What is the recommended use of uterotonic (uterine contraction inducing) agents in the management of the third stage of labor?

Use of Uterotonics in Management of Third Stage of Labour

Prophylactic uterotonic administration should be offered routinely to all women during the third stage of labour, with oxytocin 5-10 IU (intramuscular or slow intravenous) as the first-line agent, administered at the time of shoulder release or immediately after delivery of the infant. 1, 2

First-Line Uterotonic Agent

Oxytocin is the uterotonic of choice for routine prophylaxis during active management of the third stage of labour. 3, 1, 4

• Administer 5-10 IU via slow IV or intramuscular injection at the time of shoulder release or immediately postpartum 1, 2
• This reduces the risk of postpartum hemorrhage by approximately 60% compared to no prophylaxis 4
• Oxytocin has fewer side effects compared to ergot alkaloids, particularly avoiding hypertension, nausea, and vomiting 5
• The FDA indicates oxytocin specifically "to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage" 2

Second-Line Uterotonic Options

Ergometrine-oxytocin combination (Syntometrine) provides marginally superior hemorrhage prevention but carries significant adverse effects that limit routine use. 5

• Ergometrine-oxytocin reduces PPH risk (≥500 mL blood loss) by a small but statistically significant margin compared to oxytocin alone (OR 0.82,95% CI 0.71-0.95) 5
• However, no difference exists for severe PPH (≥1000 mL blood loss) between the two agents 5
• Ergometrine causes significantly more vomiting, nausea, and hypertension compared to oxytocin alone 5
• Ergometrine is contraindicated in women with hypertension or respiratory conditions due to risk of bronchospasm 3, 1, 6

Alternative Uterotonics

Misoprostol may serve as an alternative when oxytocin is unavailable, but is less effective with more side effects. 4, 7

• Misoprostol is not as effective as conventional oxytocics for routine prophylaxis 4, 7
• Consider in resource-limited settings where oxytocin storage or availability is problematic 3

Carbetocin shows promise for cesarean deliveries but requires individualized consideration. 8, 4

• Most effective uterotonic regimens after cesarean delivery include carbetocin or oxytocin as a bolus 8
• Carbetocin may be used instead of continuous oxytocin infusion in elective cesarean sections 4

Integration with Delayed Cord Clamping

Delayed cord clamping (1-3 minutes) should be combined with immediate oxytocin administration after delivery of the infant. 3, 1

• The International Confederation of Midwives and International Federation of Gynaecologists and Obstetricians removed immediate cord clamping from active management recommendations 3
• Administering oxytocin immediately after delivery hastens placental transfusion and increases infant red cell mass 3
• After placental transfusion is completed (approximately 3 minutes), controlled cord traction can commence 3
• This approach reduces maternal blood loss without compromising neonatal outcomes 1

Special Populations Requiring Modified Approach

Women with respiratory diseases (asthma, cystic fibrosis, bronchiectasis) require specific uterotonic selection. 3, 1

• Oxytocin is the uterotonic of choice for active third stage management in respiratory disease 3, 1
• Avoid ergometrine entirely as it may cause bronchospasm, particularly with general anesthesia 3, 1
• Prostaglandin F2α (carboprost) causes bronchoconstriction and is not recommended in women with asthma 3
• One case report documented acute hypoxemia resistant to supplemental oxygen when oxytocin was given to a woman with severe bronchiectasis (FEV1 32%), possibly due to increased shunting through damaged lung 3

Women receiving anticoagulants require careful attention to minimize trauma during third stage management. 1

• Active management with uterotonics enhances uterine contraction and promotes placental separation, reducing bleeding risk 1
• Careful technique is essential to minimize trauma 1

Critical Contraindications and Pitfalls

Oxytocin should be avoided in specific clinical scenarios where it may cause harm. 2

• Contraindicated in cephalopelvic disproportion 2
• Not appropriate for first-trimester pregnancy losses (blighted ovum, incomplete abortion) as primary therapy—curettage is generally considered primary 2
• Injudicious use to augment weak contractions is a risk factor for uterine rupture 1

Manual removal of placenta should not be performed routinely to reduce PPH risk. 1

• Manual removal should occur only rarely with proper technique and adequate time for spontaneous separation 6
• Should not be carried out outside specialized structures except in severe, uncontrollable PPH 1

Tranexamic Acid Consideration

Tranexamic acid (1g IV) may be added for treatment of established PPH within 1-3 hours of bleeding onset, though evidence for routine prophylaxis is inconsistent. 3, 1, 8

• The WOMAN trial (over 20,000 women) demonstrated that early tranexamic acid use (within 3 hours) reduces maternal death due to bleeding 3
• WHO updated recommendations based on this evidence 3
• Current evidence is inconsistent regarding tranexamic acid plus uterotonic versus uterotonic alone for routine prophylaxis 8
• Tranexamic acid is for treatment of established hemorrhage, not routine third stage prophylaxis 3, 1