The toxemias of pregnancy

Preface

The toxemias of pregnancy constitute a group of complications of the period of gestation which, in so far as a true knowledge of their processes is concerned, is still largely in the realm of theory and speculation. Notwithstanding this fact a fairly rational understanding of this subject now obtains and this monograph will attempt a presentation of the facts and such particular deductions as may be of value in the diagnosis and treatment of these abnormalities of the pregnant state.

The views held regarding the toxemias of pregnancy have undergone decided modifications since the early assumption that they were due merely to aberrations in the function of the kidney or liver. It is now more generally acknowledged that we are dealing rather with metabolic disturbances and that the clinical manifestations with which we are familiar are merely the expressions of localized damage to the organism. In the present work it is proposed, after tracing the development of our knowledge of the subject, to take up the etiology, symptomatology, and pathology, including the more recent studies in the chemistry of the blood and urine. The section on the urine has been contributed by Dr. F. E. Sondern, of New York, and that on the blood by Dr. J. A. Killian, of New York, to both of whom I desire to express herewith my sense of obligation. The final section is devoted to treatment and prophylaxis with particular attention to the results accomplished by adequate prenatal care.

I desire to acknowledge an indebtedness to those medical friends and colleagues who have courteously favored me with many valuable illustrations from original sources or from their published papers and books. I hope that I have not neglected to give due credit in every instance to these in the text.

George W. Kosmak

New York

Contents

CHAPTER PAGE

I. Historical i

Earliest references to toxemias of pregnancy in the writings of Hippocrates and Galen, i — Derivation of "eclampsia," i — References in Italian medical works of the Middle Ages, 2 — Introduction of term into French and German medical literature in the eighteenth century, 2 — Early English observers, 3 — Distinction between hyperemesis and eclampsia in early part of nineteenth century, 5 — Clinical knowledge of eclampsia in existence for several centuries, 11 — Modes of treatment, 11.

Chapter I Historical

Earliest references to toxemias of pregnancy in the writings of Hippocrates and Galen — Derivation of "eclampsia" — Occasional references in Italian medical works of the Middle Ages — Introduction of term into French and German medical literature in the eighteenth century — Mauriceau — Amberg — Early English observers — Burton, 1751 — Hamilton, 1781 — Distinction between hyperemesis and eclampsia in early part of nineteenth century, Bard, 1815 — Clinical knowledge of eclampsia in existence for several centuries — Modes of treatment by purgation, venesection, sedatives and alkalies — Prophylaxis a much later development — General interest in subject shown by voluminous literature.

The task of writing a historical introduction to this subject is lightened by the usual procedure adopted by most medical writers of going back to the fathers of all things medical, Hippocrates and Galen, for the necessary beginnings. In their treatises as they have come down to us, we find numerous though rather confused references to the diseases recognized to-day as the toxemias of pregnancy. Such irregularities in the normal course of gestation as manifested by constitutional disturbances were usually attributed to retention of various "humours," and while distinct references are made both to excessive vomiting and convulsive seizures, there are no specific explanations oflfered as to their cause, nor definite recommendation for their treatment. That the more violent manifestation of the toxemias of pregnancy were recognized in the time of Hippocrates may be gathered from the fact that the derivation of our word "eclampsia" is from the Greek eKkaixiru, which, meaning "flash" and conveying the idea of a sudden onset, was used by this writer to designate a rapidly developing fever. We find the word revived by Sauvage, who employed the term in his writings and in a work published in 1796, Gehler, taking it from the latter, introduced it into German medical literature. It was not until the beginning of the last century, however, that "eclampsia" superseded the more general designation of

"convulsions" as an appellation descriptive of the principal symptom associated with this complication of pregnancy. The occurrence of gestation in epileptic women led to confusion which persisted for a long time and we find that many writers in the early part of the nineteenth century still regarded the convulsions in the latter months of pregnancy as epileptic seizures.

