Hypertensive

disorders in

pregnancy Dr Lama Al-Mehaisen,MD,MRCOG

Associated professor /obstetrics and gynaecology

urogynaecology

Dr Lama Al-Mehaisen,MD,MRCOG

Associated professor /obstetrics and

gynaecology/urogynaecology

Classification of hypertension in

pregnancy There is now a widely agreed classification system for hypertension in

pregnancy.

pregnant women who develop or present with hypertension in pregnancy

have one of three conditions:

Non-proteinuric pregnancy-induced hypertension.

Pre-eclampsia.

Chronic hypertension.

.

Gestational hypertension –Gestational hypertension refers to hypertension (systolic

≥140 and <160 mmHg, and/or diastolic ≥90 and <110 mmHg) without proteinuria or

other signs/symptoms of preeclampsia-related end-organ dysfunction that develops

after 20 weeks of gestation.

Development of proteinuria upgrades the diagnosis to preeclampsia. Even without

proteinuria, women who develop a systolic blood pressure ≥160 mmHg and/or diastolic

blood pressure ≥110 mmHg or other features of severe disease are managed with the

same approach as women with preeclampsia with severe features.

Chronic/preexisting hypertension – defined as hypertension that antecedes pregnancy or

is present on at least two occasions before the 20th week of gestation or persists longer than

12 weeks postpartum. It can be primary (primary hypertension"essential hypertension") or

secondary to a variety of medical disorders

Preeclampsia superimposed upon chronic/preexisting hypertension – Superimposed

preeclampsia is defined by the new onset of proteinuria, significant end-organ dysfunction, or

both after 20 weeks of gestation in a woman with chronic/preexisting hypertension. For

women with chronic/preexisting hypertension who have proteinuria prior to or in early

pregnancy, superimposed preeclampsia is defined by worsening or resistant hypertension

(especially acutely) in the last half of pregnancy or development of signs/symptoms of the

severe end of the disease spectrum

Eclampsia refers to the development of grand mal seizures in a woman with preeclampsia

in the absence of other neurologic conditions that could account for the seizure.

Non-proteinuric pregnancy-induced hypertension (otherwise known as

gestational hypertension)

is hypertension that arises for the first time in the second half of

pregnancy and in the absence of proteinuria.

It is not associated with adverse pregnancy outcome and mild and

moderate increases in blood pressure in this setting do not require

treatment.

However, up to one-third of women who present with gestational

hypertension will progress to pre-eclampsia.

Chronic hypertension

Women who have confirmed hypertension in the first half of pregnancy most likely

have chronic hypertension.

Chronic hypertension, of whatever type, can predispose to the later development of

superimposed pre-eclampsia.

Even in the absence of superimposed preeclampsia, chronic hypertension is

associated with increased maternal and fetal morbidity and pregnancies

complicated by chronic hypertension should therefore be regarded as high risk.

The physiological fall in blood pressure that occurs in the first trimester secondary to

peripheral vasodilatation can mask chronic hypertension.

egrees of hypertension Mild: diastolic blood pressure 90–99 mmHg, systolic blood pressure 140–149 mmHg.

Moderate: diastolic blood pressure 100–109 mmHg, systolic blood pressure

150–159 mmHg.

Severe: diastolic blood pressure ≥110 mmHg, systolic blood pressure ≥160 mmHg

Pre-

PET

Preeclampsia

Preeclampsia refers to the new onset of hypertension and

proteinuria or hypertension and significant end-organ dysfunction

with or without proteinuria after 20 weeks of gestation in a

previously normotensive woman

It may also develop postpartum.

Severe hypertension or signs/symptoms of significant end-organ

injury represent the severe end of the disease spectrum

Oliguria was also removed as a characteristic of severe disease.

PREVALENCE

In a systematic review, 4.6 percent of pregnancies worldwide were complicated by preeclampsia .

Variations in prevalence among countries reflect, at least in part, differences in the maternal age distribution and proportion of nulliparous pregnant women in the population

Prevalence also varies by gestational age.

Preeclampsia is less prevalent before 34 weeks of gestation.

RISK FACTORS

1. Past history of preeclampsia (RR 8)

2. Preexisting medical conditions:

1. Pregestational diabetes This increase has been related to a variety of factors, such

as underlying renal or vascular disease, high plasma insulin levels/insulin resistance,

and abnormal lipid metabolism

2. Chronic hypertension. fivefold compared with women without this risk factor

3. Systemic lupus erythematosus

4. Antiphospholipid syndrome

3. Prepregnancy body mass index >25 and body mass index (BMI) >30 two- to threefold,

4. Chronic kidney disease (CKD) In some studies, as many as 40 to 60 percent of women

were diagnosed with preeclampsia in the latter half of pregnancy

5. Multifetal pregnancy The risk increases with increasing numbers of fetuses

6.First pregnancy (nulliparity)

7.A family history of preeclampsia

8.Prior pregnancy complications associated with placental insufficiency –Fetal growth restriction, abruption, or stillbirth

9.Advanced maternal age

(maternal age ≥35 ,Older women tend to have additional risk factors, such as

diabetes mellitus and chronic hypertension, that predispose them to developing

preeclampsia.

10.Use of assisted reproductive technology WEAK THEORY

Nulliparity

Preeclampsia in a previous pregnancy

Age >40 years or <18 years

Family history of preeclampsia

Chronic hypertension

Chronic renal disease

Autoimmune disease (eg, antiphospholipid syndrome, systemic lupus erythematosus)

Vascular disease

Diabetes mellitus (pregestational and gestational)

Multifetal gestation

Obesity

Black race

Hydrops fetalis

Woman herself was small for gestational age

Fetal growth restriction, abruptio placentae, or fetal demise in a previous pregnancy

Prolonged interpregnancy interval if the previous pregnancy was normotensive; if the previous pregnancy was preeclamptic, a short

interpregnancy interval increases the risk of recurrence

Partner-related factors (new partner, limited sperm exposure [eg, previous use of barrier contraception])

In vitro fertilization

Obstructive sleep apnea

Elevated blood lead level

Posttraumatic stress disorder

Clinical factors that have been associated with an increased risk of developing preeclampsia

Incidence

Pre-eclampsia complicates approximately 2–3% of pregnancies, but the

incidence

varies depending on the exact definition used and the population studied.

Globally, around 70,000 women die annually of pre-eclampsia, making

it a leading cause of maternal death in low-resource settings.

Pre-eclampsia is defined as hypertension of at least 140/90 mmHg recorded

on at least two separate occasions and at least 4 hours apart and in the

presence of at least 300 mg protein in a 24-hour collection of urine, arising de

novo after the 20th week of pregnancy in a previously normotensive woman

and resolving completely by the sixth postpartum week.

( preeclampsia is defined by the new onset of proteinuria, significant end-

organ dysfunction,

RISK FACTORS TO DEVELOPING PET

Risk factors for pre-eclampsia

First pregnancy.

Multiparous with a previous history of pre-eclampsia.

Pre-eclampsia in any previous pregnancy.

10 years or more since last baby.

Age 40 years or more.

Body mass index (BMI) of 35 or more.

Family history of pre-eclampsia (in mother or sister).

Booking diastolic blood pressure of 80 mmHg or more.

Booking proteinuria ( of ≥1+ on more than one occasion or quantified at ≥0.3g/24 h).

Multiple pregnancy.

Certain underlying medical conditions: pre-existing hypertension;

pre-existing renal disease;

pre-existing diabetes;

antiphospholipid antibodies.

There is no cure for pre-eclampsia other than to end the pregnancy by delivering

the baby (and placenta).

This can be a significant problem if pre-eclampsia occurs early in pregnancy, particularly

at gestations below 34 weeks.

Therefore, management strategies are aimed at minimizing risk to the mother in order to

permit continued fetal growth. In severe cases this is often not possible.

The principles of management of pre-eclampsia are

Early recognition of the symptomless syndrome.

Awareness of the serious nature of the condition in its severest

form.

Adherence to agreed guidelines for admission to hospital,

investigation and the use of antihypertensive and anticonvulsant

therapy.

Well-timed delivery to pre-empt serious maternal or fetal

complications.

Postnatal follow-up and counselling for future pregnancies.

Treatment of hypertension

The commonest cause of death in women who die of pre-eclampsia in the UK is

cerebral bleeding secondary to uncontrolled systolic blood pressure.

Therefore, the aim of antihypertensive therapy is to lower the blood pressure and

reduce the risk of maternal cerebrovascular accident without reducing uterine blood

flow and compromising the fetus.

There are a variety of antihypertensives used in the management of pre-eclampsia.

Established preventive interventions include low-dose aspirin (typically 75 mg

daily), which modestly reduces the risk of pre-eclampsia in high-risk women;

calcium supplementation may also reduce risk, but only in women with low dietary

intake.

