Which finding would the nurse recognize as indicating progression of preeclampsia to eclampsia?

Is Eclampsia Preventable?

Prevention of eclampsia requires knowledge of its etiology and pathophysiology and of methods to predict patients at high risk for development of convulsions. However, as discussed earlier, the pathogenesis of eclampsia is largely unknown. Prevention of eclampsia can beprimary, by preventing the development and/or progression of PE, or it can besecondary, by using pharmacologic agents that prevent convulsions in women with established PE. Prevention can also betertiary, by preventing subsequent convulsions in women with established eclampsia.

Current management schemes designed to prevent eclampsia are based on early detection of GH or PE and subsequent use of preventive therapy in such women.Some of the recommended preventive therapies have included close monitoring (in-hospital or outpatient),use of antihypertensive therapy to keep maternal BP less than a certain level (less than severe range or to normal values),timely delivery, and prophylactic use of magnesium sulfate during labor and immediately postpartum in those considered to have PE. These management schemes assume that the clinical course in the development of eclampsia is characterized by a gradual process that begins with progressive weight gain, followed by hypertension (mild to severe) and proteinuria, with the subsequent onset of premonitory symptoms, and ending with the onset of generalized convulsions or coma.119 This clinical course may be present in some women who develop eclampsia in developed countries. However, recent data from large series of eclamptic women from the United States and Europe indicate that approximately20% to 40% of eclamptic women do not have any premonitory signs or symptoms before the onset of convulsions.11 In many of these cases, the onset of convulsions is abrupt and does not follow an indolent progression from mild to severe disease before the onset of eclampsia.119

It is also assumed that appropriate and timely standard preventive therapy will prevent eclampsia in virtually all patients with GH-PE.119 The efficacy of in-hospital management of patients with GH or PE for the prevention of eclampsia has not been evaluated in randomized trials. Moreover, data from retrospective studies from developed countries indicate that approximately 50% of eclamptic women develop their first convulsion while in the hospital under “close medical supervision.”119 Thus early and prolonged hospitalization of women with mild hypertension or PE may not prevent most cases of eclampsia.

Several randomized trials have described the use of antihypertensive drugs versus no treatment or a placebo in the treatment of women with mild hypertension or PE. Overall, these trials revealed lower rates of progression to severe disease. However, the study design and the sample size of these trials is inadequate to evaluate potential benefits regarding prevention of eclampsia.

History

Eclampsia was defined by Celsus in 100 AD as seizures during pregnancy that abated with delivery. For the ensuing 1700 years, eclampsia was considered a pregnancy-specific seizure disorder. It was not until the mid-1800s that the similarity of the edematous eclamptic women and the dropsic patients with Bright's disease (acute glomerulonephritis) stimulated clinicians to determine whether women with eclampsia, like individuals with Bright's disease, had protein in their urine. Protein was indeed present and 50 years later an association of increased blood pressure and eclampsia was recognized. It was soon evident that hypertension and proteinuria during pregnancy, even without seizures, identified a woman with the potential for a rapidly progressive life-threatening disorder and a fetus at increased risk of stillbirth.

Epidemiology of Preeclampsia and Eclampsia

The incidence of hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, and eclampsia) has increased over the last two decades, from 57.3 per 1000 delivery hospitalizations in 1994 to 86.5 per 1000 delivery hospitalizations in 2013.25

Based on a metaanalysis of risk factors for preeclampsia, nulliparity accounts for the greatest population attributable fraction for preeclampsia at 32.3% (95% CI 27.4% to 37.0%).26 Some risk factors for preeclampsia, including age, race, and underlying medical conditions, are similar in nulliparous and parous women.27 Additional risk factors include prior preeclampsia, antiphospholipid syndrome, in vitro fertilization, and family history of preeclampsia (Table 48.2).

The impression that preeclampsia is more common among women of lower socioeconomic status may be confounded by the relationship of preeclampsia to age, race, and parity. Several studies28–31 have shown no relationship between preeclampsia and socioeconomic status. In contrast, eclampsia is clearly more common in women of lower socioeconomic status,28,30,31 a finding that is likely related to the limited availability of quality obstetric care for indigent women.

Preeclampsia has been linked to the extremes of childbearing age. This relationship has been demonstrated in older women regardless of parity,28,30,31 but the relation to young maternal age is lost after controlling for parity.

The relationship between preeclampsia and race is confounded by the higher prevalence of chronic hypertension in African Americans. A modest association between preeclampsia and African-American race has been identified in some studies,31–34 with stronger associations often seen in studies that include more severe forms of preeclampsia.35 One study showed that black race was a significant risk factor only in nulliparous women (odds ratio [OR] = 12.3; 95% confidence interval [CI], 1.6 to 100.8),35 but two large studies of nulliparous women showed no association between race and preeclampsia after controlling for other risk factors.36,37 Maternal nonwhite race appears to be related more to severity than the incidence of disease.

