Preeclampsia and Eclampsia

Preeclampsia and Eclampsia

Hypertensive Disorders of Pregnancy Classification

A normal first-trimester fall in BP can mask chronic hypertension, so hypertension first detected after 20 weeks is not always preeclampsia. Similarly, pre-existing proteinuria from chronic kidney disease can mimic preeclampsia. The diagnosis of superimposed preeclampsia relies on the new development or worsening of hypertension, proteinuria, or maternal end-organ dysfunction after 20 weeks, rather than the mere presence of hypertension and proteinuria.

Gestational Hypertension

New-onset hypertension after 20 weeks gestation without proteinuria or end-organ dysfunction.

• BP ≥140/90 mmHg on two occasions at least 4 hours apart.
• BP ≥160/110 mmHg on two occasions at least 15 mins apart.

Preeclampsia

 Gestational hypertension plus either:

A. Proteinuria

≥300 mg/24 h urine

OR

Spot Protein/creatinine ratio ≥0.3

OR

Dipstick ≥2+

B. End-Organ Dysfunction (even without proteinuria)

• Platelets <100,000/μL
• DIC
• Hemolysis
• Serum creatinine >1.1 mg/dL or Doubling of baseline creatinine
• Elevated liver enzymes above twice the normal
• Pulmonary edema(in the absence of another etiology)
• New-onset headache refractory to acetaminophen (not accounted for by another diagnosis). 
• Unexplained right upper quadrant or epigastrium Pain.
• Fetal growth restriction
• CNS symptom-Visual symptoms,hyperreflexia,altered mental status.

C.Exclusion of other Causes(Thyroid storm,Chronic HTN,Glomerulonephritis,Acute fatty liver of pregnancy etc)

Severe Preeclampsia

Presence of any severe feature:

Eclampsia

One or more new-onset generalized or focal seizures, or unexplained coma, in a woman with preeclampsia (or features suggestive of preeclampsia), that cannot be attributed to another neurological cause.

Pathophysiology

Normal Pregnancy

Trophoblasts invade spiral arteries.

Result:

• Large vessels
• Low resistance
• High flow

Placental perfusion becomes adequate.

Preeclampsia

Defective trophoblastic invasion.

Spiral arteries remain:

• Narrow
• Muscular
• High resistance

Result:Placental ischemia.

Stage 1: Placental Dysfunction

Ischemic placenta releases:

Antiangiogenic Factors

• sFlt-1 (soluble Fms-like tyrosine kinase)
• Soluble endoglin

These inhibit:

• VEGF
• PlGF

leading to endothelial dysfunction.

Stage 2: Maternal Endothelial Dysfunction

• Vasoconstriction(↑ SVR)
• Capillary Leak(Edema)
• Coagulation Activation(Microangiopathy)
• Organ Ischemia(Brain,Kidney,Liver,Placenta)

Why Proteinuria Occurs

Endotheliosis of glomerular capillaries causes:

• Loss of filtration barrier
• Increased protein leakage

Why Edema Occurs

Combination of:

• Capillary leak
• Hypoalbuminemia
• Sodium retention

Why Seizures Occur

Cerebral endothelial dysfunction causes:

• Vasospasm
• Hyperperfusion
• BBB disruption
• Vasogenic edema

This produces:Posterior Reversible Encephalopathy Syndrome (PRES) which is the major mechanism of eclamptic seizures.

Risk Factors

Clinical Features

Laboratory Abnormalities

Fetal Evaluation

Management 

Three major goals:

1. Prevent seizures
2. Control blood pressure
3. Deliver fetus at appropriate time(Delivery of the placenta is the only definitive cure for preeclampsia.)

Blood Pressure Control

• For chronic hypertension, maintain BP <140/90 mmHg based on the CHAP trial.
• These BP targets and thresholds may varies in different guidelines-AHA,NICE,ACOG.

Blood Pressure Targets in Preeclampsia

Severe hypertension (SBP ≥160 mmHg and/or DBP ≥110 mmHg, persistent for ≥15 minutes) is an obstetric emergency and requires urgent treatment, to reduce the risk of maternal stroke, intracranial hemorrhage, heart failure, and other end-organ complications.

Treatment targets

• Initial goal: Reduce mean arterial pressure (MAP) by approximately 20% over the first few hours, avoiding an abrupt fall.
• Subsequent target: Maintain BP at approximately:
• SBP 140–150 mmHg
• DBP 90–100 mmHg
• MAP ~105–115 mmHg
• Targets should be individualized according to the patient’s baseline blood pressure, comorbidities, and maternal-fetal status.

Avoid overcorrection

• Rapid or excessive BP reduction should be avoided, as it may reduce uteroplacental perfusion, leading to fetal compromise.
• Placental hypoperfusion may further promote the release of antiangiogenic, vasoconstrictive, and inflammatory mediators, potentially worsening the underlying disease process.

Blood pressure monitoring

• Non-invasive cuff BP measurement is adequate for most patients and should be performed frequently (every 5–15 minutes during acute BP control).
• Routine arterial line placement is not recommended, as oscillometric cuff measurements are generally accurate in pregnant women.
• Consider an arterial catheter only when:
• BP is extremely labile or difficult to control.
• Continuous beat-to-beat monitoring is required.
• Frequent arterial blood gas sampling is anticipated.
• The patient has shock, major hemorrhage, or is receiving multiple vasoactive infusions.

