Tocolytics

Tocolytics are medications used to delay preterm labor by inhibiting uterine contractions. They aim to prolong pregnancy for at least 48 hours, allowing time for interventions such as corticosteroid administration to enhance fetal lung maturity and the transfer of the mother to a facility equipped for premature neonatal care.

Indications for Tocolytics

• Gestational age between 24 and 34 weeks: Tocolytics are most effective during this period to delay delivery.
• Need for corticosteroid therapy: Tocolytics can provide time for administration of corticosteroids (e.g., betamethasone) to enhance fetal lung maturity.
• Maternal transfer: Allowing time to transfer the mother to a tertiary care facility with neonatal intensive care.

Contraindications for Tocolysis

• Maternal Factors: Severe pre-eclampsia/eclampsia, significant bleeding (placental abruption or previa), intrauterine infection (chorioamnionitis), advanced cervical dilation (>4 cm), or maternal instability.
• Fetal Factors: Fetal demise, lethal congenital abnormalities, or severe intrauterine growth restriction (IUGR) with compromised fetal status.

Commonly Used Tocolytics

Calcium Channel Blockers (Nifedipine)

• Mechanism: Inhibits calcium influx into smooth muscle cells, reducing uterine contractions.
• Dosage:
  • Initial dose: 10-20 mg orally.
  • Repeat dose: 10-20 mg every 4-6 hours (maximum daily dose: 160 mg).
• Side Effects: Maternal hypotension, headache, flushing, dizziness, nausea. Use cautiously in patients with cardiovascular disease.
• Advantages: Oral administration, fewer side effects compared to other tocolytics.

Beta-Agonists (Terbutaline, Ritodrine)

• Mechanism: Stimulates beta-2 adrenergic receptors in uterine smooth muscle, leading to relaxation.
• Dosage:
  • Terbutaline: 0.25 mg subcutaneously every 20-30 minutes (maximum 4 doses), or 2.5-5 mg orally every 4-6 hours.
  • Ritodrine (less commonly used): Continuous IV infusion starting at 0.05 mg/min, increasing to a maximum of 0.35 mg/min.
• Side Effects: Maternal tachycardia, palpitations, hyperglycemia, hypokalemia, tremor, pulmonary edema (rare but serious). Contraindicated in patients with uncontrolled diabetes or heart disease.

Magnesium Sulfate

• Mechanism: Competes with calcium at the cell membrane level, reducing uterine muscle contraction.
• Dosage:
  • Loading dose: 4-6 g IV over 20-30 minutes.
  • Maintenance dose: 2-4 g/hour IV infusion.
• Side Effects: Flushing, nausea, headache, respiratory depression, loss of deep tendon reflexes, magnesium toxicity (serious but rare).
• Additional Benefit: Provides neuroprotection for the fetus, reducing the risk of cerebral palsy in preterm births.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) – Indomethacin

• Mechanism: Inhibits cyclooxygenase (COX), thereby decreasing prostaglandin synthesis and uterine contractions.
• Dosage:
  • Oral: 50-100 mg initially, followed by 25-50 mg every 4-6 hours for up to 48 hours.
• Side Effects: Maternal gastrointestinal upset, fetal renal impairment, premature closure of the ductus arteriosus, oligohydramnios (when used >48 hours or beyond 32 weeks gestation).
• Limitations: Generally used for pregnancies less than 32 weeks.

Oxytocin Receptor Antagonists (Atosiban)

• Mechanism: Inhibits oxytocin-induced uterine contractions.
• Dosage: Administered as an IV bolus of 6.75 mg over 1 minute, followed by an infusion of 18 mg/hour for 3 hours, and then 6 mg/hour for up to 45 hours.
• Side Effects: Nausea, vomiting, headache, chest pain (rarely used compared to other agents).
• Advantages: Generally well-tolerated with fewer cardiovascular side effects.

Tocolytic Choice Considerations

• Nifedipine and Magnesium Sulfate are often preferred due to their effectiveness and relatively favorable side effect profiles.
• Indomethacin is typically reserved for cases <32 weeks due to concerns about fetal side effects.
• Beta-agonists are less frequently used due to the higher incidence of maternal side effects.
• Atosiban may be considered if other tocolytics are contraindicated or ineffective.

Duration of Tocolytic Therapy

• Tocolytics are generally used for short-term delay of labor (up to 48 hours), sufficient for corticosteroid administration or maternal transfer.

Monitoring During Tocolysis

1. Maternal Monitoring: BP, heart rate, respiratory rate, oxygen saturation, and deep tendon reflexes (especially for magnesium sulfate). Laboratory tests (serum magnesium, electrolytes, glucose).
2. Fetal Monitoring: Continuous fetal heart rate monitoring and ultrasound assessment of amniotic fluid volume, especially with prolonged tocolysis.