What is the recommended use and dosage of Carbetocin (a synthetic analogue of oxytocin) for postpartum women at risk of postpartum hemorrhage, particularly those with a history of uterine atony or other risk factors?

Carbetocin for Prevention of Postpartum Hemorrhage

Carbetocin 100 μg administered as a single intravenous bolus over 1 minute should be used instead of continuous oxytocin infusion in elective cesarean section for the prevention of postpartum hemorrhage, and for women delivering vaginally with at least one risk factor for PPH, carbetocin 100 μg intramuscularly decreases the need for uterine massage compared with continuous oxytocin infusion. 1

Recommended Dosing and Administration

For Cesarean Section

• Administer carbetocin 100 μg as an intravenous bolus over 1 minute immediately after delivery of the infant (specifically after placental delivery in most protocols) 1
• This single dose eliminates the need for continuous oxytocin infusion and reduces the requirement for additional therapeutic uterotonics 1
• Carbetocin demonstrates superior efficacy in maintaining uterine tone and reducing severe postpartum hemorrhage (blood loss ≥1000 mL) compared to oxytocin, with a 38% relative risk reduction (2.1% vs 3.3%; OR 0.62,95% CI 0.48-0.79) 2

For Vaginal Delivery with Risk Factors

• Administer carbetocin 100 μg intramuscularly immediately after placental delivery for women with at least one risk factor for PPH 1
• Risk factors include: previous PPH, uterine overdistension (multiple gestation, polyhydramnios, macrosomia), prolonged labor, augmented labor, grand multiparity, or chorioamnionitis 3, 1
• This approach reduces the need for uterine massage (43.4% vs 62.3%, P<0.02) and overall uterotonic intervention (44.6% vs 63.6%, P<0.02) compared to 2-hour oxytocin infusion 3

Clinical Efficacy Evidence

Superiority Over Oxytocin

• Carbetocin's long half-life (approximately 40 minutes vs 4-10 minutes for oxytocin) allows single-dose administration to achieve sustained uterine contraction 4
• Mean blood loss is reduced by approximately 30 mL compared to oxytocin, with a higher percentage of patients maintaining blood loss <500 mL (81% vs 55%, P=0.05) 4
• Enhanced early postpartum uterine involution is observed, with the uterine fundus below the umbilicus in more patients at 0,2,6, and 24 hours postpartum (P<0.05) 4

Dose Considerations

• The 100 μg dose is the established standard; lower doses (20 μg) have not demonstrated non-inferiority 5
• A study comparing 20 μg vs 100 μg carbetocin failed to confirm non-inferiority of the lower dose, with the lower confidence interval exceeding the pre-specified margin (mean difference -0.5,95% CI -1.1; p=0.11) 5
• Therefore, the 100 μg dose should be used consistently 5, 1

Safety Profile and Adverse Effects

• Adverse events with carbetocin are similar in type and frequency to oxytocin, including nausea, flushing, headache, and metallic taste 4
• No significant differences in hemodynamic parameters or serious adverse events have been reported in comparative trials 4, 3
• The single-dose administration reduces nursing workload and eliminates risks associated with prolonged IV infusions 1

Context Within Active Management of Third Stage

Active management of the third stage of labor (AMTSL) reduces PPH risk and should be offered to all women 1. This includes:

• Administration of a uterotonic agent (carbetocin or oxytocin) immediately after delivery 1
• Controlled cord traction after signs of placental separation 1
• Uterine massage after placental delivery 1

When Carbetocin Is Not Available

• Oxytocin 10 IU intramuscularly remains the first-line alternative for low-risk vaginal deliveries 1
• IV oxytocin infusion (20-40 IU in 1000 mL at 150 mL/hour) is acceptable for AMTSL 1
• Ergonovine 0.2 mg IM or misoprostol 600-800 μg (oral, sublingual, or rectal) may be used when oxytocin is unavailable, though these are second-line options 1

Critical Pitfalls to Avoid

• Do not use lower doses of carbetocin (such as 20 μg) assuming equivalent efficacy—only the 100 μg dose has proven effectiveness 5
• Do not confuse carbetocin with oxytocin dosing—carbetocin requires only a single dose, not continuous infusion 1
• Do not delay administration—give immediately after delivery of the infant (cesarean) or placenta (vaginal) to maximize effectiveness 4, 3
• Do not use ergonovine in hypertensive patients—this is an absolute contraindication due to risk of severe hypertension 1

Important Distinction: Not for Treatment of Established PPH

The evidence and guidelines presented address prophylaxis of postpartum hemorrhage, not treatment of established bleeding. For active PPH management, oxytocin remains first-line, with tranexamic acid (1 gram IV over 10 minutes within 3 hours of birth) added for clinically diagnosed PPH 6. The treatment algorithm differs substantially from prophylactic strategies 7, 8.