EFFECTS OF SUBLINGUAL MISOPROSTOL AS ADJUNCT TO OXYTOCIN FOR ACTIVE MANAGEMENT OF THIRD STAGE OF LABOUR IN PATURIENTS AT RISK OF POST-PARTUM HAEMORRHAGE IN ABAKALIKI : A COMPARISON OF 200 VERSUS 400 MICROGRAMS
NWALI Silas Alegu1, ONOH Robinson C1, EGEDE John Okafor1, OBI Vitus OKWUCHUKWU1, JOMBO Sunday Emmanuel2, OGBUINYA Oliver Onukwube1
1DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, AE-FUTH, ABAKALIKI
2DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, FMC, ASABA
Background: Postpartum Haemorrhage (PPH) still remains a major cause of maternal mortality despite adequate knowledge of its causes and treatment. Oxytocin administration is one of the major components of active management of third stage of labour (AMTSL). Evidence suggest benefit of misoprostol as an adjunct however optimal dose is yet to be determine considering the dose depended side effect profile of misoprostol. .
Objective: This study evaluated the efficacy and side effect profile of 200µg versus 400µg of prophylactic sublingual misoprostol as adjunct to AMTSL among parturient at risk for PPH.
Methods: This was a double blinded, single centre, randomized controlled trial involving two hundred and forty parturient with 2.1% drop out rate , thus 235 of them were analyzed; 117 (48.8%) and 118(49.2%) for 200 and 400 microgram group respectively. Data was analyzed using Statistical Package for Social Science (IBM SPSS) software (version 24, Chicago II, USA). Continuous variables were presented as mean and standard deviation (Mean ± 2SD), while categorical variables were presented as numbers and percentages. Chi-square test (X2) was used for comparison between groups for qualitative variables while t-test was used for comparison between groups for quantitative variables. A difference with a P value <0.05 was considered statistically significant.
Results: The mean blood loss was similar between the 200µg and 400µg groups of the study with 280.68±179.40mls and 253.86±169.80mls for the 200µg and 400µg groups respectively and p=0.240. The occurrence of primary postpartum haemorrhage (PPH) was equally similar between the two groups with incidence of 9.4% and 7.6% for the 200µg and 400µg groups respectively, p=0.7997. The risk ratio (RR) for developing PPH was 0.888 (95% CI; 0.537-1.467). The need for additional oxytocics to control bleeding was equally the same between the study groups with p=0.132. However, more participants in the 400µg group had one or more of the side effects of sublingual misoprostol compared to the participants in the 200µg group with RR 1.5759 (95% CI; 1.239-2.004), p<0.001. Shivering and fever were the side effects with significant difference between the two groups with p-values of 0.015 and 0.023 for shivering and fever respectively.
Conclusion: Sublingual misoprostol as an adjuvant to AMTSL in the doses of 200µg and 400µg are equally effective in reducing blood loss and the incidence of primary PPH, among women at increased risk for PPH. However, misoprostol induced side effects were significantly higher with 400µg.
Keywords: Active Management of Third Stage of Labour, Maternal Mortality, Misoprostol, Postpartum Haemorrhage
How to cite this article:
NWALI Silas Alegu, ONOH Robinson C, EGEDE John Okafor, OBI Vitus OKWUCHUKWU, JOMBO Sunday Emmanuel, OGBUINYA Oliver Onukwube. EFFECTS OF SUBLINGUAL MISOPROSTOL AS ADJUNCT TO OXYTOCIN FOR ACTIVE MANAGEMENT OF THIRD STAGE OF LABOUR IN PATURIENTS AT RISK OF POST-PARTUM HAEMORRHAGE IN ABAKALIKI : A COMPARISON OF 200 VERSUS 400 MICROGRAMS.International Research Journal of Obstetrics and Gynecology, 2020, 3:28. DOI: 10.28933/irjog-2020-04-1506
1. Milton SH. Normal Labour and Delivery. emedicine.medscape.com/article/260036-overview. 2016 (accessed 6th November, 2017)
2. Smith JR. Postpartum Haemorrhage. Emedicine.medscape.com/article/275038-overview#showall. 2017 (accessed 6th November, 2017)
3. Mehrabadi A, Hutcheon JA, Lee L, Kramer MS, Liston RM, Joseph KS. Epidemiological investigation of a temporal increase in atonic postpartum haemorrhage: a population-based retrospective cohort study. BJOG. 2013;120:853–862.
