Download Hypertensive Disorders of Pregnancy

Hypertensive Disorders
of Pregnancy
Case report
• You admitted a previously healthy
nullipara at 36 weeks’ gestation who
presented with new-onset periorbital
edema and is found to have blood
pressure readings of 150/100 to 155/105
mmHg, 4+ protein on urinary dipstick,
modest (ie, less than 2-fold) elevations in
her hepatic transaminases, a platelet
count of 105,000/µL and a mildly (8th
percentile) growth-restricted fetus.
Question?
• Does she have severe preeclampsia?
• Should you start parenteral magnesium
sulfate?
• Should you give antihypertensive therapy?
• Is delivery indicated?
Hypertensive Disorders of Pregnancy
• most common medical complications of
pregnancy,
• 5% to 10% of all pregnancies.
• 16% of maternal mortality in developed
countries.
• Classification include:
1. chronic hypertension (30%)
2. hypertensive unique to pregnancy (70%)
( gestational hypertension and preeclampsia).
Hypertensive Disorders of Pregnancy
• The spectrum of disease ranges from nonsevere to severe hypertension and multi organ
dysfunction.
• The incidence is dependent on:
• maternal age,
• race,
• underlying medical conditions.
HTN
• BP 140/90 or greater
• at least two occasions at least 4 hours apart but no
more than 1 week apart.
• in an upright position, after a 10-minute or longer rest
period.
• For patients in the hospital, either the patient sitting
up or in the left lateral position with the patient's arm
at the level of the heart.
• Avoidance tobacco or caffeine for 30 minutes
preceding the measurement
• Delta HTN
Abnormal proteinuria
• 300 mg or more of protein in 24 hours.
• The most accurate is obtained with a 24-hour urine
collection.
• A value of 1+ or greater correlates with 30 mg/dL.
• Proteinuria by dipstick is defined as 1+ or more on at
least two occasions at least 6 hours apart but no more
than 1 week apart.
• 24-hour urine collection should be performed the
diagnostic criteria .
• to use a clean sample, because blood, vaginal
secretions, and bacteria can increase the amount of
protein in urine.
Edema
• common finding in the gravid patient, (~50%)
• Lower extremity edema is the most typical
form.
• Pathologic edema is seen in nondependent
regions such as the face, hands, or lungs.
• Excessive, rapid weight gain of 2 pounds or
more per week is another sign of fluid
retention.
Classificationof Hypertension
• Gestational hypertension (most common)
developing after 20 weeks gestation or during the
first 24 hours postpartum without proteinuria or
other signs of preeclampsia (46%___progress to
preeclampcia
Transient hypertension resolves by 12 weeks
postpartum
– Preeclamsia or Eclampsia:
– Chronic HTN
– Superimpose preeclampsia
Classification of Hypertension
• Preeclamsia –Eclampsia developing after 20
weeks gestation with proteinuria; eclampsia is
the occurrence of seizure activity without other
identifiable causes
• Chronic hypertension prior to pregnancy, prior
to 20 weeks gestation, or after 12 weeks
postpartum
• Preeclampsia superimposed The development of
preeclampsia or eclampsia in a woman with
preexisting or chronic hypertension(New onset
pr;increase pr,or HTN,or plt <100000)
Preeclampsia or eclampsia
• Multisystemic,unknown cause,only in pregnancy
• 2%-- 7% incidence
• higher in : nulliparous women twin gestation
(14%) and previous preeclampsia (18%).
• symptoms are:
• headaches
• visual changes,
• epigastric or right upper quadrant pain
• nausea or vomiting.
Preeclampsia or eclampsia
• divided further into non-severe and severe .
• non-severe preeclampsia may progress to
fulminant disease.
• A particularly severe form of preeclampsia is
the HELLP syndrome
Criteria of Non-severe Preeclampsia
• SBP≥140 mm Hg and/or DBP ≥90 mm Hg on
two occasions at least 4 hours apart, typically
occurring after 20 weeks gestation (no more
than 1 week apart).
