What is the issue?
We set out to look at the effectiveness, risks and side effects of oxytocin given by injection into muscle (intramuscular) compared with injection into a vein (intravenous) to prevent excessive blood loss in the third stage of labour. The third stage of labour is when the placenta separates from the mother’s uterus and is delivered following the birth of the baby.
Previous studies have shown that oxytocin given to a woman during or immediately after the birth of her baby is effective in reducing excessive bleeding after vaginal birth. There is no reliable research to show whether giving oxytocin into a muscle or vein makes any difference to the effectiveness of the oxytocin or the health of the mother and baby.
Why is this important?
Blood loss during the third stage of labour depends on how quickly the placenta separates from the uterus and how well the uterus contracts to close the blood vessels to the placenta.
Most deaths of mothers related to childbirth happen in the first 24 hours after birth, mainly caused by complications of this process resulting in excessive blood loss, also known as 'postpartum haemorrhage'. Excessive bleeding is an important cause of maternal death, particularly in low-income countries, where pregnant women are more likely to be anaemic (have too few red blood cells in their blood).
Oxytocin injected into a vein may sometimes cause serious side effects, such as a sudden drop in blood pressure and an increase in heart rate, particularly when given rapidly in a small amount of solution (undiluted). The method involved in injecting oxytocin into a muscle takes much less time than is needed for injecting it into a vein. It is also more convenient for the provider, requires relatively less skill and thus can be given by providers with limited skills.
What evidence did we find?
We searched for evidence on 7 September 2017 and identified three studies (together including 1306 women) comparing intramuscular versus intravenous administration of oxytocin to women during or immediately after the birth of the baby. Studies were carried out in hospitals in Turkey (two) and Thailand (one) and recruited women having only one baby, at term (not early or late). The methods that the studies used to divide women into treatment groups were not clear, and in all three included studies women and staff would have been aware of which treatment they received. This may have had an impact on results and means we cannot be confident in the evidence.
The included studies did not report several important outcomes. Only one study reported severe blood loss (a litre or more) after birth and showed that there may be little or no difference between giving intramuscular and intravenous oxytocin. None of the women in one study needed surgery to remove their uterus (womb) after either intramuscular or intravenous oxytocin, and in another study two women needed a blood transfusion, one after intramuscular oxytocin and one after intravenous oxytocin. The quality of the evidence was low or very low, so we had very little confidence in the results. The studies did not report other important outcomes, such as death of the mother, low blood pressure, mothers' dissatisfaction with intramuscular or intravenous oxytocin, and number of babies with jaundice (yellowing of the skin). We found little or no clear difference between intramuscular and intravenous oxytocin for blood loss of 500 mL or more, use of additional drugs to reduce bleeding, and the placenta either not being delivered naturally or having to be removed by doctors.
What does this mean?
The findings from the three included studies did not clearly show which method of giving oxytocin was better for the mother or baby and more research is needed to answer this question.
There was only a small number of included studies and our important outcomes did not occur very often, so there was insufficient evidence to decide whether intramuscular or intravenous oxytocin is more effective and safer for women in the third stage of labour.
Very low-quality evidence indicates no clear difference between the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Appropriately designed randomised trials with adequate sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such studies could be large enough to detect clinically important differences in major side effects that have been reported in observational studies and should also consider the acceptability of the intervention to mothers and providers as important outcomes.
There is general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This is an update of a review first published in 2012.
To determine the comparative effectiveness and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labour after vaginal birth.
We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2017) and reference lists of retrieved studies.
Randomised trials comparing intramuscular with intravenous oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials.
Two review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.
Three studies with 1306 women are included in the review and compared intramuscular versus intravenous oxytocin administered just after the birth of the anterior shoulder or soon after the birth of the baby. Studies were carried out in hospital settings in Turkey and Thailand and recruited women with singleton, term pregnancies. Overall, the included studies were at moderate risk of bias: none of the studies provided clear information on allocation concealment or attempted to blind staff or women. For GRADE outcomes the quality of the evidence was very low, with downgrading due to study design limitations and imprecision of effect estimates.
Only one study reported severe postpartum haemorrhage (blood loss 1000 mL or more) and showed no clear difference between the intramuscular and intravenous oxytocin groups (risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.04; 256 women; very low-quality evidence). No woman required hysterectomy in either group in one study (no estimable data, very low-quality evidence), and in another study one woman in each group received a blood transfusion (RR 1.00, 95% CI 0.06 to 15.82; 256 women; very low-quality evidence). Other important outcomes (maternal death, hypotension, maternal dissatisfaction with the intervention and neonatal jaundice) were not reported by any of the included studies. There were no clear differences between groups for other prespecified secondary outcomes reported (postpartum haemorrhage 500 mL or more, use of additional uterotonics, retained placenta or manual removal of the placenta).