Jennifer Blum

Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial.

Objective  To assess the effectiveness of 600 μg oral misoprostol on postpartum haemorrhage (PPH) and postpartum anaemia in a low income country home birth situation.

Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo‐controlled trial

Please cite this paper as: Mobeen N, Durocher J, Zuberi N, Jahan N, Blum J, Wasim S, Walraven G, Hatcher J. Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo‐controlled trial. BJOG 2011;118:353–361.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial.

BACKGROUND Oxytocin, the standard of care for treatment of post-partum haemorrhage, is not available in all settings because of refrigeration requirements and the need for intravenous administration. Misoprostol, an effective uterotonic agent with several advantages for resource-poor settings, has been investigated as an alternative. This trial established whether sublingual misoprostol was similarly efficacious to intravenous oxytocin for treatment of post-partum haemorrhage in women not exposed to oxytocin during labour. METHODS In this double-blind, non-inferiority trial, 9348 women not exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three tertiary-level facilities). 978 (10%) women were diagnosed with primary post-partum haemorrhage and were randomly assigned to receive 800 microg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350. FINDINGS All randomly assigned participants were analysed. Active bleeding was controlled within 20 min with study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0.94, 95% CI 0.91-0.98; crude difference 5.3%, 95% CI 2.6-8.6). Additional blood loss of 300 mL or greater after treatment occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1.78, 95% CI 1.40-2.26). Shivering (229 [47%] vs 82 [17%]; RR 2.80, 95% CI 2.25-3.49) and fever (217 [44%] vs 27 [6%]; 8.07, 5.52-11.8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died. INTERPRETATION In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative for post-partum haemorrhage.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial

BACKGROUND Oxytocin, the gold-standard treatment for post-partum haemorrhage, needs refrigeration, intravenous infusion, and skilled providers for optimum use. Misoprostol, a potential alternative, is increasingly used ad hoc for treatment of post-partum haemorrhage; however, evidence is insufficient to lend support to recommendations for its use. This trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women receiving prophylactic oxytocin. METHODS In this double-blind, non-inferiority trial, 31 055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were randomly assigned to receive 800 mug misoprostol (n=407) or 40 IU intravenous oxytocin (n=402). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350. FINDINGS All randomly assigned participants were analysed. Active bleeding was controlled within 20 min after initial treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95-1.04; crude difference 0.4%, 95% CI -3.9 to 4.6). Additional blood loss of 300 mL or greater after treatment occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92-1.37). Shivering (152 [37%] vs 59 [15%]; RR 2.54, 95% CI 1.95-3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09-1.99) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died. INTERPRETATION Misoprostol is clinically equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour.

A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion.

Objective: To compare the safety, efficacy, and acceptability of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion in a hospital setting in Kampala, Uganda. Methods: Three hundred seventeen women with clinically diagnosed incomplete first-trimester abortions were randomized to treatment with either manual vacuum aspiration or 600 &mgr;g misoprostol orally to complete their abortions. All women received antibiotics posttreatment and were followed up 1–2 weeks later. Results: Regardless of treatment allocation, nearly all women in this study successfully completed their abortions with either oral misoprostol or manual vacuum aspiration (96.3% versus 91.5%, relative risk 1.05, 95% confidence interval 0.98–1.14). Complications were less frequent in those receiving misoprostol than those having manual vacuum aspiration (0.9% versus 9.8%, relative risk 0.1, 95% confidence interval 0.01–0.78). In the 6 hours after treatment, women using misoprostol reported heavier bleeding but lower levels of pain than those treated with manual vacuum aspiration. Rates of acceptability were similarly high among women in the 2 treatment groups, with 94.2% and 94.7% of women reporting that their treatment was satisfactory or very satisfactory in the misoprostol and manual vacuum aspiration groups, respectively. Conclusion: For treatment of first-trimester uncomplicated incomplete abortion, both manual vacuum aspiration and 600 &mgr;g oral misoprostol are safe, effective, and acceptable treatments. Based on availability of each method and the wishes of individual women, either option may be presented to women for the treatment of incomplete abortion. Level of Evidence: I

