Population pharmacokinetics of a propofol bolus administered in patients with major burns.

OBJECTIVE

In operating theaters and burn units, propofol is commonly used for sedation and anesthesia in patients with major burns. This study determined the population pharmacokinetics of propofol in burns and identified clinically significant covariates.

METHOD

Seventeen adults, age 42±10 (mean±SD) years, with 41±19% total body surface area burns, were enrolled at 16±14 days after-burn. Non-burn adults (n=19) served as controls. After an intravenous bolus of 2mg/kg propofol, the plasma concentration was determined at designated times for up to 4.5h. Concentration-time profiles were analyzed using nonlinear mixed-effect modeling.

RESULTS

A three-compartment model gave the best fit. The volume of distribution of the central compartment (V(1)) was considerably greater in the burned than non-burned group (48.4 L vs. 27.6 L, respectively). The clearances of the central (CL(1)) and slow peripheral (CL(3)) compartments were higher in burn patients (4.2 L/min vs. 1.7 L/min and 3.6 L/min vs. 1.1 L/min, respectively). Adding the covariates BURN to V(1), CL(1), and CL(3) and WT (weight) to CL(1) significantly improved the model performance.

CONCLUSION

The pharmacokinetic characteristics of a propofol bolus administered in patients with major burns were enhanced clearance and expanded volume of distribution. BURN and WT were the important covariates. For sedation or anesthesia induction, a higher than recommended dose of propofol may be required to maintain therapeutic plasma drug concentrations in patients with severe burns. Vigilance regarding the burned individual and careful titration of hypnotics to the desired effect cannot be overemphasized.