Hypertensive Disorders of Pregnancy

Hypertension in Pregnancy

• Affects 6% to 10% of pregnancies.
• A leading cause of maternal mortality, accounting for about half of all maternal deaths worldwide, along with hemorrhage.
• A major risk factor for fetal complications, including preterm birth, fetal growth restriction, and fetal/neonatal death.
• Poses significant anesthesia risks.

Classification of Hypertensive Disorders

• Includes chronic hypertension, gestational hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia.
• These disorders can be difficult to differentiate due to similar clinical presentations but different underlying causes and outcomes.
• ACOG published current knowledge and recommendations for preeclampsia care in 2013.

Gestational Hypertension

• Most frequent cause of hypertension during pregnancy, affecting about 5% of parturients.
• Characterized by elevated blood pressure after 20 weeks gestation without proteinuria.
• Resolves by 12 weeks postpartum.
• Most cases develop after 37 weeks gestation.
• Approximately 25% of patients with gestational hypertension will develop preeclampsia.
• Definitive diagnosis is made postpartum after excluding chronic hypertension.

Preeclampsia

• Defined as new-onset hypertension and proteinuria after 20 weeks gestation.
• Consider diagnosis without proteinuria if signs of end-organ involvement are present:
  • Persistent epigastric or RUQ pain
  • Persistent cerebral symptoms
  • Fetal growth restriction
  • Thrombocytopenia
  • Elevated serum liver enzymes
• Eclampsia occurs when CNS involvement leads to new-onset seizures in a woman with preeclampsia.

HELLP Syndrome

• Development of hemolysis, elevated liver enzymes, and low platelet count in a woman with preeclampsia.
• May be a variant of severe preeclampsia.
• Classification remains controversial due to potentially distinct disease processes.

Chronic Hypertension

• SBP of 140 mmHg or higher and/or DBP of 90 mmHg or higher before pregnancy or before 20 weeks gestation.
• Elevated BP that fails to resolve after delivery.
• Develops into preeclampsia in about 20% to 25% of affected patients.
• An important risk factor for unfavorable maternal and fetal pregnancy outcomes, even without preeclampsia.

Chronic Hypertension with Superimposed Preeclampsia

• Preeclampsia develops in a woman with chronic hypertension before pregnancy.
• Diagnosis is based on:
  • New-onset proteinuria
  • Sudden increase in proteinuria or hypertension, or both
  • Other manifestations of severe preeclampsia
• Increased morbidity for both mother and fetus compared with preeclampsia alone.

Preeclampsia as a Multisystem Disease

• Unique to human pregnancy.
• Characterized by diffuse endothelial dysfunction with maternal complications:
  • Placental abruption
  • Pulmonary edema
  • Acute renal failure
  • Liver failure
  • Stroke
• Neonatal complications include:
  • Indicated preterm delivery
  • Fetal growth restriction
  • Hypoxic-ischemic neurologic injury
  • Perinatal death

Cause and Management of Preeclampsia

• Specific cause is unknown.
• Management is supportive.
• Delivery of the infant and placenta is the only definitive cure.
• Defined as new-onset hypertension and proteinuria after 20 weeks gestation.
• Edema is no longer part of the diagnostic criteria.

Preeclampsia Epidemiology

• Occurs in 3% to 4% of pregnancies in the United States.
• Definitive treatment is delivery of the infant and placenta.
• A leading cause of indicated preterm delivery.
• Preterm delivery is the most common reason for NICU admission.
• Leading indication for maternal peripartum admission to an ICU.
• Clinical findings manifest as a maternal syndrome (hypertension and proteinuria with or without other systemic abnormalities) with or without an accompanying fetal syndrome (fetal growth restriction, oligohydramnios, abnormal oxygen exchange).
• In ~ 75% of cases, preeclampsia occurs without severe features near term or during the intrapartum period.
• Onset before 34 weeks gestation is associated with increased disease severity and poorer outcomes for both mother and fetus.
• The incidence of hypertensive disorders of pregnancy has nearly doubled in the past 25 years.
• Major shifts in pregnant women's demographics and clinical conditions partially explain the increase.
• Advanced maternal age is a recognized risk factor.
• Growing epidemic of obesity, increased prevalence of diabetes and chronic hypertension, and the increase in the use of assisted reproductive techniques all increase the risk for preeclampsia.

Preeclampsia Risk Factors

• Include demographic, genetic, medical, behavioral, recreational, and partner-related factors.

