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Carbetocin vs. oxytocin: In-vitro human myometrial contractions after oxytocin pre-treatment
Abstract Number: GM-3
Abstract Type: Original Research
Postpartum hemorrhage (PPH) is the main cause of maternal mortality globally. Oxytocin is the 1st-line agent for prevention of uterine atony and PPH, but myometrial exposure to oxytocin in-vivo (during oxytocin augmented labor) or in-vitro may lead to its receptor desensitization, reducing the efficacy of subsequent oxytocin administration . Carbetocin, a new oxytocin analog, is recommended by the Society of Obstetricians and Gynecologists of Canada instead of oxytocin in elective cesarean deliveries (CD), yet the supporting evidence is scarce. Our study evaluated the relative efficacy of carbetocin vs. oxytocin in-vitro in oxytocin-pretreated human myometrium.
Myometrial samples of non-laboring women undergoing elective CD were pretreated in-vitro with physiological salt solution (PSS) (control) or 10-5M oxytocin for 2h, then subjected to increasing concentrations of oxytocin or carbetocin (from 10-10 to 10-5M) in organ bath chambers at 1g tension. The amplitude and frequency of contractions during the dose-response were recorded, and area under the curve (AUC) calculated and compared between groups.
Myometrial samples of 9 women were obtained and 25 experiments performed (oxytocin n=14; carbetocin n=11). The AUC of the contractions increased with increasing drug concentration, but the dose-response curves of the 2 drugs had different slopes (Fig 1). Overall, the mean AUC during the dose-response was higher in control vs. oxytocin pretreated groups, both for oxytocin (∆17%) and carbetocin (∆27%). At the peak of the carbetocin dose-response curve (10-7M), there was a significant difference between control vs. oxytocin pretreated groups of carbetocin (p=0.03) and near significant difference between oxytocin groups (p=0.06).
Unlike previous studies, we found a higher maximal contractile effect of carbetocin than oxytocin in control groups. Similar to oxytocin, myometrial contractions were inhibited in oxytocin pretreated samples after carbetocin administration, suggesting oxytocin desensitization decreases carbetocin's efficacy. Carbetocin may be preferred over oxytocin for PPH prophylaxis after elective CD, but may be a poor choice for laboring parturients pre-exposed to oxytocin. Clinical studies are warranted to confirm these findings.
1.Am J Obstet Gynecol 2003;188:497–502
2.J Obstet Gynaecol Can 2009;31:980-93
3.Eur J Pharmacol 1998;355:203-10
4.Reprod Sci 2009;16:501-8