Second-Line Uterotonics for Uterine Atony: A Randomized Controlled Trial

We read with great interest the study by Cole et al1 published in the December 2024 issue, which assessed the effectiveness of two second-line uterotonics for managing uterine atony after prophylactic oxytocin administration during cesarean delivery. The primary outcome was uterine tone, evaluated on a scale of 0 to 10 by manual evaluation 10 minutes after uterotonic administration. Among the 100 women randomized, half received methylergonovine and half received carboprost. No significant differences in uterine tone scores or secondary outcomes were observed. Additionally, 32% of women required an additional uterotonic. We would like to highlight the importance of this trial, because robust data on second-line uterotonics are currently lacking. As a result, the use of these agents varies across countries,2 often driven more by national protocols than by high-quality evidence. This study also demonstrates the feasibility of conducting randomized trials in the context of postpartum hemorrhage (PPH), a critical clinical situation. The study raises the question of the choice of primary outcome in PPH. Their primary outcome was based on a subjective score, with sample size calculated for a minimal 1-point reduction. Although the scale has good interrater reliability, its clinical relevance remains unclear.3 Furthermore, no control group was included to evaluate the natural progression of uterine tone during cesarean delivery, such as after uterine closure or uterine massage. Total blood loss was not used as the primary outcome, because it may reflect a combination of surgical factors, rather than uterine atony, as explained by the authors. Additionally, total blood loss depends on management strategies implemented before the intervention under evaluation. In a randomized trial of intrauterine balloon tamponade, one-quarter of participants had already reached the primary endpoint (blood loss volume) at the time of randomization.4 Using the need for an additional intervention as a primary outcome is also limited, because it relies on the operator's subjective judgment. Maternal tolerance may be influenced by factors unrelated to the intervention being studied. To address this challenge, a Delphi consensus study identified 12 core outcomes for evaluating PPH interventions, including blood loss, shock, transfusion, and patient-reported outcomes.5 Standardizing clinically relevant outcomes is essential for generating evidence-based recommendations.