title: Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.
abstract: BACKGROUND
  The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope.
  
  
  METHODS
  Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 μg•mL (PROP 2) or 3 μg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use.
  
  
  RESULTS
  One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 μg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 μg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 μg•mL, respectively.
  
  
  CONCLUSIONS
  We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.
authors.affiliation: From the Systems Pharmacology Effect Control & Modeling Research Group, Anesthesiology Department, Hospital Clinic de Barcelona, Barcelona, Spain; Endoscopy Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain; Center of Research in Biomedical Engineering, Universitat Politècnica de Catalunya, Barcelona, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Universidad de Navarra, Pamplona, Spain; and Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California.
authors.forename: Xavier
authors.initials: X
authors.lastname: Borrat
authors.forename: José Fernando
authors.initials: JF
authors.lastname: Valencia
authors.forename: Rudys
authors.initials: R
authors.lastname: Magrans
authors.forename: Marc
authors.initials: M
authors.lastname: Gimenez-Mila
authors.forename: Ricard
authors.initials: R
authors.lastname: Mellado
authors.forename: Oriol
authors.initials: O
authors.lastname: Sendino
authors.forename: Maria
authors.initials: M
authors.lastname: Perez
authors.forename: Matilde
authors.initials: M
authors.lastname: Nunez
authors.forename: Mathieu
authors.initials: M
authors.lastname: Jospin
authors.forename: Erik Weber
authors.initials: EW
authors.lastname: Jensen
authors.forename: Inaki
authors.initials: I
authors.lastname: Troconiz
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Gambus
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D016099:Endoscopy, Gastrointestinal / Q000009:adverse effects*; D005683:Gagging / Q000517:prevention & control*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage*; D015742:Propofol / Q000008:administration & dosage*; D000077208:Remifentanil; D013030:Spain
chemical_list: D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D010880:Piperidines; D000077208:Remifentanil; D015742:Propofol