Pre-eclampsia and eclampsia

Pre-eclampsia and eclampsia sit at the severe end of the hypertensive-disorders-of-pregnancy spectrum, and they remain a leading cause of direct maternal death in Australia, New Zealand and the United Kingdom. The Fellowship candidate must recognise the spectrum from gestational hypertension through pre-eclampsia to eclampsia and HELLP syndrome, give magnesium sulphate for seizure prophylaxis and treatment, control the severe-range blood pressure with a safe agent, and understand that delivery is the only cure. The three pillars — magnesium, blood-pressure control and delivery — are the non-negotiables of the ED resuscitation.[1][4]

Definition and the spectrum (classification)

The hypertensive disorders of pregnancy form a spectrum, classified by the International Society for the Study of Hypertension in Pregnancy and adopted across ANZ, UK and US guidelines.[1]

Gestational hypertension is new hypertension (140 systolic or 90 diastolic, or both, on two occasions four hours apart) arising after 20 weeks of gestation, in the absence of proteinuria or end-organ dysfunction. It may evolve into pre-eclampsia. [1]

Pre-eclampsia is new hypertension after 20 weeks plus proteinuria (300 mg per 24 hours, or a protein-to-creatinine ratio of 30 mg per mmol or above) or maternal end-organ dysfunction. It is divided into pre-eclampsia without severe features and pre-eclampsia with severe features, the latter defined by a severe-range blood pressure, thrombocytopenia, progressive renal insufficiency, impaired liver function, pulmonary oedema, or new-onset cerebral or visual symptoms. [1]

Eclampsia is the new-onset, generalised tonic-clonic seizure in a woman with pre-eclampsia. HELLP syndrome — haemolysis, elevated liver enzymes and low platelets — is a severe variant that may arise with only modest blood-pressure elevation. Chronic hypertension predates the pregnancy (before 20 weeks), and chronic hypertension with superimposed pre-eclampsia carries the worst prognosis. [1]

Epidemiology and risk

Pre-eclampsia complicates roughly 2 to 8 per cent of pregnancies worldwide and is responsible for a substantial share of severe maternal morbidity and of iatrogenic prematurity. In ANZ and the UK it ranks among the commonest single causes of direct maternal death, most often through intracranial haemorrhage, hepatic rupture or eclampsia itself. [1]

The risk factors cluster into the maternal, the obstetric and the medical. Nulliparity is the strongest single risk factor; other drivers are a previous pregnancy with pre-eclampsia (recurrence around 15 to 20 per cent), a multiple pregnancy, extremes of maternal age (over 35 or under 18), obesity, IVF conception and a family history. Medical risk factors are pre-existing hypertension, renal disease, diabetes, antiphospholipid syndrome and systemic lupus erythematosus. A woman carrying twins with chronic hypertension is the textbook high-risk patient the examiner will describe. [1]

Pathophysiology

Pre-eclampsia is a two-stage disease of the placenta and the maternal endothelium. In stage one, the trophoblast fails to complete its normal second-wave invasion of the spiral arteries during the early second trimester, so the spiral arteries remain narrow, high-resistance muscular vessels instead of transforming into dilated, low-resistance conduits. The placenta is rendered chronically ischaemic.[1]

In stage two, the ischaemic placenta releases anti-angiogenic factors — principally soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin — that bind and deplete the pro-angiogenic placental growth factor (PlGF) and vascular endothelial growth factor (VEGF). The result is generalised maternal endothelial dysfunction: vasoconstriction, enhanced sensitivity to pressor agents, capillary leak, microthrombosis and activation of the coagulation cascade. This single mechanism explains every end-organ manifestation — hypertension and proteinuria from the renal endothelium, transaminitis and hepatic capsule pain from the hepatic endothelium, pulmonary oedema from the pulmonary capillary leak, thrombocytopenia from consumption, and the cerebral vasospasm and oedema that produce headache, visual disturbance and eclamptic seizures. [1]

