Transcript Preeclampsia

Hypertensive Disorders in
Pregnancy
Professor Hassan
Chairman Department of Obstetrics and Gynecology
Faculty of Medicine
King Abdulaziz University
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Definitions (Preeclampsia)
Pathogenesis
Diagnosis
Clinical Manifestations and Complications
Treatment
Eclampsia
Definitions
Preeclampsia :
• Systolic BP ≥ 140 Mm Hg Or Diastolic BP ≥ 90 Mm Hg
Occurring ≥ 20 Weeks' Gestation
• Proteinuria ≥ 300 Mg In A 24 Hour Urine Collection.
Eclampsia: The Development Of Grand Mal Seizures In A Woman With
Preeclampsia.
Chronic Hypertension:
Systolic Pressure > Or =140 mmHg, Diastolic Pressure > Or =90 mmHg,
Or Both, That Is Present Before The 20th Week Of Pregnancy.
Gestational Hypertension (Transient Hypertension Of Pregnancy):
Systolic Pressure ≥ Or =140 mmHg, Diastolic Pressure ≥ Or =90 mmHg,
Or Both, That Develop ≥ 20th Week Of Pregnancy In A Previously
Normotensive Woman, But With Out Proteinuria.
Preeclampsia superimposed upon chronic hypertension:
• New onset proteinuria or greatly increases proteinuria after 20 weeks
of gestation.
• Sudden exacerbation of BP to the severe range (systolic > or =160
mmHg or diastolic > or =110 mmHg) in the last half of pregnancy.
• or other signs of multisystem involvement such as thrombocytopenia
or transaminitis in a woman with prior hypertension.
Report of the National High Blood pressor Education program Working group on high blood
pressure in pregnancy. Am J Obs gyn 2000;183:S1-22
(Special conditions)
Preeclampsia and other Hypertensive Disorders in
Pregnancy
INCIDENCE:
• Hypertensive disorders complicate 12 to 22 percent of
pregnancies
• Preeclampsia occurs in approximately 3 to 14 percent
of all pregnancies worldwide
•Incidence ranges between 3 and 7 percent in nulliparas
and between 0.8 and 5.0 percent in multiparas
Pathogenesis
Pathogenesis of Preeclampsia
IMPAIRED TROPHOBLAST INVASION
ABNORMAL TROPHOBLAST DIFFERENTIATION
PLACENTAL ISCHEMIA
IMMUNOLOGIC FACTORS
GENETIC FACTORS
SYSTEMIC ENDOTHELIAL DYSFUNCTION
Representation of Myometrial arteries and endometrial arteries
In normal pregnancy
Invasive CTB invade maternal decidua and vasculature (zone v).
Placental Dysfunction May Initiate The Systemic Vasospasm,
Ischemia, And Thrombosis That Eventually Damages
Maternal Organs.
CNS
headache,
local
neurologica
l deficits,
and seizure
Renal
necrosis
leads to a
decreased
glomerular
filtration
rate and
proteinuria
Liver injury
from
hepatocellul
ar necrosis
causes right
upper
quadrant
pain and
elevated
liver
function
tests
Cardiovascular
manifestations
include a lower
than normal
intravascular
volume, increased
cardiac output,
and an abnormally
elevated
peripheral
vascular
resistance
Microangiopath
ic hemolysis
leads to anemia
and
thrombocytopeni
a.
Fetal: Placental infarction and abruptio placentae lead to intrauterine
growth retardation and fetal death.
Impaired Trophoblast invasion
Medical conditions that predispose to vascular
insufficiency
Obstetrical conditions that increase placental mass with a
relative decrease in placental blood flow
Placental hyperfusion/ischemia
Fetal Growth retardation
Oligohydramnios
Imbalance of prostacyclin/Thromboxane
Systemic endothelial damage
Systemic Clinical Manifestations
CNS
Renal
Hematological
Hepatic
Prevention of PET
Methods Used to Prevent Preeclampsia
High-protein and low-salt diet
Nutritional supplementation (protein)
Calcium
Magnesium
Zinc
Fish and evening primrose oil
Antihypertensive drugs including diuretics
Antithrombotic agents
Low-dose aspirin
Dipyridamole
Heparin
Vitamins E and C
Risk Factors for Preeclampsia
• Primiparity
• Prior personal or family history of preeclampsia
• Obesity
• Hypertension
• Diabetes mellitus
• Renal diseases
• Collagen vascular diseases
• Thrombophilia
• Multiple gestation
Clinical Manifestations and
Complications
Clinical Manifestation of Preeclampsia
Maternal:
Hypertension:
Renal:
Hepatic:
Hematologic:
Neurologic:
Fetal/Neonatal:
IUGR:
Clinical Manifestation of Preeclampsia
Hypertension:
Systolic BP ≥ 40 mmHg or Diastolic ≥ BP 90 mmHg in a woman who was
normotensive prior to 20 weeks of gestation.
Renal:
• Proteinuria:
≥ 0.3 g protein in a 24-hour urine specimen (or 2+ on dipstick).
Proteinuria is due, in part, to impaired integrity of the glomerular barrier and
altered tubular handling of filtered proteins (hypo filtration) leading to increased
protein excretion.
• Creatinine clearance: Decline
• Uric acid: Reduced urinary excretion of uric acid (increase serum level of uric
acid)
Edema and Intravascular volume:
edema is no longer part of the diagnostic criteria. However, sudden and rapid
weight gain and facial edema often occur in women who develop preeclampsia.
Hematologic changes:
Thrombocytopenia:
Is the most common coagulation abnormality is due to formation of
microthrombi.
The prothrombin time, partial thromboplastin time, and fibrinogen
concentration:
are affected with complications such as abruptio placentae or with severe
liver involvement.
Microangiopathic hemolysis:
Is detected by examination of a blood smear or elevation in the lactic
dehydrogenase concentration.
Liver:
Affected due to periportal hemorrhage, ischemic lesions, and microvesicular
fat deposition.
Clinically:
right upper quadrant or epigastric pain, elevated liver
enzymes and, in severe cases, subcapsular hemorrhage or hepatic rupture.
Neurologic:
Eclampsia is the most severe complications.
Early signs may include headache, blurred vision, photophobia or mental state.
Note: Only 50% of eclampsia cases have severe hypertension (> 160/110
mmHg)
No Reliable prediction for development of eclampsia in women with
preeclampsia.
Pulmonary edema:
The etiology is multifactorial.
Excessive elevations in pulmonary vascular hydrostatic pressure (PCWP).
Capillary leak, left heart failure, and iatrogenic volume overload
Fetus and placenta:
IUGR:
The fetal consequences of chronic placental hypoperfusion are fetal growth
restriction and oligohydramnios.
Severe or early onset preeclampsia results in the greatest decrements in
birth weight compared to normotensive pregnancies.
Abruptio placenta:
Is infrequent (< 1 percent) in women with mild preeclampsia, but occurs in 3
percent of those with severe disease.
The HELLP Syndrome
HELLP syndrome is a group of symptoms that occur in
pregnant women who have:
•H – Hemolytic anemia H
•EL -- elevated liver enzymes
•LP -- low Platelet count
The HELLP Syndrome
Incidence: ranged from 2 to 12 percent.
Classification:
Class I: platelet nadir below 50,000/mm
Class 2: platelet nadirs between 50,000 and 100,000/mm
Class 3: a platelet nadir between 100,000 and 150,000/mm
 Severe hypertension is not a constant or even a frequent finding
in HELLP syndrome.
Of 112 patients 66 percent had a diastolic BP of at least 110 mm
Hg,
14.5 percent had a diastolic BP of less than 90 mm Hg.
 The reported PNM has ranged from 7.7 to 60 percent.

 maternal mortality from 0 to 24 percent. Maternal morbidity is
common.
Criteria to Establish the Diagnosis of HELLP Syndrome
Hemolysis
Abnormal peripheral blood smear
Increased bilirubin <1.2 mg/dl
Increased lactic dehydrogenase >600 IU/L
Elevated liver enzymes
Increased SGOT ≥72 IU/L
Increased lactic dehydrogenase >600 IU/L
Thrombocytopenia
Platelet count <100,000/mm
It is important to emphasize that these patients
may have a variety of unusual signs and
symptoms, none of which are diagnostic of
severe preeclampsia.
Pregnant women with probable preeclampsia
presenting with atypical symptoms should have
a complete blood count, a platelet count, and
liver enzyme determinations irrespective of
maternal blood pressure.
Medical and Surgical Disorders Confused with the
HELLP Syndrome
Acute fatty liver of pregnancy
Appendicitis
Diabetes mellitus
Gallbladder disease
Gastroenteritis
Glomerulonephritis
Hemolytic uremic syndrome
Hepatic encephalopathy
Hyperemesis gravidarum
Idiopathic thrombocytopenia
Kidney stones
Peptic ulcer
Pyelonephritis
Systemic lupus erythematosus
Thrombotic thrombocytopenic purpura
Viral hepatitis
HELLP
(n=67))
Partial
HELLP
(n=71)
Severe
(n+178)
Blood products transfusion)%(
25 *
4
3
DIC)%(
15 *
0
0
Wound hematoma/infection † )%(
14 ‡
11 §
2§
Pleural effusion)%(
6‡
0
1
Acute renal failure)%(
3‡
0
0
Eclampsia)%(
9
7
9
Abruptio placentae)%(
9
4
5
Pulmonary edema)%(
8
4
3
Subcapsular liver hematoma)%(
1.5
0
0
Intracerebral hemorrhage)%(
1.5
0
0
Death)%(
1.5
0
0
MATERNAL COMPLICATIONS IN 316 PREGNANCIES WITH HELLP SYNDROME,
PARTIAL HELLP SYNDROME, OR SEVERE PREECLAMPSIA WITH NORMAL
LABORATORY VALUES Am J Obstet Gynecol 175:460, 1996 .