• Proteinuria of 300 mg in a 24-hour urine
collection or >1+ on two random sample urine
dipsticks at least 6 hours apart (no more than
1 week apart).
Criteria of Severe Preeclampsia
• SBP ≥160 mm Hg and/or DBP ≥110 mm Hg
• Proteinuria
• Oliguria <500 cc in 24 hours
• Thrombocytopenia platelet count <100,000/mm3
• Elevated liver function test results with persistent epigastric or right
upper quadrant pain
• Pulmonary edema
• Persistent, severe cerebral or visual disturbances.
HELLP syndrome
• hemolysis, elevated liver enzymes, and low
platelet count.
• hypertension and proteinuria might be absent
in 10% to 15% of women who develop HELLP
Risk Factors for Preeclampsia
Nulliparity
Chronic or vascular disease
(pregestational diabetes, renal disease, chronic
hypertension, rheumatic disease, connective tissue disease)
Molar pregnancy
hydrops
Multifetal
Fetal
gestation
Obesity and insulin resistance
Prior
pregnancy
complicated by preeclampsia
Risk Factors for Preeclampsia
Antiphospholipid antibody syndrome and thrombophilia
Family history of preeclampsia or eclampsia
Fetal aneuploidy
,Maternal infections, Maternal susceptibility genes,
Extremes of maternal age
, Partner-related factors
Etiologic Theories in Preeclampsia
• The syndrome is characterized by :
1. vasospasm;
2. hemoconcentration; and
3. ischemic changes in the placenta, kidney, liver,
and brain.
• These abnormalities usually are seen in women
with severe preeclampsia.
Etiologic Theories in Preeclampsia
Abnormal or
increased immune
response
Endothelial cell
injury
Abnormal
angiogenesis
Genetic
predisposition
Abnormal
coagulation or
thrombophilias
Etiologic Theories in Preeclampsia
Alterations in
nitric oxide levels
Increased oxygen
free radicals
Abnormal
cytotrophoblast
invasion
Dietary
deficiencies
Abnormal calcium
metabolism
Pathophysiology
Cardiovascular
• intense vasoconstriction with segmental spasm in
arterioles.
• alterations in the normal interactions of vasodilatory
(prostacyclin, nitric oxide) and vasoconstrictive
(thromboxane A2, endothelin) .
• higher arterial blood pressures (afterload).
• hemoconcentration:
• endothelial damage
leak
interstitial space, .
• lower intravascular volumes and less tolerance for the
blood loss.
Hematologic
•
thrombocytopenia (platelet count
<100,000/mm3).
• The suggested pathophysiology likely is vascular
endothelial damage or activation and higher
levels of thromboxane A2.
• microangiopathic hemolysis, (HELLP) (
schistocytes and increased LDH levels).
• A low hematocrit may signify hemolysis, and a
falsely high hematocrit may be due to
hemoconcentration.
Renal
• Vasospasm
renal perfusion GFR.
(normal pregnancy: GFR is increased up to 50%).
• creatinine rarely rise above normal pregnancy
levels (0.8 mg/dL).
• oliguria (defined as <500 cc in 24 hours) may
occur due to renal insufficiency.(ATN).
• pathognomonic renal lesion in preeclampsia is
called glomerular capillary endotheliosis, which is
swelling of the glomerular capillary endothelial
and mesangial cells.
Hepatic
• range from mildly elevated liver enzyme levels
to subcapsular liver hematomas and hepatic
rupture.
• 20% of maternal mortality in preeclampsia is
related to hepatic complications.
• The pathologic liver lesions seen on autopsy
are periportal hemorrhages, hepatocellular
necrosis, ischemic lesions, intracellular fatty
changes, and fibrin deposition
Central Nervous System
• Eclamptic convulsions major cause of maternal
mortality.
• etiology of eclampsia : coagulopathy, fibrin
deposition, and vasospasm.
• The most common finding in the brain is edema,
posterior hemispheres edema&hemorrhage:.
• headaches and visual disturbances ( scotomata;
blurred vision; and rarely, temporary blindness).