Clinical presentation

Mild or early pre-eclampsia is frequently asymptomatic, detected on routine antenatal blood-pressure measurement. The symptoms of severe disease reflect the end-organ involved: a persistent frontal or occipital headache unresponsive to simple analgesia, visual disturbance (scotomata, flashing lights, diplopia, or cortical blindness from posterior reversible encephalopathy syndrome), epigastric or right-upper-quadrant pain from hepatic capsular distension, nausea and vomiting, sudden facial or hand oedema, and reduced fetal movements from placental insufficiency. [1]

Eclampsia presents as a generalised tonic-clonic seizure, usually self-limiting but carrying the risk of hypoxia, trauma, aspiration and intracranial haemorrhage. Atypical presentations the candidate must not miss: eclampsia with a blood-pressure reading that is only mildly elevated, eclampsia in the postpartum period with no antenatal history of hypertension, and HELLP presenting as malaise and right-upper-quadrant pain mistaken for gastritis or cholecystitis. [1]

Differential diagnosis

The differential splits into the other hypertensive disorders of pregnancy (which determine the obstetric plan) and the mimics of the individual end-organ presentation (which determine the investigation). [1]

For an eclamptic seizure the broader differential is epilepsy, subarachnoid or intracerebral haemorrhage, hypoglycaemia, cerebral venous sinus thrombosis, thrombotic thrombocytopenic purpura and amniotic fluid embolism — but in any woman over 20 weeks (or recently delivered), eclampsia is the diagnosis until excluded, and magnesium sulphate is given first. [1]

Bedside assessment

Assessment runs in parallel with resuscitation and is both maternal and fetal. The ABCDE sets the priority: secure the airway of the post-ictal woman, give high-flow oxygen if hypoxic, establish two large-bore cannulae, and place the woman in the left lateral tilt to relieve aortocaval compression. Measure the blood pressure in both arms and repeat it. The neurological examination looks for hyperreflexia (a marker both of pre-eclampsia severity and of impending magnesium toxicity), visual fields, and any focal deficit that would suggest intracranial haemorrhage. Examine the lungs for pulmonary oedema, the abdomen for tender hepatomegaly, and assess the fetal condition with continuous cardiotocography. A urine dipstick of 1+ or more triggers quantification; send the baseline bloods (below) at the moment of cannulation. [1]

Investigations — values and criteria

The investigations confirm the diagnosis, grade the severity, and guide the timing of delivery. The blood pressure defines the severe range at 160 systolic or 110 diastolic. The urine is screened by dipstick and quantified by the protein-to-creatinine ratio (30 mg per mmol or above) or a 24-hour collection (300 mg or more). [1]

The blood panel — every value carries a severe-feature threshold — is the full blood count (platelets below 100 times ten to the ninth per litre is a severe feature), the urea and electrolytes (creatinine above 1.1 mg per decilitre, or doubled from baseline), the liver function tests (transaminases twice the upper limit of normal), the lactate dehydrogenase and haemolysis screen for HELLP (LDH raised, schistocytes on the film, bilirubin raised), and the coagulation (INR, APTT and fibrinogen) to detect the disseminated intravascular coagulation of severe disease or abruption. A venous gas gives the lactate and the acid-base status. The fetal assessment is the cardiotocography plus the ultrasound for growth, liquor volume and the umbilical-artery Doppler. [1]

The fullPIERS model (full Pre-eclampsia Integrated Estimate of RiSk) is a validated bedside tool that estimates the probability of a major adverse maternal outcome within 48 hours, and supports the decision to escalate or to transfer.[5]

Immediate management — the three pillars

The management of severe pre-eclampsia and eclampsia rests on three pillars, run in parallel: seizure prophylaxis and treatment with magnesium sulphate, blood-pressure control to the severe range, and delivery as the definitive cure. The obstetric, anaesthetic and neonatal teams are called at the moment of suspicion — this is never a solo emergency-medicine resuscitation.[1][4]

First, the ABCDE, intravenous access, continuous maternal and fetal monitoring, and the careful fluid balance. Pre-eclampsia is a capillary-leak state, so aggressive crystalloid loading precipitates pulmonary oedema — restrict the maintenance fluid to roughly 80 mL per hour and aim for a urine output above 0.5 mL per kg per hour. [1]

Magnesium sulphate — seizure prophylaxis and treatment

Magnesium sulphate is the cornerstone for both the prevention of the first seizure (in severe pre-eclampsia) and the treatment of the eclamptic seizure, and it is superior to diazepam and phenytoin.[2][3][4] The Magpie Trial demonstrated that magnesium sulphate at least halves the risk of eclampsia in women with pre-eclampsia, and the Collaborative Eclampsia Trial established it as the anticonvulsant of choice for the woman who has already seized.

