Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour. The Salford Third Stage Trial. Oxytocin plus ergometrine versus oxytocin alone in the active management of the third stage of labor. A placebo-controlled trial of oral ergometrine to reduce postpartum hemorrhage. Abu Dhabi third stage trial: oxytocin versus Syntometrine in the active management of the third stage of labour. Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial. Routine oxytocin in the third stage of labour: a placebo controlled randomised trial. Intraumbilical veinous injection oxytocin in the active management of third stage of labour. WHO multicentre randomised trial of misoprostol in the management of the third stage of labour. A double-blind placebo controlled randomised trial of misoprostol and oxytocin in the management of the third stage of labour. Active versus expectant management of third stage of labour: the Hinchingbrooke randomised controlled trial. The misoprostol third stage of labour study: a randomised controlled comparison between orally administered misoprostol and standard management.
To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour.
                Double blind, randomised controlled trial.
                Two metropolitan teaching hospitals in Perth, Western Australia.
                All women who expected a vaginal birth during the period of the trial. Informed consent was obtained.
                Postpartum haemorrhage, nausea, vomiting, and increased blood pressure.
                3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure.
                There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose-response for oxytocin may be warranted. To compare oxytocin plus ergometrine against oxytocin alone, when administered as part of the active management of the 3rd stage of labor, in terms of postpartum hemorrhage and manual removal of the placenta.
                A double-blind, randomized controlled trial.
                A university teaching hospital: Hope Hospital, Salford.
                All women delivering in the hospital over the period of the trial, except those for whom a cesarean section was planned, or who had significant hypertension or cardiac disease.
                Syntometrine (5 units of oxytocin with 0.5 mg of ergometrine) versus 5 units of Syntocinon (oxytocin), both given by intramuscular injection with delivery of the anterior shoulder.
                Postpartum blood loss, the length of the 3rd stage of labor, and the need for manual removal of the placenta.
                Four hundred sixty-one women were recruited, 230 allocated to ergometrine plus oxytocin and 231 to oxytocin alone. The duration of the 3rd stage of labor in each group was similar (difference in means 0.2 mins; 95% confidence interval [CI], -1.0 to 1.5) and the need for manual removal of the placenta (odds ratio [OR] 1.21; 95% CI, 0.37 to 4.00). There was less postpartum blood loss in the oxytocin plus ergometrine group, reflected in the lower incidence of primary postpartum hemorrhage (> 500 mL) (OR 0.37; 95% CI, 0.16 to 0.85).
                Judged on the basis of this trial alone, oxytocin plus ergometrine is more effective than oxytocin alone in the prevention of postpartum hemorrhage. However, evidence from other trials shows that the ergometrine component not uncommonly has side effects of nausea, vomiting, and raised blood pressure. The implications for practice therefore depend on the relative weights placed on these competing risks by women and clinicians. Further research is needed to quantify these along with research into possible differential effects on longer-term outcomes and into the implications of a higher dose of oxytocin. Active management with oral ergometrine 0.4 mg was compared with expectant management for the control of blood loss in the third stage of labor in women at low risk of postpartum hemorrhage (PPH).
                A three-arms randomized trial in which 0.4 mg ergometrine (2 tablets of 0.2 mg) was set off against placebo, both groups allowing comparison with a standard oxytocin regimen of 5 IU. Women at low risk for PPH. Of 367 parturients, 146 were randomised to ergometrine 0.4 mg, 143 to placebo and 78 to intramuscular oxytocin in a 2:2:1 design.
                Compared with placebo, ergometrine reduced blood loss with 5% (-5%; Confidence interval: -20% to +13%). Oxytocin reduced blood loss with 9% (-9%; Confidence interval: -26% to +12%) versus placebo.
                Oral ergometrine has too little effect on blood loss after childbirth in order to be a good alternative to parenteral prophylactic management. To compare the effect of oxytocin and Syntometrine when used as part of active management of third stage of labour on postpartum haemorrhage, hypertension, nausea/vomiting and retained placenta.