Preeclampsia - Demographic Risk Factors

• Advanced maternal age (40 or older) doubles the risk compared to women aged 20-29.
• Teenage pregnancy may also be a risk.
• Black women are at high risk due to increased rates of chronic hypertension, obesity, and preeclampsia.
• Black women experience more extreme hypertension, require more antihypertensive therapy, are more likely to develop eclampsia, and are more likely to die.
• Hispanic ethnicity may also be at an increased risk for developing Preeclampsia and Eclampsia.

Preeclampsia - Genetic Risk Factors

• Maternal genetic factors increase the risk.
• Pregnant women with a family history are twice as likely to develop the disorder.
• Men who fathered one preeclamptic pregnancy were nearly twice as likely to father a preeclamptic pregnancy with a different woman.
• Women with a history of preeclampsia, placental abruption, or fetal growth restriction are at increased risk in subsequent pregnancies.
• Some women have a susceptibility to obstetric conditions caused by placental dysfunction.

Preeclampsia - Medical Risk Factors

• Obesity (risk escalates with increasing BMI)
• Insulin resistance
• Chronic hypertension (increases odds 10-fold)
• Diabetes mellitus (twofold increase)
• Metabolic syndrome (obesity, hyperglycemia, insulin resistance, and hypertension)
• Chronic renal disease
• Antiphospholipid antibody syndrome
• Systemic lupus erythematosus

Preeclampsia - Behavioral Risk Factors

• Cigarette smoking during pregnancy is associated with a decreased risk of preeclampsia; women who smoke have a 30%-40% lower risk.
• Recreational physical activity during pregnancy decreases the risk of gestational hypertensive disorders, particularly in non-obese women.

Preeclampsia - Partner Risk Factors

• Limited maternal exposure to paternal sperm antigens before conception is a risk factor.
• Nulliparity triples the risk compared to parous women.
• More common in parous women conceiving with a new partner, using barrier methods of contraception, or conceiving with donated sperm.
• Long-term sperm exposure with the same partner appears protective.

Preeclampsia - Pathogenesis

• Exact mechanisms are unknown.
• The placenta is the proposed mechanism regarding disease pathogenesis.
• Delivery of the placenta results in the resolution of the disease.
• The disease can occur in the absence of a fetus (molar pregnancy)
• Contemporary beliefs generally conceive preeclampsia as a two-stage disorder.
• The asymptomatic first stage occurs early in pregnancy with impaired remodeling of the spiral arteries.
• The symptomatic second stage is characterized by the release of antiangiogenic factors from the intervillous space into the maternal circulation.

Preeclampsia Pathogenesis - Spiral Artery Remodeling

• In normal pregnancy, embryo-derived cytotrophoblasts invade the decidual and myometrial segments of the spiral arteries.
• This replaces endothelium, causing remodeling of vascular smooth muscle and the inner elastic lamina.
• The luminal diameter of the spiral arteries increases fourfold providing a low-resistance vascular pathway to the intervillous space.
• This makes them unresponsive to vasoactive stimuli.
• In a preeclamptic pregnancy, cytotrophoblast invasion is incomplete, and only the decidual segments change.
• The myometrial spiral arteries are not invaded and remodeled, and thus remain small, constricted, and hyperresponsive to vasomotor stimuli.
• Failure of normal angiogenesis results in superficial placentation.
• Placental ischemia worsens throughout pregnancy, leading to fetal growth restriction.

Preeclampsia Pathogenesis - Antiangiogenic Factors

• Reduced perfusion of the intervillous space leads to the symptomatic second stage.
• The release of antiangiogenic factors causes widespread maternal endothelial dysfunction and a systemic inflammatory response.
• Healthy endothelium prevents platelet activation, activates circulating anticoagulants, buffers the response to vasopressors, and maintains fluid in the intravascular compartment: these normal functions are disrupted in preeclampsia.
• The pregnant woman develops hypertension and proteinuria is at risk for other manifestations of severe systemic disease.
• Clinical manifestations manifest after 20 weeks gestation.

Preeclampsia Pathogenesis - Immunologic Factors

• Abnormal uteroplacental development results from complex immunologic, vascular, environmental, and genetic factors.
• The immune cells in the decidua include macrophages, dendritic cells, and natural killer (NK) cells.
• Macrophages and dendritic cells are found in greater density in preeclamptic placentas and are associated with impaired trophoblastic invasion.
• Agonistic autoantibodies to the angiotensin type I receptor (AT1) are present in many women with preeclampsia and are associated with defective remodeling of the uteroplacental vasculature. The autoantibodies activate AT1 receptors on trophoblast cells, endothelial cells, and vascular smooth muscle cells, blocking trophoblastic invasion and inducing the production of reactive oxygen species.
• Oxidative stress and the resultant oxygen free radicals may contribute to placental atherosclerosis.

