5.6 Pre-Eclampsia Flashcards
How do you define preeclampsia
Preeclampsia is described as
hypertension (> 140/90 mmHg)
+
significant proteinuria*
that develops after 20 weeks of gestation;
although preeclampsia can develop without proteinuria
and eclamptic fits can occur
with a minimally elevated blood pressure.
oedema is no longer part of the definition although it is often present.
*Significant proteinuria ?
- Urine Protein: Creatinine (PCR) > 30 mg/mmol (oR)
- Total protein excretion ≥ 300 mg per 24-hr collection of urine (oR)
- Two specimens of urine collected ≥ 4 hours apart
with ≥ 2+ on the protein reagent strip.
24-hour proteinuria is difficult to measure and
has been replaced by PCR
(protein creatinine ratio).
Where does the morbidity lie
What is important is the fact that preeclampsia is linked to
eclampsia,
HELLP
(haemolysis, elevated liver enzymes, and low platelet count)
most probably AFLP (acute fatty liver disease of pregnancy).
Some statistics
- Preeclampsia occurring before 30 weeks of pregnancy
is associated with severe morbidity
- Preeclampsia occurring before 30 weeks of pregnancy
- Up to 30% can occur after delivery (up to 6 weeks post-delivery)
- Occurs in 5%–6% of pregnancies overall
and up to 25% of hypertensive mothers
- Occurs in 5%–6% of pregnancies overall
- 1%–2% women with PET will develop eclampsia
Could you explain the pathophysiology?
A two-stage process into the pathogenesis has been explained.
- An abnormal placentation along
with endothelial dysfunction gives rise to the
spectrum of the disease. - Preeclampsia is linked to a failure of placentation,
which occurs early in pregnancy and
results in the placenta becoming hypoxic. - This leads to an immune reaction
with secretion of upregulated inflammatory mediators
from the placenta causing vascular endothelial
cell damage and dysfunction.
stage 1
Abnormal placentation and vascular remodeling
=
decreased placental perfusion
Maternal factors
* Genetic
* Behavioral
* Environmental
Stage 2
Maternal syndrome of preeclampsia
with endothelial dysfunction
Resulting endothelial dysfunction produces
an imbalance of pro- and antiangiogenic factors,
with an increase in anti-angiogenic factors.
It should be noted that these biomarkers
do not have sufficiently high positive predictive
value when used alone.
The typical hypertension which is the cardinal diagnostic feature of pre-eclampsia is a
result of the production of endogenous vasoconstrictors as a means of ensuring that
uteroplacental perfusion is sustained. It is mediated by circulating vasoactive humoral
compounds (these have been identified in blood, placenta and amniotic fluid)
Pro-angiogenic factors
Anti-angiogenic factors
+
Vascular Endothelial Growth Factor (VEGF)
Placental Growth Factor (PlGF)
Placental protein 13 (PP-13)
Pregnancy-associated plasma protein A (PAPP-A)
-
Soluble fms-like tyrosine kinase-1 receptor (sFlt-1)
Soluble Endoglin (sEng)
Asymmetric Dimethylarginine (ADMA)
Sequelae of disease
The maternal syndrome of preeclampsia is
characterised by decreased perfusion
due to vasospasm and activation of coagulation cascade with
microthrombi formation and end organ damage.
- Fluid shift:
Leaky capillaries together with a low oncotic pressure
result in a low intravascular volume and
fluid shift into the interstitial compartment
- Fluid shift:
- Vasoconstriction:
The generalised vasoconstriction will mean increased
systemic vascular resistance
- Vasoconstriction:
and in severe preeclampsia increased pulmonary pressure;
also renal, hepatic, and pancreatic dysfunction.
Vasospasm in the cerebral vasculature causes seizures and intracerebral
bleeds.
- Decreased placental blood flow:
The compromised placental blood flow
will result in IUGR (intrauterine growth retardation),
fetal distress,
the high blood pressure increases the risk of placental abruption
What risk factors are associated with the development of preeclampsia?
- Pregnancy associated factors
First pregnancy
Multiple pregnancy
Donor insemination
Molar pregnancy
Chromosomal abnormalities
___________________________
- Maternal factors
> 35 years
< 25 years
Family history of preeclampsia
Prior history of preeclampsia
(20% will develop PET in subsequent pregnancy,
2% eclampsia)
Booking diastolic blood pressure of 80 mmHg or more
Associated diabetes, obesity, chronic hypertension, and renal disease
Antiphospholipid antibodies/factor V Leiden
___________________________
Paternal factors
First-time father
Previous history of preeclampsia
How would you manage a preeclamptic woman?
