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The risk to the fetus in patients with preeclampsia relates largely to the gestational age at delivery. Risk to the mother can be significant and includes the possible development of disseminated intravascular coagulation (DIC), intracranial hemorrhage, renal failure, retinal detachment, pulmonary edema, liver rupture, abruptio placentae, and death. Therefore, astute and experienced clinicians should be in charge of the care of women with preeclampsia.
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The etiologic agent responsible for the development of preeclampsia remains unknown. The syndrome is characterized by vasoconstriction, hemoconcentration, and possible ischemic changes in the placenta, as well as maternal kidney, liver, and brain. These abnormalities are usually seen in women with preeclampsia with severe features.
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The hypertensive changes seen in preeclampsia are attributable to intense vasoconstriction thought to be due to increased vascular reactivity. The underlying mechanism responsible for increased vascular reactivity is presumed to be dysfunction in the normal interactions of vasodilatory (prostacyclin, nitric oxide) and vasoconstrictive (thromboxane A2, endothelins) substances. Another hallmark of severe disease is hemoconcentration. Accordingly, some patients with preeclampsia have lower intravascular volumes and less tolerance for the blood loss associated with delivery.
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The most common hematologic abnormality in preeclampsia is thrombocytopenia (platelet count <100,000/mm3). The exact mechanism for thrombocytopenia is unknown. Another occasional hematologic abnormality is microangiopathic hemolysis, as seen in association with HELLP syndrome. It can be diagnosed by the presence of schistocytes on peripheral smear and by increased lactate dehydrogenase or bilirubin levels or reduced haptoglobin levels. Interpretation of the baseline hematocrit level in a preeclamptic patient may be difficult. A low hematocrit may signify hemolysis and a high hematocrit may be due to hemoconcentration.
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Vasoconstriction in preeclampsia leads to decreased renal perfusion and subsequent reductions in the glomerular filtration rate (GFR). In normal pregnancy, the GFR increases by as much as 50% above prepregnancy levels. Because of this, serum creatinine levels in nonpreeclamptic patients rarely rise above normal pregnancy levels (0.9 mg/dL). Close monitoring of serum creatinine is necessary in patients with preeclampsia, as elevated levels of creatinine >1.1 mg/dL may occur due to renal insufficiency. In rare cases profound renal insufficiency may lead to acute tubular necrosis. This is usually seen in the presence of abruptio placentae, HELLP syndrome and unrecognized, severe blood loss that is not corrected.
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Hepatic damage in association with preeclampsia can range from mildly elevated liver enzyme levels to subcapsular liver hematomas and hepatic rupture. The latter 2 are usually associated with severe thrombocytopenia. Liver lesions seen on biopsy and at autopsy include periportal hemorrhages, ischemic lesions, and fibrin deposition.
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Central Nervous System
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Eclamptic convulsions are perhaps the most disturbing CNS manifestation of preeclampsia and remain a major cause of maternal mortality in developing countries. The exact etiology of eclampsia is unknown, but may be attributable to hypertensive encephalopathy or ischemia from vasoconstriction. Radiologic studies may show evidence of cerebral edema, particularly in the posterior hemispheres, which may explain the visual disturbances seen in preeclampsia. Other CNS abnormalities include headaches, altered mentation, scotomata, blurred vision, and rarely, temporary blindness.
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Management of Preeclampsia With Severe Features
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Any patient with severe features should be admitted and initially observed in a labor and delivery unit (Fig. 5-1). Initial work-up should include assessment for fetal well being, monitoring of maternal blood pressure, symptomatology and laboratory evaluation. Laboratory assessment should include hematocrit, platelet count, serum creatinine, and aspartate aminotransferase (AST). An ultrasound for fetal growth and amniotic fluid index should also be obtained. Candidates for expectant management should be carefully selected. They should also be counseled regarding the risks and benefits of expectant management. Guidelines for expectant management are outlined in Table 5-3. Fetal well being should be assessed on a daily basis by nonstress testing and weekly amniotic fluid index determination. The patient should also be instructed on fetal movement assessment. An ultrasound for fetal growth should be performed every 2 to 3 weeks. Maternal laboratory evaluation should be done daily or every other day. If the patient maintains a stable maternal and fetal course, she may be expectantly managed until 34 weeks. Worsening maternal or fetal status warrants delivery, regardless of gestational age (Table 5-3). Women with a nonviable fetus should be presented with the option of pregnancy termination.
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Maternal blood pressure control is essential with expectant management or during delivery. Medications can be given orally or intravenously, as necessary, to maintain blood pressure between 140 to 155 mm Hg, systolic and 90 to 105 mm Hg, diastolic. The most commonly used intravenous medications for this purpose are labetalol and hydralazine. Other medications can include oral rapid-acting nifedipine. Subsequent management can include oral medications such as labetalol and long acting nifedipine. The recommended dosages of medications for acute treatment of hypertension are listed in Table 5-4. Care should be taken not to drop the blood pressure too rapidly so as to avoid reduced renal and placental perfusion.
