Dataset Information

Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial.

ABSTRACT:

Objective

To determine whether intravenous oxytocin is more effective than intramuscular oxytocin at preventing postpartum haemorrhage at vaginal delivery.

Design

Double blind placebo controlled randomised trial.

Setting

University affiliated maternity unit in the Republic of Ireland.

Participants

1075 women aged 18 years or older, at term with a singleton pregnancy who were aiming for a vaginal delivery with an actively managed third stage of labour.

Interventions

Women were allocated to an intravenous bolus of oxytocin (10 IU in 1 mL given slowly over one minute) and placebo intramuscular injection (1 mL 0.9% saline) or an intramuscular bolus of oxytocin (10 IU in 1 mL) and placebo intravenous injection (1 mL 0.9% saline given slowly over one minute) at vaginal delivery. Allocation was by a secure web based randomisation service with masking of participants and clinicians to the trial intervention.

Main outcome measures

The primary outcome was postpartum haemorrhage (PPH, measured blood loss ?500 mL). Secondary outcomes were severe PPH (measured blood loss ?1000 mL), need for blood transfusion, admission to a high dependency unit, and side effects to oxytocin.

Results

Between 4 January 2016 and 13 December 2017, 1075 women were randomised and 1035 (96.3%) included in the primary and secondary analyses (517 in the intravenous oxytocin group and 518 in the intramuscular oxytocin group). The incidence of PPH was not significantly lower in the intravenous group (18.8%, 97/517) compared with intramuscular group (23.2%, 120/518): adjusted odds ratio 0.75 (95% confidence interval 0.55 to 1.03). The incidence of severe PPH, however, was significantly lower in the intravenous group (4.6%, 24/517) compared with intramuscular group (8.1%, 42/518): 0.54 (0.32 to 0.91) as was the need for blood transfusion (1.5% v 4.4%, 0.31, 0.13 to 0.70) and admission to a high dependency unit (1.7% v 3.7%, 0.44, 0.20 to 0.98). The number needed to treat to prevent one case of severe PPH was 29 (95% confidence interval 16 to 201) and to prevent one case of blood transfusion was 35 (20 to 121). The incidence of side effects to oxytocin was not increased in the intravenous group compared with intramuscular group (4.1% v 5.2%, 0.75, 0.42 to 1.35).

Conclusion

Intravenous oxytocin for the third stage of labour results in less frequent severe PPH, blood transfusion, and admission to a high dependency unit than intramuscular oxytocin, and without excess side effects.

Trial registration

Current Controlled Trials ISRCTN14718882.

SUBMITTER: Adnan N

PROVIDER: S-EPMC6122278 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial.

Adnan Nita N Conlan-Trant Rebecca R McCormick Ciara C Boland Fiona F Murphy Deirdre J DJ

BMJ (Clinical research ed.) 20180904

<h4>Objective</h4>To determine whether intravenous oxytocin is more effective than intramuscular oxytocin at preventing postpartum haemorrhage at vaginal delivery.<h4>Design</h4>Double blind placebo controlled randomised trial.<h4>Setting</h4>University affiliated maternity unit in the Republic of Ireland.<h4>Participants</h4>1075 women aged 18 years or older, at term with a singleton pregnancy who were aiming for a vaginal delivery with an actively managed third stage of labour.<h4>Intervention ...[more]