The standard IV (Zuspan) regimen is a 4 g loading dose in 100 mL of crystalloid over 20 minutes, followed by a 1 g per hour maintenance infusion for 24 hours. (The intramuscular Pritchard alternative is 4 g IV plus 10 g IM loading, then 5 g IM every four hours.) For the woman who seizes despite the loading dose, a further 2 g IV bolus over five minutes is given. Magnesium is renally excreted, so the infusion rate is halved and the level checked if the urine output falls or the renal function is impaired. [1]

Magnesium toxicity and its antidote

Magnesium toxicity is the dose-dependent, life-threatening complication of the therapy itself, and the candidate who cannot describe it fails the station. The progressive sequence is the loss of the deep tendon reflexes (the earliest sign), then somnolence and slurred speech, then respiratory depression (respiratory rate under 12 per minute), then cardiac arrest. The therapeutic range is a plasma level of 2 to 4 mmol per litre; loss of reflexes begins around 5, respiratory depression around 6 to 7, and cardiac arrest above 12. [1]

The antidote is calcium gluconate, 10 mL of 10 per cent (1 g) given intravenously over 10 minutes. Toxicity is prevented by the bedside monitoring of the reflexes, the respiratory rate and the urine output at least hourly, and by dose reduction in renal impairment. The myth that nifedipine and magnesium are absolutely contraindicated together is just that — a myth; the synergy is mild and the combination is safe with blood-pressure monitoring. [1]

Blood-pressure control

Severe-range blood pressure (160 systolic or 110 diastolic, or both) must be lowered promptly, because the uncontrolled severe range is what causes the intracranial haemorrhage. The aim is not to normalise the blood pressure but to bring it to the 140 to 150 over 90 to 100 range. Over-correction precipitates uteroplacental hypoperfusion (fetal distress, abruption) and maternal cerebral and renal hypoperfusion — the chronically vasoconstricted circulation depends on the higher pressure.[1]

The first-line IV agents are labetalol 10 to 20 mg IV every ten minutes (to a maximum of 300 mg, then an infusion), or hydralazine 5 mg IV slowly, repeated every 20 minutes to a maximum of 20 mg then an infusion. Oral nifedipine 10 mg is used for the less acute case or as a step-down. The agents that are absolutely contraindicated are the angiotensin-converting-enzyme inhibitors, the angiotensin-receptor blockers and the direct renin inhibitors — they are teratogenic and fetotoxic, causing fetal renal agenesis, oligohydramnios and neonatal renal failure. [1]

Delivery — the only cure

The definitive treatment of pre-eclampsia is the delivery of the baby and the placenta, which removes the ischaemic placenta driving the disease. The timing balances the maternal risk of continuing the pregnancy against the fetal risk of prematurity.[1]

At term (37 weeks or more), delivery is recommended for any pre-eclampsia. For severe pre-eclampsia at 34 weeks or more, stabilise with magnesium and blood-pressure control and then deliver. For severe pre-eclampsia under 34 weeks, stabilise the mother, give corticosteroids for fetal lung maturation (betamethasone 12 mg IM, two doses 24 hours apart), transfer to a tertiary centre with neonatal facilities, and deliver if the maternal or fetal condition deteriorates — expectant management is only considered in a stable inpatient under specialist obstetric care. The mode of delivery depends on the gestation, the cervical favourability and the fetal and maternal status; eclampsia itself is not an indication for Caesarean section but the unstable mother usually is delivered operatively after stabilisation. Magnesium sulphate is continued for 24 hours postpartum regardless of the mode of delivery. [1]

HELLP syndrome

HELLP — haemolysis, elevated liver enzymes, low platelets — is a severe variant of pre-eclampsia, and it may present with only modest hypertension and little or no proteinuria, which makes it easy to miss. The Mississippi and Tennessee classifications grade the severity by the platelet count, the transaminases and the LDH. The complications are the dangerous ones: disseminated intravascular coagulation, placental abruption, acute kidney injury, pulmonary oedema, and the catastrophic hepatic haematoma and rupture (sudden severe right-upper-quadrant pain and shock in a woman with HELLP is a surgical emergency). [1]

