title: A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery.
abstract: OBJECTIVE
  To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery.
  
  
  METHODS
  Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study.
  
  
  METHODS
  Tertiary pediatric cardiac ICU.
  
  
  METHODS
  Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation.
  
  
  METHODS
  Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours.
  
  
  RESULTS
  Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure.
  
  
  CONCLUSIONS
  Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in infants postoperative from open heart surgery are multifactorial. Although dexmedetomidine may play a role in decreasing heart rate immediately postoperative, the changes were not clinically significant and did not fall below postinfusion heart rates.
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, CA, USA. felicesu@stanford.edu
authors.forename: Felice
authors.initials: F
authors.lastname: Su
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nicolson
authors.forename: Athena F
authors.initials: AF
authors.lastname: Zuppa
mesh_terms: D060666:Airway Extubation; D006348:Cardiac Surgical Procedures; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007223:Infant; D007262:Infusions, Intravenous / Q000379:methods*; D007362:Intensive Care Units; D008297:Male; D011182:Postoperative Care / Q000379:methods*; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine