Tocoliticos en la amenaza de parto prematuro
DOI:
https://doi.org/10.18004/anales/2020.053.03.115Palabras clave:
parto prematuro, ocolíticos, tratamiento, ParaguayResumen
La amenaza de parto prematuro se considera hoy en día como una urgencia obstétrica en la que, si no se realiza alguna intervención desemboca en un parto prematuro. Por tanto, una vez confirmado el diagnóstico, el tratamiento consiste en la administración de tocolíticos, cuyo objetivo principal es el retraso del nacimiento ganando tiempo para administrar maduración pulmonar y neuroprotección con el fin de disminuir el síndrome de dificultad respiratoria y parálisis cerebral, así como lograr el traslado de la madre a un centro de referencia, si fuere el caso.
La elección de un fármaco u otro debe basarse en una adecuada valoración riesgo-beneficio, una vez tenida en cuenta la situación clínica de cada gestante. El empleo de tocolíticos al inicio de este proceso es esencial y en esta revisión se analiza la información disponible sobre su uso en la amenaza de parto prematuro.
Referencias
1. Salazar L, de Guirior C, Díaz D, Alcalde P, Bermejo R, et al. Alternativas terapéuticas para la tocólisis en el manejo de la amenaza de parto pretérmino. Prog Obstet Ginecol. 2016;59(2):112-8.
2. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA. 2015;314(10):1039-51.
3. Wu F, Liu G, Feng Z, Tan X, Yang C, Ye X, et al. Short-term outcomes of extremely preterm infants at discharge: a multicenter study from Guangdong province during 2008-2017. BMC Pediatr. 2019;19(1):405.
4. Practice Bulletin No. 171: Management of preterm labor. Obstet Gynecol. 2016;128(4):e155-64.
5. Patel SS, Ludmir J. Drugs for the treatment and prevention of preterm labor. Clin Perinatol. 2019;46(2):159-172.
6. Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol. 1999; 94(5 Pt 2):869-77.
7. Lam F, Gill P. Beta-Agonist tocolytic therapy. Obstet Gynecol Clin North Am. 2005;32(3):457-84.
8. Haram K, Mortensen JH, Morrison JC. Tocolysis for acute preterm labor: does anything work. J Matern Fetal Neonatal Med. 2015;28(4):371-8.
9. Smith P, Anthony J, Johanson R. Nifedipine in pregnancy. BJOG. 2000; 107(3):299-307.
10. Tsatsaris V, Cabrol D, Carbonne B. Pharmacokinetics of tocolytic agents. Clin Pharmacokinet. 2004;43(13):833-44.
11. Ruoti Cosp, M. Nifedipina. En: Ruoti Cosp M, Calabrese E, Editores. Fármacos y embarazo, que medicamentos prescribir. AMOLCA. Caracas, Venezuela. 2015.p.203-9.
12. Sweetman SC, Blake PS, McGlashan JM, et al editors. Martindale: Guía completa de Consulta Farmacoterapeutica. 2da ed. Barcelona: Pharma Editores, SL; 2006:1233.
13. Ortiz Ruiz ME, Labrador AM, Ayala Yáñez R. Uteroinhibidores actuales para el manejo de parto pretérmino. An Med (Mex) 2010; 55 (2): 85-91.
14. Manual de recomendaciones en el embarazo y parto prematuro. Ministerio de Salud Pública Dirección General de la Salud Uruguay 2018.
15. Palacio M, Cobo T, Baños N, Migliorelli F. Amenaza de parto pretérmino En: Figueras F, Gratacós E, Puerto B. Actualización en Medicina Maternofetal. Barcelona. 2015.p.247-60.
16. Flenady V, Wojcieszek AM, Papatsonis DN, Stock OM, Murray L, et al. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database Syst Rev. 2014 Jun 5;(6):CD002255.
17. Di Renzo GC, Roura LC, European Association of Perinatal Medicine-Study Group on Preterm Birth. Guidelines for the management of spontaneous preterm labor. J Perinat Med. 2006;34(5):359-66.
18. Cornette J, Duvekot JJ, Roos-Hesselink JW, Hop WC, Steegers EA. Maternal and fetal haemodynamic effects of nifedipine in normotensive pregnant women. BJOG. 2011;118(4):510-40.
19. Di Renzo GC. Safety and efficacy of new drugs in preterm labor. Expert Rev Obstet Gynecol 2007; 2 (1): 19-24.
20. Caritis SN, Chiao JP, Kridgen P. Comparison of pulsatile and continuous ritodrine administration: Effects on uterine contractility and beta-adrenergic receptors cascade. Am J Obstet Gynecol 1991; 139 (4): 1005-1011.
21. Ruoti Cosp, M. Ritodrine. En: Ruoti Cosp M, Calabrese E, Editores. Fármacos y embarazo, que medicamentos prescribir. AMOLCA. Caracas, Venezuela. 2015.p.1055-9.
22. Sweetman SC, Pharm B, PharmS FR editors. Terbutaline Sulfate. Martindale: The Complete Drug Reference. 36ª ed. China: Pharmaceutical Press; 2009:1138-40.
23. US Food and Drug Administration. FDA drug safety communication: new warnings against use of terbutaline to treat preterm labor. Disponible en: http://www. fda.gov/Drugs/DrugSafety/ucm243539.htm#ds. Acceso Enero 17, 2019.
24. Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev. 2014;(2):CD004352.
25. Karaman S, Ozcan O, Akercan F, Terek MC, Yucebilgin MS, Firat V. Pulmonary edema after ritodrine therapy during pregnancy and subsequent cesarean section with epidural anesthesia. Clin Exp Obstet Gynecol. 2004;31(1):67-9.
26. Gezginç K, Gül M, Karatayli R, Cander B, Kanat F. Noncardiogenic pulmonary edema due to ritodrine usage in preterm labor. Taiwan J Obstet Gynecol. 2008;47(1):101-2.
27. Sweetman SC, Pharm B, PharmS FR editors. Ritodrine Hydrochloride. Martindale: The Complete Drug Reference. 36ª ed. China: Pharmaceutical Press; 2009:2017-8.
28. Pisani RJ, Rosenow EC 3rd. Pulmonary edema associated with tocolytic therapy. Ann Intern Med. 1989;110(9):714-8.
29. Shinohara S, Sunami R, Uchida Y, Hirata S, Suzuki K. Association between total dose of ritodrine hydrochloride and pulmonary oedema in twin pregnancy: a retrospective cohort study in Japan. BMJ Open. 2017;7(12):e018118.
30. Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol. 1999;94(5 Pt 2):869-77.
31. Shigemi D, Aso S, Yasunaga H. Inappropriate use of ritodrine hydrochloride for threatened preterm birth in Japan: a retrospective cohort study using a national inpatient database. BMC Pregnancy Childbirth. 2019;19(1):204.
32. Shiokawa S, Sakata A, Suga Y, Isoda K, Itai S, Nagase K, et al. Incidence and risk factors of neonatal hypoglycemia after ritodrine therapy in premature labor: a retrospective cohort study. J Pharm Health Care Sci. 2019 Apr 16;5:7.
33. Golichowski AM, Hathaway DR, Fineberg N, Peleg D. Tocolytic and hemodynamic effects of nifedipine in the ewe. Am J Obstet Gynecol. 1985;151(8):1134-40.
34. Sawdy RJ, Sullivan MH, Bennett PR. The effects of non-steroidal anti-inflammatory compounds on human myometrial contractility. Eur J Obstet Gynecol Reprod Biol. 2003;109(1):33-40.
35. Conde-Agudelo A, Romero R. Transdermal nitroglycerin for the treatment of preterm labor: a systematic review and metaanalysis. Am J Obstet Gynecol. 2013;209(6):551.e1-551.e18.
36. Ruoti Cosp, M. Indometacina. En: Ruoti Cosp M, Calabrese E, Editores. Fármacos y embarazo, que medicamentos prescribir. AMOLCA. Caracas, Venezuela. 2015.p.944-9.
37. Sweetman SC, Pharm B, PharmS FR editors. Indometacin. Martindale: The Complete Drug Reference. 36ª ed. China: Pharmaceutical Press; 2009:66-9.
38. Hearne A, Nagey D. Therapeutic agents in preterm labor: Tocolytic agents. Clin Obstet Gynecol 2000; 43(4):787-801.
39. Reinebrant HE, Pileggi-Castro C, Romero CL, Dos Santos RA, Kumar S, et al. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev. 2015;(6):CD001992.
40. Zuckerman H, Shalev E, Gilad G, Katzuni E. Further study of the inhibition of premature labor by indomethacin. Part II double-blind study. J Perinat Med. 1984;12(1):25-9.
