Pre-eclampsia and Eclampsia

Elevated blood pressure during pregnancy is a significant problem affecting as many as 10% of pregnancies. In some cases, the hypertension is pre-existing, while in others, it develops over the course of pregnancy. Occasionally, it does both.

Normal Blood Pressure Changes during Pregnancy.

During the middle trimester, blood pressure (both systolic and diastolic) normally drops below early pregnancy and prepregnancy levels. Frequently, there is a widening of the pulse pressure (difference between systolic and diastolic levels). These changes are associated with the significant reduction in peripheral vascular resistence and some degree of AV shunting within the uterus and intervillous space. The decreased peripheral resistance is compensated by the relative tachycardia so often found among pregnant women.

In the third trimester, blood pressure usually rises to approximately pre-pregnancy levels. Elevations significantly higher than that are considered abnormal.

Hypertension

The definition of hypertension varies, but one common definition is the sustained elevation of BP above 140/90. Most obstetricians believe that if either the systolic or the diastolic pressure is elevated on a sustained basis, that hypertension exists. A few require that bothbe elevated. As a practical matter, in most cases of hypertension, both are elevated.

The diastolic pressure elevation is probably the more important of the two and mean arterial pressure (MAP) during the second or third trimester are used by some to assess risk. As you remember, the Mean Arterial Pressure is one-third the distance from the diastolic pressure to the systolic pressure. This can be expressed mathematically by adding two diastolic pressures to the systolic pressure, and dividing the total by three.

MAP = ^[1]2 x diastolic) + (systolic/3

During the second trimester, if the average of all MAPs ? 90, there is a significant increased risk for perinatal mortality, morbidity and impaired fetal growth dynamics.

During the 3rd trimester, MAP ? 105 indicates and increased risk

Women with pre-existing hypertension face increased risks during pregnancy for diminished uterine blood flow, pre-eclampsia, and if uncontrolled, maternal stroke. For these reasons, it is important that those with pre-existing hypertension be appropriately treated and followed during pregnancy.

Toxemia of Pregnancy is an older term for pre-eclampsia and eclampsia.

The only difference between pre-eclampsia and eclampsia is the presence of maternal seizures in eclampsia.

This is a clinical syndrome characterized by elevated blood pressure, protein in the urine, fluid retention and increased reflexes. It occurs only during pregnancy and resolves completely after pregnancy. It is seen most often as women approach full term, but it can occur as early as the 22nd week of pregnancy. Its cause is unknown, but it occurs more often in:

• • Women carrying their first child
  • Multiple pregnancies
  • Pregnancies with excessive amniotic fluid (polyhydramnios)
  • Younger (<17) and older (>35) women
  • Women with pregestational diabetes
  • Obese women
  • Women with Pre-existing hypertension, renal disease, and phospholipid syndrome
  • Women with a Personal or Family history of pre-eclampsia

Remember that blood pressure normally decreases during the middle trimester, and then rises back toward the pre-pregnancy levels. Sometimes, blood pressure becomes elevated. Sustained blood pressures exceeding 140/90 are considered abnormal.

If, after a careful search for other factors, the only abnormality that has developed during pregnancy is mild hypertension, this is called “Gestational Hypertension” and is considered less threatening than pre-eclampsia.

Importantly, those with gestational hypertension must have BPs less than 160/110, have no significant proteinuria, and no other pre-eclampsia symptoms, signs or laboratory findings. Of course, these patients need to be closely watched because some of them will go on to develop the other findings that we associate with the more dangerous pre-eclampsia.

For women with pre-pregnancy hypertension, a sustained worsening of their hypertension over pre-pregnancy levels by 30 systolic and 15 diastolic is often used to indicate the possible presence of super-imposed pre-eclampsia.

Let’s Consider the Diagnosis

Hypertension and Protein in the urine are the two essential findings used to confirm the diagnosis of toxemia of pregnancy.

