Enhanced Clearance of Propofol in Patients with Major Burns

Kwak, In Suk; Jung, Sung Won; Lee, Jin Young; Jung, Mi Hwa; Choi, Young Ryong; Won, Rim Soo; Han, Tae Hyung

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 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 were used as controls. Propofol 2 mg/kg was given intravenously over 10 seconds as a single bolus in both groups. Blood samples (n = 20) were collectedat predetermined intervals. A noncompartmental approach 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). The clearance (Cl) and total volume of distribution (Vd) of propofol were higher in the burns patients, compared with the controls, yielding a smaller area under the curve. The total half-life (t1/2) was similar in both groups.
CONCLUSIONS
There is a large increase in Vd and Cl in the burns patients compared to with the controls. The increased Cl in the burns patients is most likely to be related to the increased CI. Therefore, the initial bolus dose and maintenance infusion may have to be increased in the burns patients, provided the pharmacodynamic sensitivity is unaltered.