Preeclampsia - Maternal Systemic Disease

• The second stage is characterized by signs and symptoms resulting from widespread endothelial dysfunction, affecting various organ systems.
• The leading hypothesis suggests that as pregnancy progresses, relative placental hypoxia triggers the overexpression and release of placentally derived antiangiogenic factors into the maternal circulation.
• The vascular endothelium requires proangiogenic factors for normal function

Preeclampsia Genetic Factors

• Strong genetic basis with maternal and fetal genetic factors
• Approximately 20% of disease risk from fetal genetic factors and 30% from maternal genetic factors

Preeclampsia Prophylaxis

• Strategies studied include antiplatelet drugs, metformin, antioxidant and calcium supplementation, and dietary sodium restriction
• Low-dose aspirin use is associated with a 2% to 5% absolute reduction in the risk
• ACOG advises low-dose aspirin between 12- and 24-weeks gestation in women at high risk

Preeclampsia Clinical Presentation

• More frequent in nulliparous women and most commonly presents during the third trimester
• Early-onset preeclampsia (before 34 weeks gestation) has poorer outcomes than late-onset disease
• The disease typically regresses rapidly after delivery, with resolution of symptoms within 48 hours
• Can manifest postpartum with hypertension, proteinuria, or seizures, usually within 7 days of delivery
• Disease manifestation of severe preeclampsia occurs in all body systems as the result of widespread endothelial dysfunction

Preeclampsia - Clinical Presentation (CNS)

• Eclampsia is the outward manifestation of disease progression in the brain
• CNS manifestations include:
  • Severe headache
  • Hyperexcitability
  • Hyperreflexia
  • Coma
• Visual disturbances can include scotoma (blind spot), amaurosis (temporary loss of vision), and blurred vision
• There is a loss of cerebral vascular autoregulation, and vascular barotrauma occurs with preeclampsia and eclampsia
• Hyper perfusion of the brain causes vasogenic edema occurs most commonly in the posterior circulation; these changes may result in the posterior reversible leukoencephalopathy syndrome (PRES)

Preeclampsia - Clinical Presentation (Airway)

• The internal diameter of the trachea is reduced because of mucosal capillary engorgement
• Women with preeclampsia can have exaggerated upper airway narrowing due to pharyngolaryngeal edema
• Changes may compromise visualization of airway landmarks during direct laryngoscopy
• Signs of airway obstruction include dysphonia, hoarseness, snoring, stridor, and hypoxemia
• Parturients with Obstructive Sleep Apnea (OSA) have a twofold increase in risk
• Recurrent nocturnal desaturations might result in placental hypoxia, hypertension, and maternal endothelial dysfunction, all of which are associated with preeclampsia

Preeclampsia - Clinical Presentation (Cardio)

• Women with preeclampsia have increased vascular tone and increased sensitivity to vasoconstrictors and circulating catecholamines, which results in the clinical manifestations of hypertension, vasospasm, and end-organ ischemia
• Plasma volume may be normal but may be reduced as much as 40% in those with severe disease
• Severe preeclampsia is a hyperdynamic state
• Most affected women without clinical signs of pulmonary edema exhibit:
  • Normal to increased cardiac output
  • Hyperdynamic left ventricular function
  • Mild to moderately increased systemic vascular resistance
• The myocardium may be edematous as well as hypertrophied in severe preeclampsia

Preeclampsia - Clinical Presentation (Pulmonary)

• Pulmonary edema is a severe complication that occurs in approximately 3% of women with preeclampsia
• Risk increases in:
  • Older multigravid women
  • Women with preeclampsia superimposed on chronic hypertension or renal disease
  • Women whose preeclampsia progresses to oliguria
• Plasma colloid osmotic pressure is reduced in normal pregnancy because of decreased plasma albumin concentrations, and it is decreased even further in women with preeclampsia
• Decreased colloid osmotic pressure, increased vascular permeability, and the loss of intravascular fluid and protein into the interstitium increase the risk for pulmonary edema

Preeclampsia - Clinical Presentation (Hematologic)

• Thrombocytopenia is the most common hematologic abnormality
• Preeclampsia is the most common cause of severe thrombocytopenia in the second half of pregnancy
• Platelet counts less than 100,000 occur most commonly in women with severe disease or HELLP syndrome and correlate with the severity of the disease process
• TEG results show that women with preeclampsia without severe features are hypercoagulable, and those with severe disease are relatively hypocoagulable
• Platelets are activated in preeclampsia, and subsequent platelet degranulation is believed to account for the decrease in platelet function
• Platelet aggregation appears to account for the decrease in platelet count

Preeclampsia - Clinical Presentation (Hematologic cont.)

