Contents
- Definition
- Pathophysiology
- Diagnosis and Severity
- Antihypertensive Therapy
- Magnesium Sulphate
- Fluid Management
- Delivery and Timing
- Eclampsia Management
- Viva Questions
Definition
Pre-eclampsia (PE) is a pregnancy-specific syndrome defined as new-onset hypertension after 20 weeks of gestation with evidence of organ involvement.
ISSHP (2018) definition:
- Hypertension: SBP ≥140 mmHg or DBP ≥90 mmHg on two occasions ≥4h apart, arising after 20 weeks (previously normotensive)
- PLUS at least one of:
- Proteinuria ≥300 mg/24h (or PCR ≥30 mg/mmol)
- Acute kidney injury (creatinine >90 µmol/L UK threshold; some criteria use doubling)
- Liver involvement: transaminases >2× ULN or epigastric/RUQ pain
- Neurological involvement: new headache unresponsive to analgesia, visual disturbance, seizure
- Haematological: platelets <150 ×10⁹/L
- Uteroplacental dysfunction: intrauterine growth restriction (IUGR), abnormal Dopplers
Eclampsia: tonic-clonic seizure in the context of pre-eclampsia (or without prior PE diagnosis in some cases).
HELLP syndrome is a distinct but closely related entity: Haemolysis, Elevated Liver enzymes, Low Platelets — see separate page.
Pathophysiology
Pre-eclampsia is a two-stage disease:
Stage 1 — Defective Placentation (First Trimester)
Normal trophoblast invasion remodels spiral arteries into wide, low-resistance channels that accommodate high placental blood flow. In pre-eclampsia, this remodelling is incomplete — spiral arteries remain narrow and high-resistance. Consequence: reduced uteroplacental perfusion, placental ischaemia and oxidative stress.
Stage 2 — Maternal Syndrome (Second/Third Trimester)
The ischaemic placenta releases:
- Anti-angiogenic factors: soluble Flt-1 (sFlt-1) sequesters VEGF and PlGF (placental growth factor), reducing circulating free growth factors
- Inflammatory mediators: cytokines, micro-particles
- Oxidative stress products
These produce systemic maternal endothelial dysfunction:
- ↑ Vascular permeability → oedema, proteinuria
- ↑ Vasomotor tone → hypertension
- ↑ Prothrombotic state → platelet activation, DIC risk
- Multi-organ involvement: kidney, liver, CNS, lung, placenta
Diagnosis and Severity
Severe Features (any one qualifies):
- SBP ≥160 mmHg or DBP ≥110 mmHg on two occasions
- Platelets <100 ×10⁹/L
- Creatinine ≥100 µmol/L or doubling from baseline
- Transaminases >2× ULN and/or persistent epigastric/RUQ pain
- Pulmonary oedema (new-onset)
- New-onset headache unresponsive to paracetamol
- Visual disturbance
Investigations:
- FBC (platelets, haematocrit for haemoconcentration)
- LFTs, LDH (haemolysis marker)
- Creatinine, electrolytes, urate (rises with PE — prognostic)
- Coagulation (PT/APTT, fibrinogen — DIC risk in severe PE/HELLP)
- Urine PCR/MSU
- CTG and fetal growth assessment
Blood pressure measurement:
- Use manual sphygmomanometer (automated devices may underread in PE); korotkoff phase V (disappearance) for DBP
- Position: sitting or left lateral; upper arm at heart level
Antihypertensive Therapy
Acute severe hypertension (SBP ≥160 or DBP ≥110 mmHg)
Target: reduce SBP to <150 mmHg, DBP to <100 mmHg within 1 hour (NICE NG133)
| Agent | Route | Notes |
|---|---|---|
| Labetalol | IV (20 mg bolus, repeat/increase to max 200 mg; or infusion) | First-line IV option in UK; combined α/β blocker; use with caution in asthma |
| Nifedipine (modified release) | Oral 10–20 mg | First-line oral; avoid immediate-release sublingual (rapid BP fall) |
| Hydralazine | IV (5 mg bolus, repeat every 20 min) | Direct vasodilator; may cause maternal tachycardia, headache; crosses placenta but safely used |
| Nicardipine | IV infusion | Used in many European/US centres; not first-line in UK NICE guidance |
Avoid:
- ACE inhibitors and ARBs: fetotoxic (impair fetal renal development → oligohydramnios, IUGR, neonatal AKI)
- Diuretics: reduce placental perfusion; avoid unless pulmonary oedema
- Atenolol: associated with IUGR
Maintenance antihypertension (mild-moderate PE)
- Labetalol oral, or methyldopa, or nifedipine MR
Magnesium Sulphate
Indications
- Treatment of eclamptic seizure (first-line)
- Prophylaxis of eclampsia in severe pre-eclampsia
Evidence
Magpie Trial (2002, Lancet): 10,110 women with PE randomised to MgSO₄ vs placebo → MgSO₄ halved the risk of eclampsia (0.8% vs 1.9%); reduced risk of maternal death; no adverse neonatal effects. One of the most influential obstetric RCTs.
