Pre-eclampsia & eclampsia

Dr Shamani Singham
15
th
January 2002
Definitions - pre-eclampsia
Persistent hypertension from gestation week
20 onwards defined by either
Diastolic bp >90 mmHg
Systolic bp >140 mmHg
Or relative increase diastolic bp >15 mmHg or
systolic bp>25 mmHg
Proteinuria > 0.3g in 24 hours
Generalised oedema
Definition of Eclampsia
One or more convulsion, not caused by
other cerebral condition, in a patient with
pre-eclampsia
Definition of severe pre-
eclampsia
Features of pre-eclampsia plus one the following
Systolic bp >160 mmHg
Diastolic bp >110 mmHg
Proteinuria > 5g per 24 hours
Cerebral or visual disturbances
Oliguria < 500ml per 24 hours
Epigastric/ RUQ pain
Pulmonary oedema
Haemolysis, elevated liver enzymes and low platalet
syndrome
Epidemiology
Incidence pre-eclampsia (in the UK) 2-10%
all pregnancies
Incidence eclampsia (UK) 2-6 in 10000
deliveries with 1.8% maternal mortality and
7% fetal/ neonatal mortality
Pathogenesis
Factors predisposing
Increase Oxygen demand states
Multiple pregancies
Hydatiform mole etc
Decrease Oxygen transfer
Primigravida
Microvascular diease e.g. Hypertension, Diabetes, collagen
disease
Abnormal placentation
Genetic e.g. Angiotensin T235 gene
Immune mechanism e.g. antiphospholipid syndrome
Pathogenesis
Primary defect involves abnormal migration
of extravillous trophoblast in placenta
Myometrial vessels retain musculoelastic
architecture instead of being converted into
sinusoidal vessels( as occurs in normal pregnancy)
Defect occurs with the inhibition of second wave of
migration i.e. in second trimester
Consequence of this defect includes
Hypoperfusion and hypoxia of placenta endothelial cells
Change in ratio of vasopressor substances synthesised by
endothelium causing vasospasm
Pathophysiology - circulation
Circulation
Uteroplacental vascular resistance increases with
decrease in blood flow, leading to placental ischaemia
and fetal growth retardation
Systemic circulation 2 models
Traditional model occurs in 80% pre-eclampsia with picture
of
Decreased plasma volume
Vasoconstriction
and therefore hypoperfusion of placenta and kidney
Hyperdynamic model high CO with compensatory
vasodilation
Pulmonary oedema may complicate.



Pathophysiology - cerebral
Cerebral involvement include
Eclamptic convulsions principal sequlae
pathogenesis may be due to:
Focal cerebral vasospasm and hypoperfusion causing abnormal
electrical activity with hypertension occuring as secondary
response most likely explanation
Hypertension causes breakdown in cerebral autoregulation,
leading to overdistension of vessels and extravasation of fluid
Visual disturbances i.e. blindness (rare)
Cerebral haemorrhage

Pathophysiology - renal
Renal involvement occurs in 2 stages:
Impairment of tubular function occurs early reflected
by development of hyperuricaemia.
Serum uric acid levels are a sensitive marker of progression
and risk
Glomerular filtration impaired later in disease
reflected by proteinuria > 0.5g in 24 hours or in severe
pre-eclampsia > 5 g in 24 hours
Acute renal failure (rare) due to:
Acute tubular necrosis (more common and reversible)
Acute cortical necrosis (permanent)



Pathophysiology coagulation
Platelets
usually associated with thrombocytopaenia and
increase in mean platelet volume
Immune mediated
Increase platelet activation
Possibly due to endothelial activation or intrinsic
changes in platelets
Pathophysiology coagulation
Coagulation cascade activated to greater extent
than normal pregnancy
Increase factor VIII consumption
Increase thrombin activity
All leads to heightened risk of thrombosis
Anticoagulant protein levels decreased
Decreased antithrombin III
Decreased protein C and S
Fibrinolytic system conflicting results
Pathophysiology liver
Liver complications consists of:
Deranged liver function tests due to
vasoconstriction of hepatic bed causing
Periportal fibrin deposition
Hepatocellular necrosis
Hepatic infarction and rupture worst but rare
condition
HELLP syndrome
Pathophysiology HELLP
syndrome
Constellation of laboratory findings in pre-
eclampsia
Haemolysis- seen on peripheral blood smear and LDH
levels > 600U/L
Elevated Liver enzymes serum aspartate
aminotransferase (AST) levels > 70 U/L
Low platelets < 100,000/uL
Pathogenesis uncertain but may be due to
vasospasm

