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1.
Effect and Safety of Diluted Vasopressin Injection for Bleeding Control During Robot-assisted Laparoscopic Myomectomy in Reproductive Women With Uterine Fibroids: A Randomized Controlled Pilot Trial (VALENTINE Trial)
Park, S. J., Lee, J. W., Hwang, D. W., Lee, S., Yim, G. W., Song, G., Lee, E. J., Kim, H. S.
In vivo (Athens, Greece). 2024;38(1):431-436
Abstract
BACKGROUND/AIM: Vasopressin injected during myomectomy is known to effectively reduce bleeding but is sometimes associated with intraoperative vasoconstriction and hypertension due to systemic absorption. Although there is a growing preference for the use of diluted vasopressin, evidence of its effect and safety is still lacking. PATIENTS AND METHODS We performed a randomized controlled pilot trial to evaluate the effect and safety of vasopressin diluted in a constant volume during robot-assisted laparoscopic myomectomy (RALM), where a total of 39 women with uterine fibroids were randomly assigned into the following three groups (group 1, 0.2 IU/ml; group 2, 0.1 IU/ml; group 3, 0.05 IU/ml with a total of 100 ml of normal saline). The primary endpoint was to compare estimated blood loss (EBL), and the secondary endpoints were to compare postoperative value and drop ratio of hemoglobin, operation time, transfusion, hospitalization, and complications among the three groups. RESULTS There were no differences in the number and largest size of uterine fibroids, total weight of uterine fibroids, console time, and volumes of intravenous fluid administered during RALM among the three groups, whereas combined operation was performed more commonly in group 2 than in groups 1 and 3 (53.9% vs. 0 to 7.7%; p=0.01). The primary and secondary endpoints were also not different among the three groups. However, two patients in group 1 (15.4%) showed vasopressin-related hypertension. CONCLUSION Vasopressin diluted in a volume of 100 ml showed an effective hemostatic effect and safety during RALM (Trial No. NCT04874246 in ClinicalTrial.gov).
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2.
Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial
Brown, E., Kroll, R., Li, H., Ng, J., Pinsky, B., Rodriguez, J. W., Thomas, J., Snabes, M. C.
Obstetrics and gynecology. 2023
Abstract
OBJECTIVE To evaluate the safety and efficacy of elagolix 150 mg once-daily monotherapy in patients with heavy menstrual bleeding associated with uterine leiomyomas. METHODS A phase 4, randomized, double-blind, placebo-controlled, 6-month treatment study was conducted in premenopausal patients aged 18-51 years with heavy menstrual bleeding (defined as menstrual blood loss greater than 80 mL during one menstrual cycle) associated with uterine leiomyomas. Patients were randomized 2:1 to receive elagolix 150 mg once daily or placebo. The primary endpoint was reduction in menstrual blood loss volume to less than 80 mL at the final month and at least a 50% reduction in menstrual blood loss volume from baseline to the final month. RESULTS Of 82 randomized patients, 54 received elagolix 150 mg and 28 received placebo. With elagolix, 49.4% (95% CI 35.1-63.8%) of patients met the primary endpoint, compared with 23.3% (95% CI 7.2-39.5%) of patients who received placebo (P=.035). Statistically significant differences between elagolix and placebo in mean reduction of menstrual blood loss from baseline were seen as early as month 1 (P<.05 for months 1-3 and 5). Significantly more patients receiving elagolix experienced suppression of bleeding compared with placebo (P=.036). Greater improvements were observed in the elagolix group (vs placebo) in the proportion of patients with amenorrhea, in hemoglobin concentrations, and in health-related quality of life. No serious or severe adverse events were reported for elagolix, compared with 7.1% of participants in the placebo group having serious adverse events (coronavirus disease 2019 [COVID-19] n=1, enlarged uvula n=1). Three patients (5.6%) discontinued elagolix due to adverse events. CONCLUSION Elagolix 150 mg once-daily monotherapy significantly improved heavy menstrual bleeding associated with uterine leiomyomas compared with placebo in premenopausal patients. Treatment with elagolix 150 mg once daily was generally well-tolerated in this study, with no new safety signals. FUNDING SOURCE AbbVie Inc. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03886220.
