Eclampsia

ECLAMPSIA, eclampsia (from the Greek eklampto — to flash forth, to ignite), is the most characteristic and typical disease from the group of pathological processes of pregnancy grouped together recently under the general name of pregnancy toxemias (see). Eclampsia occurs on average once in every 250 labors; however, there are certain localities where it is observed significantly less or more frequently. In recent years in many countries, especially in our Union, thanks to a significantly expanded network of consultations and preventive observation of pregnant women, eclampsia has begun to occur much less frequently. Eclampsia may be observed during pregnancy (eclampsia sub graviditate), during labor (eclampsia sub partu), or arise for the first time only after labor (eclampsia post partum). The question of when eclampsia occurs most frequently has not been definitively resolved, but according to available statistics, and in particular according to the statistics collected by Selitsky from 18 authors (eclampsia sub graviditate — 30.5%, eclampsia sub partu — 46.8%, eclampsia post partum — 13.3%), apparently eclampsia sub partu is observed most frequently. The danger of the appearance of eclampsia increases with the increase in the period of gestation, and it is most frequently encountered in the last two months. In the first half of pregnancy (eclampsia praecox), eclampsia arises rarely, and only one case of eclampsia with a three-month miscarriage was described in the Union (Lebedev). After labor, eclampsia sets in for the most part shortly after their completion, in the very first hours; frequent cases of the onset of seizures directly during or after the expulsion of the placenta have been described. Cases of so-called late eclampsia (eclampsia tarda, tardissima), i.e., occurring in a period more remote from labor, are as rare as cases of early eclampsia during pregnancy. Only a few cases of them have been described in the literature. Eclampsia arising during pregnancy often causes its interruption; in rarer cases, the seizures cease, pregnancy continues and can reach term without their resumption (so-called intercurrent eclampsia — eclampsia intercurrens); sometimes, after a certain time, still during pregnancy, or with the onset of labor activity, or upon the completion of labor, the seizures may start again (such a form of eclampsia, at Selitsky's suggestion, bears the name of recurrent — eclampsia recurrens; the old term is relapsing). Both e. intercurrens and recurrens are observed extremely rarely. Women after observed intercurrent eclampsia need the most careful observation, because cases of its transition into recurrent with a fatal outcome have been described. The possibility of the recurrence of the disease also in a new pregnancy is not excluded. Contrary to the assertion of some authors (Stroganov), it must still be considered that repeated eclampsia is observed rarely in view of the fact that the disease, once endured, leaves behind a certain immunization. The clinic also confirms the rarity of repeated eclampsia: thus, in the statistics collected by Selitsky, out of 2,576 eclampsias, repeated eclampsia was observed in only 2.7%; the same percentage is indicated by other authors (for the example Pismenny, Alovsky — 1.3%, Vlasov — 1.7%, according to Stoeckel, on average it is encountered within the limits of 2%). Isolated cases of the repetition of eclampsia in several pregnancies have been described. In the Union, only isolated cases of repeated eclampsia in three pregnancies are known for the entire time (Primo, Stolypinsky), whereas in the foreign press there is a casuistic case where eclampsia was observed 14 times. Predisposing causes. Constitution. Age apparently exerts some influence on the appearance of eclampsia; thus, it is most frequently observed from 20 to 30 years of age, but it can also be encountered at earlier and later ages (according to Selitsky's data, it was observed from 17 to 47 years of age). Primigravidae and primiparae fall ill with eclampsia significantly more often than repeat- and multiparae; on average, eclampsia is observed in primiparae in 70–75%, in secundiparae and multiparae — in 25–30%. The influence of constitutional moments noted by old obstetricians (healthy, well-nourished women predisposed to apoplexy) was confirmed by subsequent observations. Thus, back in 1893, Kundrat spoke of an abnormal bifurcation of the aorta, a narrow aorta in eclamptic women was also pointed out in general, and in recent years, Bublichenko noted lower stature in eclamptic women, slowed metabolism, and in general a later puberty and later onset of menstruation with a tendency toward atypicality more commonly characteristic of eclamptic women. In 1934 (Ukrainian Congress of Gynecologists), Selitsky, on the basis of the microscopic picture of individual endocrine glands in pregnancy toxemias and in eclampsia, noted that there are quite profound changes in the entire endocrine system in them. These changes, consisting in one or another insufficient histological differentiation with the proliferation of connective tissue (thyroid gland, adrenal glands, ovaries, pituitary gland), in the extensive distribution of sclerotic changes in the vascular system of the endocrine network, can, in the author's opinion, be regarded as constitutional and conditioned by a definite endocrine setup, especially subject to pregnancy toxemias (the character of the changes allows them to be attributed to the type of hypoplastic constitutions according to Bartel). The opinion widespread earlier (defended by some even now) that the frequency of the occurrence of eclampsia is influenced by one or another season of the year (spring, autumn), sharp fluctuations in weather, strong winds, etc., and that these same factors determine a greater or lesser percentage of mortality, is refuted by clinical data and individual authors (Hinselmann, Stoeckel, data of the clinic of the First Moscow State University for 1890–1915). Twin pregnancy is a factor significantly favoring the onset of eclampsia. Thus, according to the data of the clinic of the First Moscow State University (1890–1915), twins (once triplets) were observed in eclampsia in 9.4%. Approximately the same is the ratio in other clinics of the Union, in the statistics of France (7.7% — Brindeau), Germany (7.4% — Bremme) and other countries. Apparently, the harmful factors consist in greater demands on the organism and in an elevated metabolism that is more easily disturbed. Polyhydramnios, as was thought earlier, does not play a predisposing role. Thus, in the clinic of the First Moscow State University for 1890–1925, polyhydramnios was never once observed in eclampsia (while by some authors the combination of polyhydramnios with eclampsia is noted in a very insignificant number of cases, e.g., Khazansky — 1.0%). A narrow pelvis can have greater significance (though still relative) as a predisposing moment. Apparently, the influence is exerted not by the narrow pelvis as such, but by the complications associated with it (substandard constitution, malpresentations, early rupture of membranes, anomaly of expulsive forces, protracted labor). Zangemeister says that a narrow pelvis is complicated by eclampsia in 8% of cases and that with it, eclampsia most frequently sets in among parturients with strong, prolonged contractions. In the clinic of the First Moscow State University for 1890–1915, complication of eclampsia by a narrow pelvis was observed in 31.4%. Etiology. Despite an endless number of experimental studies in various directions, especially at the end of the 19th and beginning of the 20th centuries, the immediate cause of the occurrence of eclampsia still remains unclarified. In the history of the development of the doctrine of eclampsia, several highly unequal periods can be noted. In the first, initial period, encompassing the time from Hippocrates to the middle of the 19th century, the conception of eclampsia was extremely limited and was based predominantly on the main external sign of the disease — convulsions. Initially, the engorgement of the organism with blood was considered the cause of the occurrence of eclampsia, whereas subsequently, at the end of the 18th and beginning of the 19th centuries, it began to be equated with epilepsy, being regarded as puerperal epilepsy (Jacqomier) or generally as a nervous disease. Individual authors adhered to this view subsequently as well, but it was definitively shaken only at the end of the 19th century by Schmorl, who proved that those patho-anatomical changes that are encountered in eclampsia are never observed either in hysteria or in epilepsy. In the forties of the 19th century, with the discovery by the Englishman Lever of protein in the urine of eclamptic women, a new period began in the doctrine of eclampsia, a period which can practically be regarded as the beginning of the scientific study of eclampsia. All attention at this time was concentrated on the kidneys. Ultimately, this created a definite era in the history of eclampsia, which can with full right be called the era of uremic theories, since eclampsia began to be regarded as acute uremia. Of the most widespread theories, one can mention the pressure of the pregnant uterus on the renal veins (Lever), the retention of urea and ammonium carbonate in the blood (Frerichs, Spiegelberg), hydremia with subsequent edema and anemia of the brain (Traube-Rosenstein) and many others. At the present time, these theories are shared by almost no one, and the majority considers that the kidneys are affected in eclampsia just like other organs. The basis for this was provided by cases of protein-free eclampsia, the different freezing point of blood in eclampsia and uremia was experimentally proved (Kronig), and finally, cases with insignificant changes in the kidneys or even entirely without them were described at autopsy.

