Preeclampsia

PreeclampsiaOmar Khayyam R. Macadato

MSU-College of Medicine

HYPERTENSIONThe National High Blood Pressure Education Program (NHBPEP) Working Group defines HYPERTENSION in PREGNANT WOMAN:

systolic blood pressure (BP) of 140 mmHg or higherdiastolic BP of 90 mmHg or higheron more than 1 occasion

Epidemiology

Etiology Multifactorial

Incidence 3% of all pregnancies

Primiparity Immunologic factors Previous pregnancy complicated by Preeclampsia/Eclampsia/HELLP

Family history of Preeclampsia BMI Pregnancy related

conditions

Risk Factors

Primipaternity Sexual co-habituation Maternal infection

Gestational age at delivery of 1st Pregnancy

Socioeconomic status Smoking

Risk Factors

Stage 0 3-8 weeks

Stage 18-18

weeks

Stage 220 weeks to birth

Poor ImmunoregulationInadequate tolerance to feto-paternal antigens during conception and implantation

Poor PlacentationDeficient trophoblast invasion and spiral artery remodelling

Clinical manifestationOver activation of maternal endothelium and systemic inflammatory network

Oxidative Stress

Endoplasmic reticulum Stress

Inflammatory Stress

Mechanisms

Mechanisms

invasive cytotrophoblasts of fetal origin invade the maternal spiral

arteries

transforms them from small-caliber resistance vessels

to high-caliber capacitance

vesselscapable of

providing placental perfusion adequate

to sustain the growing fetus

Normal Pregnancy

cytotrophoblasts fail to adopt an invasive endothelial phenotype

invasion of the spiral arteries is shallow and they remain small caliber,

resistance vessels

placental ischemia

Mechanisms

Preeclampsia

Soluble Flt-1 (sFlt-1) causes endothelial dysfunction by

antagonizing vascular endothelial growth factor

(VEGF) and placental growth factor (PlGF)

In normal pregnancy, the placenta produces modest concentrations of VEGF, PlGF, and soluble Flt-1

In preeclampsia, excess placental soluble Flt-1 binds circulating

VEGF and PlGF and prevents their interaction with endothelial cell-

surface receptors

Mechanisms

decreased prostacyclinnitric oxide productionrelease of

procoagulant proteins EN

DOTH

ELIA

L DY

SFUN

CTIO

N

Faulty placentationExcessive trophoblastsMaternal vascular

disease

Reduced Uteroplacental Perfusion

Genetic/Immunologic/Inflammatory factors

Activation of CoagulationCapillary Leak

Endothelial Activation

Vasospasm

Vasoactive Agents:

Prostaglandin Nitric oxide Endothelins

Noxious Agents:

Cytokines Lipid

Peroxidases

Pathophysiology

Multiple gestation

Hydrops fetalis

Activation of CoagulationCapillary LeakVasospasm

Abruption

Seizures

Hypertension

Liver Ischemia

Oliguria

Proteinuria

Edema

Hemoconcentration


Thrombocytopenia

Pathophysiology

Gestational HPN

• Previously normal BP• Elevated BP without proteinuria• Develops after 20 weeks of gestation and BP normalizes 12 weeks

postpartumPreeclampsia

• Previously normal BP• Elevated BP with proteinuria• Develops after 20 weeks of gestation and BP normalizes 12 weeks

postpartumEclampsia

• Hypertension in pregnancy with proteinuria along with convulsions• Preeclampsia with occurrence of grand mal seizures

Definition

Chronic HPN• Previously elevated BP• Use of antihypertensive medications before pregnancy• Develops before 20 weeks of gestation and• BP elevation persists longer than 12 weeks postpartum

Chronic HPN with Superimposed Preeclampsia

• Previously elevated BP or persists postpartum with associated signs and symptoms of preeclampsia

• Develops before 20 weeks of gestation with new-onset proteinuria• Development of HELLP syndrome

