title: Pharmacodynamic Estimate of Propofol-Induced Sedation and Airway Obstruction Effects in Obstructive Sleep Apnea-Hypopnea Syndrome.
abstract: OBJECTIVE
  Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS.
  
  
  METHODS
  In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software.
  
  
  RESULTS
  Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect≥m) for sedation scores (m≥2, 3, 4, and 5) and airway-obstruction scores (m≥2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 μg/mL and 1.53, 1.64, and 2.09 μg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05).
  
  
  CONCLUSIONS
  The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.|Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Bon-Nyeo
authors.initials: BN
authors.lastname: Koo
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.|Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seokyung
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.|Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Kang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyu Hee
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea. hanesth@yuhs.ac.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000188:drug therapy*; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011336:Probability; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D015742:Propofol
keywords: Airway obstruction; obstructive sleep apnea-hypopnea syndrome; pharmacodynamic modeling; propofol; sedation; target-controlled infusion