Dose (UK standard: modified Zuspan regimen)
- Loading dose: 4 g IV over 15–20 minutes
- Maintenance: 1 g/hour IV infusion (continue for 24 hours after last seizure or delivery, whichever is later)
- For recurrent seizure despite MgSO₄: 2 g IV over 5 minutes (further bolus)
Mechanism
- Blocks NMDA glutamate receptors → reduced neuronal excitability and seizure threshold
- Inhibits calcium entry into vascular smooth muscle → cerebral vasodilation
- May also act as a membrane stabiliser and neuroprotectant
Monitoring for toxicity
| Magnesium level | Clinical effect |
|---|---|
| 2–3.5 mmol/L | Therapeutic range |
| >3.5 mmol/L | Loss of patellar reflexes (earliest sign) |
| >5 mmol/L | Respiratory depression |
| >7.5 mmol/L | Cardiac arrest |
- Check patellar reflexes every 30–60 minutes (loss of reflexes precedes respiratory depression)
- Check RR, SpO₂, and urine output hourly (MgSO₄ is renally excreted — reduce dose in AKI)
- Antidote: 10 mL of 10% calcium gluconate IV over 5–10 minutes (reverses respiratory and cardiac effects)
Fluid Management
Pre-eclampsia involves:
- ↓ Oncotic pressure (hypoalbuminaemia from proteinuria and endothelial leak)
- ↑ Capillary permeability (endothelial dysfunction)
- ↑ Hydrostatic pressure (hypertension)
→ High risk of pulmonary oedema, particularly peripartum and postpartum when fluid shifts occur.
Principles:
- Target urine output ≥0.5 mL/kg/h — but do NOT aggressively fluid-load to achieve this
- Restrict IV fluid to <80–85 mL/hour total (including drug infusions) unless haemorrhage or clear dehydration
- Avoid diuretics unless pulmonary oedema (after delivery)
- If pulmonary oedema develops: furosemide, CPAP/NIV, consider intubation for severe hypoxaemia
- Oliguria is common in PE and usually resolves after delivery — it is not an indication for aggressive fluid loading
Delivery and Timing
Delivery is the only cure for pre-eclampsia. Timing is a balance between maternal benefit and fetal prematurity.
| Gestation | Management |
|---|---|
| ≥37 weeks | Offer delivery (NICE NG133) |
| 34–36+6 weeks | Consider delivery if severe PE; balance with neonatal prematurity risk |
| <34 weeks | Conservative management in a specialist unit if stable; steroids for fetal lung maturity (betamethasone 2 × 12 mg IM); magnesium for neonatal neuroprotection (<32 weeks) |
| Any gestation | Deliver if: uncontrolled severe hypertension, eclampsia, abruption, fetal compromise, deteriorating HELLP |
- Mode of delivery: vaginal birth is not contraindicated; CS for obstetric indications
- Regional anaesthesia preferred (avoid GA risks in difficult airway + hypertensive response to intubation)
Eclampsia Management
- Airway: left lateral position; protect from injury; call for help
- Left lateral tilt (or manual uterine displacement): prevents aortocaval compression (>20 weeks gestation)
- MgSO₄ 4 g IV over 5 minutes: first-line seizure treatment (if already on infusion, give 2 g bolus)
- If MgSO₄ fails: diazepam 10 mg IV or lorazepam 4 mg IV (second-line)
- Treat severe hypertension concurrently (SBP ≥160 mmHg → labetalol IV or nifedipine)
- Fetal monitoring and urgent obstetric review; expedite delivery
- Continue MgSO₄ infusion for 24 hours after last seizure
Intubation and ICU admission: required if eclampsia with prolonged seizure, status epilepticus, pulmonary oedema, severe hypertension with organ failure, or postpartum haemorrhage with cardiovascular compromise.
