title: Previously published midazolam-alfentanil response surface model cannot predict patient response well in gastrointestinal endoscopy sedation.
abstract: BACKGROUND
  A response surface model is a mathematical model used to predict multiple-drug pharmacodynamic interactions. With the use of a previously published volunteer model, we tested the accuracy of the midazolam-alfentanil response surface model during gastrointestinal endoscopy.
  
  
  METHODS
  We enrolled 35 adult patients scheduled for combined endoscopic procedures. Patients were sedated with intravenous midazolam and alfentanil, and monitored with real-time auditory evoked potential. Sedation Observer's Assessment of Alertness/Sedation (OAA/S) scores were recorded by an independent observer every 2 minutes. Patients with OAA/S scores of ≥ 4 were designated as "awake". Pharmacokinetic profiles were calculated using the TIVA trainer. The published response surface model was modified to make estimations more reasonable. Patient response (OAA/S score ≥ 4 or <4) was then estimated using the modified version of the model.
  
  
  RESULTS
  The average procedural times were 3.3 ± 2 minutes and 6.5 ± 2.3 minutes for esophagogastroduodenoscopy and colonoscopy, respectively. The model poorly predicted patient response during gastrointestinal endoscopic procedure sedation. Accuracy in predicting an OAA/S score of <4 was 6% for the original model and 0% for the modified model. The estimated probability of loss of response ranged from 0.04% to 2.94% at the time of arousal (OAA/S score ≥ 4) and from 0.24% to 15.55% when the patient was asleep (OAA/S score < 4).
  
  
  CONCLUSIONS
  The model showed significant synergy between midazolam and alfentanil; however, it was inadequate in predicting the response of patients undergoing sedated gastrointestinal endoscopic procedures. Future model parameter adjustments are required.
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Liou
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Chien-Kun
authors.initials: CK
authors.lastname: Ting
authors.affiliation: Department of Anesthesiology, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC. Electronic address: mytsou8095@gmail.com.
authors.forename: Mei-Yung
authors.initials: MY
authors.lastname: Tsou
mesh_terms: D000328:Adult; D015760:Alfentanil / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D016292:Procedural Sedation / Q000379:methods*; D004347:Drug Interactions; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D008875:Middle Aged; D008962:Models, Theoretical
chemical_list: D018686:Anesthetics, Intravenous; D015760:Alfentanil; D008874:Midazolam
keywords: alfentanil; gastrointestinal endoscopy; midazolam; pharmacodynamic; response surface model