Preeclampsia requires multidisciplinary team management,
and effective communication with midwives and obstetrician is crucial.
The mother should be reviewed regularly
by the whole team and the treatment plan clearly
written in the notes.
Aim
The aim is to stabilise the blood pressure until the decision to deliver is taken
whilst monitoring for signs of severe preeclampsia.
Before 34 weeks, two doses of steroids are given
to the mother to improve fetal lung maturity.
__________________________________________
Monitoring
* BP, RR, SpO2, urine output recorded on a MEoWS chart
- Strict input/output chart (fluid balance)
- Fetal monitoring in the form of cardiotocography
Vigilance
Clinical examination looking for photophobia, headache, epigastric pain,
hyperreflexia and other signs and symptoms of eclampsia
__________________________________________
Treatment
* Control of hypertension
- Prevention and control of eclamptic seizures
The Royal College of obstetricians and Gynaecologists (Green top guideline
10A) and National Institute for Health and Care Excellence (NICE CG 107)
have produced guidelines setting specific criteria for the treatment of
preeclampsia including the method for measuring blood pressure.
Discuss the medical management of hypertension in pregnancy.
The evidence base for treatment of mild to moderate chronic hypertension
in pregnancy resides in maternal benefit rather than clear evidence of
an enhanced perinatal outcome for the baby.
NICE suggests treating only moderate and severe hypertension (BP > 150 mmHg systolic and
100 mmHg diastolic pressure) and recommends
- Labetalol as the first line.
- Methyldopa
- Nifedipine
- Hydralazine
- Alpha Blockers
- Beta Blockers
- Diuretics
- Magnesium Sulphate
- Labetalol
Route and dose:
Oral—200–1600 mg in divided doses;
IV—50 mg bolus followed by titrated infusion
Mode of action:
Combined specific α1 and nonspecific β adrenoceptor antagonist.
The ratio of α:β blocking effects depend on
the route of administration—
1:3 for oral and 1:7 for intravenous
Side effects:
Bradycardia, fatigue, bronchospasm, gastrointestinal disturbances
Contraindication and caution:
Asthma, cardiac disease, phaeochromocytoma
- Methyldopa
Route and dose:
Oral only—250 mg–3 g/day in divided doses
Mode of action:
Acts as false neurotransmitter to norepinephrine
Side effects:
Postural hypotension, bradycardia, headache, haemolytic anaemia
Contraindication and caution: Liver disease, risk of postnatal depression
Nifedipine
Route and dose:
Oral only—20–90 mg od (Avoid sublingual route)
Mode of action:
Calcium channel antagonist.
Blocks the entry of calcium ions
through the L-type channels.
Side effects:
Headache, tachycardia, flushing, and visual disturbances
Contraindication and caution:
Aortic stenosis, liver disease
Hydralazine
Route and dose:
IV only 5 mg slow bolus followed by 5 mg/hr
Mode of action:
Activation of guanylate cyclase and
increase in intracellular cyclic GMP
leading to decrease in intracellular calcium,
causing vasodilatation
Side effects:
Fluid retention,
flushing,
palpitations,
headache,
dizziness,
tachycardia,
systemic lupus-like syndrome,
peripheral neuropathy
Contraindication and caution:
Severe tachycardia
- α Blockers
- α Blockers
(Prazosin/Doxazosin)
Mode of action: Highly selective α1 adrenoceptor blocker
Side effects: Syncope, headache, postural hypotension
Contraindication and caution:
No true evidence of teratogenicity but use
only if benefit outweighs risk.
- β Blockers
Mode of action:
β adrenoceptor antagonists
Side effects: Bradycardia, neonatal hypoglycaemia
Contraindication and caution: May cause IUGR; avoid in pregnancy
Diuretics
Mode of action:
Various sites of nephron;
only use in pulmonary oedema
Side effects:
Neonatal thrombocytopenia
Contraindication and caution:
Do not cause fetal malformations;
generally avoided in pregnancy
as its use might prevent the physiologic volume
expansion in normal pregnancy.
