Combination therapy – which tocolytics to use?
Combination therapy – which tocolytics to use?
 Professor Ingemar Ingemarsson
Department of Obstetrics and Gynaecology
University Hospital, Lund, Sweden
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Biography
Professor Ingemar Ingemarsson was educated at the Medical School, University of Lund, Sweden. He obtained his PhD thesis in 1975 which is entitled “Inhibition of
myometrial activity during human pregnancy by beta-adrenoceptor stimulation”. He is Professor of Obstetrics at the University Hospital of Lund and was Head of the Department from 1995 until 2000. He has also been Visiting Professor at the National University of Singapore. In 1997, he became an Honorary Fellow of the Royal College of Obstetricians and Gynaecologists, London, UK. His main research interests include fetal monitoring and preterm birth.
Abstract
The ultimate aim of tocolytic therapy is to prolong pregnancy until fetal growth and maturation is sufficient, but even a short-term delay may enable transfer to a centre with neonatal intensive care facilities and the administration of antepartum glucocorticoids to reduce hyaline membrane disease. Both of these have been shown to reduce neonatal mortality and morbidity. A prolongation of the pregnancy in extremely early weeks (23–26) can improve neonatal survival rates by approximately 3% per day and reduce the need of neonatal intensive care with a concomitant reduction in mortality and morbidity rates.
Aggressive treatment in the extremely early weeks seems therefore indicated provided that the therapy is safe for both mother and fetus. Different tocolytics act on different mechanisms of the calcium inflow in the cell, either as agonists of the uterorelaxant pathway (e.g. beta-receptor agonists), or antagonists of the uterotonic pathway (e.g. oxytocin antagonists, calcium channel blockers, prostaglandin synthetase inhibitors). A combination of drugs could therefore be more effective than single treatment but the effectiveness of such a therapy is difficult to prove when several drugs are involved. In addition, in these early gestational weeks an infectious aetiology is probably involved in at least 40% of all cases.
As a result, we have advocated a policy, not evidence-based, with the routine administration of antibiotics in addition to atosiban infusions supported by intermittent injections of terbutaline and concomitant short-term therapy with prostaglandin synthetase inhibitors or calcium channel blockers. An extended infusion time of atosiban for up to a week has been used in cases where it has been difficult to inhibit preterm labour. Such an extended treatment period has previously not been advocated with beta-agonists as infusion time of more than 24 hours may increase the risk of side effects like pulmonary oedema. With atosiban being an evidence-based tocolytic with proven safety, aggressive treatment such as described has been tested without complications. With this policy it seems that we have been successful in comparison with other perinatal centres in Sweden, in having a low rate of preterm births in weeks 23–24 (18.8%) in relation to all births in weeks 23–26, and a reduction in the time spent in neonatal intensive care. Our clinical observations will be presented.
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