Definitions
Preeclampsia
Pregnancy-induced hypertension (≥ 140/90 mmHg) with significant proteinuria and resolving within 12 weeks of conclusion of pregnancy.
Severe preeclampsia
pregnancy-induced hypertension ≥ 160/110 mmHg with significant proteinuria.
Eclampsia
Occurrence of tonic–clonic seizures in a woman after 20 weeks’ gestation (which may occur with preeclampsia) unless
explicitly explained by alternative pathology.
Incidences of 1.5- 7.7% have been reported in the developed world, and
non-proteinuric pregnancy-induced hypertension is approximately twice as common (4.2–7.9%)
Pathophysiology
the pathogenesis of preeclampsia is incompletely understood.
Relatively shallow invasion and transformation of maternal spiral arteries leads to placental damage.
The placenta releases inflammatory and vasoactive substances which act on maternal endothelium, activating platelets to release vasoconstrictory thromboxanes.
This results in increased endothelial permeability and increased systemic vascular resistance accounting for the multisystem nature of preeclampsia.
When the placenta is delivered the syndrome resolves
Maternal Preeclampsia may affect multiple organ systems.
Immediate effects
Peripheral vasoconstriction → hypertension → cerebrovascular haemorrhage, placental
abruption.
Oedema→peripheral, cerebral, hepatic (liver
rupture/failure/necrosis), pulmonary (usually iatrogenic).
Intravascular dehydration → renal failure (acute tubular necrosis).
Venous thromboembolism (VTE).
Deranged clotting/disseminated intravascular coagulation.
HELLPsyndrome (Haemolysis, Elevated Liver enzymes, Low Platelets).
Eclampsia.
Medium-term effects
Protracted antihypertensive requirement.
Prolonged hospital admission.
Interventional delivery (induction of labour,
caesarean section).
Thrombophilic state.
Long-term effects
Recurrence of gestational hypertension or
preeclampsia in future pregnancies.
Increased incidence of hypertension, renal disease and death (due to cardiovascular events).
Fetal/developmental
Immediate effects
Fetal growth restriction (FGR).
Fetal death in utero.
Short-term effects
Risk factors
Chronic hypertension
Newpartner
Renal disease
≥10years since last pregnancy
First pregnancy
Family history
Previous preeclampsia-affected
pregnancy
Barrier contraception
Multiple pregnancy
Extremes of maternal age
Short sexual cohabitation
Molar pregnancy
Obesity
Donor insemination
Fetoplacental trisomy
(Pre-gestational) diabetes
Antiphospholipid syndrome
Systemic lupus erythematosus
Other autoimmunedisease
the most significant being preexisting renal disease (20-fold increase) or hypertension (five-fold increase).
Prediction
Early pregnancy
Currently no test can accurately predict who
will develop preeclampsia early in pregnancy/ preconceptually.
A variety of clinical, biochemical and
ultrasonic markers have been examined individually or in combination (including body mass index, early pregnancy blood pressure, alpha-fetoprotein,
human chorionic gonadotrophin, oestriol, inhibin
Pregnancy-associated plasma protein-A, uric acid, placental growth factor and soluble vasculo endothelial growth factor 1.
None is adequately
specific or sensitive for wide spread clinical use.
Prematurity → respiratory distress, necrotising enterocolitis.
Neonatal death.
Long-term effects
Cerebral palsy (antepartum hypoxia).
(Early onset) hypertension, diabetes and
ischaemic heart disease in later life.
Prevention
Preventing preeclampsia
Various interventions have been tested
the majority unsuccessfully.
The following are proven to reduce
the risk of developing preeclampsia.
Low-dose aspirin (75 mg)
risk of preeclampsia reduced by 17% overall, 25% in high-risk
women, 40%reduction in progression from
non-proteinuric gestational hypertension to
preeclampsia .
Calcium-supplementation ≥ 1 g/day reduces the risk of preeclampsia by 55% overall, 88% in those at high risk.
Preventing eclampsia
Magnesium sulphate given prophylactically
reduces the risk of eclampsia by 59% in women with severe preeclampsia
Severe preeclampsia
Blood pressure ≥ 160/110 mmHg
(mean arterial pressure (MAP) 125 mmHg=diastolic blood pressure + 1/3(systolic−diastolic blood pressure)
on at least one occasion, or
two consecutive
blood-pressure readings ≥ 140/90 mmHg at least 4 hours apart with additional feature(s).
