Elevated blood pressure during pregnancy is a significant problem affecting many 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 drop below early pregnancy and prepregnancy levels. Not uncommonly, 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 both be 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. Conceptually, the MAP is one-third the distance from the diastolic pressure to the systolic pressure. This can be expressed mathematically as:

MAP = ((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.

Pre-Eclampsia

Pre-eclampsia is a clinical syndrome characterized by elevated blood pressure, and protein in the urine. Older terminology used the term “toxemia of pregnancy”, and included fluid retention and increased reflexes as part of the clinical syndrome.

Pre-eclampsia (by definition) occurs only during pregnancy and resolves completely after pregnancy. It is seen most often as women approach full term, but it can occur much earlier. It’s cause is unknown, but it occurs more often among:

• Women carrying their first child
• Multiple pregnancies
• Pregnancies with excessive amniotic fluid (polyhydramnios)
• Younger (<17) and older (>35) women

Ordinarily, blood pressure decreases during the middle trimester, compared to pre-pregnancy levels. After the middle trimester, blood pressure tends to rise back to the pre-pregnancy levels. Sometimes, blood pressure becomes elevated.

Sustained blood pressures exceeding 140/90 are considered abnormal and may indicate the presence of pre-eclampsia. For women with pre-existing 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.

Diagnosis

The presence of hypertension and proteinuria are essential to the diagnosis of pre-eclampsia.

Pregnant women can normally 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*:

Category	Negative	Trace	1+	2+	3+	4+
Dipstick Results	<15 mg/dL	15-29 mg/dL	30 mg/dL	100 mg/dl	300 mg/dl	>2000 mg/dL
Equivalent 24-hour Results*	<150 mg	150-299 mg	300-999 mg	1000-2999 mg	3-20 g	>20 g

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 but not all women with pre-eclampsia will demonstrate increased reflexes (clonus).

Most women pre-eclampsia have no symptoms. Among those who do 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, but an underlying common feature is abnormal placental development.

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 modestly 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.

Consequences

Pre-eclampsia,  and its’ variants (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 pre-eclampsia are mild, and most of the more severe forms are successfully treated (delivery) before the serious consequences can unfold. In some severe cases, even early diagnosis and treatment will prove unsuccessful in avoiding the more serious consequences.

Clinical Course

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. Others display a more aggressive disease, with deterioration of both maternal and fetal condition (severe features). Some of the points of differentiation are listed here.

Problem	Pre-Eclampsia	Severe Features
Blood Pressure	>140/90	>160/110
Proteinuria	1+ (300 mg/24 hours)	2+ (1000 mg/24 hours)
Edema	+/-	+/-
Increased reflexes	+/-	+
Upper abdominal pain	–	+
Headache	–	+
Visual Disturbance	–	+
Decreased Urine Output	–	+
Elevation of Liver Enzymes	–	+
Decreased Platelets	–	+
Increased Bilirubin	–	+
Elevated Creatinine	–	+

Pre-eclampsia with Severe Features

Pre-eclampsia with severe features is associated with blood pressures in excess of 160/110

This condition 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 of pre-eclampsia, 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.

Treatment

The definitive treatment of pre-eclampsia is delivery. The urgency of delivery depends on the gestational age and the severity of the disease and presence or absence of severe features.

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 effective reasonably effective in preventing seizures. Because the risk of eclampsia continues after delivery, MgSO4 is frequently continued for 24 to 48 hours after delivery.

Intravenous Dosing

Magnesium sulfate, 4-6 grams are given over 15 to 20 minutes, as a loading dose. This is followed by 1-3 grams every hour, so long as the patellar reflexes remain present. The magnesium is continued for 24 hours following delivery.

Intramuscular Dosing

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.

Magnesium Sulfate Toxicity

The therapeutic margin (distance between effective dose and toxicity) is relatively thin with magnesium sulfate, so some precautions need to be taken to prevent overdose. The biggest problem with MgSO4 is respiratory depression (10 meq/L) and respiratory arrest (>12 meq/L). Cardiovascular collapse occurs at levels exceeding 25 meq/L. Magnesium levels can be measured in a hospital setting, but 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.

In the case of respiratory arrest or severe respiratory depression, the effects of MgSO4 can be reversed by the administration of calcium.

Calcium Gluconate (Ca++) 1 gm IV push.

Antihypertensives

If BP is persistently greater than 160/110, administer an antihypertensive agent to lower the BP to levels closer to 140/90. This will diminish the risk of cerebral hemorrhage. Don’t drop the pressure too far (below a diastolic of 90) as uterine perfusion may be compromised.

Magnesium sulfate, used primarily as seizure prophylaxis, is a mild antihypertensive agent, due to its’ smooth muscle relaxing properties. After loading with magnesium sulfate, drops of systolic pressures and diastolic pressures are usually observed.

Labetalol is an effective antihypertensive agent, commonly used to control blood pressure in pre-eclamptic women with severe features. 20 mg is given intravenously over 2 minutes, followed by additional doses, and increasing doses every 10 minutes until the desired results are achieved.

• Initial dosing should not exceed 300 mg
• The effect of each dose takes 5-10 minutes to appear
• Beneficial effects will last 3-6 hours.

Hydralazine is another potent antihypertensive drug, widely used in the context of pre-eclampsia. 5-10 mg IV every 15-20 minutes can be administered.

• Total dose should not exceed 30 mg, and no more than 20 mg at a time.
• The effect of each dose takes10-30 minutes to appear
• Beneficial effects will last 2-4 hours.

Eclampsia

Eclampsia means that maternal seizures have occurred in association with pre-eclampsia.

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 (described above), followed by prompt delivery, often requiring a cesarean section. If convulsions persist despite MgSO4, consider using any benzodiazepine as to stop the seizures. Commonly used medications include:

• Diazepam 10 mg IV push (5-10 mg every 5-10 minutes. 5 mg/minute. Max dose 30 mg)
• Lorazepam  4 mg IV push (2 mg/minute. May be repeated in 4-6 hours)
• Midazolam 1-2 mg IV push (2 mg/minute. May be repeated every 5 minutes until seizures stop)
• General anesthesia (while setting up for a cesarean section or instrumented delivery)

HELLP Syndrome

The HELLP Syndrome is a variant of pre-eclampsia and is characterized by:

• Hemolysis
• Elevated Liver Enzymes
• Low Platelets

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

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.