CASE 1: Preterm labor with cervical changes
Ms. M, a 42-year-old woman pregnant with her second child, begins having contractions at 30 weeks’ gestation. Examination reveals that her cervix is dilated 2 cm and effaced 50%. She is given subcutaneous terbutaline to suppress her contractions. Thirty minutes later, she complains of shortness of breath and chest pain. An electrocardiogram reveals depression of the ST segment, and a chest radiograph shows mild pulmonary edema.
How should her symptoms be managed?
Preterm labor precedes delivery in about 50% of preterm births. Approximately 33% of women who have preterm labor will experience spontaneous resolution, and more than 50% of women who have preterm labor will deliver at term. Although the use of tocolytic therapy has proved to be effective at temporarily suppressing uterine activity, it has not been shown to delay delivery for more than a few hours or days.1
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of tocolytics only when a delay in labor for approximately 48 hours would improve outcome. Therefore, tocolytic therapy should be reserved for the following circumstances:
- to stop the progress of labor long enough to administer antenatal corticosteroid therapy
- to prolong pregnancy when there is an underlying self-limiting condition that can cause labor, such as pyelonephritis
- to provide time for safe transport to a facility with a higher level of neonatal care.2
Tocolytics are generally not indicated before the fetus is viable, although we lack data from randomized, controlled trials to support a specific recommendation. The approach is clearer when the fetus is near the upper limits of viability. Most studies suggest that 34 weeks’ gestation is the threshold at which the perinatal morbidity and mortality associated with delivery are too low to justify the cost and potential complications of tocolysis.3
Women who experience preterm labor without cervical changes generally should not be treated with tocolytics.2 Contraindications to tocolytic therapy include:
- lethal fetal anomaly
- nonreassuring fetal status
- maternal disease
- maternal hemorrhage with hemodynamic instability.
Beta-adrenergic agonists carry many risks
These agents have been studied in several randomized, controlled trials. Although ritodrine was approved as tocolytic therapy by the US Food and Drug Administration (FDA), it has since been removed from the US market. Terbutaline is still available but lacks FDA approval as a tocolytic.
Maternal side effects associated with beta-adrenergic agonists are thought to arise from stimulation of the beta-1 and beta-2 adrenergic receptors. Stimulation of the former increases maternal heart rate and stroke volume, whereas stimulation of the beta-2 adrenergic receptors causes the relaxation of smooth muscle, including the muscles of the myometrium, blood vessels, and bronchial tree. The resulting symptoms may include maternal tachycardia, cardiac arrhythmias, palpitations, and metabolic aberrations (including hyperglycemia, hypokalemia, and hypotension). Common symptoms associated with the administration of a beta-adrenergic agonist include tremor, shortness of breath, and chest discomfort.4 Although pulmonary edema and myocardial ischemia are uncommon, they can occur even when there is no history of underlying maternal disease.
Terbutaline has been linked to maternal deaths
Sixteen maternal deaths were reported following initial marketing of terbutaline in 1976 until 2009. Three of the 16 cases involved outpatient use of terbutaline administered by a subcutaneous pump, and nine cases involved use of oral terbutaline alone or in addition to subcutaneous or IV terbutaline. In addition, 12 cases of serious maternal cardiovascular events were reported in association with terbutaline. These events included cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia.
Because of these events, the FDA issued a black box warning for terbutaline that prohibits its use in the treatment of preterm labor for longer than 48 to 72 hours in the inpatient or outpatient setting because of the potential for serious maternal heart problems and death.5 Oral terbutaline should be avoided entirely in the prevention and treatment of preterm labor. However, the use of terbutaline for the management of acute tachysystole with an abnormal fetal heart-rate (FHR) pattern remains a reasonable course of treatment.6
Fetal tachycardia is the most common side effect of beta-adrenergic receptor agonists. For this reason, use of these drugs is not recommended when changes in FHR may be the first sign of fetal compromise, such as in patients with hemorrhage or infection. Neonatal hypoglycemia may also occur if maternal hyperglycemia is not controlled.7
Case 1 Resolved
Terbutaline is discontinued, and the patient’s pulmonary edema is treated with a single dose of furosemide. Electrolyte abnormalities resolve with discontinuation of medication. The patient stabilizes. Once her cardiorespiratory status improves, her contractions lessen and the cervix remains unchanged. She requires no further tocolysis and is discharged home. She presents again at 38 weeks in spontaneous labor.