Magnesium Sulphate
Route and dose:
IV only—4 g bolus over 10 min followed by 1 g/hr
infusion for 24 hours or 0.5 g/hr if oliguric.
(Further bolus of 2–4g over 10 min if seizures recur.)
Mode of action:
° Antagonist at calcium channels reducing systemic and cerebral vasospasm
° N-methyl D-aspartate receptor antagonist—
anticonvulsant action
° Increased production of endothelial prostacyclin
may restore thromboxane—prostacyclin imbalance
MgSO4 - aware
Caution:
Due to its vasodilatory effects,
it increases blood loss
and,
if given prior to general anaesthetic,
will also increase the duration of neuromuscular blocking agents.
Care when using along with Nifedipine as they may
interact synergistically.
Magnesium crosses the placenta leading to neonatal
hypotonia and respiratory depression.
When the decision is made to deliver the baby, what anaesthetic technique would you use?
The decision to deliver is made by the consultant obstetrician and usually
depends largely on the maternal rather than the fetal well-being as delivery
improves the maternal disease.
The mother’s safety is paramount, and the blood pressure has to be under
control to avoid complications.
The choice between general anaesthesia (GA) and regional technique will be
guided by:
- Platelets level (> 80 × 109/L on a recent blood result)
- Blood pressure control
- CTG
__________________________________________________
And also influenced by:
* Mother’s anaesthetic history
* Airway assessment
* BMI
The choice is between spinal anaesthetic and GA.
There is no evidence that an epidural technique
confers more cardiovascular stability than a spinal.
Providing there are no contraindications
(i.e. low platelets or fetal bradycardia)
a regional technique is the preferred option
What are the indications for magnesium?
The MAGPIE trial in 2002 has shown that
magnesium is effective in reducing the incidence of eclampsia.
The Collaborative Eclampsia Trial in 1995 has
proved it to be more efficient in
treating eclamptic seizures than diazepam or phenytoin.
The loading dose is 4 g over 10 to15 min
followed by 1 g/hr infusion for
24 hours or 0.5 g/hr if oliguric.
A further bolus of 2–4 g over 10 min is repeated if seizures recur.
How does magnesium work in pre-eclampsia?
- Antagonist at calcium channels
reducing systemic and cerebral vasospasm
- Antagonist at calcium channels
- N-methyl D-aspartate receptor antagonist—
anticonvulsant action
- N-methyl D-aspartate receptor antagonist—
- Increased production of endothelial prostacyclin
may restore thromboxane— prostacyclin imbalance
- Increased production of endothelial prostacyclin
How and why is the magnesium level monitored?
Higher magnesium levels in the blood
lead to undesirable and life-threatening complications,
and hence the level should be monitored.
The adequacy of treatment is assessed
by regular checking of deep tendon reflexes and by
blood levels.
The therapeutic range is 2–4 mmol/L.
What are the side effects of
hypermagnesemia?
- Loss of deep tendon reflexes, blurred vision > 5 mmol/L
- Respiratory depression > 7 mmol/L
- Cardiac conduction defects > 7.5 mmol/L
- Cardiorespiratory arrest >10 mmol/L
Loss of patellar reflexes should prompt a blood level
and the stopping of the infusion.
Toxicity is more likely to occur if renal impairment is present.
How is magnesium-induced cardiac arrest treated?
In the case of cardiac arrest:
- Stop infusion
- Start CPR
- Give 10 ml of 10% calcium gluconate intravenously
- Send blood for magnesium levels to lab immediately
- Employ further symptomatic treatment
Post-delivery care
Convulsions can occur up to 23 days after delivery. In the UK, up to 44% of
fits occur in the puerperium
Fluid balance can remain difficult in the post-operative period.
The most common time for pulmonary oedema to
occur is in the first 48–72 hours post-delivery.
This is probably as a result of large volumes of fluid given peri-operatively (in the face of oliguria and capillary-leak syndrome) mobilising from the extravascular space as the
patient improves.
Platelet count is lowest in the 24–48 hours post-delivery and HELLP presents after delivery in 30% of cases.
This demonstrates that, although delivery of the baby is the ‘cure’, it may not be the end of the
problem.
The decision to send a patient to intensive care is made on the
basis of her clinical condition (a patient may also be considered for intensive
care pre-operatively).
