title: Identifying a rapid bolus dose of dexmedetomidine (ED50) with acceptable hemodynamic outcomes in children.
abstract: BACKGROUND
  Dexmedetomidine is a highly sensitive, specific α2 adrenoceptor agonist with anxiolytic, sedative, and analgesic effects. Administration is recommended as a loading dose infused over 10 min. Clinical experience and a previous study suggested a shorter time frame might be used without causing adverse hemodynamic effects.
  
  
  OBJECTIVE
  To determine the dexmedetomidine dose that can be given as a rapid 5 s bolus to healthy children during total intravenous anesthesia (TIVA) without causing significant hemodynamic effects.
  
  
  METHODS
  ASA I-II children, aged 5-9 years, having elective surgery under TIVA were recruited. The up-and-down sequential study design was employed to determine the effective dose of dexmedetomidine, starting at 0.3 mcg·kg(-1) with 0.1 mcg·kg(-1) intervals, which caused no hemodynamic response in half the subjects (ED50). Positive responses were defined as mean blood pressure (MAP) and/or heart rate (HR) changes ≥30% from baseline. Three parametric estimators and one nonparametric estimator were used to determine the ED50.
  
  
  RESULTS
  Twenty-one subjects with median age 7.1 (range 5.4-9.5) years and median weight 23.6 (range 16.2-36.7) kg were recruited. A maximum median HR decrease of 20 b·min(-1) occurred at 50 s and a maximum median MAP increase of 12.5 mmHg occurred at 100 s after bolus dose administration. Fifteen subjects (71%) had a HR <60 b·min(-1) while one subject had a HR <40 b·min(-1) (minimum 35 b·min(-1)) for 60 s following the dexmedetomidine bolus. Four estimators led to an ED50 estimate for dexmedetomidine of 0.49 mcg·kg(-1) [95% CI 0.26-0.80 mcg·kg(-1)].
  
  
  CONCLUSIONS
  The ED50 of dexmedetomidine administered over 5 s without significant hemodynamic compromise is 0.49 mcg·kg(-1). Further work is needed to determine the 'safe' (ED5 or less) and effective dose for desired perioperative clinical outcomes.
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Joy
authors.initials: J
authors.lastname: Dawes
authors.forename: Dorothy
authors.initials: D
authors.lastname: Myers
authors.forename: Matthias
authors.initials: M
authors.lastname: Görges
authors.forename: Guohai
authors.initials: G
authors.lastname: Zhou
authors.forename: J Mark
authors.initials: JM
authors.lastname: Ansermino
authors.forename: Carolyne J
authors.initials: CJ
authors.lastname: Montgomery
mesh_terms: D000771:Anesthesia, Intravenous; D062186:Arterial Pressure / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D019990:Perioperative Care
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine
keywords: ED50; bolus; dexmedetomidine; hemodynamics; up-and-down method