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3.
Hemodynamic Effects of Oxytocin and Carbetocin During Elective Cesarean Section in Preeclamptic Patients Under Spinal Anesthesia: A Randomized Double-blind Controlled Study
Bahr, M. H., Abdelaal Ahmed Mahmoud, M. Alkhatip A., Ahmed, A. G., Elgamel, A. F., Abdelkader, M., Hussein, H. A.
Anesthesiology and pain medicine. 2023;13(1):e128782
Abstract
BACKGROUND Oxytocin and carbetocin are uterotonic medications that are used to decrease postpartum hemorrhage (PPH). However, there are not enough clinical data about the hemodynamic side effects of carbetocin. OBJECTIVES This study aimed to compare carbetocin and oxytocin hemodynamic effects in preeclamptic patients undergoing elective cesarean section under spinal anesthesia. METHODS In this double-blind, randomized controlled trial, intravenous oxytocin or carbetocin was administered to 80 women (40 per group). The hemodynamic effects, such as blood pressure (BP), heart rate (HR), and oxygen (O(2)) saturation, were measured before the operation and after 1, 5, 10, and 15 minutes of the administration of both drugs. Intragroup and intergroup comparisons were conducted during statistical analysis. RESULTS Based on the intragroup comparison, there was a significant increase in HR and a reduction in BP from baseline to all intervals after the administration of both interventions. Moreover, based on the intergroup comparison, there was a significantly more increase in HR and a decline in BP and O(2) saturation in the oxytocin group than in the carbetocin group. There were three and seven cases that required another dose of carbetocin and oxytocin, respectively. Moreover, one case developed PPH in the carbetocin group; nevertheless, two cases developed PPH in the oxytocin group. CONCLUSIONS The minimal effect of carbetocin on patients' hemodynamics suggests extending the use of this drug instead of oxytocin as a uterotonic drug in patients with preeclampsia, hemorrhagic risk factors, and/or hypertension.
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4.
A Comparative Study of the Efficacy of Intraoperative Intravenous Oxytocin and Intramuscular Oxytocin Versus Conventional Intramuscular Oxytocin for Third-Stage Labour in Elective Cesarean Section
Behuria S, Sahu M, Mohanty M, Behera S, Mohapatra K, Patnaik R, Jena S
Cureus. 2023;15(2):e35026
Abstract
Objective To study the efficacy of intraoperative IV oxytocin and intramuscular (IM) oxytocin versus conventional intramuscular oxytocin alone for active management of the third stage of labor in lower segment cesarean section (CS). The study was performed to determine the effect of 5 IU (International Unit) oxytocin infusion at the time of skin incision and that of 10 IU IM oxytocin infusion after delivery in reducing blood loss during and after CS, in comparison with the effect of administrating conventional 10 IU IM oxytocin in the same time period. In addition, it assessed the ability of the IV+IM oxytocin group to reduce the need for additional uterotonic as well as its safety determination and postoperative blood transfusion in CS. Materials and methods It is a randomized control study. The effect of 5 IU of oxytocin infusion at the time of skin incision and 10 IU of IM oxytocin (IV+IM) in reducing blood loss during and after the CS was compared to conventional 10 IU IM oxytocin. Results The study showed that the IV+IM group had a mean blood loss of 316.5 ± 74.36 ml, while the IM group had a mean loss of 403.90 ± 107.2 ml (p-value < 0.001) from placental delivery to the end of CS. A total of 90% of the patients in the IV+IM group had blood loss <50 ml compared to 95% of patients in the IM group who had a blood loss between 50 and 100 ml range from the end of cesarean to two hours postpartum. When total blood loss was compared in both groups, 84% of patients had a blood loss between 300 and 400 ml, compared to 81% of the patients in the IM group who had blood loss of 400-500 ml. Total blood loss in the IM group was 483.20 ± 115.86 ml, which was significantly higher compared to the IV group, 362.60 ± 78.07 ml (p-value=<0.001). Conclusion 5IU oxytocin infusion at the time of skin incision and 10 IU IM oxytocin after delivery of the baby significantly reduced the amount of blood loss, need for blood transfusion, and additional uterotonics during and after lower segment CS.