Normal pregnant women can lose up to 200 mg of protein in the urine in 24 hours. If protein loss exceeds 300 mg in 24 hours, this is considered proteinuria. Urine dipstick analysis for protein measures only a single point in time and does not necessarily reflect protein loss over 24 hours. Nonetheless, assuming average urine production of about a liter a day, and consistent loss throughout the 24 hour period, a 1+ finding on a spot urine is equivalent to 300 mg or more in 24 hours.

Edema is part of the classical description of pre-eclampsia, along with hypertension, proteinuria, and increased maternal reflexes. Some but not all women with pre-eclampsia demonstrate fluid retention (as evidenced by edema or sudden weight gain exceeding 2 pounds per week). Some amount of dependent edema is so common among pregnant women, that its presence, by itself, is not particularly alarming. Likewise, the absence of edema in a pregnant woman with a persistently elevated blood pressure and significant proteinuria should not dissuade you from making the diagnosis of pre-eclampsia. The diagnosis hinges on the presence of persistent hypertension and significant proteinuria.

Some but not all women with toxemia will demonstrate increased reflexes. However, everyone is different, and stress can also increase reflexes, so I don’t generally rely on the presence or absence of clonus to help me make the diagnosis of pre-eclampsia. I believe the most useful application of reflex testing is in a woman who has already been diagnosed with pre-eclampsia. In this patient, the severity of her reflex responses (3-4+, or even clonus) will help me gauge how close she may be to having an eclamptic seizure. The more brisk the reflexes, more danger of seizure.

Most women with pre-eclampsia have no symptoms. Many feel quite good and are confused about why everyone around them acts so alarmed. Among those with symptoms are such findings as:

• • Headache, usually frontal but sometimes occipital, analgesic-resistent.
  • Visual disturbances, including blurring and scotomata
  • Aching pain in the right upper quadrant, caused by stretching of the liver capsule.

Cause(s) of Pre-eclampsia

The cause or causes are not known. Some common associations are first pregnancies, pre-existing hypertension, hydatidiform mole, and those conditions which lead to overdistension of the uterus, such as polyhydramnios and multiple gestation.

Physiologically, women with this condition demonstrate peripheral vascular spasm, leading to injury of the capillary walls and leakage of intravascular fluids into the extracellular spaces. Due to the somewhat impaired kidney function that accompanies this condition, serum creatinine levels are usually modestly increased (>1.0 mg%). Hemoconcentration results in a modest increase in hemoglobin and hematocrit. Both contribute to an elevation of BUN, usually >12 mg%. Uric acid is typically >5.5 mg% due to increased production in association with peripheral vascular sluggishness.

Let’s consider the Consequences

Pre-eclampsia, eclampsia and the HEELP syndrome, are very dangerous, with potentially serious consequences for both the mother and fetus. Among these are:

• • Preterm delivery
  • Placental abruption
  • Precipitous delivery
  • Maternal convulsions
  • Decreased uteroplacental perfusion
  • Fetal growth restriction
  • Increased perinatal mortality
  • Maternal renal failure
  • Maternal disseminated intravascular coagulation (DIC) and hemorrhage
  • Liver failure
  • Pulmonary edema
  • Maternal stroke

Fortunately, most cases of toxemia of pregnancy are mild, and most of the more severe forms are successfully treated before the serious consequences can unfold. In some severe cases, even early diagnosis and treatment will prove unsuccessful in avoiding the more serious consequences.

Pre-eclampsia

Toxemia of pregnancy is subdivided into two categories: pre-eclampsia and eclampsia. The difference is the presence of seizures in women with eclampsia.

The clinical course of pre-eclampsia is variable. Some women demonstrate a mild, stable course of the disease, with modest elevations of blood pressure and no other symptoms (mild pre-eclampsia). Others display a more aggressive disease, with deterioration of both maternal and fetal condition (severe pre-eclampsia). Notice that there is no “moderate” pre-eclampsia, only mild and severe.