DIAGNOSIS AND INITIAL
EVALUATION
• Confirm the Diagnosis:
The initial goal is to distinguish women with PET
from those with other hypertensive disorders
• Assess the severity of disease (whether mild or
severe).
DIFFERENTIAL DIAGNOSIS Of Preeclampsia
•
Other causes of High Blood Pressure (renal, Vascular, Endocrinological)
Preeclampsia versus essential hypertension:
•
Onset – Hypertension occurring before the 20th week is usually due to an
underlying tendency to hypertension rather than to preeclampsia.
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Parity – Preeclampsia is far more common in primiparas than in multiparas.
•
Age – Preeclampsia is somewhat more common in both young (<20 years) and
older (>35 years) primigravidas.
•
Proteinuria: – Proteinuria is present and increases with time in preeclampsia,
occasionally reaching the nephrotic range; by comparison, protein excretion is
usually less than 1 g/day in hypertensive nephrosclerosis.
•
Plasma uric acid concentration: – Preeclampsia is typically associated with a
rise in the plasma urate level to above 5.5 to 6 mg/dL (327 µmol/L).
Criteria for Severe PET
Symptoms of CNS dysfunction:
e.g. Blurred vision, scotomata, altered mental status, severe headache
Symptoms of liver capsule distension:
Right upper quadrant or epigastric pain.
Nausea, vomiting.
Hepatocellular injury:
Serum transaminase concentration at least twice normal
Severe blood pressor elevation:
Systolic ≥ 160 mmhg or diastolic ≥ 110 mmHg on two occasions 6 hours apart
Proteinuria:
Over 5 gram in 24 hours or 3+ on two random sample four hours apart
IUGR:
Pulmonary edema or cyanosis:
Cerebrovascular accident:
Laboratory evaluation to determine disease severity and
characterize end organ involvement:
• Renal Function Evaluation:
• Quantification of protein excretion.
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•
Serum creatinine concentration
Serum uric acid concentration
• Hematological tests:
• Hematocrit
• Platelet count
• Lactic acid dehydrogenase concentration (LDH): and review of the
red blood cell smear may indicate the presence of microangiopathic
hemolysis.
• Hepatic function:
• Serum alanine and aspartate aminotransferase concentrations
(ALT,AST)
• Fetal well-being:
• Ultrasound to evaluate growth and amniotic fluid volume
•
Non stress test and Biophysical profile
Treatment of PET
The Definitive Treatment Of Preeclampsia Is Delivery
To Prevent Potential Maternal Complications.
However, Preterm Delivery Is Not Always In The Best
Interests Of The Fetus; Therefore, Exceptions To This
Recommendation May Be Made For Selected Women
Remote From Term.
In General, Intervention Is Based Upon:
- The Severity Of Preeclampsia.
- Maternal And Fetal Condition.
- Gestational Age.
Treatment of Mild PET
Women with mild disease at ≥ 37 weeks of gestation are induced if there
are no contraindications to vaginal birth.
 Expectant management for mild disease remote from term :
• Inpatient versus outpatient care: Indication for
or symptoms of disease progression
•
Hospitalization signs
Rest Vs. Restricted activity:
• Laboratory follow-up:
platelet count, creatinine, Quantification of urine protein, and liver
enzymes should be repeated once or twice weekly.
lactic acid dehydrogenase (LDH) concentration is a better sign of
hemolysis. Hemolysis can be confirmed by observation of schistocytes
on a blood smear.
• Antihypertensive agents:
- Does not alter the course of the disease nor diminish perinatal
morbidity or mortality.
- Are administered to prevent a maternal cerebrovascular accident
from severe hypertension (if systolic BP ≥160 mmHg or diastolic BP
≥ 105 to 110 mmHg.
- The goal of therapy is a systolic pressure of 140 to 155 mmHg and
diastolic pressure of 90 to 105 mmHg
• Assessment of fetal well-being:
daily fetal movement counts and nonstress testing and/or BBP at
periodic intervals
•
Assessment of fetal growth:
•
Administration of antenatal corticosteroids:
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Timing and indications for delivery:
Treatment of Severe PET
• Severe
preeclampsia
is
generally
regarded as an indication for delivery,
regardless of gestational age, to minimize
maternal as well as fetal complications.
