How to manage emergencies associated with tocolysis for preterm labor
Although short-term tocolysis usually is safe, certain agents and scenarios may increase the risk of harm. Here, four cases involving serious complications.
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Fetal effects of magnesium sulfate
CASE 2: Preterm labor treated with indomethacin
Ms. J, age 23, is 26 weeks’ pregnant with her first child. When she experienced preterm labor at 24.5 weeks’ gestation, she was given indomethacin. Now, ultrasonographic imaging reveals decreased amniotic fluid volume.
How should she be managed?
Indomethacin is a cyclooxygenase (COX) inhibitor. These drugs reduce prostaglandin production through the general inhibition of cyclooxygenase or by a specific receptor.8 Indomethacin is the most commonly used tocolytic in this class. It is a nonspecific COX inhibitor, as opposed to a COX-2 inhibitor. The latter has been associated with serious adverse outcomes in the nonobstetric population. COX-2 inhibitors now carry a black box warning or are no longer available.
Maternal contraindications for COX inhibitors include asthma, bleeding disorders, and significant renal dysfunction.
Although maternal side effects with COX inhibitors are usually mild, fetal side effects may be serious enough to cause perinatal morbidity or death.9
How indomethacin can lead to oligohydramnios
Maternal administration of indomethacin or ibuprofen can reduce fetal urine output and decrease the volume of amniotic fluid. In most cases, oligohydramnios occurs when indomethacin or ibuprofen has been given for more than 72 hours. For this reason, long-term use of a COX inhibitor should be accompanied by frequent monitoring of amniotic fluid volume by ultrasonography.
The most serious fetal complication associated with prolonged indomethacin administration (longer than 72 hours) is premature constriction of the ductus arteriosus. Ductal constriction appears to be contingent on gestational age. It has been described as early as 24 weeks’ gestation but is most common after 31 or 32 weeks. Therefore, indomethacin is not recommended for use after 32 weeks’ gestation.10
CASE 2 Resolved
The indomethacin is discontinued as soon as the decreased amniotic fluid is noted. The fluid volume returns to normal over the next 3 to 5 days. Because of the early gestational age, nifedipine is given to suppress contractions, and the patient has no further complications.
CASE 3: Preterm labor and magnesium intoxication
Ms. K experiences contractions and rapid cervical change at 32 weeks’ gestation. She is given magnesium for the preterm labor and fetal neuroprophylaxis, with nifedipine, a calcium-channel blocker, added as second-line tocolysis. Approximately 8 hours later, she reports difficulty breathing and moving.
How should her obstetrician proceed?
Calcium-channel blockers such as nifedipine are used for acute and maintenance tocolysis. This class of drugs is often selected for its relative ease of use and safety, as it has few maternal and fetal side effects. However, concomitant use of a calcium-channel blocker and magnesium sulfate can sometimes lead to neuromuscular blockade and significant respiratory depression, even necessitating mechanical ventilation.9 Treatment of these effects includes IV administration of 10% calcium gluconate (5–10 mEq), which usually reverses respiratory depression and heart block caused by magnesium intoxication. In extreme cases, peritoneal dialysis or hemodialysis may be required.
CASE 3 Resolved
The patient is given 10% calcium gluconate in the dosage described above, and she stabilizes. However, her contractions continue and she delivers at 32 weeks’ gestation. The infant does well in the NICU.
CASE 4: Preterm labor in a woman with kidney dysfunction
Ms. F, age 40, presents at 30 weeks’ gestation with regular contractions and cervical dilation of more than 3 cm. She also reports a history of kidney disease.
What steps are recommended prior to the initiation of magnesium therapy?
Magnesium sulfate has been used for more than 40 years to treat preterm labor and is still considered a first-line therapy in many centers. Although maternal side effects usually are mild, an adverse event may occur if the patient is not monitored carefully. An absence of deep-tendon reflexes should alert the clinician that magnesium levels need to be measured. Reflexes usually are lost at a serum level of 10 mEq/L or higher. When the magnesium level exceeds 13 mEq/L, cardiac arrest is a risk. IV calcium should be administered immediately in such patients.
Magnesium should be used with caution in patients with myocardial compromise. Because magnesium is eliminated by the kidneys, women with impaired renal function may experience magnesium toxicity at normal doses. If a patient has a creatinine level above 1 mg/dL, consider alternative treatment for her preterm labor. If magnesium is given, the normal loading dose (4–6 g) is appropriate, but the maintenance dose should be reduced.11
Fetal effects of magnesium sulfate
Recent studies indicate that predelivery magnesium may offer fetal neuroprotection. The minimum duration of administration for such neuroprotection is unknown but is less than 24 hours.8
Although magnesium can alter FHR patterns slightly, these changes are not clinically significant. Magnesium can also cause mild neonatal suppression at the time of delivery, but its effects quickly resolve with appropriate neonatal resuscitation. Long-term (>5 days) therapy is not recommended.
