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MS WordPerinatologist Corner - C.E.U/C.M.E. Modules
Preterm Labor and Preterm Premature Rupture of Membranes
Sponsored by The Indian Health Service Clinical Support Center
9. Tocolysis
Tocolytics for the treatment of preterm labor have been extensively studied, but have demonstrated little long term benefit. Most tocolytic agents will reduce the risk of delivery within the first 48 hours, and there are definite advantages to such delay. Nevertheless, no tocolytic agent has consistently reduced the perinatal mortality rate, the incidence of IRDS, or the number of low birth weight infants. This is true for the beta-mimetics (terbutaline, ritodrine), and the calcium channel blockers (nifedipine, magnesium sulfate). Maternal pulmonary edema has been associated with the prolonged use of all these agents, especially in women carrying twins, those with chorioamnionitis, and those subjected to enthusiastic hydration. Neonatal neuromuscular blockade and difficult resuscitation may be associated with excessive use of magnesium sulfate. Despite this agent having been shown to be equivalent to placebo for tocolysis in the meta-analysis data, it inexplicably remains the first-line tocolytic agent in many institutions! The data is conflicting as to the neuroprotective effect of magnesium sulfate, with both a lower and a higher incidence of later cerebral palsy being reported in surviving children. The meta-analysis data show a neutral effect.
Nonsteroidal anti-inflammatory agents such as indomethacin have a better success rate, as measured by lowering the occurrence of low birth weight and prolonging pregnancy. They suppress myometrial prostaglandin production, the last step in the labor cascade. Earlier retrospective reports demonstrated an association of indomethacin with neonatal necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosus, and oliguria. These findings were not confirmed when the RCT employing this agent were subjected to meta-analysis. Likewise, multivariate analysis showed that these effects were not significantly associated with the drug when outcomes were corrected for gestational age, the adverse events being ascribed to immaturity, not to the therapy. A decision analysis concluded that indomethacin tocolysis would result in a lower total number of adverse neonatal outcomes compared to no tocolysis, when restricted to a 48 hour course. Indomethacin is probably the tocolytic of choice because of best efficacy and fewest maternal side effects. It may be given as 50 mg orally q6h over 48 hours with a maximum dose of 400 mg. Greatest benefit and safety is seen when it is given at less than 32 weeks, and it should not be given if there is pre-existing oligohydramnios.
Women between 32-34 weeks, or those with a low AFI, may be more prudently treated with terbutaline 0.25 mg subcutaneously q4h x 4-6 doses. Indomethacin, being administered orally, is somewhat slow acting, so despite having the most evidence favoring its use, you may need to overlap it, or combine it, with another agent initially. Experience with parenteral nonsteroidal agents, such as ketorolac, or the newer selective COX-2 inhibitors such as rofecoxib, is promising but limited. Long-term oral tocolytics of any class really have no place in contemporary obstetrics. It will usually (but not always!) be futile to attempt to tocolyse women in active labor who are at greater than 5 cm cervical dilation, and it will also be risky to attempt to transport these women. Women with PPROM are usually not candidates for tocolysis, however tocolysis may be crucial for transport to the site of delivery.
There are thus two important advantages to the use of tocolytic agents. One is facilitating transport to a level III center for birth, an issue of great significance in our rural-based Indian Health Service setting. The other is buying time for the administration of antenatal corticosteroids.
