Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics.

1. OBJECTIVE: To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES: Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA: Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS: Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS: One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS: Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.

Surgical evacuation with intraoperative ultrasound (SEE U): A randomised controlled trial.

OBJECTIVES: To test whether intraoperative ultrasound can reduce the incidence of early and late complications following surgical removal of products of conception. DESIGN: This was a prospective, multicentre, randomised, open clinical trial to assess feasibility. It was performed in two University Teaching hospitals in the West Midlands, England. The population consisted of women aged 16 years or over who were referred for surgical management of miscarriage. Patients were randomised to surgical management of miscarriage with either continuous intraoperative ultrasound or without intraoperative ultrasound. Process outcomes included the proportion of eligible women screened and proportion of eligible women randomised, attrition rates, evaluation of outcome measurement tools and acceptability. The primary clinical outcome was a composite outcome of unsuccessful procedure or a complication. RESULTS: Fifty-nine women requiring surgical management of miscarriage were randomised. The conversion rate for entry into the trial was 59/79(75 %; 95 %CI = 64-84 %). The composite clinical outcome was attained in 5/27(19 %) patients who had surgery without ultrasound and 7/28(25 %) patients who had surgery with ultrasound (RR = 0.74;95 %CI = 0.26, 2.10). When we excluded the patients that could not attend their hysteroscopy appointment, due to COVID-19 pandemic, 5/27(19 %) of patients who had surgery without ultrasound and 5/25(20 %) of patients who had surgery with ultrasound attained the composite clinical outcome (RR = 0.93;95 %CI = 0.30, 2.90). CONCLUSIONS: This multicentre pilot study showed that a large RCT comparing surgical management of miscarriage with and without intraoperative ultrasound is feasible.

A cost-effectiveness analysis of early detection and bundled treatment of postpartum hemorrhage alongside the E-MOTIVE trial.

Timely detection and treatment of postpartum hemorrhage (PPH) are crucial to prevent complications or death. A calibrated blood-collection drape can help provide objective, accurate and early diagnosis of PPH, and a treatment bundle can address delays or inconsistencies in the use of effective interventions. Here we conducted an economic evaluation alongside the E-MOTIVE trial, an international, parallel cluster-randomized trial with a baseline control phase involving 210,132 women undergoing vaginal delivery across 78 secondary-level hospitals in Kenya, Nigeria, South Africa and Tanzania. We aimed to assess the cost-effectiveness of the E-MOTIVE intervention, which included a calibrated blood-collection drape for early detection of PPH and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination and escalation), compared with usual care. We used multilevel modeling to estimate incremental cost-effectiveness ratios from the perspective of the public healthcare system for outcomes of cost per severe PPH (blood loss ≥1,000 ml) avoided and cost per disability-adjusted life-year averted. Our findings suggest that the use of a calibrated blood-collection drape for early detection of PPH and bundled first-response treatment is cost-effective and should be perceived by decision-makers as a worthwhile use of healthcare budgets. ClinicalTrials.gov identifier: NCT04341662 .