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American Journal of Obstetrics &... Feb 2023Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide, with uterine atony estimated to account for 70% to 80% of cases, thereby... (Review)
Review
Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide, with uterine atony estimated to account for 70% to 80% of cases, thereby remaining the single most common cause. Pharmacotherapy remains the first-line preventative therapy for postpartum hemorrhage. These therapies may be single (oxytocin, carbetocin, methylergonovine, ergometrine, misoprostol, prostaglandin analogs, or tranexamic acid) or combination therapies, acting in an additive, infra-additive, or synergistic fashion to prevent postpartum hemorrhage. Evidence is strong for the use of oxytocin, the first-line uterotonic agent in the United States for prevention of postpartum hemorrhage. Although carbetocin, a long-acting analog of oxytocin, is not yet available for use in the United States, it is likely the most effective single pharmacologic therapy for prevention of postpartum hemorrhage and need for additional uterotonics. Use of second-line uterotonics such as methylergonovine, misoprostol, and carboprost in combination with oxytocin has an additive or synergistic effect and a greater risk reduction for postpartum hemorrhage prevention compared with oxytocin alone. Therefore, combined therapy rather than oxytocin alone should be advised for preventing postpartum hemorrhage. Tranexamic acid has been found to be both effective and safe for decreasing maternal mortality in women with postpartum hemorrhage, and prophylactic use of tranexamic acid may decrease the need for packed red blood cell transfusions and/or uterotonics. The WOMAN-2 Trial, designed to assess if tranexamic acid prevents postpartum hemorrhage in women with moderate to severe anemia undergoing vaginal delivery, is currently recruiting participants. The additive, infra-additive, or synergistic action of oxytocin in combination with other second-line therapies deserves further study.
Topics: Pregnancy; Female; Humans; Oxytocin; Postpartum Hemorrhage; Misoprostol; Oxytocics; Methylergonovine; Tranexamic Acid
PubMed: 36028160
DOI: 10.1016/j.ajogmf.2022.100731 -
BMC Pregnancy and Childbirth Oct 2011Rates of labour induction are increasing. We conducted this systematic review to assess the evidence supporting use of each method of labour induction. (Review)
Review
BACKGROUND
Rates of labour induction are increasing. We conducted this systematic review to assess the evidence supporting use of each method of labour induction.
METHODS
We listed methods of labour induction then reviewed the evidence supporting each. We searched MEDLINE and the Cochrane Library between 1980 and November 2010 using multiple terms and combinations, including labor, induced/or induction of labor, prostaglandin or prostaglandins, misoprostol, Cytotec, 16,16,-dimethylprostaglandin E2 or E2, dinoprostone; Prepidil, Cervidil, Dinoprost, Carboprost or hemabate; prostin, oxytocin, misoprostol, membrane sweeping or membrane stripping, amniotomy, balloon catheter or Foley catheter, hygroscopic dilators, laminaria, dilapan, saline injection, nipple stimulation, intercourse, acupuncture, castor oil, herbs. We performed a best evidence review of the literature supporting each method. We identified 2048 abstracts and reviewed 283 full text articles. We preferentially included high quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised or quasi-randomised trials.
RESULTS
We included 46 full text articles. We assigned a quality rating to each included article and a strength of evidence rating to each body of literature. Prostaglandin E2 (PGE2) and vaginal misoprostol were more effective than oxytocin in bringing about vaginal delivery within 24 hours but were associated with more uterine hyperstimulation. Mechanical methods reduced uterine hyperstimulation compared with PGE2 and misoprostol, but increased maternal and neonatal infectious morbidity compared with other methods. Membrane sweeping reduced post-term gestations. Most included studies were too small to evaluate risk for rare adverse outcomes.
CONCLUSIONS
Research is needed to determine benefits and harms of many induction methods.
Topics: Administration, Intravaginal; Dinoprostone; Female; Humans; Infusions, Intravenous; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy; Randomized Controlled Trials as Topic; Time Factors
PubMed: 22032440
DOI: 10.1186/1471-2393-11-84 -
The Cochrane Database of Systematic... Feb 2019Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. This is an update of a review last published in 2015.
