Effectiveness of Remimazolam on Preventing Adverse Reactions Caused by Carboprost Tromethamine During Cesarean Section.

PURPOSE: To evaluate the effectiveness of remimazolam in preventing adverse reactions triggered by carboprost tromethamine during cesarean section procedures. METHODS: A total of 200 parturients scheduled for cesarean sections at risk of postpartum hemorrhage in our hospital from October 2022 to July 2023 were included. The participants were assigned via random number table method to either a study group or a control group, resulting in 100 cases in each. All parturients received combined spinal and epidural anesthesia (CSEA) during cesarean section, followed by administration of carboprost tromethamine (250 µg) for preventing postpartum hemorrhage after childbirth. CSEA was performed with 1.8 to 2 mL of 0.5% bupivacaine and 7 to 10 mL of 2% lidocaine. The study group was given remimazolam via intravenous infusion at a rate of 0.3 mg/kg/h commencing at 1 minute prior to CSEA and concluding with a final dosage adjustment 20 minutes preceding the end of surgery, while the control group was given the same volume of saline within this time frame. Primary outcome measures were adverse reactions and sedative effects of the parturients. FINDINGS: Nausea and vomiting were the only adverse reactions that exhibited significant differences between groups. The study group reported significantly fewer cases (32 cases) of nausea and vomiting when compared to the 48 cases observed in the control group. Moreover, the use of remimazolam appeared to alleviate the severity of nausea and vomiting, as evidenced by the significantly lower incidence of Grade III event and the higher risk of Grade I event in comparison with the control group (P < 0.05). The Apgar scores of newborns at birth and 5 minutes after birth were compared, and no statistically significant difference was found (P > 0.05). Parturients receiving remimazolam exhibited better effective sedation outcomes and were more satisfied with the treatment when compared with controls (P < 0.05). There were no significant differences in postpartum bleeding volume at 2 and 12 hours postpartum, as well as in the duration of postpartum bleeding between the two groups (P > 0.05). IMPLICATIONS: Intravenous administration of remimazolam effectively prevents adverse reactions induced by carboprost tromethamine during cesarean section performed under CSEA, thereby improving sedative effects.

Prostaglandin Injection for Myoma Expulsion (PRIME): Case Series of a Novel Approach to Hysteroscopic Resection of FIGO Type 2 Myomas.

STUDY OBJECTIVE: To evaluate the use of dilute carboprost tromethamine injection at the endometrium/myoma junction during hysteroscopy to facilitate myoma expulsion and removal in a single procedure. DESIGN: Case series. SETTING: Single high-volume academic medical center. PATIENTS: Seven patients aged 32 to 51 years old with FIGO type 2 uterine myomas and symptoms of abnormal uterine bleeding or infertility undergoing hysteroscopic resection with a morcellation device from November 2022 to July 2023. INTERVENTION: Dilute injection of carboprost tromethamine (10 µg/mL) at time of hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was ability to complete the hysteroscopic myomectomy in a single procedure using a hysteroscopic morcellator. Secondary outcomes included total operative time, fluid deficit, and postoperative pharmacologic side effects and/or surgical complications. Among our 7 patients, all had successful single procedure complete resections of myomas ranging from 0.9 to 4.6 cm in maximal diameter. Average operative time was 30 minutes, and average fluid deficit was approximately 839 mL. The carboprost dosages used ranged from 30 to 180 µg. One patient experienced prolonged postoperative nausea and vomiting that resolved with antiemetics. One patient experienced postoperative endometritis that improved with antibiotics. CONCLUSION: In this pilot study, injection of dilute carboprost intraoperatively facilitated one-step hysteroscopic myomectomy of FIGO 2 myomas, via enhanced extrusion of the intramural portion of the fibroid into the uterine cavity, with both short operative times and acceptable fluid deficits.

Desmopressin, Misoprostol, nor Carboprost Affect Platelet Aggregability Following Traumatic Brain Injury and Aspirin.

