Published: 2021-01-28

Adjunctive misoprostol for prevention of post-partum haemorrhage: a pragmatic strategy of selective sequential administration

Nalini Mishra, Lalitha Priya Nekkanti, Poulami Barma, Ishan Mishra, Ishan Mishra


Background: To evaluate the effect of adjunctive misoprostol in preventing postpartum haemorrhage (PPH) by selective administration above threshold bleeding in order to reduce its side effects in comparison with primary prevention with oxytocin alone.

Methods: It was a prospective observational cohort study conducted at Government medical College of central India. Population included 500 low risk women delivering vaginally. After having received oxytocin as primary prevention, women were monitored for bleeding by quantitative assessment of blood loss (QBL) using an innovative drape (kept prepared at the point of care) and once bleeding crossed 350 ml mark, alternate women were given 800 µg misoprostol sublingually as an adjuvant (study group) and compared with those who did not receive adjuvant misoprostol (control group). Main outcome measure: Comparing the incidence of PPH and side effects between study and control group.

Results: 150 women had blood loss >350 ml which constituted 76 women in study and control group each. Incidence of PPH was significantly less in the study group (10.52 versus 22.36%, p<0.05, RR 0.470 95% CI= 0.216-1.024). Though side effects were more (38.15%) in study group but these were mild in nature and when the number was extrapolated to all recruited women, the incidence came down to 11.6%.

Conclusions: Sequential adjuvant misoprostol at 350 ml blood loss after primary prevention with oxytocin is an effective and pragmatic strategy for preventing PPH when compared to oxytocin alone but with reduced overall side effects owing to less number of women receiving misoprostol.


Misoprostol, Oxytocin, PPH, C. G. Drape

Full Text:



UN. Sustainable Development Goals: 17 Goals to Transform our World. United Nations. 2015. Available from: page/sdgs-17-goals-transform-world. Accessed on 14 October 2020.

Global, regional, and national age-sex specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736-88.

Torloni MR, Gomes Freitas C, Kartoglu UH, Metin G€ulmezoglu A, Widmer M. Quality of oxytocin available in low- and middleincome, countries: a systematic review of the literature. BJOG. 2016;123:2076-86.

Oliver VL, Lambert PA, Than KK, Mohamed Y, Luchters S, Verma S, et al. Knowledge, perception and practice towards oxytocin stability and quality: A qualitative study of stakeholders in three resource-limited countries. PLoS One. 2018;13(9): e0203810.

Indrayani I, Harianis S, Astuti H, Maria R. How is oxytocin cold chain in peripheral areas? And is it still effective uterotonic? Pak J Med Health Sci. 2018;12(4):1744-9.

Gallos ID, Papadopoulou A, Man R, Athanasopoulos N, Tobias A, Price MJ, Williams MJ, Diaz V, Pasquale J, Chamillard M, Widmer M. Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis. Cochrane Database Syst Rev. 2018(12).

WHO recommendations: uterotonics for the prevention of postpartum haemorrhage. Geneva: World Health Organization; 2018. Available from: Accessed on 14 October 2020.

Mishra N, Baghel M, Gupta A, Shrivastava S, Chandrawanshi H. Use of Innovative low cost drape for assessment of blood loss during delivery: A report. J South Asian Fed Obstet Gynaecol 2019;11(1):30-4.

Sitaula S, Uprety DK, Thakur A, Pradhan T. Impact of preoperative rectal misoprostol on blood loss during, and after elective cesarean delivery: a randomized controlled trial. Nepal J Obstet Gynecol. 2016;22(2):37-41.

Hernandez-Castro F, Lopez-Serna N, Trevino-Salinas EM, Soria-Lopez JA, Sordia-Hernandez LH, Cardenas-Estrada E. Randomized double-blind placebo-controlled trial of buccal misoprostol to reduce the need for additional uterotonic drugs during cesarean delivery. Int J Gynaecol Obstet. 2016;132(2):184-7.