Chemical studies have shown that azotemia is observed extremely rarely and that Ambard's constant almost always remains within normal limits. The ideas about the predominant significance of the kidneys in the etiology of eclampsia dominated for almost half a century, and only at the end of the 1880s did the attention of clinicians also focus on changes in other organs. Thus, the view of the French school (Bouchard, Riviere, and others) on the significance and role of the liver not only in a diseased but also in a healthy organism created a whole series of theories attempting to prove that eclampsia and other toxicoses of pregnancy are caused by hepatotoxemia (Pinard). The theory of hepatotoxemia, which became particularly widespread in France and America, was subsequently substantiated both by pathological-anatomical changes found and by chemical investigations carried out (bile retention, urobilinuria, more pronounced alimentary glucosuria in eclampsia, etc.). In our country, Massen believed that the dysfunction of individual organs occurs on the basis of produced toxins (leukomaines) and considered that they are formed due to the insufficient oxidative capacity of liver cells. Great attention is still paid to the liver today, both in normal and pathological pregnancy, but nevertheless, the majority believe that changes in it, as in other organs, are of a secondary nature. Almost simultaneously with the theory of hepatotoxemia, the infectious theory arose. From the moment of its appearance in France (Doléris, Blanc, Gerdes, and others), this theory had few adherents; now it has been abandoned by everyone in view of its unsubstantiated nature. At the beginning of the 20th century, the anaphylactic theory arose, proposed by Anderson and Rosenau; it found support from other authors (Loehlein, Thies, Johnstone, and others) who sought to prove it with animal experiments. Verification experiments by a number of authors (Hofbauer, Heynemann, Liepmann, Murray, Eisenreich) convincingly showed that eclampsia and anaphylaxis have nothing in common. A new era in the doctrine of eclampsia was constituted by a series of views based on the idea that all changes encountered in the organs of an eclamptic woman are of a secondary nature and occur on the basis of as-yet-unknown toxins originating from the fertilized ovum. The basis for this view was clinical observations: the favorable effect of the termination of labor on the course of the disease, autopsy data, a more detailed study of metabolism and the function of individual internal secretion glands during physiological and pathological pregnancy. In other words, the conviction grew and strengthened more and more that eclampsia is a disease of the entire organism and that without pregnancy there is not and cannot be eclampsia. The opinion expressed initially by van der Hoeven and supported by Fehling that the fetus is the source of eclampsia (since after its death the seizures weaken and twin pregnancy particularly predisposes to the disease) was completely abandoned after cases of eclampsia were described not only with a dead and macerated fetus, but also with a hydatidiform mole. The desire of some (Albeck and others) to attribute the occurrence of eclampsia to amniotic fluid also did not gain widespread acceptance for the reason that one would naturally expect that when the organism is overloaded with toxins, the amniotic fluid may also possess greater toxicity. Subsequently, the attention of obstetricians was focused on the placenta. Thus, disturbances in the chemistry of the placenta were noted, for example, fluctuations in the glycogen content of the placenta in eclampsia. Thus, Murakami (1931), in 9 cases of normal pregnancy, found the glycogen content in the placenta to range from 0.34% to 0.46% (on average 0.43%), while in the placenta of an eclamptic woman (18 cases) it was only from 0.14 to 0.27% (on average 0.17%). The placental theory that arose on this basis underwent further development, which showed that even if one cannot speak of the placenta as the source of eclampsia, one can in any case consider that disturbances in the activity of the placenta and in its correlative relationships with other endocrine glands can play a significant role in the occurrence of eclampsia. In the years associated with the beginning bloom of endocrinology, we see a desire to link eclampsia with the disruption or alteration of the functions of one or another individual internal secretion gland during pregnancy. The theories that arose one after another, attempting to ascribe the entire essence of eclampsia to the dysfunction (hypo- or hyperfunction) of any specific gland (the thyreogenic theory—Nicholson and others, parathyreogenic—Vassale, ovarian—Pinard, Belov, hypophyseal—Laimois, mammary—Sellheim), are now shared by few; the majority believe that the function of the entire endocrine system is disrupted and that eclampsia should be considered a pluriglandular disease. In modern times, there is again a certain tendency to link the occurrence of eclampsia solely with the dysfunction of one specific internal secretion gland. The greatest attention by researchers is paid to the pituitary gland. The view of eclampsia as a pituitary disorder, developed in a new light by Hofbauer, was subjected to detailed study (Anselmino and Hoffmann). Hofbauer notes that in the second half of pregnancy the liver does not function normally and that, in addition, there is hyperfunction of the pituitary gland and adrenal glands (increased secretion of the pituitary and adrenaline), while the eclamptic syndrome is caused by damage to the reticuloendothelial system of the liver and capillary endothelium by syncytial proteins, placental enzymes, and the excessive production of the posterior pituitary hormone and adrenaline. Anselmino and Hoffmann experimentally proved that the resulting propensity for dropsy, edema, hypertension, capillary spasm, coma, and convulsions is caused by the antidiuretic and vasoconstrictor component of the posterior lobe of the pituitary gland. Anselmino and Hoffmann came to the conclusion that an antidiuretic component circulates in the blood of an eclamptic woman, analogous from a pharmacological, chemical, and physical point of view to that of the posterior lobe of the pituitary gland. According to the same authors, the blood also contains a vasoconstrictor substance that can very likely be considered identical to the vasoconstrictor component of the posterior lobe of the pituitary gland (it is analogous from the chemical and physical side and differs only in pharmacological properties). By virtue of all this, Anselmino and Hoffmann believe that these toxicoses may be assigned the name of pituitotoxicoses of pregnancy. To prove the correctness of their view, Anselmino and Hoffmann cite data from the well-known American pituitary researcher Cushing, who asserts that the changes he noted in eclampsia (a large number of basophilic cells) serve as an expression of the increased function of those cells that form the hormones of the posterior lobe, and he sees an increase in the secretion of these cells in the increased amount of hyaline bodies. Fauvet, based on his experiments (1933) with the administration of pituitrin, also comes to the conclusion that the changes discovered at autopsy (in the liver, kidneys) are analogous to the changes in eclampsia. Despite the persuasiveness of these data, it is hardly possible to entirely share the viewpoint of Anselmino and Hoffmann and consider that eclampsia represents solely the consequence of hyperfunction of the pituitary gland and is a hypophyseal disorder. Undoubtedly, both in eclampsia and in other toxicoses, hyperfunction of the pituitary gland is present, but along with pathological changes in the pituitary gland in eclampsia, analogous changes are observed in a number of other endocrine glands, for which reason it is hardly correct to base the hypophyseal theory of eclampsia solely on changes in the hypophysis without taking into account changes in the thyroid gland, adrenal glands, and ovaries. Fauvet's studies, incidentally, were tested by Ohligmacher (1933), who, based on his experiments, believes that the changes described in Fauvet's organs upon the administration of pituitrin also occur upon the administration of other agents that have a harmful effect on blood vessels and blood, and that Fauvet's investigations do not prove the occurrence of eclampsia on the basis of hyperfunction of the posterior lobe of the pituitary gland. Along with certain functional and morphological changes in individual endocrine glands, numerous studies have also established metabolic disorders. Thus, a number of authors noted a more significant depletion of blood in calcium in nephrosis and in eclampsia (compared to the physiological depletion in normal pregnancy), a decrease in reserve alkalinity, a high sugar content in the blood (Benthin), an increased gas exchange (Klaften), an increase in the amount of cholesterol, an increased uric acid content, and an irregular distribution of nitrogen in the urine in eclampsia (Wesselow, Wyatt, and others). As can be seen, all types of metabolism undergo certain disorders in eclampsia, but to say at the present time what causes this and what the direct cause of the onset of eclampsia is does not appear possible. This is all the more difficult because the evaluation of the obtained data by individual authors varies, and the obtained data themselves are diverse.

