OBJECTIVE: To evaluate the efficacy of carbetocin versus oxytocin in preventing postpartum haemorrhage (PPH) in women with risk factors for PPH who were delived by caesarean section.
METHODS: This retrospective, monocentric, before-and-after cohort study assessed patients with haemorrhagic risk factors who underwent caesarean section after 24 weeks of gestation and who had haemorrhagic risk factors between August 2014 to December 2019.
RESULTS: This study enrolled 518 patients, including 250 in the oxytocin group and 268 in the carbetocin group. The use of carbetocin was independently associated with a PPH decrease compared to oxytocin use (adjusted odds ratio [OR]: 0.52; 95 % confidence interval [CI]: 0.35-0.79; p = 0.002). Carbetocin use was associated with a reduction in the need for therapy escalation (6 % vs 10.8 %; p = 0.046).
CONCLUSIONS: Carbetocin was more effective than oxytocin in preventing PPH after caesarean section in high-risk patients.

BACKGROUND: Our objective was to assess non-inferiority of the unique approach used in our institution of combined 10 IU IM (intramyometrial) and 10 IU IV (intravenous) oxytocin to carbetocin IV in preventing severe postpartum blood loss in elective cesarean sections. The design was a prospective controlled phase IV non-inferiority interventional trial. The setting was a tertiary center at University Hospital, Zurich, Switzerland.
METHODS: The population consisted of 550 women undergoing elective cesarean section after 36 completed weeks of gestation at low risk for postpartum hemorrhage (PPH). Participants were assigned to either combined oxytocin regimen (10 IU IM and 10 IU IV) or carbetocin (100 μg IV). Non-inferiority for oxytocin for severe PPH was assessed with a 0.05 margin using the Newcombe-Wilson score method. The main outcome measures were severe postpartum blood loss defined as delta hemoglobin (∆Hb, Hb prepartum-Hb postpartum) ≥30 g/L.
RESULTS: Non-inferiority of combined oxytocin (IM/IV) in preventing severe postpartum blood loss was not shown (17 women in the oxytocin group vs. 7 in the carbetocin group). The number needed to treat when using carbetocin was 28. The risk difference for ∆Hb ≥30 g/L was 0.04 (oxytocin 0.06 vs. 0.03), 95% confidence interval (CI) (0.00-0.08). No significant difference was observed for ∆Hb (median 12 [IQR 7.0-19.0] vs. 11 [5.0-17.0], p = 0.07), estimated blood loss (median 500 [IQR 400-600] vs. 500 [400-575], p = 0.38), or the PPH rate defined as estimated blood loss ≥1000 mL (12[4.5] vs. 5 [2.0], risk difference 0.03, 95% CI (-0.01 to 0.06), p = 0.16). More additional uterotonics were administered in the oxytocin group compared to the carbetocin group (15.2% vs. 5.9%, p = 0.001). Total case costs were non-significantly different in the oxytocin group (US $ 10 146 vs. 9621, mean difference 471.4, CI (-476.5 to 1419.3), p = 0.33).
CONCLUSIONS: Combined (IM/IV) oxytocin is not non-inferior to carbetocin regarding severe postpartum blood loss defined as postpartum Hb decrease ≥30 g/L in elective cesarean sections. We recommend carbetocin for use in clinical practice for elective cesarean sections.

The impact of environmental enrichment (EE) on natural rewards, including social and appetitive rewards, was investigated in male Swiss mice. EE, known for providing animals with various stimuli, was assessed for its effects on conditioned place preference (CPP) associated with ethanol and social stimuli. We previously demonstrated that EE increased the levels of the prosocial neuropeptide oxytocin (OT) in the hypothalamus and enhanced ethanol rewarding effects via an oxytocinergic mechanism. This study also investigated the impact of EE on social dominance and motivation for rewards, measured OT-mediated phospholipase C (PLC) activity in striatal membranes, and assessed OT expression in the hypothalamus. The role of dopamine in motivating rewards was considered, along with the interaction between OT and D1 receptors (DR) in the nucleus accumbens (NAc). Results showed that EE mice exhibited a preference for ethanol reward over social reward, a pattern replicated by the OT analogue Carbetocin. EE mice demonstrated increased social dominance and reduced motivation for appetitive taste stimuli. Higher OT mRNA levels in the hypothalamus were followed by diminished OT receptor (OTR) signaling activity in the striatum of EE mice. Additionally, EE mice displayed elevated D1R expression, which was attenuated by the OTR antagonist (L-368-889). The findings underscore the reinforcing effect of EE on ethanol and social rewards through an oxytocinergic mechanism. Nonetheless, they suggest that mechanisms other than the prosocial effect of EE may contribute to the ethanol pro-rewarding effect of EE and Carbetocin. They also point towards an OT-dopamine interaction potentially underlying some of these effects.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term \"active management of the third stage of labor\" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term \"active management of the third stage of labor\" as a combined intervention no longer be used. Instead, we recommend that \"third stage care\" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

