Carbetocin versus oxytocin for prevention of postpartum hemorrhage in patients with severe preeclampsia: a double-blind randomized controlled trial

ObjectiveIn patients with severe preeclampsia there is an increased risk of postpartum hemorrhage, but the hemodynamic changes associated with severe preeclampsia make the management of any kind of bleeding particularly troublesome. There are many pharmacological options for the management of postpartum hemorrhage, oxytocin being the first line of treatment. There is as yet no evidence about the safety and efficacy of using carbetocin, an oxytocin agonist, in these patients. We aimed to compare oxytocin with carbetocin for the routine prevention of postpartum hemorrhage in patients with severe preeclampsiaMethodsWe performed a prospective double-blind randomized controlled trial in 60 women with severe preeclampsia, recruited between July and September 2010. The women were randomized to receive either oxytocin or carbetocin during the third stage of labour The primary outcome measure was postpartum hemorrhage requiring additional uterotonics, and the secondary outcome measures were the difference in hemoglobin levels between groups, the development of oliguria, and hemodynamic status (mean arterial pressure and heart rate) after administration of the drug.ResultsCarbetocin was as effective as oxytocin in the prevention of postpartum hemorrhage in women with severe preeclampsia. Carbetocin had a safety profile similar to that of oxytocin, and it was not associated with the development of oliguria or hypertension in this cohortConclusionsCarbetocin is an appropriate alternative to oxytocin for the prevention of postpartum hemorrhage in women with severe preeclampsia. Considering that it appears not to have a major hemodynamic effect in women with severe preeclampsia and that it uses a lower volume per dose than oxytocin, it should be considered a valid option in the management of the third stage of labour in women with hypertensive disorders of pregnancy.     

Rectal misoprostol versus intravenous oxytocin for the prevention of postpartum hemorrhage after vaginal delivery

OBJECTIVE: To compare rectally administered misoprostol to intravenously administered oxytocin for the management of third-stage labor. STUDY DESIGN: Subjects were randomized to receive two, 200-microg misoprostol tablets rectally (study medication) plus 2 mL saline in Ringer's lactate intravenously or two lactose tablets rectally plus 20 units oxytocin in Ringer's lactate intravenously (control medication). Blood loss was determined by estimation, measurement, and change in hematocrit values from admission to postpartum day 1. Subjects were excluded if cesarean delivery was required. RESULTS: A total of 325 women underwent analysis. By estimation, 21% of subjects and 15% of controls had postpartum hemorrhage (P =.17). By using measured blood loss, we determined that 70 of 154 (46%) study subjects and 61 of 161 (38%) control subjects had postpartum hemorrhage (P =.17). For 36 (23%) misoprostol subjects and 18 (11%) oxytocin subjects at least one additional agent was required to control bleeding (P =.004). CONCLUSION: Rectal misoprostol (400 microg) was no more effective than intravenous oxytocin in preventing postpartum hemorrhage.     

Carbetocin versus oxytocin for the prevention of postpartum hemorrhage: A meta-analysis of randomized controlled trials in cesarean deliveries

Objective

Postpartum hemorrhage remains the leading cause of maternal mortality in developing countries and a significant proportion of these cases are attributable to uterine atony. In contrast to the advances made in the treatment of postpartum hemorrhage, there has been few novel prophylactic agents. This study was undertaken to analyze the effectiveness of carbetocin compared to oxytocin for the prevention of postpartum hemorrhage, in the context of cesarean deliveries.

Intravenous carbetocin versus intravenous oxytocin for preventing atonic postpartum hemorrhage after normal vaginal delivery in high-risk singleton pregnancies: a triple-blind randomized controlled trial

Purpose

To compare the effectiveness of intravenous carbetocin to that of intravenous oxytocin for prevention of atonic postpartum hemorrhage (PPH) after vaginal delivery in high-risk singleton pregnancies.

Methods

This triple-blind randomized controlled trial included singleton pregnant women who delivered at Siriraj Hospital between August 2016 and January 2017 and who were 20 years or older, had a gestational age of at least 34 weeks, had a vaginal delivery, and had at least one risk factor for atonic postpartum hemorrhage. Immediately after vaginal delivery, participants were randomly assigned to receive either 5 U of oxytocin or 100 mcg of carbetocin intravenously. Postpartum blood loss was measured objectively in mL using a postpartum drape with a calibrated bag.

Results

A total of 174 and 176 participants constituted the oxytocin and carbetocin groups, respectively. The baseline characteristics were comparable between the groups. The carbetocin group had less postpartum blood loss (146.7?±?90.4 vs. 195.1?±?146.2 mL; p?<?0.01), a lower incidence of atonic PPH (0 vs. 6.3%; p?<?0.01), less usage of additional uterotonic drugs (9.1 vs. 27.6%; p?<?0.01), and a lower incidence of postpartum anemia (Hb?≤?10 g/dL) (9.1 vs. 18.4%; p?<?0.05) than the oxytocin group. No significant differences regarding side effects were evident between the groups.

Conclusions

Intravenous carbetocin is more effective than intravenous oxytocin for the prevention of atonic PPH among singleton pregnancies with at least one risk factor for PPH.

Clinical trial registration

TCTR20160715004.

     

Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women

Objective: To compare effectiveness and tolerability of carbetocin versus oxytocin in prevention of postpartum hemorrhage (PPH) after vaginal delivery.

Methods: A prospective double-blinded randomized study conducted on 200 pregnant women randomized into two groups: Group 1 (100 women) received single 100?μg IM dose of carbetocin and Group 2 received of 5?IU oxytocin IM. Both groups received their drug after fetal and before placental delivery.

Results: There was a statistically significant difference between the two study groups regarding amount of bleeding (337.73?±?118.77 versus 378?±?143.2), occurrence of PPH (4 versus 16%), need for other uterotonics (23 versus 37%) and hemoglobin difference between before and after delivery (0.55?±?0.35 versus 0.96?±?0.62) (all being lower in carbetocin group) and measured hemoglobin 24?h after delivery (being higher in carbetocin group); however, there was no significant difference between the two study groups regarding occurrence of major PPH and the need for blood transfusion. Women in carbetocin group showed a statistically significant lower systolic and diastolic blood pressure immediately after delivery and at 30 and 60?min than women in oxytocin group. There was no significant difference between the two study groups regarding occurrence of nausea, vomiting, flushing, dizziness, headache, shivering, metallic taste, dyspnea, palpitation and itching. Women in carbetocin group experienced tachycardia more than women in oxytocin group.

Conclusions: Carbitocin is a better alternative to traditional oxytocin in prevention of PPH after vaginal delivery with minimal hemodynamic changes and similar side effects.     

A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage

OBJECTIVE: The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage. METHODS: Patients with documented singleton pregnancies were randomly assigned to two groups. The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta. The second received the opposite medication sequence. The study was double blinded. Blood loss was measured by weighing all fluids collected, visual estimation, and serial blood counts. RESULTS: 27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta. Oxytocin given after placenta delivery resulted in lower blood loss (345 vs. 400 ml, p = 0.28), lower collection bag weight (763 vs. 833 g, p = 0.55), lower change in HgB (-1.26 vs. -1.32 g, p = 0.86), lower DeltaHCT (-3.43 vs. -3.64%, p = 0.85), and a shorter third stage of labor duration (8.6 vs. 9.2 min, p = 0.75). The incidence of postpartum hemorrhage, defined as estimated blood loss >500 ml (0 vs. 14.8%) was significantly lowered with oxytocin following placental delivery (p = 0.049). CONCLUSIONS: In our study, postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery.     

Intrauterine cleaning after placental delivery at cesarean section: a randomized controlled trial

Objective: The objective of this study is to evaluate whether omission of intrauterine cleaning increases intraoperative and postoperative complications among women who deliver via cesarean section.

Methods: We randomized 206 women undergoing primary elective cesarean deliveries to intrauterine cleaning or omission of cleaning. Postpartum endomyometritis rates across groups were the primary outcome. We also examined secondary outcomes. To detect a 20% difference in infection rate between the cleaned and the non-cleaned groups (two-tailed [alpha]?=?0.05, [beta]?=?0.2), 103 women were required per group. Analysis was by intention-to-treat.

Results: Two hundred and six were randomized as follows: 103 to intrauterine cleaning and 103 to omission of cleaning after placental delivery. There were no statistically significant differences in the rate of endomyometritis between the two groups (2.0% versus 2.9%, RR =0.60; 95% CI 0.40–1.32). There were no statistically significant differences in postpartum hemorrhage rates (5.8% versus 7.7%, RR 0.75; 95% CI 0.6–1.2), hospital readmission rates (2.9 versus 3.8%, RR 0.75; 95% CI 0.5–1.6), time to return of gastrointestinal function, need for repeat surgery, or quantitated blood loss between the two groups.

