To describe PK of prolonged (>24 hrs) and HD DEX in critically ill patients and to determine if a linear relationship remains.
(i) All patients received DEX at a constant rate for the first 12 hours (doses were 0.1, 0.2, 0.45, or 0.7 mcg/kg/hr with no LD) then titrated by bedside nurse to goal sedation score. The dose allowed was 0.1–2.5 mcg/kg/hr. (ii) DEX plasma levels were obtained at predefined times.
(i) DEX retained a linear relationship at doses of 2.5 mcg/kg/hr (. (ii) PK parameters remained similar to those reported in healthy individuals. (iii) A multivariate analyses showed a significant difference in higher Cls () and shorter elimination half-life () with lower baseline SAPS II (<42) score.
To describe PK of prolonged (>48 hrs) DEX infusions in critically ill patients.
(i) All patients received a LD of 3–6 mcg/kg/hr over 10 min then a maintenance infusion of 0.1–2.5 mcg/kg/hr titrated by bedside nurse to desired sedation. (ii) DEX plasma levels were obtained at predefined times.
(i) PK parameters remained similar to those reported in healthy individuals. (ii) The elimination Cls was 57.0 L/hr (42.1, 65.6) and was 132 L (96, 189). (iii) A multivariate analyses showed that DEX Cls decreased with decreasing CO and increasing age (); was increased in patients with low albumin concentration ().
(i) 527 ICU patients enrolled in phase III studies of prolonged (>24 hrs) DEX infusion. (ii) 96% were Caucasian.
To describe PK of prolonged (>24 hrs) DEX infusions in critically ill patients.
(i) All patients received an initial infusion of 0.7 g/kg/h for 1 hour then a maintenance infusion of 0.2–1.4 g/kg/h titrated by bedside nurse to desired sedation. (ii) Maximum duration of infusion was 14 days. (iii) DEX plasma levels were obtained at baseline, 1 hr after beginning treatment, and then the same time each day. Samples were taken 24 and 48 hours after infusion ended.
(i) PK parameters remained similar to those reported in healthy individuals. (ii) The strongest covariate relationship was between DEX Cls and body weight. (iii) A multivariate analysis showed an inverse relationship between plasma albumin and ; however, this relationship did not account for interpatient variability. (iv) DEX Cls was not affected by CO or concentration levels.
P: prospective, O: observational; ICU: intensive care unit; PK: pharmacokinetics; HD: high dose; DEX: dexmedetomidine; LD: loading dose; Cls: clearance; SAPS II: Simplified Acute Physiology Score; CO: cardiac output; : volume of distribution at steady state.