Additional points in management

Iatrogenic premature delivery of the fetus is often required in severe preeclampsia.

If her condition allows, the mother should be transferred to a center with adequate facilities to care for

her baby, and prior to 34 weeks’ gestation

steroids should be given intramuscularly to the mother to reduce the chance of neonatal respiratory

distress syndrome.

In the case of spontaneous or induced labor and if clotting studies are normal, epidural anaesthesia is

indicated as it helps control blood pressure.

Ergometrine is avoided in the management of the third stage as it can significantly increase blood

pressure.

Postnatally, blood pressure and proteinuria will resolve. However, in a minority of cases one or both

persist beyond 6 weeks and this suggests the presence of underlying chronic hypertension or renal

disease.

Additionally, a careful search should be made postnatally for underlying medical disorders in women

who present with severe pre-eclampsia before 34 weeks’ gestation.

Criteria for the diagnosis of preeclampsia

Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least two occasions at least four hours apart after 20 weeks of gestation in a

previously normotensive patient AND the new onset of one or more of the following*:

•Proteinuria ≥0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥0.3 (mg/mg) (30 mg/mmol) in a random urine specimen or dipstick ≥2+ if a quantitative

measurement is unavailable

•Platelet count <100,000/microL

•Serum creatinine >1.1 mg/dL (97.2 micromol/L) or doubling of the creatinine concentration in the absence of other renal disease

•Liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory

•Pulmonary edema

•Cerebral or visual symptoms (eg, new-onset and persistent headaches not accounted for by alternative diagnoses and not responding to usual doses of analgesics¶;

blurred vision, flashing lights or sparks, scotomata)

In a patient with preeclampsia, the presence of one or more of the following indicates a diagnosis of

"preeclampsia with severe features"

Severe blood pressure elevation:

Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg on two occasions at least four hours apart while the patient is on bedrest

(antihypertensive therapy may be initiated upon confirmation of severe hypertension, in which case criteria for severe blood pressure elevation can be satisfied

without waiting until four hours have elapsed)

Symptoms of central nervous system dysfunction:

•New-onset cerebral or visual disturbance, such as:Photopsia, scotomata, cortical blindness, retinal vasospasm •Severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that persists and progresses despite analgesic therapy and not accounted for

by alternative diagnoses

Hepatic abnormality:

Severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by an alternative diagnosis or serum transaminase

concentration ≥2 times the upper limit of the normal range, or both

Thrombocytopenia:

<100,000 platelets/microL

Renal abnormality:

Renal insufficiency (serum creatinine >1.1 mg/dL [97.2 micromol/L] or a doubling of the serum creatinine concentration in the absence of other renal disease)

Pulmonary edema

DIAGNOSTIC CRITERIA

Preeclampsia

Professional guidelines generally agree that the diagnosis of preeclampsia

should be made in a previously normotensive woman with the new onset of

hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90

mmHg on at least two occasions at least four hours apart) and proteinuria after 20

weeks of gestation

In the absence of proteinuria, the diagnosis can still be made if new-onset

hypertension is accompanied by signs or symptoms of significant end-organ

dysfunction, as described before.

Preeclampsia with severe features

This diagnosis is made after 20 weeks of gestation in previously normotensive women who develop:

Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg and proteinuria (with or without signs and symptoms of significant end-organ dysfunction).

Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg (with or without proteinuria) and one or more of the following signs and symptoms of significant end-organ dysfunction:

New-onset cerebral or visual disturbance, such as:

Photopia (flashes of light) and/or scotomata (dark areas or gaps in the visual field).

Severe headache (ie, incapacitating, "the worst headache I've ever had") or headache that persists and progresses despite analgesic therapy.

Altered mental status.

Severe, persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by an alternative diagnosis or serum transaminase concentration ≥2 times upper limit of normal for a specific laboratory, or both.

<100,000 platelets/microL.

Progressive renal insufficiency (serum creatinine >1.1 mg/dL [97.3 micromol/L]; some guidelines also include doubling of serum creatinine concentration in the absence of other renal disease).

Pulmonary edema.

OVERVIEW OF PATHOPHYSIOLOGY

It involves both maternal and fetal/placental factors.