                A randomised double blind trial was conducted in the Obstetric Unit of Corniche Hospital, Abu Dhabi in the United Arab Emirates. Between 1 January 1991 and 30 June 1991, 2040 women were randomly allocated either to the oxytocin (n = 1017) or the Syntometrine (n = 1023) group. Twelve patients had to be excluded from the trial (oxytocin, 5; Syntometrine, 7) after randomisation because they no longer fulfilled the inclusion criteria. All women in the trial received either oxytocin 10 units or Syntometrine 1 ml (oxytocin 5 units+ergometrine (ergonovine) 0.5 mg) by intramuscular injection with delivery of the anterior shoulder of the baby. Relative risk with 95% confidence intervals was calculated for each variable.
                Oxytocin (10 units) alone was as effective as Syntometrine (1 ml) in preventing post-partum haemorrhage without an increase in the incidence of retained placenta. Median blood loss was similar in both groups. The incidences of nausea, vomiting and headache were significantly lower in the oxytocin group, as was the occurrence of a mean rise in diastolic and systolic blood pressures of 20 and 30 mmHg or more, respectively.
                Prophylactic administration of oxytocin 10 U in the third stage of labour, as part of active management, reduces the incidence of maternal nausea, vomiting, headache and rise in blood pressure than does Syntometrine 1 ml without adversely affecting the rate of post partum haemorrhage. To assess the effectiveness of 600 microg oral misoprostol on postpartum haemorrhage (PPH) and postpartum anaemia in a low income country home birth situation.
                Double blind randomised controlled trial.
                Twenty-six villages in rural Gambia with 52 traditional birth attendants (TBAs).
                One thousand, two hundred and twenty-nine women delivering at home under the guidance of a trained TBA.
                Active management of the third stage of labour using three 200-microg misoprostol tablets and placebo or four 0.5-mg ergometrine tablets (standard treatment) and placebo. Tablets were taken orally immediately after delivery.
                Measured blood loss, postpartum haemoglobin (Hb), difference between Hb at the last antenatal care visit and three to five days postpartum.
                The misoprostol group experienced lower incidence of measured blood loss > or =500 mL and postpartum Hb <8 g/dL, but the differences were not statistically significant. The reduction in postpartum (compared with pre-delivery) Hb > or = 2 g/dL was 16.4% with misoprostol and 21.2% with ergometrine [relative risk 0.77; 95% confidence interval (CI) 0.60-0.98; P= 0.02]. Shivering was significantly more common with misoprostol, while vomiting was more common with ergometrine. Only transient side effects were observed.
                Six hundred micrograms of oral misoprostol is a promising drug to prevent life-threatening PPH in this setting. To compare intravenous oxytocin administration (Partocon 10 IU) with saline solution in the management of postpartum haemorrhage in the third stage of labour.
                A double-blind, randomised controlled trial involving 1000 parturients with singleton fetuses in cephalic presentation and undergoing vaginal delivery, randomly allocated to treatment with oxytocin (n = 513) or 0.9% saline solution (n = 487).
                Labour ward at a central county hospital.
                Mean blood loss (total, and before and after placenta delivery); frequencies of blood loss > 800 mL, need of additional oxytocic treatment, postpartum haemoglobin < 10 g/dL; and duration of postpartum hospitalisation.
                As compared with saline solution, oxytocin administration was associated with significant reduction in mean total blood loss (407 versus 527 mL), and in frequencies of postpartum haemorrhage > 800 mL (8.8% versus 5.2%), additional treatment with metylergometrine (7.8% versus 13.8%), and postpartum Hb < 10 g/dL (9.7% versus 15.2%), and a nonsignificant increase in the frequency of manual placenta removal (3.5% versus 2.3%). There was no group difference in the mean duration of postpartum hospitalisation (4.6 versus 4.5 days, respectively).
                Administration of intravenous oxytocin in the third stage of labour is associated with an approximately 22% reduction in mean blood loss, and approximately 40% reductions in frequencies of postpartum haemorrhage (> 500 mL or > 800 mL) and of postpartum haemoglobin < 10 g/dL. Identification of risk groups for oxytocin treatment does not seem worthwhile. Oxytocin is a cheap atoxic drug and should be given routinely after vaginal delivery. To determine the role of intraumbilical vein oxytocin reducing blood loss during and after one hour of delivery of placenta and its efficacy in reducing the frequency of retained placenta.
