Hypertension in pregnancy
Marcelle Michail, MBBS, FRCA
The current recommended classification is that by the International Society
for the Study of Hypertension (ISSHP). This recognised four categories in
Gestational hypertension and/ or proteinuria developing during pregnancy
after 20 weeks’ gestation in a previously normotensive, non-proteinuric woman.
- Hypertension without proteinuria
- Proteinuria without hypertension
- Gestational proteinuric hypertension (pre-eclampsia)
Chronic hypertension and chronic renal disease
- Chronic hypertension without proteinuria
- Chronic renal disease diagnosed before, during or persisting after
- Chronic hypertension with superimposed pre-eclampsia
Unclassified hypertension and/ or proteinuria, which is found at the first
antenatal, visit after 20 weeks’ gestation in a woman whose past hypertensive
status is unknown.
Eclampsia is the occurrence of generalised convulsions during pregnancy,
labour or within 7 days of delivery in the absence of epilepsy or another
condition predisposing to convulsions.
Definition of hypertension
The ISSH defines hypertension in pregnancy as:
- One reading of diastolic pressure exceeding 110 mm Hg or
- Two consecutive diastolic arterial pressures of 90 mm Hg or greater at an
interval of at least 4 h.
Recently it has been proposed that a rise of more than 15 mm Hg above value
obtained at < 20 weeks gestation or absolute value
140/90 mm Hg may identify a group of women with pre-eclampsia more accurately.
Diastolic pressure should be recorded using Koratkoff IV sounds.
Pre-eclampsia complicates 3-5% of first pregnancies with 5-10% 0f cases being
severe. It accounts for 16% of maternal deaths in the UK.
Severe pre-eclampsia exists if one or more of the following is present:
- Arterial pressure > 160 mm Hg systolic or >
110 mm Hg diastolic on two occasions at least 6 h apart
- Proteinuria > 5 g in 24 h or >
3 + on dipstick
- Oliguria < 400 ml/day
- Cerebral signs: headache, blurred vision or altered consciousness
- Pulmonary oedema or cyanosis
- Epigastric or right upper quadrant pain
- Impaired liver function
- Hepatic rupture
- HELLP syndrome
Note that no feature of pre-eclampsia is consistently present and although
they can be used to recognise pre-eclampsia their absence never excludes it.
Pre-eclampsia becomes eclampsia with any degree of hypertension if convulsios
Generally accepted that the essential disorder is utero-placental ischaemia.
It has been proposed that abnormal placental function, perhaps related to
immune mechanisms lead to altered placental prostacyclin/thromboxane ratio,
platelet aggregation, thrombin activation and fibrin deposition in maternal
systemic vascular beds.
Another proposal is that poor placental perfusion is due to abnormal
placentation: endovascular trophoblast invasion remains superficial, rarely if
ever reaching the myometral segments. As a result the maternal spiral arteries
remain muscular and undilated with consequent placental hypoperfusion.
- Previously thought that the convulsions occur as a result of cerebral
oedema. However, recent work suggests that the underlying pathology is
vasospastic ischaemic injury.
- Where convulsions are severe and prolonged cerebral oedema can occur but
this is probably a consequence rather than a cause.
- A review of the literature concludes that, compared to normal
pregnancies, intravascular volume is reduced, cardiac output decreased and
- Increased sensitivity to normal circulating pressor agents including
vasopressin, noradrenaline and angiotensin II. Sensitivity to latter
antedates clinical presentation by weeks to months.
- In severe pre-eclampsia, plasma albumin decreased due to across leaky
- Maternal vascular prostcyclin is reduced and platelet thromboxane A2
production is increased. The resulting imbalance contributes to
platelet activation and vascular damage.
- Activation of clotting cascade is consistent finding although often not
clinically apparent. In some cases changes may antedate clinical evidence
of pre-eclampsia by several weeks.
- Thrombocytopenia occurs in 1/3 of pre-eclamptic women and DIC in 7%.
- Pulmonary oedema is not uncommon
- Occurs in about 3% of patients with severe pre-eclampsia and eclampsia;
70% of the cases develops pulmonary oedema about 70 hours after delivery.
It occurs more commonly in association with multiple organ dysfunction
than as an isolated complication.
