Prevention Of Primary Postpartum Haemorrhage Research Articles

Intramuscular oxytocin versus oxytocin/ergometrine versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: study protocol for a randomised controlled trial (the IMox study)

BackgroundPostpartum haemorrhage remains a major cause of maternal mortality and morbidity worldwide. Active management of the third stage of labour reduces the risk of postpartum haemorrhage. Oxytocin and oxytocin/ergometrine are commonly used in the UK, with oxytocin/ergometrine being more effective at preventing moderate, but not severe, blood loss. Many guidelines specifically recommend using oxytocin for all vaginal births, as it is associated with fewer adverse events. However, a survey conducted by the Southmead Hospital Maternity Research Team revealed that 71.4% of UK obstetric units still routinely use oxytocin/ergometrine. Carbetocin is a newer medication that may be as effective but has fewer side effects. No studies have directly compared all three medications.MethodsThe IMox study aims to determine the most effective, acceptable and cost-effective drug for primary prevention of postpartum haemorrhage following vaginal birth. The IMox study is a prospective, multi-centre, double-blind, randomised trial directly comparing oxytocin, oxytocin/ergometrine and carbetocin given intramuscularly for the prevention of postpartum haemorrhage in the third stage of labour. The primary effectiveness outcome is the use of an additional uterotonic drug. Secondary effectiveness outcomes reflect maternal morbidity and mortality within the immediate postpartum period. Participant questionnaires and subjective reporting of side effects will be used to evaluate maternal acceptability. Maternal quality of life utilities will be collected antenatally, and on days 1 and 14 after birth to enable a cost-effectiveness assessment of each studied drug.Participants will be pregnant women planning a vaginal birth in six hospitals in England. Participants will be approached and invited to provide consent to participate from 20 weeks gestation until in established labour. A complete sample of 5712 participants (1904 per arm) providing data for the primary outcome will allow for a robust determination of efficacy between all three study drugs. Data will be collected until participants are discharged from the hospital and on postnatal days 1 and 14 regardless of location. All analyses will be on a modified intention-to-treat basis, and additionally repeated on a per protocol basis. Data collection commenced in Feburary 2015 and was completed in August 2018.DiscussionThis study is the first to directly compare oxytocin, oxytocin/ergometrine and carbetocin in the same population for the prevention of postpartum haemorrhage following vaginal birth. Furthermore, this study will be the first to directly compute health economic outcomes from such a three-way comparison. This study is limited to using short-term outcomes, and so will not provide evidence for important outcomes such as long-term maternal psychological well-being and time to next conception.Trial registrationClinicalTrials.gov, NCT02216383. Registered on 18 August 2014. EudraCT, 2014-001948-37. Registered on 23 September 2014. ISRCTN, ISRCTN10232550. Retrospectively registered on 6 March 2018).

Tranexamic Acid versus Placebo for Prevention of Primary Postpartum Haemorrhage among High Risk Women Undergoing Caesarean Section in Abakaliki: A Randomized Controlled Trial

Objective: To evaluate the efficacy of tranexamic acid for prevention of postpartum haemorrhage among women undergoing cesarean section who were at high risk of postpartum hemorrhage. Materials and Method: This was a double blind randomized controlled trial conducted at the Alex Ekwueme Federal University Teaching Hospital Abakaliki from January 2016 to December 2017. One hundred and sixty-eight parturients at high risk of postpartum haemorrhage who underwent caesarean section were randomly assigned to receive either tranexamic acid or placebo prior to skin incision. Results: The result of the study showed that the need for additional uterotonic was higher in women in the placebo arm when compared with women in the tranexamic arm of the study (7.4% versus 33.3%, respectively). The incidence of primary post-partum hemorrhage (blood loss > 1000 ml) was significantly lower in the tranexamic acid group compared to placebo group (11.9% versus 50%, respectively, P-value < 0.0001). Conclusion: Intravenous tranexamic acid given prior to skin incision at caesarean section reduced the need for additional uterotonics and incidence of primary postpartum among high risk women.

Prophylactic uterotonics in the prevention of primary postpartum haemorrhage for unplanned out-of-hospital births: a literature review.

