Postpartum Hemorrhage in Humanitarian Settings: Heat-Stable Carbetocin and Tranexamic Acid Implementation Study in South Sudan.

Background and objective: Postpartum hemorrhage (PPH) remains a significant concern in crisis-affected contexts, where the implementation of heat-stable carbetocin (HSC) and tranexamic acid (TXA) for PPH prevention and treatment lacks evidence. This study aims to evaluate the effects of a capacity-strengthening package on the use of uterotonics for PPH prevention and detection, and the use of TXA for PPH treatment in basic maternity facilities in South Sudan.

Methods: In this implementation study, the six chosen facilities followed a stepwise sequence of PPH management: T1 (routine care), a transition period for package design; T2 (package without HSC and TXA); T3 (package and HSC); and T4 (package with HSC and TXA). The intervention comprised refresher training, an online provider community, PPH readiness kits, alarm bells, and displayed algorithms. The main outcomes were trends in prophylactic uterotonic use, including HSC, visual diagnosis of bleeding, and oxytocin and TXA use for PPH treatment. Analyses were adjusted for cluster effect and baseline characteristics. The study was registered in the Pan-African Clinical Trials Registry (PACTR202302476608339).

Results: From February 1, 2022, to February 17, 2023, 3142 women were recruited. Nearly all women received prophylactic uterotonics across all four phases, with a significant increase after T3 (T4-T1: 100%-98%; 95% CI: 4.4-0.4). Oxytocin alone was the most used in T1 (98%) and T2 (94%) and HSC alone in T3 (87%) and T4 (82%) (T4-T1: 95% CI: 75.5-83.3). PPH diagnosis tripled from 1.2% of all births to 3.6% (T2-T1: 95% CI: 0.4-5.2) and stayed roughly at 3% in T3 and T4. For treatment, universal oxytocin use in T1 and T2 decreased in T3 upon HSC initiation (T3-T2: 27%-100%; 95% CI: 95.5-49.9), whereas TXA use increased in T4 (T4-T1: 95%-0%; 95% CI: 54.6-99.0).

Conclusion and global health implications: An intervention package to improve the quality of PPH prevention and treatment can effectively increase HSC and TXA use in crisis settings. It could be scaled up in similar contexts with ongoing supervision to mitigate confusion between the existing and new medications, such as the reduced use of oxytocin for PPH treatment. Sustaining cold chain investments remain vital to ensure oxytocin quality.