Fetus and Placenta
• hallmark placental lesion in preeclampsia is acute
atherosis of decidual arteries.
• This is due in part to the abnormal adaptation of
the spiral artery cytotrophoblast interface and
results in poor perfusion.
oligohydramnios;
IUGR
abruption
fetal distress;
fetal demise.
Prediction
• No good screening test.
• doppler ultrasonography: velocity of uterine
blood flow in the second trimester. Abnormal
velocity waveform is characterized by a high
resistance index or an early diastolic notch
(unilateral or bilateral).
• No for routine screening.
.
Prediction
Proposed Methods of Prediction of Preeclampsia
Maternal serum uric acid levels
Uterine artery Doppler
determinations
Elevated second-trimester
MSAFP,hCG levels, inhibin A
Elevated sFlt-1 and endoglin
Reduced placental growth factors
Plasma fibronectin values
Midpregnancy blood pressure
measurements
Urinary calcium excretion
Urinary kallikrein concentration
Platelet activation
Calcium-to-creatinine ratio
Excessive weight gain
Prevention
Diet and exercise ; protein or
salt restriction
No reduction
Insufficient
Magnesium or zinc
No reduction
Insufficient
Fish oil
No effect
Insufficient
Calcium
Reduced high risk and with low Recommended for high risk of
baseline dietary ca
gestational hypertension and in
communities with low intake
Low-dose aspirin
19% preeclampsia; 16%
neonatal deaths
Consider in high-risk
pregnancies
Heparin
Reduced in one trial
Insufficient
Antioxidant vitamins (C, E)
No reduction
No
Antihypertensive in chronic
hypertension (I)
severe HTN reduced by half; no No
reduction in preeclampsia
Management of non-severe
preeclampsia
• Ideally, a patient who has preeclampsia should be
hospitalized at the time of diagnosis.
• 24-hour urine collection for protein,
• hematocrit,
• platelet count,
• serum creatinine value,
• (AST) level.
• ultrasonography :AFI, fetal weight, gestational
age.
Management of non-severe
preeclampsia
• The only definitive cure for preeclampsia is delivery.
• The safety of the mother and a mature newborn.
• mild preeclampsia at term (>37 weeks), the general
consensus is delivery
• who is preterm (<37 weeks),
• controversy respect level of activity, diet, antihypertensive
medications, and delivery.
• Usually, these patients do not require immediate delivery,
and expectant management is warranted
• If expectant management is chosen, the second question
then becomes where to manage the patient in the hospital
or at home
Criteria for Home Management of non-severe
Preeclampsia
• Ability to comply with recommendations
• Normal laboratory tests
• No maternal symptoms
• Reassuring fetal status with appropriate
growth
Maternal and Fetal Evaluation in non-severe
Preeclampsia
• Maternal
Daily weight
Urine dipstick; 24-hour protein once weekly
Monitoring for severe preeclampsia symptoms
Prenatal visits twice per week
Lab tests (liver function tests, hematocrit, platelet
count once or twice per week)
• Fetal
Daily fetal movement
Nonstress test twice per week or biophysical profile
once per week
Ultrasound for growth every 3 to 4 weeks
Prompt Evaluation
• Signs and Symptoms of Preeclampsia That
Warrant :
• Nausea and vomiting
• Persistent severe headache
• Right upper quadrant or epigastric pain
• Scotoma
• Blurred vision
Management of non-severe
Preeclampsia
• Induction of labor is indicated in those patients
with a favorable cervix
• At 37 weeks or beyond, if the cervix is
unfavorable, two options:
• either cervical ripening and delivery
• continued expectant management with maternal
and fetal evaluation.
• The preferred mode of delivery remains vaginal.
• A cesarean section should be performed for
obstetric indications only
Management of non-severe
Preeclampsia
• In the past, while in labor, patients with mild
preeclampsia received intravenous magnesium
sulfate (MgSO4) for seizure prophylaxis.
• There is no support in the literature for the need
or the optimal timing to begin the MgSO4
infusion, and this should be left to the discretion
of the physician.
• In mild the authors recommend to individualize
each case for the use of MgSO4.
