title: Modeling the influence of the A118G polymorphism in the OPRM1 gene and of noxious stimulation on the synergistic relation between propofol and remifentanil: sedation and analgesia in endoscopic procedures.
abstract: BACKGROUND
  The presence of the A118G single nucleotide polymorphism in the OPRM1 gene as well as noxious stimulation might affect the requirements of remifentanil for patients undergoing ultrasonographic endoscopy under sedation-analgesia with propofol and remifentanil. Bispectral index (BIS) was used as a surrogate measure of effect.
  
  
  METHODS
  A total of 207 patients were screened for A118G and randomly received different combinations of propofol and remifentanil, changed depending on the nausea response to endoscopy tube introduction. Nonlinear mixed effects modelling was used to establish the relation between propofol and remifentanil with respect to BIS and to investigate the influence of A118G or noxious stimulation. The value of k e0 for propofol and remifentanil was estimated to avoid the hysteresis between predicted effect site concentration (Ce) and BIS.
  
  
  RESULTS
  Data from 176 patients were analysed. Eleven were recessive homozygous for A118G (OPRM = 1). A total of 165 patients were either dominant homozygous or heterozygous and considered normal (OPRM = 0). The estimated values of k e0 for propofol and remifentanil were 0.122 and 0.148 min(-1). Propofol and remifentanil were synergistic with respect to the BIS (α = 1.85). EC50 estimate for propofol was 3.86 µg/ml and for remifentanil 19.6 ng/ml in normal patients and 326 ng/ml in OPRM = 1 patients. BIS increases around 4% for the same effect site concentrations with noxious stimulation.
  
  
  CONCLUSIONS
  Predicted effect site concentration of remifentanil ranging 1-5 ng/ml synergistically potentiates the effects of propofol on the BIS but has no effect in A118G patients. Noxious stimulation increases BIS values by 4% at the same concentrations of propofol and remifentanil.
authors.affiliation: Department of Anesthesia, Hospital CLINIC de Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Borrat
authors.forename: Iñaki F
authors.initials: IF
authors.lastname: Trocóniz
authors.forename: José F
authors.initials: JF
authors.lastname: Valencia
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivadulla
authors.forename: Oriol
authors.initials: O
authors.lastname: Sendino
authors.forename: Josep
authors.initials: J
authors.lastname: Llach
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
authors.forename: Mathieu
authors.initials: M
authors.lastname: Jospin
authors.forename: Erik W
authors.initials: EW
authors.lastname: Jensen
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Gambús
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000698:Analgesia / Q000379:methods; D019162:Anesthetics, Combined / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D004357:Drug Synergism; D004724:Endoscopy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D017711:Nonlinear Dynamics; D010146:Pain / Q000235:genetics* / Q000517:prevention & control; D010880:Piperidines / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015742:Propofol / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D000077208:Remifentanil; D055815:Young Adult
chemical_list: D019162:Anesthetics, Combined; D018686:Anesthetics, Intravenous; C485764:OPRM1 protein, human; D010880:Piperidines; D017450:Receptors, Opioid, mu; D000077208:Remifentanil; D015742:Propofol