What is the management of severe pre-eclampsia with severe features?

Management of Severe Pre-eclampsia with Severe Features

Severe pre-eclampsia requires immediate dual therapy with IV magnesium sulfate for seizure prophylaxis and aggressive blood pressure control with IV antihypertensives, followed by expedited delivery after maternal stabilization. 1, 2

Immediate Stabilization (First 15-30 Minutes)

Magnesium Sulfate Administration

• Administer magnesium sulfate immediately to all patients with severe pre-eclampsia - this is superior to phenytoin and diazepam for both stopping active seizures and preventing progression to eclampsia 1, 3
• Loading dose: 4-6 grams IV over 5-10 minutes (or 4-5g in 250 mL of 5% dextrose or 0.9% saline infused over 5 minutes) 1, 4
• Maintenance dose: 1-2 g/hour continuous IV infusion 1, 4
• Alternative regimen: After IV loading dose, give 4-5g IM into alternate buttocks every 4 hours 4
• Continue magnesium sulfate until 24 hours postpartum or until seizures cease 3, 4
• Target therapeutic serum magnesium level: 4-6 mg/dL (or 3-6 mg/100 mL) for seizure control 1, 4
• Do NOT exceed 5-7 days of continuous administration as this causes fetal skeletal abnormalities including hypocalcemia, skeletal demineralization, and osteopenia 4

Blood Pressure Control

• Initiate IV antihypertensive therapy immediately when BP ≥160/110 mmHg persists for more than 15 minutes 1, 2
• Target BP: Systolic 110-140 mmHg and diastolic 85 mmHg (absolute minimum <160/105 mmHg) 1, 2
• The goal is to decrease mean BP by 15-25% to prevent maternal cerebral hemorrhage while maintaining uteroplacental perfusion 1

First-Line IV Antihypertensive Options

• IV Labetalol (preferred first-line): 20mg IV bolus, then 40mg after 10 minutes, followed by 80mg every 10 minutes to maximum cumulative dose of 220mg (do not exceed 800mg in 24 hours to prevent fetal bradycardia) 1, 3
• IV Hydralazine: Alternative first-line agent 1, 2, 5
• IV Nicardipine: Alternative first-line agent 1, 2
• For pulmonary edema specifically: IV nitroglycerin (glycerol trinitrate) starting at 5 mcg/min, gradually increased every 3-5 minutes to maximum 100 mcg/min 1

Critical Drug Interactions and Contraindications

• NEVER combine magnesium sulfate with IV or sublingual nifedipine - this causes severe myocardial depression 3
• Short-acting oral nifedipine should be avoided, especially when combined with magnesium sulfate, due to risk of uncontrolled hypotension and fetal compromise 1
• Sodium nitroprusside should only be used as last resort for extreme emergencies due to risk of fetal cyanide poisoning 1
• ACE inhibitors, ARBs, and direct renin inhibitors are absolutely contraindicated due to severe fetotoxicity 1
• Diuretics are contraindicated as they further reduce plasma volume 1
• Reduce or cease antihypertensive drugs if diastolic BP falls <80 mmHg 1, 2

Critical Monitoring Requirements

Maternal Monitoring for Magnesium Toxicity

• Monitor patellar reflex (knee jerk) before each dose - reflexes begin to diminish when magnesium levels exceed 4 mEq/L and may be absent at 10 mEq/L where respiratory paralysis is a potential hazard 1, 4
• Monitor respiratory rate continuously - target ≥16 breaths/min; respiratory depression indicates toxicity 1, 4
• Hourly urine output via Foley catheter with target ≥100 mL/4 hours (or >35 mL/hour) - magnesium is removed solely by the kidneys 1, 2, 4
• Oxygen saturation on room air (maternal early warning if <95%) 1
• Continuous blood pressure monitoring 1, 2
• Assess for maternal agitation, confusion, unresponsiveness, non-remitting headache, and shortness of breath 1
• Have IV calcium gluconate immediately available to counteract magnesium toxicity 4

Laboratory Monitoring

• Obtain at least twice weekly (or more frequently with clinical deterioration): complete blood count, platelet count, liver transaminases (AST/ALT), creatinine, and uric acid 1, 2
• Monitor for HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) - maternal mortality rate 3.4% 1
• Serum magnesium levels should be monitored, especially in patients with renal impairment 4

Fetal Monitoring

• Initial ultrasound assessment at diagnosis: fetal biometry, amniotic fluid volume, and umbilical artery Doppler 1, 2
• Continuous fetal heart rate monitoring 1
• Repeat ultrasound every 2 weeks if initial assessment normal 1, 2
• More frequent monitoring of amniotic fluid and Doppler if fetal growth restriction present 2

Delivery Timing Based on Gestational Age

≥37 Weeks' Gestation

• Deliver immediately after maternal stabilization 1, 2
• Induction of labor is associated with improved maternal outcome 1

34-37 Weeks' Gestation

• Expectant conservative management is appropriate if maternal and fetal status stable 1, 2
• Deliver if any maternal or fetal deterioration occurs 1

<34 Weeks' Gestation

• Conservative expectant management at a center with Maternal-Fetal Medicine expertise 1, 2
• Expectant management in select patients between 24-32 weeks can prolong pregnancy by average of 14-15 days, improving neonatal outcomes without increasing maternal mortality 6, 7
• Administer corticosteroids for fetal lung maturity 2

<24 Weeks' Gestation

• Expectant management is associated with high maternal morbidity (27.2%) with limited perinatal benefit (94.5% intrauterine fetal loss rate, mean prolongation only 4.8 days) 6, 8
• Counsel regarding pregnancy termination 1

Absolute Indications for Immediate Delivery (Regardless of Gestational Age)

• Inability to control BP despite ≥3 classes of antihypertensives in appropriate doses 1, 2
• Progressive thrombocytopenia or progressively abnormal liver/renal function tests 1, 2
• Pulmonary edema 1
• Maternal pulse oximetry <90% or deterioration 1, 2
• Severe intractable headache, repeated visual scotomata, or eclampsia 1, 2
• Non-reassuring fetal status, reversed end-diastolic flow in umbilical artery Doppler, or stillbirth 1, 2
• Placental abruption 1, 2

Mode of Delivery

• Vaginal delivery should be considered unless cesarean delivery is required for obstetric indications 2
• Stabilize the mother first with magnesium sulfate and BP control before proceeding to delivery 3

Transport Considerations

• Medicalised transport to a specialized obstetric center should be systematically considered for all patients with severe pre-eclampsia 1, 2
• Before transfer: coordinate with obstetric and anesthetic-intensivist teams at receiving facility via phone, initiate magnesium sulfate and blood pressure control prior to transport 1, 2

Common Pitfalls to Avoid

• Do NOT attempt to diagnose "mild versus severe" pre-eclampsia clinically - all cases may become emergencies rapidly 1
• Do NOT use serum uric acid or level of proteinuria as indication for delivery 1
• Do NOT reduce antihypertensives if diastolic BP falls <80 mmHg - instead, reduce or cease them 1
• Do NOT routinely use plasma volume expansion 1, 2
• Do NOT continue magnesium sulfate beyond 5-7 days due to fetal skeletal abnormalities 4
• Do NOT exceed maximum total daily dose of 30-40g magnesium sulfate (or 20g/48 hours in severe renal insufficiency) 4