Shallow placentation and failure to remodel the spiral arteries of the decidua and myometrium early in

pregnancy, weeks to months before development of clinical manifestations of the disease, have been

well documented

Failure to establish an adequate uteroplacental blood flow can result in relatively hypoxic trophoblast

tissue, which may promote an exaggerated state of oxidative stress in the placenta

This appears to alter placental villous angiogenesis, leading to poor development of the fetoplacental

vasculature and abnormal vascular reactivity.

Placental secretion of antiangiogenic factors (sFlt-1 and endoglin) that bind vascular endothelial

growth factor and placental growth factor in the maternal circulation appears to result in widespread

maternal vascular dysfunction, leading to hypertension, proteinuria, and the other clinical

manifestations of preeclampsia

CLINICAL PRESENTATION

Most affected patients are nulliparous or at high risk for the disease.

Most present with new-onset hypertension and proteinuria at ≥34 weeks of gestation, sometimes during labor

Approximately 10 percent of affected women develop these signs and symptoms at <34 weeks of gestation (ie, early-onset preeclampsia) and rarely as early as 20 to 22 weeks.

In approximately 5 percent of preeclampsia cases, the signs and symptoms are first recognized postpartum (ie, postpartum preeclampsia), usually within 48 hours of delivery

The degree of maternal hypertension and proteinuria as well as the presence/absence of other clinical manifestations of the disease are highly variable .

Patient evaluation

Accurate assessment of blood pressure

Routine laboratory evaluation

should have a complete blood count, serum creatinine level, liver chemistries (LDH, AST, ALT), and urinary protein determination (protein:creatinine ratio or 24-hour urine protein) .

Coagulation studies (prothrombin time, partial thromboplastin time, fibrinogen) are not routinely obtained but are indicated in patients with additional complications, such as abruptio placentae, severe bleeding, or severe liver dysfunction.

Assessment of fetal status

At a minimum, a nonstress test or biophysical profile is performed.

Ultrasound is indicated to evaluate amniotic fluid volume and estimate fetal weight

Indications for neurology consultation

in women with neurological deficits/ ocular signs and symptoms, or a severe persistent headache that does not respond to a dose of acetaminophen

severe headache ("worst headache of my life") is sufficiently characteristic of subarachnoid hemorrhage that this diagnosis should prompt neurology consultation and consideration of imaging

Potential clinical findings

Hypertension Epigastric pain

Neurologic Headache

Visual symptoms Generalized hyperreflexia

Seizure Stroke

Peripheral edema Pulmonary edema

Abruptio placentae

Oliguria Transient oliguria (less than 100 mL over 4 hours) is common in labor or the

first 24 hours of the postpartum. Urine output may decrease to <500 mL/24 hours in

women at the severe end of the disease spectrum.

Potential laboratory findings

Hemolysis which is a finding in severe disease. Elevation in the serum indirect bilirubin level also

suggest hemolysis, whereas elevations in lactate dehydrogenase are usually related to liver dysfunction.

Proteinuria –

≥0.3 g protein in a 24-hour urine specimen.

Random urine protein:creatinine ratio ≥0.3 mg protein/mg creatinine (some clinicians opt to confirm presence of ≥0.3 g protein with a 24-hour collection).

Protein ≥2+ (30 mg/dL)

Proteinuria generally increases as preeclampsia progresses, but increased urinary protein excretion may be a late finding It usually remains <5 g/day,

Elevated creatinine

The physiologic increase in glomerular filtration rate (GFR) during a normal pregnancy results in a decrease in serum creatinine concentration, which falls to a range of 0.4 to 0.8 mg/dL . The serum creatinine concentration in women with preeclampsia generally remains in this range or only slightly elevated.

A creatinine level >1.1 mg/dL indicates the severe end of the disease spectrum.

Decreased platelet count

A platelet count less than 150,000/microL occurs in approximately 20 percent of

patients with preeclampsia

The severe end of the disease spectrum is characterized by a platelet count less

than 100,000/microL.

Thrombocytopenia is the most common coagulation abnormality in preeclampsia.

Hemoconcentration – Hemoconcentration may result from contraction of the

intravascular space secondary to vasospasm, as well as capillary leaking. Hematocrit

typically increases.

Coagulation studies – The prothrombin time, partial thromboplastin time, and

fibrinogen concentration are not affected by preeclampsia, unless there are additional

complications, such as severe thrombocytopenia , abruptio placentae, severe

bleeding, or severe liver dysfunction

Liver chemistries

Liver function tests are normal, except at the severe end of the disease spectrum

Elevation in the serum indirect bilirubin level suggests hemolysis.