Management of non-severe
Preeclampsia
• Pain management in labor should be individualized.
• Close monitoring of blood pressure intrapartum is
necessary.
• Antihypertensive medications to keep blood pressure
values below 160 / 110 mm Hg
• most commonly used intravenous medications for this
purpose are labetalol and hydralazine.
• not to drop the blood pressure too rapidly, lead to
reduced renal perfusion and reduced placental
perfusion.
• who receive MgSO4 also are at risk for postpartum
hemorrhage due to uterine atony.
Management of non-severe
Preeclampsia
• Patients should be monitored closely for at
least 12 to 24 hours postpartum.
• Postpartum eclampsia occurs in 25% of
patients.
• It is not clear if MgSO4 should be continued in
the postpartum period.
• There is no need for continued seizure
prophylaxis beyond 24 hours postpartum
Maternal and Fetal Complications in Severe Preeclampsia
• Maternal
Abruptio placentae (10%-40%)
Disseminated coagulopathy/HELLP syndrome
(10%-20%)
Pulmonary edema/aspiration (2%-5%)
Acute renal failure (1%-5%)
Eclampsia (<1%)
Liver failure or hemorrhage (<1%)
Stroke (rare)
Death (rare)
Long-term cardiovascular morbidity
Maternal and Fetal Complications in Severe Preeclampsia
• Fetal
Preterm delivery (15%-67%)
Fetal growth restriction (10%-25%)
Hypoxic neurologic injury (<1%)
Perinatal death (1%-2%)
Long-term cardiovascular morbidity
associated with low birth weight
Management of severe
Preeclampsia
• Any patient with severe preeclampsia should be admitted
and observed initially in a labor and delivery unit
• Workup should include assessment for fetal well-being,
monitoring of maternal blood pressures .
• Laboratory evaluation should include:
• 24-hour urine collection for total protein,
• hematocrit,
• platelet count, creatinine ,AST levels.
• Intravenous MgSO4 should be initiated at time of admission.
• initial ultrasonographic examination with umbilical artery
Doppler studies for fetal growth and amniotic fluid index
should be obtained as well.
Acute treatment of severe hypertension
Hydralazine
Labetalol
5-“10 mg i.v. every 20
min
20-40 mg i.v. every
10-15 min
30 mga
220 mga
10-20 mg p.o. every
30 min
Long-term treatment of hypertension
50 mga
Methyldopa
250 mg b.i.d.
4 g/d
Labetalol
100 mg b.i.d.
2,400 mg/d
Atenolol
50 mg q.d.
100 mg/d
Nifedipine
Avoid in women with
asthma or congestive
heart failure
Associated with IUGR
Propanolol
40 mg b.i.d.
640 mg/d
thyroid disease
Hydralazine
10 mg t.i.d.
100 mg/d
Nifedipine
10 mg b.i.d.
120 mg/d
left ventricular
hypertrophy
women with diabetes
Diltiazem
120-180 mg q.d.
540 mg/d
Thiazide diuretic
12.5 mg b.i.d.
50 mg/d
ACE inhibitors/ARB
CHF; may be added as
second agent;
not to be used if
preeclampsia
develops or IUGR is
present
Not to be used after
16-“18 wk
Management of severe
Preeclampsia
• delivery is considered in all women with
severe preeclampsia
• prolonging the pregnancy may be hazardous
to the mother with little benefit to the fetus.
• In patients at 33 to 34 weeks gestation,
steroids should be administered and delivery
planned within 48 hours unless otherwise
indicated.
Management of severe
Preeclampsia
• In patients with severe prematurity , expectant
management significantly improves neonatal
outcome.
• The goal in these patients is to gain at least 48
hours that glucocorticoids can be
administered for fetal benefit.
• They should be counseled regarding the risks
and benefits of expectant management
Management of severe Preeclampsia
• Ultrasonography for fetal growth every 2 to 3 weeks.
• Maternal laboratory evaluation should be done daily
or every other day.
• If a stable maternal and fetal course is maintained,
expectant management continued until 34 weeks.
