What is the role of magnesium sulphate in the management of preeclampsia in pregnant women?

Magnesium Sulfate in Preeclampsia: Essential for Seizure Prevention

Magnesium sulfate is the most effective and essential agent for preventing eclamptic seizures in women with severe preeclampsia, reducing seizure risk by more than half compared to placebo and demonstrating clear superiority over other anticonvulsants like phenytoin and diazepam. 1, 2, 3

Primary Clinical Indications

Magnesium sulfate should be administered to pregnant women with severe preeclampsia who meet specific criteria:

• Blood pressure ≥160/110 mmHg with significant proteinuria (≥3+) represents the clearest indication for magnesium sulfate prophylaxis 1, 4, 2

• Moderate hypertension (≥150/100 mmHg) with proteinuria (≥2+) plus signs of imminent eclampsia including severe headache, visual disturbances (scotomata), clonus, or epigastric pain warrants immediate magnesium sulfate administration 4, 2

• All cases of eclampsia require magnesium sulfate for seizure control, where it demonstrates superior efficacy compared to phenytoin (RR 0.08) and nimodipine (RR 0.33) 1, 2, 3

Evidence of Efficacy

The evidence base for magnesium sulfate is robust:

• Seizure prevention: Magnesium sulfate reduces eclampsia risk by 59% (RR 0.41,95% CI 0.29-0.58), with a number needed to treat of 100 women to prevent one case of eclampsia 3

• Maternal mortality: A non-significant trend toward reduced maternal death (RR 0.54,95% CI 0.26-1.10) exists, though the confidence interval crosses 1.0 3

• Placental abruption: Magnesium sulfate reduces placental abruption risk (RR 0.64,95% CI 0.50-0.83) 3

Standard Dosing Protocol

The evidence-based regimen consists of:

• Loading dose: 4-6 grams IV over 20-30 minutes 1, 5, 6

• Maintenance infusion: 1-2 grams per hour by continuous IV infusion 1, 6

• Alternative IM regimen: 4 grams IV loading dose followed immediately by 10 grams IM (5 grams in each buttock), then 5 grams IM every 4 hours in alternating buttocks 5, 6

• BMI-adjusted dosing: For patients with BMI ≥25 kg/m², initiate maintenance at 2 grams per hour rather than 1 gram per hour to achieve therapeutic levels 1, 4

Duration of Therapy

• Continue for 24 hours postpartum in most cases, as eclamptic seizures may develop for the first time in the early postpartum period (particularly days 3-6) 1, 4, 2

• Emerging evidence suggests that if a woman receives at least 8 grams of magnesium sulfate before delivery, continuing for a full 24 hours postpartum may not provide additional benefit, though this remains controversial 4

• Maximum duration: Never exceed 5-7 days of continuous administration, as prolonged use can cause fetal skeletal abnormalities including hypocalcemia, skeletal demineralization, and osteopenia 4, 5

Critical Safety Monitoring

Clinical monitoring is superior to routine laboratory testing:

• Patellar reflexes: Must be present before each dose; loss of reflexes occurs at magnesium levels of 3.5-5 mmol/L and signals impending toxicity 1, 5, 6

• Respiratory rate: Must be ≥12-16 breaths per minute; respiratory paralysis occurs at 5-6.5 mmol/L 1, 2, 5, 6

• Urine output: Maintain ≥30 mL/hour, as oliguria increases toxicity risk since magnesium is renally excreted 4, 2, 5

• Oxygen saturation: Maintain >90% throughout administration 1, 4

• Serum magnesium levels: Routine monitoring is NOT recommended; check levels only in specific high-risk situations including renal impairment, urine output <30 mL/hour, loss of reflexes, or respiratory rate <12 breaths/minute 2, 5

Therapeutic Range and Toxicity

• Therapeutic range: 1.8-3.0 mmol/L (or 3-6 mg/100 mL) for seizure control 5, 6

• Toxicity progression: Loss of deep tendon reflexes at 3.5-5 mmol/L → respiratory paralysis at 5-6.5 mmol/L → altered cardiac conduction at >7.5 mmol/L → cardiac arrest at >12.5 mmol/L 5, 6

• Antidote: Keep calcium gluconate (1 gram IV) immediately available to counteract magnesium toxicity 5

Critical Drug Interactions and Contraindications

Never combine magnesium sulfate with calcium channel blockers (especially IV or sublingual nifedipine), as this combination causes severe myocardial depression and precipitous hypotension—this is the most dangerous drug interaction in preeclampsia management 1, 4, 2, 5

Additional precautions:

• Fluid restriction: Limit total fluid intake to 60-80 mL/hour to prevent pulmonary edema, as preeclamptic women are at dual risk for both pulmonary edema and acute kidney injury 1, 4, 2

• CNS depressants: Reduce dosages of barbiturates, narcotics, and other sedatives when used concurrently due to additive CNS depression 5

• Neuromuscular blocking agents: Use with extreme caution as magnesium potentiates neuromuscular blockade 5

• Cardiac glycosides: Administer with extreme caution in digitalized patients, as serious cardiac conduction changes including heart block may occur 5

Special Clinical Scenarios

• HELLP syndrome: Magnesium sulfate is recommended for seizure prevention in women with HELLP syndrome 4

• Preterm delivery <32 weeks: Magnesium sulfate provides fetal neuroprotection, reducing cerebral palsy risk (RR 0.68,95% CI 0.54-0.87) without increasing mortality 4, 2

• Severe renal insufficiency: Maximum dosage is 20 grams per 48 hours with frequent serum magnesium monitoring 4, 5

Controversy: Mild Preeclampsia

The evidence does NOT support routine magnesium sulfate administration in mild preeclampsia without severe features:

• A randomized controlled trial of 222 women with mild preeclampsia showed no significant reduction in disease progression (12.8% vs 16.8%, RR 0.8,95% CI 0.4-1.5) 7

• However, systematic review data reveals that 25% of eclamptic women were normotensive and 20% had only mild-to-moderate hypertension immediately before seizure, with 25% being completely asymptomatic 8

• Current guideline consensus: Reserve magnesium sulfate for severe preeclampsia with clinical signs of seriousness; in low and middle-income countries, broader use may be justified due to favorable cost-benefit ratio and limited monitoring capabilities 4, 2

Common Side Effects

• Flushing: Occurs in approximately 24% of women receiving magnesium sulfate versus 5% with placebo (NNTH 6) 3

• Warmth sensation: Common and expected, not a sign of toxicity 3

• These side effects, while uncomfortable, do not indicate toxicity and should not prompt discontinuation if clinical monitoring parameters remain normal 3

Blood Pressure Management Considerations

Magnesium sulfate is NOT an antihypertensive agent—it prevents seizures but does not control blood pressure 2

For concurrent severe hypertension (≥160/110 mmHg):

• Use hydralazine, labetalol, or oral immediate-release nifedipine for acute blood pressure control 4, 2

• If using nifedipine, exercise extreme caution with timing relative to magnesium sulfate administration due to the risk of severe hypotension 4, 2