Preeclampsia


Criteria for the Diagnosis of Severe Preeclampsia

In patients with preeclampsia, severe preeclampsia can be diagnosed if any one of the following criteria is present:

 -  Blood pressure 160 mm Hg systolic or 110 mm Hg diastolic or higher on two separate occasions at least 6 hours apart
-   Proteinuria
 -  Random urine protein-creatinine ratio >5 mg/mg (500 mg/mmol) or proteinuria > 5 g/24 h
 -  Oliguria < 500 ml in 24 hours
 -  Cerebral or visual disturbances such as cerebrovascular accident, seizures, or visual loss
 -  Pulmonary edema
 -  Epigastric or RUQ pain
 -  Hepatocellular injury (serum transaminases at least twice normal)
 -  Serum lactate dehydrogenase (LDH): >600 IU/l
 -  Thrombocytopenia < 100
 -  Fetal growth restriction (birth weight less than 10th percentile for the gestational age)

DEFINITION

Preeclampsia involves the triad of hypertension, proteinuria, and edema that develops after the twentieth week of gestation.

Mild preeclampsia is defined as a blood pressure of >140/90 mm Hg. Severe preeclampsia is associated with a blood pressure >160/110 mm Hg, proteinuria >5 g in a 24-hr urine collection, oliguria (<400 ml/24 hr), cerebral or visual disturbances, epigastric pain, pulmonary edema, thrombocytopenia, hepatic dysfunction, or severe intrauterine growth restriction.

PHYSICAL FINDINGS/PRESENTATION

 -  Generalized swelling or nondependent edema, possibly manifested by rapid weight gain (> 4 lb/wk) even in the absence of edema
 -  RUQ pain (HELLP syndrome [hemolysis, elevated liver enzymes, and low platelet count] or subcapsular liver hematoma)
 -  Hyperreflexia or clonus.
 -  Vaginal bleeding (placental abruption)
 -  Acute or chronic fetal compromise manifested by intrauterine growth restriction or fetal tachycardia with late decelerations, respectively
 -  Wide range of symptoms attributable to multiorgan system dysfunction, involving hepatic, hematologic, renal, pulmonary, and central nervous systems
 -  Possibility of severe disease despite “normal” blood pressure readings, so a high index of suspicion must be maintained in high-risk situations
 

ETIOLOGY

 -  Exact etiology or toxic substance is unknown
 -  Theories:

  • Imbalance between thromboxane A2 (vasoconstrictor and platelet aggregator) and prostacyclin (vasodilator)
  • Abnormal trophoblastic invasion of spiral arteries
  • Increased sensitivity to angiotensin II by the muscular walls of the arteries
  • Excess circulating soluble fms-like tyrosine kinase 1 (SFlT-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role

DDx

 -  Acute fatty liver of pregnancy
 -  Appendicitis
 -  Diabetic ketoacidosis
 -  Gallbladder disease
 -  Gastroenteritis
 -  Glomerulonephritis
 -  Hemolytic-uremic syndrome
 -  Hepatic encephalopathy
 -  Hyperemesis gravidarum
 -  Idiopathic thrombocytopenia
 -  Thrombotic thrombocytopenic purpura
 -  Nephrolithiasis
 -  Pyelonephritis
 -  Peptic ulcer disease
 -  Systemic lupus erythematosus
 -  Viral hepatitis
 

WORKUP

 -  Two blood pressure measurements with the patient in lateral recumbent position 6 hr apart, with an absolute pressure >140/90 mm Hg or an increase of 30 mm Hg systolic or 15 mm Hg diastolic from baseline, an increase in the mean arterial pressure (MAP) of 20 mm Hg, or an absolute MAP >105 mm Hg
 -  Evaluation for proteinuria as defined by >0.1 g/L on urine dipstick or >300 mg protein on a 24-hr urine collection
 -  Evaluation of fetal status for evidence of intrauterine growth restriction, oligohydramnios, alteration in umbilical or uterine artery Doppler flow, or acute compromise, such as abruption.
 -  Because of the insidious nature of the disease with potential for multiple organ involvement, complete evaluation for preeclampsia in any pregnant patient presenting with central nervous system derangement or gastrointestinal symptoms after 20 wk of gestation
 -  Evaluation for associated conditions such as disseminated intravascular coagulation, hepatic dysfunction, or subcapsular hematoma

