title: Direct measurement of nitrous oxide kinetics.
abstract: BACKGROUND
  Using conscious subjects, measurement of the effects of low concentrations of anaesthetic agents can allow the dynamics of onset and offset of the agent to be measured and kinetic values estimated. However, the tests have to be rapid and preferably assess cerebral function.
  
  
  METHODS
  We used a short version of the digit symbol substitution test (DSST) that allowed frequent measurement of the impairment caused by nitrous oxide. We compared 10 min of onset and offset of breathing 5% and 30% nitrous oxide in 30% oxygen, compared with 30% oxygen only. End-tidal nitrous oxide concentrations were used to predict the concentration in a central compartment, according to a range of T(1/2) values chosen to be consistent with possible cerebral blood flow values.
  
  
  RESULTS
  We studied 19 volunteers and estimated a mean response. Only 30% nitrous oxide decreased the DSST. When DSST scores were related to the values in the predicted central compartment, the best dose-effect relationship was found when the T(1/2) was 37 s, consistent with a regional blood flow of about 120 ml 100 g(-1) min(-1).
  
  
  CONCLUSIONS
  The onset of nitrous oxide effect on DSST is rapid, consistent with the perfusion of metabolically active cerebral cortical tissues. The rate of onset is greater than previous measures based on a motor test which involved the function of subcortical structures in the central nervous system.
authors.affiliation: Department of Anaesthesia and Pain Medicine, University of Edinburgh, Royal Infirmary, 51 Little France Crescent, Edinburgh, UK. g.b.drummond@ed.ac.uk
authors.forename: G B
authors.initials: GB
authors.lastname: Drummond
authors.forename: L
authors.initials: L
authors.lastname: Fisher
authors.forename: O
authors.initials: O
authors.lastname: Pumphrey
authors.forename: R R
authors.initials: RR
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D001783:Blood Flow Velocity; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000187:drug effects; D009609:Nitrous Oxide / Q000493:pharmacokinetics*; D010100:Oxygen / Q000008:administration & dosage; D011597:Psychomotor Performance / Q000187:drug effects*; D012016:Reference Values; D055815:Young Adult
chemical_list: D018685:Anesthetics, Inhalation; D009609:Nitrous Oxide; D010100:Oxygen