                Randomized controlled trial.
                Combined Military Hospital, Multan, from June 2002 to October 2002.
                Five hundred parturient women with low risk singleton term pregnancy were enrolled in the study. Two hundred and fifty women each were included in the study and control group after randomization. The patients and health care providers both were blinded to the intervention. Primary outcome measures were kept as duration and amount of blood loss in third stage of labour. Secondary outcome measures included incidence of retained placenta, abdominal need for additional utero-tonics, frequency of postpartum pain, nausea and vomiting, fever, need for blood transfusion, establishment of breast feeding and total duration of hospital stay.
                Women in study group who received intraumbilical vein syntocinon lost 234.03 ml of blood while the control group lost 276.51 ml (p=0.001). Mean duration of third stage was 2.59 minutes in the study group and 7.67 minutes in the control group (p<0.001). The frequency of retained placenta was 1.2%, which involved only the control group. Abdominal pain was experienced by study group but the difference was not found statistically significant. Nausea and vomiting was more in study group (p=0.001). No discernible difference was found in length of hospital stay, the need for blood transfusion, fever and establishment of breast-feeding in both groups.
                The addition of intraumbilical vein syntocinon 10 units resulted in marked reduction in amount of blood loss, duration of third stage and incidence of retained placenta in comparison to intravenous 5 IU oxytocin+0.5 mg ergometrine alone. Postpartum haemorrhage is a leading cause of maternal morbidity and mortality. Active management of the third stage of labour, including use of a uterotonic agent, has been shown to reduce blood loss. Misoprostol (a prostaglandin E1 analogue) has been suggested for this purpose because it has strong uterotonic effects, can be given orally, is inexpensive, and does not need refrigeration for storage. We did a multicentre, double-blind, randomised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour.
                In hospitals in Argentina, China, Egypt, Ireland, Nigeria, South Africa, Switzerland, Thailand, and Vietnam, we randomly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly, according to routine practice, plus corresponding identical placebos. The medications were administered immediately after delivery as part of the active management of the third stage of labour. The primary outcomes were measured postpartum blood loss of 1000 mL or more, and the use of additional uterotonics without an unacceptable level of side-effects. We chose an upper limit of a 35% increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence, which was assessed by the confidence interval of the relative risk. Analysis was by intention to treat.
                9264 women were assigned misoprostol and 9266 oxytocin. 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded. 366 (4%) of women on misoprostol had a measured blood loss of 1000 mL or more, compared with 263 (3%) of those on oxytocin (relative risk 1.39 [95% CI 1.19-1.63], p<0.0001). 1398 (15%) women in the misoprostol group and 1002 (11%) in the oxytocin group required additional uterotonics (1.40 [1.29-1.51], p<0.0001). Misoprostol use was also associated with a significantly higher incidence of shivering (3.48 [3.15-3.84]) and raised body temperature (7.17 [5.67-9.07]) in the first hour after delivery.
                10 IU oxytocin (intravenous or intramuscular) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital settings where active management is the norm. To compare oral misoprostol 400 microg with intramuscular oxytocin 10 IU in the routine management of the third stage.
                Double-blind placebo controlled trial.
                Main referral hospital and its associated polyclinics in Accra, Ghana.
                Four hundred and one low risk women, in the second stage of labour with anticipated vaginal delivery, who entered labour spontaneously.
                After delivery of the anterior shoulder of the baby, the women were randomised to receive either: 1. misoprostol 400 microg powder in water orally and 1 mL normal saline intramuscular injection (placebo); or 2. powdered cellulose in water orally (placebo) and 1 mL oxytocin 10 IU intramuscular injection.
                Change in haemoglobin concentration from before delivery to 12 hours postpartum. Secondary outcomes included need for additional oxytocics, blood loss > 500 mL and > 1,000 mL, operative intervention for postpartum haemorrhage, and side effects, including nausea, vomiting, diarrhoea, shivering and elevated temperature.
