Comparative efficacy of uterotonic agents: in vitro contractions in isolated myometrial strips of labouring and non-labouring women

Can J Anaesth. 2014 Sep;61(9):808-18. doi: 10.1007/s12630-014-0190-1. Epub 2014 Jun 7.

Abstract

Purpose: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carboprost / pharmacology
  • Dose-Response Relationship, Drug
  • Ergonovine / pharmacology
  • Female
  • Humans
  • In Vitro Techniques
  • Labor, Obstetric / physiology*
  • Misoprostol / pharmacology
  • Oxytocin / pharmacology
  • Pregnancy
  • Uterine Contraction / drug effects*

Substances

  • Misoprostol
  • Oxytocin
  • Carboprost
  • Ergonovine

Associated data

  • ClinicalTrials.gov/NCT01689311