Oxytocics: Oxytocin, Ergometrine, Dinoprostone, Misoprostol & Carboprost

Learning objectives

• Classify oxytocin, ergot alkaloids and prostaglandin uterotonics.
• Use controlled oxytocin infusion safely for induction/augmentation and postpartum haemorrhage.
• Choose ergometrine, carboprost, misoprostol or carbetocin according to blood pressure, asthma, cardiac disease, gestational age and indication.
• Recognise uterine tachysystole, fetal distress, water intoxication, hypertensive crisis and uterine rupture.
• Apply a structured uterine-atony PPH response while escalating to surgery and blood products when needed.

1. Classification and core pharmacology

2. Oxytocin

Mechanism and pharmacokinetics

Oxytocin is a nonapeptide made in the hypothalamic supraoptic and paraventricular nuclei, transported to and released from the posterior pituitary. Exogenous oxytocin has a plasma half-life of about 3–5 minutes and a clinical action that changes rapidly when the infusion rate changes. Receptors increase markedly late in pregnancy and during labour; the early-trimester uterus is relatively refractory.

Oxytocin stimulates rhythmic fundal myometrial contraction with relative cervical relaxation, increases decidual/amniotic prostaglandin production and contracts postpartum uterine muscle to compress placental-bed vessels. It also has an antidiuretic effect at high doses.

Indications

• Induction of labour when continuation of pregnancy is indicated and cervix/membranes/fetus have been assessed.
• Augmentation of labour for uterine hypotonia or inadequate contractions after obstruction and malpresentation are excluded.
• Active management of the third stage and prevention/treatment of uterine-atony PPH.
• Adjunct in selected miscarriage/molar pregnancy/termination protocols under specialist and legal guidance.
• Oxytocin challenge/contraction-stress testing is historical and requires specialist monitoring.

Controlled IV induction/augmentation

• Use an infusion pump and a dedicated, clearly labelled line. The supplied teaching deck lists a low starting rate of 1–2 mIU/min; product labels may start at 0.5–1 mIU/min.
• Increase by 1–2 mIU/min every 20–30 minutes (some labels use 30–60 minutes) only when contractions and fetal heart rate are reassuring.
• Target about three contractions in 10 minutes, each lasting roughly 45–60 seconds, with adequate relaxation between contractions. Do not chase a numeric dose if the uterus is already contracting effectively.
• Reduce or stop when active labour is established, at cervical dilation around 5–6 cm, or immediately for tachysystole/fetal compromise according to protocol.

Postpartum haemorrhage doses

• Prevention: WHO recommends oxytocin 10 IU IM/IV for all births where quality-assured oxytocin and cold chain are available.
• Uterine atony: 10–40 IU may be added to 1 litre of compatible non-hypotonic crystalloid and infused at the rate needed to control bleeding; follow local PPH protocol. An IM 10 IU dose can be given after placental delivery where appropriate.
• Never give a rapid undiluted IV bolus: severe hypotension, arrhythmia and cardiac arrest can occur.

Contraindications and dangers

• Do not induce/augment with placenta previa, vasa previa, transverse lie, cord prolapse, obstructed labour, significant cephalopelvic disproportion, major previous classical uterine incision, active herpes lesions requiring caesarean, or non-reassuring fetal status where immediate birth is indicated.
• Use extreme caution with previous caesarean/uterine surgery, grand multiparity, overdistension, multiple pregnancy, polyhydramnios and high parity because rupture risk rises.
• Maternal: nausea, headache, hypotension, tachycardia, uterine rupture, water intoxication, hyponatraemia, pulmonary oedema and arrhythmia.
• Fetal/neonatal: tachysystole, reduced placental perfusion, hypoxia, acidosis, bradycardia, fetal distress and rarely death.

Water intoxication

Large volumes of dilute oxytocin over many hours can produce antidiuresis, water retention, headache, confusion, seizures and hyponatraemia. Restrict unnecessary free water, monitor fluid balance and electrolytes in prolonged/high-dose infusions and treat severe symptomatic hyponatraemia in critical care.

3. Carbetocin

Carbetocin is a long-acting oxytocin analogue used mainly to prevent PPH after caesarean or vaginal birth in selected protocols. It produces a single sustained uterine contraction without requiring a prolonged infusion.

• Typical dose: 100 micrograms IV slowly over at least one minute after birth, or IM where the product permits; verify the local formulation and indication.
• Advantages: long duration and reduced need for infusion equipment; particularly useful where oxytocin infusion is difficult.
• Adverse effects: nausea, abdominal pain, flushing, hypotension, headache, tachycardia and uterine hypertonus.
• Do not use before delivery or to induce labour; it is not a substitute for a full PPH protocol.