Abnormalities in liver chemistries are due to reduced hepatic blood flow

Hyperuricemia – The association between hyperuricemia and preeclampsia has been

known for decades. The cause is most likely related to a reduction in GFR. However, the

increase in serum uric acid is often greater than expected for mild reductions in GFR,

leading to the hypothesis that decreased tubular secretion or increased reabsorption in

the proximal renal tubules

Potential sonographic findings

Fetal ultrasound

suboptimal fetal growth due to reduced uteroplacental perfusion

Fetal growth restriction may be accompanied by oligohydramnios due to

redistribution of the fetal circulation away from the kidneys and toward more

vital organs, particularly the brain

In contrast, preeclampsia that develops clinically at term tends to be

associated with fetal growth that is appropriate for gestational age and normal

amniotic fluid volume.

Fetal anatomy is usually normal. However, three population-based studies

have reported a relationship between fetal congenital cardiac defects and

maternal preeclampsia, particularly preterm preeclampsia

How to monitor fetal complications in PET

Ultrasound assessment of:

fetal size;

amniotic fluid volume;

maternal and fetal Dopplers.

Antenatal cardiotocography, used in conjunction with ultrasound surveillance,

provides a useful but by no means infallible indication of fetal wellbeing. A loss

of baseline variability or decelerations may indicate fetal hypoxia.

Differential diagnoses

1-Preexisting hypertension versus preeclampsia

Hypertension occurring before the 20th week is usually due to preexisting hypertension rather than to preeclampsia

Proteinuria is usually present and increases with time in preeclampsia, occasionally reaching the nephrotic range

Preeclampsia is more common in nulliparas than in multiparas.

Preeclampsia is more common in older (>40 years) nulliparas

2-Superimposed preeclampsia

Reproductive age women with primary (essential) hypertension typically have no or mild proteinuria, so severe proteinuria suggests development of superimposed preeclampsia.

In women with chronic/preexisting hypertension who have proteinuria prior to or in early pregnancy, superimposed preeclampsia is difficult to diagnose definitively, but should be suspected when there is a significant worsening of hypertension (especially acutely) in the last half of pregnancy or development of signs/symptoms associated with the severe end of the disease spectrum.

An elevated uric acid level may help to distinguish superimposed preeclampsia from primary hypertension

3-Exacerbation of preexisting renal disease

Significant clues to the diagnosis of preeclampsia with severe features are the presence of systemic

manifestations of the disorder, such as thrombocytopenia; increased serum levels of

aminotransferases; and visual symptoms

Onset of disease in the first half of pregnancy suggests exacerbation of underlying renal disease

rather than preeclampsia.

Laboratory evidence suggestive of exacerbation of renal disease includes the presence of findings

specific for disease activity (eg, low complement levels in a patient with systemic lupus

erythematosus, urinalysis consistent with a proliferative glomerular disorder [red and white

cells and/or cellular casts]).

4-Antiphospholipid syndrome

Hypertension, proteinuria, thrombocytopenia, and other signs of significant end-organ dysfunction

can be seen in antiphospholipid syndrome (APS).

The absence of laboratory evidence of antiphospholipid antibodies excludes this diagnosis

5-Acute fatty liver of pregnancy (AFLP)

Anorexia, nausea, and vomiting are common clinical features of AFLP.

Low-grade fever can be present in AFLP but does not occur in preeclampsia/HELLP.

AFLP is associated with more serious liver dysfunction: hypoglycemia, elevations in serum ammonia, and disseminated intravascular coagulation are common features, while unusual in preeclampsia/HELLP.

AFLP is also usually associated with more significant renal dysfunction compared with preeclampsia/HELLP.

6-Thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS)

7-Exacerbation of systemic lupus erythematosus (SLE)

Flares of SLE are likely to be associated with hypocomplementemia and increased titers of anti-DNA antibodies

8-Pheochromocytoma

Symptoms of pheochromocytoma that help to make this distinction include generalized sweating, palpitations, tremor, pallor, dyspnea, generalized weakness, and panic attack-type symptoms.

