Eclampsia: A Critical Pregnancy Complication Demanding Enhanced Maternal Care: A Review

Background

Preeclampsia and eclampsia are 2 of the most serious complications following pregnancy and are the main causes of death of pregnant and delivering women [1,2]. Although preeclampsia affects 3–8% of pregnancies, the mortality rate of young mothers is 5–20% [1–7]. Coma, Hemolysis, Elevated Liver enzymes and Low Platelets syndrome (HELLP syndrome), disseminated intravascular coagulation (DIC), sudden cardiac arrest, pulmonary oedema, acute respiratory distress syndrome (ARDS), kidney failure, central nervous system hemorrhage, and mechanical ventilation complications constitute the main causes of death in pregnant women associated with severe preeclampsia or eclampsia [1,2]. About 50–70% of mortality of women with pregnancy, complicated by hypertension, is due to cerebrovascular incidents, and preeclampsia itself is associated with a 4-fold increase in stroke during pregnancy, childbirth, and puerperium [7,8–10].

The mortality rate of this severe pregnancy complication in fetuses and infants is estimated at 7–40%, and this is mainly the result of complications such as preterm placental abruption, placental insufficiency, intrauterine death of fetus, and complications arising from prematurity [1,11].

This review aims to present an overview of the current prevalence, diagnosis, and management of preeclampsia and the need for improved maternal care.

Proceedings in the Case of Eclampsia

Eclampsia seizure involves 3 parallel pathways of clinical proceedings administered simultaneously (3 equivalent therapeutic goals): (1) Drug treatment aims at stopping eclampsia seizures (management of convulsions) and preventing reoccurrence of eclampsia seizure and its complications; (2) Treatment with antihypertensive drugs and management of hypertensive crisis; and (3) Emergency treatment undertaken immediately during eclampsia seizure for life-saving and health maintenance of mother and fetus.

Treatment involves oxygen therapy, prevention of injuries and hypoxia, fetal surveillance, termination of pregnancy (labor) in the safest and least traumatic manner (after stabilizing the patient’s condition), and prevention of complications. Although patients with eclampsia should be treated at an intensive care medical unit, every gynecologist-obstetrician and specialist in maternal-fetal medicine should be ready to save the life of a mother and a fetus in the event of this life-threatening complication of pregnancy [12].

Actions Performed Ad Hoc Directly During Eclampsia for Life-Saving and Supervision of the Fetus and Continuous Fetal Heart Rate Monitoring

The most urgent part of the treatment is the lifesaving procedure, with airways patency assessment, maintenance of breathing and blood circulation of the mother (cardiopulmonary resuscitation), securing an adequate oxygen level of the mother and thereby of the fetus, and the prevention of injuries. Appropriate procedure and immediate therapy will reduce the morbidity and mortality rates in mothers and infants. Engagement of a larger number of trained medical personnel is essential – call for help and clear the airways, and place the patient in the left lateral position to reduce the risk of aspiration. Eclampsia is always an immediate life-threatening condition.

Combatting hypoxia and acidosis and reducing the risk of aspiration is essential. The delivery of oxygen therapy is important to maintain proper saturation level. Oxygen flow with a speed over 8–10 liters per min through the facial mask provides an oxygen concentration over 60% in the breathing mixture and reduced the risk of respiratory acidosis as a result of hyperventilation or even apnea, which accompanies the eclampsia attacks and therefore prevents multi-organ damage [1,13–15]. Control of blood oxygen saturation and its appropriate level maintenance is essential. Percutaneous pulse oximetry is a simple and essential tool for control of blood oxygen saturation.

In the event of a drop in oxygen saturation (SpO2) below 93%, the evaluation of arterial blood gas test is essential, and bicarbonates should be administered if there is acidosis [13,14]. In justified cases, intubation can be essential. In pregnant women, ventilation through the endotracheal tube provides better gas exchange than through a bag valve mask [15]. During intubation, it is often essential to use an intubation tube of a smaller diameter than that used in non-pregnant woman (0.5–1 mm) [15]. SpO2 ≤93% is linked to a 30-fold higher risk of maternal adverse outcomes compared with patients with SpO2 over 97% [13,14]. An increase in PCWP (pulmonary capillary wedge pressure) with correct CVP (central venous pressure) is a symptom of the dysfunction of the left ventricle, and as a result carries a risk of pulmonary edema [13–15].

The essential parts of a clinical procedure are appropriate positioning of the patient in a lateral position with a slightly lifted right hip (for example, with the use of a cushion) to minimize risk of aspiration of gastric contents into the respiratory system, and to prevent patient injuries, lockjaw, and tongue bite, and also to provide adequate blood flow in the utero-placental-fetal unit and to prevent inferior vena cava syndrome.

It is also essential to maintain safe patient positioning during Caesarean section, which can be obtained through slight tilting of an operating table to the left by 15°. Left lateral position is very important not only for the mother but also for the baby. It improves the hemodynamics of the circulatory system, and reduces the preload of the heart by reducing the compression of an inferior vena cava. It may be necessary to remove saliva, vomit, and alimentary contents from the patient’s mouth. The medical staff has to be very careful while performing the procedure to not provoke vomiting (risk of gag reflex), which additionally increases the risk of aspiration of stomach contents, Mendelson syndrome, and death of a patient.

An essential step is obtaining access to the vein with 1 or more venous catheter insertions required. The 3F Rule has to be followed: Fetus, Foley catheter, and assessment of rehydration and kidney function (Fluids).

Additionally, reduction of stimuli such as light, sound, touch, and pain should be reduced, as they can cause consecutive seizure attacks or even status eclampticus. Approximately 1/10 to 1/3 of patients experience further eclampsia seizures [1].

Stabilizing the mother and appropriate resuscitation procedure have a direct impact on the state of a fetus [1]. Maternal hypoxia and hypercapnia can lead to fetal heart rate disturbances in the form of bradycardia, decreased short-term variation in fetal heart rate (oscillation), late decelerations, and compensatory tachycardia.

Pulmonary edema is a very rare but life-threatening complication [12,16]. Iatrogenic fluid overload, acute severe course of disease, cardiogenic causes, and reduced oncotic pressure are the most common causes. It has to be emphasized that the risk of maternal pulmonary edema additionally increases in the period of increased workload of the circulatory system after labor. After stabilizing the patient, it is recommended to terminate the pregnancy, most often through Caesarean section. Vaginal birth is possible only when the mother’s and the fetus’s state is stabilized and also when the cervix is well prepared for labor (Bishop’s score over 5 points) [1].

Antihypertensive Medications/Treatment for Hypertensive Urgencies

According to the World Health Organization (WHO), hypertension in pregnancy and its complications cause 16% of deaths of pregnant women, even in developed countries [2,3,5]. Clinical studies indicate that proper blood pressure control of pregnant women is one of the most important factors effectively reducing the risk of deaths or acute complications and poor pregnancy outcomes. It is important to highlight the necessity of individual hypertension management treatment in pregnant women and those in labor, keeping in mind not only the conscious choice of the antihypertensive drug, clinical situation, and adverse effects of drugs, but also its effect on maintaining optimal maternal-placental and fetal circulation.

In patients with eclampsia, it is necessary to administer antihypertensive drugs with rapid effect by venous infusion. The increase of blood pressure and hypertensive orifice constitute a risk of increase in intracranial pressure, or intracranial hemorrhage, development of hypertensive encephalopathy, and risk of severe complications and deaths of mothers and infants. Proper pharmacological control of blood pressure prevents vascular complications, CNS hypoxia, kidney damage, heart attack, and threats to the fetus.

However, it is important to remember not to reduce blood pressure too rapidly due to the risk of a sudden drop of blood flow in maternal organs, including the uteroplacental blood flow and risk of fetal hypoxia, and even intrauterine fetal death. The aim of antihypertensive drug treatment is the gradual reduction in blood pressure to achieve systolic pressure of less than 150–140 mmHg and a diastolic pressure of 90–105 mmHg, and MAP II of 126–105 mmHg, with constant surveillance of fetus heart rate through cardiotocography (CTG) recording.

Sibai [1,11] advised systolic BP values lower than 160 mmHg but not lower than 140 mmHg, and a diastolic BP lower than 110 mmHg but not lower than 90 mmHg for maintenance of proper maternal cerebral perfusion pressure and uteroplacental blood flow. It is not recommended to lower BP below 10–15% of initial BP value throughout 1 h.

It has to be kept in mind that blood flow across the placenta is proportional to the average blood pressure (perfusion pressure) and reversely proportional to vascular resistance.