4. Postpartum Hemorrhage. ACOG Practice Bulletin. Clinical Management for Obstetricians and gynecologist. ACOG 2006.
5. Bateman BT, Berman MF, Riley LE, Leffert LR. The Epidemiology of Postpartum Hemorrhage in a Large, Nationwide Sample of Deliveries. Anesth Analg. 2010;110:1368–1373.
6. 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): 1066–1074.
7. Brooks M, Legendre G, Brun S, Bouet PE, Mendes LP, Meslot B et al. Use of a Visual Aid in addition to a Collector Bag to Evaluate Postpartum Blood Loss. A prospective Simulation Study Sci Rep. 2017; 7,46333;doi 10.1038/srep6333.
8. Diallo M, Sylla T, Diouf AZ, Moreira PM, Gassama O, Gueye MDN et al. Active Management of third Stage of Labour with Low Dose Oral Misoprostol and Oxytocin on Low Risk Parturients in a Sub-saharan Hospital, Dakar, Senegal. Int. J Rep Cont Obstet Gynecol. 2017;6(2):516-522.
9. Ezegwui HU, Onoh RC, Ikeako LC, Onyebuchi AK, Umeora OUJ, Ezeonu P et al. Investigating Maternal Mortality in a Public Teaching Hospital, Abakaliki, Ebonyi State, Nigeria. Ann Med Health Sci Res. 2013; 3(1): 75–80.
10. Green KI, Ojule JD, Faith MC. Primary Postpartum Haemorrhage at the University of Port Harcourt Teaching Hospital: Prevalence and Risk Factors. Niger Health J. 2015;15(3):111-117.
11. Wang Y, Zhao S. Vascular Biology of the Placenta. San Rafael (CA): Morgan and Claypool Life Sciences; 2010. Chapter 2, Placental Blood Circulation. Available from: https://www.ncbi.nim.nih.gov/books/NBK53254/ (accessed on 7th November, 2017)
12. Hellgren M: Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003, 29(2):125-130.
13. Gülmezoglu AM, Lumbiganon P, Landoulsi S, Widmer M, Abdel-Aleem H, Festin M, et al. Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial. Lancet. 2012; 379:1721–1727.
14. Chaudhuri P, Majumdar A. A randomized trial of sublingual misoprostol to augment routine third-stage management among women at risk of postpartum hemorrhage. Int J Gynaecol Obstet. 2016;132(2):191-195.
15. Prata N, Bell S, Weidert K. Prevention of postpartum hemorrhage in low-resource settings: current perspectives. Int J Women’s Health. 2013;5:737–752.
16. 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):e100175
17. Saldanha CL, Ara S, Bashir U. Sublingual misoprostol as adjunct to oxytocin during cesarean delivery in women at risk of postpartum haemorrhage. Int J Med Res 2017; 3(2);317-320.
18. 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):975-982.
19. Amin N. Prophylactic use of misoprostol in management of third stage of labour and prevention of atonic uterus. J Postgrad Med Inst 2014; 28(2):196-200.
20. Lawani OL, Iyoke CA, Onyebuchi AK. Blood transfusion trends in obstetrics at the Federal Teaching Hospital in Abakaliki, South-East Nigeria. Int J Women’s Health. 2013:5 407–412.
21. Onyebuchi AK, Lawani LO, Nkwo PO, Iyoke CA, Onoh RC, Ajah LO. Determinants of decision-to-intervention time in the management and therapeutic outcome of emergency gynecological surgeries in south east Nigeria. Ther Clin Risk Manag. 2014; 10: 577–582.