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A trial of labor is indicated in patients with severe preeclampsia if gestational age is >30 weeks and/or if cervical Bishop score is greater than or equal to 6. However, an appropriate time frame should be established regarding the achievement of active labor. Preeclamptic women receiving magnesium sulfate are also at risk for postpartum hemorrhage due to uterine atony. Patients should be closely monitored for 24 hours postpartum. Postpartum eclampsia occurs in 25% of patients; thus, MgSO4 should be continued for 24 hours after delivery. There is usually no need for continued seizure prophylaxis beyond 24 hours postpartum. Some of these patients are at risk for pulmonary edema and exacerbation of severe hypertension at 2 to 5 days postpartum. Therefore, they should receive frequent monitoring and a short course of furosemide, if needed. It is important to avoid the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-inflammatory agents for pain relief in these women due to their potential deleterious effect on maternal renal function. If needed, I recommend acetaminophen with codeine for pain relief.
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The specific laboratory abnormalities demonstrating hemolysis, elevated liver enzymes, and low platelets are shown in Table 5-5. The clinical presentation of patients with HELLP syndrome is highly variable. However, HELLP patients generally are multiparous, white females who present at less than 35 weeks’ gestation. Sibai has noted that hypertension may be absent (20%), mild (30%), or severe (50%) in women diagnosed with HELLP syndrome. Therefore, the diagnosis of HELLP syndrome cannot necessarily be ruled out in the normotensive patient who has other signs and symptoms that are consistent with preeclampsia.
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Differential Diagnosis
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HELLP may be confused with other medical conditions, particularly in the face of normotension. A list of the differential diagnoses is found in Table 5-6. HELLP can be confused with other specific medical conditions, such as acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), and lupus nephritis The differentiation among the 3 entities is based on specific laboratory findings (Table 5-7).
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The initial evaluation in women diagnosed with HELLP syndrome should be the same as that for preeclampsia with severe features. The patient with preterm gestation should be cared for at a tertiary care center. Management initially should include maternal and fetal assessment, control of severe hypertension (if present), initiation of magnesium sulfate infusion, correction of coagulopathy (if present), and maternal stabilization. Immediate delivery should be performed in patients at more than 34 weeks’ gestation. In patients less than 34 weeks without proven lung maturity, corticosteroids should be given and delivery planned for 48 hours thereafter, provided there is no worsening of maternal or fetal status in the meantime. The use of steroids, volume expanders, plasmapheresis, and antithrombotic agents in patients with HELLP have produced only marginal results, although some evidence suggests a benefit of steroid therapy for improvement in maternal platelet count. However, 2 multicenter placebo-controlled trials revealed that high-dose dexamethasone does not improve maternal outcome in patients with HELLP syndrome in the antepartum or postpartum period. This was later confirmed by the results of a recent meta-analysis of corticosteroid use in women with HELLP syndrome. Conservative management of HELLP syndrome poses a significant risk of abruptio placentae, pulmonary edema, adult respiratory distress syndrome (ARDS), ruptured liver hematoma, acute renal failure, DIC, eclampsia, intracerebral hemorrhage, and maternal death. Therefore, expectant management past 48 hours is not warranted for the minimal fetal benefits, when weighed against the profound maternal risk.
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Patients with a favorable cervix and a diagnosis of HELLP syndrome should undergo a trial of labor, particularly if they present in labor. An operative delivery in some situations may even be harmful. However, elective cesarean section should be considered in patients, at very early gestational ages, with unfavorable cervices. The anesthetist should be updated as to the trend in platelet count for patients with HELLP. Should such a patient require cesarean delivery, platelet transfusion of approximately 6 to 10 units should be initiated en route to the operating room in patients with severe thrombocytopenia. However, platelet consumption is rapid with a platelet transfusion in this setting. Intraoperative considerations should include drain placement (subfascial, subcutaneous, or both) due to generalized oozing. Postpartum management of the HELLP patient should include close hemodynamic monitoring for at least 48 hours. Serial laboratory evaluations should also be done to monitor for worsening abnormalities. Most patients should show reversal of laboratory parameters within 48 hours. Therefore, we do not recommend postpartum administration of dexamethasone at our center.
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Another potential life-threatening complication of HELLP syndrome is subcapsular liver hematoma. Clinical findings consistent with this complication include phrenic nerve pain. Pain in the pericardium, peritoneum, pleura, shoulder, and esophagus are consistent with referred pain from the phrenic nerve. Confirmation of the diagnosis can be obtained via the computed tomography, ultrasonography or magnetic resonance imaging. Conservative management in a hemodynamically stable patient with an unruptured subcapsular hematoma is appropriate, provided that close hemodynamic monitoring, serial evaluations of coagulation profiles, and serial evaluation of the hematoma with radiologic studies are performed. Should the patient decompensate hemodynamically, the diagnosis of ruptured subcapsular hematoma should be entertained. If rupture of a subcapsular liver hematoma is suspected, immediate intervention is necessary. Liver hematoma rupture with hemodynamic shock is a life threatening surgical emergency. Management should involve trauma and vascular surgeons. Correction of coagulopathy and massive blood product transfusion is essential. Typically, rupture involves the right lobe of the liver. Maternal and fetal mortality is over 25%, even with immediate intervention. The current recommendation for treating rupture of subcapsular liver hematoma in pregnancy is packing and drainage, if possible.
