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

Overview of attention for article published in Cochrane database of systematic reviews, April 2018
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

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6 news outlets
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129 tweeters
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15 Facebook pages

Citations

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30 Dimensions

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91 Mendeley
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Title
Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis
Published in
Cochrane database of systematic reviews, April 2018
DOI 10.1002/14651858.cd011689.pub2
Pubmed ID
Authors

Ioannis D Gallos, Helen M Williams, Malcolm J Price, Abi Merriel, Harold Gee, David Lissauer, Vidhya Moorthy, Aurelio Tobias, Jonathan J Deeks, Mariana Widmer, Özge Tunçalp, Ahmet Metin Gülmezoglu, G Justus Hofmeyr, Arri Coomarasamy

Abstract

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best. To identify the most effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile. We searched Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for unpublished trial reports (30 June 2015) and reference lists of retrieved studies. All randomised controlled comparisons or cluster trials of effectiveness or side-effects of uterotonic drugs for preventing PPH.Quasi-randomised trials and cross-over trials are not eligible for inclusion in this review. At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available drugs. We stratified our primary outcomes according to mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of drug administration, to detect subgroup effects.The absolute risks in the oxytocin are based on meta-analyses of proportions from the studies included in this review and the risks in the intervention groups were based on the assumed risk in the oxytocin group and the relative effects of the interventions. This network meta-analysis included 140 randomised trials with data from 88,947 women. There are two large ongoing studies. The trials were mostly carried out in hospital settings and recruited women who were predominantly more than 37 weeks of gestation having a vaginal birth. The majority of trials were assessed to have uncertain risk of bias due to poor reporting of study design. This primarily impacted on our confidence in comparisons involving carbetocin trials more than other uterotonics.The three most effective drugs for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination. These three options were more effective at preventing PPH ≥ 500 mL compared with oxytocin, the drug currently recommended by the WHO (ergometrine plus oxytocin risk ratio (RR) 0.69 (95% confidence interval (CI) 0.57 to 0.83), moderate-quality evidence; carbetocin RR 0.72 (95% CI 0.52 to 1.00), very low-quality evidence; misoprostol plus oxytocin RR 0.73 (95% CI 0.60 to 0.90), moderate-quality evidence). Based on these results, about 10.5% women given oxytocin would experience a PPH of ≥ 500 mL compared with 7.2% given ergometrine plus oxytocin combination, 7.6% given carbetocin, and 7.7% given misoprostol plus oxytocin. Oxytocin was ranked fourth with close to 0% cumulative probability of being ranked in the top three for PPH ≥ 500 mL.The outcomes and rankings for the outcome of PPH ≥ 1000 mL were similar to those of PPH ≥ 500 mL. with the evidence for ergometrine plus oxytocin combination being more effective than oxytocin (RR 0.77 (95% CI 0.61 to 0.95), high-quality evidence) being more certain than that for carbetocin (RR 0.70 (95% CI 0.38 to 1.28), low-quality evidence), or misoprostol plus oxytocin combination (RR 0.90 (95% CI 0.72 to 1.14), moderate-quality evidence)There were no meaningful differences between all drugs for maternal deaths or severe morbidity as these outcomes were so rare in the included randomised trials.Two combination regimens had the poorest rankings for side-effects. Specifically, the ergometrine plus oxytocin combination had the higher risk for vomiting (RR 3.10 (95% CI 2.11 to 4.56), high-quality evidence; 1.9% versus 0.6%) and hypertension [RR 1.77 (95% CI 0.55 to 5.66), low-quality evidence; 1.2% versus 0.7%), while the misoprostol plus oxytocin combination had the higher risk for fever (RR 3.18 (95% CI 2.22 to 4.55), moderate-quality evidence; 11.4% versus 3.6%) when compared with oxytocin. Carbetocin had similar risk for side-effects compared with oxytocin although the quality evidence was very low for vomiting and for fever, and was low for hypertension. 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.

Twitter Demographics

The data shown below were collected from the profiles of 129 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 91 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 91 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 17 19%
Student > Master 13 14%
Other 10 11%
Student > Bachelor 9 10%
Student > Ph. D. Student 9 10%
Other 18 20%
Unknown 15 16%
Readers by discipline Count As %
Medicine and Dentistry 47 52%
Nursing and Health Professions 5 5%
Agricultural and Biological Sciences 4 4%
Business, Management and Accounting 2 2%
Social Sciences 2 2%
Other 11 12%
Unknown 20 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 133. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 May 2019.
All research outputs
#126,337
of 14,332,781 outputs
Outputs from Cochrane database of systematic reviews
#256
of 10,948 outputs
Outputs of similar age
#5,418
of 275,367 outputs
Outputs of similar age from Cochrane database of systematic reviews
#13
of 184 outputs
Altmetric has tracked 14,332,781 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,948 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.8. This one has done particularly well, scoring higher than 97% of its peers.
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