title: The ED90 of prophylactic oxytocin infusion after delivery of the placenta during cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study.
abstract: BACKGROUND
  Prophylactic administration of oxytocin as a part of active management of the third stage of labor reduces the risk of postpartum hemorrhage. Prophylactic oxytocin is often administered as an infusion rather than a bolus. The aim of the current up-down sequential allocation dose-response study was to test the hypothesis that parturients who receive intrapartum exogenous oxytocin therapy, and who subsequently undergo cesarean delivery for labor dystocia, will have a higher estimated effective dose in 90% of paturients (ED90) for oxytocin infusion in the third stage of labor compared with nonlaboring parturients.
  
  
  METHODS
  The study design was a single-blinded, dual-arm, dose-response study using a 9:1 biased-coin sequential allocation method to estimate the ED90 of an infusion of prophylactic oxytocin in women undergoing cesarean delivery with neuraxial anesthesia. The experimental (laboring) group included women scheduled for intrapartum cesarean delivery after prior exposure to exogenous oxytocin, and the control (nonlaboring) group included women scheduled for elective cesarean delivery. The starting infusion rate was 18 IU/h, with an incremental dose of 2 IU/h. The outcome was satisfactory uterine tone 4 minutes after delivery as judged by the obstetrician. Secondary outcomes included requirement for additional uterotonic agents and maternal side effects (e.g., nausea and vomiting, ST-segment depression). Dose-response data for each group were evaluated by a log-logistic function and ED90 estimates derived from the fitted equations using the delta method.
  
  
  RESULTS
  Thirty-eight and 32 subjects participated in the nonlaboring and laboring groups, respectively. The oxytocin ED90 was significantly greater for the laboring group (44.2 IU/h [95% confidence interval (CI), 33.8-55.6]) compared with that for the nonlaboring group (16.2 IU/h [95% CI, 13.1-19.3]; difference in dose 28 IU/h [95% CI of difference, 26-29, P < 0.001]). Significantly more women in the laboring group (34%) than in the nonlaboring group (8%) required supplemental uterotonic agents (difference 26% [95% CI of the difference, 7%-44%, P = 0.008]). The overall incidence of side effects was greater in the laboring group (69%) than in the nonlaboring group (34%; difference 25% [95% CI of the difference, 10%-59%, P = 0.004]).
  
  
  CONCLUSIONS
  Women with prior exposure to exogenous oxytocin require a higher initial infusion rate of oxytocin to prevent uterine atony after cesarean delivery than women without prior exposure.
authors.affiliation: From the Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Anne
authors.initials: A
authors.lastname: Lavoie
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McCarthy
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Wong
mesh_terms: D000328:Adult; D002585:Cesarean Section; D002641:Chicago; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007749:Labor Stage, Third / Q000187:drug effects*; D007751:Labor, Induced / Q000009:adverse effects / Q000379:methods*; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects; D010121:Oxytocin / Q000008:administration & dosage* / Q000009:adverse effects; D010920:Placenta; D011247:Pregnancy; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D014593:Uterine Inertia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D010120:Oxytocics; D010121:Oxytocin