A randomized clinical trial comparing oral misoprostol with synthetic oxytocin or syntometrine in the third stage of labour. A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. WHO multicentre randomised trial of misoprostol in the management of the third stage of labour. Is rectal misoprostol really effective in the treatment of third stage of labor? A randomized controlled trial. Rectal misoprostol versus oxytocin in the management of the third stage of labour. Comparison of labor induction with misoprostol vs. oxytocin/prostaglandin E2 in term pregnancy. The routine use of oxytocin after oral misoprostol for labour induction in women with an unfavourable cervix is not of benefit. Randomized controlled trial of rectal misoprostol versus oxytocin in third stage management. Vaginal misoprostol versus concentrated oxytocin and vaginal PGE2 for second-trimester labor induction.
This is a multicentre, blocked, randomized trial to compare the efficacy of oral misoprostol 400 microg with current injectable uterotonic agents (oxytocin/ Syntometrine) used prophylactically in the third stage of labour. Main outcome measures were blood loss, use of a second uterotonic agent and difference in haemoglobin level from antepartum to postpartum. Data analysis from 863 women showed a statistically significant increase in both the mean blood loss (p < 0.001) and the rate of postpartum haemorrhage > 500 mL, (RR 2.72: 95% C1 1.73-4.27) in the misoprostol group compared to the oxytocin/Syntometrine group. The use of a second uterotonic agent was higher in the misoprostol group (RR 2.89: 95% Cl 2.00-4.18) as well as a greater decrease in postpartum haemoglobin (p = 0.015). Oral misoprostol 400 microg is significantly less effective than the traditional intramuscular uterotonic agents currently used and therefore cannot be considered as a viable option to these agents in the management of the third stage of labour. Post partum hemorrhage is a major cause of maternal death, particularly in developing countries, and most cases are due to an atonic uterus. Hemorrhage can occur despite active management of the third stage of labor. Presently, misoprostol (Cytotec, Searle Pharmaceuticals) is the only thermostable uterotonic agent potentially available which would be economically beneficial for developing countries where refrigeration of drugs poses a problem. The objective of the study was to compare intra-muscular Syntometrine (Sandoz Pharmaceuticals) (ampoule=5 iu oxytocin and 500 mcg ergometrine maleate) plus Syntocinon (Sandoz Pharmceuticals) (10 iu oxytocin diluted in 500 ml normal saline) intravenous infusion versus 800 mcg misoprostol per rectum for treatment of primary post partum hemorrhage in a developing country.
                Randomized single blinded two-center study, set in both a township and teaching hospital in South Africa. Sixty-four women with primary post partum hemorrhage due to an atonic uterus were recruited. The primary outcome measure was whether the hemorrhage ceased within 20 minutes of administering the first line treatment, once hemorrhage was clinically recognized.
                There was a 28.1% difference between the misoprostol arm and the Syntometrine and Syntocinon arm (p=0.01). This result had a greater than 80% power. Misoprostol performed better.
                800 mcg misoprostol per rectum is effective at treating primary post partum hemorrhage. 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. The purpose of this study was to compare misoprostol 600 microg intrarectally with conventional oxytocics in the treatment of third stage of labor.
                In a controlled trial, 1606 women were randomly grouped to receive (1) oxytocin 10 IU plus rectal misoprostol, (2) rectal misoprostol, (3) oxytocin 10 IU, and (4) oxytocin 10 IU plus methylergometrine. The main outcome measures were the incidence of postpartum hemorrhage and a drop in hemoglobin concentration from before delivery to 24 hours after delivery.
                The incidence of postpartum hemorrhage was 9.8% in the group that received only rectal misoprostol therapy compared with 3.5% in the group that received oxytocin and methylergometrine therapy (P =.001). There were no significant differences among the 4 groups with regard to a drop in hemoglobin concentrations. Significantly more women needed additional oxytocin in the group that received only rectal misoprostol therapy, when compared with the group that received oxytocin and methylergometrine therapy (8.3% vs 2.2%; P <.001). The primary outcome measures were similar in the group that received only rectal misoprostol therapy and the group that received only oxytocin therapy.
