• Heleen J Blussé van Oud-Alblas, BrillMargreke J EMJEDivision of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM, Nieuwegein, The Netherlands., PeetersMariska Y MMYMDepartment of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM, Nieuwegein, The Netherlands., Dick Tibboel, Meindert Danhof, and KnibbeCatherijne A JCAJDivision of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands. c.knibbe@antoniusziekenhuis.nl.Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM, Nieuwegei.
• Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands.
• BMC Anesthesiol. 2019 Jan 22; 19 (1): 1515.

BackgroundIn 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.MethodsFourteen 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.ResultsThe 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.ConclusionsA 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.

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