OBJECTIVE: Our study\'s primary objective was to examine the effects of four different prophylactic protocols on the prevention of postpartum hemorrhage following vaginal birth, including carbetocin only, oxytocin only, and a combination of carbetocin or oxytocin with tranexamic acid.
METHODS: A multicentric randomized controlled trial.
METHODS: This multicentric center prospective randomized controlled trial was conducted at the Department of Obstetrics and Gynecology of Bezmialem University and Van Health Teaching and Research Hospital from August 2022 to January 2023. The collected data included age, gravidity, parity, gestational age at birth, duration of delivery stages, prepartum hemoglobin and hematocrit concentrations, changes in hemoglobin and hematocrit concentrations, intrapartum blood loss, estimated blood loss after 2 h of vaginal delivery, Apgar scores at 1 and 5 min, birth weight, and neonatal intensive care unit (NICU) admission. Intrapartum blood loss was objectively measured in milliliters using a postpartum drape with a calibrated bag. The amount of bleeding was measured by subtracting the empty weight of the pads placed under the patient in the patient\'s bed within 2 h after delivery. Group I: carbetocin 100 μg/mL (n = 75), group II: oxytocin 5 IU/mL (n = 75), group III: carbetocin and tranexamic acid 50 mg/mL (n = 75), group IV: oxytocin and tranexamic acid (n = 75).
RESULTS: The hemoglobin concentration decrease significantly differed between groups (1.03 ± 1.04, 1.3 ± 0.85, 1.4 ± 0.85, 1.41 ± 0.87, respectively; p < 0.001). Group 4 has the highest decrease in hemoglobin and hematocrit concentrations. When we investigated the subgroup differences, the decrease in hemoglobin concentration was significantly higher in group 2 than group 1 (1.30 ± 0.85 vs. 1.03 ± 1.04; p = 0.023), in group 2 than group 3 (1.3 ± 0.85 vs. 1.04 ± 0.9; p = 0.013), and in group 4 than group 3 (1.41 ± 0.87 vs. 1.04 ± 0.9; p < 0.001). The decrease in hematocrit level was significantly different between groups (3.07 ± 3.23, 3.55 ± 2.44, 2.13 ± 3.09, 4.25 ± 2.52; p < 0.001, respectively). No significant differences were observed in terms of mean blood loss between the four groups (277.19 ± 208.10, 294.13 ± 198.64, 274.33 ± 199.57, and 283.97 ± 178.11; p = 0.445, respectively). Furthermore, there was no significant difference between the groups in the rate of need for blood transfusion (1.3%, 5.4%, 4%, and 4%, respectively; p = 0.6).
CONCLUSIONS: The most important limitation of the study is a relatively small number of participants.
CONCLUSIONS: In conclusion, our findings suggest that carbetocin may be more successful than oxytocin and oxytocin plus tranexamic acid regimens in terms of postpartum hemoglobin reduction, and there is no difference in terms of the need for blood transfusion when it is used for postpartum hemorrhage prophylaxis after vaginal delivery.

UNASSIGNED: 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.
UNASSIGNED: This study aimed to compare carbetocin and oxytocin hemodynamic effects in preeclamptic patients undergoing elective cesarean section under spinal anesthesia.
UNASSIGNED: 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 (O2) 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.
UNASSIGNED: 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 O2 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.
UNASSIGNED: 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.

Carbetocin and oxytocin are commonly recommended agents for active management of the third stage of labour. Evidence is inconclusive whether either one more effectively reduces the occurrence of important postpartum haemorrhage outcomes at caesarean section. We examined whether carbetocin is associated with a lower risk of severe postpartum haemorrhage (blood loss ≥ 1000 ml) in comparison with oxytocin for the third stage of labour in women undergoing caesarean section. This was a retrospective cohort study among women undergoing scheduled or intrapartum caesarean section between 1 January 2010 and 2 July 2015 who received carbetocin or oxytocin for the third stage of labour. The primary outcome was severe postpartum haemorrhage. Secondary outcomes included blood transfusion, interventions, third stage complications and estimated blood loss. Outcomes were examined overall and by timing of birth, scheduled versus intrapartum, using propensity score-matched analysis. Among 21,027 eligible participants, 10,564 women who received carbetocin and 3836 women who received oxytocin at caesarean section were included in the analysis. Carbetocin was associated with a lower risk of severe postpartum haemorrhage overall (2.1% versus 3.3%; odds ratio, 0.62; 95% confidence interval 0.48 to 0.79; P < 0.001). This reduction was apparent irrespective of timing of birth. Secondary outcomes also favoured carbetocin over oxytocin. In this retrospective cohort study, the risk of severe postpartum haemorrhage associated with carbetocin was lower than that associated with oxytocin in women undergoing caesarean section. Randomised clinical trials are needed to further investigate these findings.

