Choice of oxytocic preparation for routine use in the management of the third stage of labour: an overview of the evidence from controlled trials

Prophylactic use of oxytocics reduces the risk of postpartum haemorrhage by about 40%. The analysis presented in this paper assesses which oxytocic preparation is associated with the least risk of postpartum haemorrhage and examines the relative effects of different preparations on the length of the third stage, the risk of manual removal of the placenta, blood pressure and other side-effects. A mixture of oxytocin and ergometrine (Syntometrine) appears to be the safest and most effective prophylactic of the alternatives which have been compared, but the quality of the evidence is not satisfactory. There is scope for a randomized comparison of Syntometrine with oxytocin to obtain unbiased and more precise estimates of their relative effects on postpartum haemorrhage, blood pressure and unpleasant side-effects.     

A randomized clinical trial comparing oral misoprostol with synthetic oxytocin or syntometrine in the third stage of labour

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.     

A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour

OBJECTIVE: Syntometrine is an effective uterotonic agent used in preventing primary postpartum haemorrhage but has adverse effects including nausea, vomiting, hypertension and coronary artery spasm. Carbetocin is a newly developed long-acting oxytocin analogue that might be used as an uterotonic agent. We compare the efficacy and safety of intramuscular (IM) carbetocin with IM syntometrine in preventing primary postpartum haemorrhage. DESIGN: Prospective, double-blinded, randomised controlled trial. SETTING: Delivery suite of a university-based obstetrics unit. POPULATION: Women with singleton pregnancy achieving vaginal delivery after and throughout 34 weeks. METHODS: Three hundred and twenty-nine eligible women were randomised to receive either a single dose of 100 microgram IM carbetocin or 1 ml IM syntometrine (a mixture of 5 iu oxytocin and 0.5 mg ergometrine) at the end of second stage of labour. MAIN OUTCOME MEASURES: Difference in haemoglobin drop measured 2 days after delivery between the two groups. RESULTS: There was no difference in the drop of haemoglobin concentration within the first 48 hours between the two groups. The incidence of additional oxytocic injections, postpartum haemorrhage (blood loss > or = 500 ml) and retained placenta were also similar. The use of carbetocin was associated with significant lower incidence of nausea (relative risk [RR] 0.18, 95% confidence interval [CI] 0.04-0.78), vomiting (RR 0.1, 95% CI 0.01-0.74), hypertension 30 minutes (0 versus 8 cases, P < 0.01) and 60 minutes (0 versus 6 cases, P < 0.05) after delivery but a higher incidence of maternal tachycardia (RR 1.68, 95% CI 1.03-3.57). CONCLUSIONS: IM carbetocin is as effective as IM syntometrine in preventing primary postpartum haemorrhage after vaginal delivery. It is less likely to induce hypertension and has a low incidence of adverse effect. It should be considered as a good alternative to conventional uterotonic agents used in managing the third stage of labour.     

A Randomized Controlled Study of Prostaglandin 15-Methyl F2 alpha Compared With Syntometrine for Prophylactic Use in the Third Stage of Labour

Summary: A randomized controlled study of 112 women with singleton pregnancies at term, and no antenatal complications, admitted in spontaneous labour were randomized to receive either an intramuscular injection of 0.5 mg of Syntometrine or an intramuscular injection of 125 ug of prostaglandin 15-methyl F2 alpha at delivery of the anterior shoulder of the baby. Blood lost in the first 2 hours, and subsequent 22 hours postdelivery were collected separately and measured by colourimetric measurement of haemoglobin content. Other parameters in the third stage were measured, including need for transfusion of blood or blood products, length of the third stage, and change in haemoglobin concentration before and 24 hours after delivery. The incidence of side-effects with administration of either prostaglandin 15-methyl F2 alpha or Syntometrine were documented. The prophylactic use of intramuscular prostaglandin 15-methyl F2 alpha (Carboprost) in the active management of the third stage of labour gave similar results to prophylactic intramuscular Syntometrine in terms of length of the third stage of labour, incidence of postpartum haemorrhage and total blood loss in the first 2 hours and subsequent 22 hours after delivery. However it has the disadvantage of higher cost, as well as statistically significant increase in the incidence of profuse and frequent diarrhoea. Based on these results intramuscular injection of prostaglandin 15-methyl F2 alpha offers no advantage over intramuscular Syntometrine for routine prophylactic use to reduce blood loss in the third stage of labour.     