Additional unfavorable factors decreasing organ and tissue blood flow occurring in preeclampsia and eclampsia are contraction of the small blood vessels (prearteriol), which to a large extent are responsible for blood supply to tissues and organs, and “blood thickening” linked to movement of fluids from an intravascular space to interstitial space resulting from loss of protein, increase in hypertension, damage to vessel endothelium, and fluid gathering in tissues in the form of edema.

International guidelines indicate drugs such as Hydralazine, Labetalol, and Nifedipine as first-line drugs in the treatment of hypertensive crisis and severe hypertension [2,11,17–20]. In unconscious patients with eclampsia, it is necessary to administer drugs intravenously.

Hydralazine and Labetalol are among the most commonly-used intravenous antihypertensive drugs recommended by the American College of Obstetricians and Gynecologists [2,19] as first-line therapies in patients with eclampsia. The choice of an antihypertensive drug should be individual and based on the patient’s clinical condition, drug accessibility, the impact of the drug on a growing fetus, as well as on the medical staff’s experience [17,18,20].

Hydralazine causes dilation of blood vessels, provides systemic reduction of vessel resistance, reduces the vessel’s afterload, and relaxes precapillary arterioles by immediately affecting the smooth muscles of these blood vessels. At the same time, it shows a minimal effect on post-capillary capacitive (extra-capillary) vessels, leading to a reduction of resistance of the systemic vessels and blood pressure [21]. Reversely affecting the pathological mechanism of preeclampsia and eclampsia, Hydralazine improves maternal and fetal circulation, which contributes greatly to organ protection. Hydralazine increases umbilical vein blood flow, which additionally suggests that vasodilation properties also act on umbilical vessels and lead to an increase in intervillous-space blood flow regardless of maternal blood pressure value or heart rate [22,23]. It is argued that the improvement in placental circulation is a consequence of the vasodilation of blood vessels [22].

After administration of Hydralazine, 50% of patients showed non-life-threatening short-term adverse effects in the form of reflex tachycardia and heart pounding, and an increase in cardiac output may appear. Rarely, patients display symptoms of chest pain, dizziness, sudden fall in blood pressure, state of fear, face redness, headaches, lower abdominal pain, and fluid retention [24]. Hydralazine should not be used when a patient has maternal tachycardia of more than 100 beats per minute. Sudden hypotensive reaction and increased risk of hypotension and oliguria may appear. Hypotension can be dangerous, especially in patients with preeclampsia and eclampsia at decreased intravascular volume. It may lead to hypoperfusion (ischemia) of the utero-placental unit, reduction of utero-placental blood flow, pulse disruption, and fetal bradycardia, which can be risky for patients with hypovolemia [21,23]. This is why Hydralazine has to be taken carefully, starting with a small dose, and any decision in regard to an increase has to be made very cautiously. A change in a patient’s position may be indicated, along with a possible increase in the intravascular volume of the patient and appropriate management of the patient’s fluid supply.

Hydralazine can dilate blood vessels in the brain, worsening cerebral edema. On the other hand, effective activity of neuroprotective Hydralazine has been observed in stroke patients [25]. Literature research, together with experiments on animals, suggest the protective role of Hydralazine against deteriorating activity of acrolein secreted by damaged neurons in patients who suffered from ischemic brain stroke. Park et al [25] observed that treatment with Hydralazine not only reduced the level of acrolein but also led to less damage to the tissues, motor deficits, and neuropathic pain. Furthermore, available data suggest its protective impact on dopaminergic neurons in Parkinson’s disease in the reduction of oxidative stress [26].

Hydralazine is often administered in the hypertensive orifice as an intravenous bolus injection dose from 2.5–5 mg, with the possibility of repeated administration, if necessary, after 20 min, up to a total dose of 20 mg. It can be administered in the form of a drug infusion in a dose of 0.5–10 mg/h. It is quick to act, starting 5–20 min from administration, and is maintained from 2–6 h. Repeated boluses of the drug may be needed in order to maintain target blood pressure [17].

In hypertension patients treated with Hydralazine, it is always recommended to evaluate the fluid and electrolytes balance, central venous pressure (CVP), and intravascular volume measurement, which is essential in preventing pulmonary edema [17].

Labetalol is a non-selective beta blocker and postsynaptic inhibitor of alpha 1 receptors. It inhibits neuronal uptake of norepinephrine and dilates blood vessels. Labetalol causes a significant drop in peripheral systemic vascular resistance, slows the heart rate and reduces blood pressure while maintaining peripheral circulation at normal levels, including uteroplacental circulation, without significant impacts on maternal cerebral, renal, and coronary circulation.