• Disseminated Intravascular Coagulation (DIC) occurs in some women with preeclampsia, usually in the setting of:
  • Severe liver involvement
  • Intrauterine fetal demise
  • Placental abruption
  • Postpartum hemorrhage
• Activation of the coagulation system is marked by consumption of procoagulants, increased levels of fibrin degradation products, and end-organ damage secondary to microthrombi formation
• In advanced DIC, procoagulants decrease to a level that may lead to spontaneous hemorrhage

Preeclampsia - Clinical Presentation (Hepatic)

• See HELLP Syndrome

Preeclampsia - Clinical Presentation (Renal)

• Renal manifestations include persistent proteinuria, changes in the GFR, and hyperuricemia
• The presence of proteinuria is a defining element of preeclampsia but is no longer considered essential for diagnosis if other evidence of end-organ injury is present
• The characteristic insult is glomerular capillary endotheliosis, which manifests as glomerular enlargement and endothelial cell swelling
• Increasing urinary excretion of protein likely results from changes in the pore size or charge selectivity of the glomerular filter and impaired reabsorption

Preeclampsia - Clinical Presentation (Renal cont.)

• In normal pregnancy, the GFR increases by 40% to 60% during the 1st trimester, decreasing BUN, creatinine, and uric acid
• In preeclampsia, this increase in GFR is blunted compared with normal pregnancy
• Women with preeclampsia may have BUN and creatinine measurements in the normal range for non-pregnant women despite significantly decreased GFR relative to healthy pregnant women
• Oliguria is a possible late manifestation of severe preeclampsia and parallels the severity of the disease
• Persistent oliguria requires immediate assessment of intravascular volume status
• Progression to renal failure is rare and is typically preceded by hypovolemia, placental abruption, or DIC

Preeclampsia - Clinical Presentation (Uteroplacental Perfusion)

• It can be impaired in pregnancies complicated by preeclampsia
• Changes can result in fetal growth restriction in some pregnancies

Preeclampsia - Obstetric Management

• Centers on:
  • Decisions regarding the timing and route of delivery
  • Fetal and maternal surveillance
  • Treatment of hypertension
  • Seizure prophylaxis
• Delivery remains being the only cure for preeclampsia
• Obstetric care of women with preeclampsia without severe features differs little from routine management of healthy pregnant women, except for careful monitoring to detect the development of severe features
• Data suggests that the induction of labor for pregnancies beyond 37 weeks gestation is associated with improved maternal outcomes; outcomes are similar to those in uncomplicated pregnancies

Preeclampsia - Obstetric Management (Delivery)

• Delivery is recommended for women presenting with preeclampsia with severe features at 34 weeks gestation or later
• Expedited delivery, regardless of corticosteroid administration, is indicated for patients with:
  • Eclampsia
  • Pulmonary edema
  • DIC
  • Placental abruption
  • Abnormal fetal surveillance
  • Nonviable fetus
  • Intrauterine fetal demise
• If a woman develops refractory severe hypertension despite maximum doses of antihypertensive agents or persistent cerebral symptoms while receiving magnesium sulfate, delivery should occur within 24 to 48 hours, regardless of gestational age or corticosteroid administration

Preeclampsia - Obstetric Management (Surveillance)

• In women with preeclampsia without severe features, the goal is the detection of worsening organ dysfunction
• All women should be evaluated for signs or symptoms indicating end-organ involvement, including:
  • Severe headache
  • Visual disturbances
  • Altered mentation
  • Dyspnea
  • Right upper quadrant or epigastric pain
  • Nausea and vomiting
  • Decreased urine output
  • CNS hyperexcitability
• Admission platelet count is a predictor of subsequent thrombocytopenia
• For preeclamptic women with a platelet count exceeding 100,000, additional coagulation testing is not required because coagulopathy is rarely present in severely preeclamptic women who have a normal platelet count
• Liver function tests are obtained in all women with preeclampsia because abnormal levels indicate more severe disease and may prompt delivery; approximately 20% of women with preeclampsia have elevated serum aminotransferase levels
• Preeclampsia without severe features warrants laboratory testing at least weekly
• Preeclampsia is a known risk factor for perinatal death
• ACOG recommends daily fetal movement counts with either non-stress testing or biophysical profile testing at the time of diagnosis and regular intervals afterward

