11.2 Hypertensive Disorders of Pregnancy & Eclampsia

Hypertensive Disorders of Pregnancy & Eclampsia

Hypertensive disorders of pregnancy (HDP) represent one of the leading direct causes of maternal and perinatal mortality in Kenya, contributing to nearly 20% of maternal deaths alongside obstetric hemorrhage and sepsis. The fundamental underlying pathophysiology involves abnormal cytotrophoblast invasion of maternal spiral arteries during early placentation, resulting in failed vascular remodeling, persistent high-resistance placental circulation, placental ischemia, and the systemic release of anti-angiogenic factors (such as soluble fms-like tyrosine kinase-1 [sFlt-1] and soluble endoglin). These factors precipitate widespread maternal endothelial cell dysfunction, vasospasm, capillary leakage, and multi-organ microvascular hypoperfusion.

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1. Classification & Diagnostic Spectrum

Accurate clinical classification is crucial for determining the level of health facility required, the intensity of monitoring, and the timing of delivery.

HELLP Syndrome

HELLP syndrome is a life-threatening subtype of severe pre-eclampsia characterized by microangiopathic hemolytic anemia, hepatic sinusoidal fibrin deposition, and platelet activation/consumption:

• H (Hemolysis): Microangiopathic hemolytic anemia with schistocytes (fragmented red blood cells) on peripheral blood film, elevated serum lactate dehydrogenase (LDH > 600 U/L), and elevated indirect bilirubin (≥ 20.5 μmol/L or ≥ 1.2 mg/dL).
• EL (Elevated Liver enzymes): Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 70 U/L (or ≥ 2 times upper limit of normal).
• LP (Low Platelets): Platelet count < 100,000/μL. Class I (< 50,000/μL), Class II (50,000–100,000/μL), Class III (100,000–150,000/μL).
• Clinical Warning: Women with HELLP frequently present with severe epigastric or right upper quadrant (RUQ) pain, nausea, and vomiting due to hepatic capsular distension (Glisson's capsule stretch). Neglected HELLP carries catastrophic risk of subcapsular hepatic hematoma, liver rupture, disseminated intravascular coagulation (DIC), acute renal failure, and death.

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2. Pharmacological Antihypertensive Therapy

The therapeutic goal of antihypertensive therapy in pregnancy is to reduce maternal cerebrovascular and cardiovascular morbidity (specifically preventing hemorrhagic stroke and placental abruption) while maintaining adequate uteroplacental blood flow. Blood pressure must not be lowered too rapidly or excessively, as acute maternal hypotension severely compromises fetal placental perfusion, precipitating fetal bradycardia and hypoxia.

ANTIHYPERTENSIVE MANAGEMENT FRAMEWORK:

[Maintenance Therapy (BP 140–159 / 90–109 mmHg)]
  • Target BP: 130–140 mmHg systolic / 80–90 mmHg diastolic
  • First-line: Oral Labetalol, Methyldopa, or Nifedipine retard

[Emergency Therapy for Severe Acute Hypertension (BP ≥ 160/110 mmHg)]
  • Medical Emergency: Reduce BP to 140–150 / 90–100 mmHg within 30–60 minutes
  • First-line IV: Hydralazine (5–10 mg slow IV every 20–30 min) OR Labetalol (20 mg IV bolus)
  • Alternative Oral: Oral immediate-release Nifedipine (10 mg swallowed whole)

Maintenance Oral Antihypertensive Agents

1. Labetalol (Oral):
   • Mechanism: Combined selective alpha-1 and non-selective beta-adrenergic blocker. Decreases peripheral vascular resistance without causing reflex tachycardia or altering cardiac output.
   • Dose: Initial dose 100–200 mg orally twice daily, titrated upwards every 2 to 3 days to a maximum of 1200–2400 mg daily in 2–3 divided doses.
   • Precautions: Avoid in patients with active bronchial asthma, congestive heart failure, or severe bradycardia.
2. Methyldopa (Oral):
   • Mechanism: Centrally acting alpha-2 adrenergic receptor agonist; converted to alpha-methylnorepinephrine in the central nervous system, decreasing sympathetic outflow to the heart and peripheral vasculature.
   • Dose: Initial dose 250 mg orally 2 to 3 times daily, titrated up to a maximum of 2.0 to 3.0 g daily in 3–4 divided doses.
   • Clinical Notes: Proven long-term safety profile across decades of obstetric experience. Has a delayed onset of action (24 to 48 hours to achieve maximum effect). Common side effects include somnolence, dry mouth, postural hypotension, and maternal depression. Rarely associated with drug-induced hepatitis and Coombs-positive hemolytic anemia.
3. Nifedipine Retard / Extended-Release (Oral):
   • Mechanism: Dihydropyridine calcium channel blocker; selectively inhibits calcium ion influx into vascular smooth muscle, causing peripheral vasodilation.
   • Dose: 10 to 20 mg orally twice daily (slow-release / retard formulation), up to 60–90 mg daily.
   • Clinical Pitfall: Never prescribe sublingual short-acting nifedipine capsules. Piercing or chewing the capsule precipitates sudden, uncontrolled, precipitously profound hypotension, which triggers maternal cerebral ischemia and severe fetal distress.

