The Salford Third Stage Trial. Oxytocin plus ergometrine versus oxytocin alone in the active management of the third stage of labor. Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour. Preventing the recurrence of atonic postpartum hemorrhage: a double-blind trial. Abu Dhabi third stage trial: oxytocin versus Syntometrine in the active management of the third stage of labour. A placebo-controlled trial of oral ergometrine to reduce postpartum hemorrhage. Routine oxytocin in the third stage of labour: a placebo controlled randomised trial. The effect of intraumbilical oxytocin on the third stage of labour. A randomized controlled trial of oxytocin administered at the end of the second stage of labor versus oxytocin administered at the end of the third stage of labor in the prevention of postpartum hemorrhage. 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.
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. 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. We conducted a double-blind randomized controlled trial to compare a conventional regimen of oxytocin and ergometrine with administration of the prostaglandin E2 analogue, sulprostone, for prophylaxis of postpartum hemorrhage in high-risk women.
                Women with a history of postpartum hemorrhage > or = 1000 were assigned to two coded prophylactic regimens. Drugs, given respectively at delivery of the anterior shoulder and after delivery of the placenta, were oxytocin and ergometrine in the control group, and sulprostone and placebo in the experimental group. Eighty-one women, 69 of whom actually participated in the trial, were investigated. Both the women and the caregivers were unaware of treatment allocation.
                Although the trial was terminated prematurely there was a slight, but not statistically significant, preference for the sulprostone regimen in terms of blood loss and use of blood transfusion. No serious adverse effects were noted with either of the two regimens.
                Prostaglandins may be more effective for preventing recurrence of severe postpartum hemorrhage than the oxytocin and ergometrine combination, but they do not eliminate the risk entirely. 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. 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 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. The umbilical vein administration of oxytocin in saline was compared with umbilical vein saline alone and the traditional management of the third stage of labour. Seventy-two women were randomized to 3 groups. Group 1 received intraumbilical 20 IU of oxytocin diluted to 40 mL with saline. Group 2 received intraumbilical vein 40 mL of saline while subjects in group 3 were managed according to the standard protocol without any intraumbilical injection. No significant differences were found in terms of the length of the third stage, the blood loss in the third stage and postpartum haematocrit differences among the 3 groups. The administration of diluted oxytocin or saline do not seem to have any superiority to the traditional management of the third stage of labour. The general objective was to determine the incidence of postpartum hemorrhage when oxytocin was administered at the end of the second stage of labor compared to when oxytocin was administered at the end of the third stage. The specific objectives were to determine the mean amount of blood loss, duration of the third stage of labor, need for additional uterotonics and blood transfusion, incidence of hypotension and retained placenta, and mean difference in hemoglobin levels. A randomized controlled trial was conducted in a tertiary care training hospital. 130 women with term, singleton, live pregnancies in cephalic presentation who delivered vaginally were included. Patients were randomly allocated to receive oxytocin after the second stage or after the third stage of labor. Oxytocin was administered as a continuous intravenous infusion. The placenta was delivered by controlled cord traction after placental separation. Blood loss was measured by weight, and the corresponding volume was computed. Relative risk was calculated. Incidence of postpartum hemorrhage, volume of blood loss, duration of the third stage of labor, need for additional uterotonics and blood transfusion, incidence of hypotension and retained placenta, and difference in hemoglobin levels were the main outcome measures. There was a decreased incidence of postpartum hemorrhage (39.66% vs. 48.61%, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.55-1.21) and less amount of blood loss (557.93 ml vs. 636.84 ml, p = 0.352) when oxytocin was administered at the end of the second stage of labor. There was less need for additional uterotonics (12.07% vs. 13.89%, RR = 0.87, 95% CI = 0.35-2.14), and blood transfusion (5.17% vs. 5.56%, RR = 0.87, 95% CI = 0.22-3.99). There was a smaller mean difference in hemoglobin (16.20 g/dl vs. 20.29 g/dl, p = 0.145). Mean duration of the third stage of labor were comparable (7.93 minutes vs. 7.96 minutes, p = 0.863). However, more patients developed hypotension (3.45% vs. 1.39%, RR = 2.48, 95% CI = 0.23-26.70). All results were not statistically significant. There was no incidence of retained placenta. There is a trend towards a reduction of the risk of postpartum hemorrhage when oxytocin is administered at the end of the second stage of labor. This is not accompanied by an increased risk for any morbidity. 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.
                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.
                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).
                In our study, postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery.
                Copyright 2004 S. Karger AG, Basel
Oxytocin appears to be beneficial for the prevention of postpartum haemorrhage. However, there is insufficient information about other outcomes and side-effects hence it is difficult to be confident about the trade-offs for these benefits. There seems little evidence in favour of ergot alkaloids alone compared to either oxytocin alone, or to ergometrine-oxytocin, but the data are sparse. More trials are needed in domiciliary deliveries in developing countries, which shoulder most of the burden of third stage complications.
[Note: The ten citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]