title: Pharmacokinetics of midazolam administered by continuous intravenous infusion to intensive care patients.
abstract: OBJECTIVE
  To determine the pharmacokinetics of continuously infused midazolam in patients during intensive care.
  
  
  METHODS
  Descriptive trial.
  
  
  METHODS
  General ICU in a Swiss hospital.
  
  
  METHODS
  Eight critically ill patients requiring mechanical ventilation.
  
  
  METHODS
  To achieve an appropriate level of long-term sedation, the rate of iv infusion of midazolam in ICU patients was adjusted individually to between 6 and 15 mg/hr. Blood samples were taken during and after the continuous infusion of midazolam.
  
  
  METHODS
  Measurements included plasma concentration time profiles of midazolam and pharmacokinetic parameters, such as elimination half-life, clearance, and volume of distribution.
  
  
  RESULTS
  The elimination half-life was prolonged (mean 5.4 vs. 2.3 hrs) and the volume of distribution was larger (3.1 vs. 0.9 L/kg) in patients vs. healthy volunteers. The clearance did not differ between groups (6.3 vs. 4.9 mL/min/kg in patients vs. volunteers, respectively).
  
  
  CONCLUSIONS
  The increased volume of distribution in our critically ill patients is the major determinant for the observed slower elimination of midazolam. It is unlikely that the hepatic metabolism of midazolam was impaired in these patients.
authors.affiliation: Intensive Care Unit, Hospital San Giovanni, Bellinzona, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Malacrida
authors.forename: M E
authors.initials: ME
authors.lastname: Fritz
authors.forename: P M
authors.initials: PM
authors.lastname: Suter
authors.forename: C
authors.initials: C
authors.lastname: Crevoisier
mesh_terms: D000328:Adult; D003422:Critical Care; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood / Q000188:drug therapy; D013997:Time Factors
chemical_list: D008874:Midazolam