- Occurs as a result of (a) a low COP in association with increased
intravascular hydrostatic pressure, and (b) increased capillary
- PVR normal or reduced
- Laryngeal oedema
- The cause of the hepatic dysfunction is not clear but it may result from
periportal hepatic necrosis, subcapsular haemorrhage or fibrin deposition
in hepatic sinusoids.
- Spontaneous hepatic rupture is rare but potentially lethal complication,
which carries 60% mortality.
- The impaired liver function can affect clearance of drugs metabolised by
- The type of proteinuria in pre-eclampsia is non-selective; the increased
permeability allows large molecular weight proteins to appear in the
- The majority of cases have mild to moderately diminished renal perfusion
and glomerular filtration. This is caused by glomerular swelling,
narrowing of the glomerular capillary lumen and fibrin deposition in the
endothelial cells (glomerular capillary endotheliosis).
- Acute tubular necrosis is often the cause of the reversible renal
failure and this has a good prognosis.
- Abruptio placentae, DIC and hypovolaemia usually precede the renal
- Impairment of placental perfusion caused by placental disease and
vasospasm almost certainly the major reason for the high incidence of
fetal loss, intrauterine growth retardation and perinatal mortality.
- It has been found that there is a shift of the oxyhaemoglobin curve to
the left in these patients and this decrease oxygen availability.
Prediction in pre-eclampsia
Currently, there is no ideal predictive test that fulfils all desired
The two most important predictive factors remain nulliparity and family
Uterine artery Doppler: may detect abnormal waveforms at 16-18 weeks
gestation (due to impaired trophoblastic invasion of the spiral arteries)
Elevated maternal levels of plasma urate have been shown to correlate with
the risk of fetal mortality and are widely used as an indication for early
History of chronic hypertension
Family history of pre-eclampsia
The Collaborative Low Dose Aspirin study (CLASP):
Multicentre study aimed to investigate benefits of low dose aspirin (60 mg)
and any fetal/neonatal or maternal side effects
It was concluded that:
- Routine prophylactic or therapeutic use of antiplatelet therapy for all
women at risk of developing pre-eclampsia or IUGR is not recommended.
- There is a small risk of increased peripartum haemorrhage.
- Groups of patients who benefit history of early onset pre-eclampsia and
- No increased neonatal morbidity or mortality.
- No increased maternal mortality.
Recent studies demonstrated that calcium supplements reduced the incidence of
hypertension, pre-eclampsia and preterm delivery. Controlled trials are needed
to confirm if there is any significant reduction in perinatal mortality.
Management of pre-eclamptic ideally should be multidisciplinary.
Control of blood pressure
- It is recommended that arterial pressure of greater than 170/110 mmHg
should be treated with urgency with the aim of maintaining pressure below
170/110 but above 130/90 mmHg. The aim should be to prevent intracerebral
haemorrhage while not affecting uteroplacental blood flow and maternal renal
function. Precipitous reduction in blood pressure should be avoided by
adequate volume expansion before the use of vasodilators.
- In mild cases, blood pressure control can usually be achieved within 12
hours by oral loading and then regular dosing with methyldopa, augmented
with hydralazine if necessary.
In case of severe refractory hypertension:
- the most widely used agent
- Main advantage is the extensive experience of its use
- given either as intermittent bolus doses (5- 10 mg every 20 min
- or as continuous infusion (5- 20 mg/hr) following an initial 5 mg
- onset of action: 20 –30 min
- one of the drawbacks of hydralazine is that its side effects (headache,
tremor and vomiting) mimic the symptoms of impending eclampsia
- given either as bolus dose of 50 mg repeated at 30 min as necessary or
as continuous infusion at 20- 160 mg/hr
- Onset of action: 5- 20 min
- Equally effective to hydralazine, sometimes preferable because of
relative freedom from maternal side effects
- severe pre-eclampsia - impairs the capacity of the fetus to cope
with intrauterine stress and it may attenuate the usual signs of fetal
- unlicensed for use in pregnancy
- Shown to be satisfactory in the management of hypertension in pregnancy
- Should be used with caution if MgSO4 is being given concurrently as
potentiation may occur leading to profound hypotension
- Other antihypertensives such as GTN and SNP are used less frequently as
their hypotensive effect occurs rapidly with a risk of hypotension and
reduced uteroplacental blood flow. Direct arterial pressure measurement is
- GTN: - initial rate of infusion at 10 mg/min titrated against response.
