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Postpartum hemorrhage (PPH) is a leading cause of maternal mortality in the developed and under-developed world, and uterine atony is the major contributing factor. Clinical guidelines for drug treatment of PPH vary internationally, and there are minimal comparative pharmacological data for the various uterotonic compounds used. The aim of this study was to evaluate a range of contractile parameters in human pregnant myometrium, for the uterotonic agents used clinically in the management of atonic PPH.
Myometrial biopsies were obtained from 19 patient donors undergoing elective cesarean delivery at term. The effects of the uterotonic agents oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips. The potency (expressed as pEC50) and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15 minute exposure.
The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments mean contractile force was the parameter that separated the agents. Oxytocin was not statistically different from carboprost or syntometrine but was superior to all other agents. There was a wide difference in potencies using both measures of contractility, with oxytocin and carbetocin being most potent. There were no significant differences in the peak amplitude of response between agents, except for misoprostol, which was inactive.
Consideration of the pharmacological effects of these compounds in vitro indicates that oxytocin is the most efficient of all compounds in achieving sustained uterine contractility, followed closely by syntometrine and carboprost. These findings question the potential clinical efficacy of misoprostol in the management of post-partum hemorrhage.