Eclampsia historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Navneet Kaur M.B.,B.S.

Overview

The importance of historical perspective lies in the fact that our current understanding of pathophysiology, classifications and management strategies is influenced by past hypotheses and scientific contributions, which have also shaped our current practice trends. The term is derived from Greek and refers to a flash, a term used by Hippocrates to designate a fever of sudden onset. Various theories have been proposed from time to time such as the theory of four humours, wet and dry theory, wandering womb theory during ancient times; dominant humour theory and Mauriceau’s suppressed lochia flow theory during the middle ages; During the 18th and the 19th century, physicians started noting the association of various symptoms such as headache, body edema, short term loss of vision, severe pain in the stomach, etc. during later months of pregnancy and the development of convulsions. Smith’s theory of toxic elements came during the same period. Extensive advancements in uncovering the pathophysiological changes were made in the 20th century, such as the trophoblastic shallow invasion theory and endothelial disorder theory. Various treatments were offered from time to time depending upon the theories proposed such as purging, bloodletting, altered diets, getting rid of toxic elements, placing the patient in a warm bath, opiates, etc. during the 20th century increased focus was placed on routine prenatal care and early recognition of warning signs and symptoms. In the early 20th century the use of magnesium sulphate was popularised and safety was established which still guides our treatment protocols.

Historical Perspective

Over time various theories and treatments based on those theories have been proposed.

Ancient Times

Theories

• THEORY OF FOUR HUMORS
  • In late 5^thand early 4^th BCE
  • The balance between Four humors, blood, phlegm, yellow bile, and black bile, resulted in health and illness.

• WET AND DRY THEORY
  • Women’s skin was considered wet, porous, and soft and it was thought that she could accumulate lots of moisture which resulted in an overabundance of fluids and led to illness.

• WANDERING WOMB THEORY
  • Hippocrates believed that dried up uterus wandered the body in search of moisture, and as it wandered the body, it could wreak havoc upon the liver, spleen, lungs, and head, leading to disease.

Treatments Offered

Treatment directed towards the restoration of internal equilibrium by mechanisms that increased elimination of excess fluids and could consist of:

• Altered diets
• Purging
• Blood-letting

Middle Ages

During the middle ages, between 400 CE and 700 CE, scientific progress, especially medical, came to a standstill as the Christians were opposed to human science and dissection. many medical schools were closed, such as at Athens and Alexandria. Hence, the main focus was on the compilation and rewriting. Later, the Christian influence began to decline and new theories emerged. In 1619, the word "eclampsia" first appeared in Varandaeus' treatise on gynecology.

Theories

• DOMINANT HUMOR THEORY
  • One theory that emerged suggested that one humor dominated the other humors and controlled an individual's physical and emotional characteristics, and was responsible for the signs and symptoms of eclampsia.

• MAURICEAU'S THEORY
  • In 17^th century, when medicine gained momentum again, Francois Mauriceau helped establish obstetrics as a specialty. He was the first to systematically describe eclampsia, and to note that primigravidas were at a greater risk for convulsions compared to multigravidas. He attributed convulsions to either suppressed lochia flow which could lead to inflammation, pain in the head, convulsions, suffocation, and death, or intrauterine fetal death which could lead to foul-smelling humors and predispose a woman to convulsions.

Treatments Offered

Increasing Christian beliefs greatly influenced treatments which consisted of charms, amulets, prayers. However, as time passed treatments offered in ancients times were again practiced, such as phlebotomies.

18^th and 19^th Century

Theories

• In the 18^th century, Bossier de Sauvages discerned eclampsia from epilepsy and believed that convulsions transpired due to nature trying to free the morbid elements from the organism. He also noted that eclampsia was acute in nature and epilepsy was chronic because convulsions due to eclampsia resolved once the precipitating cause was removed but epilepsy recurred over time. He also pointed out that eclampsia was not restricted to pregnancy and severe hemorrhage, various sources of pain, and vermicular infestations were several species of eclampsia.

• In 1797, Demanet noted a connection between edematous women and eclampsia.

• In 1843, John Lever discovered albumin in the urine of eclamptic women.

• In 1843, Dr Robert Johns pointed out an association between premonitory warnings, such as headache, short term loss of vision, severe pain in the stomach, edema of the hands, arms, neck and face, during the later months of pregnancy and the development of convulsions.

• In the 19^th century physicians continued to propose more theories. Dr Thomas Denman(1821) in his work entitled "Introduction to the Practice of Midwifery", concentrated on labours affected by convulsions. He attributed convulsions to specific customs and behaviours analogous to living in big cities and towns but also noted that the largest risk came from the uterus. According to him, expansion of the uterus during pregnancy placed considerable pressure on the descending blood vessels, resulting in regurgitation of blood in the head and overload of cerebral blood vessels resulted in convulsions.