Risk of methaemoglobinaemia if a dose of 7 mcg/kg/min is exceeded
- SNP: -initial dose 0.25 mcg/kg/min, increased according to response.
Risk of fetal cyanide toxicity and death (recent studies failed to show
evidence of cyanide accumulation in the fetus)
Prevention and control of fits
Felt to be indicated if fits thought to be imminent in some units while
others start treatment only after first fit.
Dispute regarding the most effective means of controlling convulsions with
most British and European doctors using anticonvulsant and most American using
The Collaborative Eclampsia Trial:
Aim: to compare MgSO4, diazepam and phenytoin in the treatment of
eclampsia (multicentre study).
- MgSO4 should be the drug of choice for eclampsia
- Phenytoin caused more maternal and neonatal morbidity
- Diazepam and phenytoin had more recurrent convulsions compared with MgSO4
A large multicentre trial (MAGPIE Trial) is now underway comparing MgSO4
with placebo in women with pre-eclampsia.
Use of MgSO4 in eclampsia
Loading dose: 4-6 g IV over 15 min
Maintenance: 1-2 g/hr infusion for at least 24 hr after the last convulsion
4.0- 6.5 mmol/l
nausea and vomiting
loss of patellar reflex
6.5- 7.5 mmol/l
> 10 mmol/l
When MgSO4 is used monitoring should include regular measurement
of plasma concentration of Mg and assessment of tendon reflexes for hypotonia.
Indication for delivery
Patient at term or at a gestation where viability of the fetus is not a
At any stage of pregnancy for:
- Maternal complication such as:
- Fetal complications such as:
- Cardiotocographic abnormalities
Treatment of oliguria
The definition of oliguria used in clinical practice includes a urine output
of < 20-30 ml/hr for 2 consecutive hours. The
diagnosis of oliguria should be based on at least a 4 hours period.
The most appropriate initial management is fluid management. If there is no
response to a fluid challenge, CVP/PAWP should be measured before deciding
further treatment. Repetitive unmonitored fluid administration should be
avoided as this may lead to pulmonary oedema especially in the postpratum
Poor renal function in these patients has a good prognosis.
Anaesthesia and analgesia in patients with pre-eclampsia
Regional anaesthesia has been the anaesthetic management of choice for
labour and caesarean section in pre-eclamptic patients.
Epidural analgesia reduces plasma catecholamines levels as well as improving
intervillous blood flow.
A coagulopathy is considered an absolute contraindication to regional
analgesia. The risk of epidural haematoma is difficult to quantify and may
occur spontaneously even in the absence of risk factors. It has been
recommended that regional block should be avoided if platelet count is less
than 80.000/mm3 or the bleeding time is prolonged.
The risk of epidural haematoma with the use of low-dose aspirin has not been
quantified, but in the CLASP study there has been no epidural complication
that could be attributable to the use of aspirin.
The choice of anaesthetic technique in pre-eclamptic requiring caesarean
section is controversial. A well-managed incremental epidural anaesthesia is
the technique of choice for most patients, providing relatively smooth control
of blood pressure, maintaining utero-placental perfusion, optimising fetal
outcome and eliminating the airway and haemodynamic problems associated with
Spinal anaesthesia is often discouraged in patients with pre-eclampsia
because of the risk of severe hypotension. This view has been challenged by a
recent study, showing a poor correlation between the degree of hypotension
during regional anaesthesia and neonatal umbilical acid-base status.
General anaesthesia, if required, can present problems; these include:
Occurs in approximately 0.04% of deliveries.
- Potentially difficult intubation, laryngeal oedema may not become
apparent until laryngoscopy
- Exaggerated hypertensive response to intubation may increase the risk of
cerebrovascular accident, increase myocardial oxygen requirement, induce
cardiac arrythmias, induce pulmonary oedema and reduce uterine blood flow.
MgSO4 has been used to control both catecholamine release and
the pressor response. It was found that pre-treatment with 40 mg/kg is
superior to either lignocaine or alfentanil. Short acting opioids have
been used at induction of anaesthesia e.g. fentanyl 2.5 mcg/kg and
alfentanil 10 mcg/kg. Esmolol proved to be useful not only for intubation
but also for extubation due to its rapid onset and short duration of
- Impaired intervillous blood supply.
- Difficulties related to neuromuscular blockers in the mother receiving
MgSO4. Fasiculations may not occur after suxamethonium, with
potentiation if the action of non-depolarising agents.