Definition

Ideal: mercury manometer• Alternative: aneroid, digital, or other automated devices• Cuff should cover: 2/3 of arm or at least 80% of pt’s arm

circPosition: seated, supine, or left lateral recumbent position • Should be rested at least 5-10 minutes• Not smoked or ingested caffeine 30 min. before measurement

Bladder is inflated 30 mmHg above point of radial pulse extinction• Deflation: 2 mmHg per beat

Methods of Indirect Measurement of BP

Systolic BP: 1st clear tapping sound (Korotkoff phase I)• Diastolic BP: disappearance of tapping sounds (Korotkoff

phase V) OR• Present near 0: softening of sounds (Korotkoff phase IV)If BP taken for the 1st time: take BP of both arm, subsequent determination is done on the arm with higher BP• Arm with the higher values will be used for all BP

measurementsFor white coat HPN: ambulatory BP monitoring• Instruct proper BP monitoring if BP monitoring is done at

home

Methods of Indirect Measurement of BP

Screening maneuvers• Mean Arterial Pressure• Roll over test• MAP-2 with Roll over test• 48 hour BP monitoring• 24 hours ambulatory BP

with heart rate• Hyperbaric Index

Laboratory Test• Doppler Velocimetry• Fibronectin• Hematocrit• Proteinuria• Serum uric acid

Laboratory Test• Hemoglobinuria• Masternal Serum AFP• Hypocalciuria• Glucose intolerance• Inhibin AOthers:

biochemical markers

Predictive Test for HPN in Pregnancy

Biochemical Markers

Calcium SupplementationDose: 1.5 to 2 g per day before 32 weeks AOG until delivery

Antiplatelet agentsASA or dipyridamole: reduce risk of preeclampsia by 17%

Insufficient evidence on othersAntioxidants, nitric oxide, rest, exercise, diuretics, ↓ed salt intake, marine oil, prostaglandin

Preeclampsia Prevention

PREE

CLAM

PSIA

MILD No manifestations of any of severe preeclampsia

SEVERE

BP SBP ≥ 160 or DBP ≥ 110

Laboratories

Elevated serum creatinine

Thrombocytopenia

Hepatocellular dysfunction (↑ed AST and ALT)Pulmonary edema

Microangiopathic hemolysis

Urine≥5 g/24h or ≥ 3 in 2 random urine sample (q4h)

Oliguria <500ml/24h

IUGR or Oligohydramnios

Symptoms of End-organ involvement

Headache

Visual disturbances

Epigastric pain or RUQ pain

Criteria for home health careAbility to comply with recommendationDiastolic BP <100 mm HgSystolic BP <140 mm HgProteinuria < 1,000 mg/24 hr OR < 2+ on dipstickPlatelet count > 120,000/mmNormal fetal growth and testingNo indications for delivery

Gestational Hypertension and Mild Preeclampsia

Tim

ing

of D

eliv

ery

Gestational Age ≥ 40

weeks• Bishop score > 5 • Fetal weight < 10th percentile• Non-reactive non-stress test

(NST)


weeks with:• Labor• Rupture of membranes• Vaginal bleeding• Abnormal biophysical profile• Criteria for severe preeclampsia


weeks with: DELI

VER

Expectant management: remote from term with mild preeclampsia

Maternal and fetal well-being at least once weekly

• BP each visit• Platelet count and liver enzymes at regular

intervals• NST at regular interval• Fetal growth every 2 to 3 weeks

MEDICATIONSAnti-HPN meds will be given only if there is an increase in BP reading.Not recommended:• Magnesium sulfate and other anti-convulsants• Low-dose aspirin and high dose calcium for

