Oxytocin Receptor Agonists

Oxytocin receptor agonists are synthetic forms of the hormone oxytocin. Oxytocin and its longer-acting analogue carbetocin start and strengthen uterine contractions, prevent and treat postpartum haemorrhage and promote milk ejection. Oxytocin is also the usual drug for induction and augmentation of labour. Correct dilution, infusion rate and monitoring prevent most harm.

Mechanism. They bind oxytocin receptors on myometrium, which rise sharply near term. Receptor activation raises calcium and produces rhythmic contraction. Oxytocin also has weak antidiuretic action, so prolonged high-dose infusion causes water retention.

Pharmacokinetics. Oxytocin is broken down in the gut, so it is given by injection. Intravenous onset is immediate; half-life 3 to 5 minutes; steady state in 40 minutes. Carbetocin is a stable analogue with a half-life of about 40 minutes, and onset in 2 minutes.

Induction and augmentation of labour.

• Mix 10 IU in 500 mL of sodium chloride 0.9% (20 milliunits/mL), or 30 IU in 500 mL by local convention.
• Start at 1 to 2 milliunits/min (3 to 6 mL/h of the 10 IU in 500 mL mixture).
• Increase by 1 to 2 milliunits/min every 30 minutes until three to four contractions occur in 10 minutes; usual maximum 20 milliunits/min, and rarely higher in specialist units.
• Use an infusion pump. Stop or reduce the infusion for hyperstimulation or abnormal foetal heart rate.

Prevention of postpartum haemorrhage.

• 10 IU intramuscularly after birth of the baby, or 5 IU by slow intravenous injection over at least 1 to 2 minutes.
• Caesarean birth: 5 IU slowly intravenously, then an infusion of 10 IU/h for 4 hours if needed.
• Carbetocin 100 micrograms intravenously over 1 minute at caesarean birth, or intramuscularly after vaginal birth.

Treatment of atony. 10 IU intravenously or intramuscularly, then 20 to 40 IU in 1 litre of crystalloid at 125 to 250 mL/h.

Other uses. Oxytocin nasal spray for milk ejection is rarely used; synthetic oxytocin is not a treatment for postpartum depression.

• First-line. Prevention of PPH at every birth; induction and augmentation of labour; treatment of uterine atony.
• Alternative. Carbetocin where a single heat-stable dose is needed, especially at caesarean birth; mechanical methods (balloon catheter) for induction with scarred uterus.
• Specialist. Incomplete miscarriage and termination at later gestation (high dose, specialist units); delivery of the placenta with retained tissue.
• Emergency. PPH from atony.

Selection. Oxytocin is first choice for induction when the cervix is favourable. If the cervix is unfavourable, ripen first with a prostaglandin or balloon catheter. Do not start oxytocin within 6 hours of vaginal dinoprostone gel or within 30 minutes of removing a pessary.

Contraindications. Cord presentation or prolapse; foetal distress that needs immediate delivery; obstructed labour or cephalopelvic disproportion; placenta praevia and vasa praevia; transverse lie; previous classical caesarean or major uterine surgery (induction); hypersensitivity; severe pre-eclampsia (relative, for fluid reasons).

Serious adverse effects.

• Uterine hyperstimulation, abnormal foetal heart rate, uterine rupture (especially with scarred uterus or grand multiparity), placental abruption.
• Hypotension, tachycardia and flushing after a rapid intravenous bolus.
• Water intoxication with hyponatraemia, headache, confusion, seizures after prolonged high-dose infusion in large volumes of glucose.
• Nausea, vomiting, neonatal jaundice.

Major interactions. Prostaglandins (hyperstimulation); inhalational anaesthetics and some vasopressors (hypotension or hypertension); ergometrine adds hypertension.

Common prescribing errors.

• Giving a 10 IU intravenous bolus.
• Wrong dilution or confusing milliunits and units.
• Failing to stop the infusion in hyperstimulation.
• Starting too soon after a prostaglandin.
• No continuous foetal monitoring.

Special groups.

• Pregnancy: used for induction at or after term under supervision.
• Breastfeeding: compatible; promotes milk ejection.
• Children and adolescents: dose as adults.
• Older adults: not applicable.
• Kidney: monitor fluid balance and sodium.
• Liver: no adjustment.
• East Africa: infusion pumps may be unavailable, so use a labelled drip rate chart and one-to-one care; check cold chain; avoid induction where continuous foetal monitoring or caesarean access is absent; stop and refer for hyperstimulation.

Monitoring. Contractions every 30 minutes; foetal heart rate continuously or every 15 minutes; maternal pulse, blood pressure; fluid balance; sodium with high doses.

Referral and escalation. Tachysystole not settling after stopping the infusion; abnormal foetal heart rate; prolonged labour; uterine rupture signs (pain, bleeding, recession of presenting part); postpartum haemorrhage.

Comparison with alternative classes. Oxytocin is titratable and quickly reversible, which makes it safer than prostaglandins for augmentation. Prostaglandins ripen the cervix, which oxytocin does not.