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5.
Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin
Edelman A, Boniface E, Schrote K, Messerle-Forbes M, O'Donnell A, Jensen JT, Han L
American journal of obstetrics and gynecology. 2023
Abstract
BACKGROUND Some users of the etonogestrel contraceptive implant experience bothersome bleeding which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown but it is likely multi-factorial (e.g. impaired angiogenesis, 'leaky' fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, anti-proliferative, and anti-angiogenic proprieties which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE To evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN The study was a randomized, double blind, placebo-controlled trial. We enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting and randomized them to either 600 mg Theracumin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. We defined "frequent" as two or more independent bleeding or spotting episodes and "prolonged" as 7 or more consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical exam as well as a negative gonorrhea/chlamydia and pregnancy test. Enrolled participants initiated study treatmentfollowing three consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30-days of enrollment, subjects were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. We defined bleeding as a day that required the use of protection with a pad, tampon, or liner, and spotting as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. Secondary outcomes including total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha 0.05 to demonstrate a 6-day difference between groups. RESULTS From February 2021 to November 2022, 58 individuals enrolled in the study with 93% (n=54) completing 30 days of treatment (curcumin 26, placebo 28). One individual in the curcumin arm did not experience a qualifying bleeding event and thus never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups including length of implant use at study enrollment [placebo: 521 days (SD 305), curcumin 419 days (SD 264)]. Study groups did not differ in regard to any bleeding-related outcome [mean days without bleeding or spotting: curcumin 16.7 (SD 6.9), placebo 17.5 (SD 4.8), p = 0.62; mean bleeding-free days: curcumin 23.4 (SD 4.9), placebo 22.4 (SD 4.5), p = 0.44; bleeding episodes: curcumin 2.0 (SD 0.8), placebo 2.1 (SD 0.8), p = 0.63]. Satisfaction with the implant as contraception and acceptability of bleeding over the study period also did not differ by study group (p = 0.54 and p = 0.30, respectively). CONCLUSION Daily use of curcumin did not improve bleeding patterns in users of the etonorgestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.
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6.
The efficacy of three regimes of uterotonic agents for prevention of postpartum blood loss at undergoing cesarean section: a prospective randomized clinical trial
Çetin, Ç, Dural, H. R., Özcan, P., Tanoğlu, F. B., Kütük, M. S., Pasin, Ö, Ateş, S.
Ginekologia polska. 2023
Abstract
OBJECTIVES To compare the efficacy of three regimes of uterotonic agents on PPH in women undergoing cesarean section in our RCT. MATERIAL AND METHODS This study was a randomized controlled study (NCT05083910) performed at the Bezmialem Vakif University between July 2021 and January 2022. All women were randomly allocated into three groups: Group I (n = 52) - oxytocin only; Group II (n = 52) - the combination of oxytocin plus intrauterine misoprostol; Group III (n = 52) - carbetocin only. The primary outcome measures were: PPH to evaluate with the change between the concentrations of preoperative and postoperative hemoglobin, hematocrit and intraoperative blood loss. RESULTS The blood loss characteristics, including the change in hemoglobin and the change in hematocrit concentration, intraoperative blood loss, intraoperative additional hemostatic uterine sutures and the need for additional uterotonics, were lowest in group III, although all groups were comparable in terms of blood loss parameters. Group III had the highest blood loss ratio, exceeding 1000 mL. For the combination of oxytocin and intrauterine misoprostol, the ARR was 3.8% (95% CI 20.02-12.33), with a RR of 1.18 (95% CI 0.58-2.39) and a NNT of 26 (95% CI 8.1-4.9); for carbetocin, the ARR was 5.8% (95% CI 22.15-10.61), with a RR of 1.27 (95% CI 0.63-2.53) and a NNT of 17 (95% CI 9.41-4.51). CONCLUSIONS Our results demonstrate that carbetocin shows no superiority in the prevention of PPH in women undergoing cesarean section. Oxytocin still seems to be a highly effective alternative to prevent PPH.
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7.
Preliminary efficacy, feasibility and safety of intra-umbilical oxytocin to reduce the time to placental delivery at caesarean section: an exploratory randomized trial
Middleton, K., Mbengo, F., Mavundla, T. R., Hofmeyr, G. J.