The management is the same three pillars — magnesium sulphate, blood-pressure control, and prompt delivery — with the addition of active correction of any coagulopathy before delivery. Dexamethasone is no longer recommended for the treatment of established HELLP; it has no role beyond fetal lung maturation. [1]

Complications and pitfalls

The maternal complications are eclampsia, intracranial haemorrhage and stroke (the leading causes of death), pulmonary oedema, hepatic rupture and infarction, HELLP, disseminated intravascular coagulation, placental abruption, acute kidney injury or renal cortical necrosis, posterior reversible encephalopathy syndrome, retinal detachment and death. The fetal complications are intrauterine growth restriction, abruption, iatrogenic prematurity and intrauterine death. [1]

Prognosis and disposition

With rapid magnesium sulphate, blood-pressure control and delivery, the maternal mortality is low in the developed setting, but the morbidity — intensive-care admission, transfusion, hepatic or cerebral injury and psychological trauma — is substantial. All women with severe pre-eclampsia, eclampsia or HELLP are admitted under the obstetric team to the labour ward or the high-dependency unit; intensive care is reserved for the woman with organ failure, refractory pulmonary oedema or an eclamptic seizure complicated by aspiration or intracranial haemorrhage. Magnesium sulphate continues for 24 hours postpartum, and the blood pressure often peaks at three to six days postpartum before it settles. A woman with pre-eclampsia should be counselled at discharge on the future cardiovascular and metabolic risk — pre-eclampsia is a marker of later hypertension, stroke and ischaemic heart disease — and on aspirin prophylaxis (150 mg nocte from 12 weeks) in the next pregnancy. [1]

Special populations

The postpartum presentation is the trap: pre-eclampsia and eclampsia may arise de novo after the delivery, most often within the first 48 hours but up to six weeks postpartum, peaking at 48 hours to two weeks. A normal antenatal course does not exclude it, and the postpartum seizure or the new severe-range blood pressure in a recently delivered woman is managed exactly as the antenatal disease — magnesium sulphate, blood-pressure control, and exclusion of intracranial haemorrhage and the other mimics.[6]

The woman with a previous pregnancy affected by pre-eclampsia is offered aspirin prophylaxis and enhanced surveillance in the next pregnancy. The woman with pre-existing hypertension, renal disease or antiphospholipid syndrome is at high risk of superimposed pre-eclampsia, the combination that carries the worst outcomes. In the rural and remote setting the role of the emergency physician is to diagnose, give the magnesium sulphate and control the blood pressure, and to organise the retrieval with the infusion running. [1]

Evidence and regional guidelines

The contemporary evidence base rests on four landmark contributions. The Collaborative Eclampsia Trial (1995) established that magnesium sulphate is superior to diazepam and to phenytoin for the treatment of eclampsia.[3] The Magpie Trial (2002) showed that magnesium sulphate at least halves the risk of eclampsia in women with pre-eclampsia and reduces maternal mortality.[2] The Duley Cochrane review (2010) consolidated the anticonvulsant evidence for pre-eclampsia.[4] The fullPIERS model (2011) provided the validated bedside prediction of the adverse maternal outcome.[5] The guidelines are the ISSHP 2021 classification (Magee 2022), the NICE NG133, the RCOG, the ACOG Practice Bulletin 222, and the SOMANZ guidance in Australia and New Zealand.[1][6]

Severe features — the thresholds the examiner recites

The single most common short-answer question is the list of severe features that trigger magnesium sulphate and expedited delivery. Pre-eclampsia is reclassified as pre-eclampsia with severe features when any one of the following is present, on a background of new hypertension after 20 weeks.[1]

