Five unit bolus oxytocin at cesarean delivery in women at risk of atony: a randomized, double-blind, controlled trial.

BACKGROUND: I.v. bolus oxytocin is used routinely during cesarean delivery to prevent postpartum hemorrhage. Its adverse hemodynamic effects are well known, resulting in a recent change in dose from 10 IU to 5. Whether a 5 IU bolus has any advantages over infusion alone is unclear. We tested the hypothesis that a 5 IU i.v. bolus of oxytocin before the initiation of a continuous infusion decreases the need for additional uterotonic drugs in the first 24 hours after delivery in women with risk factors for uterine atony undergoing cesarean delivery, compared with infusion alone. METHODS: A prospective, randomized, double-blind, controlled trial was conducted in 143 subjects undergoing cesarean delivery with at least 1 risk factor for uterine atony. Subjects received 5 IU bolus of oxytocin or normal saline i.v. over 30 seconds after umbilical cord clamping. All subjects received an infusion of 40 IU oxytocin in 500 mL normal saline over 30 minutes, followed by 20 IU in 1 L over 8 hours. The primary outcome was the need for additional uterotonics in the first 24 hours after delivery. Secondary outcomes included uterine tone as assessed by the surgeon (5-point Likert scale: 0 = "floppy," 4 = "rock hard"), estimated blood loss, side effects of bolus administration, and the oxytocin bolus-placental delivery interval. RESULTS: There was no difference in the need for additional uterotonic drugs in the first 24 hours between groups. There was a significant difference in uterine tone immediately after placental delivery (P < 0.01) (2.8 in the oxytocin group [95% confidence interval 2.6-3.0] vs 2.2 in the saline group [95% confidence interval 1.8-2.5]), which disappeared after 5 minutes. There were no differences in observed or reported side effects between groups. CONCLUSIONS: We found that a 5 IU i.v. bolus of oxytocin added to an infusion did not alter the need for additional uterotonic drugs to prevent or treat postpartum hemorrhage in the first 24 hours in women undergoing cesarean delivery with risk factors for uterine atony, despite causing an initial stronger uterine contraction. Our study was not powered to find a difference in side effects between groups. These results suggest that an oxytocin infusion may be adequate without the need for a bolus, even in high-risk patients.

Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium.

The ovarian surface epithelium (OSE) is the precursor of common epithelial ovarian carcinomas. In the present study, we examined the molecular mechanisms and possible physiological basis for the propensity of OSE cells to undergo epithelio-mesenchymal transition (EMT) in response to environmental influences. We hypothesized that EMT may be a homeostatic mechanism that permits displaced OSE to assume a stromal phenotype within the ovarian cortex. We report that EGF in conjunction with hydrocortisone is the EMT-inducing factor of OSE as shown by changes to a fibroblast-like morphology and growth pattern. EGF increased cell motility, enhanced the activities of secreted pro-matrix metalloproteinase (MMP)-2 and -9, and enhanced expression and activation of Erk and integrin-linked kinase (ILK). Increased ILK expression correlated with the activation of PKB/Akt, the phosphorylation of GSK-3beta, and the increased expression of cyclin E and cdk2 kinase. EGF withdrawal resulted in a more epithelial morphology and reversal of the EGF-induced activation of signaling pathways and pro-MMP activity. In contrast, treatment of EGF-treated cells with specific inhibitors of phosphatidylinositol 3-kinase, Mek, or ILK inhibited the inhibitor-specific pathways. The inhibitors caused suppression of EGF-induced migration and pro-MMP-2/-9 activities but did not lead to any change in EGF-induced mesenchymal morphology. ILK small interfering RNA inhibited Akt phosphorylation and reduced pro-MMP-2/-9 activities but had no effect on Erk activation or cell morphology. These results indicate that the EGF-induced morphological and functional changes in OSE cells are controlled by distinct signaling mechanisms working in concert. EMT of OSE cells displaced by ovulation likely permits their survival and integration with a fibroblast-like identity within the stroma. Failure to do so may lead to the formation of epithelium-derived inclusion cysts, which are known preferential sites of malignant transformation.