Because of this, Essen-Moller is entirely correct in stating that it is not yet possible to untangle the complex problem of chemical processes in eclampsia, especially since we still have a poor grasp of the reactions of the maternal organism during normal pregnancy. The entire complexity and multifaceted nature of the changes occurring in eclampsia are also illustrated by highly valuable research in the field of the vegetative nervous system and the cellular elements of the reticulo-endothelial system. Investigations of recent years have revealed the significance that the reticulo-endothelial apparatus has in normal and pathological pregnancy. Benda contributed much to clarifying the role and significance of this system in eclampsia, having experimentally proven that the cells constituting it possess a protective function, an antitoxic action in the broadest sense, and that in the event of their insufficiency, intermediate metabolism slag products and toxins are produced in excessive amounts and toxemia arises. Benda, investigating the functional capacity of capillary endothelium using the meningeal permeability phenomenon, showed that permeability increases during normal pregnancy in the last weeks, sub partu, and undergoes especially significant changes in eclampsia. The author considers them so typical that he deems it possible to be guided by the hemolysin reaction also for differential diagnosis purposes. Benda attributes these changes to toxins originating from the ovum, and believes that pregnancy toxemias, and eclampsia in particular, are an expression of insufficient protective capacity and activity of reticulo-endothelial cells. The noted changes in the reticulo-endothelium have recently led to a new explanation of the occurrence of eclampsia. Thus, Belikov and Manevich (1935) believe that some substances are formed during pregnancy that are split under normal conditions, whereas in toxemias they are not split due to a functional disturbance of the intermediate metabolism organ, the cells of the reticulo-endothelium. Assuming that the origin of these substances is connected with the placenta, Belikov and Manevich think that they are toxins of a bacterial or animal toxin character, or that they represent allergens. They lean toward the latter on the grounds that these as-yet-unknown toxic substances are not revealed in every pregnant woman (they are formed in every pregnancy, but do not sensitize every organism). They tested their point of view with an intracutaneous test on pregnant women with and without toxemia using the serum of an eclamptic patient taken at the height of the seizure. Belikov and Manevich came to the conclusion that most likely an allergic reaction is present and that in pregnant women and women in labor, as toxemia phenomena increase, sensitivity to the eclamptic serum also grows. The preliminary, highly interesting observations of Belikov and Manevich allowed them to state that this reaction may have prognostic significance, that one can assume a desensitizing effect of this skin test, that there is apparently some allergen in the eclamptic serum, and that eclampsia represents a peculiar allergic state, from which the thought of the possibility of desensitizing eclampsia patients logically follows (it must be noted that for the first time a skin reaction during pregnancy for its diagnosis was used in 1914 by Engelhorn with placental emulsion, and in 1934 with placenta lysates by Chaikovsky and Turetskaya with very encouraging results). The vegetative nervous system, as a number of observations show, also plays a certain role in pregnancy, and apparently along with the prevailing phenomena of vagotonia, there are also symptoms of sympathicotonia, i.e., there is a general increase in the excitability of the entire system. All these recent studies largely confirm the view established among the majority of obstetricians that eclampsia is a disease of the entire organism as a whole, and not of any individual organ, and that all the changes occurring in it in individual systems (vegetative, endocrine, etc.) and organs (liver, kidneys) cannot be approached in isolation, but must be viewed in aggregate, i.e., considering their lesion to be secondary on the basis of as-yet-unknown toxins originating, apparently, nonetheless from the ovum. The predominance of certain symptoms or the preferential lesion of a particular organ can easily be explained either by the selective action of toxins, by the constitutional characteristics of the sick person, or finally from the point of view of the locus minoris resistentiae of one or another system or organ. The pathological anatomy of eclampsia began to be studied only in the middle of the 19th century. At first, attention was focused only on the kidneys, and only in 1889 were characteristic changes in the liver described by Jürgens (hepatitis haemorrhagica). Subsequently, other changes were also noted: hemorrhages in the meninges, hemorrhages into the gastrointestinal tract, fatty infiltration of perivascular stellate cells in the liver, albuminoid degeneration and degenerative fatty degeneration of nerve cells up to their complete necrosis in the cerebral cortex and in other parts of the brain (Yagodzinsky and others). We owe a more detailed study of the pathological anatomy of eclampsia to Schmorl, who established (1896) that there is a definite picture of organ changes peculiar only to eclampsia, which is not found in any other diseases. Subsequently, this also served to discover a new form of eclampsia—eclampsia without convulsions, recognized at the present time by almost all obstetricians. Autopsy data, aside from the similarity of pathologico-anatomic changes in the convulsive and non-convulsive forms of eclampsia, indicate a greater severity of changes in eclampsia without convulsions, which fully explains the high mortality percentage (above 70%) observed in it. As an example, one can point to cerebral hemorrhages. Thus, if more or less significant hemorrhages into the brain and membranes are noted in 10% of all fatally terminating cases of eclampsia with convulsions, in its non-convulsive form cerebral hemorrhages are already observed in 26% (Schlosser, 1923) and even 43% (Hermann, 1929). The pathological symptom complex of organ lesions consists of degenerative processes in the kidneys (degenerative fatty degeneration, cloudy swelling, and predominantly necrosis of the epithelium of the convoluted and partly straight tubules), in the liver (hemorrhagic and anaemic necroses, granular degeneration, numerous thrombi), in the heart (albuminoid and fatty degeneration of the myocardium), in the vascular system (thrombi), and in the brain (softenings, hemorrhages, granular degeneration of the cells of the gray matter of the cerebral cortex). The most typical changes are considered to be in the liver; Konstantinovich already believed that they were so characteristic as to allow the diagnosis of eclampsia to be made on the autopsy table. Among rarer lesions, rupture of the liver capsule with subsequent hemorrhage into the abdominal cavity (first Kolosov, then Herz, Kotelnikov, Markov), cases of gastro- and esophagomalacia (Selitsky), and encephalomalacia (Klaus) have been noted. All these changes were confirmed by a number of authors in Europe and the Soviet Union (Nikiforov and others), with some pointing out that in cases where chloroform was used, a more severe pathologico-anatomic picture was observed (Pozharisky). Pozharisky recommends distinguishing cases at autopsy: 1) "pure" eclampsia, 2) eclampsia + chloroform, 3) eclampsia + chloroform + sepsis, since higher degrees of degenerative organ lesions were noted in cases where a greater amount of chloroform was used, while the isolation of sepsis is necessary eclampsia because the latter can obscure the main picture. Changes in the endocrine glands were also described, though they did not present anything characteristic (Brindeau). In recent years, however, certain characteristic features have been described in the ovaries (Walthard, Kushnir-Selitsky, Pozharisky)—significant atresia of follicles, development of the interstitial gland. The large number of Call-Exner glandular vesicles discovered (Kushnir-Selitsky) (soon confirmed by Pozharisky) allowed these authors to view this phenomenon as hyperovaria, while still not considering it the primary cause of the occurrence of eclampsia. In addition to the above-indicated changes in the endocrine glands described by Selitsky and in the pituitary gland by Cushing, Goldschmidt and Fürstner described a peculiar change in the pituitary gland: along with clearly expressed changes characteristic of pregnancy, an entire system of cysts of larger and smaller size was stated (in the intermediate lobe, a state more reminiscent of childhood). There are also studies of the placenta (Ulezko-Stroganova, Schmorl, Brindeau, Nattan-Larrier, and others) and of the children of eclamptic mothers. In the placenta, hemorrhagic infarcts, syncytial hyperplasia, enlargement of the chorionic lumen (Jaworsky), diffuse hemorrhages, and sometimes even necroses were most frequently noted. Schmorl points out that hemorrhages are observed often, but not as a rule; they are of various sizes and different ages and are located partly in the center, partly on the surface. The view expressed at the time (Jaworsky) that all these phenomena are caused by periarteritis of fetal vessels is also confirmed by recent data.