MANEGMENT AND PROGNOSIS

General approach:

Delivery — Preeclampsia with features of severe disease is generally regarded as an indication for

delivery at ≥34+0 weeks of gestation after maternal stabilization or with labor or prelabor rupture of

membranes

Delivery minimizes the risk of development of serious maternal complications, such as cerebral

hemorrhage, hepatic rupture, renal failure, pulmonary edema, seizure, bleeding related to

thrombocytopenia, myocardial infarction, stroke, acute respiratory distress syndrome, retinal injury, or

abruptio placentae, and fetal complications such as growth restriction and fetal demise

With the exception of fetal growth restriction, any of these life-threatening complications can occur

suddenly.

PREECLAMPSIA WITH FEATURES OF SEVERE DISEASE

Expectant management of selected cases Pregnancies in which the fetus has not attained a viable gestational age, pregnancies ≥34

weeks of gestation, and pregnancies in which the maternal and/or fetal condition is unstable are not candidates for expectant management.

Attempting to prolong pregnancy in these settings subjects the mother and fetus to significant risks with relatively small potential benefits; therefore, delivery is preferable.

Expectant management allows administration of a course of antenatal corticosteroids and may provide time for further fetal growth and maturation.

For consideration of this approach, both the mother and fetus should be stable, closely monitored in a hospital with an appropriate level of newborn care, and cared for by, or in consultation with, a maternal-fetal medicine specialist.

Limiting expectant management to pregnancies ≥24 weeks and <34 weeks of gestation. Selection of appropriate candidates for this approach and management of these pregnancies are discussed separately.

PREECLAMPSIA WITHOUT FEATURES OF SEVERE DISEASE

General approach

Term pregnancies: Delivery — at ≥37 weeks of gestation (HYPITAT trial )

Women with preeclampsia benefited from early intervention, without incurring an increased risk of

operative delivery or neonatal morbidity:

Routine induction was associated with a 30 % reduction in the composite maternal outcome

The induced group had a significantly lower rate of cesarean delivery

Preterm pregnancies:

Expectant management

At preterm gestational ages, the risks of serious sequelae from disease progression need to be balanced with

the newborn risks from preterm birth.

When mother and fetus are stable

However, at any gestational age, evidence of severe hypertension,or nonreassuring tests of fetal well-being

are generally an indication for prompt delivery.

Prior to 34+0 weeks, guidelines from major medical organizations generally recommend expectant

management of preeclampsia without features of severe disease,

Components of expectant management

Inpatient versus outpatient care

Patient education

Activity

Laboratory follow-up

Monitoring blood pressure and treatment of hypertension .

Assessment of fetal growth

Assessment of fetal well-being

Antenatal corticosteroids

Timing of delivery

INTRAPARTUM MANAGEMENT

Route of delivery The route of delivery is based on standard obstetrical indications.

Intrapartum monitoring Continuous maternal-fetal monitoring is indicated intrapartum

Fluids

Fluid balance should be monitored closely to avoid excessive administration, since women with preeclampsia are at risk of pulmonary edema and significant third-spacing, especially at the severe end of the disease spectrum.

A maintenance infusion of a balanced salt or isotonic saline solution at approximately 80 mL/hour is often adequate for a patient who is nil by mouth and has no ongoing abnormal fluid losses, such as bleeding

Oliguria that does not respond to a modest fluid bolus (eg, a 300 mL fluid challenge) suggests renal insufficiency and should be tolerated to reduce the potential for iatrogenic pulmonary edema

In patients with renal insufficiency, it is important to revise the maintenance infusion rate to account for the volume of fluid used to infuse intravenous medications.

Management of hypertension

Severe hypertension in labor should be treated promptly with intravenous labetalol (avoid in patients with asthma) or hydralazine or oral nifedipine to prevent stroke

Antihypertensive medications do not prevent eclampsia.

ANTIHYPERTENSIVE MEDICATION

Methyldopa

is a centrally acting antihypertensive agent

It has a long-established safety record in pregnancy.

However, it can only be given orally,

it takes upwards of 24 hours to take effect and has a range of unpleasant side-effects include ng sedation and depression. These properties limit its usefulness.

Labetalol

is an alpha-blocking and beta-blocking agent. It has a good safety record in pregnancy and can be given orally and intravenously. It is

the first drug of choice in most national guidelines including the current National

Institute for Health and Care Excellence (NICE) guideline, Hypertension in Pregnancy.

Nifedipine is

a calcium-channel blocker with a rapid onset of action.

It can, however, cause severe headache that may mimic worsening disease.

In severe cases of fulminating disease, an intravenous infusion of hydralazine or labetalol can be titrated rapidly against changes in the blood pressure.

Drug Initial dose Follow-up

Labetalol

20 mg IV gradually over 2 minutes.