INTRODUCTION: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA. METHODS: Male C57BL/6 mice were randomized into seven groups (n = 5 each): untouched, ASA only, Saline/TBI, ASA/TBI, ASA/TBI/DDAVP 0.4 µg/kg, ASA/TBI/misoprostol 1 mg/kg, and ASA/TBI/carboprost 100 µg/kg. TBI was induced via a weight drop model 4-h after ASA (50 mg/kg) gavage. Mice were given an intraperitoneal injection of DDAVP, misoprostol, or carboprost 10 minutes after TBI. In vivo testing was completed utilizing tail vein bleed. Mice were sacrificed 30-min posttreatment and blood was collected via cardiac puncture. Whole blood was analyzed via Multiplate impedance aggregometry, rotational thromboelastometry, and TEG6s. RESULTS: Mice receiving misoprostol after ASA/TBI demonstrated decreased tail vein bleeding times compared to ASA only treated mice. However, mice treated with misoprostol following ASA and TBI demonstrated decreased platelet aggregability compared to untouched mice and TBI only mice within the arachidonic acid agonist pathway. By contrast, DDAVP and carboprost did not significantly change platelet aggregability via adenosine diphosphate or arachidonic acid following ASA and TBI. However, DDAVP did decrease the platelet contribution to clot via rotational thromboelastometry. CONCLUSIONS: Reversal of medication-induced platelet inhibition has become increasingly controversial after TBI. Based on these results, DDAVP, misoprostol, nor carboprost consistently improve platelet aggregability following TBI in those also treated with ASA.

Sufentanil for carboprost-induced adverse reactions during cesarean delivery under combined spinal-epidural anesthesia.

OBJECTIVES: Carboprost plays an important role in managing refractory uterine atony and severe postpartum hemorrhage. However, it is associated with challenging adverse reactions. We aimed to evaluate the clinical effects of low dose sufentanil on the prevention of adverse events associated with carboprost during cesarean delivery. MATERIAL AND METHODS: Patients were randomly divided into two groups: a placebo control group (group C, n = 15) that received an intravenous infusion of 1 mL of normal saline 2 min before carboprost and a sufentanil group (group S, n = 15) that received 5 µg of sufentanil. The primary outcome was the incidence of nausea and vomiting following carboprost administration. RESULTS: The incidence of nausea, vomiting, and gastrointestinal discomfort was significantly lower in group S than in group C (p < 0.05). CONCLUSIONS: The prophylactic use of low dose sufentanil reduces the incidence of gastrointestinal side effects caused by carboprost administration during cesarean section.

Effect of continuous infusion of a subhypnotic dose of propofol on nausea and vomiting after carboprost administration at cesarean delivery: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate whether continuous infusion of propofol at a subhypnotic dose prevents nausea and vomiting following carboprost administration at cesarean delivery. METHODS: A prospective, randomized, double-blind, placebo-controlled trial conducted at West China Second University Hospital, from June 28, 2017 to January 30, 2018. Pregnant women were randomly allocated to propofol or saline infusion immediately before receiving carboprost at cesarean delivery under combined spinal-epidural (CSE) anesthesia. Propofol was given at an infusion rate of 1.0 mg/kg/h following a loading dose of 0.3 mg/kg. Primary outcome was incidence of intraoperative nausea and vomiting (IONV). Potential sedative effect of propofol infusion was assessed using Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scoring and continuous Bispectral Index (BIS) monitoring. RESULTS: The incidence of IONV was lower in patients who received propofol compared with saline (46.7% vs 76.7%, OR 0.27; 95% CI, 0.092-0.78, P = 0.016 for nausea; 26.7% vs 53.3%, OR 0.50; 95% CI, 0.25-0.95, P = 0.032 for retching; 10.0% vs 50.0%, OR 0.11; 95% CI, 0.03-0.44, P < 0.001 for vomiting). There were no differences in MOAA/S scoring or BIS between the two groups. CONCLUSION: A subhypnotic dose of propofol reduces the incidence of nausea and vomiting following carboprost administration at cesarean delivery under CSE anesthesia, without measurable effect on patients' consciousness or alertness. ClincalTrials.gov: NCT03185156.

