There's no good evidence that magnesium sulfate is effective as a tocolytic agent, it causes unpleasant side effects in the mother, it can cause serious harm to the newborn, and better tocolytics are available, so it's time to quit using it, Dr. David A. Grimes and Dr. Kavita Nanda charged in a strongly worded editorial.
Evidence of magnesium sulfate's ineffectiveness has been available for years, and its continued use, “reflects inadequate progress toward rational therapeutics in obstetrics,” wrote the authors, both obstetrician-gynecologists at Family Health International, Research Triangle Park, N.C. (Obstet. Gynecol. 2006;108:986–9).
“I'm old enough to recall the days in which we used intravenous ethanol to try to stop labor,” Dr. Grimes said in an interview. “It was a horrible, horrible treatment, and it didn't work. When I talk to residents today about that practice, they laugh. My concern is that 30 years from today young physicians will look back and laugh at giving IV [intravenous] Epsom salts to try to stop labor.”
Dr. Grimes drew an analogy to the farmers of yore, who sometimes allowed their animals to overgraze the common village green. “A lot of medical procedures and practices have overgrazed on our medical commons for far too long without appropriate rationale.” Obstetrics is full of examples of things that were routinely done and are no longer done because they are inappropriate, wasteful, or harmful, he said.
The persistence of magnesium sulfate tocolysis is puzzling, especially in light of a 2002 metaanalysis by the Cochrane Collaboration, Dr. Grimes said. The meta-analysis included 2,000 women in 23 randomized, controlled trials in which magnesium sulfate was compared with no tocolytic or to alternative tocolytics. The authors found no evidence that magnesium sulfate had clinical benefit for short-term (48 hours or less) or long-term tocolysis, and some evidence that it may be actively harmful to the newborn (Cochrane Database Syst. Rev. 2002;CD001060).
While acknowledging that the evidence is inconsistent, Dr. Grimes estimated that magnesium sulfate tocolysis may be responsible for 1,900–4,800 fetal and neonatal deaths each year in the United States alone. He said that to his knowledge, Canada and the United States are the only two countries in the industrialized world in which magnesium sulfate remains the predominant tocolytic.
As to why the practice has persisted, Dr. Grimes cited the power of medical tradition and lack of familiarity with the evidence. “The Cochrane Library is growing in visibility, but the rank-and-file practitioner still may not be aware of or have access to this valuable source of medical information,” he said.
Not everyone is convinced that the Cochrane Database meta-analysis is the last word on magnesium sulfate tocolysis. Dr. Brian C. Brost of the Mayo Clinic, Rochester, Minn., pointed out that only one of the studies included in the analysis was a randomized trial comparing magnesium sulfate with placebo. The others compared magnesium sulfate with alternate tocolytics, and there were various end points as well, making the studies difficult to compare with each other.
In an interview, Dr. Brost said that it is extremely difficult to do randomized, blinded, controlled trials of tocolysis for ethical and practical reasons. For one thing, because of magnesium sulfate's prominent and unpleasant side effects, women know instantly whether they've been given this drug, a placebo, or another drug, making true blinding impossible. Also, if a woman's contractions stop or slow after the administration of a tocolytic, it's difficult to know whether the change was an effect of the tocolytic or a simple coincidence.
Nevertheless, Dr. Brost does believe that it's time to stop using magnesium sulfate tocolysis, although he admitted that it's still part of his practice. But even if magnesium sulfate merely slowed contractions without stopping them, he said, that would allow steroids to have a better effect, which would improve the outcome for some infants.
He also suggested that the transition to alternate tocolytics may be hastened if the American College of Obstetricians and Gynecologists issued a stronger statement than that in its practice guideline which states, “all [tocolytic agents] have demonstrated only limited benefit. Hence, there is no clear first-line tocolytic drug.”
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