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Toxemia of Pregnancy (Preeclampsia/Eclampsia) - MD Anaesthesiology Notes

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1. DEFINITION & CLASSIFICATION

• De novo hypertension (BP ≥140/90 mmHg) after 20 weeks of gestation in a previously normotensive woman
• Plus proteinuria (≥300 mg/24h, or protein:creatinine ratio ≥0.3) OR evidence of multisystem organ dysfunction

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2. CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY

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3. RISK FACTORS

• Primigravida (most common)
• Multiple gestation (10-20% in twins; up to 90% in quadruplets - due to larger placental mass)
• Extremes of age (maternal age >40)
• Chronic hypertension, diabetes, renal disease
• Collagen vascular disease, antiphospholipid syndrome
• Previous history of preeclampsia
• Hydatidiform mole
• Obesity

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4. PATHOPHYSIOLOGY (Critical for Anaesthesiology)

Primary Event: Failure of Spiral Artery Remodeling

Cascade:

Inadequate spiral artery remodeling
         ↓
Placental ischemia/hypoxia
         ↓
Release of anti-angiogenic factors (sFlt-1, soluble endoglin)
- sFlt-1 antagonizes VEGF and PlGF
- Soluble endoglin antagonizes TGF-β
         ↓
Generalised maternal endothelial dysfunction
         ↓
Multiple organ effects (see below)

Vasoconstrictor/Vasodilator Imbalance:

• ↓ PGI₂ (prostacyclin) and PGE₂ (vasodilators)
• ↑ Thromboxane A₂ (vasoconstrictor, platelet aggregant)
• Result: systemic vasospasm, hypertension, platelet aggregation

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5. MULTISYSTEM PATHOPHYSIOLOGY (Anaesthesia Perspective)

A. Cardiovascular

• Generalized vasospasm with increased SVR
• Despite sodium/water retention, fluid shifts from intravascular to extravascular space → hypovolemia (plasma volume up to 30-40% below normal in severe disease)
• Hemoconcentration and hypoproteinemia
• Increased cardiac output initially; may progress to left ventricular dysfunction
• Risk of pulmonary edema

B. Respiratory/Airway

• Airway edema of tongue, epiglottis, pharynx - CRITICAL for anaesthesiologists; may result in difficult or failed intubation
• Pulmonary edema in ~2% of severe preeclampsia (from magnesium infusion, circulatory overload, cardiac failure, or aspiration during convulsions)
• Pulmonary V/Q mismatch in severe cases; however, PaO₂ typically within normal limits

C. Renal

• Glomerular endotheliosis: swelling of glomerular endothelial cells + fibrin deposition → capillary luminal constriction
• Reduced renal blood flow and GFR
• ↓ Uric acid clearance (hyperuricemia is a marker of disease severity)
• Oliguria and proteinuria (may reach nephrotic levels of 10-15 g/24h in severe disease)
• In severe cases: elevated urea and creatinine (creatinine >1.1 mg/dL = severe feature)

D. Hepatic

• Periportal necrosis from decreased hepatic blood supply
• Subcapsular hemorrhage → RUQ/epigastric pain (classic symptom)
• Rarely: hepatic capsule rupture → massive intra-abdominal hemorrhage
• Elevated AST, LDH, alkaline phosphatase; bilirubin usually unaltered

E. Hematologic/Coagulation

• Thrombocytopenia (platelet count 100-150 × 10⁹/L typically; <100 × 10⁹/L = severe feature) due to consumptive coagulopathy at sites of endothelial damage
• Elevated fibrin degradation products (FDPs) less frequent
• Plasma fibrinogen usually normal (unless placental abruption occurs)
• Prolonged PT/aPTT if procoagulant factor consumption is significant
• Risk of DIC

F. CNS

• Cerebral vasospasm and edema → headache, visual disturbances, seizures (eclampsia)
• Hyperreflexia, clonus
• Risk of cerebral hemorrhage (particularly with severe/uncontrolled hypertension)

G. Uteroplacental

• Chronic placental hypoperfusion → fetal IUGR, chronic fetal hypoxia
• Placental infarction, retroplacental hemorrhage
• Increased risk of abruptio placentae
• Prematurity and perinatal death

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6. HELLP SYNDROME

• H = Hemolysis (microangiopathic hemolytic anemia - schistocytes on peripheral smear; LDH >600 U/L; total bilirubin >1.2 mg/dL)
• EL = Elevated Liver enzymes (AST, ALT elevated but usually <500 U/L)
• LP = Low Platelets (<100,000/μL; suspicious if <150,000/μL)

• Occurs in ~10% of severe preeclampsia
• More common in multigravidae (unlike preeclampsia itself)
• Hypertension may be absent initially - can masquerade as gastroenteritis, cholecystitis, hepatitis, pancreatitis, pyelonephritis (epigastric/RUQ pain is cardinal symptom)
• Up to 7 days postpartum onset is possible
• Complications: DIC, spontaneous hepatic/splenic hemorrhage, end-organ failure, abruptio placentae, intracranial bleeding, maternal and fetal death
• Platelet transfusion may be required before regional anaesthesia or surgery

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7. DIAGNOSTIC CRITERIA (Severe Preeclampsia)

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8. ANTIHYPERTENSIVE THERAPY

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9. MAGNESIUM SULFATE - THE KEY DRUG

Indications:

• Seizure prophylaxis in preeclampsia with severe features
• Treatment of eclamptic seizures
• Preferred over phenytoin and diazepam (demonstrated superiority in the Magpie trial - 10,000 women)

Regimen:

• Loading dose: 4-6 g IV over 20-30 minutes
• Maintenance: 1-2 g/h IV continuous infusion
• Therapeutic range: 4-8 mEq/L (4.8-9.6 mg/dL)

Toxicity - Monitor Closely:

ANAESTHESIA-CRITICAL: Magnesium-Muscle Relaxant Interaction

• Magnesium acts at the myoneural junction - inhibits acetylcholine release, reduces motor end-plate sensitivity
• Potentiates and prolongs both depolarizing and non-depolarizing neuromuscular blockers
• Non-depolarizing muscle relaxants should be given in reduced doses with neuromuscular monitoring (train-of-four) to avoid overdose
• Suxamethonium dose may also need modification

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10. ANAESTHETIC MANAGEMENT OF PREECLAMPSIA

Pre-anaesthetic Assessment:

• Assess airway (edema of tongue, epiglottis, pharynx - expect difficult airway)
• Coagulation profile (platelet count before regional anaesthesia)
• Volume status (intravascular volume is often depleted)
• BP control status
• Current magnesium therapy and serum levels
• Fetal wellbeing

Regional vs General Anaesthesia:

• Epidural, spinal, or combined spinal-epidural (CSE) can be used for labor and delivery
• Neuraxial analgesia in volume-repleted, appropriately positioned (left uterine displacement) patients does NOT cause unacceptable hypotension
• May significantly improve placental perfusion (epidural analgesia increases placental intervillous blood flow by up to 75%)
• Women with severe preeclampsia actually show lower risk of hypotension during spinal anaesthesia than normotensive women - due to increased vascular tone from vasospasm
• Incidence and severity of hypotension is similar with spinal and epidural
• Contraindications to regional: severe coagulopathy, refractory maternal hemodynamic instability, patient refusal

• Ensure BP is adequately controlled
• Judicious hydration (cautious - risk of pulmonary edema)
• Avoid acute drops in BP - poorly tolerated by mother and fetus
• Have vasopressors (phenylephrine, ephedrine) readily available
• Platelet count must be adequate (generally ≥80,000/μL for spinal; higher threshold for epidural in some centres)

General Anaesthesia (when neuraxial is contraindicated or emergent):

1. Difficult airway: Edema of tongue, epiglottis, larynx, pharynx - have difficult airway equipment ready; consider awake fibreoptic intubation if significant airway edema
   • Use smaller ETT size (consider 6.0-6.5 mm)
   • Prepare for failed intubation drill
2. Hypertensive response at intubation/extubation:
   • Laryngoscopy and intubation cause marked systemic and pulmonary hypertension
   • Increases risk of cerebral hemorrhage and pulmonary edema
   • Attenuate with: labetalol, esmolol, lignocaine (1.5 mg/kg IV), magnesium, fentanyl, or remifentanil before intubation
   • In patients with impaired coagulation, laryngoscopy may provoke profuse bleeding
3. Rapid sequence induction (RSI) is mandatory (full stomach - aspiration risk)
   • Cricoid pressure
   • Pre-oxygenation
4. Drugs to avoid:
   • Ketamine - avoid in uncontrolled hypertension (sympathomimetic, raises BP further)
   • Ergot alkaloids (ergometrine/methylergometrine) - avoid (causes severe hypertension); use oxytocin instead for uterine contraction
   • Avoid excessive fluid loading (pulmonary edema risk)
5. Neuromuscular blockade:
   • Magnesium sulfate potentiates all neuromuscular blockers
   • Use reduced doses of non-depolarizing agents (rocuronium, vecuronium, atracurium)
   • Mandatory neuromuscular monitoring (train-of-four)
   • Suxamethonium for RSI: dose modification may be needed; response can be prolonged
   • Sugammadex availability recommended if rocuronium used
6. Volatile agents: Generally safe; all volatiles cause uterine relaxation (uteroplacental blood flow considerations)
7. Postoperative monitoring: Preeclampsia can worsen or first present postpartum - continue close BP and neurological monitoring for at least 24-48 hours

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11. MANAGEMENT OF ECLAMPSIA (Convulsions)

Immediate Management (ABCDE):

1. Airway - maintain airway, positioning (left lateral), prevent aspiration
2. Oxygen - high-flow oxygen, suction
3. IV access - secure immediately
4. Terminate seizure: Magnesium sulfate 4-6 g IV over 5-10 min
   • If already on Mg: give additional 2 g bolus or increase infusion rate; alternative - diazepam 5-10 mg IV
   • If refractory: phenytoin, thiopentone, intubation and ventilation
5. Antihypertensive - treat BP ≥160/110 aggressively
6. Deliver the fetus - definitive treatment; timing and mode depends on gestational age and maternal condition
7. Continue magnesium for 24 hours after last seizure or delivery (whichever is later)

Postpartum Eclampsia:

• Can occur up to 4-6 weeks postpartum (most within 48 hours)
• Maintain vigilance postpartum

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12. PROPHYLAXIS

• Low-dose aspirin (81 mg/day) from 12-28 weeks (ideally before 16 weeks) in high-risk women until delivery - recommended by ACOG
• Mechanism: shifts TXA₂/PGI₂ balance toward vasodilation and anti-platelet effect
• Calcium supplementation in women with low dietary calcium intake

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13. DEFINITIVE TREATMENT

• Without severe features: Expectant management until 37 weeks (term)
• With severe features at ≥34 weeks: Delivery indicated
• With severe features at <34 weeks: Individualized; expectant management in-hospital with intensive monitoring; deliver if maternal/fetal deterioration
• Proteinuria and hypertension usually resolve within 1-2 weeks after delivery

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14. COMPLICATIONS SUMMARY

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15. KEY ANAESTHESIA EXAM POINTS (Quick Recall)

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