A randomised controlled trial of intramuscular syntometrine and intravenous oxytocin in the management of the third stage of labour

Objective To compare the efficacy and safety of intravenous oxytocin with intramuscular syntometrine in the management of the third stage of labour
Design A prospective randomised trial
Setting A university teaching hospital
Methods A total of 991 women having a singleton pregnancy and vaginal delivery were randomised by a computer-generated number to receive either 1ml syntometrine intramuscularly or 10 units of intravenous Syntocinon after delivery of the anterior shoulder of the fetus
Main outcome measures Blood loss during delivery, rate of postpartum haemorrhage, need for repeated oxytocics, haemoglobin level before and 24 hours after delivery, duration of third stage, need for manual removal of placenta and sides effects including hypertension, nausea, vomiting, headache and chest pain
Results The use of intravenous oxytocin was associated with a reduction in postpartum blood loss (   P < 0.001  ) but there was no difference in the risk of postpartum haemorrhage in the need for repeated oxytocic injections and the drop in peripartum haemoglobin level between the two groups. There was also no difference in the risk of prolonged third stage, or in the need for manual removal of placenta. The use of syntometrine was associated with a higher risk of hypertension (RR 2.39, 95% CI 1.00–5.70). Other side effects were mild in nature with no differences between the two groups
Conclusions There are no important clinical differences in the effectiveness of intramuscular syntometrine and intravenous oxytocin for the prevention of postpartum blood loss. Intravenous oxytocin is less likely to cause hypertension     

A prospective cohort study of oxytocin plus ergometrine compared with oxytocin alone for prevention of postpartum haemorrhage

Objective To determine the safety and efficacy of intramuscular oxytocin plus ergometrine compared to intravenous oxytocin for prevention of postpartum haemorrhage, and the significance of administration at the end of the second stage of labour compared with that after the third stage.
Design A prospective cohort study.
Setting A university affiliated tertiary medical centre.
Participants Two thousand one hundred and eighty–nine women delivering singletons during 40 consecutive weeks.
Main outcome measures Postpartum haemorrhage (> 500 ml), prolonged third stage (> 30 min), retained placenta (>60min), elevated blood pressure (systolic > 150 mmHg, diastolic > 100 mmHg).
Results The rate of postpartum haemorrhage was not significantly different for oxytocinergometrine compared with oxytocin, when administered at the end of the second stage of labour (odds ratio 1.10, 95% confidence interval (CI) 0.75–1.61) or after the third stage (odds ratio 0.95, 95% CI 0.68–1.34). The patients receiving oxytocics at the end of the second stage of labour had significantly lower rates of postparturn haemorrhage, for both oxytocinergometrine (odds ratio 0.69, 95% CI 0.49–0.98) and oxytocin (odds ratio 0.60, 95% CI 0.41–0.87), compared with those treated after the third stage.
Conclusion Administration of oxytocin alone is as effective as the use of oxytocin plus ergometrine in the prevention of postpartum haemorrhage, but associated with a significantly lower rate of unpleasant maternal side effects. Oxytocics administered after delivery of the fetal head compared with after the placental expulsion are associated with a significantly lower rate of postpartum haemorrhage.     

Routine oxytocin in the third stage of labour: a placebo controlled randomised trial

Objective To compare intravenous oxytocin administration (Partocon® 10 IU) with saline solution in the management of postpartum haemorrhage in the third stage of labour.
Design 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).
Setting Labour ward at a central county hospital.
Main outcome measures 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.
Results 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 15.2%), 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).
Conclusions 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.     

Postpartum haemorrhage--a continuing problem

The factors responsible for postpartum haemorrhage (PPH) in singleton vaginal deliveries, not complicated by a retained placenta, were identified by comparing labour characteristics in 86 women who had a PPH (blood loss greater than 500 ml) with 351 women whose blood loss at delivery was less than 350 ml. Primiparity, induction of labour by amniotomy/oxytocin, forceps delivery, long first and second stages, oxytocin compared with syntometrine (oxytocin plus ergometrine maleate), as a prophylactic oxytocic, were identified as significant risk factors. Epidural analgesia contributed indirectly to an increase in the risk of postpartum haemorrhage. The changes in labour ward practice over the last 20 years have resulted in the re-emergence of PPH as a significant problem.     

Postpartum haemorrhage—a continuing problem

Summary. The factors responsible for postpartum haemorrhage (PPH) in singleton vaginal deliveries, not complicated by a retained placenta, were identified by comparing labour characteristics in 86 women who had a PPH (blood loss > 500 ml) with 351 women whose blood loss at delivery was < 350 ml. Primiparity, induction of labour by amniotomy/ oxytocin, forceps delivery, long first and second stages, oxytocin com-pared with syntometrine (oxytocin plus ergometrine maleate), as a prophylactic oxytocic, were identified as significant risk factors. Epi-dural analgesia contributed indirectly to an increase in the risk of postpartum haemorrhage. The changes in labour ward practice over the last 20 years have resulted in the re-emergence of PPH as a significant problem.     

A double-blind placebo controlled randomised trial of misoprostol and oxytocin in the management of the third stage of labour

Objective To compare oral misoprostol 400 μg with intramuscular oxytocin 10 IU in the routine management of the third stage.
Design Double-blind placebo controlled trial.
Setting Main referral hospital and its associated polyclinics in Accra, Ghana.
Population Four hundred and one low risk women, in the second stage of labour with anticipated vaginal delivery, who entered labour spontaneously.
Methods After delivery of the anterior shoulder of the baby, the women were randomised to receive either: 1. misoprostol 400 μg 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.
Main outcome measures Change in haemoglobin concentration from before delivery to 12 hours postpartum. Secondary outcomes included need for additional oxytocics, blood loss > 500 mL and > 1000 mL, operative intervention for postpartum haemorrhage, and side effects, including nausea, vomiting, diarrhoea, shivering and elevated temperature.
Results 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  ).
Conclusions 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.     

The misoprostol third stage of labour study: a randomised controlled comparison between orally administered misoprostol and standard management

Objective To compare misoprostol with standard oxytocic regimens in the prevention of postpartum haemorrhage.
Design Randomised controlled trial.
Setting Obstetric unit in a large teaching hospital.
Methods One thousand women randomised to 500 μg misoprostol given orally or to standard oxytocic regimens of oxytocin, oxytocin with ergometrine, or ergometrine.
Main outcome measures Incidence of postpartum haemorrhage and the incidence and severity of side effects.
Results 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°C, 95% CI 0.26, 0.42).
Conclusion 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.     

Prevention of postpartum haemorrhage with the oxytocin analogue carbetocin

Postpartum haemorrhage is the leading cause of maternal mortality worldwide: 67–80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a half-life approximately 4–10 times longer than that reported for oxytocin. It combines the safety and tolerability profile of oxytocin with the sustained uterotonic activity of injectable ergot alkaloids. Furthermore, carbetocin can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. Data from three randomised controlled trials in caesarean delivery and a meta-analysis indicate that carbetocin significantly reduces the need for additional uterotonic agents or uterine massage to prevent excessive bleeding compared with placebo or oxytocin. The risk of headache, tremor, hypotension, flushing, nausea, abdominal pain, pruritus and feeling of warmth was similar in women who received carbetocin or oxytocin. The findings from two more recent double-blind randomised trials and one retrospective study suggest that carbetocin may also represent a good alternative to conventional uterotonic agents for prevention of postpartum haemorrhage after vaginal deliveries. A reduced need for additional uterotonics was observed with carbetocin vs. oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. In these studies of vaginal deliveries, carbetocin was associated with a low incidence of adverse effects and demonstrated a better tolerability profile than syntometrine. Carbetocin had a long duration of action compared with intravenous oxytocin alone and a better cardiovascular side effect profile compared with syntometrine. In addition to being an effective treatment for the prevention of postpartum haemorrhage following caesarean delivery, carbetocin may also become the drug of choice for postpartum haemorrhage prevention after vaginal delivery in high-risk women and those who suffer from hypertensive disorders in pregnancy. Preeclampsia is still a contraindication to the administration of carbetocin in the EU, and further studies would be required to assess the cardiovascular effects of carbetocin before it can be advocated for routine use in preeclamptic patients. Further research is required to assess whether prophylactic carbetocin is superior to conventional uterotonic agents following vaginal delivery in low-risk women.     

Blood loss after caesarean section: depending on the management of oxytocin application?

Purpose

Oxytocin donation in caesarean section is used to reduce postpartum blood loss. Cardiovascular side effects such as tachycardia, hypotension and decreased cardiac output are known and seem to depend on the way of application, whereas the blood loss is said to be similar. We aimed to examine that extent of haemorrhage in our own patients.

Method

In July 2011, the perioperative oxytocin management was changed and the postpartum was oxytocin bolus abolished. Retrospectively, we reviewed the pre- and postpartum haemoglobin in all women who had undergone caesarean section in the year 2011 at the University Hospital of Schleswig-Holstein, Campus Luebeck.