• Dr William Tyler Smith(1849) in his work, “Parturition and the Principles and Practice of Obstetrics” challenged Denman's notion of cerebral congestion. He speculated that pregnancy was a state of increased fullness in Circulation. Dr Smith pointed out that if cerebral congestion was the rationale for seizures more cases would be anticipated during the second stage of labor as contractions during the second stage would interfere the most with the circulation of blood. He proposed other rationales such as:
  1. mechanical or emotional stimulus applied to the spinal cord
  2. variations in the wind, temperature, other atmospheric alterations
  3. bloodletting
  4. irritation of the uterus, uterine passages, intestinal canal, and the stomach
  5. the toxic elements
  • SMITH'S THEORY OF TOXIC ELEMENTS: Dr Smith speculated that the health of the pregnant woman depended on the exponential increase in the elimination of the waste elements, such as secretion of the bowels, and debris from the maternal and fetal system. Failure to eliminate such wastes could result in "toxemia", in which morbid elements accumulate in the system and could irritate the nervous system.

• In 1897, Vaquez and Nobecort were credited with the discovery of eclamptic hypertension and the concept of preeclamptic state was recognized. The presence of edema, headache, and proteinuria now raised concerns about the possibility of convulsions.

Treatments Offered

In the early 1800s:

• Bloodletting: In the early 1800s, it continued as a staple in the treatment and prevention of eclampsia. The quantity and frequency of bloodletting were determined by the strength of the patient and the severity of symptoms. The initial site for bleeding was the arm and repeated if necessary, that is if the convulsions persisted. In some cases, the jugular vein or temporal artery were also opened.
• Opiates: They were employed to curtail irritability of the female organs.
• Splashing cold water on patients face
• Placing the patient in a warm bath

If all other methods were ineffective, the Physician had to decide between expediting the childbirth or letting natural labor to start. According to Dr Denman, delivery was only hastened when the mother displayed the indications of being physiologically ready such as completion of dilation, rupturing of membranes, or descent of the fetus, because interventions in the early stage of labor could increase maternal mortality.

In the late 1800s:

• Elimination of Toxins: When Smith’s theory of toxic elements emerged, treatments were targeted at the elimination of overabundant toxins. Some believed that meat toxins provoked eclampsia and advised against the consumption of meat products and prescribed diets consisting of vegetables, fruits and milk products.
• Preventative therapies: Now women with preeclamptic states, those who had headaches and edema of the upper extremities, were increasingly recognised and admitted to lying-in hospitals where they underwent procedures such as bleeding and purging to prevent seizures.

20^th Century

Extensive advancement occurred in uncovering the pathophysiological changes associated with eclampsia and several alterations were brought about in the classification of preeclampsia-eclampsia disease throughout the century.

Theories

• Trophoblastic Shallow Invasion Theory: In the 1960s, numerous groups described differences in the physiology of the placentas from patients affected by pre-eclampsia versus the placentas from patients not affected by the same. Subsequently, after conducting the placental bed biopsies, it was discovered that Placental trophoblast cells failed to adequately invade the maternal spiral arteries and convert the arteries from small muscular vessels into large, low resistant vessels in pre-eclampsia. With the lack of spiral artery conversion in preeclampsia, arterial lumen diameter and distensibility was restricted which resulted in the restriction of blood flow to the placenta and growing fetus. These findings have been instrumental for the current understanding of eclampsia.
• The Hydatoxi lualba ( a parasitic worm) theory: This theory was published in the American Journal of obstetrics and gynaecology,1983. According to this theory, a worm-like organism was attributed to the development of preeclampsia-eclampsia. The basis of this theory was the finding of Hydatoxi lualba in the samples, which consisted of peripheral blood, bloody fluid on the maternal surface of the placenta, and umbilical cord blood gathered from women with preeclampsia-eclampsia. But, this theory was soon refuted as other research groups illustrated that cellulose residue from laboratory paper products, starch powder from gloves, and altered staining techniques elicited identical worm-like organisms.
• Roberts and colleagues, 1989: Dr Robert and colleagues posited preeclampsia to be an Endothelial disorder. Drawing from the past trophoblastic shallow invasion theory, they further hypothesized that the ischemic placenta released a damaging factor into the maternal circulation. This circulating factor could be responsible for the endothelial dysfunction and in turn result in the activation of the coagulation cascade, abnormalities in blood pressure, and loss of fluid from the intravascular fluid space.

