title: Pharmacodynamic modelling of the bispectral index response to propofol-based anaesthesia during general surgery in children.
abstract: BACKGROUND
  This study describes a pharmacodynamic model during general anaesthesia in children relating the bispectral index (BIS) response to the anaesthetic dosing of propofol, fentanyl, and remifentanil.
  
  
  METHODS
  BIS, heart rate, mean arterial pressure, sedation scores, and anaesthetic protocols from 59 children aged 1-16 yr undergoing general surgery were considered for the study. Anaesthesia was performed with propofol, fentanyl, and remifentanil. A sigmoid model assuming additive interaction of propofol, fentanyl, and remifentanil was fitted to individual BIS as effect variable. The pharmacodynamic parameters were estimated by non-linear regression analysis. The ability of BIS to predict anaesthetic drug effect was quantified by the prediction probability Pk.
  
  
  RESULTS
  BIS started at a baseline of 90 (9), decreased during induction to 30 (14) and remained at 57 (10) during anaesthesia. BIS predicted the anaesthetic drug effect with a Pk of 0.79 (0.08). The EC(50 Propofol) and the k(e0 Propofol) were 5.2 (2.7) microg ml(-1) and 0.60 (0.45) min(-1), respectively. The k(e0 Propofol) decreased from approximately 0.91 min(-1) at 1 yr to 0.15 min(-1) at 16 yr. The EC(50 Remifentanil), k(e0 Remifentanil), EC(50 Fentanyl), and the k(e0 Fentanyl) were 24.1 (13.0) ng ml(-1), 0.71 (0.32) min(-1), 8.6 (7.4) ng ml(-1), and 0.28 (0.46) min(-1), respectively.
  
  
  CONCLUSIONS
  The effect equilibration half-time of propofol in children was age dependent. The pharmacodynamics of fentanyl and remifentanil in children were similar to those reported in adults. The BIS showed a close relationship to the modelled effect-site concentration, and therefore, it may serve as a measure of anaesthetic drug effect in children older than 1 yr.
authors.affiliation: Department of Anaesthesiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany. christian.jeleazcov@kfa.imed.uni-erlangen.de
authors.forename: C
authors.initials: C
authors.lastname: Jeleazcov
authors.forename: H
authors.initials: H
authors.lastname: Ihmsen
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Ammon
authors.forename: H
authors.initials: H
authors.lastname: Schwilden
authors.forename: J
authors.initials: J
authors.lastname: Schüttler
authors.forename: J
authors.initials: J
authors.lastname: Fechner
mesh_terms: D000293:Adolescent; D000375:Aging / Q000097:blood; D000771:Anesthesia, Intravenous / Q000379:methods; D019162:Anesthetics, Combined / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D005283:Fentanyl / Q000097:blood / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D016343:Monitoring, Intraoperative / Q000379:methods; D010880:Piperidines / Q000097:blood / Q000494:pharmacology; D015742:Propofol / Q000097:blood / Q000494:pharmacology*; D000077208:Remifentanil
chemical_list: D019162:Anesthetics, Combined; D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil; D005283:Fentanyl; D015742:Propofol