Preventing postpartum hemorrhage after cesarean delivery: a network meta-analysis of available pharmacologic agents.

BACKGROUND: Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior. OBJECTIVE: We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery. METHODS: We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy. RESULTS: A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the "estimated blood loss" network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48-143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the "additional uterotonic" network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130-218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus. CONCLUSION: Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus.

Refractory uterine atony: still a problem after all these years.

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality, and uterine atony is the leading cause of postpartum hemorrhage. Risk factors for uterine atony include induced or augmented labor, preeclampsia, chorio-amnionitis, obesity, multiple gestation, polyhydramnios, and prolonged second stage of labor. Although a risk assessment is recommended for all parturients, many women with uterine atony do not have risk factors, making uterine atony difficult to predict. Oxytocin is the first-line drug for prevention and treatment of uterine atony. It is a routine component of the active management of the third stage of labor. An oxytocin bolus dose as low as 1 IU is sufficient to produce satisfactory uterine tone in almost all women undergoing elective cesarean delivery. However, a higher bolus dose (3 IU) or infusion rate is recommended for women undergoing intrapartum cesarean delivery. Carbetocin, available in many countries, is a synthetic oxytocin analog with a longer duration than oxytocin that allows bolus administration without an infusion. Second line uterotonic agents include ergot alkaloids (ergometrine and methylergonovine) and the prostaglandins, carboprost and misoprostol. These drugs work by a different mechanism to oxytocin and should be administered early for uterine atony refractory to oxytocin. Rigorous studies are lacking, but methylergonovine and carboprost are likely superior to misoprostol. Currently, the choice of second-line agent should be based on their adverse effect profile and patient comorbidities. Surgical and radiologic management of uterine atony includes uterine tamponade using balloon catheters and compression sutures, and percutaneous transcatheter arterial embolization.

Effect of carboprost tromethamine injection combined with modified B-lynch suture and carboprost methylate suppositories in parturients with placenta previa.

OBJECTIVE: To investigate the clinical value of carboprost tromethamine injection combined with modified B-lynch suture and carboprost methylate suppositories in the treatment of placenta previa parturients with postpartum hemorrhage after cesarean section. METHODS: A total of 102 parturients with placenta previa and postpartum hemorrhage after cesarean section in our hospital were selected as the study subjects, and they were divided into Group A (carboprost tromethamine injection combined with modified B-lynch suture, n=35), Group B (carboprost methylate suppositories, n=34), and Group C (carboprost tromethamine injection, n=33) in accordance with a random number table. The amounts of hemorrhaging and clinical indices in the three groups were recorded, and the rescue effects were compared among the three groups. RESULTS: The amount of hemorrhaging in Group A was significantly lower than that in Groups B and C during surgery and 24 h after surgery (P < 0.05). There were markedly improved clinical indices in Groups A, B and C, showing statistical significance (P < 0.05). There were statistically significant differences in hemostatic failure rate, hysterectomy, postoperative abdominal pain and puerperal infection between Groups A and B (P < 0.05). The intraoperative indices, postoperative infection, effective hemostasis rate and rate of advanced postpartum hemorrhage in Group A were remarkably higher than those in Groups B and C (P < 0.05), showing statistical significance (P < 0.05). There were statistically significant differences in blood oxygen saturation and pulse among the three groups before surgery and 2 h after surgery (P < 0.05). CONCLUSION: Carboprost tromethamine injection combined with modified B-lynch suture and carboprost methylate suppositories can reduce the amount of hemorrhaging and the risk of postoperative infection in placenta previa patients with postpartum hemorrhage after cesarean section.