prevention of progression to severe preeclampsia

Monitoring and Medications

Severe Preeclampsia

5-6% of all pregnancies worldwide

5-10% - severe

Local incidence: 2-5%2nd most common cause of maternal death

High perinatal mortality and morbidity rate: Iatrogenic prematurity

Definitive treatment: Delivery of fetus and placenta

Incidence

Criteria for the diagnosis of Severe Preeclampsia

CNS

Dysf

unct

ion • Blurred

vision

• Scotomata

• Altered mental status

• Severe headache

Liver

cap

sule

dist

entio

n or

ru

ptur

e • Persistence right quadrant pain

• Epigastric pain

Bloo

d pr

essu

re

crite

ria• Sitting SBP ≥160 mm Hg

• DBP ≥110 mm Hg

• * On 2 separate occasions at rest or at least 6 hours apart

Ecla

mps

ia • Generalized seizure

• Unexplained coma in setting of preeclampsia in absence of neurologic d/o


Pulm

onar

y ed

ema

or

cyan

osis• Excessi

ve fluid accumu-lation in the lungs

Cere

brov

ascu

lar a

ccid

ent

(CVA

) • Acute loss of brain function

• Altered mental status

• coma

Corti

cal B

lindn

ess • Partial or

total loss of vision in normal appearing eye

IUGR

• EFW < 5 percentile for gestational age

• EFW <10 percentile for gestational age with evidence of fetal compromise

Coag

ulop

athy

and

Th

rom

bocy

tope

nia • Prolonged

prothrombin time: >1.4s

• Low fibrinogen: <300 mg/dl

• Low platelet: <100,000 mm3

Due to disturbance of

vasculature that supplies

the brain

Damage to the visual region of occipital cortex


Prot

einu

ria • >5 g per 24h or ≥3+ on 2 random urine samples collected at least 4 hours apart Ol

igur

ia a

nd/o

r Ren

al

Failu

re • Urine output <500 ml per 24h

• Serum creatinine: >1.2 mg/dl

HELL

P Sy

ndro

me • Hemolysis:

• Abnormal peripheral smear

• total bilirubin >1.2 mg/dl

• LDH >600 U/L• Elevated

liver enzyme:

• ALT > 70 U/L• LDH > 600 U/L

• Low platelet:

• Platelet <100,000 mm3

Hepa

toce

llula

r in

jury• Serum

transaminase ≥ 2x the normal

Activation of CoagulationCapillary LeakVasospasm

Hypertension

Seizures

Proteinuria

Edema

Hemoconcentration


Thrombocytopenia

Pathophysiology Multiple factors

Oliguria

↓ed kidney perfusion

Liver Ischemia

↓ed liver perfusion

Severe headache

Cortical blindness

Altered mental status

Scotomata

Blurred vision

Occipital cortex

damage

CNS Dysfunction

Hepatocellular damage

↓ed brain perfusion

RUQ pain/abd’l pain ↑ed

ASTPulmonary

edema

HELLP SYNDROME

ARF

Uteroplacental

insuffieciency

IUGR

Eclampsia

Complications

Signs and symptoms

Process

Abruption

Oligohydramnios

ManagementOb

ject

ives

of

man

agem

ent

Reduce severity or prevent progression of disease process

Prevent convulsions

Control severe hypertension

Deliver the fetus at the optimum time and with the least trauma

Detect and appropriately treat end-organ damage

Completely restore the health of the mother

• Safety of mother and fetus

Main objective

• Stabilization of mother’s condition

• Confirmation of gestational age

• Assessment of fetal well-being

Initial

Management

Indications for Delivery

Epigastric/RUQ pain w/ AST or ALT

>2x the normal

Persistent platelet count

<100,000/mm3

Persistent headache,

visual change,

eclampsia Maternal

Oliguria or serum

creatinine levels ≥1.5

mg/dl

Persistent severe oligo-

hydramnios

SOB/chest tightness w/ rales and/or

Pulse Oximetry: <94% or

Pulm. edema

Suspected abruption placentae, progressive

labor, rupture of

membranes

DELIVER

Umbilical artery

Doppler imaging with

reverse diastolic

blood flow

Persistent BPP≤ 4

(evaluated 6 hours apart)