Preeclampsia - Obstetric Management (Fluids)

• Clinicians should restrict fluids unless monitoring is used to assess response to fluid administration and volume expansion is not recommended: fluids should be limited to 80 mL/hr or 1 mL/kg/hr Volume expansion is not recommended, and fluids should be limited to 80 mL/hr or 1 mL/kg/hr
• In the case of hemorrhage, losses should be replaced appropriately; administration of additional fluid may be considered before intravenous hydralazine, neuraxial anesthesia, or immediate delivery

Preeclampsia - Obstetric Management (Antihypertensives)

• Antihypertensive medications are used to treat severe hypertension (SBP ≥ 160 or DBP ≥ 110)
• The goal is to prevent adverse maternal events such as:
  • Hypertensive encephalopathy
  • Cerebrovascular hemorrhage
  • Myocardial ischemia
  • Congestive heart failure
• Acute control of maternal blood pressure is critical, and rapid changes in maternal perfusion pressure may adversely affect uteroplacental perfusion and oxygen delivery to the fetus
• Antihypertensive medications should be carefully titrated to avoid abrupt changes in maternal blood pressure

Preeclampsia - Obstetric Management (Antihypertensives Goals)

• The goal of antihypertensive therapy is to lower the MAP by no more than 15% - 25%
• Target SBP = 120-160
• Target DBP = 80-105
• Commonly used drugs include labetalol, hydralazine, and nifedipine
• ACOG recommends labetalol or hydralazine as a first-line treatment for acute-onset, severe hypertension in pregnant or postpartum patients

Treatment of Acute Severe Hypertension in Preeclampsia / Eclampsia

• See chart for specific dosing

Preeclampsia Antihypertensives - Labetalol

• Combined alpha and beta-adrenergic receptor antagonist with a 1:7 ratio of alpha to beta antagonism when administered IV
• It should be avoided in women with severe asthma or congestive heart failure
• Has efficacy similar to IV hydralazine but with fewer maternal side effects
• Neonates born to mothers who took beta blockers demonstrated increased rates of neonatal hypoglycemia and bradycardia

Preeclampsia Antihypertensives - Hydralazine

• Exerts a potent direct vasodilating effect
• Plasma volume expansion before administration decreases the risk for maternal hypotension
• Other side effects include:
  • Tachycardia
  • Palpitations
  • Headaches
  • Neonatal thrombocytopenia
• In clinical trials, hydralazine was associated with more maternal tachycardia and palpitations and less neonatal bradycardia and hypotension when compared to labetalol

Preeclampsia Antihypertensives - Nifedipine

• Calcium entry-blocking agent that lowers blood pressure by relaxing arterial and arteriolar smooth muscle
• It can be administered as a long-acting oral medication once the severe hypertension has stabilized
• There is an increased risk for sudden cardiac death in the following patients:
  • Known coronary artery disease (CAD)
  • Long-standing diabetes mellitus or aortic stenosis
  • Women older than 45 years of age
• In the absence of contraindications, nifedipine is now recommended as a first-line agent in women for whom IV access is difficult

Preeclampsia - Seizure Prophylaxis

• The routine use of magnesium sulfate for seizure prophylaxis in women with preeclampsia with severe features is an established practice
• There is clear evidence that magnesium sulfate is the best available agent for the prevention of recurrent seizures in women with eclampsia
• Magnesium does not affect fetal and/or neonatal outcomes such as stillbirth, perinatal death, or neurosensory disability
• Treatment with magnesium increases the risk for maternal respiratory depression and cesarean delivery

Preeclampsia - Seizure Prophylaxis (Side Effects)

• Other side effects of magnesium sulfate include:
  • Feeling warm or flushed
  • Nausea/vomiting
  • Muscle weakness
  • Hypotension
  • Dizziness
  • Drowsiness/confusion
  • Headache
• In general, magnesium sulfate is not indicated for seizure prevention in preeclampsia without severe features, and studies have failed to show a difference in the number of women who progressed to severe preeclampsia

Preeclampsia - Seizure Prophylaxis (Mechanism of Action)

• The mechanism of the anticonvulsant activity of magnesium sulfate is not well understood
• Historically, it was thought that eclamptic seizures were the result of cerebral vasospasm
• it was believed that the cerebral vasodilating properties of magnesium reduced the rate of eclamptic seizures by relieving vasospasm
• Newer evidence suggests that magnesium sulfate may protect the blood-brain barrier or act centrally at the NMDA receptors to raise the seizure threshold