Emergency Management of Acute Severe Hypertension (BP ≥ 160/110 mmHg)

Severe acute hypertension in pregnancy is an obstetric emergency. Intervention must begin within 30 to 60 minutes of confirmation.

• IV Hydralazine Protocol:
  • Administer 5 to 10 mg slow IV push over 3 to 5 minutes.
  • Recheck blood pressure every 15 minutes.
  • If blood pressure remains ≥ 160/110 mmHg after 20 to 30 minutes, administer a repeat dose of 5 to 10 mg IV.
  • Maximum cumulative dose: 20 to 30 mg.
  • If ineffective, switch to IV Labetalol.
  • Hydralazine side effects: Reflex tachycardia, maternal headache, flushing, nausea.
• IV Labetalol Protocol:
  • Administer an initial bolus of 20 mg IV over 2 minutes.
  • Recheck blood pressure after 10 minutes.
  • If BP remains ≥ 160/110 mmHg, administer 40 mg IV; if still uncontrolled after another 10 minutes, administer 80 mg IV; if still uncontrolled, administer a final 80 mg IV (maximum cumulative dose: 220 to 300 mg).
• Oral Immediate-Release Nifedipine (Alternative):
  • Administer 10 mg orally swallowed whole with water (never chewed or sublingual). Repeat 10 to 20 mg in 30 minutes if BP remains ≥ 160/110 mmHg (maximum single dose 20 mg; daily maximum 120 mg).

Absolute Contraindications in Pregnancy

• Angiotensin-Converting Enzyme (ACE) Inhibitors (e.g., Enalapril, Captopril, Lisinopril) and Angiotensin II Receptor Blockers (ARBs) (e.g., Losartan, Valsartan, Telmisartan): Strictly contraindicated throughout pregnancy. Exposure leads to severe fetal fetotoxicity: fetal renal tubular dysgenesis, severe persistent oligohydramnios (Potter sequence), pulmonary hypoplasia, neonatal anuria/renal failure, calvarial hypoplasia (defective skull bone development), and intrauterine fetal death.
• Mineralocorticoid Receptor Antagonists (e.g., Spironolactone): Contraindicated due to anti-androgenic effects and risk of feminization of male fetuses.
• Diuretics (e.g., Furosemide, Hydrochlorothiazide): Generally avoided because maternal plasma volume is already severely contracted in pre-eclampsia; diuretics further diminish placental perfusion. Reserved strictly for life-threatening acute pulmonary edema.

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3. Magnesium Sulphate (MgSO4) Anticonvulsant Protocol

Magnesium Sulphate is the internationally established gold standard neuroprotective agent for both the prevention of seizures in severe pre-eclampsia and the treatment and recurrence prevention of seizures in eclampsia. Landmark trials (the Collaborative Eclampsia Trial and the Magpie Trial) conclusively demonstrated that MgSO4 is far superior to Diazepam, Phenytoin, and lytic cocktails in preventing recurrent convulsions and reducing maternal death without causing maternal respiratory depression or neonatal depression.

PRITCHARD REGIMEN (Standard Kenya MOH Protocol):

[LOADING DOSE (Combined IV + IM)]
  • Intravenous Component: 4 g of MgSO4 as a 20% solution (20 mL)
    given slowly IV over 10 to 15 minutes.
  • PLUS Intramuscular Component: 10 g of MgSO4 as a 50% solution (20 mL total)
    given as 5 g (10 mL) deep IM into EACH upper outer quadrant of the buttocks
    (mixed with 1 mL of 2% plain lidocaine in each syringe to minimize pain).
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[MAINTENANCE DOSE (Intramuscular)]
  • 5 g of MgSO4 (50% solution, 10 mL with 1 mL 2% lidocaine)
    administered deep IM into ALTERNATING buttocks every 4 hours.
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[DURATION OF THERAPY]
  • Continue maintenance doses for 24 hours after delivery OR
    for 24 hours after the last convulsion, whichever occurs LATER.