Efficacy of Electroacupuncture Combined with Tropisetron in Treating Carboprost Tromethamine-Induced Nausea and Vomiting during Cesarean Section under Lumbar Anesthesia.

OBJECTIVE: We evaluated the efficacy of electroacupuncture combined with tropisetron in treating carboprost tromethamine-induced nausea and vomiting during cesarean section under lumbar anesthesia. METHODS: A total of 264 patients aged 22-40 years were enrolled, who received carboprost tromethamine and suffered nausea and vomiting during cesarean section under lumbar anesthesia. The patients were divided randomly into the control group, electroacupuncture group, tropisetron group, and electroacupuncture + tropisetron group. RESULTS: Compared to the control group, the nausea and vomiting scores decreased at T3 in both the electroacupuncture and electroacupuncture + tropisetron groups, and decreased at T4 in the electroacupuncture group, tropisetron group, and electroacupuncture + tropisetron group; the motilin, gastrin, and 5-hydroxytryptamine (5-HT) levels decreased at T5 in the other 3 groups. Compared to the electroacupuncture + tropisetron group, the nausea and vomiting scores increased at T3 in the control and tropisetron groups, and increased at T4 in the other 3 groups; the motilin, gastrin, and 5-HT levels increased at T5. CONCLUSIONS: Our study suggested that electroacupuncture combined with tropisetron could effectively relieve carboprost tromethamine-induced nausea and vomiting during cesarean section under lumbar anesthesia. The effect was better than its single application, and the reduced 5-HT, motilin, and gastrin levels might be involved in the underlying mechanism.

Cervical dilatation and preparation prior to outpatient hysteroscopy: a systematic review and meta-analysis.

BACKGROUND: There are uncertainties about the benefit of routine cervical preparation and/or cervical dilatation before outpatient hysteroscopy. OBJECTIVE: To determine if cervical preparation and/or routine mechanical dilatation reduces pain during outpatient hysteroscopy. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL and CENTRAL were searched on 19 October 2020, using keywords 'hysteroscopy', 'cervical preparation', 'cervical ripening', 'cervical dilatation', 'outpatient', 'office' and/or 'ambulatory' and associated medical subject headings. SELECTION CRITERIA: Randomised controlled trials investigating the benefit of cervical preparation and/or cervical dilatation on pain in women undergoing outpatient hysteroscopy were included. DATA COLLECTION AND ANALYSIS: Two independent reviewers selected eligible trials and extracted data on pain, feasibility, adverse events and satisfaction/acceptability for meta-analysis. MAIN RESULTS: The literature search yielded 807 records, of which 24 were included for review and 19 provided data for meta-analysis. No trials investigated the role of routine mechanical cervical dilatation. Cervical preparation significantly reduced pain during outpatient hysteroscopy; standard mean difference (SMD) -0.67, 95% confidence interval (CI) -1.05 to -0.29. Feasibility also improved as priming provided significantly easier hysteroscopic entry (SMD 0.89, 95% CI 0.32-1.46), greater cervical dilatation (SMD 0.81, 95% CI 0.08-1.53) and shorter procedural times (SMD -0.51, 95% CI -0.88 to -0.13). Cervical preparation, however, incurred significantly more adverse effects, mainly comprising genital tract bleeding, abdominal pain and gastrointestinal symptoms (odds ratio 2.94, 95% CI 1.58-5.47). There were limited data regarding satisfaction, acceptability and complications. CONCLUSIONS: Cervical preparation reduces pain and improves feasibility associated with outpatient hysteroscopy but increases the risk of adverse effects. TWEETABLE ABSTRACT: Cervical preparation before outpatient hysteroscopy reduces pain, enhances feasibility but increases adverse effects.

Remifentanil for Carboprost-Induced Adverse Reactions During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia.