Preeclampsia - Seizure Prophylaxis (Administration)

• No agreement exists regarding:
  • The ideal time to initiate treatment with magnesium
  • The best loading and maintenance doses
  • The optimal duration of therapy
• Many OBs administer a loading dose of 4-6 grams over 20-30 minutes, followed by a maintenance dose of 1-2 grams/hour
• Expert opinion recommends that women with preeclampsia with severe features undergoing cesarean delivery should receive magnesium sulfate at least 2 hours before the procedure, during surgery, and for 24 hours postpartum

Preeclampsia - Seizure Prophylaxis (Toxicity)

• Elimination is carried about via renal excretion, and serum magnesium levels may rise dangerously high if renal insufficiency is present
• Side effects of hypermagnesemia include:
  • Chest pain and tightness
  • Palpitations
  • Nausea
  • Blurred vision
  • Sedation
  • Transient hypotension
  • Pulmonary edema (rare)
• Normal range for serum magnesium (non-pregnant) = 1.7 – 2.4 mg/dL
• Therapeutic range = 5 – 9 mg/dL
• Reflex testing is used as a clinical screen for hypermagnesemia; when deep tendon reflexes are preserved, the more serious side effects are typically avoided
• Patellar reflexes are lost at serum magnesium levels ~ 12 mg/dL
• Respiratory arrest occurs at levels between 15 and 20 mg/dL
• Asystole can occur if levels exceed 25 mg/dL
• Preeclamptic women with renal impairment should be monitored closely because magnesium toxicity can occur with normal therapeutic dosing

Preclampsia - Seizure Prophylaxis (Mag Toxicity Treatment)

• Treatment of suspected magnesium toxicity includes:
  • Immediate discontinuation of the infusion
  • Administration of calcium gluconate 1g over 10 minutes
• In the rare event of respiratory compromise, the patient may require tracheal intubation and mechanical ventilation until spontaneous ventilation returns

Preeclampsia Route of Delivery

• Vaginal delivery should be attempted in all women with preeclampsia without severe features, assuming no other indications for cesarean delivery exist
• Vaginal delivery should also be attempted in most women with severe disease, especially those beyond 34 weeks gestation
• Cesarean delivery is appropriate when the maternal or fetal condition mandates immediate delivery or when other indications for cesarean delivery exist

Preeclampsia Corticosteroids

• All women who develop preeclampsia with severe features or HELLP syndrome between 24 and 34 weeks of gestation should receive a course of corticosteroid therapy to help accelerate fetal lung maturity
• Infants of mothers who received betamethasone exhibited a significant reduction in the rate of neonatal respiratory distress syndrome and reduced rates of intraventricular hemorrhage, infection, and death
• Corticosteroids also help improve the maternal platelet count in those with HELLP syndrome

Preeclampsia Complications

• Increased risk for maternal morbidity and mortality including:
  • HELLP Syndrome
  • CVA
  • Pulmonary edema
  • Renal failure
  • Placental abruption
  • Eclampsia
• More common in women with early-onset preeclampsia and in women with pre-pregnancy medical conditions such as diabetes mellitus, chronic renal disease, and thrombophilia

Preeclampsia - Complications (CVA)

• Although the absolute risk of cerebrovascular accident (CVA) is low, preeclampsia significantly increases the risk of intracerebral and subarachnoid hemorrhage, as well as ischemic stroke
• Stroke remains the leading cause of death in women with preeclampsia
• The endothelial dysfunction of preeclampsia contributes to:
  • Edema
  • Vascular tone instability
  • Platelet activation
  • Local thrombosis
• Reversible cerebral edema is the most common CNS feature of preeclampsia or eclampsia The loss of cerebral autoregulation causes hyperperfusion that leads to interstitial or vasogenic edema

Preeclampsia - Complications (CVA cont.)

