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Anesthetic Pharmacology
Anesthesia and Pain Medicine 2007;2(4):190-196.
Published online October 30, 2007.
Nonlinear Mixed Effect Modeling of Propofol Population Pharmacokinetics in Patients with Major Burn
In Suk Kwak, Kwang Min Kim
Department of Anesthesiology and Pain Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
Major burns can alter the pharmacokinetics of the commonly used drugs during the perioperative period. This study was carried out to define the population pharmacokinetics of propofol in the burned patients during the subacute hyperdynamic phase of the injury. METHODS: Twenty adults, aged 43.7 +/-2.3 years, with total body surface area burn of 44.0 +/-22.2%, were examined at 14.1 +/-2 days after the injury (mean +/-SD). Age and sex gender matched unburned patients served as controls. Propofol 2 mg/kg was given intravenously over 10 seconds as a single bolus in both groups. Blood samples (n = 20) were collected at predetermined intervals. Nonlinear mixed effect modeling was used for the pharmacokinetic analyses of the propofol concentrations, which were determined by HPLC. The cardiac index was measured by esophageal echocardiography. RESULTS: The burns patients had a significantly higher cardiac index (CI). Propofol population pharmacokinetics has shown that clearance (Cl) and total volume of distribution (Vd) of propofol were higher in the burned patients. The significant model influencing covariates are the history of burn injury, extent of the injury and body weight. CONCLUSIONS: There is a large increase in Vd and Cl in the burns patients compared to with the controls. Therefore, the initial bolus dose and short duration infusion may have to be increased in the burns patients, provided the pharmacodynamic sensitivity is unaltered.
Key Words: burns, cardiac index, pharmacokinetics, propofol
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