BACKGROUND: Oxytocin and its analogue carbetocin are uterotonics whose prophylactic use is recommended to prevent postpartum haemorrhage, which is one of the leading causes of maternal deaths worldwide. However, both drugs can cause specific adverse effects and haemodynamic challenges.
OBJECTIVE: The aim of this work was to exploratively examine reports of adverse drug events of both drugs and to establish a comparative haemodynamic profile.
METHODS: Using data extracted from the World Health Organization\'s pharmacovigilance database VigiBase, a descriptive analysis was performed of all reports for oxytocin and carbetocin as a suspected or interacting drug followed by a disproportionality analysis for haemodynamic events. Reporting odds ratios (ROR) of carbetocin for hypertension, hypotension, tachycardia, and bradycardia were calculated, with oxytocin-related reports serving as comparators.
RESULTS: Oxytocin and carbetocin were mentioned as suspected or interacting drugs in 11,258 and 374 reports, respectively. Resulting RORs for carbetocin were 3.45 (95%CI: 1.72-6.92) for hypertension, 2.65 (1.64-4.28) for hypotension, 2.84 (1.79-4.49) for tachycardia, and 2.00 (0.87-4.60) for bradycardia, when compared to oxytocin. Of 231 patients for whom oxytocin-related tachycardia was reported, 2.6% died, and of 91 patients for whom bradycardia was reported, 2.2% died. No deaths were reported with carbetocin for any of the haemodynamic adverse events.
CONCLUSIONS: Compared to oxytocin, carbetocin showed an elevated reporting for adverse hypertension, hypotension, and tachycardia in pharmacovigilance data. Clinicians should be aware of their patients\' individual susceptibility and the possibility of haemodynamic deterioration until causal inferences are possible.

UNASSIGNED: Oxytocin is routinely administered after delivery for prophylaxis and treatment of postpartum hemorrhage, but it is associated with considerable cardiovascular side-effects. Carbetocin, a synthetic oxytocin analogue, has a myometrial contraction effect of 60 min when given IV, compared with 16 min for oxytocin.
UNASSIGNED: To investigate whether there are differences in cardiovascular effects between oxytocin and carbetocin up to 1 h after treatment.
UNASSIGNED: Sixty-one healthy pregnant women undergoing elective cesarean section in spinal anesthesia were randomized to receive an IV bolus of either five units (8.3 µg) of oxytocin or 100 µg of carbetocin after delivery of the baby. Heart rate (HR), mean arterial blood pressure, ECG ST index, oxygen saturation (SaO2), and photoplethysmographic digital pulse wave analysis variables were recorded before and at 1, 5, 20, and 60 min after drug administration. Vasopressor use, uterine tonus, total bleeding, and need for additional uterotonics were also assessed. Repeated measurement ANOVA was used for statistical analyses.
UNASSIGNED: The drugs had equal vasodilatory and hypotensive effects. Oxytocin, but not carbetocin, caused a decrease in HR at 1 min and a sustained decrease in cardiac left ventricular ejection time. Aggregate vasopressor use was higher in the carbetocin group. Neither drug caused any change in ST index, SaO2, or subjective cardiac symptoms. Uterine tonus, need for additional uterotonics, or total bleeding did not differ significantly between the groups.
UNASSIGNED: Single doses of oxytocin and carbetocin had similar dilatory effects on vascular tonus, where the difference in aggregate vasopressor use can be attributed to a more persistent hypotensive effect of carbetocin. A transient negative chronotropic and sustained negative inotropic effect occurred after oxytocin. Neither drug showed any alarmingly adverse effects. Differences in drug effects may be attributed to differences in oxytocin and vasopressin receptor signaling pathways.

Placenta interception is extremely rare, and herein, we report the case of a 33-year-old woman with placenta interception during cesarean section caused by carbetocin, which was intravenously injected immediately after delivery of the infant to prevent postpartum hemorrhage. There was no sign of placental separation in the third stage of labor. A protuberance with gross subserous blood vessels in the left fundus of the uterus was detected and was misdiagnosed as placental accreta. The patient was transferred to the district referral hospital to manage the protuberance after stitching up the incision. On opening the original incision in the tertiary hospital, the protuberance disappeared, and the placenta was found in the lower segment of the uterus cavity. The intercepted placenta showed a spontaneous resolution from the uterine wall and was removed intact. This case report details the typical presentation of placenta interception to make obstetricians aware of the possibility that carbetocin might lead to this adverse event.