Postpartum bleeding lower with prophylactic carbetocin vs oxytocin

First-line prophylactic treatment with carbetocin during the third stage of labour works better than oxytocin at reducing the risk of postpartum haemorrhage (PPH), according to a study from Australia.

Significantly fewer women who received carbetocin vs oxytocin experienced postpartum blood loss of between 500 and 999 mL (moderate PPH; 26.7 percent vs 30.4 percent; p=0.001) and of at least 1,000 (severe PPH; 9.9 percent vs 12.5 percent; p=0.001). The median blood loss was 410 vs 460 mL, respectively (p<0.001). [BJOG 2025;doi:10.1111/1471-0528.18358]

Use of additional uterotonics (28.5 percent vs 30.6 percent; p=0.077) or blood transfusions (2.4 percent vs 2.7 percent; p=0.524) did not significantly differ between carbetocin and oxytocin. However, carbetocin was associated with greater reductions in admissions to the high-dependence care unit (4.6 percent vs 5.9 percent; p<0.001) and in the length of hospital stay (median, 37.8 vs 41.2 days; p<0.001).

Outcomes across birth types

Looking at outcomes across birth types, the most pronounced differences were observed in the normal vaginal birth group. Compared with oxytocin, carbetocin treatment resulted in significantly lower rates of moderate PPH (11.9 percent vs 17.2 percent p<0.001) and severe PPH (5 percent vs 7.6 percent; p=0.003) and decreased use of additional uterotonics (14.5 percent vs 21.8 percent; p<0.001).

The percentage of women who had PPH did not significantly differ between carbetocin and oxytocin in the assisted vaginal birth group (moderate PPH: 31.6 percent vs 35 percent; p=0.289; severe PPH: 17.6 percent vs 21.4 percent; p=0.146) and the emergency caesarean group (moderate PPH: 46.3 percent vs 49 percent; p=0.342; severe PPH: 17.9 percent vs 18.4 percent; p=0.840).

Across all birth types, carbetocin was associated with a significant reduction in the length of hospital stay. High-dependence care unit admissions were reduced only in the normal vaginal birth and elective and emergency caesarean section groups.

Predictors of PPH

Instrumental vaginal birth, primiparity, labour duration, and severe perineal trauma were associated with significantly increased odds of PPH in the vaginal birth group. In the caesarean section group, risk factors for PPH included twin birth, increased birthweight, and emergency caesarean section.

For both the vaginal birth and caesarean section analyses, carbetocin significantly reduced the odds of PPH compared with oxytocin.

The analysis included 6,235 women, of whom 3,001 received oxytocin and 3,234 received carbetocin. Relative to the oxytocin group, the carbetocin group was older (mean age 31 vs 30.6 years), had a higher proportion of multiparous women (59.5 percent vs 56.6 percent), a lower proportion of twin births (1.2 percent vs 1.8 percent), and a lower proportion of women who had labour induction (34 percent vs 38.6 percent). The length of the first stage, the second stage, and the overall length of labour were significantly lower in the carbetocin than the oxytocin group.

The main outcome measures were weighed blood loss and the rates of moderate and severe PPH.

A look at guidelines

Recent guidelines recommend using carbetocin in the primary prevention of PPH after caesarean section, but this recommendation is not yet included in the official guidelines from the WHO. [Anaesthesia 2019;74:1305-1319; https://l1nq.com/vic-au-guideline]

Compared with oxytocin, carbetocin has a greater biological effect, a longer half-life, and is more heat-stable, according to the investigators. Prior data have shown that PPH after vaginal birth is comparable between the two drugs but is significantly reduced with carbetocin when used in the context of caesarean section. [Int J Obstet Anesth 2019:40:14-23; BJOG 2010;117:929-936]

“Our results highlight the potential advantages of carbetocin when used for vaginal births,” they said.

Cost-effective

“PPH contributes to long-term disability and severe maternal morbidity associated with substantial blood loss, including shock and organ dysfunction,” the investigators noted. The present data suggest that prophylactic carbetocin treatment during childbirth may reduce maternal morbidity and lower hospital costs, they added. [BMC Pregnancy Childbirth 2018;18:214; BJOG 2015;122:202-210]

In Australia, carbetocin costs 23 AUD per unit as opposed to only 1.1 AUD per unit of oxytocin. The investigators pointed out that the higher initial cost of the drug could be offset by the savings from a shorter length of hospital stay and reduced admission to the high-dependence care unit.

“In addition, reduced PPH rates are likely to result in reduced maternal morbidities in the postnatal period, coinciding with further cost benefits for the healthcare system,” the investigators said.

More studies evaluating the cost-effectiveness of using carbetocin for all vaginal births and caesarean section deliveries are required, they added.