• The development of any worsening change in maternal
or fetal status warrants delivery regardless of
gestational age.
• A woman with a nonviable fetus should be terminated.
• above 23 weeks, expectant
Management of severe Preeclampsia
• Maternal blood pressure control
• Medications orally or by the intravenous
route
• management of acute hypertension are
hydralazine and labetalol.
• avoid a sudden drop blood pressure
precipitating cerebral ischemia, decreased
renal perfusion, and decreased placental
perfusion.
Intrapartum management
• Include:
• close blood pressure control,
• continuous fetal monitoring, and
• intravenous MgSO4 administration.
• urinary catheter should be placed in order to closely monitor fluid
balance. Urine output should be >100 cc every 4 hours.
• A trial of labor is indicated in patients with severe preeclampsia.
• Pain management ( Epidural anesthesia is a reasonable option),
• uterine atony while receiving continuous MgSO4 infusion.
Methylergonovine (Methergine) is contraindicated in these
patients.
• MgSO4 continue for 24 hours postpartum.
• monitor blood pressure, reflexes, and fluid
status.
Expeditious Delivery in Severe Preeclampsia
• Maternal
Uncontrolled severe hypertension (160 /110 mm Hg)
despite maximum doses of antihypertensive (i.v.
labetalol [220 mg], hydralazine, and oral nifedepine)
Eclampsia or persistent cerebral symptoms
Pulmonary edema
Placenta abruption
Thrombocytopenia (platelet count less than 100,000)
or elevated liver enzymes (HELLP syndrome)
Serum creatinine of 1.2 mg/dL or more or oliguria
(<0.5 mL/kg per hour)
Expeditious Delivery within 48-72 Hours in Severe Preeclampsia
• Fetal
Severe fetal growth restriction (<5th percentile
for gestational age)
Persistant oligohydramnios (amniotic fluid index
of <5 cm on at least two occasions >24 hours
apart)
Umbilical artery Doppler studies with persistent
reverse end-diastolic flow
Biophysical profile <4 on two occasions at 4 hours
apart
Repetitive late deceleration or severe variable
deceleration or loss of variability
Diagnosis of HELLP Syndrome
Hemolysis
Abnormal peripheral smear
LDH >600 U/L
Bilirubin >1.2 mg/dL
Elevated liver enzymes
Serum AST >70 U/L
LDH >600 U/L
Low platelets
Platelet count <100,000/mm3
Differential Diagnosis of HELLP Syndrome
• Acute fatty liver of pregnancy
Appendicitis
Cerebral hemorrhage
Diabetes insipidus
Gallbladder disease
Gastroenteritis
Glomerulonephritis
Hemolytic uremic syndrome
Hyperemesis gravidarum
Idiopathic thrombocytopenia
Pancreatitis
Pyelonephritis
Systemic lupus erythematosus
Thrombophilias
Thrombotic thrombocytopenic purpura
Viral hepatitis, including herpes
Eclampsia
• much higher in developing countries.
• major cause of maternal and perinatal
morbidity and mortality worldwide.
• wide spectrum of signs and symptoms, from
mild isolated hypertension to multiorgan
failure.
• Prevention of eclampsia is one of the goals in
treating preeclamptic patients with MgSO4
Management of Eclampsia
• During seizure, the main therapy is supportive care.
1. avoiding injury,
2. maintaining oxygenation,
3. minimizing the risk of aspiration.
• Most seizures are self-limited, lasting 1 to 2 minutes.
• hypoxia or acidosis both in mother and fetus.
• MgSO4 is the drug of choice for the prevention
• 10% of eclamptic women receiving MgSO4 will have
further seizures.
Management of the Eclamptic Patient
• Avoid injury
– Padded bedside rails
– Physical restraints
• Maintain oxygenation to mother and fetus
– Oxygen at 8-10 L per minute by face mask
– Monitor oxygenation and metabolic status with transcutaneous pulse
oximetry or arterial blood gas measurements
• Minimize aspiration
– Lateral decubitus position
– Suctioning of vomitus and oral secretions
– Obtain chest x-ray after cessation of convulsion to rule out aspiration
• Initiate MgSO4 to prevent recurrent seizures
• Control severe hypertension
• Initiate the delivery process
Management of the Eclamptic Patient
• abnormalities in the fetal heart rate pattern.