Gräfenberg considers that changes in the vascular apparatus of the placenta are just as characteristic as changes in the liver of eclamptic women, and even allow one to speak of the specific nature of these lesions, and that generally there is no eclamptic placenta without hemorrhages. Pathological-anatomic changes in children, according to the opinion of the majority of authors (Schmorl, Meyer-Wirz, Pozharisky, and others), do not present anything special and do not allow one to say that the disease of the mother damaged the fetus to one degree or another or served as the cause of its death (Esch). The lesions of the liver, kidneys, multiple hemorrhages, and others still found in children in isolated cases, as well as high infant mortality, cannot at the present time exclude the possibility of a direct harmful effect of eclampsia on the intrauterine fetus. Symptomatology. Clinic. In former times, eclampsia was viewed rather narrowly; the symptoms observed during it were considered in isolation, and practically the entire disease was reduced to only one of the main and characteristic signs—convulsions. Now, thanks to clinical observations (Mikhnov, Vag, and others) and data from pathological-anatomic research, the view on eclampsia has expanded to a significant degree. Convulsions as such, even if they remain the dominating phenomenon in the disease, still do not include the entire concept of "eclampsia," but are considered only one of the symptoms. Clinical observations show that eclampsia, or rather, the eclamptic attack, is almost always preceded by a series of precursors and that only in exceptional cases do convulsions arise acutely, suddenly, without prior pathological signs. This entire rather diverse group of prodromal symptoms has now been assigned the name eclamptism (Vag). Many consider that the disease must be counted not from the moment of the appearance of the first attack, but from the appearance of the first signs of eclamptism (or preeclampsia). Eclamptism is composed of a series of subjective and objective symptoms. The former include headaches, dizziness, nausea (often also vomiting), pain in the epigastric region, weakening of vision, drowsiness, difficult breathing, sometimes twitching contractions of individual facial muscles, sensory anomalies, and others. Objective prodromal phenomena consist of changes in the circulatory system, impairment of kidney function (decrease in diuresis, appearance of protein and formed elements in the urine), increase in body weight, and others (most frequently observed are tense pulse, hypertension, dropsy, oliguria, less frequently jaundice, itching, cyanosis). The convulsive stage (appearance of the attack) in the majority of cases arises with a rapid increase in the objective and subjective symptoms indicated above, of which hypertension is of the most essential significance. A large role is assigned by some (Zangemeister) to the edema of the entire body, the so-called dropsy of pregnant women. In the convulsive stage, three periods are distinguished: 1) the period of excitation, 2) the period of tonic convulsions, and 3) the period of clonic convulsions (some distinguish four periods, referring to the fourth as the coma setting in upon the conclusion of the attack). The period of excitation is very short-lived (15–30 seconds, maximum 1 minute) and can only be caught with careful observation of the patient. All pathological phenomena are concentrated exclusively on the face and head. Slight twitchings of individual groups of facial muscles, continuous lowering and raising of the eyelids, rolling of the eyes upward, throwing back of the head, general excitation are characteristic symptoms of the first period (sometimes twitchings of the upper extremities and disorderly, uncoordinated movements are observed). The second period of tonic convulsions is also very brief (maximum 20–30 seconds) and is considered by some even as a continuation of the period of excitation. The eyes in the period of excitation become motionless, the head is thrown back and to the side, the jaws are firmly clenched, all muscles are tense, breathing stops, cyanosis appears (the most dangerous period!). Immediately following the tonic convulsions, clonic convulsions set in, constituting the third period of the convulsive stage. The period of clonic convulsions is the longest (lasting on average 1–2 minutes, often its duration is even greater, reaching up to 5 minutes, and Tarnier in one case noted its duration even at 20 minutes). Upon the conclusion of the second period, the patient takes a deep breath, following which clonic convulsions begin on the face and extremities, while the trunk remains in a relatively quiescent state. The most intense and sharply expressed convulsions are on the face and upper extremities. By the time the third period ends, foam with an admixture of mucus appears from the mouth, often stained with blood due to damage to the mucous membranes or biting of the tongue. If measures are not taken in good time, there can be significant injuries to the tongue (dislocations of the lower jaw are even described). Upon the conclusion of the clonic convulsions, coma sets in. The duration and character of the comatose state are varied: the coma can continue until the next attack (observed in the intervals between subsequent attacks as well), but it can also be short-lived; the patient recovers consciousness between individual attacks, sometimes asks for a drink, complains of a headache, asks or answers questions, and so on. In the convulsive stage at the height of the attack or shortly after its conclusion, the pathological symptoms observed earlier may increase (e.g., increase in protein in the urine, oliguria, hypertension, and others), or new pathological phenomena may develop—jaundice, difficult breathing, pulmonary edema, high temperature, and others. The convulsive stage in the majority of cases is distinguished by a certain regularity, and attacks can follow one another in a definite gradualness (intervals between individual attacks average half an hour, an hour, two hours, and so on), but cases are also observed without any periodicity and regularity. The number of attacks can be extremely varied; there are, and not so rarely, cases in which only one attack is observed. Sometimes their number can reach 100, 200, or even more (in the majority of cases the number of attacks is insignificant, which was noted earlier as well; Selitsky). Although convulsions always present a definite danger to the patient, nevertheless the number of attacks does not always have absolute significance. Thus, far from being an exception, a fatal outcome ensues after 1–2 attacks, and, on the other hand, recovery after a large number of them (a case of recovery after 207 attacks is even described; Jardine); mortality after only one attack appears rather significant: according to Selitsky—9.6%; Astrinsky, Bliznyanskaya, and Gleizer indicate that out of 7 cases ending in death, only in 2 was a significant number of attacks observed. The cessation of attacks and the return of consciousness do not always signify the end of the disease. True, in the majority of cases upon the conclusion of attacks everything quickly returns to normal, the amount of protein critically decreases, diuresis increases, edema passes, and so on, but sometimes a series of subsequent post-eclamptic complications is observed. Thus, an almost constant phenomenon upon the return of consciousness is amnesia, psychoses are frequent (in 5%) (more often of a manic character, hallucinatory state). Subsequent complications on the part of the heart and lungs are also observed, and cases ending fatally a long time after the conclusion of attacks from bronchopneumonia and other complications have even been described. Eclampsia can sometimes take a different course as well, and the symptom considered most characteristic and typical—convulsions—may be absent in the disease. This relatively recently described form—eclampsia without convulsions—clinically proceeds with all the symptoms usual for eclampsia and in the majority of cases ends fatally (according to Selitsky's statistics, in 71%). Diagnosis usually does not present difficulties (with the exception of eclampsia without convulsions, which is sometimes completely incorrectly interpreted as preeclampsia or eclamptism). In differential diagnosis, one must take into account hysteria, epilepsy (epilepsy, as some indicate, e.g., Albeck, can indeed proceed with phenomena of eclamptism, but hypertension is absent in it, nor is there the characteristic triad of Zangemeister—dropsy, nephropathy, and hypertension), cerebrospinal meningitis, tumors, and brain diseases in general. In doubtful cases, a great help is the anamnesis, data on the course of pregnancy, its term, and a detailed clinical study (urine, character of blood pressure). In differentiating uremia and eclampsia, one must take into account that uremia, unlike eclampsia, most often arises in earlier months, chronic inflammation of the kidneys is present in the anamnesis, and in addition it is usually accompanied by retinitis albuminurica (in diagnosis, a great help is the study of urea, residual nitrogen, and indican in the blood). Finally, in diagnosis, one must also keep in mind more rarely occurring cases of poisoning (with carbolic acid—Löhlein, with corrosive sublimate—Olshausen), proceeding sometimes with symptoms similar to eclampsia.

