Administration of 400 μg of misoprostol to augment routine active management of the third stage of labor. A randomized controlled trial of prophylactic sublingual misoprostol versus intramuscular methyl-ergometrine versus intramuscular 15-methyl PGF2alpha in active management of third stage of labor. Sublingual compared with oral misoprostol for cervical dilatation prior to vacuum aspiration: a randomized comparison. Sublingual misoprostol before first trimester abortion: a comparative study using two dose regimens. Oral misoprostol for third stage of labor: a randomized placebo-controlled trial. Oral misoprostol in the third stage of labor. WHO multicentre randomised trial of misoprostol in the management of the third stage of labour. A double-blind randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of the third stage of labor. Low-dose sublingual misoprostol versus methylergometrine for active management of the third stage of labor.
To assess the effectiveness and safety of the administration of misoprostol, an orally active prostaglandin, in addition to routine uterotonic therapy as part of the active management of the third stage of labor.
                The present study was a hospital-based, decentralized, multi-center, randomized, placebo-controlled, double-blind trial. We enrolled 1103 women (out of a target sample size of 1180) at 4 hospitals in South Africa, Uganda, and Nigeria. Participants received a sublingual dose of 400 μg of misoprostol or a placebo, in addition to standard active management of the third stage of labor, after vaginal birth.
                The baseline characteristics of the participants were comparable. The difference in the primary outcome of blood loss of 500 mL or more within 1 hour of randomization was not significant between the 2 groups (misoprostol 22/546 [4.0%] versus placebo 35/553 [6.3%]; relative risk, 0.64; 95% confidence interval, 0.38-1.07). Shivering and pyrexia occurred more frequently in the misoprostol group. No maternal deaths occurred.
                The present study did not confirm a beneficial effect of administering 400 μg of misoprostol, in addition to routine uterotonic therapy, during the third stage of labor, but was consistent with other trials showing a cumulative modest benefit. Where routine uterotonics are available for prophylactic use, any potential benefit of misoprostol might not outweigh the likelihood of adverse effects.
                Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. To compare the efficacy and side effects of 0.2 mg methyl-ergometrine IM, 400 microg misoprostol sublingual and 125 microg 15 methyl PGF2alpha IM in active management of third stage of labor.
                Two hundred low risk pregnant women with induced or spontaneous labor were randomized to receive either 400 microg misoprostol sublingually or 0.2 mg methyl-ergometrine intramuscularly or 125 microg 15-methyl PGF2alpha intramuscularly, after the delivery of anterior shoulder of baby. The main outcome measures were: blood loss more than 500 ml, need for additional oxytoxic drug, change in hemoglobin level and side effects due to drugs.
                The median estimated blood loss, blood loss more than 500 ml, need for additional oxytocic drug and change in hemoglobin levels were similar in all three groups. The significant side effects in the misoprostol group were shivering, pyrexia (temperature > 38 degrees C) and vomiting, which were self-limiting. Diarrhea was significantly more in the 15 methyl PGF2alpha group. Three women in methyl-ergometrine group underwent manual removal of placenta. One woman in misoprostol group received blood transfusion.
                Sublingual misoprostol appears to be as effective as intramuscular methyl-ergometrine and intramuscular 15-methyl PGF2alpha in the prevention of postpartum hemorrhage. It can be a good alternative in resource poor setting. The aim of the study was to compare the effect of oral and sublingual administration of misoprostol for cervical priming prior to vacuum aspiration. Thirty-two first-time-pregnant women with 8-12 weeks amenorrhea were randomly assigned to receive 400 microg misoprostol either orally or sublingually 3 h prior to surgery. The degree of baseline dilatation and the cumulative force needed for dilatation of the cervical canal did not differ between the two treatment groups. However, the number of patients in whom a strong force was needed was significantly higher following oral than following sublingual treatment. It was shown that sublingual administration is more effective than oral administration of misoprostol for cervical priming and is associated with less blood loss but a higher frequency of side effects. Various methods have been described for preoperative cervical priming prior to vacuum aspiration (VA) in first trimester pregnancy termination, to facilitate cervical dilatation and shorten the abortion procedure. Recently misoprostol a prostaglandin E1 analogue has been shown to be effective in facilitating cervical dilatation prior to VA. Misoprostol offers several advantages over the other prostagland in analogues including stability at room temperature, ease of administration and minimal side effects.
                To determine the optimal dosage and dosing interval for the use of misoprostol administered sublingually for pre-abortion cervical dilatation.
                This was a prospective randomised study conducted at Comprehensive Rural Health Project, Ballabgarh the rural health centre under Centre for Community Medicine, AIIMS, New Delhi.
                One hundred and twenty pregnant women between 6-11 weeks of gestation opting for voluntary medical termination of pregnancy were (MTP) randomly allocated to either 200 microg or the 400 microg misoprostol group. Vacuum aspiration was performed either two or three hours after administration of sublingual misoprostol. Using Hegar's dilators, degree of cervical dilatation before vacuum aspiration was measured. Other parameters assessed included the amount of additional dilatation required, intra-operative blood loss and associated side effects.
                Statistical analysis was conducted using chisquare, the student's t and the Mann-Whitney U tests to examine the difference between the two groups.