A Systematic Review of the Relationship between Blood Loss and Clinical Signs

Introduction This systematic review examines the relationship between blood loss and clinical signs and explores its use to trigger clinical interventions in the management of obstetric haemorrhage. Methods A systematic review of the literature was carried out using a comprehensive search strategy to identify studies presenting data on the relationship of clinical signs & symptoms and blood loss. Methodological quality was assessed using the STROBE checklist and the general guidelines of MOOSE. Results 30 studies were included and five were performed in women with pregnancy-related haemorrhage (other studies were carried in non-obstetric populations). Heart rate (HR), systolic blood pressure (SBP) and shock index were the parameters most frequently studied. An association between blood loss and HR changes was observed in 22 out of 24 studies, and between blood loss and SBP was observed in 17 out of 23 studies. An association was found in all papers reporting on the relationship of shock index and blood loss. Seven studies have used Receiver Operating Characteristic Curves to determine the accuracy of clinical signs in predicting blood loss. In those studies the AUC ranged from 0.56 to 0.74 for HR, from 0.56 to 0.79 for SBP and from 0.77 to 0.84 for shock index. In some studies, HR, SBP and shock index were associated with increased mortality. Conclusion We found a substantial variability in the relationship between blood loss and clinical signs, making it difficult to establish specific cut-off points for clinical signs that could be used as triggers for clinical interventions. However, the shock index can be an accurate indicator of compensatory changes in the cardiovascular system due to blood loss. Considering that most of the evidence included in this systematic review is derived from studies in non-obstetric populations, further research on the use of the shock index in obstetric populations is needed.

Prevention of postpartum hemorrhage with misoprostol

As a stable, orally active and cheap uterotonic, misoprostol would appear ideally suited to the prevention of postpartum hemorrhage (PPH) in the developing world. Following numerous clinical trials, it appears that misoprostol prophylaxis using an oral or sublingual dose of 600 μg is more effective than placebo at preventing PPH in community births (relative risk 0.59, 95% confidence intervals 0.41–0.84), but not in hospital settings (RR 1.23, 95% CI 0.86–1.74). It is, however, not as effective as injectible oxytocin (RR 1.34, 95% CI 1.16 to 1.55). Misoprostol is therefore indicated for prevention of PPH in settings where injectible conventional uterotonics are not available. In the event of continued hemorrhage, a minimum of 2 h should lapse after the original dose before a second dose is given. If the initial dose was associated with pyrexia or marked shivering, at least 6 h should lapse before the second dose is given.

Is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care? Results from a randomised trial in Burkina Faso, West Africa.

Objectives  Previous research has demonstrated the effectiveness of misoprostol for treatment of incomplete abortion; however, few studies have systematically compared misoprostol’s effectiveness with that of standard surgical care. This study documents the effectiveness of a single 600 micrograms dose of oral misoprostol versus manual vacuum aspiration (MVA) for treatment of incomplete abortion in a developing country setting.

Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: a multicentre, double-blind randomised trial

BACKGROUND Post-partum haemorrhage is a leading cause of global maternal morbidity and mortality. Misoprostol, a prostaglandin analogue with uterotonic activity, is an attractive option for treatment because it is stable, active orally, and inexpensive. We aimed to assess the effectiveness of misoprostol as an adjunct to standard uterotonics compared with standard uterotonics alone for treatment of post-partum haemorrhage. METHODS Women delivering vaginally who had clinically diagnosed post-partum haemorrhage due to uterine atony were enrolled from participating hospitals in Argentina, Egypt, South Africa, Thailand, and Vietnam between July, 2005, and August, 2008. Computer-generated randomisation was used to assign women to receive 600 microg misoprostol or matching placebo sublingually; both groups were also given routine injectable uterotonics. Allocation was concealed by distribution of sealed and sequentially numbered treatment packs in the order that women were enrolled. Providers and women were masked to treatment assignment. The primary outcome was blood loss of 500 mL or more within 60 min after randomisation. Analysis was by intention to treat. This study is registered, number ISRCTN34455240. FINDINGS 1422 women were assigned to receive misoprostol (n=705) or placebo (n=717). The proportion of women with blood loss of 500 mL or more within 60 min was similar between the misoprostol group (100 [14%]) and the placebo group (100 [14%]; relative risk 1.02, 95% CI 0.79-1.32). In the first 60 min, an increased proportion of women on misoprostol versus placebo, had shivering (455/704 [65%] vs 230/717 [32%]; 2.01, 1.79-2.27) and body temperature of 38 degrees C or higher (303/704 [43%] vs 107/717 [15%]; 2.88, 2.37-2.50). INTERPRETATION Findings from this study do not support clinical use of 600 microg sublingual misoprostol in addition to standard injectable uterotonics for treatment of post-partum haemorrhage. FUNDING Bill & Melinda Gates Foundation, and UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Treatment of incomplete abortion and miscarriage with misoprostol

A literature review was conducted to determine whether misoprostol is an effective treatment for incomplete abortion and, if so, to recommend an appropriate regimen. All English language articles published before October 2007 using misoprostol in at least one of the study arms were reviewed to determine the efficacy of misoprostol when used to treat incomplete abortion in the first trimester. All available unpublished data previously presented at international scientific meetings were also reviewed. Sufficient evidence was found in support of misoprostol as a safe and effective means of non‐surgical uterine evacuation. A single dose of misoprostol 600 μg oral is recommended for treatment of incomplete abortion in women presenting with a uterine size equivalent to 12 weeks gestation.