title: Remifentanil-sevoflurane interaction models of circulatory response to laryngoscopy and circulatory depression.
abstract: BACKGROUND
  Sevoflurane and remifentanil are commonly combined to produce the hypnotic and analgesic effects required for clinical anaesthesia. Previous studies have characterized interactions between several i.v. drugs and inhalation agents. Aiming to extend this effort, we developed two new mathematical models to characterize the interactions manner and strength between sevoflurane and remifentanil.
  
  
  METHODS
  Sixty-five adult Chinese patients undergoing elective operations received a target-controlled infusion of remifentanil (0-10 ng ml(-1)) and inhaled sevoflurane (0.3-3.4 vol.%) at various randomly selected target concentration pairs. After reaching pseudo-steady-state drug levels, the circulatory response to laryngoscopy and any circulatory depression (a side-effect) were observed for each pair of target concentrations. The pharmacodynamic interactions between sevoflurane and remifentanil were investigated by response surface methodology. NONMEM software was used to estimate the model parameters.
  
  
  RESULTS
  The response surface models revealed significant synergy between sevoflurane and remifentanil. When the target remifentanil concentration was increased from 0 to 10 ng ml(-1), the C50, sevo decreased from 2.6 to 0.38 vol.% for the prevention of circulatory response to laryngoscopy and from 3.53 to 1.46 vol.% for the induction of circulatory depression.
  
  
  CONCLUSIONS
  The new models can be used to characterize the interactions between these two drugs both qualitatively and quantitatively. Remifentanil significantly decreased the amount of sevoflurane required to eliminate patient response to clinical stimuli, thus reducing the likelihood of side-effects, specifically circulatory depression.
authors: The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors: S S
authors: SS
authors: Bi
authors: C H
authors: CH
authors: Deng
authors: T Y
authors: TY
authors: Zhou
authors: Z
authors: Z
authors: Guan
authors: L
authors: L
authors: Li
authors: H Q
authors: HQ
authors: Li
authors: L P
authors: LP
authors: Zhang
authors: L
authors: L
authors: Yang
authors: W
authors: W
authors: Lu
mesh_terms: D000328:Adult; D019162:Anesthetics, Combined / Q000008:administration & dosage / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007828:Laryngoscopy; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D000077208:Remifentanil; D000077149:Sevoflurane; D055815:Young Adult
chemical_list: D019162:Anesthetics, Combined; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D000077208:Remifentanil