- Potential aspiration of gastric content.
- Teenage patients and mother with multiple pregnancies have a higher risk
of developing fits.
- Eclampsia, which occurs antenatally, carries more complications than when
the condition develops in the intrapartum or postpartum periods.
- Complications include:
- HELLP syndrome
- Pulmonary oedema
- Cardiorespiratory arrest
- Aspiration of gastic content
- Neurological abnormalities
- Transient deficit
- Transient cortical blindness
- Retinal detachment
- Intracerebral bleed
Haemolysis, elevated liver enzymes and low platelet count
Severe form of pre-eclampsia. Complicates 0.3% of all pregnancies and
between 4 and 20% of those with severe pre-eclampsia. 30% of the cases occur
in the postpartum period. Associated with increased maternal and fetal
mortality and morbidity.
The clinical signs and symptoms include epigastric pain, upper abdominal
tenderness, proteinuria, hypertension, jaundice, nausea and vomiting. The
syndrome may occur in the absence of overt hypertension. The disease may
progress to haematuria, oliguria, acute tubular necrosis, cortical necrosis
Laboratory values used to diagnose HELLP syndrome are:
- Haemolysis, defined by abnormal peripheral blood smear
- Increased bilirubin (³ 1.2 mg/dl) or
increased lactate dehydrogenase (³ 600 u/l)
- Increased serum aspartate aminotransferase (³
- Low platelet count (< 100 ´
- The ultimate treatment is delivery of products of conception. Complete
recovery usually occurs spontaneously although some further deterioration of
laboratory parameters may occur for 24- 48 hours.
- The choice of anaesthetic technique depends on the condition of the
patient and the fetus. Regional techniques may be contraindicated because of
coagulation disturbances. The drugs used should have minimal hepatic and
renal metabolism. Blood glucose should be monitored as severe hypoglycaemia
has been reported in the HELLP syndrome.
Rare complication of pre-eclampsia/eclampsia
Initially haemorrhage intrahepatic and contained by liver capsule but may
rupture into peritoneal space leading to further haemorrhage, shock and death
if not adequately treated
Pre-eclamptic patients with right upper quadrant or epigastric pain should
be considered at risk for this complication. Low platelets and raised
transaminases increase this risk.
Diagnosis often made at time of Caesarian for sudden onset of fetal
distress. When diagnosis suspected antepartum CT, ultrasound, peritoneal
lavage and hepatic arteriography are useful in making a diagnosis
Exploratory laparotomy and C-section recommended for all cases of
subcapsular haematoma diagnosed antepartum. Indications for exploratory
laparotomy during any period of observation are:
Survival better in patients treated by evacuation of haematoma, packing of
liver bed and drainage of operative site than in patients treated with hepatic
- continued need for transfusion
- deterioration of vital signs
- worsening pain or peritoneal signs
- progressive expansion of haematoma
- suspected infected haematoma.
2.3% of pre-eclamptics and 23.6% of eclamptics
Complete or partial separation of a normally implanted placenta prior to the
birth of the fetus.
Ultrasound useful in excluding placenta praevia - main differential
May need admission to intensive care for further support. (NB consideration
of the fetus is usually irrelevant, as fetal death has almost invariably
occurred in severe cases.)
- third trimester vaginal bleeding. Present in 80%, concealed in 10-20%.
Latter can result in development of Couvelaire uterus, in which
retroplacental haemorrhage extravasates into myometrium. This may be a
source of underestimation of blood loss and may lead to uterine atony
- Pain in 50%. Uterine tenderness and contractions in > 20%. Tenderness
almost invariable in severe abruption
- DIC in severe abruption. Almost never occurs in the absence of fetal
Associated with increased risk of pre-eclampsia but there is no evidence
that treating the hypertension decreases the risk.
Patients with only moderate hypertension should stop treatment prior to
conception because of the risks of teratogenesis.
If patients diagnosed as having chronic hypertension during pregnancy treat
only those in whom it presents an immediate hazards (eg patients with BP >
170/110) using methyldopa +/- hydralazine.
If patient already on beta-blocker it is probably safe to continue but if
she has to be started on treatment methyldopa is preferable.
If diuretics are essential for good blood pressure control they can be
continued but exacerbate decreased circulating volume if pre-eclampsia
Reserpine and ACE inhibitors should not be used.
© Marcelle Michail September 1999