The angiogenic biomarkers — sFlt-1 and PlGF

The failed second-wave trophoblastic invasion shifts the placental balance of the angiogenic factors. The ischaemic placenta over-secretes soluble fms-like tyrosine kinase-1 (sFlt-1), a decoy receptor that binds and depletes the placental growth factor (PlGF) and the vascular endothelial growth factor, producing the generalised endothelial dysfunction that explains every end-organ manifestation. The sFlt-1 to PlGF ratio is now a validated adjunct: a ratio below 38 (Elecsys assay) excludes pre-eclampsia within one week with a very high negative predictive value, while a ratio above 85 (early-onset) or 110 (late-onset) predicts the imminent disease. The ratio does not replace the clinical judgement, but it shortens the "is it pre-eclampsia?" uncertainty in the woman with the borderline blood pressure and the atypical symptoms.[1]

The eclamptic seizure in the ED — minute by minute

The eclamptic seizure is a generalised tonic-clonic convulsion in a woman with pre-eclampsia. It is usually self-limiting (one to two minutes) but it carries the risk of the hypoxia, the aspiration, the trauma and the intracranial haemorrhage. The ED response is run in parallel: protect the airway, give magnesium, control the blood pressure, and prepare for delivery AFTER the stabilisation.[3][4]

Severe pre-eclampsia — the first hour at the bedside

The magnesium regimens compared

The three named regimens all deliver magnesium sulphate for the seizure prophylaxis and treatment; the choice depends on the setting and the venous access.[3][4]

The antihypertensive agents compared

The first-line agents for the severe range are labetalol, hydralazine and nifedipine; the choice is informed by the comorbidity and the onset required. [1]

HELLP — the criteria, the classifications, the catastrophes

HELLP is Haemolysis, Elevated Liver enzymes, Low Platelets. It is a severe variant of pre-eclampsia, and uniquely it may present with only the modest hypertension and the minimal proteinuria, which makes the bedside recognition harder. [1]

Delivery timing — the gestation ladder

Prevention — aspirin and surveillance

The woman identified as moderate- or high-risk for pre-eclampsia in the first trimester is offered low-dose aspirin 150 mg nocte from 12 weeks until 36 weeks. The ASPIRIN trial and the meta-analysis of the individual-patient data established that the aspirin reduces the preterm (under 37 weeks) pre-eclampsia by about 60 per cent in the high-risk woman, with the greatest benefit when it is started before 16 weeks.[7] Calcium 1 to 1.5 g daily is recommended where the dietary intake is low. The surveillance in the high-risk woman includes the regular blood pressure, the urinalysis and the third-trimester growth and umbilical-artery Doppler scans.

Long-term maternal cardiovascular sequelae

A woman who has had pre-eclampsia carries roughly a doubled lifetime risk of the cardiovascular disease — the ischaemic heart disease, the stroke, the hypertension, the venous thromboembolism and the chronic kidney disease. The risk is higher and earlier after the preterm pre-eclampsia, the recurrent pre-eclampsia and the HELLP. The discharge is the opportunity for the primary prevention: advise on the future risk, optimise the weight, the blood pressure and the lipids, and arrange the primary-care follow-up. The shared aetiology (the endothelial dysfunction and the metabolic syndrome) is the explanation, not the vindication.[6]

Landmark trials — the evidence base

Exam pearls

• New hypertension after 20 weeks plus proteinuria or end-organ dysfunction = pre-eclampsia; the seizure = eclampsia. Do not wait for the textbook blood pressure.
• Magnesium sulphate is the prophylaxis AND the treatment: 4 g IV over 20 minutes, then 1 g per hour for 24 hours. A further 2 g bolus for the recurrent seizure. Calcium gluconate 10 mL of 10 per cent is the antidote.
• Monitor magnesium hourly: reflexes present, respiratory rate 12 or above, urine output above 0.5 mL per kg per hour. Loss of reflexes is the earliest toxicity sign.
• Target the blood pressure to 140 to 150 over 90 to 100 — never normal. Labetalol, hydralazine or nifedipine only; ACE inhibitors, ARBs and renin inhibitors are forbidden.
• Delivery is the only cure; magnesium continues for 24 hours postpartum.
• HELLP is haemolysis plus elevated liver enzymes plus low platelets — a severe variant, may have only modest hypertension.
• Postpartum pre-eclampsia or eclampsia up to six weeks — a normal antenatal course does not exclude it.
• Capillary leak: do not fluid-load. Restrict maintenance fluid, watch for pulmonary oedema. [1]

Exam practice

Red flags