PMID: 30181338

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Project description:BackgroundPostpartum haemorrhage remains a major cause of maternal mortality and morbidity worldwide. Active management of the third stage of labour reduces the risk of postpartum haemorrhage. Oxytocin and oxytocin/ergometrine are commonly used in the UK, with oxytocin/ergometrine being more effective at preventing moderate, but not severe, blood loss. Many guidelines specifically recommend using oxytocin for all vaginal births, as it is associated with fewer adverse events. However, a survey conducted by the Southmead Hospital Maternity Research Team revealed that 71.4% of UK obstetric units still routinely use oxytocin/ergometrine. Carbetocin is a newer medication that may be as effective but has fewer side effects. No studies have directly compared all three medications.MethodsThe IMox study aims to determine the most effective, acceptable and cost-effective drug for primary prevention of postpartum haemorrhage following vaginal birth. The IMox study is a prospective, multi-centre, double-blind, randomised trial directly comparing oxytocin, oxytocin/ergometrine and carbetocin given intramuscularly for the prevention of postpartum haemorrhage in the third stage of labour. The primary effectiveness outcome is the use of an additional uterotonic drug. Secondary effectiveness outcomes reflect maternal morbidity and mortality within the immediate postpartum period. Participant questionnaires and subjective reporting of side effects will be used to evaluate maternal acceptability. Maternal quality of life utilities will be collected antenatally, and on days 1 and 14 after birth to enable a cost-effectiveness assessment of each studied drug. Participants will be pregnant women planning a vaginal birth in six hospitals in England. Participants will be approached and invited to provide consent to participate from 20 weeks gestation until in established labour. A complete sample of 5712 participants (1904 per arm) providing data for the primary outcome will allow for a robust determination of efficacy between all three study drugs. Data will be collected until participants are discharged from the hospital and on postnatal days 1 and 14 regardless of location. All analyses will be on a modified intention-to-treat basis, and additionally repeated on a per protocol basis. Data collection commenced in Feburary 2015 and was completed in August 2018.DiscussionThis study is the first to directly compare oxytocin, oxytocin/ergometrine and carbetocin in the same population for the prevention of postpartum haemorrhage following vaginal birth. Furthermore, this study will be the first to directly compute health economic outcomes from such a three-way comparison. This study is limited to using short-term outcomes, and so will not provide evidence for important outcomes such as long-term maternal psychological well-being and time to next conception.Trial registrationClinicalTrials.gov, NCT02216383 . Registered on 18 August 2014. EudraCT, 2014-001948-37. Registered on 23 September 2014. ISRCTN, ISRCTN10232550. Retrospectively registered on 6 March 2018).

Project description:BackgroundThere is general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This is an update of a review first published in 2012.ObjectivesTo determine the comparative effectiveness and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labour after vaginal birth.Search methodsWe searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2017) and reference lists of retrieved studies.Selection criteriaRandomised trials comparing intramuscular with intravenous oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials.Data collection and analysisTwo review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.Main resultsThree studies with 1306 women are included in the review and compared intramuscular versus intravenous oxytocin administered just after the birth of the anterior shoulder or soon after the birth of the baby. Studies were carried out in hospital settings in Turkey and Thailand and recruited women with singleton, term pregnancies. Overall, the included studies were at moderate risk of bias: none of the studies provided clear information on allocation concealment or attempted to blind staff or women. For GRADE outcomes the quality of the evidence was very low, with downgrading due to study design limitations and imprecision of effect estimates.Only one study reported severe postpartum haemorrhage (blood loss 1000 mL or more) and showed no clear difference between the intramuscular and intravenous oxytocin groups (risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.04; 256 women; very low-quality evidence). No woman required hysterectomy in either group in one study (no estimable data, very low-quality evidence), and in another study one woman in each group received a blood transfusion (RR 1.00, 95% CI 0.06 to 15.82; 256 women; very low-quality evidence). Other important outcomes (maternal death, hypotension, maternal dissatisfaction with the intervention and neonatal jaundice) were not reported by any of the included studies. There were no clear differences between groups for other prespecified secondary outcomes reported (postpartum haemorrhage 500 mL or more, use of additional uterotonics, retained placenta or manual removal of the placenta).Authors' conclusionsVery low-quality evidence indicates no clear difference between the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Appropriately designed randomised trials with adequate sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such studies could be large enough to detect clinically important differences in major side effects that have been reported in observational studies and should also consider the acceptability of the intervention to mothers and providers as important outcomes.

Project description:BackgroundPostpartum haemorrhage (PPH) causes about 70,000 maternal deaths every year. Tranexamic acid (TXA) is a life-saving treatment for women with PPH. Intravenous (IV) TXA reduces deaths due to PPH by one-third when given within 3 h of childbirth. Because TXA is more effective when given early and PPH usually occurs soon after childbirth, giving TXA just before childbirth might prevent PPH. Although several randomised trials have examined TXA for PPH prevention, the results are inconclusive. Because PPH only affects a small proportion of births, we need good evidence on the balance of benefits and harms before using TXA to prevent PPH. TXA is usually given by slow IV injection. However, recent research shows that TXA is well tolerated and rapidly absorbed after intramuscular (IM) injection, achieving therapeutic blood levels within minutes of injection.MethodsThe I'M WOMAN trial is an international, multicentre, three-arm, randomised, double-blind, placebo-controlled trial to assess the effects of IM and IV TXA for the prevention of PPH in women with one or more risk factors for PPH giving birth vaginally or by caesarean section.DiscussionThe trial will provide evidence of the benefits and harms of TXA for PPH prevention and the effects of the IM and IV routes of administration. The IM route should be as effective as the IV route for preventing bleeding. There may be fewer side effects with IM TXA because peak blood concentrations are lower than with the IV route. IM TXA also has practical advantages as it is quicker and simpler to administer. By avoiding the need for IV line insertion and a slow IV injection, IM administration would free up overstretched midwives and doctors to focus on looking after the mother and baby and expand access to timely TXA treatment.Trial registrationClinicalTrials.gov NCT05562609. Registered on 3 October 2022. ISRCTN Registry ISRCTN12590098. Registered on 20 January 2023. Pan African Clinical Trial Registry PACTR202305473136570. Registered on 18 May 2023.