African health sciences. 2023;23(3):1-7
Abstract
BACKGROUND Delayed placental separation either after vaginal birth or caesarean birth is an important cause of postpartum haemorrhage, among other causes such as uterine atony. Intra-umbilical oxytocin has been shown to reduce the time to placental delivery after vaginal birth. However, the efficacy of intra-umbilical oxytocin to reduce the time to placental delivery following caesarean section birth is not known. OBJECTIVES To explore the preliminary efficacy, feasibility and safety of intra-umbilical oxytocin to reduce the time to placental delivery at caesarean section. METHODS A double-blind, placebo-controlled, exploratory randomized clinical trial was conducted at a tertiary hospital in the Eastern Cape Province, South Africa. A total of 66 women undergoing elective caesarean section were enrolled in the study and randomized into oxytocin group (n = 33) receiving an intra-umbilical infusion of 20 units of oxytocin in 30ml saline, and placebo group (n = 33) receiving an intra-umbilical infusion of 30ml saline. Data were analysed using Epi Info and RevMan software. Preliminary efficacy was assessed by examining the time elapsed from birth of the baby to complete delivery of the placenta; blood loss more than 500 ml; the need for manual removal of the placenta; and the completeness of the placenta. Feasibility was determined by observing the successful insertion of the catheter and injection of the solution. Safety was evaluated by investigating adverse effects of the procedure. RESULTS Four women (12%) in the placebo group had a delayed placental delivery compared to one (3%) in the oxytocin group. The mean time from birth to placental delivery was 159 (SD 61) seconds in the placebo group and 143 (SD 45) seconds in the oxytocin group. There was no statistically significant difference between the two groups. Feasibility of the procedure was confirmed by successful insertion of the catheter and injection of the majority of the solution in all 66 cases. No adverse effects of the procedure were identified. CONCLUSION Administration of intra-umbilical oxytocin is feasible, safe and has potential to reduce the time of placental delivery at caesarean section. Further studies involving larger sample sizes are justified.
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8.
Heat stable carbetocin or oxytocin for prevention of postpartum hemorrhage among women at risk: A secondary analysis of the CHAMPION trial
Ghosh, R., Owa, O., Santos, N., Butrick, E., Piaggio, G., Widmer, M., Althabe, F., Qureshi, Z., Lumbiganon, P., Katageri, G., et al
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2023
Abstract
OBJECTIVE To examine whether the observed non-inferiority of heat-stable carbetocin (HSC), compared with oxytocin, was influenced by biologic (macrosomia, parity 3 or more, or history of postpartum hemorrhage [PPH]) and/or pharmacologic (induction or augmentation) risk factors for PPH. METHODS The present study is a secondary analysis of the CHAMPION non-inferiority randomized trial-a two-arm, double-blind, active-controlled study conducted at 23 hospitals in 10 countries, between July 2015 and January 2018. Women with singleton pregnancies, expected to deliver vaginally with cervical dilatation up to 6 cm were eligible. Randomization was stratified by country, with 1:1 assignment. Women in the intervention and control groups received a single intramuscular injection of 100 μg of HSC or 10 IU of oxytocin, respectively. The drugs were administered immediately after birth, and the third stage of labor was managed according to the WHO guidelines. Blood was collected using a plastic drape. For this analysis, we defined a woman as being at risk if she had any one or more of the biologic or pharmacologic risk factor(s). RESULTS The HSC and oxytocin arms contained 14 770 and 14 768 women, respectively. The risk ratios (RR) for PPH were 1.29 (95% confidence interval [CI] 1.08-1.53) or 1.73 (95% CI 1.51-1.98) for those with only biologic (macrosomia, parity 3 or more, and PPH in the previous pregnancy) or only pharmacologic (induced or augmented) risk factors, respectively, compared with those with neither risk factors. CONCLUSIONS Findings reinforce previous evidence that macrosomia, high parity, history of PPH, and induction/augmentation are risk factors for PPH. We did not find a difference in effects between HSC and oxytocin for PPH among women who were neither induced nor augmented or among those who were induced or augmented.
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9.