Viva Questions
1. Explain the pathophysiology of pre-eclampsia and why it causes such diverse systemic effects.
Pre-eclampsia is a two-stage disease. In early pregnancy, defective trophoblast invasion fails to adequately remodel uterine spiral arteries — they remain narrow and high-resistance, leading to placental ischaemia and oxidative stress. The ischaemic placenta then releases anti-angiogenic factors (particularly sFlt-1, which sequesters free VEGF and PlGF) along with inflammatory mediators, causing systemic maternal endothelial dysfunction. This endothelial dysfunction is the final common pathway for all the systemic manifestations: increased vascular permeability causes oedema and proteinuria; loss of vasodilatory NO production causes hypertension; platelet activation causes thrombocytopenia; endothelial injury in the liver causes transaminitis and subcapsular haemorrhage; renal endothelial swelling (glomerular endotheliosis) causes proteinuria and AKI; and cerebral endothelial dysfunction causes the neurological features including eclampsia. The placenta is the source of the problem, which is why delivery is the only cure.
2. How does magnesium sulphate prevent and treat eclampsia? What are the toxicity concerns and how do you monitor for them?
Magnesium sulphate reduces seizure threshold through multiple mechanisms: blocking NMDA glutamate receptors to reduce neuronal excitability, inhibiting calcium entry into vascular smooth muscle to produce cerebral vasodilation, and membrane stabilisation. The Magpie Trial showed it halved eclampsia risk in women with pre-eclampsia and is first-line for both prevention (severe PE) and treatment (eclampsia). The therapeutic range is approximately 2–3.5 mmol/L. Toxicity progresses predictably: patellar reflex loss precedes respiratory depression — check reflexes every 30–60 minutes. Respiratory depression occurs at levels >5 mmol/L; cardiac arrest at >7.5 mmol/L. MgSO₄ is renally excreted; reduce the maintenance infusion in AKI (monitor serum levels). The antidote is 10 mL of 10% calcium gluconate IV, which reverses magnesium toxicity immediately by competitive inhibition at calcium channels. Always have calcium gluconate drawn up at the bedside.
3. A woman with severe pre-eclampsia at 32 weeks becomes oliguric (urine output 15 mL/h) despite a fluid challenge of 500 mL. What do you do?
Oliguria in pre-eclampsia is very common and does not warrant aggressive fluid loading. The underlying pathology — reduced renal perfusion secondary to vasospasm, and reduced glomerular filtration from endothelial swelling — is unlikely to be corrected by fluids. More importantly, aggressive fluid loading in pre-eclampsia is hazardous: reduced oncotic pressure (hypoalbuminaemia) combined with increased capillary permeability and hypertension creates a high risk of pulmonary oedema. Oliguria typically resolves spontaneously after delivery. My approach: stop the fluid challenge; check for other reversible causes (urinary catheter patency, sepsis, acute blood loss); monitor urine output, creatinine, and acid-base; restrict IV fluids to ≤80 mL/hour total; do not give diuretics (worsen placental perfusion). If creatinine is rising significantly or metabolic acidosis develops, consult nephrology. Expedite delivery if feasible given gestation and clinical condition. The oliguria is a manifestation of the disease, not a fluid-responsive state.
4. What are the risks of general anaesthesia in severe pre-eclampsia and how are they mitigated?
General anaesthesia carries specific heightened risks in severe pre-eclampsia. (1) Failed intubation: airway oedema (pharyngeal, laryngeal) is common in PE; have a difficult airway plan, smaller ETT (size 6–6.5), call for senior anaesthetist. (2) Hypertensive response to laryngoscopy: the sympathetic response to intubation can cause dangerous hypertensive surges, raising risk of stroke, aortic dissection, or LV failure; attenuate with remifentanil (1 mcg/kg IV), alfentanil, or magnesium (2g IV). (3) Aspiration risk: pregnancy + PE (impaired gastric motility) increases risk; rapid sequence induction essential. (4) Drug interactions: MgSO₄ potentiates neuromuscular blocking agents — reduce NMB dose and monitor TOF carefully; MgSO₄ also enhances volatile agent MAC effects. For these reasons, regional anaesthesia (spinal or epidural) is strongly preferred for caesarean section in severe PE, unless contraindicated (significant coagulopathy, thrombocytopenia <80 ×10⁹/L, or haemodynamic instability requiring urgent surgery).