Introduction:Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide. Protocols for the use of prophylactic uterotonics in strategy to prevent PPH have been implemented for in-hospital births following recommendation from the National Institute for Health and Care Excellence (NICE). There are currently no guidelines for prophylactic uterotonic use in out-of-hospital (OOH) births by ambulance crews despite inappropriate birthing conditions and difficulties in obtaining a timely response from community midwives. The aim of this article is to review the use of uterotonic drugs used for the prevention of PPH which could be administered in OOH births.Methods:The PubMed and ScienceDirect databases were searched for papers discussing the use of prophylactic uterotonics in the third stage of labour, utilising the MeSH keywords: third stage labour, prophylactic, uterotonic. Primary studies, meta-analyses and systematic reviews published between 1998 and 2018 were eligible for inclusion. A review of the full text of the included papers was undertaken using the Critical Appraisal Skills Programme (CASP) checklists.Results:Of the published articles, 392 were returned, 25 of which met the inclusion criteria. Following assessment of the full text, 11 papers were included for discussion, including a large randomised control trial (WOMAN trial) on the use of tranexamic acid (TXA), which while not a uterotonic drug, was considered a significant drug in the context of PPH management.Conclusions:PPH is a low incidence, but high risk complication of childbirth. While it is possible for paramedics to administer uterotonics during the third stage of labour, there have been no OOH trials with paramedics to explore whether prophylactic use is safe and effective in the OOH births before arrival (BBA) scenario. Further research is required to determine the efficacy of prophylactic uterotonics in reducing PPH within pre-hospital care.

Comparison of the effect of carbetocin versus oxytocin during cesarean section in women with high risk of postpartum hemorrhage

Objectives To compare the hemodynamic effects of oxytocin and carbetocin and to assess the efficacy of these two drugs in terms of blood loss and the additional uterotonic needed in cesarean section in women with high risk of primary postpartum hemorrhage (PPH). Background Prevention of PPH is a major issue owing to its effect on maternal morbidity and mortality. Although oxytocin is the most widely accepted uterotonic agent, carbetocin can be given as an intravenous bolus instead of continuous oxytocin infusion. Patients and methods This is a prospective, randomized controlled study conducted from March 2016 and October 2017 within the Department of Obstetrics and Gynecology in Menoufia University Hospitals. The study included 100 pregnant women with high risk of PPH; women were divided randomly into group A, which received oxytocin infusion of 20 international units, and group B, which received 100 μg carbetocin as an intravenous bolus. Results Regarding the hemodynamic effects, there was a significant lower reduction in blood pressure within the oxytocin group. Significantly more women needed additional uterotonic agents in the oxytocin group. Uterine fundal level was significantly below 2 cm from the umbilical point in carbetocin group. The mean cost in oxytocin group is lower with a highly significant difference. Conclusion Single injection of carbetocin has more safe hemodynamic profile and less need of uterotonics, but the introduction of oxytocin appears to provide improved clinical outcomes along with cost savings.

Efficacy and Safety of Carbetocin in Comparison to Oxytocin for the Prevention of Primary PPH during Caesarean Section: An Open Label Randomized Control Trial

&#x0D; Background: Postpartum hemorrhage (PPH) is a potentially life-threatening complication of both vaginal and caesarean delivery. The most frequent cause of postpartum hemorrhage is uterine atony, when the uterus fails to contract fully after delivery of the placenta. For the prevention of this uterine atony we need an effective uterotonic drug. Till now oxytocin is used for enhancing uterine contraction after delivery. But oxytocin has some limitations like shorter halflife, less contraction time and more side effects, whereas carbetocin has prolonged duration of action which ensures more contraction time and less adverse effects. So, carbetocin considered as a good alternative over oxytocin for the prevention of primary PPH in caesarean section.&#x0D; The Aim of Study: To see the efficacy and safety of carbetocin over oxytocin for the prevention of primary PPH during caesarean section.&#x0D; Patients and Methods: A randomized-controlled trial was conducted in the Institute of Child and Mother Health (ICMH), Dhaka, Bangladesh over a period of nine months from January to September 2016. Ninety-four patients who had got admitted in ICMH undergoing caesarean section at term were randomized into two groups receiving either 10IU oxytocin or 100μg carbetocin, after the operation. Outcome measures such as primary PPH, massive blood loss, need for additional uterotonic drug, additional blood transfusion as well as adverse effects were all documented.&#x0D; Results: This study had shown that carbetocin is superior in comparison to oxytocin for the prevention of primary PPH following caesarean section. Each patient obtained either a single dose of 100 microgram carbetocin intravenously or 10 IU of oxytocin during caesarean section. Massive blood loss occurred in 6.4%patients, blood transfusion needed in 17% patients and additional uterotonic needed for 25.5% patients in oxytocin group but in carbetocin group no massive blood loss occurred, only 2.1% patient needed immediate blood transfusion and no patient was required additional uterotonics. There were no major adverse effects observed in both the groups. No patients had developed PPH in carbetocin group. But 12.8% patients had developed primary PPH in oxytocin group.&#x0D; Conclusion: Carbetocin appears to be an effective new drug than oxytocin for the prevention of primary postpartum hemorrhage in caesarean section.&#x0D; J Bangladesh Coll Phys Surg 2019; 37(1): 19-24&#x0D; &#x0D;

