Grand Rounds

What are the Possible Causes of a PPH that is Unresponsive to First Line Uterotonics?

BACKGROUND AND PURPOSE:

A better understanding of maternal characteristics associated with refractory PPH (unresponsive to first line uterotonics) may help improve treatment
Widmer et al. (BJOG, 2019) examined the maternal characteristics and causes associated with refractory postpartum hemorrhage (PPH)

Secondary analysis of the WHO CHAMPION trial data
- CHAMPION trial: double blind, noninferiority RCT comparing the effectiveness of prophylactic IM carbetocin with oxytocin administered immediately after vaginal birth
Setting
- 23 hospitals in 10 countries
Participants
- Women from the CHAMPION trial who received uterotonics as first-line treatment of PPH
Study design
- Data collected: Sociodemographic factors | Pregnancy and childbirth factors
- Causes of PPH: Uterine atony | Vaginal/perineal/cervical tear | Retained placenta | Coagulopathy
- Compared women with refractory PPH (unresponsive to first-line uterotonics for PPH) to women who were responsive to first-line PPH treatment
- Multivariate analysis
Primary outcome
- Maternal characteristics
- Causes of PPH

29,539 women randomized in the CHAMPION trial
- 3061 (10.4%) received additional uterotonics for PPH
- 16.2% were in the refractory group (did not respond to first-line treatment) | 83.8% responded to initial first-line treatment
Higher odds of refractory PPH vs responsive for the following
- Patient induced or augmented with uterotonics
  - Adjusted odds ratio (aOR) 1.35 (95% CI, 1.07 to 1.72)
- Episiotomy or tears requiring suturing
  - aOR 1.82 (95% CI, 1.34 to 2.48)
- Babies with birthweights ≥3500 g
  - aOR 1.33 (95% CI 1.04 to 1.69)
3 maternal deaths were reported, all in the refractory group
- Placental abruption | Placental retention | Uterine atony

PPH ≥1000 ml

Atony was the sole PPH cause in
- Responsive group: 53.2%
- Refractory group: 31.5%
Tears were the sole cause in
- Responsive group: 12.8%
- Refractory group: 28%
A placental problem was the sole cause in
- Responsive group: 11%
- Refractory group: 5.6%

Refractory PPH vs responsive to uterotonics show different causal patterns
Induction with uterotonics, episiotomies or tears requiring suturing, and babies ≥3500 g are associated with refractory PPH
Women who respond to first-line uterotonics are more likely to have atony vs trauma as the sole cause of PPH | In refractory PPH cases, both atony and trauma showed similar causal rates

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