Anesth Pain Med.  2007 Oct;2(4):190-196.

Nonlinear Mixed Effect Modeling of Propofol Population Pharmacokinetics in Patients with Major Burn

• Kwak IS
• Kim KM

Abstract

BACKGROUND: 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.

Keyword

burns; cardiac index; pharmacokinetics; propofol

MeSH Terms

Adult
Body Surface Area
Body Weight
Burns*
Chromatography, High Pressure Liquid
Echocardiography
Humans
Perioperative Period
Pharmacokinetics*
Propofol*
Propofol