Several medical disorders may predispose women to preeclampsia. Chronic hypertension is a well-recognized risk factor, and 25% of women with this condition develop preeclampsia during pregnancy.38,39 Chronic renal failure with40,41 or without diabetes mellitus42–44 is another important risk factor.

The presence and severity of pregestational diabetes mellitus is independently associated with an increased risk for preeclampsia, particularly in the setting of diabetic microvascular disease.40,45 Studies suggest a 20% risk for the disease overall in diabetic patients.40,45 The risk varies according to disease severity, with an 11% to 16% risk with White's class B diabetes, a 21% to 23% risk with class C diabetes, a 35% to 40% risk with class D diabetes, and up to 70% risk with classes F and R diabetes.40,45,46

Eclampsia

Eclampsia is the occurrence of generalized tonic-clonic seizures in association with preeclampsia. It affects about 1 in 2500 deliveries in the United States and may be much more common in developing countries, affecting as many as 1% of parturients. Up to 10% of maternal deaths are due to eclampsia (Duley, 1992).

Most cases of eclampsia occur within 24 hours of delivery. Almost 50% of seizures occur before the patient's admission to labor and delivery, about 30% are intrapartum, and the remainder are postpartum. There is a considerable drop in the risk of eclampsia by 48 hours postpartum, seizures occurring in less than 3% of women beyond that time. Most patients have antecedent features suggestive of preeclampsia, although in some cases eclampsia may occur without warning. If eclampsia is left untreated, repetitive seizures become more frequent and of longer duration, and ultimately, status eclampticus develops. Maternal and fetal mortality may be as high as 50% in severe cases, especially if the seizures take place while the patient is far from medical care.

Randomized controlled trials have demonstrated the clear superiority of magnesium sulfate for the treatment of eclampsia over all other anticonvulsants (Duley and Gulmezoglu, 2002; Duley and Henderson-Smart, 2002b, 2002c). Intravenous magnesium sulfate is given as a 4-g bolus over 5 minutes followed by a maintenance infusion of 1 to 2 g/hr for 24 hours after delivery. Subsequent seizures may be treated by further bolus injections; in refractory cases, second-line treatment with other anticonvulsants may be required, or the patient may have to be paralyzed and ventilated.

Delivery after an eclamptic seizure should take place in a controlled, careful manner. There is little to be added by performing a “crash” cesarean section (Coppage and Polzin, 2002). The patient should be stabilized first. Vaginal delivery is possible in most cases, although cesarean delivery may be indicated if the status of the cervix is unfavorable or fetal compromise is ongoing despite control of seizures and maternal stabilization. Infants born to mothers after eclampsia require careful monitoring after birth.

Preeclampsia or Eclampsia

The risk factors for development of preeclampsia and its sequelae (e.g., hypertension, proteinuria, vasospasm, thrombocytopenia, abnormal liver function, endothelial cell damage, and acute respiratory distress syndrome) are well known, even though the cause is not. Severe hypertension is associated with stroke and intracranial bleeding that can result in maternal death. The goal of antihypertensive therapy is to prevent maternal morbidity by decreasing systolic blood pressure to less than 160 mm Hg and diastolic pressure to less than 110 mm Hg. At the same time, treatment should not impair uteroplacental perfusion or cause fetal compromise. A review of stroke associated with severe preeclampsia suggests that systolic hypertension may be more important than diastolic for preventing stroke related to severe preeclampsia.53 The authors found that 93% of associated strokes were hemorrhagic, 54% of women died, and almost all who lived had severe, permanent disability. All women had a systolic pressure greater than 155 mm Hg while only 12% had a diastolic pressure greater than 110 mm Hg.

In 2015, the American College of Obstetricians and Gynecologists (ACOG) updated their committee opinion, “Emergent Therapy for Acute-Onset, Severe Hypertension with Preeclampsia or Eclampsia.”54 A hypertensive emergency is defined as lasting 15 minutes or longer with a systolic pressure greater than 160 mm Hg or diastolic pressure greater than 110 mm Hg. Intravenous labetalol and hydralazine and oral nifedipine are considered first-line treatments, and the document includes order sets. If these medications fail to control the patient's blood pressure, ACOG recommends “emergent consultation with an anesthesiologist, maternal-fetal medicine subspecialist, or critical-care specialist to discuss second-line intervention.” Recommendations may then include additional intravenous antihypertensive medications and placement of an arterial line to more accurately track blood pressure changes.