Labetalol is an effective drug and generates relatively minor adverse effects. This drug is well tolerated by patients with congestive heart failure and after myocardial infarction. Labetalol almost immediately decreases blood pressure, mostly by vasodilation and a drop in heart rate. It is a cardio-selective drug that does not generate endogenous sympathomimetic activity. It is mostly recommended in patients displaying hypertension accompanied by tachycardia and myocardial ischemia [17,18,24]. Labetalol may cause bradycardia in mother and fetus [24].

Labetalol cannot be administered together with calcium channel blockers due to its depressive effect on the heart. It should not be used by women with left ventricle dysfunction, asthma or, atrioventricular (AV) heart block due to the risk of bradycardia. It may lead to hypoglycemia, fetal bradycardia, or fetal growth restriction (FGR) when administered in the first trimester of pregnancy. It is advised to administer Labetalol in a dose starting at 10–20 mg during the first 2 min and, depending on the patient’s reaction and response, it can be repeated with a dose of 20 mg, or even by increasing the dose to 40–60 mg or 80 mg every 20–30 min, or up to a maximum dose of 300 mg per day, when required. Labetalol begins acting after 5 min from a bolus dose, and peak activity is reached 10–20 min after administration. The half-life of the drug is 6 h. Labetalol can be administered by continuous intravenous injection, starting with a dose of 1–2 mg per min, and subsequently, depending on the needs of the patient, a dose of 5–10 mg per hour can be administered, up to a dose of 300 mg per day.

The literature suggests similar effectiveness of Hydralazine and Labetalol in severe hypertension treatment in patients with a pregnancy complicated by preeclampsia or eclampsia. Sometimes Labetalol is perceived as safer than others in hospital treatment. However, Hydralazine is still the most commonly-used antihypertensive drug, especially in cases of lack of stabilized blood pressure during Labetalol treatment. Hydralazine is a drug well known in obstetrics and its adverse effects are usually acceptable. Apart from this, it seems that its influence on a mother’s and placental blood circulation is not insignificant. The choice of antihypertensive medication depends on the clinician’s experience, knowledge of the drug, and knowledge on its adverse effects, but one should be very careful with the drug’s activity assessments, as there have been few randomized clinical studies [17].

Regardless of the first choice of drug being administered (Labetalol or Hydralazine), a change of drug should be considered when the first choice has not brought desired results after 3 doses [21]. At the same time, in the event of medication change, an interval between the dose of a newly-chosen drug and administration of the last dose of a first-choice drug should be maintained [27]. The lower effectiveness of Hydralazine compared to Nifedipine and worse maternal and perinatal results suggest that Hydralazine should not be used as a first-choice drug in treatment of preeclampsia. However, Vigil-De Gracia’s research did not indicate that one of the drugs provides better results than another [20,28]. Similar results were obtained by Duley and Arulkumaran [17,18].

Urapidil is a drug that can be used in exceptional situations. It has immediate results and its activity ends by the time the intravenous infusion is finished. No significant contraindications or long-term adverse effects have been noted [29]. It does not cause reflex tachycardia and it does not generate any increase in cerebral pressure. Urapidil (Ebrantil) stimulates the serotoninergic receptors and blocks the postsynaptic receptors α1. It is most commonly used intravenously in doses of 12.5–50 mg (max. 100 mg/day) [29]. Initially, it can be administered via infusion pump at 2 mg per minute, and subsequently at 9 mg per hour. In the event of a lack of reduction in blood pressure (for example during treatment with Urapidil), nitroglycerine can be administered in a form of continuous intravenous injection, initially at 5 mg/min, and increased every 5 min up to 100 mg/min if needed. It is important to be alert for a sudden fall in blood pressure during treatment with nitroglycerine [30].

Research suggests that atenolol has minimal impact on systolic blood pressure in patients with severe preeclampsia [31,32]. Furthermore, taking into account its association with the induction of intrauterine fetal growth restriction (FGR) and the availability of other effective drugs from the same group, use of atenolol during pregnancy should be avoided [31–36]. In the event of hypertension complicated by heart rhythm disturbances, especially to achieve the desired reduction of heart rate, it may be beneficial to administer Metoprolol at a dose of 25–50 mg.