OBJECTIVES
To compare the effects of active versus expectant management of the third stage of labour on severe primary postpartum haemorrhage (PPH) and other maternal and infant outcomes.To compare the effects of variations in the packages of active and expectant management of the third stage of labour on severe primary PPH and other maternal and infant outcomes.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World health Organization International Clinical Trials Registry Platform (ICTRP), on 22 January 2018, and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. Cluster-randomised trials were eligible for inclusion, but none were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias, carried out data extraction and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included eight studies, involving analysis of data from 8892 women. The studies were all undertaken in hospitals, seven in higher-income countries and one in a lower-income country. Four studies compared active versus expectant management, and four compared active versus a mixture of managements. We used a random-effects model in the analyses because of clinical heterogeneity. Of the eight studies included, we considered three studies as having low risk of bias in the main aspects of sequence generation, allocation concealment and completeness of data collection. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below.The evidence suggested that, for women at mixed levels of risk of bleeding, it is uncertain whether active management reduces the average risk of maternal severe primary PPH (more than 1000 mL) at time of birth (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, 3 studies, 4636 women, I = 60%; GRADE: very low quality). For incidence of maternal haemoglobin (Hb) less than 9 g/dL following birth, active management of the third stage may reduce the number of women with anaemia after birth (average RR 0.50, 95% CI 0.30 to 0.83, 2 studies, 1572 women; GRADE: low quality). We also found that active management of the third stage may make little or no difference to the number of babies admitted to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, 2 studies, 3207 infants; GRADE: low quality). It is uncertain whether active management of the third stage reduces the number of babies with jaundice requiring treatment (RR 0.96, 95% CI 0.55 to 1.68, 2 studies, 3142 infants, I = 66%; GRADE: very low quality). There were no data on our other primary outcomes of very severe PPH at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management reduces mean maternal blood loss at birth and probably reduces the rate of primary blood loss greater than 500 mL, and the use of therapeutic uterotonics. Active management also probably reduces the mean birthweight of the baby, reflecting the lower blood volume from interference with placental transfusion. In addition, it may reduce the need for maternal blood transfusion. However, active management may increase maternal diastolic blood pressure, vomiting after birth, afterpains, use of analgesia from birth up to discharge from the labour ward, and more women returning to hospital with bleeding (outcome not pre-specified).In the comparison of women at low risk of excessive bleeding, there were similar findings, except it was uncertain whether there was a difference identified between groups for severe primary PPH (average RR 0.31, 95% CI 0.05 to 2.17; 2 studies, 2941 women, I = 71%), maternal Hb less than 9 g/dL at 24 to 72 hours (average RR 0.17, 95% CI 0.02 to 1.47; 1 study, 193 women) or the need for neonatal admission (average RR 1.02, 95% CI 0.55 to 1.88; 1 study, 1512 women). In this group, active management may make little difference to the rate of neonatal jaundice requiring phototherapy (average RR 1.31, 95% CI 0.78 to 2.18; 1 study, 1447 women).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, for example, omitting ergot and deferring cord clamping, but we have no direct evidence of this here.
AUTHORS' CONCLUSIONS
Although the data appeared to show that active management reduced the risk of severe primary PPH greater than 1000 mL at the time of birth, we are uncertain of this finding because of the very low-quality evidence. Active management may reduce the incidence of maternal anaemia (Hb less than 9 g/dL) following birth, but harms such as postnatal hypertension, pain and return to hospital due to bleeding were identified.In women at low risk of excessive bleeding, it is uncertain whether there was a difference between active and expectant management for severe PPH or maternal Hb less than 9 g/dL (at 24 to 72 hours). Women could be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries.It must be emphasised that this review includes only a small number of studies with relatively small numbers of participants, and the quality of evidence for primary outcomes is low or very low.
Topics: Birth Weight; Constriction; Delivery, Obstetric; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Labor Stage, Third; Oxytocics; Placenta; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 30754073
DOI: 10.1002/14651858.CD007412.pub5 -
American Journal of Translational... 2021To investigate the clinical value of carboprost tromethamine injection combined with modified B-lynch suture and carboprost methylate suppositories in the treatment of...
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 ( < 0.05). There were markedly improved clinical indices in Groups A, B and C, showing statistical significance ( < 0.05). There were statistically significant differences in hemostatic failure rate, hysterectomy, postoperative abdominal pain and puerperal infection between Groups A and B ( < 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 ( < 0.05), showing statistical significance ( < 0.05). There were statistically significant differences in blood oxygen saturation and pulse among the three groups before surgery and 2 h after surgery ( < 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.
PubMed: 34377258
DOI: No ID Found -
Assessment of carboprost tromethamine for reducing hemorrhage in laparoscopic intramural myomectomy.Experimental and Therapeutic Medicine Sep 2015The 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...
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 (χ=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.