In eclampsia without convulsions, the entire pathological symptom complex is more sharply expressed; its main distinguishing features are coma and high temperature (which almost never occurs in eclamptism) and a rapid, stormy, often lightning-fast course with a rapid change of pathological phenomena, in contrast to eclamptism, in which, alongside a milder clinical picture, the development of the disease almost always, in any case very frequently, has a slower, sluggish character (hence, of course, the outcomes of eclamptism and eclampsia without convulsions also differ: in the former the mortality rate is close to zero, especially in those clinics that evaluate it and carry out active prophylaxis as needed, whereas in eclampsia without convulsions the mortality rate is colossal). Additionally, one must bear in mind that the possibility of a direct transition of eclamptism, bypassing the convulsive stage, into eclampsia without convulsions naturally cannot be excluded. Prognosis. Long-term results. It is often very difficult to definitely predict the outcome of eclampsia in any given case. The clinical picture, course, and development of the disease can vary within significant limits, which is quite understandable given that the toxins still unknown to us may be of various characters, and the resistance of the organism itself may also vary. Although based on a number of symptoms and the degree of their manifestation, as well as the general picture of the disease, modern clinical practice distinguishes milder, moderately severe, and severe cases, this still appears quite conditional, since a case that seems mild and unthreatening, not only initially but also during the further development of eclampsia, can suddenly and unexpectedly take a severe course or end rapidly in death immediately after a seizure (maladie des surprises; Llames-Massini). Early diagnosis, a detailed assessment of the clinical picture, and attention to every single symptom and the entire pathological symptom complex in general are of exceptional importance. Along with paying due attention to the eclamptic seizure, no less attention should be paid to the state of the most important organs (liver, kidneys, heart, lungs), focusing on the organs with predominant lesions (which is important in terms of therapeutic intervention) both before the onset of the seizure, at its peak, and after its termination. With the development of seizures during the transition of eclamptism into the convulsive stage, the prognosis always remains serious and must be made with great caution; one can navigate it only through tireless, careful observation of the patient; a sharply negative attitude must be taken toward managing cases of eclampsia in absentia, by consultation, or by telephone, as recommended by Stroganov (1930). Among the particularly unfavorable factors are deep coma, jaundice, and high temperature; especially severe are those cases where, along with these symptoms, there are marked hypertension, respiratory disorders, a significant amount of blood in the urine (hemorrhagic form), and anuria. Symptoms that worsen the prognosis are the complete absence of urine and phenomena of pulmonary edema beginning shortly after the first seizures in combination with hypertension. One must also not lose sight of the fact that with the above-mentioned symptoms, a drop in blood pressure may also be observed, which is especially unfavorable when it appears in the presence of changes in cardiac activity, or after high degrees of hypertension, or is observed after frequent attacks (Henkel). Llames-Massini believes that the prognosis appears particularly severe in the presence of blood in the urine and the combination of anuria with high temperature. Zangemeister attaches importance to the time of appearance of oliguria or anuria; in cases where it is observed before delivery, the prognosis does not worsen, whereas if it is observed after the end of labor, the prognosis becomes more severe; in addition, Zangemeister believes that anuria in the absence of seizures appears more favorable. Spickmann, who specifically studied the question of oliguria and anuria in eclampsia (studying 76 cases), came to the conclusion that anuria can lead to a fatal outcome even without the presence of seizures and that the interrelation between oliguria or anuria and hypertension is of great importance. If anuria continues in such cases, the prognosis always remains severe. The amount of protein cannot serve as a criterion for the severity of the disease (Skrobansky, Selitsky); protein-free severe forms with a fatal outcome are not so rarely observed, and Llames-Massini even considers cases with significant albuminuria to be the most favorable prognostically. Irregularities in the pulse (frequent, irregular) and disorders of cardiac activity also worsen the prognosis. The number of seizures may have a definite prognostic significance: the more seizures, the more serious the prognosis (however, the significance of a large number of seizures is not absolute). Cases are particularly severe in which, along with the intensity (regardless of their number) and longer duration of the seizures, they follow one another rapidly; the prognosis is also severe in those cases where, with relatively large intervals between individual attacks, the patient is in a deep unconscious or comatose state with anuria and hypertension. Maternal mortality in eclampsia does not represent a definite, constant value, but is subject to rather significant fluctuations depending on a whole series of endogenous and exogenous factors. It varies depending on many causes—on the environment and the influences to which the patient is subjected during pregnancy, and on how soon she comes under medical observation after the onset of the first seizure or even the first manifestations of eclamptism. Indicative in this regard are cases of eclampsia externa (eclampsia that began outside an institution), which yield a significantly higher mortality rate compared to eclampsia interna (which developed within the institution). The preventive direction in obstetrics that has become widely developed in the Union and the experience of consultations for women convincingly show what tremendous importance systematic, regular observation of the pregnant woman has, and what an effect this has not only on reducing the percentage of eclamptism and eclampsia, but also on reducing severe forms, on a milder course of the disease in the event of its appearance, and on lowering the percentage of maternal and infant mortality. Age and the number of previous pregnancies are of importance; thus, mortality is higher at a younger age (under 20) and in elderly multiparae (especially in elderly primiparae). The latter is explained by a large percentage of heart diseases, changes in the vascular system, and a greater tendency to hemorrhages. Thus, Hermann states that cerebral hemorrhages in eclampsia are detected at autopsy in 7% of cases, and in elderly ones in 12.2%. The question of which eclampsia presents the greatest danger—eclampsia sub gravidate, sub partu, or post partum—has not yet been definitively resolved and is interpreted variously. A more favorable prognosis in recurrent eclampsia still requires additional confirmation, but available data allow us to speak of a milder course thereof (a lower mortality rate, a smaller number of seizures per patient: 2.3 versus 10.1 in other cases, versus 4.7 seizures in intercurrent eclampsia, 19.3 in recurrent, and 19.7 in cases ending fatally), which, on the other hand, does not contradict the theoretical interpretation of recurrent eclampsia (Mikhnov, Vinay, Ascoli, Selitsky, Belikov and Manevich, etc.). In the maternal mortality of eclamptic women, other factors must also be taken into account, among which is the increased tendency to postpartum diseases and death from subsequent septic processes, which is not so rarely observed. Hermann, analyzing the causes of death in eclampsia, indicates that in 70% of cases the cause of death is eclamptic changes, while in the remaining 30% the cause of death is distributed as follows: 10% are due to hemorrhages, uterine ruptures, and infection, 10% to aspiration pneumonia, and 10% to cerebral hemorrhages. Summarizing all the above regarding the prognosis in eclampsia, one can come to a very definite conclusion that one must be very cautious in the prognostication of this disease and approach critically the statistics that strive to defend one or another line of conduct in eclampsia (conservative, active, or any other eclampsia-related line) by summing up all cases without exception without appropriate subdivision and without taking into account the many factors mentioned above. On average, in modern clinics of the Union and abroad, the mortality rate ranges from 2–5 to 10–12%. Infant mortality is also a far from constant value and can depend on the gestational age, the time of the patient's admission to the institution, and sometimes on one or another applied therapy. The average percentage of infant mortality at the present time ranges from 10 to 25 (in individual statistics of recent years, the percentage appears lower and in some clinics drops even to 2–5). The long-term results of eclampsia have in general not yet been sufficiently studied.

The study of the long-term outcomes of eclampsia actually began with clarifying the question of whether eclampsia recurs in a newly ensuing pregnancy. In the long-term outcomes of eclampsia, significance may attach to the nature of the suffered eclampsia, the degree of its severity, greater or lesser damage to one or another organ; the constitution of the patient also leaves its mark. Lepage pointed out (1912) that in terms of long-term outcomes, the prognosis is better in women who suffered eclampsia in their first pregnancy; Stroebe, speaking (1932) about the fact that in general, after past gestoses, recovery proceeds slowly in many women, emphasizes that the general weak condition is especially noticeable in asthenics. By virtue of all this, to form a clear idea of a woman's future after eclampsia, it is necessary to take into account not only the fact of past eclampsia, but also to consider those pathological symptoms that were observed during it. It is clear, for example, that restitutio ad integrum in the kidneys will occur sooner and the percentage of transition to chronic nephritis will be less in cases of milder kidney damage in eclampsia; similarly, the number of subsequent complications from the nervous system and psyche will be greater in hemiplegia that ended in recovery and in cases proceeding with a pronounced psychosis. The long-term outcomes of eclampsia in most cases appear quite favorable. Blandeau (1897), in a dissertation on the subject of albuminuria in multiparae (23 women who had suffered albuminuria or eclampsia in the past), pointed out that in 91.3% no recurrence of the disease was observed. Baisch (1913), having followed 170 women (110 after kidney disease during pregnancy and 60 after eclampsia), came to the conclusion that prolonged disability after eclampsia is observed in 10%; a certain mortality rate is also noted, since in subsequent years out of 110 renal patients 9 died, and out of 60 eclamptic women 6. Selitsky described 15 cases, in 12 of which the long-term outcomes appeared favorable, in one case acute nephritis of pregnant women passed into a chronic form, in another deviations in the psyche were noted during 3 months of observation, and finally the third case ended in death after late post-eclamptic psychosis. In recent years, the opinion that post-eclamptic psychoses in the vast majority of cases end favorably and result in recovery without any intellectual defects has also received confirmation (Ziman). All these far from exhaustive data regarding the long-term outcomes of eclampsia still allow us to say that despite the fact that in a fairly large percentage of cases they are favorable, nevertheless in a number of cases the disease leaves noticeable traces on