The efficacy of intrauterine misoprostol during cesarean section in prevention of primary PPH, a randomized controlled trial

Background: Postpartum hemorrhage is the leading cause of maternal mortality worldwide.Aim: To compare the incidence of postpartum hemorrhage in women eligible for elective cesarean section (CS) delivery when using intrauterine misoprostol added to oxytocin versus oxytocin alone.Design, Setting, Participants: This parallel randomized controlled trial study was conducted in two institutions in Egypt (Kasralainy and Aljazeerah hospital) 0.300 women eligible for elective CS delivery were enrolled in the study.Interventions: Before randomization, all women received the same preparations. After randomization; in the study group (N = 150), intrauterine misoprostol was used after placental delivery. In the control group (N = 150), the routine oxytocin alone was used.Results: Both groups were comparable (p-value >.05) with regard to the age, BMI, and gestational age as well as hemoglobin and hematocrit levels. The incidence of postpartum hemorrhage was significantly lower (p = .018) in the study group (1.33%) than the control group (6.67%). The absolute risk reduction was 5.3% (CI 95%: 0.8–10.6%) with a relative risk of 0.20 (CI 95%: 0.05–0.90) and number needed to treat (NNT) 19 (CI 95%: 125–9). Moreover, the needs for a blood transfusion, extra uterotonics or additional interventions were significantly lower in the study group than in the control group (p < .05). All the three parameters of blood loss ie the mean blood loss, and the mean reductions of hemoglobin and hematocrit levels were significantly (p-value <.05) lower in the study group (mean and SD) (442.59 and 151.33 mL,0.46 and 0.3 g/dL, and 0.84 and 0.56%), respectively than in the control group (591.01 and 287.97 mL,1.2 and 1.39 g/dL, and 3.47 and 3.52%), respectively. Adverse events were comparable between groups; these were fever, nausea, and vomiting and shivering.Conclusion: Intrauterine misoprostol (400 mg) when added to oxytocin is safe and effective in decreasing the incidence of postpartum hemorrhage (PPH) and reducing the amount of postpartum blood loss in case of elective CS delivery.

Carbetocin in prevention of postpartum hemorrhage: Experience in a tertiary medical center of Taiwan

ObjectiveThe aim of this retrospective observational study was to determine the efficacy of carbetocin in reducing blood loss and primary postpartum hemorrhage (PPH) in vaginal and cesarean deliveries in a tertiary hospital in Taiwan. Materials and methodsEligible gravid women (27–41 weeks) with available data were categorized into those treated prophylactically with and without carbetocin. The primary outcome was blood loss and incidence of primary PPH as measured by intrapartum/intraoperative and postpartum (recovery room) blood loss. ResultsA total of 1069 deliveries were evaluated. Maternal age (∼31 years of age), body mass index (∼27 kg/m2) and parity (∼1.4) were similar among those treated with and without carbetocin for both vaginal and cesarean deliveries. The majority [749/1069 (70.1%)] of deliveries were vaginal; a similar proportion of women undergoing vaginal [221/749 (29.5%)] and cesarean [110/320 (34.4%)] deliveries received prophylactic carbetocin for prevention of PPH. Among vaginal deliveries, there was no significant difference in intrapartum (p = 0.083) or postpartum (p = 0.925) blood loss, or incidence of PPH (p = 0.092) between women with versus without carbetocin prophylaxis. However, there was a significant reduction in the intraoperative and total blood loss among cesarean deliveries with versus without carbetocin prophylaxis (p < 0.001). The incidence of PPH was higher [84/320 (26.3%)] among cesarean than among vaginal deliveries [62/749 (8.3%)], but was significantly lower among cesarean deliveries with [18 (16.36%)] versus without [66 (30.45%); p = 0.003] carbetocin prophylaxis. ConclusionIn Taiwan, prophylactic use of carbetocin resulted in significantly less blood loss and incidence of PPH in cesarean than in vaginal deliveries.