Perez-Rumbos A, Reyna-Villasmil E Rondon-Tapia M, Reyna Villasmil N. Rectal misoprostol or intramuscular oxytocin in the management of the third phase of labour. Perinatología y Reproducción Humana 2017;31(2):78-84.

Sallam HF, Shady NW. Adjunctive sublingual misoprostol for secondary prevention of post-partum hemorrhage during cesarean delivery: double blind placebo randomized controlled trial. Int J Reprod Contracept Obstet Gynecol. 2018;7(2):495-502.

Asmat R, Ashraf T, Asmat F, Asmat S, Asmat N. Effectiveness of per rectal misoprostol versus intramuscular oxytocin for prevention of primary postpartum haemorrhage. J Coll Phys Surg Pak. 2017;27(1):13-7.

Diallo M, Sylla T, Diouf AA, Moreira PM, Gassama O, Gueye MD, et al. Active management of third stage of labour with low doses of oral misoprostol and oxytocin on low: risk parturient in a Sub-Saharan hospital, Dakar, Sénégal. Int J Reprod Contracept Obstet Gynecol. 2017;6(2):516-22.

Shady NW, Sallam HF, Elsayed AH, Abdelkader AM, Ali SS, Alanwar A, et al. The effect of prophylactic oral tranexamic acid plus buccal misoprostol on blood loss after vaginal delivery: a randomized controlled trial. J Matern Fet Neonat Med. 2017;27:1-7.

Gavilanes P, Morales MF, Velasco S, Teran E. Sublingual misoprostol is as effective as intravenous oxytocin to reduce intra-operative blood loss during cesarean delivery in women living at high altitude. J Matern Fet Neonat Med. 2016;29(4):559-61.

Othman ER, Fayez MF, El Aal DEMA, El-Dine Mohamed HS, Abbas AM, Ali MK. Sublingual misoprostol versus intravenous oxytocin in reducing bleeding during and after caesarean delivery: a randomized clinical trial. Taiwanese J Obstet Gynecol. 2016;55(6):791-5.

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 Gynecol Obstet. 2016;132:191-5.

Morfaw F, Fundoh M, Pisoh C, Ayaba B, Mbuagbaw L, AndersonL N, Thabane L. misoprostol as an adjunct to oxytocin can reduce postpartum-haemorrhage: a propensity score-matched retrospective chart review in Bamenda-Cameroon, 2015-2016. BMC Pregnanc Childbirth. 2019;19:257.

Chaudhuri P, Majumdar A. Sublingual misoprostol as an adjunct to oxytocin during cesarean delivery in women at risk of postpartum hemorrhage. Int J Gynecol Obstet. 2015;128:48-52.

Quibel T, Ghout I, Goffinet F, Salomon LJ, Fort J, Javoise S, et al. Active management of the third stage of labor with a combination of oxytocin and misoprostol to prevent postpartum hemorrhage: a randomized controlled trial. Obstet Gynecol. 2016;128 (4):805-11.

Raghavan S, Geller S, Miller S, Goudar SS, Anger H. Misoprostol for primary versus secondary prevention of postpartum haemorrhage: a cluster-randomised non-inferiority community trial BJOG. 2016;123:120-7.

Pakniat H, Khezri MB. The effect of combined oxytocin–misoprostol versus oxytocin and misoprostol alone in reducing blood loss at cesarean delivery: a prospective randomized double-blind study. J Obstet Gynecol India. 2015;65(6):376-81.

Uncu Y, Karahasan M, Uyaniklar Ö, Uncu G. Prophylactic misoprostol for the prevention of postpartum hemorrhage: a randomized controlled trial. Eur Revi Med Pharm Sci. 2015;19:15-22.

Morris JL, Winikoff B, Dabash R, Weeks A, Faundes A, Gemzell‐Danielsson K, et al. FIGO’s updated recommendations for misoprostol used alone in gynecology and obstetrics. Int J Gynecol Obstet. 2017;138:363-6.