title: Bispectral index dynamics during propofol hypnosis is similar in red-haired and dark-haired subjects.
abstract: BACKGROUND
  We have previously shown that red hair is associated with increased desflurane requirement for immobility, compared with dark hair. The effect of red hair on IV anesthetic requirement remains unknown. We tested the hypothesis that the propofol concentration in the effect site associated with half maximal electroencephalogram response, Ce50, is at least 50% higher in subjects with red hair.
  
  
  METHODS
  We modeled the propofol concentration versus electroencephalogram response relationship using a 2-step approach in 29 healthy dark- and red-haired volunteers receiving a propofol infusion to produce loss of consciousness. Bispectral Index (BIS) was the measure of drug effect. The parameters of a 3-compartment pharmacokinetic model were fit to measured arterial propofol concentrations. The relationship between effect-site propofol concentration (Ce) and BIS was characterized using a sigmoid Emax model. Model performance and accuracy of the estimated parameters were evaluated using accepted metrics and bootstrap resampling. The effect of hair color on the Ce50 for BIS response in the final model was assessed using a threshold of 6.63 (P<0.01) in reduction of -2 log likelihood. The influence of body weight on the model was also assessed.
  
  
  RESULTS
  The inclusion of hair color as a model covariate did not improve either the pharmacokinetic or the pharmacodynamic model. A separate analysis for the dark- and red-haired subjects estimated a median (95% confidence interval) Ce50 BIS of 2.71 μg/mL (2.28-3.36 μg/mL) and 2.57 μg/mL (1.68-3.60 μg/mL), respectively. Body weight was a significant covariate for the CL1 and V1.
  
  
  CONCLUSIONS
  Red hair phenotype does not affect the pharmacokinetics or pharmacodynamics of propofol.
authors.affiliation: Department of Anesthesia, University of Louisville, Louisville, KY, USA. agdoufas@stanford.edu
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Doufas
authors.forename: Mukadder
authors.initials: M
authors.lastname: Orhan-Sungur
authors.forename: Ryu
authors.initials: R
authors.lastname: Komatsu
authors.forename: Rolf
authors.initials: R
authors.lastname: Lauber
authors.forename: Ozan
authors.initials: O
authors.lastname: Akca
authors.forename: Steven L
authors.initials: SL
authors.lastname: Shafer
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000328:Adult; D000465:Algorithms; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics / Q000494:pharmacology*; D001499:Bayes Theorem; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D056805:Consciousness Monitors; D004562:Electrocardiography / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006200:Hair Color / Q000502:physiology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D017711:Nonlinear Dynamics; D015742:Propofol / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D002245:Carbon Dioxide; D015742:Propofol