watch closely, but I do not think every woman who has an elimination of urea of 1 per cent is necessarily in danger of eclampsia. I believe in eliminative treatment in conjunction with the homoeopathic remedy. I concur with what Dr. Bishop has said about hot baths, and clearing out the bowels, and that all the enuncitories of the body should be stimulated.
I believe that we may lose mother and baby, too, if we wait too long. You can do something with a live baby, and you cannot with a dead baby, and of course we want to save the mother. I do not believe in giving much opium in these cases. I trust that something definite will come out of the study of these important glands.
H. D. Bishop, M. D.: I want to call your attention again to the statistics reported by Lang. I think in reading a paper it is almost impossible to grasp the importance of statistics. I believe his statistics are very important and very suggestive. Lang first began to make observations in 1898. The queer thing about it is that he made no deductions about it whatever. I think in 1900 Lang made this report of a series of 133 women examination of whose thyroids were made during pregnancy. He found 108 with normal enlargement of the thyroid, in three cases he found doubtful, and 22 cases in which enlargement was absent, and here is the important point about these 22, 20 of the 22 showed toxemia of pregnancy, and of the other two cases in which enlargement was absent, one had albuminuria, and both developed eclampsia, and both had nephritis previously.
Another point. In regard to the use of the iodine preparations. I believe in their use in all cases of toxemia, and especially in those cases where the excretion of urea is diminished. I was very glad to hear what our secretary said about his experience. My experience has been same as his, viz.: that the iodide-of-potassium increased the amount of urea, bringing it up to normal. I have given the iodide-of-potash in 5-grain doses three times daily. I have tried the iodide 2nd Trit., but I really think I have the best results from thyroid Ext. given in 5-grain doses three times a day.
G. B. Stearns, M. D.: I simply wish to corroborate what the last speaker said about the hand as a dilator, knowing exactly what can be done with the hand. Introducing one finger, then another, and another, seems to supplement all other methods.