Results

We found a significantly higher blood loss in those patients who were treated without oxytocin bolus but only with oxytocin infusion (?10.5 vs. ?9?g/dl).

Conclusion

We recommend to do further studies to clarify the advantage and contraindications of using oxytocin boluses and until to use the oxytocin bolus again in healthy patients but to avoid it in patients with cardiovascular risk.     

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.     

Prospective study of intramuscular ergometrine compared with intramuscular oxytocin for prevention of postpartum hemorrhage

AIM: To compare the efficacy and safety of intramuscular oxytocin with intramuscular ergometrine in the management of postpartum hemorrhage during the third stage of labor. METHODS: Women who had been pregnant for more than 35 weeks and delivered cephalic singletons vaginally without predelivery administration of oxytocics were included. The cases considered to be at high risk were excluded, such as those who had uterine fibroids, a previous cesarean section, previous postpartum hemorrhage, or severe anemia. Five units of oxytocin or 0.2 mg of methylergometrine were administered intramuscularly immediately after delivery of the baby. RESULTS: Compared with intramuscular ergometrine, the use of intramuscular oxytocin was associated with a significant reduction in mean total postpartum blood loss (288.16 g vs 354.42 g, P = 0.004), frequency of postpartum hemorrhage (> or=500 mL: 10.9% vs 20.32%, relative risk [RR] = 0.54, 95% confidence interval [CI] = 0.32-0.91), and need for therapeutic oxytocics (5.13% vs 12.3%, RR = 0.42, 95% CI = 0.19-0.91). There were no differences between the groups in terms of the mean duration of the third stage, the mean level of hemoglobin on the second postpartum day, and the frequency of postpartum hemorrhage (> or =1000 mL), or manual removal of placenta. Few side-effects were found, with no significant differences between the groups. CONCLUSIONS: The routine use of intramuscular oxytocin is more effective than the use of intramuscular ergometrine for prevention of postpartum hemorrhage in the third stage of labor.     

Use of oxytocin to prevent haemorrhage at caesarean section—A survey of practice in the United Kingdom

Objective

To establish the views and current practice of obstetricians and anaesthetists with regard to the use of oxytocin to prevent haemorrhage at caesarean section.

Study design

A national survey of all lead consultant obstetricians and anaesthetists for the labour ward in the United Kingdom. A postal questionnaire was sent to all clinicians with one subsequent reminder to non-responders. The use of oxytocin bolus and infusion, perceived side effects of intravenous oxytocin, estimated blood loss at caesarean section, and willingness to participate in a future clinical trial were explored.

Results

The response rate was 84% (365 respondents). A slow bolus of 5 IU oxytocin was the preferred approach of obstetricians and anaesthetists (153, 86% and 171, 92%, respectively). Oxytocin infusions were used routinely by 72 clinicians (20%) with selective use for particular clinical circumstances by 289 (80%). Most clinicians used either 30 IU (158, 43%) or 40 IU (192, 53%) infusions over 4 h, with a total of 38 different regimens. The perceived risk of side effects with an oxytocin infusion was low. Estimated “average” blood loss varied (150–1500 ml) with 56 clinicians (17%) and 93 (28%) reporting a >20% risk of postpartum haemorrhage for elective and emergency caesarean sections, respectively.

Conclusion

There is wide variation in the use of oxytocin at caesarean section reflecting limited research in this area. Excess haemorrhage is considered to occur frequently and the perceived risk of oxytocin bolus and infusion is low. Further research is required addressing the optimal use of oxytocic agents at caesarean section.     

Blood pressure changes when uterine stimulants are used after normal delivery.

Use of an automatic sphygmomanometer showed that intravenous ergometrine given immediately after delivery caused significant elevation of diastolic blood pressure in all 10 normotensive women studied. Blood pressure was also raised in some patients following the use of intramuscular oxytocin and ergometrine (Syntometrine). Uterine stimulants for use after delivery must be chosen with care.     