the state of the entire organism and on individual organs. Along with the need to study this important issue in more detail in the future, the clinic at the present moment should take long-term outcomes into more account. Prophylaxis. Therapy. It is quite natural that since the etiology of the disease is unknown, there can be no question of rational therapy. By virtue of this, one must try to prevent the occurrence of eclampsia by known and available prophylactic measures. The best prophylaxis of eclampsia is the most careful possible attitude towards all pathological symptoms included in the concept of eklamptism, their detailed analysis and the desire not to allow the aggravation of these pathological phenomena and their transition into the convulsive stage. On the other hand, to no lesser extent the obstetrician should strive to prevent the occurrence of the phenomena of eklamptism as well. This, if not always, then in any case very frequently can be achieved by rational prophylaxis of every pregnant woman from the first months of pregnancy. The inadequacy of the measures taken in some cases can be explained not only by our scant knowledge in this matter, but also by the inferiority of the woman's organism, infantilism of certain systems, and past infections. Therefore, the prophylaxis of eclampsia and other complications of pregnancy should be viewed more broadly, carried out more deeply, and not when pregnancy has already set in, but when it does not yet exist—in the earlier years of girls and young women. Upon the onset of pregnancy, the best guarantee of its normal course is regular visits to prenatal clinics and, in the event of even slight deviations, admission to the pregnancy ward. Special attention should be paid to eklamptism. It must always be remembered that eklamptism or pre-eclampsia, signifying already a certain degree of overload of the organism with toxins, not only in a number of cases can pass into eclampsia, but sometimes (and not so rarely), especially in cases of underestimation of the entire pathological symptom-complex of individual symptoms, with prolonged unjustified expectancy, can also end fatally. The main therapy of eklamptism even in mildly expressed cases is absolute rest, bed rest, a salt-free milk diet, depending on the case, and Volhard's dry diet, restriction of fluid intake, regular bowel evacuation (in more acute cases, the use of drastica). In addition, agents aimed at affecting the entire organism have been used with some success: various kinds of solutions—Ringer-Locke, Ringer's (with the addition of 10% gelatin or gum arabic), calcium salts, glucose, normal horse serum. With appropriate indications, bloodletting is also rational, which should not exceed 300–400 cm³ (massive bloodlettings of about 1,500–2,000 cm³ recommended by Salén and his co-workers should be avoided). Hypnotics (Wesselow and Wyatt) and narcotics in whatever [ECLAMPSIA]

in any form (such as, for example, the large doses of chloral hydrate recommended even by Vinay) must have no place whatsoever and should be completely excluded from the means used in eklamptism. The use of various kinds of diuretics, diaphoretics, baths of any kind, and wet packs is also irrational (whereas dry warmth often brings substantial benefit). In sharply pronounced pathological pictures, with the escalation of symptoms, the deterioration of the general condition, and the development of a precomatose state, radical measures up to the termination of pregnancy become necessary. The guiding factor for delivery is not any single prevailing symptom, but the sum of all pathological symptoms and the general condition of the patient. Special emphasis should not be placed on certain symptoms or on the damage to a separate organ (e.g., the kidneys), since it is known that in eklamptism and eclampsia, escalating phenomena from the kidneys, a large amount of protein, and others do not always serve as a criterion of the severity of the process, whereas the escalation of renal phenomena in combination with any other symptoms already represents a sufficiently formidable sign. Consequently, the summation of the entire group of symptoms and their critical evaluation based on continuous, unremitting observation must serve as the basis for judging the necessity of transitioning from conservative therapy to more radical therapy. When proceeding with delivery, one must always take into account that alongside the emptying of the uterus, the very nature of the intervention is of exceptional importance—delivery must be cautious; all methods of forced delivery (accouchement forcé), especially metreurysis, as methods causing increased reflex irritations, should not be used at all in eklamptism. The rationality of the indicated measures and the performance of major operations not with a light hand (non larga manu), but under strictly weighed indications, is fully justified both by theoretical considerations and available clinical data demonstratively showing that the best results are obtained with an individual approach and that very often a timely performed operation not only protects against eclampsia, but at times is also the only means to avoid a lamentable outcome. Significantly worse results are observed among authors adhering to the extreme viewpoint of conservative therapy, who adhere to the principle of maximum expectancy and principally reject the need for surgical intervention. Particularly indicative in this regard are the data of Konrad (1934). Konrad, who principally adheres to a conservative viewpoint, nevertheless had to terminate pregnancy in 20.6% of cases, and out of 26 cases in which convulsions were subsequently observed, 23 died (88.4%). No less interesting is the material of Gyllensvärd (1930), which shows what enormous importance timely initiated therapy and timely performed intervention have. Indeed, clinical data of authors adhering either to principally active therapy (Essen-Möller) or individual therapy (Margaret Basden, Astrinsky, Bliznyanskaya and Gleyser, Sakharov, Selitsky, etc.) convince us that eklamptism is a serious disease that forces the obstetrician to always be on guard, requiring the termination of pregnancy and even the performance of Caesarean section not so rarely (termination of pregnancy according to Essen-Möller in 72.2%, according to Selitsky in 33%; Caesarean section according to Astrinsky-Bliznyanskaya-Gleyser in 20.5%, according to Selitsky in 15.2%). At the same time, the mortality rate appears to be significantly lower: in Essen-Möller, Astrinsky-Bliznyanskaya-Gleyser, and Selitsky, it is even equal to 0. The opinion of M. Basden and Siedentopf that by timely intervention in preeclamptic toxemia we protect the mother and child from prolonged intoxication, and thereby from possible late damages that occur sooner with excessive delay in terminating pregnancy, is entirely correct. In the therapy of eclampsia itself in its convulsive stage, one should be based on the same principles that are carried out in eklamptism. Fixing our attention on the appearance of a seizure, qualifying the onset of convulsions as a new additional symptom in the pathological symptom complex of eklamptism and as a further degree of organism intoxication, we nevertheless should not focus all our attention solely on a single seizure. In the therapy of eclampsia, one should also proceed from the fundamental principle that eclampsia is a disease not of individual organs, but of the entire organism, and that its actual cause is the fertilized ovum in toto, since without pregnancy there is no eclampsia. In addition, one must take into account that in eclampsia, as generally in any gestational toxicosis, a whole series of various variants in the course of the disease can be observed, the damage to one or another organ can be different, and the reaction of each individual organism will also be different. In view of this, depending on the predominance of damage to one or another organ, our therapy should also be different. There can be no mechanical approach to processes with a very diverse course, nor can there be treatment according to pre-prepared tables and defined schemes; each of our interventions must be strictly justified and must proceed from the picture and features of each individual case. The injection of morphine, the use of one or another remedy in general, must be as justified as the performance of venesection or the termination of pregnancy either by Caesarean section or by any other means. Therefore, the main task is to place the eclamptic organism in such conditions and create such an environment as to facilitate its fight against developed and developing toxins, and to try to neutralize them as far as possible, and if necessary, to remove the primary source of toxin formation. Taking into account the characteristics of the organism of each patient, unequal resistance, and also knowing on the basis of clinical experience that the virulence of the toxins produced is far from always equivalent, and that the course of eclampsia is of an extremely diverse character, one must treat not the disease, not its individual symptoms, but the patient. The main features of this therapy are the individualization of each individual case, exact clinical accounting of observed symptoms, determination of the degree of damage to one or another organ (cases of eclamptism with prevailing phenomena from the brain, kidneys, lungs, heart) and the prescription of corresponding treatment depending on this. This therapy, standing on the principle of individualization, does not strive to conduct all cases without exception with the help of rapid, cautious delivery, but applies it only in the presence of an indication for rapid emptying of the uterus. In the same way, individual therapy also uses all other means (see below), but only each applied means must have its clinical justification. Special caution with the use of narcotics must be observed in cases with a deep comatose or unconscious state. The clinic also shows that one can dispense entirely with the use of narcotics (Selitsky, subsequently the clinic of Kurdinovsky, and some others). This is fully understandable, since narcotics are powerless to eliminate, neutralize, or detoxify the toxins still unknown to us that cause convulsions and other pathological symptoms. Even in those times when the concept of eclampsia was rather narrow and everything was reduced only to a seizure, we encounter indications that narcotics in general, and individual narcotic drugs in particular, are far from indifferent in such processes as eclampsia, especially when used in large doses. Already in Antoine Petit (1723–1794) it is stated that opium preparations kill the mother and child; later Halbertsma (1878) pointed out that in cases where labor is progressing or artificial delivery is expected, narcotics should be used as little as possible. Krönig at the international congress in Rome and subsequently (1894, 1901) insisted on the necessity of reducing narcotics in eclampsia. Knape (1904) said that in severe cases they worsen the comatose state and by virtue of this bring only harm. By virtue of all this, individual authors as early as the late 19th and early 20th centuries in their practical life did not use narcotics at all in eclampsia. In the very recent period, a significant revival is noted around the question of the use of narcotics in eclampsia; it is pointed out that narcotics, in whatever form they are used, are not specific remedies in eclampsia. Most noteworthy are the experiments of Fee (1928), Kennedy and Onortis, and a number of authors from the laboratory of the famous physiologist Savich. Thus, Fee noted a sharp decrease in diuresis in animals upon the administration of morphine; Kennedy and Onortis additionally proved the depressing effect of morphine on the water balance center and the resulting increase in intracranial pressure, delayed excretion of urine, intestinal juice, and increased tissue and brain edema. The laboratory of Savich (Savich, Derginsky, and ...]