•Repeat BP measurement at 10-minute intervals:If BP remains above

target level at 10 minutes, give 40 mg IV over 2 minutes. •If BP remains above target level at 20 minutes, give 80 mg IV over 2

minutes. •If BP remains above target level at 30 minutes, give 80 mg IV over 2

minutes. •If BP remains above target level at 40 minutes, give 80 mg IV over 2

minutes.

Cumulative maximum dose is 300 mg. If target BP is not achieved,

switch to another class of agent.

A continuous IV infusion of 1 to 2 mg/minute can be used instead of intermittent therapy or started after 20 mg IV

dose.

Requires use of programmable infusion pump and continuous noninvasive monitoring of blood pressure and heart rate.

Adjust dose within this range to achieve target blood pressure.

Cumulative maximum dose is 300 mg. If target BP is not achieved,

switch to another class of agent.

Hydralazine 5 mg IV gradually over 1 to 2 minutes.*

Adequate reduction of blood pressure is less predictable than with IV labetalol.

•Repeat BP measurement at 20-minute intervals:If BP remains above

target level at 20 minutes, give 5 or 10 mg IV over 2 minutes,

depending on the initial response. •If BP remains above target level at 40 minutes, give 10 mg IV over 2

minutes, depending on the previous response.

Cumulative maximum dose is 30 mg. If target BP is not achieved, switch

to another class of agent.

Nifedipine immediate release

10 mg orally.

May be associated with precipitous drops in BP in some women, with associated FHR decelerations for which

emergency cesarean delivery may be indicated. As such, this regimen is not typically used as a first-line option and is

usually reserved only for women without IV access . If used, FHR should be monitored while administering short-acting

nifedipine.

•Repeat BP measurement at 20-minute intervals:If BP remains above

target at 20 minutes, give 10 or 20 mg orally, depending on the initial

response. •If BP remains above target at 40 minutes, give 10 or 20 mg orally,

depending on the previous response.

If target BP is not achieved, switch to another class of agent.

Nifedipine extended release 30 mg orally.

If target BP is not achieved in 1 to 2 hours, another dose can be

administered.

If target BP is not achieved, switch to another class of agent.

Nicardipine (parenteral)

The initial dose is 5 mg/hour intravenously by infusion pump and can be increased to a maximum of 15 mg/hour.

Onset of action is delayed by 5 to 15 minutes; in general, rapid titration is avoided to minimize risk of overshooting

dose.

Requires use of a programmable infusion pump and continuous noninvasive monitoring of blood pressure and heart

rate.

Adjust dose within this range to achieve target BP.

Seizure prophylaxis

Candidates for seizure prophylaxis

We administer intrapartum and postpartum seizure prophylaxis to all women with preeclampsia, based

on data from randomized trials that demonstrated that magnesium sulfate treatment reduced the risk of

eclampsia as seen In the MAGPIE trial (magnesium sulfate for prevention of eclampsia trial)

It is important to emphasize that seizure prophylaxis does not prevent progression of disease unrelated

to convulsions.

Approximately 10 to 15 percent of women in labor with preeclampsia without severe features will

develop signs/symptoms of preeclampsia with severe features (eg, severe hypertension, severe

headache, visual disturbance, epigastric pain, laboratory abnormalities) or abruptio placentae, whether

or not they receive magnesium therapy

We do not administer seizure prophylaxis to women with only gestational hypertension pregnancy-

related hypertension

it is recommended that magnesium sulfate should be used for the prevention and treatment of seizures

in women with preeclampsia with severe features.

Seizure prophylaxis

Magnesium sulfate

magnesium sulfate was safer and more effective for prevention of recurrent seizures than phenytoin, diazepam, and pethidine).

The primary effect is thought to be central.

Hypotheses states its function as membrane stabilization in the central nervous system secondary to its actions as a nonspecific calcium channel blocker

Another theory is that it promotes vasodilatation of constricted cerebral vessels by opposing calcium-dependent arterial vasospasm, thereby reducing cerebral barotrauma

Contraindications

myasthenia gravis

pulmonary edema

Timing

Magnesium sulfate for seizure prophylaxis is usually initiated at the onset of labor

or induction, or prior to and throughout the duration of a cesarean delivery

It is usually not administered to stable antepartum patients, but is sometimes

given to women with preeclampsia with severe features while they are being

considered for expectant management.