Occasional references are found in the Italian medical works of the Middle Ages, but it is not until the eighteenth century that we meet with well recognized descriptions of the toxemias of pregnancy. Mauriceau, writing in the latter part of the seventeenth century, presents certain definite notions of these disorders. He attributes intractable vomiting to the cessation of menstruation, which caused "corrupt humours cleaving to the insides of the stomach, which being impossible to be evacuated by so many preceding vomitings because they adhere so fast, must be purged away by stool; to effect which they need a dissolvent, which may be a gentle purge ... In perturbations and dejections of the belly, and in spontaneous vomitings, if the matter be purged away, the patient finds ease and comfort; if not, the contrary ... If the vomiting continues daily, almost without intermission, although the woman observes a good diet, and after she hath been reasonably purged, we must rest there, lest something worse happen, for which we may incur the blame; she being then in great danger of miscarriage. And when the hiccough takes them through emptiness proceeding from too much evacuation caused by these continual vomitings, it is very bad."

Amberg reported, in 171 3, his observations on convulsions, which are interesting enough to be repeated in detail. He describes the case of a young lady twenty-six years of age "who had gone about one-half her time with child and had not yet been bled, was invaded with convulsions of the hands, feet, head, mouth, and cheeks, which terrified her greatly, and rendered her apprehensive of their being succeeded by an apoplexy or epilepsy." She consulted Dr. Amberg who prescribed as follows: "Phlebotomy in the arm immediately to eight ounces. A teaspoonful every morning of a 'nervous powder' to be repeated in the afternoon at four o'clock and at bedtime." The majority of the ingredients of this powder cannot be duplicated in the present-day pharmacopoeia, but were evidently designed for their refrigerant and laxative effects. Amberg states that, after continuing these medicines for two days, she "perceived no more of her convulsions, and she was happily delivered of a healthful child."

Burton, in his essay Tozvards a New System of Midwifery, London, 1751, in the part devoted to the diseases of pregnant women, repeats the earher contention that some of these disorders arise solely from the stoppage of the menstrual flux ; others from the motions and bulk of the fetus, secundines and waters. He claims that the "stoppage of the menstrual flux cavises vomiting, loss of appetite, nausea, faintings, vertigo, pains in the stomach, shortness of breath and cough, all of which generally abate about the third month of pregnancy, or sooner. From the second cause also proceed vomiting, shortness of breath, cough, incontinence and suppression of urine, and constipation. Likewise pains in the back and groin, varices, piles, and swellings of the legs, thighs and pudenda." "These vomitings," he states, "seem to be occasioned by various causes which require different methods of relieving them. First, they may be caused by too great a distention of the blood vessels, whereby the nerves may be so pressed as to occasion that convulsive motion of the diaphragm, stomach, bowels and abdominal muscles which we call vomiting. Secondly, the vomiting may be occasioned by the remains of undigested food, being either too great in quantity or by being too acrimonious." The second cause, he moreover observes, "may proceed from too great extension of the womb, which sometimes will rise over-high in the abdomen, especially in people whose bones that form the lower part of the hypogastric region, are too straight, or as it is commonly called 'straight-hipped' . . . The appetite very often, nay generally, is depraved from the beginning of pregnancy, for the blood vessels being so much distended, by pressing on the nerves may hinder their action, so as to prevent their use in causing the sensation of hunger. Sometimes also this may proceed from the little consumption of the humours, the vessels being full; whence nature has not as great a demand, as the child consumes so little ; and as the mother seems to perspire less than usual, as appeared from the seeming heaviness and torpor, which pregnant women so often complain of."

An interesting reference to "convulsions and lethargy occurring in labor" is found in a treatise by Madame Le Boursier du Coudray, Chief Midwife of Paris, published in 1777.

"It sometimes happens that a woman will have convulsions before she goes into labour. If such an accident happens, a competent doctor or surgeon should be called, as the condition is dangerous to both mother and child, and a careful examination should be made to find out just how they are doing. While awaiting this assistance, the patient should be bathed with pure water, and care should be taken that none of it be allowed to touch her face or her throat, as this will increase the violence of the convulsions, as will likewise spirituous liqueurs. If labor begins during the convulsion, and the child presents well, there is hope for the patient and delivery should be hastened as much as possible. If there be a bad presentation, or version must be done, this will serve to greatly increase the irritation of the nervous system already so greatly disturbed; therefore it is better to await patiently the course of nature . . . There is another state apt to prove fatal to the woman, that is when she falls into a lethargy; all the resources of the animal economy being exhausted, so that there is nothing left to assist her in giving birth to the child. Under these conditions it is necessary to make delivery as promptly as possible, as that is the sole hope of saving the mother's life. I have often found myself in both the situations above outlined, and having called in skilled and competent (medical) people, I am able to state that none of my mothers died, and I was able even to deliver some living children."