Sodium nitroprusside is used only in exceptional circumstances, as a last resort, in a life-threatening hypertension crisis, when other drugs cannot overcome this condition. Complications such as violent vasodilation in women with a reduced volume of circulating blood have been observed. Another concern is the risk of sodium nitroprusside toxicity (related to toxic metabolites: cyanides and thiocyanates).

Diuretics have to be avoided because they can cause intravascular volume depletion. Use of diuretics may lead to worsening of the utero-placental and placental-fetal blood flow, and may worsen thromboembolic risk, and thus increase the threat to the life of the mother and fetus [36]. Exceptions in which the use of diuretics such as Furosemide in pregnant women is acceptable are the risk of pulmonary edema or cerebral edema.

More possibilities of diuretics administration appear after birth, and also in certain conditions. Diuretic drugs intensify the pathogenic mechanism of preeclampsia, leading to additional thickening of the blood at already disturbed organ perfusion, including the kidneys (it is allowed to be administered when the glomerular filtration rate [GFR] is over 30 ml/min).

The desired result may be different if a certain drug is used together with other medications. The increase in dosage of an antihypertensive drug doubles the effect of the drug, whereas the addition of a second antihypertensive drug results in up to a 5-fold intensification of its effect. This has an enormous clinical significance. Furthermore, it is essential to gradually reduce the blood pressure (BP: about 10% to a maximum 15% of initial value of BP in 1 hour). At the same time, the onset of drug action and peak of drug activity has to be taken into account prior to administration of the second dose of the drug, which can prevent iatrogenic hypotension that is too violent. It is essential to maintain proper blood flow in the utero-placenta-fetal unit and to maintain proper blood circulation in the maternal brain and other vital organs [17].

Maternal hypoxia and hypercarbia may stimulate uterine contraction, which can lead to fetal heart rhythm abnormalities [1]. During eclampsia seizures, and immediately afterwards, bradycardia in a fetus is often observed. Furthermore, a too-sharp reduction of BP leads to placental hypoperfusion and is a threat to a growing fetus. Hypoxia and acidosis are fetal CNS damage risk factors. At a subsequent stage of antihypertensive treatment, Nifedipine can be used and taken orally by conscious patients at a dose of 5–10 mg [2,37–39]. This can be repeated after 5–30 min [38].

Anticonvulsant Therapy and Prophylaxis of the Recurrence of Eclampsia

All patients suffering from seizure of unknown etiology during pregnancy, labor, or after childbirth at postpartum should be treated like patients with eclampsia seizure until a diagnosis is made. Magnesium sulphate (MgSO4) is the drug of first choice and is the criterion standard in treatment of eclampsia. It effectively overcomes eclampsia seizure and prevents subsequent eclamptic convulsions. Despite the strong effectiveness of magnesium sulphate in treatment and prophylaxis of eclampsia, the mechanism of its functioning is not yet fully known [1,40]. Magnesium sulphate is not a typical anti-convulsive drug against. It shows significant vasodilation properties decreasing peripheral resistance and dilating peripheral vascular system and cerebral vessels. It leads to a fall in systemic blood pressure, dilating small distal brain capillaries, and reverses brain hypoxia caused by contraction of the blood vessels. It protects the vascular endothelium, contributing to increased production of prostacyclin and nitric oxide. It also protects the blood–brain barrier, limiting cerebral edema, and has central activity through inhibition of NMDA (N-methyl-D-aspartate) receptors, leading to reduced convulsive readiness [40]. In addition, magnesium sulphate, through the reduction of acetylcholine secretion, blocks neuromuscular transmission [41,42]. It stops and prevents convulsions, decreasing the risk of death in patients with eclampsia and severe preeclampsia.

Clinical research analysis and literature data confirm that magnesium sulphate treatment in patients with eclampsia is essential and not just an option to consider. The loading dose of magnesium sulfate is equal to 4–6 g applied within 15–20 minutes, with a subsequent intravenous magnesium sulfate infusion with a dose of 1–2 g per hour [1,19,43]. Sibai [1] recommends an intravenous infusion of 2 g magnesium sulphate per hour after administering the loading dose. An intravenous infusion should be maintained for at least 24 h postpartum, or at least 24 h after the last eclampsia seizure. Kidney functioning has to be monitored as well. In the event of kidney dysfunction, there is a risk of magnesium sulphate adverse effects. A level of creatinine over 1.2 mg/dL or oliguria defined as below 30 mL of excreted urea per hour for the next 4 h constitutes an indication for the administration of MgSO4 in the form of intravenous infusion at a smaller therapeutic dose of 1 g/h.