                Demographic characteristics were similar. There was no significant difference in change in haemoglobin concentration between the two groups (0.60 g/dL for misoprostol and 0.55 g/dL for oxytocin; relative difference 9.6%; 95% CI 20.5-39.6%; P = 0.54). There were no significant differences in secondary outcomes with the exception of shivering, which occurred more frequently in the misoprostol group (22.2% vs 5.7%; relative risk 4.73; 95% CI 2.31-9.68; P < 0.0001).
                In low risk women oral misoprostol appears to be as effective in minimising blood loss in the third stage of labour as intramuscular oxytocin. Shivering was noted more frequently with misoprostol use, but no other side effects were noted. Misoprostol has great potential for use in the third stage of labour especially in developing countries. This study tested the hypotheses that active management of the third stage of labour lowers the rates of primary postpartum haemorrhage (PPH) and longer-term consequences compared with expectant management, in a setting where both managements are commonly practised, and that this effect is not mediated by maternal posture.
                1512 women judged to be at low risk of PPH (blood loss >500 mL) were randomly assigned active management of the third stage (prophylactic oxytocic within 2 min of baby's birth, immediate cutting and clamping of the cord, delivery of placenta by controlled cord traction or maternal effort) or expectant management (no prophylactic oxytocic, no cord clamping until pulsation ceased, delivery of placenta by maternal effort). Women were also randomly assigned upright or supine posture. Analyses were by intention to treat.
                The rate of PPH was significantly lower with active than with expectant management (51 [6.8%] of 748 vs 126 [16.5%] of 764; relative risk 2.42 [95% CI 1.78-3.30], p<0.0001). Posture had no effect on this risk (upright 92 [12%] of 755 vs supine 85 [11%] of 757). Objective measures of blood loss confirmed the results. There was more vomiting in the active group but no other important differences were detected.
                Active management of the third stage reduces the risk of PPH, whatever the woman's posture, even when midwives are familiar with both approaches. We recommend that clinical guidelines in hospital settings advocate active management (with oxytocin alone). However, decisions about individual care should take into account the weights placed by pregnant women and their caregivers on blood loss compared with an intervention-free third stage. To compare misoprostol with standard oxytocic regimens in the prevention of postpartum haemorrhage.
                Randomised controlled trial.
                Obstetric unit in a large teaching hospital.
                One thousand women randomised to 500 microg misoprostol given orally or to standard oxytocic regimens of oxytocin, oxytocin with ergometrine, or ergometrine.
                Incidence of postpartum haemorrhage and the incidence and severity of side effects.
                Postpartum haemorrhage occurred in 12% of women given misoprostol and in 11% of women given standard oxytocic drugs (relative risk (RR) 1.10, 95% confidence interval (CI) 0.79, 1.55). Blood loss of 1000 mL or more occurred in 2% of women in each group. Nausea, headache, dizziness and tiredness were less frequent with misoprostol (RR (95% CI) 0.71 (0.59, 0.84); 0.53 (0.38, 0.74); 0.73 (0.61, 0.87) and 0.88 (0.83, 0.94) respectively). The main side effects of misoprostol were shivering (RR 1.95, 95% CI 1.69, 2.25) and a rise in temperature (difference in mean rise 0.34 degrees C, 95% CI 0.26, 0.42).
                Oral misoprostol for the prevention of postpartum haemorrhage was comparable to standard oxytocics. Many side effects were less common with misoprostol but shivering and pyrexia were more common. Larger randomised trials are needed before establishing the equivalence between misoprostol and standard oxytocic drugs in the prevention of postpartum haemorrhage.
The use of ergometrine-oxytocin as part of the routine active management of the third stage of labour appears to be associated with a small but statistically significant reduction in the risk of PPH when compared to oxytocin for blood loss of 500 ml or more. No statistically significant difference was observed between the groups for blood loss of 1000 ml or more. A statistically significant difference was observed in the presence of maternal side-effects, including elevation of diastolic blood pressure, vomiting and nausea, associated with ergometrine-oxytocin use compared to oxytocin use. Thus, the advantage of a reduction in the risk of PPH, between 500 and 1000 ml blood loss, needs to be weighed against the adverse side-effects associated with the use of ergometrine-oxytocin.