Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis

Abstract

Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current standard oxytocin. Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin. Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies. Carbetocin had the most favourable side-effect profile amongst the top three options; however, most carbetocin trials were small and at high risk of bias.Amongst the 11 ongoing studies listed in this review there are two key studies that will inform a future update of this review. The first is a WHO-led multi-centre study comparing the effectiveness of a room temperature stable carbetocin versus oxytocin (administered intramuscularly) for preventing PPH in women having a vaginal birth. The trial includes around 30,000 women from 10 countries. The other is a UK-based trial recruiting more than 6000 women to a three-arm trial comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018.Consultation with our consumer group demonstrated the need for more research into PPH outcomes identified as priorities for women and their families, such as women's views regarding the drugs used, clinical signs of excessive blood loss, neonatal unit admissions and breastfeeding at discharge. To date, trials have rarely investigated these outcomes. Consumers also considered the side-effects of uterotonic drugs to be important but these were often not reported. A forthcoming set of core outcomes relating to PPH will identify outcomes to prioritise in trial reporting and will inform futures updates of this review. We urge all trialists to consider measuring these outcomes for each drug in all future randomised trials. Lastly, future evidence synthesis research could compare the effects of different dosages and routes of administration for the most effective drugs.

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women

“…For every maternal death, a larger number suffer serious morbidity, including multi‐organ failure and peripartum hysterectomy . There is strong evidence, and widespread recommendation, for the routine administration of uterotonics to prevent postpartum haemorrhage at caesarean section . Despite the availability of uterotonic drugs, there has been a rising incidence of atonic postpartum haemorrhage in developed countries that has been attributed to various factors including: advanced maternal age; multiple pregnancy; induction and/or augmentation of labour; obesity; and the rising incidence of caesarean section .…”

International consensus statement on the use of uterotonic agents during caesarean section

“…There were no trials that investigated ergot alkaloids or prostaglandins, alone or in combination with oxytocin, vs. placebo as a first‐line prophylactic treatment at caesarean section. Prophylactic use of carbetocin alone during caesarean section did not decrease the rate of postpartum haemorrhage compared with placebo . In a sub‐group analysis evaluating the risk of blood loss ≥ 500 ml at caesarean section, only the combination of an infusion of 20 IU oxytocin plus sublingual misoprostol 400 μg was superior to oxytocin alone (RR 0.69, 95%CI 0.51–0.92; pairwise analysis).…”

“…In a sub‐group analysis evaluating the risk of blood loss ≥ 500 ml at caesarean section, only the combination of an infusion of 20 IU oxytocin plus sublingual misoprostol 400 μg was superior to oxytocin alone (RR 0.69, 95%CI 0.51–0.92; pairwise analysis). For major postpartum haemorrhage (blood loss ≥ 1000 ml), there was no evidence for differences between any agent and oxytocin alone . The lack of directly comparable studies makes it difficult to draw definite conclusions.…”

“…They have a plasma half‐life of 30–120 min. The most frequent adverse effects include hypertension, nausea and vomiting . Ergot alkaloids may produce peripheral vasoconstriction that leads to elevated systemic arterial pressure and central venous pressure.…”

A systematic review of the cost‐effectiveness of uterotonic agents for the prevention of postpartum hemorrhage

“…Given the paucity of available evidence on uterotonic cost‐effectiveness, for the purposes of informing the WHO guideline update process, we created a logic model on cost‐effectiveness considerations across the different uterotonic options to aid decision makers and other stakeholders (Table ). In this approach, we used up‐to‐date evidence on the relative effectiveness and safety of the different uterotonic agents relative to oxytocin from an updated Cochrane systematic review and NMA . We tabulated the risk ratios of desirable and undesirable effects.…”