Table 2.
Studies evaluating pharmacokinetics in critically ill patients.
| Citation | Study Design | Population | Objective | Intervention | Results |
|---|---|---|---|---|---|
|
Iirola et al. (2011) [46] |
P, O | (i) 13 ICU patients. (ii) All Caucasian. |
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 (r
2 = 0.95). (ii) PK parameters remained similar to those reported in healthy individuals. (iii) A multivariate analyses showed a significant difference in higher Cls (P = 0.006) and shorter elimination half-life (P = 0.036) with lower baseline SAPS II (<42) score. |
|
| |||||
|
Iirola et al. (2012) [47] |
P, O | 21 ICU patients. | 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 V ss was 132 L (96, 189). (iii) A multivariate analyses showed that DEX Cls decreased with decreasing CO and increasing age (P = 0.009); V ss was increased in patients with low albumin concentration (P = 0.002). |
|
| |||||
|
Välitalo et al. (2013) [48] |
P, O | (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 µg/kg/h for 1 hour then a maintenance infusion of 0.2–1.4 µg/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 V ss; 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; V ss: volume of distribution at steady state.