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The rate of eclampsia in the United States is 0.05% to 0.1%, and much higher in developing countries. Eclampsia continues to be a major cause of maternal and perinatal morbidity/mortality worldwide. The maternal mortality rate is approximately 1% to 2%. The perinatal mortality rate ranges from 13% to 30%. Eclampsia can occur antepartum (50%), intrapartum (25%), or postpartum (25%). In the postpartum period, eclampsia can develop as late as 4 weeks.
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During the eclamptic seizure, the main therapy is supportive care. Management of eclampsia is as follows:
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Avoid injury: Padded bed rails, restraints
Maintain oxygenation: O2, pulse oximetry, arterial blood gas assessment
Minimize aspiration: Lateral decubitus position, upper airway suction
Initiate magnesium sulfate
Control blood pressure
Move toward delivery (corticosteroids if <28 weeks and stable condition at a center with expertise in management of eclampsia)
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Most seizures are self-limited, lasting 1 to 2 minutes. Magnesium sulfate is the drug of choice for the prevention of eclampsia and should also be used for prevention of recurrent seizures. Approximately 10% of eclamptic women receiving magnesium sulfate will nevertheless have more seizures. Immediately following an eclamptic seizure, it is common to see abnormalities in the fetal heart rate pattern. These include fetal bradycardia, decreased variability, late decelerations, and reflex tachycardia. They typically resolve within 5 to 10 minutes after the convulsion. It is important not to proceed directly to cesarean delivery after a seizure, if at all possible. Vaginal delivery is the preferred birth route, even after an eclamptic seizure. Cesarean delivery should be performed for obstetric indications only. Induction of labor may be performed with oxytocin or prostaglandins, with the patient maintained on magnesium sulfate throughout her labor course. Careful attention must be given to the overall fluid status of the patient. Patients with eclampsia may have profound hemoconcentration. Because of this, close hemodynamic monitoring is required in the setting of epidural anesthesia and/or of severe blood loss. Patients who are hypovolemic will not respond well to acute blood loss, yet it is also important to limit fluids, as these patients have capillary leakage and are predisposed to developing pulmonary edema. Magnesium sulfate should be continued for 24 hours postpartum. Intracranial imaging is typically not warranted unless coma or focal neurologic signs persist or the diagnosis is uncertain. Postpartum eclampsia is a diagnostic dilemma. Any woman seizing in the postpartum period should be considered to have eclampsia; however, other disorders must be ruled out. Patients who develop postpartum eclampsia usually will have symptoms prior to seizure activity including severe, persistent headache, blurred vision, photophobia, epigastric pain, nausea and vomiting, and transient mental status changes. Therefore, it is important to educate patients to report these symptoms to healthcare providers so as to initiate preeclamptic evaluation. Eclamptics should receive MgSO4 for at least 24 hours after seizure activity. If the patient has normal laboratory values and hypertension is controlled, she can be discharged in a few days with instructions to report symptoms and to return in 1 week for outpatient evaluation.
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The use of magnesium sulfate in the management of preeclamptic patients is for the prevention of eclamptic seizures. The exact mode of action of MgSO4 for preventing seizures is unknown, although it has been in use since the early twentieth century to prevent recurrent seizures and other associated maternal/perinatal complications. The recommended regimen is presented in Table 5-8. The intravenous route is the preferred method, as intramuscular injection of magnesium sulfate is very painful and occasionally can cause gluteal abscess formation. Magnesium sulfate is not a benign medication. Patients receiving MgSO4 are at increased risk for postpartum hemorrhage due to uterine atony. This should be anticipated and steps should be taken to ensure availability of crossmatched blood, if the need arises. Monitoring patients for signs of magnesium toxicity should be done throughout the course of administration; this includes eliciting deep tendon reflexes, assessing mental status, checking respiratory rate, and monitoring urine output. Table 5-8 lists the clinical findings associated with various serum magnesium levels. If a patient develops signs of magnesium toxicity, the infusion should be stopped immediately. The patient should then be evaluated for respiratory compromise by examination and pulse oximetry; oxygen should be administered and a serum magnesium level should be obtained. If magnesium toxicity is diagnosed, the patient should be treated with 10 mL of 10% calcium gluconate solution, infused over 3 minutes. Calcium competitively inhibits magnesium at the neuromuscular junction and decreases the toxic effects. The impact of calcium is transient and the patient should be closely monitored for continued magnesium toxicity. Should respiratory or cardiac arrest occur, immediate resuscitation including intubation and mechanical ventilation should be initiated.
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