Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: Preliminary study*

Abstract

OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine and monitor any dexmedetomidine-related adverse events in postoperative pediatric patients requiring short-term mechanical ventilation, analgesia, and sedation in the pediatric intensive care unit (PICU). DESIGN: Prospective, case series. SETTING: Operating room and PICU in a large, urban children's hospital. Enrollment from February 14 to November 25, 2002. PATIENTS: Ten children (4 months to 7.9 yrs of age) who received postoperative infusions of dexmedetomidine. INTERVENTIONS: Toward the end of the operation, patients received dexmedetomidine at 1 microg/kg per hr for 10 mins. The anesthesiologist then titrated the infusion, as clinically indicated, to a rate of 0.2-0.7 microg/kg per hr. In the PICU, the infusion was titrated by the nursing staff based on assessment with a modified Ramsey Sedation Scale, while maintaining heart rate and blood pressure within normal limits for age. Dexmedetomidine was continued until the intensivist felt the patient no longer benefited, but for no longer than 24 hrs. MEASUREMENTS AND MAIN RESULTS: At specified times during the infusion and after discontinuation, dexmedetomidine plasma concentrations were determined. Pharmacokinetic parameters were calculated using a two-compartment model. Vital signs, sedation scores, adjunct sedative or analgesic medications, and adverse events were recorded. Average duration of infusion was 18.8 hrs (range, 8-24 hrs). Means (+/-sd) were calculated for the following: clearance, 0.57 (+/-0.14) L/hr per kg; volume of distribution at steady state, 1.53 (+/-0.37) L/kg; and terminal elimination half-life, 2.65 (+/-0.88 hrs)-all similar to published values in adults. There were no serious adverse events related to dexmedetomidine. CONCLUSIONS: Dexmedetomidine, administered as a continuous infusion, produces consistent, predictable concentrations in children and infants. Further evaluations of the safety, efficacy, and pharmacodynamics of dexmedetomidine are warranted.