Randomized controlled trial comparing 200μg and 400μg sublingual misoprostol for prevention of primary postpartum hemorrhage.

To compare efficacy and adverse effects of 200μg and 400μg misoprostol for prevention of postpartum hemorrhage (PPH). In a randomized control trial, women with term singleton pregnancies in active labor attending University College Hospital, Ibadan, Nigeria, were enrolled between July 2011 and February 2012. Participants were randomly assigned using random numbers (block size four) to receive 200μg or 400μg sublingual misoprostol after delivery of the anterior shoulder, alongside intravenous oxytocin. Investigators were masked to group assignment, but participants were not. The primary outcomes were blood loss up to 1h after delivery, PPH (blood loss ≥500mL), and adverse effects. Overall, 62 patients were assigned to each group. No significant differences between the 200-μg and 400-μg groups were recorded in mean peripartum blood loss (307±145mL vs 296±151mL; P=0.679) and PPH occurrence (5 [8.1%] vs 6 [9.7%] women; P=0.752). Noticeable adverse effects were reported by 16 (25.8%) women in the 200-μg group and 42 (67.7%) in the 400-μg group (P<0.001). Risk of shivering was significantly lower with 200μg than 400μg (relative risk 0.33, 95% confidence interval 0.19-0.58). Blood loss and PPH occurrence did not differ by misoprostol dose, but a 200-μg dose was associated with a reduction in adverse effects. Pan Africa Clinical Trials Registry: PACTR201505001107182.

Adjunctive rectal misoprostol versus oxytocin infusion for prevention of postpartum hemorrhage in women at risk: A randomized controlled trial

The aim of this study was to evaluate the efficacy of adjunctive rectal misoprostol compared to oxytocin infusion in the prevention of primary postpartum hemorrhage after routine active management of the third stage of labor in women with identifiable risk factors for uterine atony. A double-blind randomized controlled trial was carried out at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. A total of 264 parturients with known risk factors for postpartum hemorrhage were randomized to receive either rectal misoprostol (600 µg; n = 132) or oxytocin infusion (20 IU in 500 mL; n = 132) after routine active management of the third stage of labor. Intrapartum blood loss was measured using a combination of the BRASSS-V calibrated drapes and differential pad weighing. Hematocrit was measured intrapartum and 24 h postpartum. There was no significant difference (P = 0.07) in the mean intrapartum blood loss between the misoprostol (387.28 ± 203.09 mL) and oxytocin (386.73 ± 298.51 mL) groups. There was also no difference in the requirement for additional intervention for uterine atony (P = 0.74). Postpartum hematocrit drop and blood transfusion were, however, significantly less in the misoprostol group. Rectal misoprostol is as effective as oxytocin infusion as an adjunct for prevention of postpartum hemorrhage in women with risk factors for uterine atony and is associated with a lower hematocrit drop and blood transfusion postpartum. However, shivering, pyrexia and vomiting are more frequent with misoprostol, though usually self-limited.

