title: Steady-state plasma concentrations of midazolam in critically ill infants and children.
abstract: OBJECTIVE
  To determine the steady-state plasma concentrations of midazolam in critically ill infants and children.
  
  
  METHODS
  Prospective uncontrolled study conducted over 18 months.
  
  
  METHODS
  Regional pediatric intensive care unit in a children's hospital.
  
  
  METHODS
  Thirty-eight infants and children, aged 1 month to 13 years, requiring midazolam as sedation during mechanical ventilation. The patients were divided into three age groups: (1) infants less than 12 months (n = 16); (2) children 1-2 years (n = 12); and (3) children aged 3 years and older (n = 10).
  
  
  METHODS
  A single blood sample was collected once steady-state plasma concentrations of midazolam were achieved during a continuous intravenous infusion. Plasma clearance was calculated from the plasma concentrations and infusion rate.
  
  
  RESULTS
  The plasma clearance was higher in children aged 3 years and older (median plasma clearance 13.0 mL/min/kg) than in infants and children 1-2 years old (median plasma clearance 3.1 and 2.3 mL/min/kg, respectively) (Kruskal-Wallis analysis of variance, p < 0.01). The midazolam infusion rates were similar for the three groups studied (Kruskal-Wallis analysis of variance, p > 0.05). The plasma concentrations of midazolam were significantly lower in children 3 years and older (median plasma concentration 128 ng/mL) than in infants and children 1-2 years old (median plasma concentrations 395 and 790 ng/mL, respectively) (Kruskal-Wallis analysis of variance, p < 0.05).
  
  
  CONCLUSIONS
  The plasma clearance in children 3 years and older was higher than in infants and children up to 2 years old. There was considerable interindividual variation in the steady-state plasma concentrations of midazolam in critically ill infants and children.
authors.affiliation: Institute of Child Health, Alder Hey Children's Hospital, Liverpool, England.
authors.forename: J
authors.initials: J
authors.lastname: Hughes
authors.forename: A M
authors.initials: AM
authors.lastname: Gill
authors.forename: H
authors.initials: H
authors.lastname: Mulhearn
authors.forename: E
authors.initials: E
authors.lastname: Powell
authors.forename: I
authors.initials: I
authors.lastname: Choonara
mesh_terms: D000293:Adolescent; D000375:Aging / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008874:Midazolam / Q000008:administration & dosage / Q000097:blood*; D010372:Pediatrics; D011446:Prospective Studies
chemical_list: D008874:Midazolam