title: High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety.
abstract: BACKGROUND
  Dexmedetomidine is an α(2)-receptor agonist used for sedation in the intensive care unit (ICU). Although dexmedetomidine is labeled for sedation in critically ill patients at doses up to 0.7 μg/kg/h, recent studies have used more liberal dosing regimens. However, to our knowledge, no study has assessed the clinical impact of doses greater than 0.7 μg/kg/h when compared to doses within the Food and Drug Administration--approved labeling.
  
  
  OBJECTIVE
  To compare the clinical efficacy and safety of high (HD) and low (LD) doses of dexmedetomidine for sedation in the ICU.
  
  
  METHODS
  This retrospective study included a sample of patients who received dexmedetomidine in medical, surgical, medical/surgical, and cardiothoracic ICUs between January 1, 2008, and December 1, 2009. Patients were included in the LD group if their maximum dose was less than 0.7 μg/kg/h or in the HD group if any dose was more than 0.7 μg/kg/h. Efficacy was determined by the percentage of Richmond Agitation and Sedation Scale (RASS) scores for each patient maintained at goal sedation (-1 to +1), and safety was determined by the incidence of hypotension and bradycardia.
  
  
  RESULTS
  Forty-three of 133 patients received HD dexmedetomidine. Patients in the LD group had a significantly higher percentage of RASS scores at goal (60.0% vs 48.6%; p = 0.03), while those in the HD group experienced a higher percentage of RASS scores classified as undersedated (19.2% vs 4.9%; p = 0.001). There was no significant difference in the incidence of hypotension or bradycardia between groups.
  
  
  CONCLUSIONS
  Patients treated with HD dexmedetomidine had fewer RASS scores at goal. Our data suggest that increasing the dose of dexmedetomidine may not enhance sedation efficacy or lead to an increased incidence of adverse effects. Patients who have not achieved goal sedation at doses of 0.7 μg/kg/h or less may not respond further to increased doses.
authors.affiliation: The Ohio State University, Columbus, OH, USA.
authors.forename: G Morgan
authors.initials: GM
authors.lastname: Jones
authors.forename: Claire V
authors.initials: CV
authors.lastname: Murphy
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Gerlach
authors.forename: Erin M
authors.initials: EM
authors.lastname: Goodman
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Pell
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001919:Bradycardia / Q000139:chemically induced; D003422:Critical Care / Q000379:methods; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine