title: When is a bispectral index of 60 too low?: Rational processed electroencephalographic targets are dependent on the sedative-opioid ratio.
abstract: BACKGROUND
  Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.
  
  
  METHODS
  Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.
  
  
  RESULTS
  Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics.
  
  
  CONCLUSIONS
  Although clinical sedation increases significantly even with the addition of a small to moderate dose of remifentanil to a sevoflurane anesthetic, the BIS and AAI are insensitive to this change in clinical state. Therefore, during "opioid-heavy" sevoflurane-remifentanil anesthetics, targeting a BIS less than 60 or an AAI less than 30 may result in an unnecessarily deep anesthetic state.
authors.affiliation: Department of Radiology, The University of California, San Francisco, California, USA.
authors.forename: Sandeep C
authors.initials: SC
authors.lastname: Manyam
authors.forename: Dhanesh K
authors.initials: DK
authors.lastname: Gupta
authors.forename: Ken B
authors.initials: KB
authors.lastname: Johnson
authors.forename: Julia L
authors.initials: JL
authors.lastname: White
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Pace
authors.forename: Dwayne R
authors.initials: DR
authors.lastname: Westenskow
authors.forename: Talmage D
authors.initials: TD
authors.lastname: Egan
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D019162:Anesthetics, Combined / Q000009:adverse effects / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000009:adverse effects / Q000494:pharmacology*; D016292:Procedural Sedation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects / Q000494:pharmacology*; D016343:Monitoring, Intraoperative / Q000379:methods; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology*; D000077208:Remifentanil; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D019162:Anesthetics, Combined; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D000077208:Remifentanil