Review finds best uterotonic drug for treatment of postpartum hemorrhage
Delhi: Oxytocin is more effective and has less side-effects than misoprostol for the treatment of postpartum hemorrhage (PPH), suggests a recent Cochrane Review. Misoprostol given with oxytocin does not improve effectiveness and is associated with more side effects.
The researchers further find that there is limited evidence for most uterotonic agents used as first‐line treatment of PPH. There is no evidence for several drugs used currently such as Syntometrine, injectable prostaglandins, and ergometrine.
Postpartum haemorrhage (PPH) defined as excessive bleeding during childbirth is the leading cause of maternal death worldwide. This is caused by failure of uterine contraction. The orld Health Organization (WHO) recommends all women be given uterotonic drugs -- drugs that make the uterus contract more effectively -- to reduce the risk for excessive bleeding. Despite administration of uterotonic agent, some women still experience heavy bleeding that leads to death. In these cases, further administration of uterotonic agents as 'first‐line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first‐line' treatment of PPH.
William R Parry Smith, University of Birmingham, Birmingham, UK, and colleagues aimed to identify the most effective uterotonic agent(s) with the least side‐effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side‐effect profile.
For the purpose, the researchers searched the online databases and included randomised controlled trials or cluster‐randomised trials that compared the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH.
The primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. The review included a total of seven trials, involving 3738 women from 10 countries. All trials were conducted in hospital settings.
Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed‐dose combination) plus oxytocin infusion.
Key findings of the study include:
- Pairwise meta‐analysis of two trials (1787 participants), suggests that misoprostol, as first‐line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47) compared with oxytocin.
- Low‐certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57).
- The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66), maternal death or severe morbidity (RR 1.98, low‐certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, low‐certainty).
- The risk of side‐effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, high‐certainty) and fever (2 trials, 1787 participants, RR 3.43, low‐certainty).
- According to pairwise meta‐analysis of four trials (1881 participants) generating high‐certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin.
- An important benefit of using the misoprostol plus oxytocin combination over oxytocin alone could not be ruled out, for additional blood loss of 500 mL or more (RR 0.84, moderate‐certainty).
- Important benefits or harms for additional blood loss of 1000 mL or more could not be ruled out(RR 0.76, moderate‐certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09 moderate‐certainty).
- Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, high‐certainty), and vomiting (2 trials, 1482 participants, RR 1.85, high‐certainty) compared with oxytocin alone.
- The indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, moderate‐certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, low‐certainty) compared with misoprostol alone.
- The combination makes little or no difference to vomiting (RR 0.75, high‐certainty) compared with misoprostol alone.
- Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, low‐certainty), maternal mortality or severe morbidity (RR 0.55, low‐certainty), use of additional uterotonics (RR 0.76, low‐certainty), and fever (RR 0.90, low‐certainty).
"We found that oxytocin is probably more effective than misoprostol and is also associated with less side‐effects. Giving misoprostol together with oxytocin probably does not improve effectiveness and increases side‐effects. The evidence for most available drugs used as first‐line treatment of postpartum haemorrhage is limited, with no evidence found for several drugs currently in use.," concluded the authors.
"Uterotonic agents for first‐line treatment of postpartum haemorrhage: a network meta‐analysis," is published in the Cochrane Library.