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

• Published in: BMC anesthesiology 2019-01, Vol.19 (1), p.15-12, Article 15
• Main Authors: Blussé van Oud-Alblas, Heleen J, Brill, Margreke J E, Peeters, Mariska Y M, Tibboel, Dick, Danhof, Meindert, Knibbe, Catherijne A J
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Analysis; Anesthesia; Anesthesiology; Anesthetics, Intravenous - administration & dosage; Anesthetics, Intravenous - pharmacokinetics; Anesthetics, Intravenous - pharmacology; Auditory evoked potentials; Bispectral index; Central nervous system agents; Child; Consciousness Monitors; Evoked Potentials, Auditory - physiology; Female; Humans; Male; Models, Biological; Monitoring, Intraoperative - methods; Orthopedic surgery; Pharmacodynamics; Pharmacokinetics; Phenols (Class of compounds); Population; Population PKPD modeling; Propofol; Propofol - administration & dosage; Propofol - pharmacokinetics; Propofol - pharmacology; Remifentanil; Remifentanil - administration & dosage; Scoliosis; Scoliosis - surgery; Studies; Surgery; Teenagers; Wakefulness - physiology; Young Adult; Youth
• ISSN: 1471-2253; 1471-2253
• DOI: 10.1186/s12871-019-0684-z

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. 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. 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 (EC ) 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 ke of 0.102 min , ke of 0.121 min and ke of 0.172 min . 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.