• Once confirmed, SBP ≥ 150-160 mmHg or DBP ≥ 110 should be treated within 30-60 minutes
• MAP & DBP may not reflect the true risk for stroke SBP > 160 is a far superior predictor of stroke
• Most strokes are hemorrhagic (93%)
• Most strokes (57%) occur in the postpartum period
• Close attention to blood pressure control throughout the peripartum period is the mainstay of stroke prevention

Preeclampsia - Complications (Pulmonary Edema)

• Clinical presentation: worsening dyspnea and orthopnea with concurrent signs of respiratory compromise such as tachypnea, rales, and hypoxemia
• Many cases occur postpartum, usually within 2-3 days after delivery, and management is directed at treating the underlying cause
• Initial treatment includes:
  • Supplemental oxygen
  • Fluid restriction
  • Diuretic therapy (furosemide)

Preeclampsia - Complications (Renal Failure)

• Acute renal failure is a rare but serious complication of severe preeclampsia and HELLP syndrome
• Divided into 3 categories:
  • Prerenal (renal hypoperfusion)
  • Intrarenal (intrinsic renal parenchymal damage)
  • Postrenal (obstructive uropathy)
• The majority of cases (83% - 90%) are from prerenal and intrarenal pathologic processes (most commonly acute tubular necrosis) and resolve completely after delivery

Preeclampsia - Complications (Placental Abruption)

• Occurs in approximately 2% of women with preeclampsia and results in increased perinatal morbidity and mortality
• Threefold increased risk for placental abruption in women with preeclampsia
• Management depends on:
  • The extent of abruption
  • Associated hypotension, coagulopathy, or fetal compromise
• Also associated with the development of DIC

Preeclampsia - Complications (HELLP)

• Characterized by Hemolysis, Elevated Liver enzymes, and a Low Platelet count
• Associated with increased rates of maternal morbidities, including:
  • DIC
  • Placental abruption
  • Pulmonary edema
  • Acute renal failure
  • Liver hemorrhage or failure
  • Acute Respiratory distress syndrome
  • Sepsis
  • Stroke
  • Death

Preeclampsia - Complications (HELLP cont.)

• Seventy percent of women with HELLP syndrome deliver preterm, contributing to prematurity-related perinatal morbidity and mortality
• The onset occurs antepartum (70%) and postpartum (30%)
• Hemolysis = presence of microangiopathic hemolytic anemia. It is the classic hallmark of HELLP syndrome
• Maternal signs and symptoms include:
  • RUQ or epigastric pain
  • Nausea and vomiting
  • Headache
  • Hypertension
  • Proteinuria
• Diagnosis can be challenging because multiple disorders can mimic HELLP syndrome

Preeclampsia - Complications (HELLP Management)

• In most patients with HELLP, delivery is delayed 24-48 hours to allow for corticosteroid administration to accelerate fetal lung maturity for women less than 34 weeks gestation if maternal and fetal condition remain stable
• Women with HELLP syndrome who have not yet reached 34 weeks should be managed in a tertiary care facility with a NICU capable of caring for a compromised preterm neonate Clinical management is similar to that for severe preeclampsia and includes:
  • IV magnesium sulfate for seizure prophylaxis
  • Antihypertensive medications to maintain SBP below 160 and DBP less than 110 mmHg

Preeclampsia - Complications (HELLP - Platelets)

• The platelet count can fall dramatically in the presence of HELLP syndrome and should be evaluated before the administration of neuraxial anesthesia
• Women with a platelet count less than 50,000 are at significantly increased risk for bleeding, and general anesthesia is the method of choice for cesarean delivery
• Administration of dexamethasone may improve the platelet count in women with HELLP syndrome
• Platelet transfusions are indicated in the presence of (1) significant bleeding and (2) in all parturients with a platelet count less than 20,000
• For women with a platelet count of less than 40,000 who are scheduled for cesarean delivery, the pre-incision administration of 6-10 units of pooled platelets or 1-2 units of apheresis platelets is recommended

Preeclampsia - Complications (HELLP - Liver)

• Rupture of a subcapsular hematoma of the liver is a life-threatening complication of HELLP syndrome and severe preeclampsia that presents as:
  • Abdominal pain
  • Nausea and vomiting
  • Headache
• The pain worsens over time and becomes localized to the epigastric area or RUQ
• Hypotension and shock typically develop, and the liver is enlarged and tender
• Hematoma rupture with shock is a surgical emergency
• Patients with fulminant liver failure may require liver transplantation
• The most common causes of death = coagulopathy and exsanguination

Preeclampsia Anesthetic Management - General

• The anesthetic management of a woman with preeclampsia without severe features differs little from the management of a healthy pregnant woman, but there is a potential for rapid progression to the severe form
• The anesthesia provider must recognize the unpredictability of the development and progression of severe preeclampsia and should always be prepared for immediate cesarean delivery
• The pre-anesthetic assessment of the woman with confirmed or suspected preeclampsia should focus on (1) airway examination, (2) maternal hemodynamic and coagulation status, and (3) fluid balance

