Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis (2020)

Type of publication:
Systematic Review

Author(s):
*Parry Smith, William R; Papadopoulou, Argyro; Thomas, Eleanor; Tobias, Aurelio; Price, Malcolm J; Meher, Shireen; Alfirevic, Zarko; Weeks, Andrew D; Hofmeyr, G Justus; Gülmezoglu, Ahmet Metin; Widmer, Mariana; Oladapo, Olufemi T; Vogel, Joshua P; Althabe, Fernando; Coomarasamy, Arri; Gallos, Ioannis D

Citation:
The Cochrane Database of Systematic Reviews; Nov 2020; vol. 11 ; p. CD012754

Abstract:
BACKGROUND Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, 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. OBJECTIVES 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.SEARCH METHODSWe searched the Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies. SELECTION CRITERIA All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.DATA COLLECTION AND ANALYSIS Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our 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. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.MAIN RESULTS Seven trials, involving 3738 women in 10 countries, were included in this review. 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. 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, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) 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, 95% CI 1.00 to 6.64). 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, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, 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, 95% CI 0.57 to 2.94, 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, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, 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, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, 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, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty). AUTHORS’ CONCLUSIONS The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.

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Reflective doctors and cool babies (2019)

Type of publication:
Conference abstract

Author(s):
*Charlesworth D.; Cunningham S.; Dudley L.; Bentley F.; Oguntimehin J.; Fairclough S.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; Jun 2019; vol. 126 ; p. 45

Abstract:
Introduction In 2014, the RCOG launched the ‘Each Baby Counts’ initiative which included the aim of reducing the number of neonates who are left severely disabled by preventable incidents in labour. The initial report concluded that a different outcome may have been achieved in 76% of cases if different care had been received. Around the same time, reflective practice among doctors faced a significant challenge secondary to negative perceptions of its use in litigation, and resilience continued to be tested as work pressures, insufficient staff numbers, and public perceptions continued to increase. With the interplay between all these factors being crucial in achieving the state of experiential learning necessary to achieve the EBC goals, we look at a different method for reflective practice and quality improvement. Methods In 2015, we launched a series of measures inspired by EBC to reduce our rates of neonates requiring therapeutic hypothermia. One key component of our programme was a change in how our RCAs were undertaken. We changed RCA leads to include staff at all levels from across the multidisciplinary team, promoted a reflective journey and thematic analysis, changed our meetings to include staff recommended by the EBC report to achieve a more multidisciplinary and inclusive representation, promoted team learning, and fed back via casebased, reflective teaching. We then undertook a 48-month retrospective audit from 01/2015 to 12/2018 to see if we had improved care. Results In 2015, our therapeutic hypothermia annual incidence was 12, 11 in 2016, 7 in 2017, and 2 by 12/2018. Thematic analysis of our cases revealed a change in precipitating factors from preventable to unpredictable, and we subsequently increased the proportion of cases in which we concluded we could not improve the end outcome (though learning was identified in all). Staff empowerment increased, hierarchies flattened, and our ability to identify key targeted improvements increased to facilitate change and drive improvement. Conclusion We discovered that, if conducted well, with reflection as a key component, and the aim to promote a culture of learning and becoming, RCA can be used as a powerful teaching tool in training, and to promote improved patient care. As more staff engaged in our new RCA process, feedback indicated an increase in resilience and a more open culture of learning, unhindered by more traditional elements of reflective learning.

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A national survey on the uterotonic use for the prevention of postpartum haemorrhage (2019)

Type of publication:
Conference abstract

Author(s):
*Stephanou M.; Gallos I.; Coomarasamy A.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; Jun 2019; vol. 126 ; p. 148-149

Abstract:
Objective: To map the current national practice of the first line uterotonic drug given for the prevention of
postpartum haemorrhage (PPH) at both vaginal and caesarean section deliveries. Design A prospective national survey was carried out by contacting maternity units by means of telephone contact. Survey questions were set out to evaluate the uterotonic drug of choice in accordance with local hospital policy which was then compared with national guidance.
Methods: Maternity units across England were identified using the NHS Maternity Statistics 2016-2017 data available from NHS Digital. 136 NHS trusts were identified and 143 maternity units were contacted. Responses were collected by means of telephone communication with each of the maternity units. Maternity governance leads were the first point of contact followed by labour ward coordinators and senior labour ward doctors. The Health Research Authority Ethics toolkit was applied and determined that Research and Ethics council approval was not required.
Results: All 143 maternity units identified were contacted to answer the survey. 118 (82.5%) responses were obtained for the uterotonic of choice used for the prevention of postpartum haemorrhage at vaginal birth, of which 75 (63.5%) maternity units administered oxytocin with ergometrine combination as the first-line uterotonic. 116 (81%) responses were collected for the uterotonic of choice at caesarean section, where 95 (81.9%) administered intravenous oxytocin as first line.
Conclusion: The National Institute of Clinical Excellence (NICE) and World Health Organization (WHO)
guidelines recommend oxytocin as the first-line uterotonic of choice for the prevention of postpartum
haemorrhage. This survey has shown that current UK practice conflicts with both international and national guidance, favouring oxytocin with ergometrine over oxytocin alone at vaginal birth. Postpartum haemorrhage is a significant cause of morbidity and mortality; it is recommended that further attention be paid towards the first line uterotonic agent used for the prevention of a PPH in line with the most current up to date evidence.

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