Pharmacokinetics of dexmedetomidine infusions for patients in the intensive care unit

Introduction

To date the pharmacokinetics of the sedative agent, dexmedetomidine, has only been reported in volunteers [1,2]. This study investigated the pharmacokinetic profile of dexmedetomidine infusions in human patients requiring postoperative sedation and ventilation in the ICU.

Methods

Ten adult patients who were expected to require a minimum of 6 hours of postoperative sedation and ventilation were studied. Patients received a loading dose of dexmedetomidine (DEX) of 2.5 µg/kg/h over 10 min (approx 0.42 µg/kg) followed by a maintenance infusion rate of 0.7 µg/kg/h. Alfentanil infusion was commenced if additional analgesia was required. The Ramsay sedation score and Bispectral Index (BIS) were used to measure depth of sedation. Blood samples were obtained for measurement of plasma concentrations of DEX immediately prior to infusion start (t = 0), at 5, 10, 20, 30, 45, 60, min, 2, 3.5, 6, 10, 14, 19 and 24 h if the patient was still receiving a DEX infusion. Samples were also obtained at 0, 10, 25, 40, 60, 90 min and 2, 3, 4, 5, 6, 12, 24 h post infusion termination. Plasma DEX concentrations were measured using a gas chromotographic-mass spectrometer method (Oneida Research Services Inc, Whitesboro, NY, USA). Pharmacokinetic parameters were estimated by noncompartmental methods [3].

Results

Median (interquartile range) Ramsay, BIS and APACHE II scores were 4.5 (4.2-4.6), 53 (45-58), 13 (12-16) respectively. Tabular results are expressed as mean (SD).

Conclusion

Previously reported [2] DEX subjects' clearances range from 46.3 (8.3) to 35.3 (6.8) l/h, V_ss range from 88.7 (22.9) to 102.4 (20.3) l and t_1/2 from 1.78 (0.30) to 2.5 (0.61) h. Although these patient pharmacokinetic values appear slightly greater, the results are generally comparable to those previously reported for subjects.

Supported by Abbott UK.

Table 1