Conclusions: Our randomized controlled trial provides evidence suggesting that omission of intrauterine cleaning during cesarean deliveries in women at low risk of infection does not increase intraoperative or postoperative complications.     

Efficacy of oxytocin versus carbetocin in prevention of postpartum hemorrhage after cesarean section under general anesthesia: a prospective randomized clinical trial

Objective: To compare the use of carbetocin and oxytocin in the prevention of postpartum hemorrhage after cesarean section.

Methods: The present study was a prospective double-blind randomized controlled clinical trial performed in two university-based hospitals in Tehran, Iran. Two hundred and twenty women with the gestational age of more than 37 weeks, who needed cesarean operation, participated in the study. Patients were assigned to receive either a single 100?μg IV dose of carbetocin or a standard 30-international unit IV infusion of oxytocin during 2?h after delivery of placenta. The primary outcome measures were postpartum hemorrhage requiring additional uterotonic drugs, bleeding volume, and the hemoglobin drops.

Results: There were meaningful differences in carbetocin versus oxytocin group regarding the hemoglobin drops (1.01 versus 2.05, p?=?.01), bleeding volume (430.68?CC versus 552.6?CC, p?p?p?Conclusions: It may be concluded that carbetocin is a good alternative modality to conventional uterotonic agents such as oxytocin for the prevention of postpartum hemorrhage after cesarean sections.

Registration ID in IRCT: NCT02079558     

Utilization of carbetocin for prevention of postpartum hemorrhage after cesarean section: a randomized clinical trial

Purpose  

A randomized study involving pregnant women was conducted to compare the effectiveness of a single intravenous (IV) injection of carbetocin with that of a standard 2-h oxytocin IV infusion with respect to intraoperative blood loss in the prevention of uterine atony after cesarean section (CS). The two treatments also were compared for safety and ability to maintain adequate uterine tone and to reduce the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition.     

Combination of motherwort injection and oxytocin for the prevention of postpartum hemorrhage after cesarean section

Objective: To evaluate the efficacy and safety of motherwort injection combined with oxytocin for preventing postpartum hemorrhage (PPH) after cesarean section (CS).

Methods: From March 2011 and February 2013, a randomized study was conducted on 165 primipara undergoing CS. 83 and 82 cases were placed into the combination of oxytocin and motherwort group and oxytocin group, respectively. Blood loss was calculated and measured during three periods: from placental delivery to the end of CS, from the end of CS to 2?h postpartum and from 2?h postpartum to 24?h postpartum. Vital signs were also measured.

Results: Blood loss in the period from placental delivery to the end of CS was similar (P?=?0.58) in these two arms. The quantity of total blood loss from the end of CS to 2?h postpartum (P?=?0.03) and from 2?h postpartum to 24?h postpartum (P?=?0.01) were significantly reduced in the combination of oxytocin and motherwort group. No significant abnormal vital signs were observed. Mild, transient side effects occurred more often in the combination of oxytocin and motherwort group.

Conclusions: It is efficacious and safe that combination use of motherwort injection and oxytocin could reduce blood loss and prevent PPH after CS.     

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery

Objective: To assess and compare the effectiveness and safety of single IV polus dose of carbetocin, versus IV oxytocin infusion in the prevention of PPH in obese nulliparous women undergoing emergency Cesarean Delivery.

Methods: A double-blinded randomized-controlled trial was conducted on 180 pregnant women with BMI >30. Women were randomized to receive either oxytocin or carbetocin during C.S. The primary outcome measure was major primary PPH >1000?ml within 24?h of delivery as per the definition of PPH by the World Health Organization Secondary outcome measures were hemoglobin and hematocrit changes pre- and post-delivery, use of further ecobolics, uterine tone 2 and 12-h postpartum and adverse effects.

Results: A significant difference in the amount of estimated blood loss or the incidence of primary postpartum haemorrhage (>1000?ml) in both groups. Haemoglobin levels before and 24-h postpartum was similar. None from the carbetocin group versus 71.5% in oxytocin group needed additional utrotonics (p?<?0.01). The uterine contractility was better in the carbetocin group at 2, and 12-h postpartum (p?<?0.05).

Conclusions: A single 100-µg IV carbetocin is more effective than IV oxytocin infusion for maintaining adequate uterine tone and preventing postpartum bleeding in obese nulliparous women undergoing emergency cesarean delivery, both has similar safety profile and minor hemodynamic effect.     