Pritchard or Zuspan? Know Which One You Are Describing

Examiners test this distinction because the two regimens are routinely confused:

The combined IV-plus-IM loading dose with 4-hourly IM maintenance described above is the Pritchard regimen. Zuspan is the continuous-infusion alternative. Both deliver the same total magnesium burden over 24 hours; Pritchard is the protocol of choice in a sub-county hospital precisely because it does not depend on a working pump.

Management of Breakthrough Seizures on MgSO4

If a patient has a recurrent convulsion while already receiving maintenance Magnesium Sulphate:

• Do not abandon MgSO4 for diazepam.
• Administer an additional 2 g IV bolus of Magnesium Sulphate as a 20% solution (10 mL) slowly over 5 minutes.

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4. Clinical Toxicity Monitoring Rubric & Antidote

Magnesium is eliminated almost exclusively by renal glomerular filtration. When renal perfusion or glomerular filtration rate falls (common in severe pre-eclampsia with oliguria), magnesium accumulates rapidly in the blood, leading to neuromuscular blockade, respiratory paralysis, and cardiac arrest.

CLINICAL MONITORING CRITERIA (MANDATORY BEFORE EVERY 4-HOURLY DOSE):

1. Deep Tendon Reflex (Patellar / Knee-Jerk Reflex): MUST BE PRESENT
   • Loss of patellar reflex is the EARLIEST clinical sign of magnesium toxicity.
   • If absent: Withhold the dose immediately.

2. Respiratory Rate: MUST BE ≥ 16 BREATHS PER MINUTE
   • Magnesium suppresses the central respiratory drive and blocks neuromuscular transmission.
   • If < 16 breaths/min: Withhold the dose and assess for respiratory depression.

3. Urine Output: MUST BE ≥ 30 mL/HOUR (or ≥ 100 mL over previous 4 hours)
   • Insert an indwelling Foley catheter with a urometer to monitor hourly urine output.
   • If < 30 mL/hr: Magnesium is not being cleared; withhold dose to prevent accumulation.

Correlation Between Serum Magnesium Levels & Clinical Manifestations

The Antidote for Magnesium Toxicity

If patellar reflexes are absent, respiratory rate drops below 16/minute, or severe toxicity occurs:

1. Stop the Magnesium Sulphate infusion or withhold intramuscular injections immediately.
2. Administer the specific biochemical antidote:
   • 10% Calcium Gluconate: Administer 10 mL (1.0 g) as a slow intravenous injection over 10 minutes.
   • Calcium directly antagonizes the inhibitory action of magnesium at the neuromuscular junction and myocardial membranes.
3. Administer high-flow supplemental oxygen (10–12 L/min via non-rebreather mask) and provide assisted ventilation (bag-valve-mask or endotracheal intubation) if spontaneous respiratory effort is inadequate.

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5. Definitive Obstetric Management

The delivery of the fetus and placenta is the only definitive cure for pre-eclampsia and eclampsia. All medical therapies (antihypertensives and magnesium sulphate) are stabilizing temporizing measures designed to prevent maternal stroke, renal failure, and seizures before and during delivery.

• Indications for Immediate Delivery (Regardless of Gestational Age):
  • Eclampsia (once maternal convulsions are controlled and hypoxia corrected)
  • Uncontrolled severe hypertension refractory to maximal doses of 2 antihypertensive classes
  • Progressive renal impairment or persistent oliguria
  • HELLP syndrome or worsening thrombocytopenia (< 100,000/μL)
  • Acute pulmonary edema
  • Suspected placental abruption
  • Non-reassuring fetal status or intrauterine fetal demise
• Fetal Lung Maturation: In pre-eclampsia with severe features between 24 and 34 weeks of gestation, if maternal and fetal clinical parameters permit a 24- to 48-hour period of stabilization, administer Intramuscular Dexamethasone (6 mg IM every 12 hours for 4 doses) or Betamethasone (12 mg IM 24 hours apart for 2 doses) to stimulate fetal pulmonary surfactant production and reduce neonatal respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis.
• Route of Delivery: Vaginal delivery is the preferred route if the maternal condition is stable, the cervix is favorable, and there is no cephalopelvic disproportion or fetal distress. Perform artificial rupture of membranes and oxytocin induction. Emergency cesarean section is reserved for standard obstetric indications, unfavorable cervix when urgent delivery within hours is mandatory, or acute fetal distress.