In the case of a lack of access to a vein or difficulties with intravenous administration of this drug, it is possible to administer magnesium sulphate via intramuscular injection to each buttock up to a maximum dose of 10 g, and then a dose of 5 g every 4 h [44]. However, possible symptoms suggesting HELLP syndrome or bleeding diathesis have to be considered (these are contraindications of this drug’s use via intramuscular injection). In this method of administration, increased fluctuation of magnesium and decreased stability of drug level in the patient’s blood are observed. The author’s clinical experience shows that a dose of 1 g magnesium sulphate per hour infused after a loading dose of 4 g can be effective in the treatment of eclampsia, or even in a cessation eclamptic state and prophylaxis of a recurrence of eclampsia seizure [45]. At the same time, it limits the risk of adverse effects and possible overdose of magnesium sulfate.

In the event of eclampsia seizure recurrence, which is observed in 1/3 of women, it is recommended to administer an additional dose of 2 g or even 4 g of magnesium sulphate by intravenous therapy within a few minutes (at a dose of 2 g within 3–5 min, or a dose of 4 g within 10 min), or optionally an increase of a drug dose in continuous intravenous injection up to 2 g per hour [1,11,17]. There is no need for monitoring magnesium level in the blood of patients undergoing therapy by routine laboratory test if there has been improvement in the patient’s condition and no concerning symptoms have appeared. It is, however, necessary to constantly monitor clinical symptoms of possible magnesium sulphate overdose at least once an hour. Diuresis per hour, patellar reflex, and the number of breaths per minute have to be assessed. The decrease of diuresis below the level of 25 mL per hour (especially within the following few hours, eg, diuresis below 100 mL within 4 h), respiratory depression (decrease in breathing rate below 14/min), and weakened muscular strength and patellar reflexes may point to an overdose of magnesium sulphate and an urgent need to administer 1 g of calcium gluconate (slow intravenous administration of 10 ml of 10% solution within 10 min) [1,11,40]. However, it has to be emphasized that the initial diuresis can result in oliguria as the consequence of the pathological mechanism of preeclampsia/eclampsia itself. Achievement of diuresis above 25 mL, up to 40 mL in the next few hours, is a good sign that suggests slow steady recovery of a patient and disease regression. In the event of magnesium sulphate overdose and the depressive influence on the respiratory system that it carries, intubation and artificially-supported breathing may be needed. Failures in the treatment of seizures, and repetition of subsequent seizures, usually result from delay in diagnosis and treatment, lack of immediate administration of magnesium sulphate, lack of extended continuous intravenous therapy of magnesium sulphate, insufficient monitoring, and lack of reduction in blood pressure in patients after an eclamptic attack. Reduction in abnormally high blood pressure is the factor conditioning not only eclampsia treatment but also preventing intracranial hemorrhage. A reoccurrence of seizures and seizure readiness is observed in patients whose blood pressure values have not been properly monitored.

Drug control of BP prevents vascular complications in the CNS (central nervous system).

It must be emphasized that systolic BP below 140–150 mmHg and diastolic BP below 90 mmHg minimizes the risk of hemorrhagic stroke [17] and that hypertensive encephalopathy (HE), a massive increase in intracranial pressure, or intracerebral hemorrhage raises mothers’ morbidity and mortality rates.

In the event of the lack of effectiveness of magnesium sulphate therapy in therapeutic doses (which occurs in approximately 10% of patients), diazepam in a dose of 5–10 mg can be administered or phenytoin at a dose of 250mg intravenously (250-750-1250 mg) depending on the body mass, within 12 h. The therapeutic level of phenytoin is 12 mg/ml. Vigil-De Gracia et al recommend a dose of 100 mg of phenytoin every 6 h for 24 h [20,44]. Diazepam can have an adverse effect on the fetus, such as risk of hypoxia and a lower Apgar score.

If eclampsia seizure reoccurs during therapy with magnesium sulphate at therapeutic doses, Sibai recommends an application of 4 mg of Lorazepam within 3–5 min [1,11].