Use of invasive monitoring is rarely necessary in obstetric patients. They are usually young, previously healthy women with few or no comorbidities. However, arterial lines are low risk and can be useful in patients whose blood pressures are consistently above 160/110 mm Hg and when vasodilator infusions are deemed necessary. They may also be helpful for patients with coagulopathy who need frequent blood draws, and when the patient is obese or has marked edema that makes venipuncture difficult. If pulmonary edema develops, the arterial line can be used to monitor arterial blood gases. In contrast, central venous monitoring entails higher risk and has not been shown to affect outcome. A central venous pressure or pulmonary artery catheter may be useful if there is cardiac failure or pulmonary edema, a large alveolar-arterial oxygen gradient, or oliguria despite fluid administration and afterload reduction. Available nursing resources must be considered before initiating invasive monitoring: can the nursing staff manage a central venous pressure or pulmonary artery catheter in the labor and delivery unit, or will ICU admission be necessary?

Eclampsia

Eclampsia is the occurrence of generalized tonic-clonic seizures in association with preeclampsia. It affects approximately 1 in 2500 deliveries in the United States and may be much more common in developing countries, affecting as many as 1% of parturients. Up to 10% of maternal deaths are due to eclampsia (Duley, 1992).

Most cases of eclampsia occur within 24 hours of delivery. Almost 50% of seizures occur before the patient’s admission to the labor and delivery department, approximately 30% are intrapartum, and the remainder are postpartum. There is a considerable drop in the risk of eclampsia by 48 hours postpartum, with seizures occurring in less than 3% of women beyond that time. Most patients have antecedent features that are suggestive of preeclampsia, although in some cases eclampsia may occur without warning. If eclampsia is left untreated, repetitive seizures become more frequent and of longer duration, and ultimately status eclampticus develops. Maternal and fetal mortality may be as high as 50% in severe cases, especially if the seizures occur while the patient is far from medical care.

Randomized controlled trials have demonstrated the clear superiority of magnesium sulfate for the treatment of eclampsia over all other anticonvulsants (Duley and Gulmezoglu, 2002; Duley and Henderson-Smart, 2002b, 2002c). Intravenous magnesium sulfate is given as a 4-g bolus over 5 minutes followed by a maintenance infusion of 1 to 2 g/hr for 24 hours after delivery. Subsequent seizures can be treated with further bolus injections. In refractory cases, second-line treatment with other anticonvulsants may be required, or the patient may have to be paralyzed and their lungs ventilated.

Delivery after an eclamptic seizure should take place in a controlled, careful manner. There is little to be added by performing an emergency cesarean section (Coppage and Polzin, 2002). The patient’s condition should be stabilized first. Vaginal delivery is possible in most cases, although cesarean delivery may be indicated if the status of the cervix is unfavorable or if fetal compromise is ongoing despite control of seizures and maternal stabilization. Infants born to mothers after eclampsia require careful observation after birth.

Eclampsia

Eclampsia has been considered a form of hypertensive encephalopathy on the basis of similarities in clinical, radiologic, and pathologic features.16,59,60 The fluid accumulation often observed during pregnancy may accentuate the tendency for brain edema to develop. However, several findings suggest that eclampsia is more than hypertensive encephalopathy. There is not always a good correlation between symptoms and signs of eclampsia and level of blood pressure and blood pressure is reported as only minimally elevated in 23% of patients.61 Several findings suggest that vascular endothelial damage may play a role in preeclampsia/eclampsia.61,62 Preeclampsia/eclampsia is a multisystem disorder characterized by abnormal vascular response to placentation that is associated with increased systemic vascular resistance, enhanced platelet aggregation, activation of the coagulation system, and endothelial cell dysfunction.63 Production of placental anti-angiogenic factors, specifically soluble fms-related tyrosine kinase 1 and soluble endoglin, have been shown to be upregulated in pre­eclampsia. These placental anti-angiogenic factors are released into the maternal circulation; their actions disrupt the maternal endothelium and result in hypertension, proteinuria, and the other systemic manifestations of preeclampsia/eclampsia.64 Generalized endothelial dysfunction may lead to increased sensitivity to normally circulating pressor agents and impaired synthesis of vasoactive compounds, which may result in vaso­spasm and reduced organ perfusion; platelet activation with transitory platelet-rich microvascular occlusion; activation of the coagulation cascade, and loss of fluid from the intravascular compartment.65

The classic clinical presentation of eclampsia consists of epileptic seizures or coma manifesting during the third trimester or early puerperium in women who already have the pre-eclamptic symptom triad of edema, proteinuria, and hypertension. However, hypertension or proteinuria may be absent in 10–15% of women who develop HELLP syndrome (hemolysis, elevated liver enzymes, or low platelet counts) and in 38% of those who develop eclampsia.63 It has been reported that a substantial subset of women diagnosed with late postpartum eclampsia had not been identified as pre-eclamptic before seizure onset. It remained unclear whether this represented a true variant of the clinical presentation of eclampsia or merely reflected decreased caretaker attention towards pre-eclamptic signs in the postpartum period.66