Project description:Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting.

Project description:There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

Project description:ObjectiveTo assess whether secondary prevention, which preemptively treats women with above-average postpartum bleeding, is non-inferior to universal prophylaxis.DesignA cluster-randomised non-inferiority community trial.SettingHealth sub-centres and home deliveries in the Bijapur district of Karnataka, India.PopulationWomen with low-risk pregnancies who were eligible for delivery with an Auxiliary Nurse Midwife at home or sub-centre and who consented to be part of the study.MethodsAuxiliary Nurse Midwifes were randomised to secondary prevention using 800 mcg sublingual misoprostol administered to women with postpartum blood loss ≥350 ml or to universal prophylaxis using 600 mcg oral misoprostol administered to all women during the third stage of labour.Main outcome measuresPostpartum haemoglobin ≤7.8 g/dl, mean postpartum blood loss and postpartum haemoglobin, postpartum haemorrhage rate, transfer to higher-level facilities, acceptability and feasibility of the intervention.ResultsMisoprostol was administered to 99.7% of women as primary prevention. In secondary prevention, 92 (4.7%) women had postpartum bleeding ≥350 ml, of which 90 (97.8%) received misoprostol. The proportion of women with postpartum haemoglobin ≤7.8 g/dl was 5.9 and 8.8% in secondary and primary prevention clusters, respectively [difference -2.9%, one-sided 95% confidence interval (CI) <1.3%]. Postpartum transfer and haemorrhage rates were low (<1%) in both groups. Shivering was more common in primary prevention clusters (P = 0.013).ConclusionSecondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis based on the primary outcome of postpartum haemoglobin. Secondary prevention could be a good alternative to universal prophylaxis as it medicates fewer women and is an acceptable and feasible strategy at the community level.Tweetable abstractSecondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis.

Project description:BackgroundPostpartum haemorrhage (PPH) is a major cause of maternal morbidity. Bleeding is caused by a combination of physical causes, such as failure of the uterus to contract or operations, and is made worse by impairment of the blood clotting system. A number of studies have shown that low levels of the blood clotting factor fibrinogen are associated with progression of bleeding, the need for invasive interventions and transfusions of red blood cells and fresh frozen plasma (FFP). This trial will investigate whether early infusion of fibrinogen concentrate during a major PPH, with the aim of correcting a low fibrinogen to a level that is normal for delivery, based on the Fibtem test, reduces the total number of allogeneic blood products (red blood cells, FFP, cryoprecipitate and platelets) transfused after study medication until discharge, compared to placebo.Methods/designThis is a prospective, randomised, double-blind placebo controlled trial. Women will enter an observational phase and if their Fibtem levels fall they will be randomised in the interventional phase. A total of 60 women will be randomised and women are eligible for the trial if they meet all of the following inclusion criteria: age 18 years or over, gestation ≥24 + 0 weeks, haemorrhage of about 1500 ml and on-going bleeding without another complication or haemorrhage of about 1000 ml and caesarean section/uterine atony/placental abruption/placenta praevia/cardiovascular instability or microvascular oozing. Participants with a Fibtem A5 < 16 mm will be randomly allocated to receive either a bolus infusion of fibrinogen concentrate or placebo (isotonic saline). The dose of fibrinogen concentrate or placebo will be calculated based on the woman's ideal body weight for height and the measured Fibtem A5 with the aim of increasing the Fibtem A5 to 23 mm.DiscussionThe trial aims to provide evidence on the efficacy and safety of fibrinogen concentrate during acute bleeding in an obstetric setting.Trial registrationISRCTN ref: ISRCTN46295339 (01.07.2013); EudraCT: 2012-005511-11 (28.11.2012), UKCRN ref: 13940.

Dataset Information

Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial.

Objective

Design

Setting

Participants

Interventions

Main outcome measures

Results

Conclusion

Trial registration

Publications

Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial.

Similar Datasets

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