PURPOSE: Carboprost may induce adverse reactions when used to treat postpartum hemorrhage. We aimed to explore the effects of intravenous infusion of low-dose remifentanil to prevent such reactions. METHODS: We enrolled parturient patients scheduled for elective cesarean section. Anesthesiologist administered combined spinal epidurals at the L3/4 interspace, with 0.5% hyperbaric bupivacaine subarachnoid space injections (1.5-2.5 ml). We randomly divided parturient patients, administered carboprost during surgery, into the remifentanil group (group R) and the control group (group C). Patients in group R received an intravenous target-controlled infusion of remifentanil (target effect-site concentration, 1.5 ng/ml) simultaneously with a carboprost tromethamine injection (250 µg). Patients in group C received a normal saline infusion with carboprost. We recorded and analyzed the incidence of carboprost-related adverse reactions (vomiting, nausea, chest congestion, flushing, hypertension, tachycardia, cough, and shivering), and assessed patient comfort using a numerical rating scale ([NRS], on which 0 was very uncomfortable and 10 was very comfortable). RESULTS: After applying inclusion and exclusion criteria, we conducted statistical analysis of the data from 70 women. The incidence of vomiting was significantly lower in group R than in group C (14.3 vs. 51.4%, p < 0.01); and the incidence of nausea, chest congestion, facial flushing, and hypertension were significantly lower in group R than in group C (all p < 0.01). Furthermore, the patients' comfort scores were significantly higher in group R than in group C (8.0 ± 1.8 vs. 3.6 ± 2.1, p < 0.01). CONCLUSION: Our results demonstrate that an intravenous low-dose remifentanil infusion can effectively prevent carboprost-related adverse reactions during cesarean delivery under combined spinal and epidural anesthesia. CLINICAL TRIAL REGISTRATION: We pre-registered this study at http://www.chictr.org.cn/showproj.aspx?proj=27707 (ChiCTR1800016292).

Efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss: A meta-analysis of randomized controlled trials.

Motherwort (YiMuCao), a traditional Chinese herb, has been shown beneficial effects for women's diseases. This meta-analysis aimed to evaluate the efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang from their inception to December 2017. Randomized controlled trials that determined the add-on effects of motherwort injection to carboprost for prevention of post-partum blood loss were eligible. Pooled risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used to summarize the effect sizes. Eight trials including 1276 pregnant women fulfilled the inclusion criteria. Prophylactic use of motherwort injection add-on therapy significantly reduced the post-partum 2 h (MD -127.5 mL; 95% CI -149.13 to -105.88) and 24 h (MD -146.85 mL; 95% CI -179.77 to -113.94) blood loss and incidence of post-partum hemorrhage (RR 0.28; 95% CI 0.17-0.45) than carboprost. Moreover, adjunctive treatment with motherwort injection significantly decreased the length of the third stage of labor (MD -3.41 min; 95% CI -4.33 to -2.49) and duration of lochia (MD -7.13 days; 95% CI -8.49 to -5.76). There was no statistical significant difference in the incidence of adverse events (RR 0.76; 95% CI 0.50-1.16). Prophylactic use of motherwort injection add-on therapy to carboprost tromethamine could reduce post-partum blood loss. However, more well-designed trials are necessary to confirm the findings of this study due to the methodological flaws of the included trials.

[Clinical multicenter study of carboprost methylate suppository for cervical ripening prior to diagnostic hysteroscopy].