A recent systematic study and meta-analysis has shown that women who have had pre-eclampsia have an increased risk of cardiovascular disease, including an almost fourfold increased risk of hypertension and an approximately twofold increased risk of fatal and non-fatal ischemic heart disease, stroke, and venous thromboembolism in later life.67 The mechanism underlying this association remains to be defined. Whether these long-term observations are due to persistent and subtle endothelial damage as a result of pre-eclampsia remains unknown.68

C Eclampsia

Eclampsia is the most severe hypertensive complication of pregnancy. It is a combination of preeclampsia (hypertension, proteinuria, edema) and convulsions, coma, or death. It is usually superimposed on preeclampsia during or just after labor; in only 25% of cases do convulsions begin before labor.

The only thing that is known for sure about the cause of preeclampsia/eclampsia is that it arises in the uteroplacental unit. Delivery is followed by a reversal of the disease, although hypertension and the risk of convulsions persist for a few hours after delivery. Postulated causes include the underperfusion of the uteroplacental unit with the release of factors that constrict vessels and/or increase sensitivity to pressors. There may be reduced production of vasodilators like nitric oxide and dilating eicosanoids. The search for the humoral mechanisms of eclampsia is one of the ongoing treasure hunts of modern medical science.

The fetal complications of eclampsia/preeclampsia include prematurity, low birth weight, deformity, and death. It is the leading cause of prematurity; one in three premature deliveries is marked by preeclampsia. All of these consequences are probably caused by the underperfusion of the fetoplacental unit.

Eclampsia

Eclampsia, by definition a “severe feature,” is the occurrence of generalized tonic-clonic seizures in association with PE. It affects approximately 1 in 2500 deliveries in the United States and may be much more common in developing countries, affecting as many as 1% of parturients. Up to 10% of maternal deaths are due to eclampsia in the United States (Creanga et al., 2015).

Most cases of eclampsia occur immediately prior to or within 24 hours of delivery. Almost half of seizures occur before the patient's admission to the labor and delivery department, approximately 30% are intrapartum, and the remainder are postpartum. There is a considerable drop in the risk of eclampsia by 48 hours postpartum, with seizures occurring in less than 3% of women beyond that time. Most patients have antecedent symptoms that are suggestive of PE, although in some cases eclampsia may occur without warning. If eclampsia is left untreated, repetitive seizures become more frequent and of longer duration, and ultimately status eclampticus may develop. Maternal and fetal mortality are as high as 50% in severe cases, especially if the seizures occur while the patient is remote from medical care.

Randomized controlled trials have demonstrated the clear superiority of magnesium sulfate for the treatment of eclampsia over all other anticonvulsants (Duley and Gulmezoglu, 2002; Duley and Henderson-Smart, 2002b, 2002c). Intravenous magnesium sulfate is given as a 4 g bolus over 5 minutes followed by a maintenance infusion of 1–2 g/h for 24–48 hours after delivery. Subsequent seizures can be treated with further bolus injections. In refractory cases, second-line treatment with other anticonvulsants may be required. Rarely, the patient may require pharmacologic paralysis and mechanical ventilation.

Delivery after an eclamptic seizure should take place expeditiously but in a controlled, careful manner. There is little value in performing an emergency cesarean section (Coppage and Polzin, 2002) in response to a seizure. Stabilization and optimization of both maternal and fetal status are important prerequisites for delivery procedures. Once magnesium sulfate has been administered and maternal vital signs controlled, vaginal delivery is preferable in most cases. Potential indications for cesarean include a significantly unfavorable cervix, evidence of ongoing fetal compromise, or inability to achieve acceptable blood pressure control. Infants born to mothers after eclampsia require careful observation after birth.

Complete references used in this text can be found online at www.expertconsult.com

Eclampsia

Eclampsia is a form of posterior reversible encephalopathy. Occurring during the second half of pregnancy or the puerperium, eclampsia presents with proteinuria and clinical and imaging manifestations identical to hypertensive encephalopathy. Hypertension may not be severe, so additional effects on brain endothelial cell permeability are probably important. There is evidence of generalized endothelial cell dysfunction with abnormal vascular reactivity.143 An underlying inflammatory response may be causative, but other potential etiologies have also been hypothesized.

Cerebral venous sinus thrombosis is another complication of pregnancy and delivery and can present with findings similar to those seen with eclampsia. MRI and venography are usually adequate to distinguish the two diseases, showing obstructed venous sinuses or ischemia with cytotoxic edema on diffusion-weighted sequences in cerebral venous sinus thrombosis.

Treatment includes delivery of the fetus and intravenous magnesium.144 Other antihypertensive medications and anticonvulsants can also be used. Prognosis is good if treatment is initiated quickly.