• bradycardia,
• decreased variability, late decelerations, and reflex tachycardia.
• These abnormalities typically resolve within 5 to 10 minutes after the
convulsion.
• not to proceed directly to cesarean
• Stabilization of the mother is the priority.
• . If prolonged signs of fetal compromise occur indicating possible
abruptio placentae, consideration should be given to proceed with
operative delivery.
• Vaginal delivery is the preferred route after an eclamptic seizure.
• Induction of labor should be performed with oxytocin or
prostaglandins.
• maintained on MgSO4 throughout her labor.
Regimens of Magnesium Sulfate in eclampsia
• Loading dosage: -4-6 g i.v. over 20-30 min (6 g of 50%
solution diluted in 150 cc D5W)
• Maintenance dosage:
Additional 2 g over 5-10 min (1-2 times) can be given
with persistent convulsions
If convulsions persist (2% of cases), give 250 mg
sodium amobarbital i.v. over 5 min
In status eclampticus: intubation and muscular
paralysis
Intramuscular dosage: 10 g i.m. (20 mL of 50% MgSO4,
one half of the dose in each buttock
Clinical Finding
Serum Level
Loss of patellar reflex
10meq/l
Feeling of warmth, flushing
Double vision
Somnolence
Slurred speech
Muscular paralysis
Respiratory difficulty
Cardiac arrest
>10meq/l
Management of Magnesium Toxicity
•
•
•
•
Discontinue MgSO4 infusion
Begin supplemental oxygen administration
Obtain serum magnesium level
Administer 1 g calcium gluconate (10 cc 10%
calcium gluconate) by slow intravenous push
• Repeat calcium gluconate administration, if
necessary
• If respiratory arrest occurs, begin
cardiopulmonary resuscitation.
chronic hypertension
• The management differs for the low-risk group
versus the high-risk group.
• low-risk group have, by definition, mild
hypertension without evidence of organ
damage.
• The high-risk group has either severe
hypertension (SBP 160 /110 mm Hg) or mild
hypertension with evidence of organ
involvement.
chronic hypertension
• Low risk:
• Weekly nonstress tests should begin at 34
weeks.
• increased to twice weekly with evidence of
growth restriction or oligohydramnios.
• low-risk group may continue their pregnancies
up to 41 weeks,
chronic hypertension
• high-risk :
• use of antihypertensive pharmacotherapy.
• first-trimester 24-hour urine collection for total protein
level.
• visits in the first and second trimesters should be every 2 to
3 weeks
• then weekly in the third trimester if clinically indicated.
• ultrasonography for estimated fetal weight and amniotic
fluid volume every 4 weeks starting at 26 weeks.
• Weekly nonstress testing or biophysical profile
assessments should begin at 28 weeks.
chronic hypertension
• low-risk chronic hypertension who do not develop superimposed
preeclampsia have pregnancy outcomes similar to those of the
general population.
• Antihypertensive not affect perinatal outcome and is not necessary,
• if the SBP reaches 160 /105 mm Hg, or target organ damage
develops.
• 24-hour urine for protein determination in the first trimester
• at least monthly visits in the first and second trimester
• .Visits should be every 1 to 2 weeks after 32 weeks, looking
carefully for the development of superimposed preeclampsia.
• ultrasonography for fetal growth and amniotic fluid assessment
every 4 weeks beginning at 32 weeks,
chronic hypertension
• visits and fetal testing may need to be increased
dependent on (increasing HTN, superimposed
preeclampsia, decreased AF volume, or IUGR.
• superimposed preeclampsia is suspected or
uncontrolled hypertension develops, the patient
should be hospitalized, preferably at a tertiary care
center.
• timing of delivery is dependent on complications and
gestational age.
• In general, pregnancies in patients with high-risk
chronic hypertension should not be continued past 40
weeks.