Relevance. Toсolytic therapy is the only method that is used in the treatment of pregnant women with preterm labor. However, the effectiveness and safety of this therapy is still a matter of debate. One of the least studied issues of this problem is the safety of therapy, which is primarily manifested by the frequency of side effects.
The aim is to carry out a comparative study of the safety of the most common tocolytic agents - atosiban, nifedipine and hexoprenaline sulfate.
Material and methods. The study included 173 pregnant women with threatening premature births in a period of 28 to 34 weeks. In 54 cases, tocolysis with nifedipinum, 57 with atosiban, 62 with hexoprenaline was performed. To assess the effectiveness of tocolysis, clinical and instrumental methods of control (ultrasound with cervicometry) were used. The primary outcome points were the frequency of prolongation of pregnancy at 48 h and the incidence of side effects, including those requiring the termination of tocolysis.
Results. Prolongation of pregnancy at 48 h was achieved in groups of nifedipine, atosiban and hexoprenaline sulfate, respectively in 46 (85.19%), 55 (96.49%) and 53 (77.40%) pregnant. Atosiban showed significantly higher efficacy. In 8 cases of tocolysis with nifedipine and 3 - hexoprenaline, the tocolysis protocol was not performed due to intolerance of treatment. In these observations, the highest frequency of preterm labor occurred. After excluding these observations from the analysis of differences in the frequency of prolongation of pregnancy was not. The overall frequency of adverse events in the groups was 38.9, 12.3 and 82.3%, and was significantly lower in the atosiban group than nifedipine and hexoprenaline sulfate.
Conclusions. The effectiveness of tocolysis is affected by the tolerability of the drugs. Atosiban showed the best of the three drug safety profile. With comparable efficacy, atosiban has proven to be a drug that, to a greater extent than nifedipine and hexoprenaline sulfate, meets the current requirements for tocolytic drugs.
Key words: premature birth, tocolysis, tocolytic therapy, nifedipine, atosiban, hexoprenaline sulfate.
About the Author
O.R.Baev*, O.N.Vasilchenko, A.O.Karapetyan
V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
1. Saveleva G.M., Shalina R.I., Kurtser M.A. i dr. Prezhdevremennye rody kak vazhneishaia problema sovremennogo akusherstva. Akusherstvo i ginekologiia. 2012; 2: 4–10. [in Russian]
2. Khodzhaeva Z.S., Fedotovskaia O.I., Kholin A.M. Medikamentoznaia terapiia ugrozhaiushchikh prezhdevremennykh rodov. Akusherstvo i ginekologiia. 2013; 5: 17–22. [in Russian]
3. Doyle LW et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009; 1: CD004661.
4. Baev O.R., Vasilchenko O.N., Karapetian A.O. i dr. Sravnenie tokoliza geksoprenalinom i atozibanom. Med. sovet. 2017; 2: 57–61. [in Russian]
5. Husslein P, Roura L, Dudenhausen J et al. on behalf of the TREASURE study group. Clinical practice evaluation of atosiban in preterm labour management in six European countries. BJOG 2006; 113 (Suppl. 3): 105–10.
6. Jorgensen JS, Weile LK, Lamont RF. Preterm labor: current tocolytic options for the treatment of preterm labor. Expert Opin Pharmacother 2014; 15 (5): 585–8.
7. Spiesser-Robelet L, Martin B, Carceller AM et al. Adverse effects and hemodynamic effects of nifedipine as a tocolytic. J Gynecol Obstet Biol Reprod (Paris) 2015; 44 (7): 614–20.
8. Crowther CA, Brown J, McKinlay CJ, Middleton P. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2014; 8: CD001060. DOI: 10.1002/14651858.CD001060.pub2
9. Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev 2014; 2: CD004352. DOI: 10.1002/14651858.CD004352.pub3
10. Van Vliet Elvira OG, Nijman Tobias AJ, Schuit Ewoud et al. Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. Lancet 2016; 387 (10033): 2117–24.
11. Nijman TAJ, Goedhart MM, Naaktgeboren CN et al. The effects of nifedipine and atosiban on perinatal brain injury: a secondary analysis of the APOSTEL III trial Ultrasound Obstet Gynecol 2017. DOI: 10.1002/uog.17512
12. De Heus R, Mulder EJ, Derks JB, Visser GH. The effects of the tocolytics atosiban and nifedipine on fetal movements, heart rate and blood flow. J Matern Fetal Neonatal Med 2009; 22: 485–90.
13. Clouqueur E, Gautier S, Vaast P et al. [Adverse effects of calcium channels blockers used as tocolytic treatment]. J Gynecol Obstet Biol Reprod (Paris) 2015; 44 (4): 341–56. DOI: 10.1016/j.jgyn.2014.12.012 [Article in French]
14. Vercauteren M, Palit R, Soetens F et al. Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics. Acta Anaesthesiol Scand 2009; 53: 701–9.
15. Van Veen AJ, Pelinck MJ, van Pampus MG et al. Severe hypotension and fetal death due to tocolysis with nifedipine. BJOG 2005; 112: 509–10.
16. Chan LW, Sahota DS, Yeung SY et al. Side-effect and vital sign profile of nifedipine as a tocolytic for preterm labour. Hong Kong Med J 2008; 14: 267–72.
For citation:Baev O.R., Vasilchenko O.N., Karapetyan A.O. Modern tocolysis and adverse effects of tocolytics. Gynecology. 2018; 20 (2): 46–50. DOI: 10.26442/2079-5696_2018.2.46-50