Preeclampsia Anesthetic Management - Airway/Monitoring

• Generalized edema can involve the airway and obscure visualization of anatomic landmarks at laryngoscopy
• NIBP monitoring is appropriate in uncomplicated severe preeclampsia, although automatic blood pressure devices may underestimate blood pressure in preeclampsia
• The most frequent indications for radial artery catheter insertion are:
  • The need for continuous blood pressure monitoring during the induction of and emergence from general anesthesia
  • Frequent arterial blood gas measurements
  • Use of calculated systolic pressure variation to estimate intravascular volume status

Preeclampsia Anesthetic Management - Neuraxial Anesthesia

• The major advantages of neuraxial anesthesia are (1) control of hypertension and (2) the avoidance of the need for airway manipulation Continuous lumbar epidural analgesia or CSE analgesia are the preferred methods of pain management
• Advantages include:
  • High-quality analgesia
  • Reduction in levels of circulating catecholamines and stress-related hormones
  • Mean for rapid initiation of epidural anesthesia for emergency cesarean delivery
  • Possible improvement in intervillous blood flow
• Early initiation of neuraxial analgesia is recommended in the absence of contraindications in all patients with preeclampsia with severe features, especially in women with HELLP syndrome, obesity, or concern for fetal status

Preeclampsia Anesthetic Management - Neuraxial Special Considerations

• The administration of neuraxial analgesia to women with preeclampsia does not differ from that of healthy women, except for 4 special considerations:
  • Assessment of coagulation status
  • IV hydration before neuraxial administration of a local anesthetic
  • Treatment of hypotension
  • Use of epinephrine-containing local anesthetic solutions

Preeclampsia Anesthetic Management - Coagulation

• Platelets contribute to coagulation and hemostasis in two ways:
  • Adhesive and cohesive functions lead to the formation of the hemostatic plug
  • Activation of the coagulation process Activated platelets release adenosine diphosphate, serotonin, thromboxane A2, and other adhesive proteins, coagulation factors, and growth factors
• Women with preeclampsia without severe features are usually hypercoagulable compared to women with an uncomplicated pregnancy and should not be denied neuraxial labor analgesia Women with preeclampsia with severe features may develop thrombocytopenia, which increases the risk for bleeding into the epidural space or spinal space during a neuraxial procedure

Preeclampsia Anesthetic Management - Coagulation cont.

• Neuraxial hematoma formation can result in permanent neurologic injury
• In the past, a platelet count greater ≥ to 100,000 was considered necessary for the safe administration of neuraxial analgesia
• Currently, many anesthesia providers agree that neuraxial procedures may be performed in pregnant women without other risk factors if the platelet count is higher than 80,000
• There is a consensus that a platelet count less than 50,000 precludes the administration of neuraxial analgesia
• For women with a platelet count between 50,000 – 80,000, the risks and benefits must be weighed against the risks associated with general anesthesia for the individual patient

Preeclampsia Anesthetic Management - Coagulation Low Platelet Count

• If the platelet count is low (80,000 – 100,000), early epidural catheter insertion is recommended in anticipation of worsening thrombocytopenia
• In the presence of thrombocytopenia or abnormal results of liver function tests, the PT and aPTT should be assessed before the initiation of neuraxial analgesia
• The risk for epidural hematoma exists not only at the time of epidural catheter placement but also at the time of its removal
• In patients with thrombocytopenia, the catheter should not be withdrawn from the epidural space until there is evidence of an acceptable (and increasing) platelet count.
• A platelet count of 75,000 – 80,000 is acceptable for epidural catheter removal

Preeclampsia Anesthetic Management - Coagulation Low Platelet Strategies

• If the decision is made to proceed with neuraxial analgesia when the platelet count is less than 100,000, the following suggestions may help reduce the risk for epidural hematoma:
  • The most skilled anesthesia provider available should perform the procedure to minimize the number of needle passes and subsequent bleeding
  • A single-shot spinal technique may be preferable to an epidural technique because of the smaller needle size
  • Use of a flexible wire-embedded epidural catheter, if available, may reduce epidural vein trauma
  • The patient should be carefully monitored after delivery for neurologic signs that may signal bleeding into the epidural space
  • The platelet count should be checked for a return to normal measurements (75,000 – 80,000)
  • Imaging studies and neurosurgical consults should be obtained immediately if there is any question of an epidural hematoma

Preeclampsia Anesthetic Management - Intravenous Hydration

• The rapid administration of a large bolus of IV fluid (preload) results in only a transient increase in central venous pressure and has little impact on the risk for