LAB TESTS

 -  High-risk patients: baseline assessment of renal function (24-hr urine collection for protein and creatinine clearance), platelets, blood urea nitrogen, creatinine, liver function tests (LFTs), and uric acid should be obtained at the first prenatal visit.
 -  CBC (hemoglobin, hematocrit, platelets) may show signs of volume contraction or HELLP syndrome.
 -  LFTs (aspartate aminotransferase, alanine aminotransferase, LDH) are useful in evaluation for  HELLP syndrome or to exclude important differentials.
 -  Hyperuricemia (Uric acid lever)or increased creatinine may indicate decreasing renal function.
 -  Prothrombin time, partial thromboplastin time, and fibrinogen should be checked to rule out DIC.
 -  Peripheral smear may demonstrate microangiopathic hemolytic anemia.
 -  Complement levels can be used to differentiate from an acute exacerbation of a collagenvascular disease.
 -  Increased levels of SFlT-1 and reduced levels of PlGF predict subsequent development of preeclampsia.

IMAGING STUDIES

 -  CT scan of head if atypical presentation of eclampsia, possibility of intracerebral bleed, or prolonged postictal state
 -  Sonogram of fetus to evaluate for intrauterine growth restriction , amniotic fluid, placenta
 -  Sonogram of maternal liver if suspect subcapsular hematoma

TREATMENT

NONPHARMACOLOGIC THERAPY
Bed rest in left lateral decubitus position


ACUTE GENERAL Rx
Delivery is the treatment of choice and the only cure for the disease. This must be taken in the context of the  gestational age of the fetus, severity of the preeclampsia, and the likelihood of a successful induction and reliability of patient.
 -  Administer Magnesium sulfate 6 g IV loading dose, with 2 to 3 g maintenance or phenytoin at 10 to 15 mg/kg loading dose, then 200 mg IV q8h starting 12 hr after loading dose.
    -  Hydralazine 10 mg IV,
    -  Labetalol 20 to 40 mg IV,
    -  Nifedipine 20 mg SL
can be used for acute blood pressure control.
 -  Continuous fetal monitoring is needed.
 -  Epidural is anesthesia of choice for pain management in labor or cesarean section.
 -  All patients undergoing induction of labor should receive anti-seizure medications regardless of severity of disease.

CHRONIC Rx
 -  Mild preeclampsia < 37 wk: Close observation for worsening maternal or fetal condition, with delivery at >37 wk with favorable cervix or at 40 wk regardless of cervical status.
 -  Severe preeclampsia:

  • In the presence of maternal or fetal compromise, labor, or > 34 wk: Delivery.
  • 28 to 34 wk: Consider steroids with close monitoring,
  • < 24 wk: Consider termination of pregnancy.

 -  Methyldopa is drug of choice for long-term blood pressure control during pregnancy.

DISPOSITION
- Preeclampsia is a progressive and unpredictable disease process; a course of expectancy should be managed with caution. Up to 20% of patients who have seizures are normotensive.

REFERRAL

Obstetric management is indicated because of the insidious nature of the disease, with transfer of all cases ,34 wk to a facility with a level three nursery.

PEARLS & CONSIDERATIONS COMMENTS

 -  Low-dose aspirin 81 mg qd and calcium supplementation 1500 mg qd can be considered in high-risk patients to decrease the risk of recurrence.
 -  Begin after first trimester.
 -  Although the absolute risk of ESRD in women who have had preeclampsia is low, preeclampsia is a marker for an increased risk of subsequent ESRD.
 -  The development of preeclampsia may be one of the earliest identifiable risk markers for potential future cardiovascular disease in women. It has been shown that women who develop preeclampsia have a higher incidence
of cardiovascular risk factors including components of the metabolic syndrome within 1 yr of delivery.