POSTPARTUM HAEMORRHAGE

Objective: To determine the frequency, risk factors and existing practice for the management of massive primary postpartum hemorrhage (PPH). Study design: Retrospective cross-sectional study. Setting: Department of Obstetrics &amp; Gynaecology at Kuwait Teaching Hospital, Peshawar. Materials and methods: this study was performed from June 2008 to June 2010. Women who developed massive primary PPH after admission or were admitted with it, were included in the study. Medical record files of these women were reviewed for maternal mortality and morbidities which included mode of delivery, possible cause of postpartum hemorrhage, supportive medical and surgical intervention. Data was entered in the pre-structured proforma. Estimates of blood loss were made on history, visual parameters and patient’s condition. All the data was analyzed by using statistical computer soft ware SPSS 6. Results: During the study period total number of obstetrical admissions were 2944. Forty nine out of 2769 (1.76%) deliveries, developed massive primary PPH. The highest frequency of massive primary PPH was observed in grand multiparous patients. Uterine atony was the most common cause of the complication. Birth attendants other than doctor and delivery outside the study unit were significantly associated with the adverse outcome in these patients. Seventy five percent patients,(36/49) who had massive PPH, delivered vaginally. High dependency unit (HDU) was required in 12% (6/49) of women. Only one caesarian hysterectomy was done. There was one maternal mortality. Blood transfusions were required in 82% (40/49) of the patients. Conclusions: Postpartum hemorrhage can be a preventable condition if early identification and timely management of this complication and its risk factors is observed. Uterine atony is the leading cause of immediate PPH. The main risk factors for PPH due to uterine atony are high parity, a large fetus, multiple fetuses, hydramnios, or past history of PPH. Determining the frequency, risk factors and management of primary postpartum hemorrhage will help design stepwise protocols for prevention and management of primary PPH in our setup.

Inability to predict postpartum hemorrhage: insights from Egyptian intervention data

BackgroundKnowledge on how well we can predict primary postpartum hemorrhage (PPH) can help policy makers and health providers design current delivery protocols and PPH case management. The purpose of this paper is to identify risk factors and determine predictive probabilities of those risk factors for primary PPH among women expecting singleton vaginal deliveries in Egypt.MethodsFrom a prospective cohort study, 2510 pregnant women were recruited over a six-month period in Egypt in 2004. PPH was defined as blood loss ≥ 500 ml. Measures of blood loss were made every 20 minutes for the first 4 hours after delivery using a calibrated under the buttocks drape. Using all variables available in the patients' charts, we divided them in ante-partum and intra-partum factors. We employed logistic regression to analyze socio-demographic, medical and past obstetric history, and labor and delivery outcomes as potential PPH risk factors. Post-model predicted probabilities were estimated using the identified risk factors.ResultsWe found a total of 93 cases of primary PPH. In multivariate models, ante-partum hemoglobin, history of previous PPH, labor augmentation and prolonged labor were significantly associated with PPH. Post model probability estimates showed that even among women with three or more risk factors, PPH could only be predicted in 10% of the cases.ConclusionsThe predictive probability of ante-partum and intra-partum risk factors for PPH is very low. Prevention of PPH to all women is highly recommended.

A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia

Glanzmann Thrombasthenia (GT) is a rare autosomal recessive disorder which usually manifests as severe mucocutaneous bleeding and is caused by deficiency of the platelet glycoprotein IIb-IIIa. Pregnancy in women with GT presents particular challenges as there is increased risk of both maternal and foetal bleeding. To improve understanding and clarify the optimum management of pregnancy in this disorder, we performed a systematic review of the world literature of pregnancy and GT. This identified three single-centre case series of patients with GT that included brief descriptions of women in pregnancy and 31 detailed case reports of 40 pregnancies in 35 women that resulted in 38 live births. Among the detailed case reports, ante-natal bleeding was described in 50% of pregnancies but was usually mild and occurred at mucocutaneous sites. Primary postpartum haemorrhage (PPH) was reported in 34% of pregnancies and secondary PPH in 24%. PPH was frequently severe and occurred up to 20 days after delivery. There was a wide variation in approach to prevention and treatment of PPH but most women received platelet transfusion, sometimes with additional recombinant FVIIa and anti-fibrinolytics. Maternal alloimmunization against platelet antigens was reported in 73% of pregnancies and was associated with four neonatal deaths. These data emphasize the need for multidisciplinary management of pregnancy in women with GT. Delivery plans should recognize the need for prevention and aggressive treatment of PPH and should minimize foetal bleeding risk in pregnancies complicated by alloimmunization.

