Doses and routes of administration for uterotonic agents to prevent postpartum haemorrhage

Papadopoulou, Argyro ORCID: 0000-0001-9409-8608 (2024). Doses and routes of administration for uterotonic agents to prevent postpartum haemorrhage. University of Birmingham. M.Sc.

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Abstract

Background: Postpartum haemorrhage (PPH) is the most common cause of maternal mortality and serious morbidity after childbirth, worldwide. Inadequate uterine tone after the birth of the baby can lead to excessive bleeding from the open vessels on the placental bed. Therefore, the administration of drugs that increase uterine contractility is recommended for all births. However, there is still uncertainty about the best route and dose of administration for each of the available uterotonic drugs.
Objectives: To perform two network meta-analyses, one to specify the route of administration, and one to specify the dose, that maximise the effectiveness of each of the available uterotonic drugs without increasing the risk for side effects. A ranking of the available options will be generated for all primary and secondary outcomes.
Selection criteria: Population: Randomised controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. Interventions: Systemically administered uterotonic drugs of any route and dose for PPH prevention. Comparison: Any other uterotonic drug, or a different route or dose of a given drug, or placebo, or no treatment. Outcomes (primary): PPH ≥500 mL and PPH ≥1000 mL.
Data collection and analysis: Data will be extracted from the eligible studies and entered on an electronic database. Risk of bias and trustworthiness assessments will be performed. Direct, indirect and network meta-analyses will be conducted, and results will be summarised as risk ratio with 95% confidence intervals (CI) for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. The certainty of generated evidence will be assessed according to the GRADE approach. Results with relative and absolute treatments effects will be summarised in Summary of Findings tables. Cumulative probabilities will be calculated and the surface under the cumulative ranking curve (SUCRA) will be used to create a ranking of the available drugs.
Main results: One hundred eighty-one studies involving 122,867 randomised women were included in the Routes-NMA. Results suggest that carbetocin IV(B), ergometrine plus oxytocin combination IM, oxytocin IV(B+I), and oxytocin IV(B) are probably more effective in preventing PPH and related morbidity outcomes, when compared with oxytocin IM. Intramuscularly administered oxytocin and carbetocin have a favourable side effects profile.
One hundred eighty-two studies with 132,593 randomised participants were included in the Doses-NMA. Carbetocin 100 mcg, ergometrine >200 mcg, and ergometrine plus oxytocin combination 500 mcg plus 5 IU rank among the best options for preventing excessive bleeding, use of additional uterotonics, and administration of a blood transfusion. However, when comparing these uterotonics against oxytocin 10 IU the generated evidence varies from very low to moderate certainty without statistically significant results, and thus findings are inconclusive. Carbetocin 100 mcg is associated with a favourable side effects profile.
Authors’ conclusions: Although carbetocin IV(B), ergometrine plus oxytocin combination IM, oxytocin IV(B+I), and oxytocin IV(B) are among the top uterotonics for PPH prevention, these uterotonics also increase the risk for side effects. In terms of which dose of administration maximises effectiveness results are unclear.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):