FetalSevere fetal

growth restrictionUncontrolled

severe HPN, despite max doses of anti-HPN agents

Repetitive late or

variable heart rate

deceleration

Fetal death

Complications

Perinatal

Perinatal death0-16.6%

Non-reassuring fetal status

26-75%

Abruptio placentae4.1-22.9%

Maternal

HELLP Syndrome4.1-27.1%

Acute Renal Failure:<1%

Eclampsia<1%

Pulmonary Edema0-8.5%

EclampsiaPreeclampsia with generalized tonic-clonic convulsions

Common in the last trimester

Other causes excluded, all pregnant women with convulsions

Contractions increase in frequency and intensity as convulsion occurs, duration of labor is shortened

Complications: (1) Pulmonary edema (2) Blindness

Magnesium Sulfate Therapy

Drug of choice for prevention of seizuresDrug is considered when women is at risk for eclampsia: moderate to severe preeclampsia (at least BP 150-160/100-110 mm Hg)

Can be given in 2 ways: (2) intermittent intramuscular

injections

(1) continuous intravenous infusions

When given, regularly assess: Maternal

reflexes

Urine output

Oxygen saturation

Respiratory rate

Continuous intravenous infusion• Loading dose: 4-6 g dose of MgSO4 diluted in 100 ml of IVF administered over 15-20 min• Begin 2 g/h in 50 ml of IV maintenance infusion• Measure serum Mg level at 4-6 h and adjust infusion to maintain levels between 4 and 7

mEq/L• MgSO4 is discontinued 24 h after delivery

Intermittent intramuscular injections• Give 4 g MgSO4 as 20% solution of intravenous at a rate not to exceed 1 g/min• Follow with 10 g of 50% MgSO4 solution:

• 5 g (one-half) injected deep in the upper outer quadrant of both buttocks through a 3-inch-long, 20 gauge needle.

• If convulsion persists after 15 min, give up to 2 g more IV as 20% solution at a rate not to exceed 1 g/min. (if the woman is large up to 4 g may be given slowly)

• Every 4 h thereafter: 5 g of 50% solution of MgSO4 deep IM upper outer quadrant of alternate buttocks, assuring that:• Patellar reflex is present• Respirations are not depressed• Urine output during the previous 4 h exceeded 100 ml

• MgSO4 is discontinued 24 h after delivery



PHARMACOLOGY

Clearance: renal excretion

Avoid toxicity by ensuring:

Urine output is adequate

Patellar/biceps reflex present

No respiratory depression

Therapeutic level:

4-7 mEq/L (4.8-8.4 mg/dl)

TOXICOLOGY

10 mEq/L (12 mg/dl)

>10 mEq/L (>12 mg/dl)

Loss of patellar reflexes

Respiratory depression

UO below 20 ml/hr

STOP giving MgSO4

Calcium gluconate 1 g (10 ml) over 10 minutes

Control of Blood Pressure

ANTI-HPN Treatment

Start if: BP below 160/110 mm Hg but

with markers of severe diseaseAimSBP: 140-155 mm HgDBP: 90-105 mm Hg

BP≥160/110 mm Hg

Gestational OR Chronic HPN

Contraindicated/Avoided

Postpartum HPN

Urgent control of Severe HPN

DRUGS

Labetolol Hydralazin

e Nifedipine IV

Nicardipine

Methyldopa Second line agent:

• Labetolol• Nifedipine• Hydralazine• Beta-receptor

blocker• Hydrochlothiazide

ACE-I ARB Diuretics

Given if BP >150/100 mm Hg PP: Drugs used

during antepartum

Diuretics Avoid NSAIDs PP

Phar

mac

olog

y Labetalol (C)

> 10 to 20 mg IV, then 20 to 80 mg every 20 to 30 minutes> maximum of 300 mg;> for infusion: 1 to 2 mg/min

