title: Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study.
abstract: BACKGROUND
  We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation.
  
  
  METHODS
  Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered.
  
  
  RESULTS
  Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation.
  
  
  CONCLUSIONS
  The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability.
  
  
  BACKGROUND
  clinicaltrials.gov Nr. NCT00641563.
authors.affiliation: Department of Intensive Care Medicine, Bern University Hospital, Inselspital, and University of Bern, Freiburgstrasse, Bern, Switzerland. matthias.haenggi@insel.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Haenggi
authors.forename: Heidi
authors.initials: H
authors.lastname: Ypparila-Wolters
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hauser
authors.forename: Claudio
authors.initials: C
authors.lastname: Caviezel
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
authors.forename: Ilkka
authors.initials: I
authors.lastname: Korhonen
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004338:Drug Combinations; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D019277:Entropy; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D014644:Genetic Variation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008874:Midazolam / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage*; D000077208:Remifentanil; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D010880:Piperidines; D020927:Dexmedetomidine; D000077208:Remifentanil; D008874:Midazolam