Intravenous carbetocin shot is superior to oxytocin infusion for placental delivery in second trimester abortion: a pilot randomized controlled trial

Objective: To study the efficacy of 100?μg intravenous shot of carbetocin compared to 20?IU oxytocin intravenous infusion to prevent placental retention in second trimester medical termination of pregnancy.

Methods: A double-blinded randomized controlled trial was conducted at Ain Shams University Maternity Hospital from 1 April 2013 to 30 November 2013. A total of 132 women between 14 and 24 weeks gestation indicated for termination were randomized to receive either 20?IU oxytocin infusion (n?=?66) or 100?μg carbetocin shot (n?=?66) after fetal expulsion. Patients were observed for time elapsed between fetal and placental expulsion, presence of placental retention and blood loss.

Results: Third stage was 33.4?±?20.4?min in oxytocin group & 23.1?±?16.8?min in carbetocin group (p?=?0.002). Eight patients (12.1%) in oxytocin group had complete placental retention versus two patients (3.0%) in carbetocin group (p?=?0.05). Eight patients (13.8%) received oxytocin had remnants of placenta compared to four patients (6.2%) received carbetocin (p?=?0.04). Sixteen patients (24.2%) received oxytocin and six patients (9%) received carbetocin needed surgical curettage (p?=?0.04). Third stage blood loss was 87.2?±?33.7?ml in carbetocin and 206.9?±?35.2?ml in oxytocin groups (p?=?0.001).

Conclusion: Carbetocin is superior to oxytocin infusion for management of placental delivery in second trimester abortion.     

A prospective randomized clinical trial comparing two oxytocin induction protocols.

OBJECTIVE: Our objective was to compare the safety and efficacy of two accepted oxytocin induction protocols that differ in oxytocin dose increments. STUDY DESIGN: At the Carolinas Medical Center in Charlotte, North Carolina, 151 women with indications for induction of labor were prospectively randomized into one of two oxytocin induction protocols. Safety and efficacy of the two protocols were analyzed with two-tailed t tests and chi 2. RESULTS: Time from induction to establishment of a regular labor pattern was significantly shorter in the experimental group compared with the traditional group (p = 0.03). However, no significant difference was seen from onset of induction to time of delivery. Incidences of hyperstimulation were not significantly different between the two protocols, but there was a trend toward a higher incidence of fetal heart rate changes in the experimental group (p = 0.08). CONCLUSION: These data suggest that induction with larger dose increments will shorten time to adequate labor without an associated increase in uterine hyperstimulation or poor neonatal outcome. The differences in heart rate changes are concerning and merit further investigation. If confirmed by further studies, an increased risk of cord compression could outweigh the benefit of a faster onset of contractions.     

Rectal misoprostol versus intravenous oxytocin for prevention of postpartum hemorrhage

Objective

To assess the effectiveness of 800 μg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH).

Methods

A total of 514 women in labor were randomized into two groups (257 women in each). Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 μg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously.

Results

Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P = 0.54, P = 0.25, and P = 0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P < 0.001).

Conclusions

Routine use of 800 μg of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings.     

A double-blind, randomized, placebo-controlled trial of misoprostol and routine uterotonics for the prevention of postpartum hemorrhage

Objective

To assess the effects of 400-μg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage.

Methods

A double-blind, placebo-controlled, randomized study was performed. After delivery of the child, eligible women received routine uterotonics and were randomly allocated to receive 400-μg misoprostol or placebo sublingually. The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets.

Results

In total, 672 women received misoprostol and 673 received placebo. The baseline data were similar for both groups. Misoprostol plus routine uterotonics reduced postpartum blood loss, but the effect was not significant for blood loss of at least 500 mL (relative risk [RR] 0.96; 95% confidence interval [CI], 0.63-1.45) or blood loss of at least 1000 mL (RR 0.50; 95% CI, 0.15-1.66). Misoprostol also reduced the need for non-routine oxytocin, manual removal of the placenta, and hysterectomy, but these differences were not significant either. Misoprostol was associated with pyrexia and moderate/severe shivering. There was no death in either group.

Conclusion

Misoprostol plus routine uterotonics resulted in modest reductions of blood loss in the third stage of labor, but the effects did not reach statistical significance. Larger studies are recommended.     

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in infertile women with twin pregnancy undergoing elective cesarean delivery

Objective

To compare the efficacy and safety of carbetocin with those of oxytocin infusion in women with twin pregnancy undergoing elective cesarean delivery.