Aminoglycoside pharmacokinetic parameters in neurocritical care patients undergoing induced hypothermia.

STUDY
OBJECTIVE: To determine the effects of mild-to-moderate induced hypothermia-a neuroprotectant and/or therapeutic strategy for the management of intracranial hypertension in neurologically injured patients-on the pharmacokinetics of aminoglycoside therapy.
DESIGN: Pharmacokinetic analysis.
SETTING: Critical care unit at a university-affiliated hospital. PATIENTS: Three patients, aged 22, 24, and 47 years, who received tobramycin and had documented tobramycin levels while undergoing induced hypothermia for more than 24 hours for intracranial hypertension.
MEASUREMENTS AND MAIN RESULTS: For each of the three patients, predicted pharmacokinetic parameters (volume of distribution, first-order elimination rate constant, half-life, and renal drug clearance) based on population data were compared with their actual pharmacokinetic parameters that were calculated based on observed tobramycin serum levels. All three patients had a normal creatinine clearance, estimated according to established methods. When pharmacokinetic parameters were calculated after the first tobramycin dose using a one-compartment method, all patients had a slower first-order elimination rate and a larger volume of distribution compared with predicted population estimates.
CONCLUSION: These findings suggest that induced hypothermia may result in impaired elimination of aminoglycosides. Caution should be exercised when attempting to use predicted pharmacokinetic parameters to dose aminoglycosides in this patient population, and first-dose pharmacokinetics should be considered to optimize the dose and dosing interval early in the course of therapy. Further investigation of this phenomenon with greater numbers of patients are needed to confirm these findings and to determine optimal dosing strategies of aminoglycosides in patients undergoing induced hypothermia.