Speranskaya, Gorbunova (1932, 1933, 1935) also came to the conclusion that morphine has a strongly pronounced antidiuretic property, has a depressing effect on the intestines as well, and that, moreover, it can be a factor in water poisoning of the body and the appearance of convulsions. Clinicians also confirm the harmful effect of morphine (Brovkin, Alovsky, Chernozubova, Siegel, and others). The inexpediency of using morphine and narcotic drugs in general is also indicated by the clinical results of the State Scientific Institute of Mother and Child Protection named after Lebedeva for 1926-1930 and data from the Ivanovo Institute of Mother and Child Protection for 1.5 years: the Ivanovo Institute of Mother and Child Protection (Chernozubova, 1935). Treatment. Total cases: Mothers (recovered, died, mortality percentage), Children (mortality percentage). Drug therapy according to Stroganov's method: 91, 81, 10, 11%, 2.1%. Non-narcotic therapy: 44, 41, 3, 2.1%. ¹ One case in non-narcotic therapy is reduced—delivered dying from the village, died 15 minutes after admission, and two cases of child mortality—perforation of the fetal head, one in each group. Indications for delivery in eclampsia sub graviditate et sub partu will be not only frequently recurring seizures, but also a continuing unconscious state and especially coma between convulsions, high hypertension, soft frequent pulse, labored breathing (especially with initial symptoms of pulmonary edema), a sharp violation of perspiratio insensibilis, oliguria, anuria, and others. Rapid delivery may be indicated even without frequent seizures in a general severe condition and long-lasting coma. Delivery must be cautious. Expectation is possible in moderate seizures with long intervals, in the absence of coma, severe symptoms from the heart, kidneys, lungs, and with slight hypertension. With a weakly expressed pathological symptom complex, under unceasing observation of the patient, it is possible to wait for the spontaneous termination of labor. In both cases, in the absence of contraindications from the heart, bloodletting may be performed. It should be moderate (200-400 cm³), since one must always take into account the possibility of bleeding during delivery and postpartum. After bloodletting or independently of it, the administration of one or another solution (Ringer's, Locke's, glucose) in small quantities (300-400 cm³) or normal horse serum (30-50 cm³) may be indicated. In phenomena of cardiac weakness, the periodic use of cardiaca is rational (camphor, digalen, etc.—every 2-3 hours or less often); in labored breathing or beginning symptoms of pulmonary edema, the repeated use of dry cupping is very useful, and the use of cardiac remedies is also expedient. In severe cases, especially with predominant symptoms of brain damage (coma), extreme caution is necessary with narcotics. In eclampsia sub partu at the beginning of the first stage of labor, the course of action will be similar to therapy in eclampsia sub graviditate. With sufficient dilation of the cervix, rupture of the amniotic sac, application of forceps, or under appropriate conditions, version is indicated. In postpartum eclampsia, the indicated individual approach is also carried out (bloodletting can be used more widely—400-600 cm³ in the absence, of course, of contraindications). Along with one or another therapy, the care of the eclamptic patient is of exceptional importance. In addition to observing silence and isolating the patient, it is necessary to maintain cleanliness, turn her onto her side (to avoid the formation of bedsores), wipe the mouth, and protect the tongue from bites and injuries during attacks (the latter is achieved by inserting a metal spoon wrapped in a handkerchief or a rubber wedge before the seizure; Liepmann). Modern trends in the therapy of eclampsia are not limited to the above: there are other views, which in general can be divided into 3 groups—conservative-expectant therapy, active therapy, and so-called "middle line" therapy. Conservative-expectant therapy consists of a number of therapeutic agents and measures aimed at stopping seizures or affecting certain pathological symptoms. Proponents of this direction are fundamentally against radical intervention and resort to rapid delivery only in exceptional cases. The main principle of this therapy is predominantly influencing some specific symptom (e.g., weakened urinary excretion function, the desire to reduce the increased excitability of the nervous system and stop convulsions). The arsenal of proposed therapeutic agents is extremely diverse, with the largest group being narcotics. In the era of uremic theories of eclampsia, along with the widespread use of narcotics, diuretic and diaphoretic agents were very common, and hot baths and wet wraps were in great use. All these remedies are now almost never used, because clinical observations have shown that they enhance the comatose state, weaken cardiac activity, and contribute to respiratory disorders and more frequent seizures. An exceptional place in expectant therapy is occupied by various kinds of narcotics. Of these, chloroform inhalations, morphine, and chloral hydrate were the most widespread. The rather discouraging results obtained involuntarily forced an increase in doses, leading to the creation of combined methods based on the combined action of medicinal substances. Among Russian methods, the best known is the so-called "prophylactic" method of Stroganov. The method consists of the systematic administration of narcotics at regular intervals, in creating appropriate conditions to avoid reflex irritations, in isolating the patient and maintaining the proper functioning of the main vital functions: kidneys, skin, lungs, and heart. Stroganov's scheme: start of treatment—0.015 (0.02-0.01) Morphine muriate subcutaneously under light chloroform anesthesia; 1 hour from the start of treatment—2.0 (2.5-1.5) chloral hydrate (if conscious per os with milk, in unconscious ones—per rectum under chloroform with milk and 100 cm³ of physiological saline + 100 cm³); 3 hours from the start of treatment—0.015 (0.02-0.01) Morphine muriate subcutaneously under light chloroform anesthesia (20-40 drops); 7 hours from the start of treatment—2.0 chloral hydrate similar to the previous one (2.5-1.5); 13 hours from the start of treatment—1.5 (2.0-1.0) without chloroform anesthesia, if there was no seizure for 8-10 hours; 21 hours from the start of treatment—1.5 (2.0-1.0) without chloroform anesthesia, if there was no seizure for 3-10 hours. During the first two days, 7.0 of chloral hydrate and 0.03 of morphine muriate are administered; in severe cases in robust subjects, the largest doses are administered—9.0 of chloral hydrate and 0.04 of morphine muriate. The intake of morphine and chloral hydrate is increased in severe eclampsia, and decreased in mild postpartum forms. If seizures repeat, bloodletting of 400 cm³ is recommended. Delivery only under appropriate conditions. In severe eclampsia in the absence of contraindications—rupture of the amniotic sac in primiparae when the os is dilated to 3 fingers, in multiparae to 2 fingers. Warm maintenance of the patient, enemas of milk and saline solution, oxygen inhalation, cardiaca. Stroganov considered the combined action of narcotics to be the main thing in his method and also pointed out that chloral hydrate is a kind of specificum and a sort of antidote to toxins formed in eclampsia. However, despite the comforting data cited by Stroganov, this method is far from being practiced by all clinics both in our Union and abroad. This can be explained by the fact that other authors obtain less favorable treatment results, and also by the fact that apparently some prefer a more active course of action, while others adhere to more individual principles of treatment and refrain even from the relatively wide use of narcotics on the grounds of their harmful effect. Bloodletting can also be referred to conservative therapy. It does not represent an independent type of therapy, but is part of some combined methods, used under appropriate indications by proponents of the individual direction and adherents of other methods of therapy. Bloodletting is used repeatedly, in small amounts (100-200 cm³) or in the form of so-called massive venesection (400-500 cm³ and more). The viewpoint on venesection is not uniform; some (Zweifel) attach exceptional importance to it, while others quite rightly note that the effect is not always lasting and that it can even have a harmful effect (Zangemeister). It is not rational to perform bloodletting broadly and indiscriminately in every eclampsia. Bloodletting must also have its specific indications, and when performed in the presence of contraindications, it brings only harm. The main contraindication is impaired cardiac activity, especially in combination with coma. Zangemeister believes that venesection is contraindicated in phenomena of edema of the medulla oblongata, in the presence of high temperature, frequent small pulse, coma, and sharp pallor.