Severe headache with visual disturbance.
Epigastric pain.
Clonus.
Papilloedema.
Liver tenderness.
Platelet count 100 × 109/l.
Alanine aminotransferase 50 iu/l.
Creatinine 100 mmol/l.
Proteinuria ≥ 300 mg/24 hour urine collection, or urinary protein/creatinine ratio (PCR) 30 mg/mmol
Pending results, bedside semi-quantitative
analysis on mid-stream or catheter specimen urine of ≥ 1+protein.
Eclampsia
Occurrence of tonic–clonic seizure in pregnant woman(preeclampsia may be mild or undiagnosed prior to seizure) unless undoubtably explained by alternative pathology.
General
High-dependency obstetric care setting withone-to-one experienced midwifery care.
Wide-bore intravenous access.
Urinary catheter with hourly measuring chamber.
Multidisciplinary review by senior obstetric and anaesthetic staff 4-hourly
low threshold for involvement of consultant obstetrician and anaesthetist.
Inform neonatologist if delivery is considered 34 weeks’ gestation.
Monitoring
Hourly measurement/documentation of maternal observations (blood pressure, pulse, respiratory rate, oxygen saturation, temperature, urine output, neurological status).
Blood pressure (including MAP) and pulse
measured every 15 minutes until stabilised.
Oxygen saturations should be monitored
continuously medical review if 95% on air.
Meticulous fluid balance is essential to avoid
pulmonary oedema.
Deep tendon reflexes and clonus: 4-hourly.
****Consider use of invasive arterial blood-pressure monitoring if***
Unstable blood pressure.
Persistent severe hypertension (more than one agent to control blood pressure).
Inaccurate indirect maternal blood pressure
measurement.
Discrepant automated/manual readings.
Obesity.
Haemorrhage 1000ml/delivery complications.
Hypoxia requiring arterial blood gas monitoring.
Difficult venepuncture.
Request the following urgent investigations
full blood count,renal and liver function tests,urate,blood group and save serum.
Clotting studies if platelet count 100 × 109/l.
Frequency of re-testing depends upon results, clinical situation and therapy.
Fetal well-being
Once initial maternal management instituted, fetal heart rate monitoring should be commenced if gestation ≥ 24 weeks (intermittent fetal heart auscultation for viability 24 weeks).
Ensure the maternal condition is stable before acting upon fetal compromise.
Following stabilisation, ultrasound assessment of fetal growth, liquor and umbilical artery Doppler to identify FGR/plan delivery.
Management
1)Bloodpressure control
2)Fluid input 83 ml/hour
3)Catheterise
4)Hourly urine output
Blood pressure trend can be measured using automated blood-pressure reading machines but
should be verified with manual blood-pressure measurement (Korotkoff phase 5 to indicate diastolic blood pressure) as very few automated blood-pressure analysers are validated for use in pregnancy.
Very high readings are particularly
important to check manually as automated
analysers tend to underestimate blood pressure.
Control blood pressure to 160/105 mmHg
(MAP 125mmHg)gradually to reduce
immediate risk of cerebral haemorrhage.
A suggested protocol for initial management
(1) Oral labetalol 200 mg, repeated after
30 minutes if required.
(2) If oral medication fails to control hypertension then give intravenous labetalol 50 mg over
5 minutes, repeated after 10 minutes if
required (maximum 4 doses)
(3) Intravenous labetalol infusion 20 mg/hour, doubling the infusion rate every 30 minutes if required (maximum 160 mg/hour).
(4) If labetalol is ineffective, intravenous
hydralazine bolus 5 mg over 5 minutes,
repeated every 20 minutes if required
(maximum4doses).
(5) Intravenous hydralazine infusion 1 mg/hour,increasing every 30 minutes if required (maximum5mg/hour).
(6) Intravenous hydralazine bolus should be
2.5–5 mg over 5 minutes.
Maintain blood pressure within the range
140–150/80–90 mmHg or booking blood pressure (whichever is higher) to ensure adequate utero-placental perfusion
rapid or prolonged hypotension may precipitate fetal compromise
Seizure prophylaxis
Magnesium sulphate should be commenced at diagnosis of severe preeclampsia/eclampsia.
continuing until 24 hours following delivery/last seizure/commencement of magnesium sulphate therapy, whichever is the later.
Administer magnesium sulphate according to the Collaborative Eclampsia Trial protocol.
4g magnesium sulphate over 5–10minutes,
followed by an infusion of 1 g/hour.
Seizures treated with further 2 g magnesium
sulphate bolus dose and increase infusion rate to 1.5 g/hour.
Monitor renal function (not magnesium levels) 6-hourly during magnesium therapy.
In the absence of oliguria ( 80 ml per 4-hour
period), magnesium toxicity is rare.
In oliguria consider cessation of magnesium sulphate until urine output improves.
Signs of magnesium toxicity include respiratory rate 12 per minute whilst awake and absence of deep tendon reflexes
check respiratory rate hourly and reflexes 4-hourly as a minimum.
Treat magnesium toxicity with 10 ml of 10%
calcium gluconate intravenously over 10 minutes and cessation of magnesium sulphate infusion.
Involve senior obstetricians and anaesthetists.
Thromboprophylaxis
Graded compression stockings should be applied provided no contraindications exist.
Consider use of pneumatic compression devices e.g. ‘Flotron boots’, particularly in those with additional VTE risk factors or contraindication to compression stockings.
Prophylactic heparin should be commenced as soon as possible and recommenced as
soon as possible following delivery.
Dose calculated according to pre/early pregnancy weight.
Potential for imminent ( 12–24 hours) delivery should be assessed prior to every administration (withhold if necessary).
Heparin should not be administered 6hours
from insertion/removal of spinal/epidural
anaesthesia.
Epidural catheter not to be removed within
12 hours of heparin administration.
Prophylactic heparin should be continued for a minimum of the duration of hospital stay.
Fluid management
Limit input to 83 ml/hour (2 litres/24 hours)
including therapeutic infusions (e.g. magnesium/ antihypertensives)
administer fluids orally
where possible (if intravenous, via infusion
pump/syringe).
Large volume fluid losses should be replaced but not exceeded.
Antenatal oliguria is not an indication for
alteration of fluid input.
If concerned involve senior obstetric/anaesthetic/renal physicians and expedite delivery.
Delivery
the definitive treatment of preeclampsia/
eclampsia is delivery,however this is inappropriate until the maternal condition is stable, even with fetal compromise.
Timing of delivery
37 weeks’ gestation
after maternal stabilisation, regardless of severity of preeclampsia .
34–37 weeks’ gestation
delivery is rarely associated with adverse maternal or fetal outcomes (consider betamethasone for fetal lung maturity.
evidence lacking) therefore
delivery should be considered.
A randomised controlled trial is currently addressing this issue.
34 weeks
delivery indicated only if severe
maternal/fetal compromise.
Individualised clinical/biochemical parameters for delivery 34 weeks should be documented by the senior obstetrician.
If delivery is anticipated within 2 weeks, corticosteroids (e.g. 2 doses of betamethasone 12 mg
intramuscularly 24 hours apart) should be administered to reduce the risk of surfactant deficiency lung disease.
Severe, deteriorating disease in mothers of fetuses of pre-viable weight/gestational age is an indication to offer termination of pregnancy on maternal health grounds.
Place of delivery
Dueto potential sudden changes in maternal
condition in utero transfer is generally
inappropriate in severe preeclampsia/eclampsia.
ex utero transfer of the baby to a relevant facility is usually preferred.
If transfer is planned, all maternal observations must be stable, blood pressure maintained 160/105 mmHg without evidence of fetal compromise.
The patient should be accompanied
by a senior midwife and anaesthetist.
Transfer notes and investigation results with the patient.
Mode of delivery
No benefit exists to elective caesarean over vaginal delivery, provided no contraindication to vaginal delivery exists .
However, under 32 weeks’
gestation, caesarean section is preferred due to the high risk of failed induction of labour.
There is no evidence to support limiting the duration of the active second stage of labour.
The full range of analgesia options should be
made available to women with severe
preeclampsia during delivery.
Regional anaesthesia is generally safe if
platelets ≥ 80 × 109/l.
Routine fluid loading should not be given;
hypotension should be managed with
judicious aliquots of phenylephrine.