> Lower incidence of maternal hypotension and other adverse effects, displaces hydralazine; > Avoid in women with asthma or congestive failure. > Not available locally

Hydralazine (C)

> 5 mg IV or IM, then 5 to 10 mg every 20 to 40 minutes; once BP controlled repeat every 3 hours; > for infusion: 0.5 to 10.0 mg/hr; if no success with 20 mg IV or 30 mg IM, consider another drug

A drug of choice according to NHBEP; long experience of safety and efficacy

Nifedipine (C)

> Tablets recommended only: 10 to 30 mg PO, repeat in 45 minutes if needed

Should be used with caution if concomitantly used with MgSO4

IV Nicardipine

> D5W 90 mL + Nicardipine 10 mg in solusetConcentration = 0.1 mg/mL> Start drip at 10 ugtts/min (equivalent to 1 mg/hr).> Maximum dose 10mg/hr*Note: The IV infusion site must be changed every 12 horus

Should be used with caution if concomitantly used MgSO4

DRUG Dose and Route

Precautions and Adverse Effects

Drugs: Gestational HPN or Chronic HPN

Methyldopa (B)

Seco

nd li

ne a

gent

s

Preferred agent:0.5 to 3.0 g in 2 divided

dosage

Labetolol (C)

Nefidipine (C)

Hydralazine (C)

Beta Blockers (C)

Drug Dose ConcernsDrug of choice (NHBEP)

Safety after 1st trimester

200 to 1200 mg/d in 2-3 divided dose

30 to 120 mg/d slow release prep

May be assoc. with fetal growth restriction

May inhibit labor and synergistic action with MgSO4

in lowering BPUseful in combination with

sympatholytic agentsMay cause neonatal thrombocytopenia

May ↓ uteroplacental blood flow May impair fetal response to hypoxia Risk of IUGR when start 1st or 2nd Tri (Atenolol) Associcated with neonatal hypoglycemia

50 to 300 mg/d in 2-4 divided doses

Depends on specific agent

Drugs: Gestational HPN or Chronic HPN

Hydrochlothiazide (C)

Cont

rain

dica

ted

Second line agents:

12.5 to 25.0 mg/d

ACE-I

ARB

Drug Dose Concerns Can cause volume contraction and

electrolyte d/o Useful in combination with

Methyldopa and vasodilator to mitigate fluid retention

Leads to fetal loss in animals Human use is associated with:1. Cardiac defects2. oligohydramnios3. Fetopathy 4. Growth restriction5. Renal agenesis6. Neonatal anuric renal

failure

Drugs: Eclampsia

Cont

rol o

f se

izure

s MgSO4 For prevention and reduction of recurrence

Diazepam Loading dose: 10 mg IV over

2 min

Followed by: IV infusion 40 mg in 500 ml Normal saline for 24 h

After 24 h: 20 mg in 500 ml

NS, slowly reduced

PhenytoinOnly for seizure

prevention

Dose: initial - 1 g slow IV d by 100 mg every 6 hours for the next 24 hours

Anti-

HPN

Ther

apy Hydralazi

neDrug of choice

IV boluses of 5 to 10 mg at 20-30 min interval until desired BP attained

Clonidine Next recommended drug IM: 75-150 mcg

Nifedipine 5-10 mg orally NOT sublingual

Labetalol Initial dose: 20 mg IV bolus

If desired BP not attained w/in 10 min, give 40 mg then 80 mg every 10

minutes

> 34 weeksDeliver

Mode: vaginal delivery

Delivery

Betamethasone: 12 mg IM every 24 h for 2 doses

Dexamethasone: 6 mg IM every 12 h for 4 dosesGiven between 23-34 weeks

for fetal lung maturity

Corticosteroids

Vaginal delivery is not easy and imminent

Failure of progress after induction

Fetal compromise

Oligohydramnios

DEFINITION: Amniotic fluid index < 5cm

Fetal Growth

restriction

Chromosomal Abnormalities

Demise

Congenital anomalies

Postterm pregnancyRuptured membranes

Placental

AbruptionTwin-twin transfusion

Maternal Preeclampsia

Uteroplacental insufficiency

Diabetes

Hypertension

Drugs

Prostaglandin synthase inhibitorsACE Inhibitors

Idiopathic

Fetal well-being studies

Biophysical profile

Non-stress test

Doppler velocimetry

Most widely used for assessment of fetal well being

Hypothesis: HR of non-acidotic fetus temporarily increase in response to movement