22. Kumar SA, Sanjayi S. Sublingual misoprostol to reduce blood loss at caesarean delivery . J obstet Gynaecol. 2012; 62(2) : 162-167.
23. Asmat F, Ashraf T, Asmat S, Asmat N, Asmat R. Effectiveness of per-rectal misoprostol versus intramuscular oxytocin for prevention of PPH. J coll phy surg. 2017; 27(1): 13-17.
24. Tang OS, Gemzell-Danielsson K, Ho PC. Misoprostol: Pharmacokinetic Profiles, Effects on the Uterus and Side-effects. Int J Gynecol Obstet. 2007;99:S160-S167.
25. Morris JL Winikoff B, Dabash R, Weeks A, Faundes A, Gemzell-Danielsson K. FIGO’s updated recommendations for misoprostol used alone in gynecology and obstetrics. Int J Gynecol Obstet. 2017; 138: 363–366.
26. Elati A, Elmahaishi MS, Elmahaishi MO, Elsraiti OA, Weeks AD. The effect of misoprostol on postpartum contractions: a randomised comparison of three sublingual doses. BJOG. 2011;118(4):466-473.
27. Hofmeyr GJ, Gülmezoglu AM, Novikova N, Lawrie TA. Postpartum misoprostol for preventing maternal mortality and morbidity. Cochrane Database Syst Rev. 2013;15(7):CD008982.
28. World Health Organization. Recommendations for the prevention of postpartum haemorrhage. Geneva: WHO; 2007.
29. Guerriero C, Cairns J, Jayaraman S, Roberts I, Perel P, Shakur H. Giving tranexamic acid to reduce surgical bleeding in sub-Saharan Africa: an economic evaluation. Cost Eff Resour Alloc 2010; 8(1):1.
30. Sentilhes L, Daniel V, Darsonval A, Deruelle P, Vardon D, Perrotin F et al. Study protocol. TRAAP – TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery: a multicenter randomized, double-blind, placebo-controlled trial. BMC Pregnancy Childbirth 2015; (15)135 1-15
31. Vlassoff M, Diallo A, Philbin J, Kost K, Bankole A. Cost-effectiveness of two interventions for the prevention of postpartum hemorrhage in Senegal. Int J Gynecol Obstet. 2016;133:307-311.
32. Kodkany BS, Derman RJ, Sloan NL. Pitfalls in Assessing Blood Loss and Decision to Transfer. In B-Lynch C, Keith LG, Lalonde AB, Karoshi M (eds) Textbook of Postpartum Haemorrhage: A comprehensive guide to evaluation, management and surgical intervention. Sapiens Publishing. 2010; 81-88
33. Brant HA. Blood loss at caesarean section. J Obstet Gynaecol 1966; 73: 456-9.
34. Duthie SJ, Ghosh A, Ng A, Ho PC. Intra-operative blood loss during elective lower segment caesarean section. Br J Obstet Gynaecol 1992; 99:364–7
35. Bose P, Regan F, Paterson Brown S. Improving the accuracy of estimated blood loss at obstetric haemorrhage using clinical reconstruction. BJOG 2006; 113(8):919-924.
36. Jayaraman S, Chalabi Z, Perel P, Guerriero C, Roberts I. The risk of transfusion transmitted infections in sub-Saharan Africa. Transfusion 2010; 50(2):433–42.
37. Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B et al. A Systematic Review of the Relationship between Blood Loss and Clinical Signs. PLoS ONE. 2013;8(3): e57594.
38. Table. ACOG. Teaching module on postpartum hemorrhage. 2010. w w w . a c o g . o r g / A C O G _ D i s t r i c t s / d i s t 1 j f
39. Al Kadri HM, Anazi BK, Tamim HM. Visual estimation versus gravimetric measurement of postpartum blood loss: A prospective cohort study. Arch Gynecol Obstet 2011; 283(6), 1207–1213.
40. Stafford I, Dildy G, Clark S, Belfort M. Visually estimated and calculated blood loss in vaginal and cesarean delivery. Am J Obstet Gynecol 2008;199: 519.e1-e7
41. Gharoro EP, Enabudoso EJ. Relationship between visually estimated blood loss at delivery and postpartum change in haematocrit. J Obstet Gynaecol. 2009; 29:517–20.