If general anaesthetic is necessary, anticipate pressor effects of intubation in preeclampsia and allow adequate time for its management, usually with opiates, even in the context of severe fetal compromise.
H2 antagonists (e.g. ranitidine) should be
administered prior to caesarean delivery.
Management of the third stage
Active management, with intramuscular oxytocin (10 iu) rather than ergometrine-containing products, is optimal due to increased risk of postpartum haemorrhage.
Eclampsia
Eclampsia affects 1/2000 pregnancies in the UK.
It may occur prior to diagnosis of preeclampsia.
Unless there is objective evidence to the contrary, any tonic-clonic seizure in the third trimester of pregnancy should be regarded as eclampsia until proven otherwise.
Call all emergency personnel.
inform consultant
obstetrician and consultant anaesthetist.
Ensure safety (patient and team).
Systematic assessment of the patient as per
Advanced Life Support algorithm paying
particular attention to prevention of supine
hypotension by use of a wedge or tilt.
Administer magnesium sulphate bolus (4 g over 10 minutes) as described above.
In persistent seizures refractory to magnesium sulphate, consider diazepam, thiopentone or phenytoin.
Intubation, ventilation and muscle relaxation may be required if seizures do not respond to second-line drug therapy.
Send blood for magnesium level if patient was receiving magnesium sulphate prophylaxis prior
to seizure (aim 2–4 mmol/l).
Once seizure has resolved, perform full
neurological examination, examine for other Causes (electrolyte imbalance, sepsis, drug/alcohol withdrawal) and treat accordingly.
Neuroimaging (CT/MRI) may be used to exclude other causes of seizure including intracerebral bleed, particularly if focal neurological signs persist.
If antenatal, consider delivery when maternal condition stable.
Emergency documentation should be of a high standard.
Debrief the patient, family and clinical team.
Report as an adverse incident for risk
management.
In the case of further seizures in a patient
receiving magnesium sulphate administer a
further 2 g bolus.
Treatment of HELLP
Nospecific therapy exists, spontaneous resolution should occur postnatally as with severe preeclampsia.
Corticosteroids lead to quicker improvement of haematological parameters but no improvement in maternal outcomes has been demonstrated and therefore should not be administered for this purpose.
Postpartum management
Continue fluid restriction for the duration of
magnesium infusion or until diuresis occurs.
Postnatal oliguria, e.g. urine output
0.5 mg/kg/hour for 4 hours, in the presence
of normal renal function tests, is not generally considered an indication for intervention.
acute tubular necrosis is a rarer event than
iatrogenic pulmonary oedema.
However, monitor persistent oliguria with 6-hourly renal function tests.
In the presence of arising creatinine,
intervention may be considered, guided by
accurate fluid balance.
Monitor in hospital with measurement of
maternal observations at least 4-hourly following discontinuation of magnesium sulphate, until at least the fifth postnatal day as per NICE guidance .
Anticipate postnatal antihypertensive
requirements to prevent delayed discharge.
Recommended agents include labetalol or
nifedipine (modified-release form).
If methyldopa was used antenatally this should be withdrawn (replaced if necessary) after delivery .
Ensure thromboprophylaxis is maintained.
Discharge from hospital if asymptomatic of
preeclampsia with stable blood pressure
150/100 mmHg, if facility exists for
alternate-days blood-pressure assessment as a minimum.
Follow up with the general practitioner within 2weeks of discharge and with hospital consultant 6–8 weeks following delivery.
Antihypertensives often require a graded
withdrawal.
Approximately 20% of patients
require ongoing antihypertensive medication 6 months after delivery and 13% of women will have chronic hypertension .
Consider antiphospholipid antibody/inherited thrombophilia screen particularly if early-onset preeclampsia ( 28 weeks) or FGR.
Ensure proteinuria has subsided, if still present re-check in 3 months and/or consider referral to renal physicians according to local protocol.
Debrief regarding antenatal and postnatal
events.
Preconceptual counselling prior to future pregnancies
Risk of gestational hypertension is 13–53%
dependent on severity/gestation of onset
and persistence of additional risk factors.
Risk of preeclampsia is 16% (25% if severe
preeclampsia, HELLP or delivery 34 weeks,
55%if delivery 28 weeks).
Long-term cardiovascular health
assess risk of chronic hypertension and modifiable risk factors for cardiovascular disease.
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