• Delivery is usually by the vaginal route,
with cesarean delivery reserved for the
usual obstetrical indications.
Treatment of Severe PET
• Anticonvulsant therapy:
• Control of Blood Pressure:
• Preparation for Delivery:
• Prevention of Complications:
Anticonvulsant therapy: Magnesium
Sulphate:
• Initiated at onset of labor or induction or prior to CS
delivery and continued for 24 hours postpartum
• The most common regimen:
• A loading dose of 4 to 6 g intravenously in 150 ml of
5% Dextrose Injection, at a rate not exceeding 3 ml per
minute
followed by 1 to 2 g per hour as a continuous infusion.
•
Maintenance Dose: is given only if;
- A patellar reflex is present (loss of reflexes being
the first manifestation of symptomatic
hypermagnesemia)
- Respirations exceed 12 per minute.
- The urine output exceeds 100 mL per four hours.
Magnesium sulfate –Mechanism of action
• It prevent eclampsia in part by selectively dilating the cerebral
vasculature and relieving the cerebral vasospasm associated with
preeclampsia It exerts this vasodilatory effect by:
•
Decreasing the release of acetylcholine at motor end plates within
the neuromuscular junction, thereby suppressing nerve transmission
to vascular smooth muscle.
•
Acting as a physiologic calcium antagonist to lower the
intracellular calcium concentration within vascular smooth-muscle
cells, which is necessary for activation of the myosin-actin
contractile unit.
•
Blocking excitatory amino acid receptors, including N-methyl-Daspartate receptors, which have been implicated in the initiation and
propagation of seizures .
Complication of magnesium: sulfate:
Rapid infusion:
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, a rare side effect of magnesium sulfate administration.
Magnesium toxicity is related to serum concentration:
- loss of deep tendon reflexes occurs at 8 to 10 mEq/L
- respiratory paralysis at 10 to 15 mEq/L,
- cardiac arrest at 20 to 25 mEq/L.
Antidote:
Calcium gluconate (1 g intravenously over at 5 to 10 minutes) may
be administered to counteract magnesium toxicity.
Antihypertensives
Hydralazine (Apresoline):
Decreases systemic resistance by means of direct
vasodilation of arterioles Adult Dose Initial: 5 mg IV
Maintenance: 5-10 mg IV q20-30min
Labetalol (Normodyne):
Used as an alternative to hydralazine in eclampsia. It
blocks beta1-adrenergic, alpha-adrenergic, and beta2adrenergic receptor sites,
Adult Dose20-30 mg IV initially; 40-60 mg IV q10-20 min;
not to exceed 300 mg
• INTRAPARTUM CARE:
Close, continuous maternal-fetal monitoring:
- worsening hypertension:
- deteriorating maternal hepatic:
- renal.
- cardiopulmonary
- hematologic function:
- uteroplacental insufficiency or abruption
(often manifested by nonreassuring fetal heart rate
tracings, vaginal bleeding).
Eclampsia
Eclampsia
• Eclampsia refers to the occurrence of one or more generalized
convulsions and/or coma in the setting of preeclampsia and in the
absence of other neurologic conditions.
• The clinical manifestations appear anytime from the second
trimester to the puerperium.
• INCIDENCE AND EPIDEMIOLOGY:
An eclamptic seizure occurs in 0.5 percent of mildly preeclamptic
pregnancies and 2 percent of severe preeclamptics.
• Antepartum (38 to 53 percent)
• Intrapartum (18 to 36 percent),
• < or =48 hours postpartum (5 to 39 percent),
• >48 hours postpartum (5 to 17 percent).
CLINICAL MANIFESTATIONS AND DIAGNOSIS:
Maternal:
• Eclamptic seizures are almost always self-limiting and seldom last
longer than 3 to 4 minutes.
• The diagnosis of preeclampsia/eclampsia sometimes may not be
suspected prior to the development of seizures in women with
relative hypertension (ie, blood pressure elevated compared to
patient's baseline, but less than 140/90 mmHg) and no proteinuria.
• Fifteen to 22 percent of eclamptic women have no evidence of
proteinuria prior to their seizure.
DIFFERENTIAL DIAGNOSIS Of Eclampsia:
•
Cerebrovascular accident (hemorrhage, arterial or venous thrombosis).
•
Hypertensive disease (hypertensive encephalopathy,
pheochromocytoma). (
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Space-occupying lesions of the central nervous system (brain tumor,
abscess).
•
Metabolic disorders (hypoglycemia, uremia, inappropriate antidiuretic
hormone secretion resulting in water intoxication).
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Infection (meningitis, encephalitis).
Thrombotic thrombocytopenic purpura or thrombophilia
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Idiopathic epilepsy.
•
Use of illicit drugs (eg, methamphetamine, cocaine)
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Cerebral vasculitis.