Oral misoprostol for the prevention of primary post‐partum hemorrhage during third stage of labor

To assess the effectiveness of oral misoprostol compared with methylergometrine in the prevention of primary post-partum hemorrhage during the third stage of labor. This was a randomized controlled trial of 864 singleton low-risk pregnant women. The outcomes were total blood loss, duration of the third stage of labor and peripartal change in hematocrit. Comparisons were by the chi2-test and Student t-test. Relative risks were calculated for side-effects profile. A P-value of less than 0.05 was statistically significant. The biodata of all the participants were similar. The mean blood loss for the misoprostol and methylergometrine groups was 191.6 +/- 134.5 mL and 246.0 +/- 175.5 mL, respectively (95% CI: -79.3 to -39.5 mL). The mean duration of the third stage of labor was 19.6 +/- 2.4 min and 9.4 +/- 3.3 min in the misoprostol and methylergometrine groups, respectively (95% CI: 9.82-10.58 min). More subjects had blood loss >500 mL, 42 (9.7%) versus 6 (1.4%), and peripartal hematocrit change greater than 10%, 38 (8.8%) versus 5 (1.2%), in the methylergometrine group than in the misoprostol group, respectively. Also, more subjects received additional oxytocic in the methylergometrine group, compared to the misoprostol group (80 [18.5%] versus 33 [7.6%] patients, respectively). Orally administered misoprostol was more effective in reducing blood loss during the third stage of labor than intramuscular methylergometrine. However, there were more subjects in the misoprostol group in whom duration of the third stage of labor was greater than 15 min and who also had manual placental removal than in the methylergometrine group.

Current strategies for the prevention of postpartum haemorrhage in the third stage of labour.

Despite evidence that active management of the third stage of labour reduces the incidence of postpartum haemorrhage, expectant management is still widely practised. Factors accounting for this situation include the desire for a more natural experience of childbirth, the philosophy that active management is unnecessary in low-risk women, and avoidance of the adverse effects of conventional uterotonic agents. This review will evaluate the various strategies currently used for the prevention of primary postpartum haemorrhage. Since publication of the first systematic review comparing active with expectant management in 1988, active management of the third stage using oxytocics has become increasingly adopted. Recent surveys, however, show that there are still wide variations in practice around the world. Recent interest has focused on the use of misoprostol for the prevention of postpartum haemorrhage. Carbetocin, an oxytocin receptor agonist, shows promise but has not been evaluated for use after vaginal births. Active management of the third stage of labour is superior to expectant management in terms of blood loss, postpartum haemorrhage and other serious complications, but is associated with unpleasant side effects and hypertension when ergometrine is included. Intramuscular oxytocin results in fewer side effects. Oral and rectal misoprostol has been extensively assessed and found to be less effective than conventional oxytocics with more side effects. Until alternative regimes of misoprostol are studied in large controlled trials, misoprostol is not recommended for routine use in the third stage of labour. Of the remaining uterotonic agents evaluated, intramuscular carbetocin appears the most promising.

Randomized Controlled Trial of Rectal Misoprostol Versus Oxytocin in Third Stage Management

Objective: To compare rectal misoprostol with oxytocin for routine management of the third stage of labour.Study design: A total of 240 parturient women were randomized, at three University of Toronto teaching hospitals, to receive either rectal misoprostol (400 µg) after delivery of the infant or parenteral oxytocin (5 units IV or 10 units IM) with the delivery of the anterior shoulder, when possible, or 5 units IV or IM after the delivery of the placenta.The primary outcome measure was change in hemoglobin (Δ[Hgb]) from admission in early labour to day one postpartum.Setting: The labour ward of three University of Toronto teaching hospitals: St. Michaels, Toronto General, and Mount Sinai.Population: Labouring women either nulliparous or muciparous with no known risk for excessive third stage blood loss; vertex presentation; no previous Caesarean delivery; induced, spontaneous, or augmented labour.Results: No difference in Δ[Hgb] was observed between the two groups; the Δ[Hgb] in the oxytocin and misoprostol groups were 1.43 g/L (95% confidence interval [Cl], 1.2–1.6 g/L) and 1.59 g/L (95% Cl, 1.4–1.8 g/L) respectively (p = 0.35). Secondary outcome measures (excessive third stage bleeding, duration of third stage of labour, need for manual removal of the placenta or the need for additional oxytocics) did not differ between the two groups.Conclusion: Rectal misoprostol is of equivalent efficacy to parenteral oxytocin for the prevention of primary postpartum hemorrhage. Rectal misoprostol is an appropriate uterotonic agent for routine management of the third stage of labour.

A prospective randomised trial to compare the efficacy and safety of Hemabate and Syntometrine for the prevention of primary postpartum haemorrhage

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2α) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2α and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2α is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2α.