Antihypertensive Drugs Used in Preeclampsia

Drugs Contraindicated During Pregnancy

Fluid Management 

Preeclampsia is characterized by systemic endothelial dysfunction, resulting in increased capillary permeability, reduced plasma oncotic pressure, and third-space fluid sequestration. Consequently, despite the presence of generalized edema, many patients are relatively intravascularly volume depleted. Administered intravenous fluids readily leak into the interstitial space, increasing the risk of pulmonary edema without significantly improving intravascular volume.

Principles of fluid therapy

• Avoid routine liberal fluid administration.
• Administer only the minimum fluid required to maintain intravascular perfusion and provide medications.
• For women who are nil per os (NPO), maintenance fluids should be given cautiously (e.g., 50–80 mL/hour of an isotonic crystalloid or dextrose-containing maintenance fluid, adjusted to clinical needs).
• Several guidelines recommend restricting total fluid intake to approximately 80 mL/hour (excluding ongoing losses and essential medications) unless there are additional indications such as hemorrhage or sepsis.
• Avoid excessive fluid boluses, as they markedly increase the risk of pulmonary edema, particularly in patients with severe preeclampsia or renal impairment.

Management of oliguria

• Do not treat oliguria with repeated fluid challenges.
• If hypovolemia is suspected, a single small fluid bolus (250–300 mL isotonic crystalloid) may be given while closely monitoring the clinical response.
• If urine output does not improve after this limited fluid challenge, additional fluids are usually not beneficial and may be harmful. Instead, reassess for alternative causes such as acute kidney injury, severe vasoconstriction, or evolving multiorgan dysfunction.
• Routine use of central venous pressure (CVP) to guide fluid therapy is not recommended because it poorly predicts fluid responsiveness.

Seizure Management 

• Initial steps are same as of any seizure management i.e check RBS,Protect airway etc.
• Give Magnesium  
• if  ongoing convulsive seizures lasting >5 minutes:Give Benzodiazepine

—midazolam—10mg IM

—Lorazepam—0.1 mg/kg IV (based on ideal body weight, not actual)

Magnesium Sulfate

• Seizure prevention(preeclampsia with severe features.)-MAGPIE Trial
• In cases where magnesium sulfate IV is contraindicated, leviteracetam can be used for prophylaxis.(valproic acid & fosphenytoin are contraindicated). 
• Seizure treatment (but Magnesium isn’t effective for terminating  seizures that are actively ongoing.)
• If seizure is unclear due to eclampsia still give it with levetiracetam unless contraindicated.

 Contraindications—Myasthenia gravis,Heart block,Severe hypocalcemia.

Mechanism

• NMDA antagonism
• Cerebral vasodilation
• Reduces neuronal excitability
• Magnesium sulfate is NOT an antihypertensive drug.

Why does BP sometimes fall after magnesium?

Magnesium causes:

• Mild peripheral vasodilation
• Reduced catecholamine release
• Reduced vasospasm

Magnesium Sulfate Regimens

Dose Adjustment in Renal Impairment

Magnesium is excreted exclusively by the kidneys.

For women with:

• Serum creatinine >2.5 mg/dL
• Oliguria
• GFR <30 ml/min

Recommendations:

• Give the standard 4 g IV loading dose.
• withhold the maintenance infusion (Some says decrease the dose i.e 0.5gm/hr)
• serum magnesium levels every 4–6 hours Based on these Give sos  Doses.

Duration of Therapy (Both Regimens)

Routine serum magnesium monitoring is not required in women with normal renal function.

Recurrent seizure while on magnesium(Breakthrough seizure)

—Give 2 g IV magnesium sulfate over 3–5 minutes.

—Most eclamptic seizures are self-limited but if Persistent seizures        >5 minutes(Status Epilepticus)

• Start Antiseizure medication—Levetiracetam(first line) ,Lacosamide(second line)
• Intubate
• Anesthetic infusion—Propofol(Class B),Midazolam(Class C),Thiopentone (less commonly used)

Evaluate for alternative diagnoses:

• Intracranial hemorrhage
• Cerebral venous sinus thrombosis
• Ischemic stroke
• PRES
• Meningitis
• Epilepsy

Therapeutic Serum Magnesium Levels

ECG changes (prolonged PR interval and widened QRS) at 5–10 mEq/L

Management of Toxicity

1. Stop magnesium infusion.
2. Administer oxygen and support ventilation.
3. Give 10 mL of 10% calcium gluconate (1 g) IV slowly over 3–5 minutes.
4. Repeat if needed.
5. Consider diuretics if renal function is adequate.
6. Hemodialysis for severe toxicity or renal failure.

Timing of Delivery(Decision by obstetrics team)

Delivery Recommended Regardless of Gestation

• Eclampsia
• HELLP
• Pulmonary edema
• DIC
• Placental abruption
• Uncontrolled hypertension despite three classes of antihypertensive agents
• Persistent neurologic symptoms
• Fetal compromise

References

1. Katsi V, Svigkou A, Dima I, Tsioufis K. Diagnosis and Treatment of Eclampsia. J Cardiovasc Dev Dis. 2024 Aug 23;11(9):257. doi: 10.3390/jcdd11090257. PMID: 39330315; PMCID: PMC11432638.
2. Irwin RS, Rippe JM. Irwin and Rippe’s Intensive Care Medicine. 9th ed.