Objective: To evaluate the effectiveness of carboprost methylate suppository for cervical ripening before diagnostic hysteroscopy in premenopausal women. Methods: From July 2014 to July 2015, 1 614 women who were undergone diagnostic hysteroscopy in 12 hospitals were randomly assigned into study group (n=1 209) and control group (n=405) . The cases in study group were given 1 mg carboprost methylate suppository in vagina before hysteroscopy, the cases in control group were given 1 mg placebo. The extent of cervical ripening, the time of dilated cervix, pain scoring, incidence of drug side reactions after 24, 48, 72 hours, satisfaction degree of operators and patients, the time of hysteroscopy, incidence of complications between the two groups were observed and compared. Results: (1) Mean cervical widths in the study and control groups were 6.11±1.11 and 5.95±1.11, and showed a significant difference (P=0.034) ; the percentage of women requiring cervical dilatation in study group was lower than the percentage in control group significantly [28.3% (342/1 209) versus 34.6% (140/405) , P=0.020]. (2) The time of dilated cervix in study group was shorter than the time in control group significantly [ (34±25) versus (52±49) s, P=0.028] for the patients whose mean cervical widths≤4. (3) There was no significant difference in pain scores between the two groups (P>0.05) . (4) The incidence of side reactions 24, 48, 72 hours after operation were no significant difference between the two groups (P>0.05) . (5) The satisfaction degree of operators and patients, the time of hysteroscopy, incidence of complications between the two groups were no singnifcant difference between the two groups (all P>0.05) . Conclusion: Application of carboprost methylate suppository by vagina before hysteroscopy is an effective and safe method of cervical ripening.

Uterotonic Medications: Oxytocin, Methylergonovine, Carboprost, Misoprostol.

Uterine atony is a common cause of primary postpartum hemorrhage, which remains a major cause of pregnancy-related mortality for women worldwide. Oxytocin, methylergonovine, carboprost, and misoprostol are commonly used to restore uterine tone. Oxytocin is the first-line agent. Methylergonovine and carboprost are both highly effective second-line agents with severe potential side effects. Recent studies have called into question the effectiveness of misoprostol as an adjunct to other uterotonic agents, but it remains a useful therapeutic in resource-limited practice environments. We review the current role these medications play in the prevention and treatment of uterine atony.

Carboprost Versus Oxytocin for Active Management of Third Stage of Labor: A Prospective Randomized Control Study.

BACKGROUND AND OBJECTIVES: Postpartum hemorrhage is the single largest and leading cause of maternal morbidity and mortality not only in developing countries but also in developed countries. The present study is an attempt to evaluate the scope of using prophylactic intramuscular carboprost tromethamine 125 µg in comparison with intramuscular oxytocin 10 units for the active management of third stage of labor. MATERIALS AND METHODS: Two hundred pregnant women at term with spontaneous onset of labor were included in the study and were randomly divided into 2 groups of 100 women each. Group A and group B were given injection oxytocin 10 units and injection carboprost tromethamine 125 µg intramuscularly, respectively, at the time of delivery of anterior shoulder. The main outcome measures with respect to third stage of labor were: duration, blood loss by volume, difference in hemoglobin, need for additional oxytocics and side effects. RESULTS: Subjects who received carboprost tromethamine 125 µg showed a significant reduction in duration of third stage of labor (p < 0.05) and blood loss (p < 0.01) when compared to the subjects who received oxytocin 10 units. Likelihood of occurrence of postpartum hemorrhage was reduced without significant side effects except for diarrhea. Additional need for other uterotonics after carboprost was significantly less compared to oxytocin. CONCLUSION: Intramuscular carboprost 125 µg is a better cost-effective alternative as compared to 10 units intramuscular oxytocin in active management of third stage of labor.

In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when P<0.05. There were no significant differences in the peak amplitude of response between agents, except for misoprostol, which was inactive. There was a wide difference in potencies using both measures of contractility, with oxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol.

Assessment of carboprost tromethamine for reducing hemorrhage in laparoscopic intramural myomectomy.