With mild pre-eclampsia, the patient has mildly elevated blood pressures, at least 140/90, but not as high as 160/110. She will have 1+ protein on her urine spot checks, which represent 24 hour production of between 300 and 1000 mg. She may or may not have edema and increased reflexes.

With severe pre-eclampsia, she will have at least one additional finding beyond the expected findings for pre-eclampsia. These additional findings include the symptoms of upper abdominal pain, severe headaches, and visual disturbances. Additional findings include laboratory tests showing decreased urine output (less than 500 ml in 24 hours), decreased platelets (less than 100,000 per ml) increased creatinine, increased uric acid, and increased liver enzymes of ALT and AST.

The definitive treatment of pre-eclampsia is delivery.

The urgency of delivery depends on the gestational age of the fetus, the status of the fetus, and the severity of the disease of the mother.

Severe pre-eclampsia usually requires urgent delivery (within hours) more or less regardless of gestational age. In this situation, the risk of serious complications (placental abruption, growth restriction, liver failure, renal failure, hemorrhage, coagulopathy, seizures, death) will generally take precedence over the fetal benefit of prolonging the pregnancy. Induction of labor is preferred, unless the maternal condition is so tenuous and the cervix so unfavorable that cesarean section is warranted.

In milder cases, particularly if remote from term or with an unfavorable cervix, treatment may range from hospitalization with close observation to initial stabilization followed by induction of labor following preparation of the cervix over the course of several days. In the most mild, selected cases, outpatient management might be considered with careful monitoring of maternal and fetal condition.

Magnesium Sulfate

Traditionally, magnesium sulfate(MgSO4) has been used to treat pre-eclampsia. Magnesium sulfate, in high enough doses, is a reasonably effective anti-convulsant, mild anti-hypertensive and mild diuretic. While other agents may be more potent in each of these individual areas, none combines all three of these features into a single drug. The world’s experience with magnesium sulfate to treat pre-eclampsia is extensive and these unique features provide considerable reassurance in employing it in these clinical settings. Magnesium sulfate is given IM, IV or both. All are reasonably effective in preventing seizures. Because the risk of eclampsia continues after delivery, MgSO4 is frequently continued for 24 to 48 hours after delivery.

• • Magnesium sulfate 10 gm in a 50% solution, one-half (5 gm) IM, injected deeply into each upper outer buttock quadrant. Every 4 hours thereafter, Magnesium sulfate 5 gm IM is injected into alternating buttocks. Repeat injections are postponed if patellar reflexes are absent. Because these injections are painful, 1 ml of 2% lidocaine is sometimes added to the magnesium. This schedule gives therapeutic levels of magnesium (4-7 meq/L)
  • Because IM magnesium sulfate does not initially achieve its therapeutic levels for 30 to 45 minutes, in cases of severe pre-eclampsia, an IV bolus of magnesium sulfate can be added. 4 gm magnesium sulfate as a 20% solution can be given slowly over at least 5 minutes, followed by the IM injections described above.
  • Magnesium sulfate 4 gm IV, slowly, over at least 5 minutes, followed by 2 gm IV/hour. Some prefer a higher loading dose of 6 gm.

The therapeutic margin (distance between effective dose and toxicity) is relatively thin with magnesium sulfate, so some precautions need to be taken. If magnesium levels are sub-therapeutic, the patient will still be vulnerable to seizures. If magnesium levels are too great, the most serious problem is respiratory depression (occurring at around 10 meq/L) and respiratory arrest (occurring at >12 meq/L). Cardiovascular collapse occurs at levels exceeding 25 meq/L. Magnesium levels can be measured in a hospital setting, with a target range of between 5 to 8 meq/L. Clinical management works about as well and is non-invasive.