Prolonged antepartum therapy (more than five to seven days) should be avoided as

it has been associated with adverse effects on fetal bones when it was

administered for long-term tocolysis

Seizure prophylaxis

Rapid infusion of magnesium sulfate causes diaphoresis, flushing, and warmth, probably

related to peripheral vasodilation and a drop in blood pressure. Nausea, vomiting,

headache, muscle weakness, visual disturbances, and palpitations can also occur

Dyspnea or chest pain may be symptoms of pulmonary edema, which is a rare side

effect.

Although magnesium sulfate is a weak tocolytic, labor duration does not appear to be

affected by its administration

The risk of postpartum hemorrhage, possibly related to uterine atony from magnesium's

tocolytic effects, was slightly increased in one trial

Rarely, hypocalcemia becomes symptomatic (myoclonus, delirium, electrocardiogram

abnormalities).

Cessation of magnesium therapy will restore normal serum calcium levels

Toxicity — Magnesium toxicity is uncommon in women with good renal function

Toxicity correlates with the serum magnesium concentration:

loss of deep tendon reflexes occurs at 3.5 to 5.0 mmol/L),

respiratory paralysis at 5.0 to 6.5 mmol/L),

cardiac conduction is altered at >7.5 mmol/L)

cardiac arrest occurs at >12.5 mmol/L

When to check magnesium levels — We obtain serum magnesium levels every six hours as an adjunct to

clinical assessment in patients who have:

A seizure while receiving magnesium sulfate

Clinical signs/symptoms suggestive of magnesium toxicity (eg, absent patellar reflex, respiratory rate

≤12 breaths/minute)

Renal insufficiency (creatinine >1.1 mg/dL [110 micromol/L)

Following serum magnesium levels is not required if the woman's clinical status is closely monitored

every one to two hours for signs and symptoms of potential magnesium toxicity and no abnormalities

are noted.

Antidote

Calcium gluconate

15 to 30 mL of a 10 percent solution (1500 to 3000 mg) intravenously over 2 to 5 minutes is

administered to patients in cardiac arrest or with severe cardiac toxicity related to

hypermagnesemia

Calcium chloride

5 to 10 mL of a 10 percent solution (500 to 1000 mg) intravenously over two to five minutes

is an acceptable alternative but is more irritating and more likely to cause tissue necrosis

with extravasation.

POSTPARTUM CARE

General postpartum care

monitor vital signs every two hours while the patient remains on magnesium sulfate,

repeat laboratory tests (eg, platelet count, creatinine, liver function tests) daily until two

consecutive sets of data are normal or trending to normal. Postpartum patients receiving both

magnesium and opioids are at a higher risk for cardiopulmonary depression.

Pain should be controlled with the minimally effective dose of opioid

Persistent severe hypertension should be treated; some patients will have to be discharged on

antihypertensive medications, which are discontinued when blood pressure returns to normal.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes exacerbate hypertension,

NSAIDs should be used preferentially over opioid analgesics [

We suggest frequently monitoring blood pressure in the hospital or at home for the first 72

hours postpartum and if it is in an acceptable range, then blood pressure is measured at a

follow-up visit 7 to 10 days postdelivery.

Some patients will require longer monitoring; continued follow-up is needed

until all of the signs and symptoms of preeclampsia have resolved. Alternative

diagnoses should be sought in those with persistent abnormal findings after

three to six months

Some women are diagnosed with preeclampsia for the first time after

delivery. We suggest administration of magnesium sulfate to those with new-

onset hypertension and headache or blurred vision, severe hypertension.

PROGNOSIS

Prognostic issues include the risk of recurrent preeclampsia and related

complications in subsequent pregnancies and long-term maternal health risks.

Recurrence 16 percent developed recurrent preeclampsia and 20 percent

developed hypertension alone in a subsequent pregnancy

The recurrence risk varies with the severity and time of onset of the initial episode

Women with early-onset, severe preeclampsia are at greatest risk of recurrence

The risk of preeclampsia in a second pregnancy is much lower (5 to 7 percent) for

women who had preeclampsia without severe features in their first pregnancy and

less than 1 percent in women who had a normotensive first pregnancy (excluding

abortions)

Recurrent preeclampsia is more likely following a singleton pregnancy with

preeclampsia than a twin pregnancy with preeclampsia

Prevention of recurrence

Low-dose aspirin therapy during pregnancy modestly reduces the risk of

preeclampsia in women at high risk for developing the disease.