Steady-state plasma concentrations of midazolam in critically ill infants and children

OBJECTIVE: To determine the steady-state plasma concentrations of midazolam in critically ill infants and children. DESIGN: Prospective uncontrolled study conducted over 18 months. SETTING: Regional pediatric intensive care unit in a children's hospital. PATIENTS: 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). MAIN OUTCOME MEASURES: 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.