When performing bloodletting, one must also take into account the magnitude of blood pressure and it is better not to resort to it when hypertension is not particularly high. Martin performs bloodletting under the control of blood pressure and lets out enough blood until the blood pressure according to Riva-Rocci drops below 100 (on average up to 1,000 cc). One must also refrain from excessively copious bloodlettings exceeding 1,000 cc (especially universally for every eclampsia), the more so antepartum. Copious bloodlettings met with many weighty objections from the participants of the All-Ukrainian Conference of Gynecologists in 1934. The objections boiled down to the fact that they cannot be widely recommended, their use is permissible only in a clinic, and they can affect the course of eclampsia and lead to undesirable long-term consequences. Among other combined methods, the so-called Dublin method enjoys the greatest distribution in England. It consists of 1) washing out the stomach and bowels, 2) subcutaneous injection of a solution of sodium bicarbonate (500-600 cc), 3) subcutaneous administration of morphine in 19

and 4) giving laxatives (if the seizures continue, all this is repeated again). Quite widely used are other medicinal agents and methods, but they cannot be considered exclusively from the standpoint of conservative therapy, since under appropriate indications they are readily used by proponents of both active therapy and "middle line" therapy. These include artificial respiration, oxygen inhalation, dry cupping, hot compresses to the kidney region (Gubarev), all kinds of cardiac remedies (especially camphor, digalen) and the introduction of various solutions (Ringer's, Locke's, sodium bicarbonate, glucose, etc.) and various sera (serum of a pregnant woman, horse N-serum). Of other remedies, special attention is currently given to magnesium sulfate, luminal, pernocton, somnifene, and calcium chloride, but it is not yet possible to draw any final conclusions regarding all these remedies at present in view of the contradictory results obtained by different authors. Many authors (Savich, Brovkin, Alovsky, Lazard, Trapl, Arnaldo de Moraes, Konrad, etc.) confirm the narcotic effect of magnesium salts on the central nervous system, established as early as 1905 by Meltzer and Auer, noting their positive effect in eclampsia and advantages over morphine (Savich, Brovkin, Wodon). L. MacPhail (Mc Neill, 1934), using magnesium sulfate (20 cm³ of a 10% solution intravenously, repeatedly), came to the conclusion that under its influence blood pressure drops, edema subsides, diuresis increases, seizures are stopped (Arnaldo de Moraes adheres to the same doses of MgSO₄, additionally combining phlebotomy and a laxative). Konrad uses 20 cm³ of 10% MgSO₄ in a 20% glucose solution (according to Lazard); Alton and Lincoln recommend spinal injections in doses of 1 cm³ of a 25% solution for every 8 kg of weight (when doses are exceeded, they are balanced by an intravenous infusion of 10 cm³ of a 25% solution of calcium chloride). In our Union, MgSO₄ was used by Alovsky, Brovkin, and others. Brovkin injects 200 cm³ of a 3% solution of MgSO₄ subcutaneously into the breast tissue repeatedly (no earlier than 4 hours later, no more than 4 times a day) and additionally uses 1,000 cm³ of a solution warmed to 38° (NaBr-5.0, KCl-0.2, CaCl₂-0.2, NaHCO₃-0.2, Glucosae-100.0, Aq. destil.-1,000.0). Brovkin notes the excellent antispasmodic effect of MgSO₄, as well as its lowering of intracranial pressure (10 cm³ of a 5% solution of calcium chloride eliminate the effect of MgSO₄); along with its administration, careful delivery is not ruled out, thorough care is provided, and warmth is applied to the kidney region (out of 64 cases of eclampsia and 5 cases of severe eclamptism, maternal and child mortality was 4.3%). However, these favorable results have not been obtained by everyone, which is why a number of authors consider further observations on MgSO₄ necessary. Among other, more rarely used measures, one can point to blood transfusion and autohemotherapy, which, however, have not even received relatively widespread distribution. Relatively rare are references to the performance of lumbar puncture (Kronig) and postpartum curettage of the uterus. Kidney decapsulation, proposed in 1903 by Edebohls in cases of complete anuria, now has few supporters. Individual "heroic" operations—tracheostomy (Schwab), trepanation of the skull (Zangemeister), excision of the breasts (Sellheim), extirpation of the uterus (Zangemeister)—met with sharp criticism from the moment of their appearance, were almost never used in practice, and at present are only of historical interest. Active therapy is based on the fact that without pregnancy there is no eclampsia, and therefore strives to empty the uterus as soon as possible. These ideas, which became widespread from the beginning of the 20th century, actually arose much earlier. Thus, obstetricians of the 17th and 18th centuries (e.g., Mauriceau) already noted that the end of the birth process has a favorable effect on the course of eclampsia. In the era we are experiencing, forced delivery (accouchement forcé) was initially widespread, and was later abandoned due to the reflex irritations it caused. The trend of "rapid and careful delivery," which replaced "forced delivery," strove not only to empty the uterus, but to do this carefully and quickly, and to avoid reflex irritations. It was subsequently proven statistically that timely delivery by careful means is important, and a difference in the mortality percentage was revealed depending on the time elapsed from the beginning of the first seizure. Nowadays, active therapy in its pure form—delivery at the beginning of the disease after almost the first seizure—is practiced by very few schools. Most authors believe that active therapy should take place in eclampsia, but carrying it out in every case is inexpedient. Among the main, principal proponents of active therapy are Stoeckel, Waldstein, Llames-Massini, and others, who presented statistics with more than encouraging results: Stoeckel—8.4% maternal mortality; Waldstein—1.7% maternal mortality, directly from eclampsia—0.9% and child mortality 10.1%; Llames-Massini, having obtained 0% maternal and child mortality with classical and vaginal Cesarean section, says that white statistics for mothers and viable children are given only by early surgical therapy. Wagner (1924) is also a proponent of active intervention: out of 19 cases of transperitoneal Cesarean section and 3 vaginal ones, he did not have a single fatal outcome. Wagner rightly notes that in eclampsia, careful anesthesia, speed of operation (no more than 20 minutes), careful suturing, and good postoperative care are of great importance. Therapy of the so-called middle line (Engelmann) adheres to an individual approach, strives primarily to eliminate reflex and irritating factors, recognizes delivery as a factor contributing to the speedy passage of the convulsive stage, but performs it almost exclusively when it is technically easily feasible. Judging by the literature, this type of therapy has a fairly large number of supporters. Engelmann (1923), summarizing the results of "middle therapy" for eclampsia and noting a significant decrease in the percentage of mortality (over the last 2 years, 10% maternal mortality) with this management method, nevertheless quite correctly points out that this largely depends on more active prevention. Which of the currently existing methods of eclampsia therapy to give preference to is more than difficult to say on the basis of published statistics. It is also difficult to navigate the available material because cases are cited summarily with an indication of how many cases were managed conservatively, actively, what medicinal substances were used, what the mortality percentage was, but without a detailed subdivision of cases by severity and without appropriate characteristics. There is no idea of the very nature of the seizure, generally about the convulsive stage, nor is there a characteristic of the general symptom complex, manifestations of particularly important pathological symptoms. And without such a comprehensive approach, it is naturally difficult to draw any guiding conclusions, difficult to talk about which method of treatment for eclampsia is most effective. All individual excerpts from the rather large material available clearly show that in our future conclusions for judging the advantages of one or another therapy in general, one or another method in particular, we must proceed not only from bare figures alone, from the mortality percentage alone, but must also take into account many other factors. In other words, a radical reform of eclampsia statistics is needed; attempts to carry this out have already been made in recent times by individual authors (Seitz, 1930; Skrobansky, 1933). Skrobansky considers it highly doubtful that only such a criterion as the percentage of mortality could be used as a basis to clarify the question of the effectiveness of one or another method, and furthermore believes that it is unacceptable to compare the results of two methods, one of which is used in more severe cases or only when the rest of the therapy proves unsuccessful. Seitz, speaking of the need for a more detailed differentiation of eclampsia cases by their severity, places special emphasis on preeclampsia and believes that one of the essential moments for deciding the question of the advantages of one or another course of action in eclampsia is the percentage of transition of eclamptism (preeclampsia) into the convulsive stage. It should be noted that in order to develop a more rational treatment of eclampsia until the etiological factor of the disease is clarified, a more detailed clinical study of individual symptoms [e.g., works specifically dedicated to the study of the eclamptic seizure (Tesauro), the cause of death in eclampsia (Caffier, 1934), etc.] and a deeper familiarity with the pathoanatomical picture should be of significant benefit.

The most acceptable therapy at the present time, one that best corresponds to our modern understanding of the multifaceted nature of eclampsia, is individual therapy, in which, depending on the course of the process and given the appropriate indications, one or another of the methods available and known to us at the present time are used, and gentle delivery operations are performed. Infantile eclampsia see Spasmophilia.