                Rectal misoprostol is significantly less effective than oxytocin plus methylergometrine for the prevention of postpartum hemorrhage. To compare the effect of rectal misoprostol with intramuscular oxytocin in the routine management of the third stage in a rural developing country.
                A randomized controlled trial was performed at two district hospitals in Ghana, West Africa. Four hundred fifty women in advanced labour were enrolled. The only exclusion criterion was a known medical contraindication to prostaglandin administration. Women were randomized to receive rectal misoprostol 800 microg or intramuscular oxytocin 10 IU with delivery of the anterior shoulder. The main outcome measure was change in hemoglobin concentration from before to after delivery. Secondary outcomes included the need for additional uterotonics, estimated blood loss, transfusion, and medication side effects.
                Demographic characteristics were similar in each treatment group. There was no significant difference between treatment groups in change in hemoglobin (misoprostol 1.19 g/dL and oxytocin 1.16 g/dL; relative difference 2.6%; 95% confidence intervals [CI]-16.8% to 19.4%; P = 0.80). The only significant secondary outcome was shivering, which was more common in the misoprostol group (misoprostol 7.5% vs. oxytocin 0.9%; relative risk 8.0; 95% CI 1.86-34.36; P = 0.001).
                Rectal misoprostol 800 microg is as effective as 10 IU intramuscular oxytocin in minimizing blood loss in the third stage of labour. Rectal misoprostol has a lower incidence of side effects than the equivalent oral dose. This confirms the utility of misoprostol as a safe and effective uterotonic for use in the rural and remote areas of developing nations where other pharmacologic agents may be less feasible. To compare the efficacy and safety of intravaginal and oral misoprostol vs. oxytocin/prostaglandin E2 (PGE2) gel for third trimester labor induction.
                Two hundred twenty-four pregnant women were randomized to induction of labor either with misoprostol or oxytocin and PGE2 gel. Patients in the misoprostol group (n = 112) received 100 micrograms intravaginal misoprostol followed by 100 micrograms p.o. every 2 h. The oxytocin/PGE2 group consisted of 112 patients who underwent PGE2 cervical instillation 6 h before continuous oxytocin infusion. The perinatal, intrapartum and neonatal characteristics of both groups were determined.
                Induction to active phase of labor was successfully achieved in 96 women (85.7%) in the misoprostol group vs. 86 women (76.8%) in the oxytocin/PGE2 group, but the drug initiation-delivery interval was significantly shorter in the misoprostol group (9.2 +/- 2.4 h) than in the oxytocin/PGE2 group (15.2 +/- 3.2 h, P < 0.001). The incidence of adverse intrapartum outcomes was similar for both methods. Intravaginal misoprostol 100 micrograms followed by a single oral dose of 100 micrograms misoprostol safely produced labor and a vaginal delivery in 70% of patients. More than three tablets were required in only 10% of patients. There was a higher prevalence of cesarean section for failed induction in the oxytocin/PGE2 group than in the misoprostol group (13.4 vs. 6.3%, P < 0.001). The neonatal outcomes of both groups were also similar.
                Misoprostol is significantly more effective for labor induction than oxytocin/PGE2 gel. The maternal intrapartum and neonatal outcomes were the same for both induction regimens. From a clinical and perinatal perspective, misoprostol is an acceptable choice for labor induction. Induction of labour with misoprostol is often augmented with oxytocin with the possible consequence of uterine hypercontractility. It is important to determine whether the use of oxytocin in this circumstance has benefit as well as risk.
                To compare two regimens for labour induction in women with an unfavourable cervix: oral misoprostol vs. oral misoprostol routinely followed by oxytocin.
                A prospective randomised trial in which 200 women with an unfavourable cervix received either oral misoprostol 25 microg every 3 h (group 1, n = 100) or two such doses routinely followed by oxytocin (group 2, n = 100). Outcomes included change in Bishop score, induction delivery interval, oxytocin requirement, contraction abnormalities, mode of delivery and neonatal outcome.