Progression of preeclampsia-eclampsia classification during the 20th Century

The table adapted from A Historical Overview of Preeclampsia-Eclampsia

Year	Citation	Milestone
1903	Chesley, 1978	“pre-eclamptic state” included in textbooks
1961	Chesley, 1978	preeclampsia-eclampsia restricted to the obstetric definition

Progression of preeclampsia-eclampsia classification during the 20th Century ( Adapted from A Historical Overview of Preeclampsia-Eclampsia )

Obstetrical Textbook Publication Year & Citation	Terminology	Classification Description
1966 Eastman & Hellman (1966)	Toxemias of pregnancy	A. acute toxemia of pregnancy (pre-eclampsia and eclampsia); chronic hypertensive disease with pregnancy; unclassified toxemia B. preeclampsia diagnostic criteria: presence of hypertension, edema, or proteinuria after 24 weeks gestation
1976 Pritchard & McDonald (1976)	hypertensive disorders of pregnancy	A. “toxemias of pregnancy” replaced with “hypertensive disorders of pregnancy” B. preeclampsia diagnostic criteria: development of hypertension with proteinuria, edema, or both commencing after 20 weeks gestation
1988 Hibbard (1988)	pregnancy induced hypertension	A. under the classification of hypertensive disorders of pregnancy, preeclampsia was further grouped under “pregnancy induced hypertension,” which also included hypertension that developed during pregnancy excluding the features of preeclampsia B. preeclampsia diagnostic criteria: mild to moderate preeclampsia- presence of hypertension and edema; severe preeclampsia- presence of hypertension and proteinuria with or without edema or cerebral or visual disturbances after 20–24 weeks gestation

Treatments Offered

In the late 19^th and early 20^th a myriad of protocols was embarked towards the treatment of eclampsia. The physicians in Netherlands and Germany originally endorsed aggressive management consisting of prompt abdominal or vaginal cesarean section. But the aggressive management was associated with exceptionally high maternal mortality rates. Thereafter, a more conservative approach amassed popularity and was widely used. Tweedy of Dublin and Russia's Stroganoff were the forerunner physicians behind the conservative management.

• Tweedy's Rationale for Conservative Management: According to Tweedy, accelerating labor and delivery could instigate convulsions via the induction of reflex stimulation. He proposed that physicians should avert from performing vaginal examinations, abdominal palpations, kidney massages, cold air blasts, dilation of the cervix to evade reflex stimulation. His management protocol included:
  • Patient’s sedation (included morphine).
  • If a patient went into labour, Tweedy believed that the application of forceps was acceptable if the os safely permitted their application.
• Stroganoff's Approach: Stroganoff’s primary objective was to terminate seizures because he believed that convulsions disrupted the functions of the heart, lungs, liver, and kidney. He ignored the pregnancy, treated the eclampsia, and waited for the natural onset of labour. Stroganoff allowed inspections and treatments under light anaesthesia, keeping the patient in a dark and quiet space to avoid any sensory stimuli. To further sedate the patient, if required, and to decrease the convulsions Morphine and chloral hydrate were also administered. In case of respiratory decompensation, oxygen was given. He examined the pulse as well as other cardiac functions regularly and if the pulse was feeble, digitalis was administered. Once the cervix was dilated to 6 cm, the membranes were artificially ruptured and labour was allowed to progress naturally.
• The Introduction of Magnesium Sulfate: In 1906, Horn first employed ''magnesium sulphate'', which is the current mainstay of treatment, to manage preeclampsia-eclampsia. During the 1920s the parenteral use of magnesium sulphate was popularised by Dr Lazard and Dorsett. Dr Lazard in his work illustrated that treatment with intravenous magnesium sulphate was both efficacious as well as safe.
• After the 1960s: Very few alterations have been made in the management of pre-eclampsia since the 1960s. This can be discerned from the texts used to educate pupils in healthcare fields. The management options recommended were:
  • Routine prenatal care:
    • Management commenced with routine prenatal care which entailed regular blood pressure measurements, maternal weight checkups, urine analysis, to recognize any early signs and symptoms.
  • Management of patients diagnosed with preeclampsia:
    • Frequent BP measurements, urine analysis, bed rest, weight check-ups, fetal surveillance, assessment for maternal headaches, blurry vision, and epigastric pain, etc.
  • Management of patients with fulminating pre-eclampsia or the development of eclampsia:
    • Magnesium sulphate was given to manage convulsions
    • Antihypertensives were administered to tackle acute hypertension
    • Delivery: The decision to move forward with the vaginal delivery or the Cesarean section depended on various factors such as gestational age, condition of the cervix, maternal condition, and fetal condition.