A Comparative Study of Sublingual Misoprostol Versus Intramuscular Oxytocin in the Active Management of Third Stage of Labor
Mishra S, Tirkey S, Prasad A, Trivedi K
Cureus. 2023;15(1):e33339
Abstract
Objective Misoprostol has attracted low-income low-resource countries for the active management of the third stage of labor. The objective of this study was to compare the efficacy of sublingual misoprostol and intramuscular oxytocin in the active management of the third stage of labor. Study design This was a prospective randomized controlled trial in which a total of 407 healthy pregnant women having singleton pregnancy, cephalic presentation, and normal vaginal delivery were divided into two groups. In the first group (n=203), women received 600 µg misoprostol tablet sublingually, and in the second group (n=204), women received 10 IU of intramuscular oxytocin, within 1 minute of the delivery of the baby during the third stage of labor. Three patients from the first group and four patients from the second group were excluded from the analysis due to traumatic postpartum hemorrhage (PPH). The primary outcome was an incidence of PPH. Secondary outcomes were the duration of the third stage of labor, amount of blood loss, fall in hemoglobin concentration after 48 hours of delivery, need for additional uterotonics, and side effects of the drugs. Data were compared using the chi-square and independent samples t-test. Results The incidence of PPH was 6.5% in the misoprostol group as compared to 2% in the oxytocin group (p=0.026). The misoprostol group also had significantly higher blood loss (293.75±125.8 mL) and a greater fall in hemoglobin level (0.58±0.25 g/dL) as compared to that in the oxytocin group (226.13±98.44 mL and 0.45±0.20 g/dL) (p<0.001). The mean duration of the third stage of labor was significantly higher in the misoprostol group (5.31±2.1 min) as compared to that in the oxytocin group (3.65±1.75 min) (p<0.001). The additional need for uterotonics was recorded in 15% of the study participants in the misoprostol group as compared to 8% in the oxytocin group (p=0.028). The incidence of side effects such as shivering and fever was significantly higher in the misoprostol group as compared to the oxytocin group. No significant difference between the two groups was observed concerning the incidence of nausea, vomiting, diarrhea, and headache. Conclusion Intramuscular oxytocin is a safe and useful alternative to sublingual misoprostol in facilitating the third stage of labor with minimal blood loss, fewer incidences of hemorrhage, and fewer adverse effects.
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10.
Efficacy of Ibuprofen Lysine on First-Trimester AbortionRelated Pain and Hemorrhage: A Randomized TripleBlinded Clinical Trial
Najmi, Z., Dabiri Oskoei, A., Tofighi, S., Gholami, H., Garrosi, L., Amini, F.
Archives of Iranian medicine. 2023;26(4):212-217
Abstract
BACKGROUND Some recent trials have reported high efficacy for nonsteroidal anti-inflammatory drugs (NSAIDs) in relieving medical abortion-related pain. The aim of this study was to determine the beneficial effect of oral NSAIDs (ibuprofen lysine) in reduction of pain and hemorrhage in first-trimester medical abortion. METHODS This randomized triple-blinded clinical trial was performed on 98 pregnant women who were candidate for medical abortion within the first-trimester period (gestational age<12 weeks). The participants were randomly assigned to receive ibuprofen lysine (684 mg orally every 4 hours) or placebo. All patients were initially treated with misoprostol (800 µg every 3 hours). Pain intensity and rate of hemorrhage were assessed every hour up to 15 hours after receiving the first dose of misoprostol by visual analogue scaling (VAS) and pictorial blood loss assessment chart (PBAC), respectively. RESULTS Assessing the mean pain score within 15 hours of receiving misoprostol showed significantly lower pain intensity within the first 10 hours of assessment in the group receiving NSAID in comparison with the control group (P<0.001). The bleeding rate was also significantly lower in the NSAID group at the fifth (P=0.013) and ninth (P=0.040) hour of receiving misoprostol compared to the control group. We found no difference in abortion-related complication rate between the NSAID and placebo groups (8.3% versus 8.0%, P=0.952). CONCLUSION The use of NSAIDs (ibuprofen lysine) is a good pharmacological analgesic option for relieving medical abortionrelated pain and hemorrhage.