The aim of the present study was to evaluate the effect of carboprost tromethamine on blood loss during laparoscopic myomectomy (LM) in females. Ninety women, who were scheduled for LM due to symptomatic uterine myomas, were randomly divided into three groups. Twenty-four women were intramyometrially injected with 12 IU diluted vasopressin (vasopressin group), 30 cases received a deep intramuscular injection of 250 µg carboprost tromethamine 30 min prior to myomectomy (carboprost group), and 36 cases received an intramuscular injection of 250 µg carboprost tromethamine followed by a 20 IU oxytocin intravenous infusion at a rate of 120 mU/min during the procedure (carboprost plus oxytocin group). The procedure time, amount of hemorrhage, postoperative reduction in hemoglobin levels, adverse effects, bowel deflation time and time of postoperative hospital stay were compared. The procedure time, amount of hemorrhage and postoperative reduction in hemoglobin levels were not significantly different between the carboprost group and the vasopressin group (P>0.05). In the carboprost plus oxytocin group, the procedure time, amount of hemorrhage and postoperative reduction in hemoglobin levels were 24.3±2.6 min, 51.1±8.4 ml and 6.9±1.5 g/l, respectively, which were significantly less than those in the vasopressin and carboprost groups (all P<0.05). In the carboprost and carboprost plus oxytocin groups, the incidence of mild uterine contraction pain was significantly higher than in the vasopressin group (χ2=12.913, P=0.002). The incidences of other side-effects were not significantly different among the three groups. The times for bowel deflation and postoperative hospital stay were marginally increased in both the carboprost and carboprost plus oxytocin groups, compared with the vasopressin group, although no significant differences were found among the three groups (P>0.05). Deep intramuscular injections of carboprost tromethamine prior to performing myomectomy could be an effective approach for reducing blood loss from intramural LM, in particular when combined with oxytocin intravenous infusion.

Simultaneous determination of carboprost methylate and its active metabolite carboprost in dog plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application to a pharmacokinetic study.

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500µL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150×2.0mm, 5µm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5→329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2→323.2, and 357.1→321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of ≤6.75% and accuracy (as relative error) of ≤7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate.

A comparison of oxytocin and carboprost tromethamine in the prevention of postpartum hemorrhage in high-risk patients undergoing cesarean delivery.

The aim of this study was to compare carboprost with oxytocin for the prevention of postpartum hemorrhage (PPH) in females with a high risk of PPH undergoing cesarean delivery. Patients were randomly divided into three groups that received different uterotonics (oxytocin, carboprost and oxytocin plus carboprost) during cesarean section, following the delivery of the infant. A total of 117 females (age range, 19-40 years) at 35-40 weeks gestation who delivered by cesarean between December, 2010 and May, 2012 were included in this study. There were 29 cases of twins, 12 cases of polyhydramnios, 23 cases of placenta previa and 53 cases of fetal macrosomia. There were 37 patients in the oxytocin group, 36 in the carboprost group and 44 in the oxytocin plus carboprost group. No significant differences were identified in maternal age, gravidity/parity, gestational age and reason for cesarean delivery between the three groups. The median blood loss in the oxytocin, carboprost and oxytocin plus carboprost groups was 610, 438 and 520 ml, respectively. The blood loss in the carboprost group was significantly lower than that in the oxytocin and oxytocin plus carboprost groups (both P<0.05). Vomiting occurred in eight patients from the carboprost group, two from the oxytocin group and two from the oxytocin plus carboprost group (P=0.036). Carboprost was more effective than oxytocin in preventing PPH in high-risk patients undergoing cesarean delivery.

MID-TRIMESTER MTP USING ENDOCERVICAL PGE2 GEL AND SERIAL INTRAMUSCULAR CARBOPROST.

60 cases of mid-trimester pregnancy were terminated using endocervical PGE2 gel (for achieving cervical priming) followed by serial intramuscular injections of carboprost. In this prospective study, 56 cases were multiparae with gestational age varying between 15-22 weeks. The induction-abortion-interval was 8.4h ± 0.8h with a success rate of 100%. The incidence of incomplete abortion was 5% and check curettage was performed in 16.6% cases. Gastrointestinal side effects were common. Vomiting occurred in 42% cases and diarrhoea in 50%. Febrile morbidity was seen in 8.3% cases. There were no complications of the procedure. The method was highly acceptable to the patients being non-invasive and allowing ambulation throughout. This method of elective mid-trimester abortion is an effective alternative to the other commonly used methods like extra-amniotic ethacridine lactate or intra-amniotic hypertonic saline instillation.