Carbetocin versus oxytocin after caesarean section: similar efficacy but reduced pain perception in women with high risk of postpartum haemorrhage

Objective: To compare the effectiveness of carbetocin with oxytocin with respect to maintain adequate uterine tone and to reduce the incidence and severity of postpartum haemorrhage. Moreover safety, adverse effects and the need of additional medications were evaluated. Methods: Prospective controlled clinical trial. We compared the effect of a single dose of carbetocin (n?=?55) with oxytocin infusion (n?=?55) in a women population undergoing to elective caesarean section with regional subarachnoid anaesthesia with at least one risk factor for postpartum haemorrhage. Results: The mean ± SD of postoperative pain in the day of surgery in carbetocin group was significantly lower than in oxytocin group and remained significant till the third day after caesarean section. In the day of surgery and the first day after surgery, women of carbetocin group who needed analgesic drugs were significantly lower than women of oxytocin group. The differences of diuresis and of diuretic drugs need were not statistically significant between the two groups. Conclusions: A single carbetocin injection is efficacious and safe on the maintenance of uterine tone and on the limitation of blood losses, in peri- and in postoperative period. In addition, carbetocin was able to reduce pain perception during postoperative days improving quality life of women.     

Carbetocin versus syntometrine for the third stage of labour following vaginal delivery—a double-blind randomised controlled trial

Objective  Prevention of postpartum haemorrhage is essential in the pursuit of improved health care for women. However, limited literature is available for comparing the use of oxytocin agonist carbetocin with syntometrine in women undergoing vaginal deliveries. We aimed to compare intramuscular carbetocin with intramuscular syntometrine for the routine prevention of postpartum haemorrhage in women who deliver vaginally.
Design  Prospective double-blind randomised controlled trial.
Setting  Tertiary referral centre.
Population  Pregnant women with no contraindication for vaginal delivery recruited from January 2005 to April 2008.
Methods  Participants were randomised to receive either syntometrine or carbetocin during the third stage of labour.
Main outcome measures  Primary outcome measure was postpartum haemorrhage requiring additional uterotonics. Secondary outcome measures were the incidence of postpartum haemorrhage (≥500 ml), severe postpartum haemorrhage (≥1000 ml) and adverse effects profile.
Results  Women in the carbetocin group (13.5%) and in the syntometrine group (16.8%) had postpartum haemorrhage requiring additional uterotonics ( P  =   0.384). 1.6% of women in each group had postpartum haemorrhage ( P  =   1.0) and the estimated blood loss during the third stage of labour was similar between the two groups ( P  =   0.294). Women who had syntometrine were four times more likely to experience nausea (RR = 4.2; 95% CI 2.2–7.8) and vomiting (RR = 4.3; 95% CI 1.9–9.5) compared with women who had carbetocin. Tremor, sweating, retching and uterine pain were also more likely in the syntometrine group compared with the carbetocin group ( P  <   0.05).
Conclusions  Carbetocin has an efficacy similar to syntometrine for prevention of postpartum haemorrhage, but is associated with less adverse effects.     

Misoprostol use during the third stage of labor.

OBJECTIVES: To systematically review the efficacy of misoprostol compared with placebo or other uterotonics in preventing maternal morbidity associated with the third stage of labor. METHODS: We identified, retrieved, evaluated, abstracted data, and assessed the quality of all published studies (from January 1996 to May 2002) which assessed misoprostol's efficacy in minimizing uterine blood loss during the third stage of labor. Seventeen studies included 28170 subjects; of these, approximately one-half received misoprostol with the remainder receiving either a placebo or another uterotonic agent. An estimate of the odds ratio (OR) and risk difference for dichotomous outcomes was calculated using a random- and fixed-effects model. Continuous outcomes were pooled using a variance-weighted average of within-study difference in means. RESULTS: In assessing studies comparing misoprostol with placebo, those who received oral misoprostol had a decreased risk of needing additional uterotonics (OR 0.64, 95% confidence interval 0.46, 0.90). Compared with placebo, use of misoprostol was associated with an increased risk for shivering and pyrexia. In contrast, in studies comparing misoprostol with oxytocin, oxytocin was associated with significantly lower rates of postpartum hemorrhage, maternal shivering and pyrexia. In studies comparing misoprostol with Syntometrine, misoprostol was associated with higher rates of the need for additional uterotonic agent as well as shivering. CONCLUSIONS: Misoprostol was inferior to oxytocin and other uterotonics with regard to any of the third stage of labor outcomes assessed. However, when compared to placebo, misoprostol had a decreased risk of needing additional uterotonics. Thus, in less-developed countries where administration of parenteral uterotonic drugs may be problematic, misoprostol represents a reasonable agent for the management of the third stage of labor. Additional randomized clinical trials examining objective outcome measures (i.e. need for blood transfusion or 10% hemoglobin change) may further define benefits and risks of misoprostol use during the third stage of labor.