Hamilton, in his Treatise on Midzvifery, published in Edinburgh in 1 78 1, refers to the alteration in the blood in the pregnant state which may account for many of the symptoms of pregnancy; particularly the appearance of a general, and sometimes of a local, plethora. He believes, however, that "many of the symptoms appear to be entirely of the nervous kind, and not readily explicable ... In the advanced states of pregnancy the pressure of the uterus on the surrounding parts produces many complaints." He refers to convulsions during pregnancy as possibly occurring in the early months, although more common in the latter months, and at the commencement of labor. He states that the "a.ppearance of epileptic fits in pregnant women is frightful; the symptoms are alarming; and the event is always precarious, often fatal." It is interesting to note Hamilton's description of the prodromal stage of which he says "headache, intolerably violent, or tense pain or oppression about the prsecordia, are the most common presaging symptoms." The exciting cause he believes to be "uterine irritability communicated by sympathy to the encephalon, in some instances probably originating from the struggle or convulsive motions of the fetus, arising from its awkward or hampered position, and pressure of the gravid uterus interrupting the circulation through the abdominal viscera, disturbing their functions and changing the determination both of the circulating fluid and nervous energy." Hamilton, it is stated in a footnote by Dr. Burns, was among the first English writers to employ the term "eclampsia."

In an English book by S. H. Jackson published in London, 1801, entitled Cautions to Women Respecting the State of Pregnancy, the writer, in describing the irritations of the stomach, claims that it would be nearer the truth "if we suppose them to arise either from pressure against the inside of the liver and gall-bladder, or on the great vessels belonging to the heart. This pressure is most likely to occur in persons of small stature and it is not infrequently accompanied by some degree of jaundice,"

In the early years of the nineteenth century we begin to find more clear-cut references to hyperemesis and eclampsia. In Heath's Translation of Baudelocque's Midwifery, published in Philadelphia in 1807, puerperal convulsions are stated "to depend on sudden and great emotions of the mind, or a sanguine plethora, or an excessive flooding, or on a fullness of the primse vise, on an extreme sensibility of the uterine fibers, a violent distention of the edge of the orifice of the uterus, and of the parts which form the entrance of the pudendum. . . . The occurrence of all these causes is not necessary to produce convulsions ; a single one is sufficient. All convulsions are not of the same nature nor affect the organs, nor equally disturb the harmony of the functions. Sometimes they present a frightful spectacle, at other times the countenance is tranquil. Sometimes the understanding does not return for hours or even days after these convulsions."

In Bard's Compendium of Midzvifery, published in New York in 181 5, we find extended references to hyperemesis and convulsive seizures. The writer insists that in intractable cases of vomiting relief is obtained only from a removal of five to six ounces of blood for three or four successive days rather than at one time. In accordance with the belief prevailing at that date he describes the convulsions of the latter months of pregnancy as "epileptic fits" to which women are peculiarly subject in pregnancy. He also states that "women who are inhabitants of populous cities and in the higher spheres of life, who have been delicately bred and who indulge themselves in a dissipated and luxurious life, are much more liable to these dreadful and fatal diseases than the more hardy inhabitants of the country, or than such as from constant labor and exercise enjoy robust constitutions." This scarcely agrees with our observation of the present day that eclampsia is as prevalent among the poor as among the well-to-do. It is probably even more prevalent among the poor, unless proper supervision is maintained.

