title: Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose.
abstract: OBJECTIVE
  The purpose of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 90% of females (ED90) undergoing elective Cesarean delivery (CD) under spinal anesthesia.
  
  
  METHODS
  We conducted a double-blind dose-finding study of carbetocin. Forty females undergoing elective CD received carbetocin intravenously upon delivery of the fetus. The dose of carbetocin for each patient was determined according to a biased-coin up-and-down sequential allocation scheme designed to cluster doses close to ED90. The initial dose was 10 μg, with increments/decrements of 5 μg. The anesthesiologist, obstetrician, and patient were blinded to the dose. The obstetrician assessed the uterine tone at one-minute intervals for five minutes after carbetocin administration. In case of unsatisfactory tone, additional uterotonics were administered. The primary outcome was requirement for additional intraoperative uterotonics. Secondary outcomes were postoperative requirement for additional uterotonics within 24 hr of delivery, estimated blood loss and side effects.
  
  
  RESULTS
  The ED90 of carbetocin was 14.8 μg (95% confidence interval 13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no requirement of additional intraoperative uterotonics. Two patients (5%) required postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood loss was 786 (403) mL and the overall incidence of hypotension (decrease in systolic blood pressure ≥ 20% baseline) was 37.5%.
  
  
  CONCLUSIONS
  Based on our study, the ED90 of carbetocin at elective CD is less than one-fifth the currently recommended dose of 100 μg. This study was registered at clinicaltrials.gov (NCT-01651130).
authors.affiliation: Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Room 781, Toronto, ON, M5G 1X5, Canada.
authors.forename: Mubeen
authors.initials: M
authors.lastname: Khan
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Balki
authors.forename: Iram
authors.initials: I
authors.lastname: Ahmed
authors.forename: Dan
authors.initials: D
authors.lastname: Farine
authors.forename: Gareth
authors.initials: G
authors.lastname: Seaward
authors.forename: Jose C A
authors.initials: JC
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000775:Anesthesia, Spinal; D002585:Cesarean Section / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D010120:Oxytocics / Q000008:administration & dosage / Q000627:therapeutic use*; D010121:Oxytocin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D010120:Oxytocics; D010121:Oxytocin; C020731:carbetocin