The patellar reflexes (knee-jerk) disappear as magnesium levels rise above 10 meq/L. Periodic checking of the patellar reflexes and withholding MgSO4 if reflexes are absent will usually keep your patient away from respiratory arrest. This is particularly important if renal function is impaired (as it often is in severe pre-eclampsia) since magnesium is cleared entirely by the kidneys.

Likewise, respiratory depression occurs prior to respiratory arrest, so breathing can be monitored and magnesium withheld if respirations are less than 12 breaths/minute.

Finally, since magnesium is excreted in the urine, should renal failure occur, an unaltered dose of magnesium is likely to result in hypermagnesemia. As long as urine output exceeds 100 ml in 4 hours, no modification of the magnesium is necessary on the basis of impaired renal function.

In the case of respiratory arrest or severe respiratory depression, the effects of MgSO4 can be quickly reversed by the administration of calcium. The favored dosage of Calcium Gluconate (Ca++) is 1 gm IV over 5 minutes. This should be given only in the event of life-threatening depression, because milder forms of hypermagnesemia can be effectively controlled by reducing the magnesium dose. Understand that when you abruptly reverse the effects of the magnesium, you are also removing the protective halo against seizures.

If BP is persistently greater than 160/110, an antihypertensive agent is usually given to lower the BP to levels closer to 140/90. There are a number of commonly-used agents used for this purpose:

• • Labetalol 20 mg IV with another 20 mg every 10 minutes to a maximum dose of 300 mg. The followup doses may be increased up to 80 mg at a time.
  • Nifedipine 30 mg (Sustained Release) orally once a day. May be increased to 60 mg once a day.
  • Hydralazine 5-10 mg IV every 15-20 minutes.

Regardless of the medication, try not to drop the pressure too far (below a diastolic of 90) as uterine perfusion may be compromised.

Let’s talk for a while about Eclampsia

Eclampsia means that a previously pre-eclamptic patient experiences maternal seizures.

These tonic/clonic episodes last for several minutes and may result in bite lacerations of the tongue. During the convulsion, maternal respirations stop and the patient turns blue because of the desaturated hemoglobin in her bloodstream. As the attack ends, she gradually resumes breathing and her color returns. Typically, she will remain comatose for varying lengths of time. If convulsions are frequent, she will remain comatose throughout. If infrequent, she may become arousable between attacks. If untreated, convulsions may become more frequent, followed by maternal death. In more favorable circumstances, recovery occurs.

Eclampsia should be aggressively treated with magnesium sulfate, followed by prompt delivery, often requiring a cesarean section. If convulsions persist despite MgSO4, consider Valium 10 mg IV push.

It’s important to remember that there can be other causes for seizures in pregnant women, among them strokes, hypoxia, hemorrhage, illicit drug use, brain tumors, infection and a variety of metabolic disorders.

During an eclamptic seizure, the fetal heart rate will typically respond with a bradycardia, lasting 3 to 5 minutes, followed by a reactive tachycardia with decreased variability and occasional decelerations. While troubling to watch, these changes will generally resolve with the return of maternal oxygenation and placental perfusion. Occasionally, a placental abruption occurs in association with the eclamptic seizure and in those cases, the fetal heart rate abnormalities fail to resolve, prompting consideration for immediate delivery.

There is also the HELLP Syndrome, H-E-L-L-P

The HELLP Syndrome is characterized by:

• • Hemolysis (H)
  • Elevated Liver Enzymes (EL)
  • Low Platelets (LP)

This serious condition is associated with severe pre-eclampsia and the treatment is similar…delivery with prophylaxis against maternal seizures.

In addition, these patients may need platelet transfusions, particularly with platelet counts well below 50,000. Despite this, oozing is frequently an on-going problem until the HELLP syndrome gradually cools off.

Unlike pre-eclampsia, patients with HELLP syndrome may continue to experience clinical problems for days to weeks or even months.

If the HELLP syndrome is mild, it may gradually resolve spontaneously, but more severe forms often require intensive, prolonged care to achieve a favorable outcome.