Bard believes, moreover, that "women are most liable to convulsions at the commencement of labor when the first dilatation of the extremely sensitive os uteri seems to bring them on. They are more apt to occur in a first, than in subsequent labors, from the great apprehension and terror which some women suffer on that occasion; and perhaps for a similar reason, whose labor is brought on by some dangerous accident, some sudden stroke of affliction, who have suffered convulsions on a former occasion, and those unhappy women, who, instead of rejoicing in the birth of the child, dread consequent reproach more than the pain and danger."

Further interesting observations are contained in the paragraph in which Bard states that "the danger of convulsions is in general in proportion to the advanced state of pregnancy, except when they occur after labor pains have begun, when a speedy delivery frequently carries them off; in other respects the danger is to be estimated more from the health and constitution of the patient, from the violence of the fits and from the stupor and apoplectic symptoms by which they are succeeded, than from the frequency of their recurrence. When each succeeding fit is more violent, and when they leave the patient more and more comatose, the danger is most imminent."

The conceptions held at the beginning of the last century on the toxemias of pregnancies are clouded by the interpretation which these writers placed on clinical symptoms. Thus, John Burns, a lecturer on midwifery in the medical school at Glasgow, designates by the term "febrile state," a train of symptoms now recognized as purely toxic in character. He believes that in such cases it is merely necessary to keep the bowels open and to take away a little blood. Burns also describes another so-called "species of fever" which affects women about the middle of pregnancy and makes its attacks suddenly like a "regular paroxysm of ague." The patient complains of headache, loathing for food, foul, dry tongue, considerable thirst, and is constipated. He states that the disease is very obstinate and often ends in abortion, after which, if the women do not sink speedily, they begin to recover but remain long in a "chlorotic state which, if not relieved, may terminate in phthisis." He even suspects that this disease originates from the bowels and bears a "great analogy to infantile remitting fever."

Burns, in another chapter, refers to headache as an alarming symptorn and in connection with the same describes very satisfactorily the syndrome now known as the pre-eclamptic stage, characterized by giddiness, visual disturbances, etc. In such circumstances, he says, "she is seized with apoplexy or epilepsy," and believes that these diseases are to be prevented by immediate recourse to bloodletting and laxatives. The quantity of blood which is to be removed must be determined by the severity of the symptoms, the habit of the patient, and the effect of the evacuations. If the headache is accompanied with edema, digitalis is recommended as a useful addition to the treatment. Burns also states that "if the patient is seized with apoplexy there is seldom any attempt made to expel the child; whereas in epilepsy if the paroxysm be protracted, the child may be expelled if the patient be not early cut off by a fatal coma. In some instances palsy either succeeds an apoplectic attack or follows headache and vertigo. This disease does not commonly go off until delivery takes place, but it may be prevented from becoming severe by mild laxatives and light diet."

In describing edema associated with pregnancy Burns mentions the severe cases in which "epilepsy" may result. When the edema is severe it may be attended with convulsions or it may predispose to puerperal disease, and he therefore insists that the edema must be reduced by bloodletting and purgatives.

The subject of vomiting in pregnancy is described by Burns in a very interesting manner, especially his reference to the necessity in severe cases of having the patient refrain from 'eating and giving her nourishing "clysters." Moreover, if the vomiting is bilious and accompanied with pains in the right side and shoulder, cough, and other symptoms of hepatitis, a seton should be immediately introduced into the side and a very gentle course of mercury given. If the vomiting becomes troublesome at the end of pregnancy "it is proper to detract blood and confine the patient to bed. Cloths dipped in laudanum should be applied to tne pit of the stomach and a grain of solid opium given internally." But he does not say anything about induction of abortion in such cases nor mention the possible fatal result.

