title: Comparative efficacy of uterotonic agents: in vitro contractions in isolated myometrial strips of labouring and non-labouring women.
abstract: OBJECTIVE
  To compare the in vitro contractile responses to oxytocin, ergonovine, prostaglandin F2 alpha (PGF2α), and misoprostol in isolated myometrium from non-labouring and labouring pregnant women.
  
  
  METHODS
  Myometrial strips obtained from labouring (with or without oxytocin augmentation) and non-labouring women undergoing Cesarean deliveries were subjected to a dose-response testing with oxytocin, ergonovine, PGF2α, or misoprostol (10(-10) M to 10(-5) M). The amplitude and frequency of contractions, motility index (MI) (amplitude × frequency), and area under the curve during the dose-response period were recorded. The primary outcome was the motility index. Data were analyzed using linear regression models.
  
  
  RESULTS
  We performed 130 experiments in myometrial strips obtained from 46 women. The overall MI (√gram·contractions·10 min(-1) [√g·c·10 min(-1)]) was greatest for oxytocin (mean 5.10 √g·c·10 min(-1); 95% confidence interval [CI] 4.70 to 5.50) than for ergonovine (mean 3.46 √g·c·10 min(-1); 95% CI 3.13 to 3.80; P < 0.001), PGF2α (mean 2.64 √g·c·10 min(-1); 95% CI 2.40 to 2.87; P < 0.001), and misoprostol (2.52 √g·c·10 min(-1); 95% CI 2.22 to 2.82; P < 0.001). The MI for oxytocin was significantly lower in augmented labour (mean 4.11 √g·c·10 min(-1); 95% CI 3.48 to 4.73) than in non-augmented labour (mean 5.19 √g·c·10 min(-1); 95% CI 4.39 to 6.00; P = 0.04) or in absence of labour (mean 5.80 √g·c·10 min(-1); 95% CI 5.36 to 6.24; P < 0.001). Nevertheless, in augmented labour, oxytocin still produced superior contractions compared with other uterotonic drugs. Responses to ergonovine, PGF2α, and misoprostol were unaffected by labour or prior exposure to oxytocin.
  
  
  CONCLUSIONS
  Oxytocin induces superior myometrial contractions compared with ergonovine, PGF2α, and misoprostol. The effect of oxytocin is reduced in myometrium of women with oxytocin-augmented labour; however, it is still superior to the other uterotonics. This trial was registered at ClinicalTrials.gov: NCT01689311.
authors.affiliation: Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Room 19-104, Toronto, ON, M5G 1X5, Canada, mrinalini.balki@uhn.ca.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Balki
authors.forename: Magda
authors.initials: M
authors.lastname: Erik-Soussi
authors.forename: John
authors.initials: J
authors.lastname: Kingdom
authors.forename: Jose C A
authors.initials: JC
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D002260:Carboprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004874:Ergonovine / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007743:Labor, Obstetric / Q000502:physiology*; D016595:Misoprostol / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D016595:Misoprostol; D010121:Oxytocin; D002260:Carboprost; D004874:Ergonovine