[Effect of remifentanil on propofol pharmacokinetics with target controlled infusion in elderly patients].

Objective: To investigate the effects of remifentanil administered by target-controlled infusion (TCI) with different plasma concentration and time on pharmacokinetics of propofol in elderly patients.

Methods: Thirty-two ASA I-II patients (65-82 years old) undergoing elective lower abdominal operations were divided into 4 groups randomly: TCI propofol combined with epidural block (group A, n=8); TCI remifentanil with plasma concentration 4 μg/L and propofol (group B, n=8); TCI remifentanil with plasma concentration 7 μg/L and propofol (group C, n=8); and TCI propofol and remifentanil (plasma concentration 4 μg/L) with infusion time longer than 4 hours (group D, n=8). Propofol was infused by target-controlled infusion with plasma concentration 3 mg/L in the 4 groups. bispetral index (BIS), heart rate (HR), blood pressure (BP) were recorded during operation. Blood samples were collection from radial arterial catheter. Samples of 2 mL of arterial blood were taken at 0, 1, 3, 5, 10, 15, 30 min and then every 30 min after the start of the infusion of propofol, and at 0, 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, 240, 360, 480, 720, 1440 min after the termination of the infusion of propofol. Propofol concentrations in blood were measured by reversed-phase high-performance liquid chromatography (HPLC). The pharmacokinetics analyses were performed using the nonlinear mixed-effects model approach implemented in NONMEM computer program. After obtaining the best NONMEM model with covariates, the influence of coadministered remifentanil on the model was examined.

Results: In all the patients, the depth of anesthesia was enough (BIS value=40-60), and the circulatory system function was stable during operation. The final model of propofol pharmacokinetics in the three groups (A+B, A+C, and A+D groups) was best described by a three-compartment mammillary model. The values of objective function (OFV) were -810.1, -714.4, and -896.4. Addition of remifentanil covariate effects to the final model resulted in no improvement in the objective function.

Conclusion: target-controlled infusion of propofol combined with different plasma concentration of remifentanil or remifentanil infusing more than 4 hours had no effect on pharmacokinetics of propofol in elderly patients.