                In the 200 microg misoprostol group 33% achieved a dilatation of > or = 8 mm compared with 71% of women in the 400 microg misoprostol group. The odds ratio was 95.8 (95% CI 10.2-842.9) for 400 microg misoprostol for successful preoperative cervical dilatation of > or = 8 mm. The mean baseline cervical dilatation for 400 microg and 200 microg misoprostol was 8.2 mm and 6.0 mm respectively (P < 0.001). The use of 400 mg misoprostol with an evacuation interval of two hours appears to be the optimal dosage and evacuation interval. Increasing the time interval beyond two hours did not confer any additional advantage on the rate of successful cervical dilatation but was instead associated with an increased incidence of side effects such as preoperative vaginal bleeding, abdominal pain and shivering.
                Our study has shown that Sublingual administration of 400 microg of misoprostol at least two hours before procedure is effective for preoperative cervical dilatation before vacuum aspiration in first trimester pregnancy termination. There is no additional advantages of increasing the dosing interval upto three hours. To investigate whether orally administered misoprostol during the third stage of labor is efficient in reducing postpartum blood loss.
                In a double-masked trial, during vaginal delivery women were randomly assigned to receive a single oral dose of misoprostol (600 microg) or placebo in third stage of labor, immediately after cord clamping. The third stage of labor was managed routinely by early cord clamping and controlled cord traction; oxytocin was administered only if blood loss seemed more than usual. Blood loss was estimated by the delivering physician and differences in hematocrit were measured before and after delivery.
                Mean (+/- standard error of the mean) estimated blood loss (345 +/- 19.5 mL versus 417 +/- 25.9 mL, P = .031) and hematocrit difference (4.5 +/- 0.9% versus 7.9 +/- 1.2%, P = .014) were significantly lower in women who received misoprostol than those who received placebo. Fewer women in the misoprostol group had postpartum hemorrhage (blood loss of at least 500 mL), but that difference was not statistically significant (7% versus 15%, P = .43). Additional oxytocin before or after placental separation was used less often in the misoprostol group (16% versus 38%, P = .047). There were no differences in the length of third stage of labor (8 +/- 0.9 minutes versus 9 +/- 1 minutes, P = .947). There were no differences in pain during third stage of labor, postpartum fever, or diarrhea, but shivering was more frequent in the misoprostol group.
                Oral misoprostol administered in the third stage of labor reduced postpartum blood loss and might be effective in reducing incidence of postpartum hemorrhage. To compare the efficacy of intravenous ergometrine, intramuscular oxytocin, and oral misoprostol in the control of postpartum hemorrhage.
                Mean blood loss, rates of blood loss between 500 and 1000 ml, hematocrit fall greater than 10%, and need for additional oxytocic agents and nature and rates of adverse effects were assessed in this prospective, randomized, controlled study.
                All outcomes were similar in the 3 groups. The main adverse effects in the misoprostol group were temperatures higher than 99 degrees F, which normalized within 2 h and shivering, which was mild and self-limiting.
                Oral misoprostol is as effective as conventional oxytocic agents in preventing postpartum hemorrhage and can be recommended for use in low-resource settings. 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 aim of this study was to compare the efficacy and safety of oral misoprostol 400 mug with intramuscular syntometrine in the management of the third stage of labor.
                This was a double-blind randomized controlled trial conducted in a tertiary care hospital. Three hundred and fifty-five women randomized to receive either oral misoprostol 400 mug or intramuscular syntometrine in the third stage of labor were studied. The change in hemoglobin level from before to 48 h after delivery, use of additional oxytocics and treatment related side effects were the main outcome measures.
                There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss. The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group. There were no differences in the incidence of nausea, headache, diarrhea and pyrexia between the two groups.
                Orally administered misoprostol at a dose of 400 mug is an acceptable alternative in preventing post-partum blood loss, as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects. To compare the efficacy and side-effects of low-dose sublingual misoprostol and i.v. methylergometrine for active management of the third stage of labor.
                The study subjects were three hundred low-risk women with term pregnancy and spontaneous onset of labor. These women received either one (100 microg/tablet) or two tablets of misoprostol (200 microg) sublingually or 1 mL (200 microg) of methylergometrine, i.v. injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were the need for additional oxytocic drugs, blood loss >or=500 mL, change in hemoglobin levels and side-effects.
                Post-partum hemorrhage (>or=500 mL blood loss) did not occur in any of the women, but above-average bleeding occurred in 2.0% of cases in groups I, II (sublingual misoprostol 100 microg and 200 microg respectively) and III (methylergometrine), despite additional oxytocics used in 5.0%, 4.0% and 3.0% cases in groups I, II and III respectively (P>0.05). The change in hemoglobin levels at 24 h post-partum were 0.8%, 0.7% and 0.8% in groups I, II and III respectively (P>0.05).
                A low dose of sublingual misoprostol appears to be as effective as a low dose of i.v. methylergometrine in the prevention of post-partum hemorrhage in low-risk cases. So given the advantages of its stability at room temperature, low cost and easy route of administration, misoprostol appears to be a better choice, and a low dose is enough. However, larger studies in low-risk as well as high-risk cases are needed to advocate routine use of a low dose at the primary level.
Oral or sublingual misoprostol shows promising results when compared with placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of the management of the third stage of labour are used or not. As side-effects are dose-related, research should be directed towards establishing the lowest effective dose for routine use, and the optimal route of administration.
Neither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the management of the third stage of labour especially for low-risk women; however, evidence has been building for the use of oral misoprostol to be effective and safe in areas with low access to facilities and skilled healthcare providers and future research on misoprostol use in the community should focus on implementation issues.