Frequently asked questions on tocolytics
Frequently asked questions on tocolytics
 Professor Hanns Helmer
Department of Obstetrics and Gynecology
University of Vienna, Vienna, Austria
view the video introduction:
Biography
Professor Hanns Helmer graduated from the University of Vienna in 1987. Following a Fellowship with Anna-Riitta Fuchs at Cornell University Medical College, New York, he completed his residency at the University of Vienna, General Hospital. Professor Helmer has been a Senior Physician in the Department of Obstetrics and
Gynaecology at the University of Vienna since 1999.
Abstract
Our understanding of the regulation of myometrial smooth muscle contraction-relaxation is still incomplete. Fundamental differences exist in its regulation and that of other smooth muscles and constitute a conundrum in our understanding. It has to be mentioned that there is no clear evidence that the use of tocolytic drugs improve outcomes, as stated in the Clinical Green-Top Guidelines of the Royal College of Obstetricians and Gynaecologists. However, as the Royal College concludes, tocolysis should be considered if the few days gained would be put to good use, such as completing a course of corticosteroids, or in-utero transfer.
With regards to Clinical Management of preterm labour, the American College of Obstetrics and Gynecology gives some general recommendations for the use of tocolytic medication. ACOG: “If tocolytic drugs are used, the choice of drug should be individualized and based on maternal condition, potential drug side effects, and gestational age”. Some countries of the European Union recommend in their guidelines, the use of atosiban in patients with diabetic conditions or heart problems, due to the cardiovascular side effects of beta-agonists. But in general, there are no recommendations on which tocolytic to use in certain subgroups of pregnant women suffering of preterm labour. Where tocolysis is used, recent trends have favoured agents with lower maternal side-effect profiles, including calcium channel blockers and the oxytocin receptor antagonist atosiban. Recently, several inhibitors of cyclooxygenase-2 (COX-2), the enzyme required to produce the prostaglandins most likely involved in preterm labour, have been developed. These agents may be more effective tocolytics or exhibit a better side-effect profile than the nonspecific NSAIDs currently used as tocolytics.
Magnesium maintenance therapy is one example used after an episode of threatened preterm labour in an attempt to prevent the onset of further preterm contractions. According to a Cochrane review there is not enough evidence to show any difference between magnesium maintenance therapy and either placebo or no treatment, or alternative therapies (ritodrine or terbutaline). Terbutaline maintenance therapy has also failed to decrease the risk of preterm birth by prolonging pregnancy. Although there seems to be a trend that uterine quiescence could be prolonged by subcutaneous atosiban application compared to placebo, we require further investigation into this area. It is difficult to find clinical evidence for tocolytic treatment for multiple gestations and PPROM. In general, the obstetrician has to be aware that this is a very different situation from that of the singleton with intact membranes. It has to be considered that corticosteroid lung maturation of twins or multiple pregnancies induces uterine contractions, often treated by use of tocolysis.
Future tocolytic research includes the possible use of multiple agent therapies, along with the development of more selective treatments with low side-effect profiles. Such agents include prostaglandin F2-alpha receptor antagonists and the oxytocin receptor antagonist atosiban with more favourable pharmacological properties. Future research into tocolytic therapies must focus on evaluating health outcomes from treatments rather than simply the ability to prolong pregnancy, and consequently the design of appropriate clinical studies needs careful consideration with respect to issues such as inclusion criteria, sample size and the selection of appropriate outcome measures.
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