4. Ergot derivatives

Ergometrine and methylergometrine

Ergot alkaloids act directly on uterine smooth muscle and produce rapid, forceful, prolonged or tetanic contraction. This is why they are unsuitable for induction/augmentation and useful only after the baby is delivered.

Adverse effects include nausea, vomiting, severe hypertension, headache, chest pain, coronary vasospasm, stroke, seizures and peripheral ischaemia/gangrene with prolonged exposure. Check BP before every dose.

5. Prostaglandin oxytocics

5.1 Dinoprostone (PGE2)

Dinoprostone softens and ripens the cervix and stimulates uterine contractions. It is useful for cervical ripening before induction and selected termination/miscarriage protocols.

• Vaginal tablet: commonly 3 mg, repeat after 6–8 hours if necessary; maximum depends on the product, often 6 mg.
• Vaginal pessary: 10 mg modified-release over up to 24 hours; remove when labour begins, membranes rupture, contractions become excessive or fetal compromise develops.
• Cervical gel: approximately 0.5 mg in the cervical canal; repeat only according to product/local induction protocol.
• Adverse effects: uterine tachysystole, nausea, vomiting, diarrhoea, fever, chills, tachycardia and rare uterine rupture.

5.2 Carboprost (15-methyl PGF2alpha)

Carboprost produces powerful uterine contraction and is used for refractory atonic PPH after oxytocin and uterine massage when no contraindication exists.

• Dose: 250 micrograms (1 mL) deep IM; may repeat every 15–90 minutes if required. Maximum is commonly 8 doses (2 mg), but follow local protocol.
• Contraindication: asthma or severe reactive airway disease. Use caution in cardiac, pulmonary, renal or hepatic disease.
• Adverse effects: bronchospasm, wheeze, nausea, vomiting, diarrhoea, fever, hypertension and chest tightness.

5.3 Misoprostol (PGE1 analogue)

Misoprostol is heat-stable and useful where injectable uterotonics or cold chain are unavailable. Dose and route are indication-specific.

6. Monitoring and stopping rules

• Before induction: confirm indication, gestational age, presentation, fetal wellbeing, cervical assessment, pelvic adequacy, placenta location and absence of contraindication.
• During infusion: continuous fetal heart-rate monitoring where indicated, contraction frequency/duration/relaxation, maternal pulse/BP, pain, fluid balance and progress.
• Stop oxytocin/prostaglandin immediately for more than five contractions in 10 minutes, contractions lasting over two minutes, rising resting tone, abnormal fetal heart rate or maternal symptoms.
• Management of tachysystole: stop uterotonic, left lateral position, call for help, assess fetal status, correct hypotension, consider acute tocolysis such as terbutaline 0.25 mg SC where protocol allows and expedite birth if unresolved.
• With PPH, quantify blood loss, obtain large-bore IV access, crossmatch blood, give tranexamic acid when indicated, search for the 4 Ts (Tone, Trauma, Tissue, Thrombin) and escalate early.

7. PPH due to uterine atony: medication sequence

1. Call the obstetric haemorrhage team; ABCs, oxygen as needed, uterine massage, bladder emptying and rapid assessment.
2. Oxytocin infusion/IM according to protocol—the first-line uterotonic in most settings.
3. If bleeding persists, choose a second-line uterotonic based on contraindications: methylergonovine if no hypertension, carboprost if no asthma, misoprostol where appropriate, or carbetocin in prevention protocols.
4. Give tranexamic acid early when PPH criteria are met and within the recommended time window; this is not a uterotonic but reduces death from bleeding.
5. Move rapidly to balloon tamponade, compression sutures, uterine artery embolisation or surgery when medication fails; do not cycle uterotonics indefinitely.

8. Clinical cases

9. High-yield points

• Oxytocin is titrated by contraction pattern and fetal response, not by a fixed “maximum” dose alone.
• Oxytocin 10 IU IM/IV is a standard PPH-prevention dose where recommended; rapid IV bolus is dangerous.
• Ergometrine/methylergonovine causes tetanic contraction and vasoconstriction: use after delivery for atony, never in hypertension/pre-eclampsia.
• Carboprost is powerful for refractory atony but contraindicated in asthma.
• Dinoprostone ripens the cervix; misoprostol is heat-stable but dose/route are indication-specific.
• Tachysystole and fetal distress mean stop the uterotonic immediately and reassess.

10. Sources and further reading

• Supplied SlideShare: Oxytocics and tocolytics.
• WHO recommendations on uterotonics for prevention of PPH.
• WHO uterotonic update.
• DailyMed: oxytocin injection.
• DailyMed: methylergonovine.
• DailyMed: carboprost.