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NIHR Signal Intravenous oxytocin reduces severe bleeding after vaginal delivery

Published on 27 November 2018

doi: 10.3310/signal-000685

Routine oxytocin injected directly into the bloodstream, rather than into the muscle, after birth results in fewer people suffering severe bleeding (postpartum haemorrhage).

The overall rate of postpartum haemorrhage (PPH) or side effects was similar between the groups, but the intravenous group had fewer severe haemorrhages, needed fewer blood transfusions and fewer admissions to high dependency care. Intramuscular route oxytocin is currently recommended in the UK, partly due to concerns about side effects.

This trial, carried out in a single maternity unit in the Republic of Ireland, randomised 1,075 women to receive either intravenous or intramuscular oxytocin after giving birth. The incidence of severe PPH was small, 66 women amongst about 1,000 and the trial did not detect a difference for the 217 women who had all grades of bleeding. This study provides further evidence on the effectiveness and safety of intravenous oxytocin given during the third stage of labour in women without cardiovascular disease. However, as a single trial, it may not be the final word on the topic.

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Why was this study needed?

Bleeding after delivery, postpartum haemorrhage (PPH), is one of the leading causes of mortality worldwide, and severe blood loss the second highest cause of direct maternal death in the UK. The incidence of all severities of PPH has been rising in the UK reaching 13.8% in 2012-2013. The most common cause of PPH is the uterus failing to contract after delivery.

Oxytocin, a drug that contracts the uterus, is used to prevent or treat PPH. Giving oxytocin intravenously results in a more rapid effect but has been associated with a fast heart rate and low blood pressure. Therefore in 2010, the Royal College of Obstetricians and Gynaecologists (RCOG) implemented a new protocol recommending intramuscular oxytocin.

There have been concerns that the incidence of PPH has increased after this recommendation, so this trial aimed to compare directly the two routes of administration.

What did this study do?

This randomised controlled trial included 1,075 women aged 18 years or older with singleton pregnancies at 37 weeks gestation or more. All were aiming for a vaginal birth. Participants were randomly allocated to receive either intravenous oxytocin and intramuscular placebo (517 women) or intramuscular oxytocin and intravenous placebo (518 women).

Labour was managed as usual. The injections were administered immediately after delivery. A standardised protocol was used to measure blood loss. The analysis took into consideration other factors that may influence bleeding such as assisted vaginal delivery (forceps or ventouse).

The trial was well-conducted and double blind. But it was only carried out in one centre with a small sample size.

What did it find?

  • A similar number of women had PPH, 18.8% of the intravenous group and 23.2% of the intramuscular group (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.55 to 1.03).
  • Fewer women had severe PPH in the intravenous group, 4.6% compared with 8.1% of the intramuscular group (aOR 0.54, 95% CI 0.32 to 0.91).
  • The need for blood transfusion was lower in the intravenous group, 1.5% of women compared with 4.4% of the intramuscular group (aOR 0.31, 95% CI 0.13 to 0.70).
  • Admission to a high dependency unit was lower in the intravenous group, 1.7% compared with 3.7% of the intramuscular group (aOR 0.44, 95% CI 0.20 to 0.98).
  • Side effects from oxytocin, such as low blood pressure and raised heart rate, were not increased in the intravenous group, occurring in 4.1% of women compared with 5.2% of the intramuscular group (aOR 0.75, 95% CI 0.42 to 1.35). No maternal deaths occurred, and no hysterectomies were carried out.
  • Subgroup analysis showed women without previous births had the largest (6.9 percentage points) absolute benefit from intravenous oxytocin. Severe PPH in the intravenous group occurred in 16 women (6.3%) compared with 33 (13.2%) in the intramuscular group (aOR 0.45, 95% CI 0.24 to 0.84).

What does current guidance say on this issue?

Intramuscular oxytocin in the third stage of labour is recommended in the 2016 RCOG guideline to prevent PPH in women who have delivered vaginally. For women delivering by caesarean section, who will already have intravenous access, slow intravenous injection of oxytocin is recommended. NICE guidelines, updated in 2017, also recommend intramuscular oxytocin during the third stage of labour.

Both RCOG and NICE guidelines advise a slow intravenous injection of oxytocin in the management of PPH (during active bleeding).

What are the implications?

This study provides further evidence on the safety and effectiveness of intravenous oxytocin in women with no cardiovascular disease in the third stage of labour.

The evidence is in line with the use of intravenous oxytocin in women who have caesarean sections. However, many women in stand-alone midwifery led units do not already have intravenous access.

Further studies will be required on a larger scale if the intravenous route is to become routine for first time mothers and those having inductions.

Citation and Funding

Adnan N, Conlan-Trant R, McCormick C, Boland F, Murphy DJ. Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial. BMJ. 2018;362:k3546.

The study was funded by Trinity College, University of Dublin and Coombe Women and Infants University Hospital.

Bibliography

Knight M, Nair M, Tuffnell D et al. Saving lives, improving mothers’ care - lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2013–15. MBRRACE-UK. 2017.

Health and Social Care Information Centre. NHS Maternity Statistics – England, 2013–2014. London: Health and Social Care Information Centre; 2015.

Joint Formulary Committee. British National Formulary (online). Oxytocin. London: BMJ Group and Pharmaceutical Press. [Accessed on 20 November 2018].

Mavrides E, Allard S, Chandraharan E et al. on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG. 2016;124:e106-49.

NICE. Intrapartum care for healthy women and babies. CG190. London: National Institute for Health and Care Excellence. 2014 (updated 2017).

Why was this study needed?

