Carboprost Tromethamine

Postpartum haemorrhage is a leading cause of maternal mortality, particularly in low-income and middle-income countries. Several pharmacological agents, such as oxytocin, ergot alkaloids, prostaglandins, and tranexamic acid, have been used prophylactically to prevent postpartum haemorrhage. However, the optimal prophylactic regimen and the comparative efficacy of these agents and their combinations have not been fully elucidated for individuals undergoing caesarean delivery. We aimed to conduct a network meta-analysis to assess different agents for postpartum haemorrhage prophylaxis in caesarean deliveries.

In this systematic review and meta-analysis, we conducted a Bayesian network meta-analysis of randomised controlled trials (RCTs) evaluating the relative effectiveness of different prophylactic agents and their combinations for postpartum haemorrhage in caesarean deliveries. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Web of Science from database inception to Nov 7, 2023, for RCTs that enrolled adult pregnant women (ie, older than 18 years) undergoing a caesarean delivery; compared prophylactic strategies (monotherapy or combination drug therapy) with placebo or another active prophylactic regimen; administered prophylactic strategies of any parenteral dosage or regimen systemically before surgical incision or immediately after birth for preventing postpartum haemorrhage; and reported our prespecified endpoints of interest. Quasi-randomised trials, trials evaluating prophylactic strategies exclusively comparing different dosages, routes, or regimens of the same prophylactic agent, trials that included vaginal delivery, single-arm studies, conference abstracts, studies not published in English, and studies with overlapping populations were excluded. Ten authors reviewed study reports and supplementary materials and extracted the data. Two authors performed these tasks independently for each study. For data reported in graphical format, extraction was performed with graph digitising web software. The primary outcome was postpartum haemorrhage (ie, blood loss of ≥1000 mL following caesarean delivery). We fitted a Bayesian random-effects network meta-analysis model to compare multiple regimens simultaneously, with results presented as risk ratios (RRs) and their respective 95% credible intervals (CrIs). Only strategies reported by two or more studies were included in the network. If a prophylactic strategy was reported by only one study, it was included if at least 1000 patients were allocated in each study group. We also synthesised head-to-head RCTs separately to assess differences between regimens with league tables. To assess the hierarchy of treatments based on efficacy, we estimated surface under the cumulative ranking curve (SUCRA) probabilities. This review is registered at PROSPERO, CRD42023488236.

The search strategy yielded 3339 studies. After removing duplicates, 2241 studies remained, of which a total of 2022 were excluded on the basis of title or abstract screening. After full-text review, 167 RCTs (with 44 817 patients) evaluating monotherapy with or various combinations of oxytocin, carbetocin, carboprost, ergot alkaloids, misoprostol, and tranexamic acid were included in the final analysis. Across all 167 studies, 12 868 patients received oxytocin monotherapy, 5849 patients received tranexamic acid monotherapy, 2964 patients received carbetocin monotherapy, 1773 patients received misoprostol monotherapy, and 100 patients received carboprost monotherapy. The most common combination therapy was tranexamic acid plus oxytocin (n=5331) followed by misoprostol plus oxytocin (n=2983). Oxytocin plus tranexamic acid (RR 0·44 [95% CrI 0·33-0·58]) and carbetocin (0·54 [0·37-0·74]) were the only interventions that were more effective than oxytocin alone in reducing postpartum haemorrhage. Oxytocin plus tranexamic acid ranked as the most effective intervention for postpartum haemorrhage prophylaxis with a SUCRA probability value of 0·85. Most prophylactic combinations reduced intraoperative blood transfusions and the need for additional uterotonics. Two maternal deaths were reported among 29 412 patients. No significant heterogeneity was detected for postpartum haemorrhage (I²=6%), blood transfusion (I²=0%), and additional uterotonics (I²=7%).

Carbetocin alone and oxytocin plus tranexamic acid were superior to oxytocin monotherapy for preventing postpartum haemorrhage in caesarean deliveries. Oxytocin plus tranexamic acid ranked as the most effective intervention for postpartum haemorrhage prevention. These results are crucial in highlighting the comparative efficacy and hierarchy of prophylactic agents for postpartum haemorrhage prevention, especially given the widespread availability and low cost associated with oxytocin and tranexamic acid.

None.

Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study’s aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants’ views on the two treatments and the consent process.

COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services.

This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.

NCT16416766 .