Misoprostol sublingual is safer and more effective in the treatment of postpartum hemorrhage vaginal delivery? A systematic review and meta-analysis
DOI:
https://doi.org/10.11606/issn.1679-9836.v104i3e-230726Keywords:
Misoprostol, Puerperal hemorrhage, Postpartum hemorrhage, Oxytocin, Natural childbirthAbstract
OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness of sublingual misoprostol compared to oxytocin in the treatment of postpartum vaginal delivery bleeding. METHODS: Searches were conducted on PubMed, Cochrane, and Embase up to Jul 25, 2024. The search strategy utilized Medical Subject Headings terms and accessible text terms. No language limitations were applied. The inclusion criteria comprised randomized controlled trials (RCTs) involving women who underwent postpartum vaginal delivery and received sublingual misoprostol or oxytocin within the same timeframe. Exclusions included cesarean delivery, alternative routes of misoprostol administration, combination with other drugs, or labor induction. Outcomes analyzed included postpartum hemorrhage, hemoglobin reduction, and side effects between the two groups. Three independent reviewers decided on abstracts, full texts, and data extraction. Meta-analysis employed Review Manager software, calculating odds ratios for dichotomous data and weighted mean differences, with 95% confidence intervals for continuous data. Among 217 studies, 10 met the inclusion criteria, involving 5,041 pregnant women. RESULTS: Sublingual misoprostol-treated postpartum hemorrhage in 2,517 (49.9%) patients. Fever (OR 6.05; 95% CI 2.63-13.91; P<0.0001; I2=87%) and shivering (OR 5.04; 95% CI 2.76-9.20; P<0.00001; I2=91%) were significantly high with misoprostol. No significant differences were found between sublingual misoprostol and oxytocin for postpartum hemorrhage (OR 0.55; 95% CI 0.15-2.02; P=0.37; I2=95%) or hemoglobin decline (OR 0.44; 95% CI 0.15-1.31; P=0.14; I2=97%). CONCLUSION: Oxytocin appears to be a safer and more effective alternative than sublingual misoprostol for treating postpartum hemorrhage in vaginal deliveries, with an associated increase in side effects with the latter.
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References
Ministério da Saúde (BR). Protocolo de Misoprostol. Brasília: Editora MS; 2012.
Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367(9516):1066-74. Doi:10.1016/S0140-6736(06)68397-9.
International Federation of Gynecology and Obstetrics. FIGO treatment of postpartum hemorrhage with misoprostol: FIGO guidelines [Internet]. London: FIGO; 2012 https://www.figo.org/sites/default/files/uploads/project-publications/Miso/PPH%20treatment/Annotated%20versions/4172%20Brief%20Portuguese%20Treatment_0.pdf
Mousa HA, Blum J, Abou El Senoun G, Shakur H, Alfirevic Z. Treatment for primary postpartum hemorrhage. Cochrane Database Syst Rev. 2014;(2):CD003249. Doi:10.1002/14651858.CD003249.pub3.
Silva FRF, Ramos MS, Partata AK. Misoprostol: propriedades gerais e uso clínico. Rev Cient ITPAC. 2013;6(3):4.
Barros CSD, Moraes AD, Souza LN, Barros ID, Rodrigues NFD, Rodrigues ND, et al. Maternal mortality from postpartum hemorrhage: an integrative literature review. Res Soc Dev. 2022;11(3):1-7. Doi:10.33448/rsd-v11i3.25123.
World Health Organization. WHO recommendations for the prevention and treatment of postpartum hemorrhage [Internet]. Geneva: WHO; 2012 https://www.who.int/publications/i/item/9789241548502.
Escobar MF, Nassar AH, Theron G, Barnea ER, Nicholson W, Ramasauskaite D, et al. FIGO recommendations on the management of postpartum hemorrhage. Int J Gynaecol Obstet. 2022;157(S1):3-50. Doi:10.1002/ijgo.14116.
Lopes JC, Freitas CF, Fontinele LF, Novellino AM. Efficacy of the use of sublingual misoprostol versus oxytocin in the prevention of postpartum vaginal hemorrhage: a systematic review and meta-analysis [Internet]. PROSPERO; 2023.
Jonathan ACS, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing the risk of bias in randomized trials. BMJ. 2019;366:l4898. Doi: 10.1136/bmj.l4898
Atukunda EC, Siedner MJ, Obua C, Mugyenyi GR, Twagirumukiza M, Agaba AG. Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial. PLoS Med. 2014;11(11):e1001752. Doi: 10.1371/journal.pmed.1001752.
Bellad MB, Tara D, Ganachari MS, Mallapur MD, Goudar SS, Kodkany BS, et al. Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin: a double-blind randomised controlled trial. BJOG. 2012;119(8):975-82; discussion 982-6. Doi: 10.1111/j.1471-0528.2012.03341.x.
Bhatti K, Mahar T, Hafeez R, Shoaib-u-Nisa. A randomized controlled trial on prevention of postpartum hemorrhage with sublingual misoprostol or oxytocin. Med Forum. 2014;25(1):10-3.
Chaudhuri P, Biswas J, Mandal A. Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in low-risk women. Int J Gynaecol Obstet. 2012;116(2):138-42. Doi: 10.1016/j.ijgo.2011.09.016.
Dao B, Blum J, Barrera G, Ramadan C, Dabash E, Darwish E, et al. Side effect profiles for misoprostol and oxytocin in the treatment of postpartum hemorrhage. Int J Gynaecol Obstet. 2009;107:Suppl2:S93-S96. Doi: 10.1016/S0020-7292(09)60573-7
Mishra S, Tirkey S, Prasad A, Trivedi K. A comparative study of sublingual misoprostol versus intramuscular oxytocin in the active management of third stage of labor. Cureus. 2023;15(1):e33339. Doi:10.7759/cureus.33339.
Narrey N, Thakre S, Lemos CL, Tripathi S, Upadhyay R. Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage: a competitive study. Int J Toxicol Pharmacol Res. 2023;13(3):73-9.
Sandoval J, Fuentes V, Urrutia K. Sublingual misoprostol compared with intramuscular oxytocin in the prevention of postpartum hemorrhage. Rev Peru Ginecol Obstet. 2015;50(4):212-6.
Shaheen N, Khalil S. Safety and efficacy of 600 µg sublingual misoprostol versus 10 U intramuscular oxytocin for management of third-stage labor. Rawal Med J. 2019;44(1):137-40.
Tewatia R, Rani S, Srivastav U, Makhija B. Sublingual misoprostol versus intravenous oxytocin in prevention of postpartum hemorrhage. Arch Gynecol Obstet. 2014;289(4):73-42. Doi:10.1007/s00404-013-3026-2.
Winikoff B, Dabash R, Durocher J, et al. Treatment of postpartum hemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labor: a double-blind, randomized, non-inferiority trial. Lancet. 2010;375(9710):210-6. Doi:10.1016/S0140-6736(09)61924-3.
Elati A, Weeks A. Risk of fever after misoprostol for the prevention of postpartum hemorrhage: a meta-analysis. Obstet Gynecol. 2012;120(5):1140-8. Doi:10.1097/AOG.0b013e3182707341.
Ioannidis JP, Evans SJ, Gøtzsche PC, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141(10):781-8. Doi:10.7326/0003-4819-141-10-200411160-00009.
World Health Organization. The selection and use of essential medicines: report of the 20th WHO Expert Committee [Internet]. Geneva: WHO; 2015 [cited 2023 Jun 5]. http://apps.who.int/medicinedocs/documents/s22190en/s22190en.pdf.
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