Etomidate and Ketamine Significantly Reduce Gravid Human Uterine Contractility Ex Vivo; Oxytocin Reverses Effects

Effective uterine contractions are crucial for successful labor, delivery, and preventing postpartum hemorrhage (PPH), a leading cause of maternal mortality. Uterine atony, the failure of the uterus to contract adequately after delivery, is the primary cause of PPH. While oxytocin is the standard treatment for uterine atony, its effectiveness can be compromised by prior exposure or desensitization of oxytocin receptors (OTR). The impact of commonly used intravenous anesthetic agents on myometrial contractility, particularly in the presence of oxytocin, remains a critical gap in understanding how to optimize uterine tone during and after Cesarean deliveries.

Researchers conducted an ex vivo laboratory study using individual myometrial strips obtained from 29 patients undergoing elective Cesarean delivery. The strips were subjected to concentration-response testing in organ bath chambers with intravenous agents: propofol, etomidate, and ketamine. Drugs were applied in 0.5 log molar increases from 10-7 M to 10-4 M, with or without co-administration of oxytocin. A control group received oxytocin alone. The primary outcome measured was the motility index (amplitude × frequency), with contractility parameters recorded using organ bath chamber assays.

All studied intravenous anesthetic drugs produced a concentration-dependent decrease in uterine contractility. The motility index significantly decreased with increasing concentrations of each study drug. Specifically, the overall motility index with etomidate was -6% (95% CI [-77 to -13]; n=29; P=0.007) and with ketamine was -66% (95% CI [-82 to -35]; n=29; P<0.001) compared to the oxytocin control group. The difference for propofol was not statistically significant (-38%; 95% CI [-70 to 29]; n=25; P=0.47).