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In vitro human myometrial contractility with various uterotonic agents and their combinations
Abstract Number: O2-04
Abstract Type: Original Research
Introduction: Oxytocin (OT) is the most widely used uterotonic agent in the prevention of PPH; additional drugs such as carboprost (CARB) and ergonovine (ERG) are used if OT alone proves ineffective. The comparative efficacy of the individual uterotonics, as well as of their combinations is still poorly understood. We hypothesized that the use of ERG or CARB in combination with OT would improve contractility compared to OT alone in myometrial strips, pretreated or not with OT.
Methods: This in-vitro study was done on myometrial samples obtained from term pregnant women undergoing CS under regional anesthesia. After obtaining spontaneous contractions in organ baths, the samples were either pretreated with OT 10-5M (Experimental) or physiological salt solution (Control) for 2h. This was followed by dose-response testing with OT, ERG, or CARB [10-10 to 10-5M]), either alone or in combination with a fixed low dose (10-10M) (LDOx) or high dose (10-6M) (HDOx) OT. The amplitude, frequency and motility index (MI=ampxfreq) of contractions during the dose response period were analyzed with linear regression models, and compared among the groups. The primary outcome was the MI across the study groups.
Results: 169 experiments were done from samples obtained from 56 women. Fig 1 shows Control and Experimental groups: OT (n=24); ERG (n=26); CARB (n=23); ERG+LDOx (n=25); ERG+HDOx (n=26); CARB+LDOx (n=23); and CARB+HDOx (n=22). The MI of OT was significantly higher in Control vs. Experimental group (p<0.001). When all Control groups were compared, the MI of OT was higher than ERG (p<0.001), CARB (p<0.001), ERG+LDOx (p<0.001) and CARB+LDOx (p<0.001). However, in OT pretreated groups, all the combination groups exhibited significantly superior contractility response compared to OT alone.
Discussion: We observed attenuation of OT-induced contractility in OT pretreated myometrial strips, confirming the previously established OT-receptor desensitization phenomenon.1Among the three uterotonics, OT appears to be the most effective drug if the myometrium is not pre-exposed to OT. However, in the OT pretreated myometrium, a synergistic response is evident, and the combination of OT with either ERG or CARB produces superior response compared to OT alone. This implies that other uterotonics should be considered early in the event of poor responsiveness of myometrium to OT, especially if the uterus is preexposed to OT during labor.
Reference:1.Balki M. Anesthesiology 2013;119:552-61