Magnesium sulphate should be given early to prevent seizures in preeclampsia with severe features [17] and magnesium sulphate therapy should be continued during labor and Caesarean section [42,46]. Discontinuation of MgSO4 is linked to eclampsia seizure recurrence risk. Phenytoin and benzodiazepines can be used if there are contraindications for the use of magnesium sulphate or when MgSO4 is ineffective [1,17,47].

CNS (central nervous system) imaging studies, such as MRI or CT, are not recommended for routine use in eclamptic patients [1]. Most often, MRI or CT discloses characteristics of cerebral oedema in white matter and closely-located grey matter, mostly in the parietal and occipital lobe [48]. However, in seizures resistant to treatment and concerning symptoms such as paralysis, vision impairment, blindness, and prolonged coma or mental confusion, MRI or CT have to be performed urgently [1,44,49,50].

Pulmonary edema is a very severe complication that is estimated to occur in 3% of patients with severe preeclampsia. The risk of pulmonary edema increases with the number of deliveries, age of the patient, and fluid workload, and it has a high maternal mortality rate [1,2,11]. It is important to perform an echocardiographic examination whenever cardiomyopathy is suspected.

Pulmonary artery catheterization is rarely required, but it may be necessary in patients with heart disorders, cardiac failure, and pulmonary hypertension. The amount of excreted urine has to be monitored, and the 3-F rule has to be kept in mind, which is Fluid, Fetus, and Foley catheter, reaching an hourly diuresis level of over 25 mL, also in the postpartum period. Reaching hourly diuresis of over 25 mL, especially in the range of 25–40 mL, is a sign of a patient’s improvement.

All patients with eclampsia, and after eclamptic seizures, should be treated in an intensive care unit (ICU). However, taking into account not only clinical realities, especially in developing countries, and literature reviews, this is not always possible.

Furthermore, only about 50% of patients with eclampsia have hypertension. About 1/3 of patients with eclampsia do not have severe hypertension or proteinuria [1,11,40,46].

In 1/5 of patients with preeclampsia, a very rapid course of the disease is observed, although 1 week prior to the eclampsia seizure, these patients may not show clinical symptoms of this condition at all [40]. It is necessary for all gynecologists-obstetricians and maternal-fetal medicine specialists to be fully prepared for eclampsia, although it is very rare.

Stabilization of the patient’s condition and maintenance of the patient’s blood pressure at normal levels are the priority. The recovery of the patient and prevention of recurrent eclampsia convulsions is not possible without reduction of blood pressure. However, lack of blood pressure stabilization and its increase (uncontrolled jumps in BP) are one of the main causes of eclampsia recurrence.

Recommendations to Improve Maternal and Fetal Outcomes

Labor is the only currently known causal factor and is the most effective treatment for preeclampsia and eclampsia. Antihypertensive treatment is a symptomatic, medical strategy that allows the postponement of pregnancy termination/delivery until the stops fetus is maturity and the patient and fetus are prepared for delivery. In the case of severe preeclampsia, delivery is always beneficial for the mother and it constitutes the onset of causal therapy, but it is not always beneficial for the fetus (especially when the due date is distant), because of prematurity and its complications.

Better understanding of etiological and pathological mechanisms underlying preeclampsia development has vital meaning for new methods of its diagnosis and for treatment, and finally for the prevention of eclampsia. It is not known why eclampsia occurs in some patients and not in others. Mahendra et al emphasize that there is no existing evidence that an increase in intracranial pressure precedes an eclampsia attack [51]. However, cerebral edema and the occurrence of vascular abnormalities in Doppler’s method research in patients with eclampsia, along with neurological symptoms, such as persistent headache, vision impairment, hyperactivity or stroke, have been confirmed. It seems that vasogenic edema is the main factor leading to abnormalities and results from an increase in BP and from the increase in the permeability of vascular endothelium and brain autoregulation disturbances. Cerebral edema and an increase in intracranial pressure have crucial meaning for the occurrence of neurological symptoms, and eclampsia as a result.

Recommended eclampsia prevention methods through the administration of magnesium sulphate in all patients with severe preeclampsia can decrease the risk of seizures by 10 times, from 3.4% to 0.3% [52]. Sullivan et al recommend the extended use of magnesium sulphate for over 24 h because the risk of eclamptic seizures is still high in the first 24 h postpartum [43]. Discontinuation of magnesium sulphate and lack of blood pressure stabilization or uncontrolled jumps in blood pressure are the main causes of eclamptic seizures recurrence.