002 Oxytocin use in labour increases postpartum haemorrhage due to uterine atony

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The use of oxytocin to induce or augment labour is an established, commonly used practice that underpins a lot of modern obstetric practice. This technique is a undoubtedly a useful tool which has allowed us to improve maternal and fetal outcomes. For example to induce a timely delivery when maternal illness such as PET occurs or to avoid an operative delivery for a mother when their spontaneous progress in labour is slow.

However, like most things in medicine (and life in general) there is no such thing as a “free lunch” and it is perhaps a less well recognised fact that the use of oxytocin in labour – especially at higher doses and for prolonged periods – is associated with an increased risk of postpartum haemorrhage due to uterine atony.

Uterine atony is becoming more common in developed countries:

The incidence of uterine atony causing postpartum haemorrhage in developed countries has increased markedly in the last 2 decades – one of the important factors contributing to this is thought to be the increased prevalence and use of oxytocin during labour.

1. Lutomski JE¹, Byrne BM, Devane D, Greene RA. Increasing trends in atonic postpartum haemorrhage in Ireland: an 11-year population-based cohort study. BJOG. 2012 Feb;119(3):306-14. 
2. Epidemiological investigation of a temporal increase in atonic postpartum haemorrhage: a population-based retrospective cohort study.

What is the mechanism underlying this phenomenon?

• Exposure to oxytocin used during labour over time leads to downregulation and desensitisation of the oxytocin receptors on the myometrium. This leads to a decreased response to oxytocin when used after delivery as a uterotonic to prevent PPH.¹
• “Fatigued / tired myometrium”. Women who are not progressing well and have been in prolonged labour may have a “tired” myometrium (it is a muscle and it tires after prolonged use). These women may often then receive augmentation with oxytocin in an effort to achieve vaginal delivery. The presence of the oxytocin infusion could also be considered a marker of the presence of a “fatigued / tired” uterus in these individuals.²

1. Oxytocin exposure during labor among women with postpartum hemorrhage secondary to uterine atony. Am J Obstet Gynecol 2011; 204: 56.e1-6.

2. Predictors of severity in primary postpartum hemorrhage. Arch Gynecol Obstet. 2015 Dec;292(6):1247-54.

Recognise these patients BEFORE delivery. Anticipate and prepare for uterine atony!

In Theatre: When patients come from labour ward to theatre for a non elective caesarean during the patient assessment and the team time out specifically enquire about the length of labour & oxytocin use, duration and dose.

In Labour Ward: The midwifery and obstetric team should specifically have a discussion regarding their planned management of the third stage in patients on oxytocin infusions.

Oxytocin is still the best first line uterotonic but anticipate that it may not be effective.

In vitro rat and human studies indicate that oxytocin is less effective in myometrium exposed to oxytocin in labour, but still appears to be more effective than the other uterotonics – at least in vitro anyway.¹

Use oxytocin first but start with your highest recommended dose of oxytocin don’t wait until haemorrhage is already well established! At our institution at caesarean delivery I would give a 2-3 unit bolus (and I personally repeat this a few times every few minutes if there is haemodynamic stability) and start the 40u/500ml infusion at 250ml/hr.

1 – Comparative efficacy of uterotonic agents: in vitro contractions in isolated myometrial strips of labouring and non-labouring women. Can J Anaesth. 2014 Sep;61(9):808-18.

In the presence of oxytocin receptor downregulation will the other uterotonics still work?

The ergot and prostaglandin F2α uterotonic drugs work via different receptors and there is in vitro and in vivo evidence that the myometrial response to these drugs is maintained.¹ We should consider using these early but don’t forget the contraindications and anticipate the adverse effects!

Adverse effects and contraindications:

Ergometrine: Avoid in hypertensive disorders or serious cardiac disease (eg Pre-eclampsia, ischaemic Heart Disease), and anticipate nausea / vomiting

Carboprost: Bronchospasm, pulmonary vasoconstriction

In these patients I personally get the obstetric team to check the uterine tone within 2-3 minutes after giving oxytocin and if the tone is poor I immediately administer one of these drugs if there are no contraindications.

1 – Oxytocin pretreatment of pregnant rat myometrium reduces the efficacy of oxytocin but not of ergonovine maleate or prostaglandin F 2 alpha. Reprod Sci. 2010 Mar;17(3):269-77.

Be prepared to use non pharmacological therapies early.

Some patients may fail to respond adequately to all the uterotonic drugs and early use of physical and surgical therapies will be reqiured. These measures are often used simultaneously with the escalating pharmacological treatments.

• Bakri balloon tamponade
• Compression sutures (eg B-Lynch)
• Uterine artery ligation / embolisation
• Hysterectomy

Consider tranexamic acid early

• See the results of the WOMAN trial.

If we cease the oxytocin infusion will the receptors recover?

The short answer is yes. As soon as the decision to have a caesarean is made the oxytocin infusion should be ceased to allow the uterus to rest, and the oxytocin receptors to recover.

This recently published retrospective cohort study of women undergoing caesarean for labour arrest  demonstrated decreased blood loss with a longer recovery time (time from cessation of the oxytocin infusion to delivery).¹

1. The association between the time from oxytocin cessation during labour to Cesarean delivery and postpartum blood loss: a retrospective cohort study. Can J Anaesth. 2017 Aug;64(8):820-827.

 Take Home Points

1. Use the minimum effective dose of oxytocin in labour – and always look to titrate the dose down when possible.
2. Cease oxytocin as soon as the decision is made to proceed to caesarean delivery for obstructed labour / failure to progress. This allows time for myometrium to rest and oxytocin receptor desensitisation to reverse.
3. Recognise the women who are at risk and prepare for uterine atony at delivery.
4. Anticipate. Give the larger doses of oxytocin and add alternative uterotonics early (ergometrine, carboprost). These may all be ineffective – move to physical /surgical measures early (bakri, compression sutures, uterine artery ligation).
5.  Staff experienced in the management of uterine atony and haemorrhage should be involved early – (ideally before delivery as this is  a predictable phenomenon).

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