Bleeding after delivery, postpartum haemorrhage (PPH), is one of the leading causes of mortality worldwide, and severe blood loss the second highest cause of direct maternal death in the UK. The incidence of all severities of PPH has been rising in the UK reaching 13.8% in 2012-2013. The most common cause of PPH is the uterus failing to contract after delivery.

Oxytocin, a drug that contracts the uterus, is used to prevent or treat PPH. Giving oxytocin intravenously results in a more rapid effect but has been associated with a fast heart rate and low blood pressure. Therefore in 2010, the Royal College of Obstetricians and Gynaecologists (RCOG) implemented a new protocol recommending intramuscular oxytocin.

There have been concerns that the incidence of PPH has increased after this recommendation, so this trial aimed to compare directly the two routes of administration.

What did this study do?

This randomised controlled trial included 1,075 women aged 18 years or older with singleton pregnancies at 37 weeks gestation or more. All were aiming for a vaginal birth. Participants were randomly allocated to receive either intravenous oxytocin and intramuscular placebo (517 women) or intramuscular oxytocin and intravenous placebo (518 women).

Labour was managed as usual. The injections were administered immediately after delivery. A standardised protocol was used to measure blood loss. The analysis took into consideration other factors that may influence bleeding such as assisted vaginal delivery (forceps or ventouse).

The trial was well-conducted and double blind. But it was only carried out in one centre with a small sample size.

What did it find?

  • A similar number of women had PPH, 18.8% of the intravenous group and 23.2% of the intramuscular group (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.55 to 1.03).
  • Fewer women had severe PPH in the intravenous group, 4.6% compared with 8.1% of the intramuscular group (aOR 0.54, 95% CI 0.32 to 0.91).
  • The need for blood transfusion was lower in the intravenous group, 1.5% of women compared with 4.4% of the intramuscular group (aOR 0.31, 95% CI 0.13 to 0.70).
  • Admission to a high dependency unit was lower in the intravenous group, 1.7% compared with 3.7% of the intramuscular group (aOR 0.44, 95% CI 0.20 to 0.98).
  • Side effects from oxytocin, such as low blood pressure and raised heart rate, were not increased in the intravenous group, occurring in 4.1% of women compared with 5.2% of the intramuscular group (aOR 0.75, 95% CI 0.42 to 1.35). No maternal deaths occurred, and no hysterectomies were carried out.
  • Subgroup analysis showed women without previous births had the largest (6.9 percentage points) absolute benefit from intravenous oxytocin. Severe PPH in the intravenous group occurred in 16 women (6.3%) compared with 33 (13.2%) in the intramuscular group (aOR 0.45, 95% CI 0.24 to 0.84).

What does current guidance say on this issue?

Intramuscular oxytocin in the third stage of labour is recommended in the 2016 RCOG guideline to prevent PPH in women who have delivered vaginally. For women delivering by caesarean section, who will already have intravenous access, slow intravenous injection of oxytocin is recommended. NICE guidelines, updated in 2017, also recommend intramuscular oxytocin during the third stage of labour.

Both RCOG and NICE guidelines advise a slow intravenous injection of oxytocin in the management of PPH (during active bleeding).

What are the implications?

This study provides further evidence on the safety and effectiveness of intravenous oxytocin in women with no cardiovascular disease in the third stage of labour.

The evidence is in line with the use of intravenous oxytocin in women who have caesarean sections. However, many women in stand-alone midwifery led units do not already have intravenous access.

Further studies will be required on a larger scale if the intravenous route is to become routine for first time mothers and those having inductions.

Citation and Funding

Adnan N, Conlan-Trant R, McCormick C, Boland F, Murphy DJ. Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial. BMJ. 2018;362:k3546.

The study was funded by Trinity College, University of Dublin and Coombe Women and Infants University Hospital.

Bibliography

Knight M, Nair M, Tuffnell D et al. Saving lives, improving mothers’ care - lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2013–15. MBRRACE-UK. 2017.

Health and Social Care Information Centre. NHS Maternity Statistics – England, 2013–2014. London: Health and Social Care Information Centre; 2015.

Joint Formulary Committee. British National Formulary (online). Oxytocin. London: BMJ Group and Pharmaceutical Press. [Accessed on 20 November 2018].

Mavrides E, Allard S, Chandraharan E et al. on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG. 2016;124:e106-49.

NICE. Intrapartum care for healthy women and babies. CG190. London: National Institute for Health and Care Excellence. 2014 (updated 2017).

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

Published on 6 September 2018

Adnan, N.,Conlan-Trant, R.,McCormick, C.,Boland, F.,Murphy, D. J.

Bmj Volume 362 , 2018

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.

Direct maternal death is a maternal death resulting from a direct complication of the pregnancy, delivery or management.

The third stage of labour is the delivery of the placenta.

Postpartum haemorrhage: more than 500ml blood lost after the baby has been born. Severe PPH is defined as greater than 2,000 ml.

Expert commentary

In the third stage of labour, routine use of drugs that contract the uterus prevent postpartum haemorrhage, whereas early cord clamping causes harm and cord traction is unnecessary. Oxytocin is the first line as it is cheap, effective and has few side effects.

This double-blind study compared the intramuscular with the intravenous route and found that blood loss was reduced in the intravenous arm, but only in groups with higher rates of postpartum haemorrhage like nulliparous and induced women. The intravenous oxytocin was given over one minute, and no significant hypotension was seen.

The way forward is clear: give slow intravenous oxytocin to those with a cannula already in situ - those who have been induced, augmented, delivering twins or with epidurals. Those at low risk can safely continue to use intramuscular oxytocin.

Andrew Weeks, Professor of International Maternal Health, Sanyu Research Unit, University of Liverpool; Consultant Obstetrician, Liverpool Women's Hospital

The commentator declares no conflicting interests