Normal or reactive:≥2 accelerations of ≥15 bpm lasting for ≥15 sec within 20 min

Nonreactive:Does not contain at least 2 accelerations

Uteroplacental insufficiency:Absent acceleration during 80-min period with variability or late deceleration following spontaneous uterine contractions

Non-stress test

Biophysical Profile

Fetal Breathi

ng Amniotic fluid

volume

5 biophysical variables

Fetal Tone

Fetal mov’t

Nonstress testHighest

score: 10

Biophysical Profile

NST2 ≥2 accelerations of

≥15 bpm lasting for ≥15 sec within 20

min

0 0 or 1 acceleration in 20-40 min

Fetal Breathin

g

2 ≥1 ep rhythmic breathing lasting

≥30 sec w/in 30 min

0 <30 sec of breathing in 30 min

Fetal mov’t

2 ≥3 discrete or body limb movement

w/in 30 min

0 <3 discrete movements

Fetal tone

2 ≥1 ep of ext and flex of extremity OR

opening/closing of hand w/in 30 min

0 No movement or no extension/felxion

AF volume

2 Single vertical pocket >2cm

0 Largest single vertical pocket

<2cm

Modified Biophysical Profile

Modified BPP

NSTUTZ assessment of AF

Requires less time

Excellent method of fetal surveillance

Biophysical Score Interpretation Recommended

management

10 Normal, nonasphyxiated

No fetal indication for interventionRepeat test weeklyRepeat 2x weekly for postterm and diabetic

8 Normal fluid

Normal, nonasphyxiated fetus

No fetal indication for interventionRepeat test per protocol

8 oligohydramni

osChronic fetal asphyxia suspected

Deliver if ≥37 weeks, otherwise repeat test

6 Possible fetal asphyxia

IF:AF is abnormal: deliverNorma AF >36 weeks w/ favourable cervix: deliverRepeat test <6: deliverRepeat test >6: observe and repeat per protocol

4 Probable fetal asphyxia Repeat test on same day: if ≤6 - deliver

0-2 Almost certain fetal asphyxia Deliver

Non-invasive way to assess blood flow characterizing downstream impedance

Umbilical artery systolic/diastolic ratio is commonly used Doppler index

Ratio compares max systolic flow with end-diastolic flow: evaluate downstream impedance to flow

Consider abnormal if elevated above 95th percentile OR if diastolic flow is absent or reversed

Doppler of the uterine and uteroplacental arteries at 24 weeks is an effective test to predict Preeclampsia

Doppler Velocimetry

Doppler Velocimetry

ABSENCE OF END-DIASTOLIC FLOW

NORMAL DIASTOLIC FLOW

REVERSED END-DIASTOLIC FLOW

ABNORMALITY BPS FREQUENCY DECISION TO DELIVER (FETAL)

Elevated Indices Only Weekly

Abnormal BPS or Term or >36 weeks with no fetal growth

AEDV Twice weekly Abnormal BPS or >34 weeks proven maturity or conversion to REDV

REDV Daily Any BPS < 10/10 or >32 weeks dexamethasone given

REDV-UVP Three times daily

Any BPS < 10/10 or >28 weeks dexamethasone given

DOPPLER ABNORMALITY AND FREQUENCY OF BPS

Preeclampsia

Health & Medicine

Transcript of Preeclampsia