The subject of eclampsia is also dealt with by Burns in the chapter on complicated labor, in which he states that convulsions of various kinds may occur either during pregnancy or labor. One species is the consequence of great exertion, excessive fatigue, tedious labor, or profuse hemorrhage. The attack comes on without much warning and generally terminates with delirium. The muscles about the face and chest are chiefly affected and the pulse is small, compressible, and f requent, the face pale, the eyes sunk, the extremities cold. The fits succeed very quickly and soon terminate in a fatal syncope. In treating the condition he refers to the necessity of keeping the patient quiet, and says that opium is of great service and that delivery is usually necessary. He also describes hysterical convulsions as more common during gestation than during labor. In these cases there is no foaming at the mouth, no working with the tongue, etc. The most frequent species of puerperal convulsions, however, is epileptic, which occurs fifty times for once that the other appears. Convulsions may affect the patient suddenly and severely, at stool or sitting in a chair. Presently, he says, the convulsion ends in a short stupor from which the woman awakes unconscious of having been ill, but in a short time the same scene is generally repeated ; or, perhaps, although the convulsions have gone off, the stupor remains. It is not, however, unusual for the fit to be preceded by some Symptoms which, to the attentive observer, indicate its approach. These are headache, pain in the stomach with unsupportable sickness, ringing in the ears, dazzling of the eyes or appearance of substances floating before them, slow pulse, and drowsiness during the pains.

How well the above description fits our modern conception of an eclamptic seizure, although we do not recognize the distinction between "hysterical epilepsy and the other convulsions." It is very likely that most of the cases of epilepsy or hysterical convulsions observed by the author were true eclamptic seizures. He admits that they are dependent on the pregnancy but goes no farther in advancing any theory as to their causation. Burns' directions for treatment are interesting. In the first place he cautions against injuries to the tongue and advises the insertion of a piece of wood between the teeth. Next the patient should be bled, or, when this cannot be done, further cupping in the temples and back part of the neck must be tried. If the convulsions recur the bleeding may be repeated, and he believes there is more danger from taking too little blood than from copious evacuations. From forty to eighty ounces of blood were taken from some of these cases of puerperal convulsions. He insists that bloodletting tends to relax the os uteri. After this a "smart clyster is given. The head is then shaved and blistered, the blister being proper though the fit have gone off." A small dose of calomel or solution of salts may also be given with advantage when the patient can swallow. The bladder must likewise be emptied, for its distention may cause convulsions. An interesting observation is that the depletion reduces the risk of "fatal oppression of the brain or extravasation of blood within the skull and that consequently the convulsion is mitigated." Termination of the labor is advocated, which is favored by the bloodletting. The dilatation of the cervix by the hand should be resorted to and the child delivered with as little violence as possible. Burns believes that the use of medicaments, such as opium, musk and camphor, is not advisable without resort to the other procedures. If the patient is seen before the fits have occurred, preventive treatment includes emptying the bowels, use of an emetic and, in the presence of violent pains in the stomach, doing a venesection and giving an opiate. The appearance of headache also calls for the use of the lancet. Purgatives, he concludes, are a very important part of the treatment, and he has had better results from this than other methods, which makes him incline to the belief that an "incorrect state of the bowels is one of the most powerful predisposing causes of puerperal convulsions, and may also be the chief exciting cause."

James Blundell, in his Principles and Practice of Obstetrics (Am. ed. 1834), devotes considerable space to the subject of convulsions, and the following extracts from his book are of interest. Thus he says:

"Where convulsions do not actually occur there is sometimes a very obvious tendency to the attack, flushing of the face, throbbing of the carotids, severe pains in the head, and sensations of the brain, as if it were too large for its receptacle, which, indeed, in a certain sense, it is, in consequence of the blood flowing into it too copiously."

"Unhappily for the safety of the patient, she may be seized without premonitory symptoms; still, however, premonitory signs sometimes occur. Tremors of the whole muscular system, shudderings, crampy pains in the region of the stomach, cerebral afflux of blood, flushing and tumidity of the face, throbbing of the carotid arteries, severe and splitting pains of the head, stammering, and perhaps failure of utterance, constitute some of the leading prognostics. Sometimes the patient becomes deaf, and more frequently her sight is affected, dazzled with light, or blinded. When the fit supervenes, the woman becomes entirely insensible, and, together with this insensibility, she has a violent commotion of the voluntary muscles. . . . When these attacks have continued ... a few minutes ... we find the patient recovering [but] sometimes the patient lies deaf or blind or incapable lo TOXEMIAS OF PREGNANCY

of speaking ... as if the sensorium had received some permanent injury.