42. Ali AH, Ramadani HM. Assessment of blood loss during cesarean section under general anesthesia and epidural analgesia using different methods. AJAIC 2006; 9: 25–34.
43. Atukunda EC, Mugyenyi GR, Obua C, Atuhumuza EB, Musinguzi N, Tornes YF, et al. Measuring Post-Partum Haemorrhage in Low Resource Settings: The Diagnostic Validity of Weighed Blood Loss versus Quantitative Changes in Hemoglobin. PLoS ONE. 2016;11(4): e0152408.
44. Ambardekar S, Shochet T, Bracken H, Coyaji K, Winikoff B. Calibrated delivery drape versus indirect gravimetric technique for the measurement of blood loss after delivery: a randomized trial. BMC Pregnancy and Childbirth. 2014;14:276
45. Chua S, Ho LM, Vanaja K, Nordstrom L, Roy AC, Arulkumaran S. Validation of a laboratory method of measuring postpartum blood loss. Gynecol Obstet Invest. 1998; 46(1):31–33.
46. Pravez T, Abbas Z. Misoprostol use in Obs and Gynae. J.K .practioner 2005; 12(2) : 94-97.
47. Rekha P, Latha K. Sublingual misoprostol to reduce blood loss at caesarean section. Int J Modn Res Revs. 2014; 2(10) : 444-446.
48. Hofmeyr GJ, Gülmezoglu AM, Novikova N, Linder V, Ferreira S, Piaggio G. Misoprostol to prevent and treat postpartum haemorrhage: a systematic review and meta-analysis of maternal deaths and dose-related effects. Bull World Health Organ. 2009;87:666–677.
49. Mavrides E, Allard S, Chandraharan E, Collins P, Green L, Hunt BJ, Riris S, Thomson AJ on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG 2016;124:e106–e149.
50. Olefile KM, Khondowe O, M’Rithaa D. Misoprostol for prevention and treatment of postpartum haemorrhage: A systematic review. Curationis. 2013;36(1):E1-10.
51. Ugwu IA, Oluwasola TA, Enabor OO, Anayochukwu-Ugwu NN, Adeyemi AB, Olayemi OO. Randomized controlled trial comparing 200 μg and 400 μg sublingual misoprostol for prevention of primary postpartum hemorrhage. Int J Gynae Obstet 2016;133(2)173–177.
52. 2006 Population and Housing Census; Population distribution by Sex, State, LGA, Senatorial District. National Population Commission Abuja Nigeria. April 2010.
53. Ibekwe PC, Dimejesi IB. Obstetric indices at the Ebonyi State University Teaching Hospital, Abakaliki, south east Nigeria. Nig J Med. 2008;17(4): 399-402
54. Ebonyi State Government Strategic Health Development Plan (2010-2015). Ebonyi State Ministry of Health. March, 2010
55. Zhong B. How to Calculate Sample Size in Randomized Controlled Trial? J Thorac Dis. 2009;1: 51-54.
56. Uthman SG, Garba MA, Danazumi AG, Mandara MU, Sylvester NH. How some demographic factors affects postpartum haemorrhage prevention in Maiduguri, Nigeria. Open J Obstet and Gynecol. 2013: 203-207.
57. Prick BW, von Schmidt auf Altenstadt JF, Hukkelhoven CWPM, Bonsel GJ, Steegers EAP, Mol BW. Regional differences in severe postpartum hemorrhage: a nationwide comparative study of 1.6 million deliveries.BMC Pregnancy and Childbirth. 2015; 15:43. DOI 10.1186/s12884-015-0473-8.
58. Bajwa SK, Bajwa KJS, Kaur H, Goraya SPS, Singh A, KaurIshar H. Management of third stage of labor with misoprostol: A comparison of three routes of administration. Perspect Clin Res. 2012;3(3):102–108.
This work and its PDF file(s) are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.