                The improvement in Bishop score with two misoprostol doses in all 200 women was highly significant (2.9 +/- 1.5 to 6.6 +/- 1.9, P < 0.0001). The induction delivery interval, Caesarean delivery rate, vaginal delivery rate within 24 h, contraction abnormalities and neonatal outcome were similar in both groups. Contraction abnormalities were remarkably low with either regimen (1%). Routine addition of oxytocin 3 h after the second misoprostol dose (group 2) resulted in the maximum oxytocin dose (64 mU/min) being given to more women (66% in group 2; 36% in group 1).
                There was no benefit of routine addition of oxytocin after two doses of misoprostol. Reduced oxytocin requirement was observed when it was added only if needed. Both regimens achieved 85-87% vaginal deliveries with low incidence of hypercontractility. To compare rectal misoprostol with oxytocin for routine management of the third stage of labour.
                A total of 240 parturient women were randomized, at three University of Toronto teaching hospitals, to receive either rectal misoprostol (400 microg) after delivery of the infant or parenteral oxytocin (5 units i.v. or 10 units i.m.) with the delivery of the anterior shoulder, when possible, or 5 units i.v. or i.m after the delivery of the placenta. The primary outcome measure was change in hemoglobin (Delta[Hgb]) from admission in early labour to day one postpartum.
                The labour ward of three University of Toronto teaching hospitals: St. Michael's, Toronto General, and Mount Sinai.
                Labouring women either nulliparous or multiparous with no known risk for excessive third stage blood loss; vertex presentation; no previous Caesarean delivery; induced, spontaneous, or augmented labour.
                No difference in Delta[Hgb] was observed between the two groups; the Delta[Hgb] in the oxytocin and misoprostol groups were 1.43 g/L (95% confidence interval [CI], 1.2-1.6 g/L) and 1.59 g/L (95% CI, 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.
                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. To compare the efficacy, side effects, and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostaglandin (PGE(2)) for second-trimester labor induction.
                One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were randomly assigned to receive either vaginal misoprostol 600 microg 1x, 400 microg every 4 hours 5x (misoprostol group, n = 60) or escalating-dose concentrated oxytocin infusions (277-1,667 mU/min) plus vaginal PGE(2) 10 mg every 6 hours 4x (oxytocin group, n = 66). Both groups received concurrent extra-amniotic saline infusion for cervical ripening. Women who failed their assigned regimen received 20 mg of PGE(2) suppositories every 4 hours until delivery. Analysis was by intent to treat.
                Demographic characteristics were similar between study groups. Median induction-to-delivery interval was significantly shorter in the misoprostol group (12 hours) than in the oxytocin group (17 hours; P <.001). There was a higher induction success rate at 24 hours in the misoprostol group (95%) than in the oxytocin group (85%; P =.06), although this difference did not reach statistical significance. The incidence of live birth (25% versus 17%), chorioamnionitis (5% versus 2%), and postpartum hemorrhage greater than 500 mL (3% versus 3%) were similar between the misoprostol and oxytocin groups, respectively. Diarrhea (2% versus 11%; P =.04), nausea/emesis (25% versus 42%; P =.04), and retained placenta requiring curettage (2% versus 15%; P =.008) were significantly less common in the misoprostol group when compared with the oxytocin group, respectively. Isolated intrapartum fever, however, was more frequent in the misoprostol group (67%) than in the oxytocin group (21%; P <.001).
                Compared with concentrated oxytocin plus low-dose vaginal PGE(2), high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals, fewer side effects, a lower incidence of retained placenta, and comparable incidence of live birth.
There is insufficient evidence to show that the addition of misoprostol is superior to the combination of oxytocin and ergometrine alone for the treatment of primary PPH. Large multi-centre, double-blind, randomised controlled trials are required to identify the best drug combinations, route, and dose of uterotonics for the treatment of primary PPH. Further work is required to assess the best way of managing women who fail to respond to uterotonics therapy.