41. Besinger RE, Niebyl JR, Keyes WG, Johnson TR. Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor. Am J Obstet Gynecol. 1991;164(4):981-6.
42. Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ. Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ. 2012;345:e6226.
43. Rundell K, Panchal B. Preterm Labor: Prevention and Management. Am Fam Physician. 2017;95(6):366-372.
44. Vermillion ST, Scardo JA, Lashus AG, Wiles HB. The effect of indomethacin tocolysis on fetal ductus arteriosus constriction with advancing gestational age. Am J Obstet Gynecol. 1997;177(2):256-9.
45. Dathe K, Hultzsch S, Pritchard LW, Schaefer C. Risk estimation of fetal adverse effects after short-term second trimester exposure to non-steroidal anti-inflammatory drugs: a literature review. Eur J Clin Pharmacol. 2019;75(10):1347-1353.
46. Beaute JI, Friedman KG. Indomethacin induced ductus arteriosus closure in midgestation fetus. Clin Case Rep. 2018 ;6(3):506-508.
47. Loe SM, Sanchez-Ramos L, Kaunitz AM. Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis. Obstet Gynecol. 2005;106(1):173-9.
48. Vermillion ST, Newman RB. Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants. Am J Obstet Gynecol. 1999;181(5 Pt 1):1083-6.
49. Kirshon B, Moise KJ Jr, Wasserstrum N, Ou CN, Huhta JC. Influence of short-term indomethacin therapy on fetal urine output. Obstet Gynecol. 1988;72(1):51-3.
50. Hammers AL, Sanchez-Ramos L, Kaunitz AM. Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis. Am J Obstet Gynecol. 2015;212(4):505.e1-13.
51. van der Heijden BJ, Carlus C, Narcy F, Bavoux F, Delezoide AL, Gubler MC. Persistent anuria, neonatal death, and renal microcystic lesions after prenatal exposure to indomethacin. Am J Obstet Gynecol. 1994;171(3):617-23.
52. Eronen M, Pesonen E, Kurki T, Teramo K, Ylikorkala O, Hallman M Increased incidence of bronchopulmonary dysplasia after antenatal administration of indomethacin to prevent preterm labor. J Pediatr. 1994 May;124(5 Pt 1):782-8.
53. Jensen EA, Dysart KC, Gantz MG, Carper B, Higgins RD, Keszler M, et al. Association between use of prophylactic indomethacin and the risk for bronchopulmonary dysplasia in extremely preterm infants. J Pediatr. 2017;186:34-40.e2
54. López Gómez L, Marín Gabriel MA, Encinas B, de la Cruz Troca JJ, Rodríguez Marrodán B. Oxytocin receptor antagonist (Atosiban) in the threat of preterm birth: Does it have any effect on breastfeeding in the term newborn? Breastfeed Med. 2018;13(2):123-128.
55. Phaneuf S, Asbóth G, MacKenzie IZ, Melin P, López Bernal A. Effect of oxytocin antagonists on the activation of human myometrium in vitro: atosiban prevents oxytocin-induced desensitization. Am J Obstet Gynecol. 1994;171(6):1627-34.
56. Aguarón G, Aguarón A, Melchor JC. Manejo de la Amenaza de Parto Pretérmino: ¿Atosiban o Nifedipino? En: Gallo Vallejo Editores. Embarazo y Parto Pretérmino. Editorial AMOLCA.
57. Arrowsmith S1, Wray S. Oxytocin: its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol. 2014;26(6):356-69.
58. Sweetman SC, Pharm B, PharmS FR editors. Atosiban. Martindale: The Complete Drug Reference. 36ª ed. China: Pharmaceutical Press; 2009:2005-6.
59. Flenady V, Reinebrant HE, Liley HG, Tambimuttu EG, Papatsonis DN. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev. 2014;(6):CD004452.
60. van Vliet EOG, Nijman TAJ, Schuit E, Heida KY, Opmeer BC, Kok M, et al Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. Lancet. 2016;387(10033):2117-24.
61. Miyazaki C, Garcia RM, Ota E, Swa T, Oladapo OT, Mori R. Tocolysis for inhibiting preterm birth in extremely preterm birth, multiple gestations and in growth-restricted fetuses: a systematic review and meta-analysis. Reprod Health. 2016;13:4.
