Using Nifedipine as a Tocolytic in Preterm Labor

Peter S. Bernstein, MD, MPH, FACOG; Mary King, MD

Disclosures

August 18, 2004

Question

Can the calcium channel blocker nifedipine be used as a tocolytic in preterm labor? What regimen should be used?

John V Mutton, FRCOG, FRACOG

Response From the Expert

Peter S. Bernstein, MD, MPH
Associate Professor of Clinical Obstetrics & Gynecology and Women's Health, Division of Maternal-Fetal Medicine, Dept. of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York

 

Preterm labor remains a difficult issue in current obstetrics. Preterm birth still plays a major role in perinatal mortality and morbidity in developed countries, accounting for 60% to 80% of all neonatal deaths among infants without congenital anomalies. The rate of preterm delivery in the United States has not decreased, but rather has increased to 12% in 2002, partly due to an increased rate of preterm induction.

Tocolysis is the use of medication to prevent preterm delivery. Preterm labor is defined as regular uterine contractions causing cervical dilation. Several classes of medications are used for tocolysis, including beta-adrenergic agents, calcium channel blockers, prostaglandin synthetase inhibitors such as indomethacin, and magnesium sulfate.

Efficacy in delaying delivery for 24-48 hours has been shown with beta-adrenergic agents, such as ritodrine; however, they cause unpleasant maternal side effects, such as palpitations, and can cause pulmonary edema, myocardial ischemia, and arrhythmia.

Magnesium sulfate is also commonly used, and has similar efficacy to terbutaline. It is better tolerated, but the patient must be monitored for toxic effects, such as respiratory depression or even cardiac arrest, which can occur at supertherapeutic levels.Common maternal side effects include flushing, nausea, headache, drowsiness, and blurred vision. Magnesium crosses the placenta and can cause respiratory and motor depression of the neonate.

Indomethacin has also been shown to have efficacy similar to that of ritodrine. It is associated with infrequent maternal side effects, but it readily crosses the placenta and can cause oligohydramnios if used for more than 48 hours. Usually the amniotic fluid reaccumulates, but persistent fetal anuria, renal microcystic lesions, and neonatal death have been reported. Indomethacin can also cause premature closure or constriction of the ductus arteriosus, which can lead to persistent fetal circulation after birth. This effect is more common after 32 weeks' gestation, so it is recommended that therapy should be discontinued by 32 weeks.

Calcium channel blockers reduce calcium influx into cells, reducing muscle contractility. Nifedipine has been used in the majority of studies. A 2002 meta-analysis reviewed 12 randomized-controlled studies involving 1029 women and found that nifedipine is more effective than ritodrine and is clearly safer. Because each individual trial has been small, this is the best evidence to date that nifedipine can be used for tocolysis. The investigators found a reduced risk of delivery within 7 days and at less than 34 weeks' gestation. Cessation of treatment due to adverse reaction occurred in 1 of 419 patients, vs 29 of 414 with other tocolytics. The nifedipine-treated neonates also had decreased risk of respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage.

The recommended protocol consists of 20 mg orally stat, followed by 20 mg orally after 30 minutes if contractions persist, followed by 20 mg orally every 3-8 hours for 48-72 hours as indicated. The maximum dose is 160 mg/day. After 72 hours, if maintenance is required, patients can be changed to long-acting nifedipine 30-60 mg daily. Contraindications include allergy to nifedipine, hypotension, hepatic dysfunction, concurrent use of beta-mimetics, transdermal nitrates, or other antihypertensive medication. Hypotension can occur with concurrent use of nifedipine and magnesium. Hypotension is a side effect; however, it is minimal in normotensive patients. Other commonly reported side effects are tachycardia, palpitations, flushing, headaches, dizziness, and nausea. Continuous monitoring of the fetal heart rate is recommended as long as the patient has contractions, and the patient's pulse and blood pressure should be monitored every 30 minutes for the first hour, then hourly for the first 24 hours, then every 4 hours.

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