From the Editor

Is the end of an era here for magnesium sulfate tocolysis?

OBG Manag. 2007 January;19(1):6-10

References

1. Stan C, Boulvain M, Hirsbrunner-Amagbaly P, Pfister R. Hydration for treatment of preterm labour. Cochrane Database Syst Rev. 2002;(2):CD003096.-

2. Crowther CA, Hiller JE, Doyle LW. Magnesium sulfate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev.

3. Papatsonis D, Flenady V, Cole S, Liley H. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev. 2005;(3):CD004452.-

4. King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev. 2002;(4):CD000246.-

5. Duckitt K, Thornton S. Nitric oxide donors for the treatment of preterm labour. Cochrane Database Syst Rev. 2002;(3):CD002860.-

6. King J, Flenady V, Cole S, Thornton S. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev. 2005;(2):CD001992.-

7. King JF, Flenady VJ, Papatsonis DNM, Dekker GA, Carbonne B. Calcium channel blockers for inhibiting preterm labour. Cochrane Database Syst Rev. 2003;(1):CD002255.-

8. Anotayanonth S, Subhedar NV, Neilson JP, Harigopal S. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev. 2004;(4):CD004352.-

9. Reid DE. A Textbook of Obstetrics. Philadelphia: WB Saunders; 1962.

10. Pritchard JA, MacDonald PC, Gant NF.Williams Obstetrics, 17th ed. Norwalk, Conn: Appleton-Century Crofts; 1985.

11. Grimes DA, Nanda K. Magnesium sulfate tocolysis. Time to quit. Obstet Gynecol. 2006;108:986-989

12. Abbas OM, Nassar AH, Lanj NA, Usta IM. Acute pulmonary edema during tocolytic therapy with nifedipine. Am J Obstet Gynecol. 2006;195:e3-e4

13. Parasuraman R, Gandhi MM, Liversedge NH. Nifedipine tocolysis associated atrial fibrillation responds to DC cardioversion. BJOG. 2006;113:844-845

14. van Geijn HP, Lenglet JE, Bolte AC. Nifedipine trials: effectiveness and safety aspects. BJOG. 2005;112(Suppl1):79-83

15. Oei SG. Calcium channel blockers for tocolysis: a review of their role and safety following reports of serious adverse events. Eur J Obstet Gynecol Reprod Biol. 2006;126:137-145

In the absence of demonstrated clinical efficacy and a concern over potentially negative neonatal effects, obstetricians should consider strictly limiting their use of magnesium for tocolysis.¹¹

If not magnesium, what?

Cochrane analyses indicate that data reliably support the superiority of two tocolytics over controls: calcium-channel blockers and betamimetics (TABLE). The calcium-channel blocker nifedipine has been demonstrated to reduce the risk of birth within 7 days of initiating treatment and of birth prior to 34 weeks’ gestation, compared with betamimetics. Women in preterm labor who are receiving a calcium-channel blocker are less likely to require discontinuation of the treatment due to adverse effects compared with women treated with a betamimetic. Given the demonstrated clinical efficacy of calcium-channel blockers and their few adverse side effects, these agents should be more widely used as tocolytics.

Nifedipine. This calcium-channel blocker has the longest and widest use as a tocolytic. A typical regimen is to administer nifedipine, 10 mg orally, every 20 minutes up to 4 doses as needed to reduce contractions and avoid hypotension. Maintenance treatment is nifedipine, 20 mg orally, every 4 to 8 hours. The maximum daily dosage is in the range of 120 to 180 mg. Nifedipine inhibits voltage-dependent L-type calcium channels, which leads to vascular and other smooth-muscle relaxation and negative inotropic and chronotropic effects on the heart.

Not surprisingly, nifedipine has been reported to be associated with many adverse cardiovascular side effects, including acute pulmonary edema,¹² arrhythmias,¹³ and hypotension. Caution is advised when using nifedipine in multiple-gestation pregnancy and maternal cardiac disease.^14,15 Many authorities strongly caution against the use of nifedipine with magnesium or betamimetics because of additive adverse effects on the cardiovascular system.

If the goal of therapy is to complete a course of betamethasone, then nifedipine may be discontinued after 48 hours. Alternatively, the medication can be continued to achieve another endpoint, such as prolonging pregnancy up to 34 weeks when a condition such as polyhydramnios is present.

We need research

Preterm delivery is a major public health problem, and more research is required to identify the fundamental biologic causes of preterm labor. In the near future, basic science discoveries will be translated from the bench to the bedside, resulting in new treatments for the real causes of preterm labor that will be far superior to available tocolytics.

For more on magnesium sulfate tocolysis, please see Medical Verdicts.

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Is the end of an era here for magnesium sulfate tocolysis?

References

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