62. Klumper J, Breebaart W, Roos C, Naaktgeboren CA, van der Post J, Bosmans J, et al. Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study. BMJ Open. 2019;9(11):e029101.
63. de Heus R, Mol BW, Erwich JJ, van Geijn HP, Gyselaers WJ, Hanssens M, et al. Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study. BMJ. 2009;338:b744.
64.Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, et al. An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol. 2000;182(5):1173-83.
65. Nijman TAJ, Goedhart MM, Naaktgeboren CN, de Haan TR, Vijlbrief DC, Mol BW, et al. Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial. Ultrasound Obstet Gynecol. 2018 Jun;51(6):806-812.
66. Shaikh S, Shaikh AH, Akhter S, Isran B. Efficacy of transdermal nitroglycerine in idiopathic pre-term labour. J Pak Med Assoc. 2012;62(1):47-50.
67. Yallampalli C, Dong YL, Gangula PR, Fang L. Role and regulation of nitric oxide in the uterus during pregnancy and parturition. J Soc Gynecol Investig. 1998;5(2):58-67.
68. Sweetman SC, Pharm B, PharmS FR editors. Glyceryl Trinitrate. Martindale: The Complete Drug Reference. 36ª ed. China: Pharmaceutical Press; 2009:1298-9.
69. Duckitt K, Thornton S, O’Donovan OP, Dowswell T. Nitric oxide donors for treating preterm labour. Cochrane Database Syst Rev. 2014 May 8;(5):CD002860.
70. Lemncewicz A, Laudańska H, Laudański T, Karpiuk A, Batra S. Permeability of fetal membranes to calcium and magnesium: possible role in preterm labour. Hum Reprod. 2000;15(9):2018-22.
71. Ruoti Cosp M. Magnesio, Sulfato de En: Ruoti Cosp M, Calabrese E, Editores. Fármacos y embarazo, que medicamentos prescribir. AMOLCA. Caracas, Venezuela. 2015.p.1038-40.
72. Elliott JP, Lewis DF, Morrison JC, Garite TJ. In defense of magnesium sulfate. Obstet Gynecol. 2009 Jun;113(6):1341-8.
73. McNamara HC, Crowther CA, Brown J. Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour. Cochrane Database Syst Rev. 2015;(12):CD011200.
74. 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.
75. Kim MK, Lee SM, Oh JW, Kim SY, Jeong HG, Kim SM, et al. Efficacy and side effect of ritodrine and magnesium sulfate in threatened preterm labor. Obstet Gynecol Sci. 2018;61(1):63-70.
76. Shepherd E, Salam RA, Manhas D, Synnes A, Middleton P, et al. Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002988.
77. Holcomb WL Jr, Shackelford GD, Petrie RH. Magnesium tocolysis and neonatal bone abnormalities: a controlled study. Obstet Gynecol. 1991;78(4):611-4.
78. Schanler RJ, Smith LG Jr, Burns PA. Effects of long-term maternal intravenous magnesium sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
79. American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine. Committee Opinion No. 573: Magnesium sulfate use in obstetrics. Obstet Gynecol. 2013;122(3):727-8.
80. Elliott JP, Morrison JC, Bofill JA. Risks and Benefits of Magnesium Sulfate Tocolysis in Preterm Labor (PTL). AIMS Public Health. 2016;3(2):348-356.
81. Vogel JP, Nardin JM, Dowswell T, West HM, Oladapo OT. Combination of tocolytic agents for inhibiting preterm labour. Cochrane Database Syst Rev. 2014;(7):CD006169.
82. van Vliet E, Dijkema GH, Schuit E, Heida KY, et al. Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis. BJOG. 2016;123(11):1753-60.
83. Parry E, Roos C, Stone P, Hayward L, Mol BW, McCowan L. The NIFTY study: a multicentre randomised double-blind placebo-controlled trial of nifedipine maintenance tocolysis in fetal fibronectin-positive women in threatened preterm labour. Aust N Z J Obstet Gynaecol. 2014;54(3):231-6.
84. Younger JD, Reitman E, Gallos G. Tocolysis: Present and future treatment options. Semin Perinatol. 2017 Dec;41(8):493-504.
85. Sanchez-Ramos L, Huddleston JF. The therapeutic value of maintenance tocolysis: an overview of the evidence. Clin Perinatol. 2003;30(4):841-54.