Assessment of mother
Maternal assessment should include:
History and examination
Serial or continuous blood pressure monitoring
Urinanalysis for proteinuria quantification for degree
of severity
Blood test include
FBC for platelet count and morphology
U&E for renal function
Serum uric acid useful early and for progression
LFT
ABG
Fluid balance urine output, CVP, Sa02 etc
ECG
Assessment of fetus
Fetal monitoring:
Cardiotocography for acceleration, loss of
variability or decelerations
Fetal ultrasound may be useful for fetal size and
liqour volume estimation
Placental blood flow by measurement of uterine
artery Doppler end diastolic flow
Management
Principles of management:
Maintain placental perfusion with delivery
timed appropriately
Control of blood pressure
Prevention of seizures
Control of fluid balance
Management general measures
ICU admissions include pre and post-partum
patients
Pre- delivery care specifically include
Positioning in lateral decubitus
Regular fetal HR monitoring
Ranitidine decrease volume and acidity gastric
contents
IV steroids may be required for premature deliveries
Correction of coagulopathy / thrombocytopaenia


Management Antihypertensive
therapy
Treatment required when
Systolic bp > 160 mmHg
Diastolic bp > 110 mmHg
Hydralazine : agent of choice
Causes direct arteriolar vasodilation
Improves renal and uteroplacental blood flow
Labetalol : causes rapid decrease in arterial bp
without compromising uteroplacental flow
May cross placenta but fetal complications rare
Management Antihypertensive
therapy
Nifedipine : causes direct relaxation of arteriolar
smooth muscle
Maintains uterine perfusion
Can cause uterine muscle relaxation increase risk of
post partum haemorrhage
Contra-indicated with use of Mg
Sodium nitroprusside : hypertensive emergencies
Diazoxide : may be useful in refractory cases
Nitroglycerin : useful especially when pulmonary
oedema complicates situation

Management Antihypertensive
therapy
Unsuitable therapies :
Methyldopa slow onset
Clonidine rebound hypertension on cessation
B-blockers risk of hepatotoxicity, decrease
uteroplacental perfusion, fetal complications
ACE-Inhibitors contraindicated in pre-delivery
because of intrauterine death, oliguria, renal failure in
mum and neonate
Diuretics tend to be avoided because further deplete
intravascular volume
Loop diuretics used in pulmonary oedema secondary to fluid
overload
Management Anticonvulsant
therapy
Magnesium sulphate : anticonvulsant of choice in
USA
Collabrative Eclampsia Trial (1995)
Action by
antagonism of calcium and hence decreased systemic and
cerebral vasospasm
Increase release of PGI2 by vascular endothelium
Other effects in parturient include:
Tocolysis
Decreased cathecholamine release
Mild antihypertensive
Increases renal and uterine blood flow

Management anticonvulsant
therapy
Magnesium continued
Renally excreted so reduce dose in renal
failure
Therapeutic level 2-4 mmol/l ; must monitor for
toxicity
Repeated seizures despite therapeutic levels
need to consider others
Management Anticonvulsant
therapy
Phenytoin : effective in pre-eclampsia
Central anticonvulsant activity
No effect on uterine tone, fetal HR or neonatal
tone
Highly protein bound
Diazepam : effective especially if needed
acutely but causes fetal/ neonatal
complications
Management of eclamptic
seizures
Airway protection
Maintain oxygenation
Control of seizures
Continued convulsions may indicate other
cerebral pathology
Management may involve treatment cerebral
oedema
Delivery of fetus when mother stabilised
Management fluid balance
Balance between need for volume
expansion versus development fluid
overload and consequently pulmonary and
cerebral oedema
Risk of fluid overload may occur in post-
partum period secondary to auto transfusion
of uteroplacental blood volume into
systemic circulation
Conclusion
Pre-eclampsia is due to a primary disturbance of placental
vasculature, leading to increase systemic vascular
resistance and potential for multiorgan disturbances /
failure secondary to vasospasm.
Mainstay of management is early diagnosis, prevention of
hypertension and seizures.
Severe pre-eclampsia requires intensive management and
the ultimate cure being delivery of fetus.
Note however, that eclamptic seizures and pulmonary
oedema often occur in the post-partum period.

Bibliography
SP Salas(1999), What causes pre-eclampsia? Ballieres Clinical
Obstetrics and Gynaecology Vol 13, No 1, pp41-57.
L Kenny, PN Baker (1999), Maternal pathophysiology in pre-
eclampsia. Ballieres Clinical Obstetrics and Gynaecology, Vol 13, No
1, pp59-75.
P Moran, JM Davison(1999), Clinical management of established pre-
eclampsia. Ballieres Clinical Obstetrics and Gynaecology, Vol 13, No
1, pp77-93.
JJ Walker(2000), Pre-eclampsia. Lancet 356 , pp1260-65.
TE Oh, Intensive Care Manual 4
th
edition(1997)