PubMed: 26622459
DOI: 10.3892/etm.2015.2649 -
Ginekologia Polska 2023Carboprost plays an important role in managing refractory uterine atony and severe postpartum hemorrhage. However, it is associated with challenging adverse reactions.... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Humans; Pregnancy; Female; Sufentanil; Cesarean Section; Carboprost; Anesthesia, Epidural; Anesthesia, Spinal; Vomiting; Nausea; Double-Blind Method
PubMed: 35419799
DOI: 10.5603/GP.a2021.0262 -
Frontiers in Pharmacology 2020Carboprost may induce adverse reactions when used to treat postpartum hemorrhage. We aimed to explore the effects of intravenous infusion of low-dose remifentanil to...
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 51.4%, < 0.01); and the incidence of nausea, chest congestion, facial flushing, and hypertension were significantly lower in group R than in group C (all < 0.01). Furthermore, the patients' comfort scores were significantly higher in group R than in group C (8.0 ± 1.8 3.6 ± 2.1, < 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).
PubMed: 32695003
DOI: 10.3389/fphar.2020.00980 -
BMJ Clinical Evidence Apr 2011Loss of more than 500 mL of blood following childbirth is usually caused by failure of the uterus to contract fully after delivery of the placenta, and occurs in over... (Review)
Review
INTRODUCTION
Loss of more than 500 mL of blood following childbirth is usually caused by failure of the uterus to contract fully after delivery of the placenta, and occurs in over 10% of deliveries, with a 1% mortality rate worldwide. Other causes of postpartum haemorrhage include retained placental tissue, lacerations to the genital tract, and coagulation disorders. Uterine atony is more likely in women who have had a general anaesthetic or oxytocin, an over-distended uterus, a prolonged or precipitous labour, or who are of high parity.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug interventions and of drug interventions to prevent primary postpartum haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: active management of the third stage of labour, carboprost injection, controlled cord traction, ergot compounds (ergometrine/methylergotamine), immediate breastfeeding, misoprostol (oral, rectal, sublingual, or vaginal), oxytocin, oxytocin plus ergometrine combinations, prostaglandin E2 compounds, and uterine massage.
Topics: Administration, Oral; Carboprost; Female; Humans; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Postpartum Period
PubMed: 21463537
DOI: No ID Found -
Experimental and Therapeutic Medicine Jan 2014The 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...
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.
PubMed: 24348762
DOI: 10.3892/etm.2013.1379 -
Computational and Mathematical Methods... 2022Carboprost tromethamine injection has a high safety factor in clinical application and has a good effect on uterine smooth muscle and vasoconstriction. Carboprost... (Randomized Controlled Trial)
Randomized Controlled Trial
Cohort Study Summary of the Effects of Carboprost Tromethamine Combined with Oxytocin on Infant Outcome, Postpartum Hemorrhage and Uterine Involution of Parturients Undergoing Cesarean Section.
BACKGROUND
Carboprost tromethamine injection has a high safety factor in clinical application and has a good effect on uterine smooth muscle and vasoconstriction. Carboprost aminobutyriol combined with oxytocin may be beneficial to infant outcome and uterine involution after cesarean section.
OBJECTIVE
To investigate the effects of carboprost tromethamine combined with oxytocin on infant outcome, postpartum hemorrhage, and uterine involution in parturients undergoing cesarean section.
METHODS
A total of 120 parturients undergone cesarean section in our hospital from February 2019 to April 2021 were selected as the object of study. The parturients were randomly divided into control group ( = 60) and research group ( = 60). The control group was treated with oxytocin, and the research group was treated with carboprost aminobutyriol combined with oxytocin. The amount of maternal bleeding, uterine floor decline index, the end of lochia, poor rate of uterine involution, infant outcome, and the incidence of adverse drug reactions were compared between the two groups.
RESULTS
The amount of bleeding in the research group was significantly lower than that in the control group ( < 0.05). The position of the last uterine floor and the index of uterine floor downward movement in the research group were significantly higher than those in the control group ( < 0.05). The disappearance time of bloody lochia and serous lochia in the research group was significantly shorter than that in the control group ( < 0.05). The end time of lochia in the research group was higher than that in the control group, and the rate of uterine involution in the research group was lower than that in the control group ( < 0.05). The neonatal weight and Apgar score in the research group were higher than those in the control group, and the hospitalization rate of neonatal ICU in the research group was significantly lower than that in the control group. The incidence of adverse reactions in the research group was significantly lower than that in the control group ( < 0.05).
CONCLUSION
Carboprost aminobutyriol combined with carbestatin can effectively prevent the occurrence of bleeding after cesarean section, improve uterine involution, and improve neonatal birth quality, which is worth popularizing.
Topics: Carboprost; Cesarean Section; Cohort Studies; Drug Combinations; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome; Tromethamine
PubMed: 36060654
DOI: 10.1155/2022/2233138