Carboprost 250micrograms/1ml solution for injection ampoules

IntroductionExcessive 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.Methods and analysisCOPE 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.Ethics and disseminationThis 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.Trial registration numberISRCTN16416766.

Abstract licence: CC BY 4.0

BackgroundPostpartum 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.MethodsIn 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.FindingsThe 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%).InterpretationCarbetocin 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.FundingNone.

Abstract licence: CC BY

Abstract Background: No well-designed and systematic evaluation of the efficacy and safety of leonurus japonicus injection (LJI) in combination with carboprost tromethamine has been found. Therefore, we undertook a meta-analysis to assess the efficacy and safety of carboprost tromethamine combined with LJI for the prevention of postpartum hemorrhage in high-risk pregnant women to provide new evidence-based medical evidence for clinical treatment. Methods: This systematic review and meta-analysis would be performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The following databases including EMBASE, MEDICINE, Wanfang, China National Knowledge Infrastructure database, and Cochrane central controlled trial registries were searched by 2 reviewers from inception to July 2021. Mesh and keyword search terms were “motherwort,” “Yimucao,” “leonurus japonicas,” “carboprost tromethamine,” and “postpartum hemorrhage.” Any cohort studies that assessed the efficacy and safety of carboprost tromethamine combined with LJI for the prevention of postpartum hemorrhage would be included. P < .05 was set as the level of significance. Results: The review would add to the existing literature by showing compelling evidence and improved guidance in clinic settings. OSF registration number: 10.17605/OSF.IO/2WC53.

Abstract licence: CC BY 4.0

To investigate adverse reactions to carboprost reduced by intravenous esketamine administered after childbirth via cesarean delivery with the patient under combined spinal-epidural anesthesia. The study enrolled pregnant women aged 20–40 years, with American Society of Anesthesiologists (ASA) class II or III, and a gestational age of 37 weeks or more. These women had a scheduled cesarean section procedure with the administration of combined spinal-epidural anesthesia. Patients were randomized to receive esketamine 0.5 mg/kg (Group E) or volume-matched normal saline (Group C) immediately after fetal delivery, prior to carboprost administration (250 µg intramuscularly). The primary outcome was the incidence of vomiting during surgery. The secondary outcomes were the incidence of adverse reactions (nausea, chest rigidity, flushed face, tachycardia, cough, shivering), vital signs (HR, RR, MAP, SPO2) and postoperative pain assessed using a Visual Analogue Scale (VAS). Eighty-one pregnant women completed the study. The incidence of vomiting (22.5% vs. 56.1%, p < 0.001) and the incidence of nausea, chest rigidity, flushed face, and hypertension were significantly lower in group E than in group C (all p < 0.01), but the incidence of tachycardia was higher in group E (45% vs. 19.5%, p < 0.001). Furthermore, the patients’ arterial partial pressure of oxygen was significantly higher in group E than in group C (91.90 ± 5.14 vs. 79.76 ± 3.96, p < 0.001). Postoperative pain at the incision site, as assessed by Visual Analogue Scale (VAS) score, was significantly reduced at 6 h in the Esketamine group compared to the control group. However, there was no significant difference in uterine contraction pain between the two groups at any time point. For women undergoing cesarean delivery under combined spinal-epidural anesthesia, intravenous esketamine administered after delivery of the fetus and prior to carboprost administration during cesarean section under combined spinal - epidural anesthesia was associated with a reduction in the incidence of carboprost - induced adverse reactions and a decrease in postoperative incision pain at 6 h. However, it did not significantly affect postoperative uterine contraction pain. Chinese Clinical Trial Registry (Registration number# ChiCTR2100054985); Date of Registration: 30/12/2021.

Abstract licence: CC BY-NC-ND 4.0

Abstract Objectives To investigate reduce adverse reactions to carboprost of intravenous esketamine administered after childbirth via cesarean delivery with the patient under combined spinal-epidural anesthesia. Methods The study involved women within the age bracket of 20 and 40 years, with American Society of Anesthesiologists (ASA) class II or III, and a gestational age of 37 weeks or more. These women had a scheduled cesarean section procedure with the administration of combined spinal-epidural anesthesia. Patients were randomized to receive esketamine 0.5 mg/kg (Group E) or volume-matched normal saline (Group C) after delivery of the fetus, before carboprost administered. The primary outcome was the incidence of vomiting during surgery. The secondary outcomes were the incidence of adverse reactions (vomiting, nausea, chest rigidity, flushed face, tachycardia, cough, shivering), vital signs (HR, RR, MAP, SPO2) and blood gas analysis of intraoperative, as well as VAS score for postoperative pain. Results Eighty-one pregnancy women completed the study. The incidence of vomiting (22.5% versus 56.1%, p 

Abstract licence: CC BY 4.0