"Causes of convulsions: The Immediate causes are very obscure; they appear sometimes to depend upon a loaded state of the vessels of the brain ; at other times the brain appears to be influenced by distant irritations, either in the uterus, or in the digestive organs, and again, in some cases, puerperal convulsions, are induced, apparently by a peculiar irritability of the nervous system.

"That the uterine organs are In some way Implicated is evident, from the convulsions being of a character . . . peculiar to the state of either pregnancy or parturition. Some writers assign three especial causes which may give rise to this disease, namely, general irritability of the constitution. Irritability of the uterus from distension and an overloaded state of the system.

"The custom of manner of living, the seasons or climate, and the general state of the health of the patients, are not wholly undeserving of being classed among the causes of these convulsions.

"To persons prone to cerebral afflux, convulsions may occur In the middle and earlier months sometimes, but still more frequently in the end of pregnancy.

"When convulsions attack a patient in the progress of gestation, she may have a single fit only or several, the Intervals being usually irregular and somewhat long, not of a few minutes only, but of hours perhaps, or even days.

"Sooner or later. If the fit continues, parturition of itself commences. This can happen ... In those cases also In which the disease Is associated with apoplexy, so that during the whole time the woman is either comatose or convulsed. ... Be at the bedside, therefore, In these convulsive cases, and watch, for as the paroxysms return the labor may advance, and the fetus may suddenly emerge.

"Should you ask me, in what manner convulsions are produced, I should reply that the more probable and Immediate cause of them is a pressure on the brain, and perhaps on the spinal marrow also. This pressure sometimes results from the effusion of blood, still more frequently from the effused water, and most frequently of all from mere congestion. . . , An Increased action of the vessels produces an accumulation of blood In the genitals, In the wattles of birds, and In the breasts of women during suckling and ... I think it Is not improbable that In these convulsions and convulsive propensities of women, a cerebral congestion, with pressure and Irregular circulation,

HISTORICAL II

and an increased action of the carotid and vertebral arteries, have a large share in producing the disease.

"In the end of gestation women are sometimes attacked with apoplexy, in which condition they may be for hours or days, recovering gradually afterward or ultimately sinking. Under apoplectic attacks, I believe, labor does not so readily come on as under convulsive attack; nevertheless, I would advise you to examine the os uteri occasionally, and take care that the child is not born unperceived. In its nature, though there are no spasms, I look upon this disease as strictly analogous to the convulsions of which I have been speaking, and I would therefore, treat it upon the same principle."

I have quoted a certain number of historical references in extenso to show that the clinical knowledge of the toxemias of pregnancy has been in existence for several centuries and that methods of treatment now in use were then employed for similar purposes, including purging, venesection, and the administration of sedatives and alkalies. It is perhaps rather discouraging to be compelled to make an admission, in reviewing the history of this subject, that we have not made any noteworthy advances except in a better knowledge of associated pathology and the chemistry of the urine and, more recently, the chemistry of the blood. The clinical picture of an eclamptic seizure painted by Burns in 1811 is not, except for certain details, very far removed from that described in modern obstetrical textbooks. Nor have we determined with any degree even approximating to certainty, what are the precise etiological factors underlying the production of these various abnormalities in the pregnant state. This uncertainty regarding etiology makes our modern modes of treating hyperemesis, eclampsia and the other toxemias, largely empirical. For example, whether to resort in the treatment of eclampsia to immediate delivery, or to employ palliative measures is a question by no means settled, and arrays of facts and figures are presented by both groups of observers, radical and conservative, in defense of their individual claims. The incidence and the mortality of the toxemias of pregnancy still remains high, although recent years have v/itnessed great improvement, particularly in eclampsia, where preventive measures have undoubtedly proved their value. But there is much yet to be learned, and before us is a task worthy of the earnest attention of medical investigators, in which the combined thought and labor of clinician and laboratory worker, rather than either alone, must be brought to bear on the problem. It is problematical where the search will lead us and what epochmaking discovery will reveal one or more etiological factors that will serve as a basis for rational tlierapeiitics. Or, perhaps, prophylaxis alone, as in so many other diseases, will point the way to an eradication of these serious complications of the pregnant state.