BMC Anesthesiology (Jan 2019)

Population pharmacokinetic-pharmacodynamic model of propofol in adolescents undergoing scoliosis surgery with intraoperative wake-up test: a study using Bispectral index and composite auditory evoked potentials as pharmacodynamic endpoints

  • Heleen J. Blussé van Oud-Alblas,
  • Margreke J. E. Brill,
  • Mariska Y. M. Peeters,
  • Dick Tibboel,
  • Meindert Danhof,
  • Catherijne A. J. Knibbe

DOI
https://doi.org/10.1186/s12871-019-0684-z
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 12

Abstract

Read online

Abstract Background In adolescents limited data are available on the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol. In this study we derived a PK-PD model for propofol in adolescents undergoing idiopathic scoliosis surgery with an intraoperative wake-up test with reinduction of anesthesia using both Bispectral Index (BIS) and composite A-line ARX index (cAAI) as endpoints. Methods Fourteen adolescents (9.8–20.1 years) were evaluated during standardized propofol-remifentanil anesthesia for idiopathic scoliosis surgery with an intraoperative wake-up test with reinduction of anesthesia. BIS and cAAI were continuously measured and blood samples collected. A propofol PKPD model was developed using NONMEM. Results The time courses of propofol concentrations, BIS and cAAI values during anesthesia, intra-operative wakeup and reduction of anesthesia were best described by a two-compartment PK model linked to an inhibitory sigmoidal Emax PD model. For the sigmoidal Emax model, the propofol concentration at half maximum effect (EC50) was 3.51 and 2.14 mg/L and Hill coefficient 1.43 and 6.85 for BIS and cAAI, respectively. The delay in PD effect in relation to plasma concentration was best described by a two compartment effect-site model with a keo of 0.102 min− 1, ke12 of 0.121 min− 1 and ke21 of 0.172 min− 1. Conclusions A population PKPD model for propofol in adolescents was developed that successfully described the time course of propofol concentration, BIS and cAAI in individuals upon undergoing scoliosis surgery with intraoperative wake-up test and reinduction of anesthesia. Large differences were demonstrated between both monitors. This may imply that BIS and cAAI measure fundamentally different endpoints in the brain.

Keywords