title: Repetitive rapid increases in desflurane concentration blunt transient cardiovascular stimulation in humans.
abstract: BACKGROUND
  Rapid increases in desflurane concentrations above minimum alveolar concentration (MAC) can cause transient (2-4-min) circulatory changes, possibly from stimulation of rapidly-adapting airway receptors. We hypothesized that the initial increase in concentration would produce greater changes than subsequent increases.
  
  
  METHODS
  Anesthesia was induced with propofol in nine volunteers (25 +/- 1 yr old, mean +/- SE) and maintained with 4% end-tidal desflurane for 32 min. We increased the desflurane to 8% (1.1 MAC) in 1 min, maintained this concentration for 10 min, and then decreased it to 4% for 32 min. We repeated this process twice. After 1 week, 5 subjects were treated similarly except that the second increase in concentration occurred 10 min and (on a separate occasion) 75 min after the initial increase. Four subjects received the initial increase after 75 rather than 32 min of anesthesia. In four we applied the repeated sequences in a background of 60% nitrous oxide. When a minimal cardiovascular response followed an increase of anesthetic concentration, a 60-s supramaximal 100-Hz tetanic stimulus was applied to an ulnar nerve percutaneously to test for sympathetic responsiveness.
  
  
  RESULTS
  The initial increase in concentration increased heart rate (HR) from 57 +/- 2 to a peak of 119 +/- 7 beats/min (P < 0.05); mean arterial blood pressure (MAP) from 66 +/- 3 to 119 +/- 5 mmHg (P < 0.05); and plasma epinephrine by > 10-fold (P < 0.05). The second and third increases in desflurane concentration increased HR and MAP by less than 20% of the initial increases, regardless of the timing of the later concentration increases. Responses to initial concentration increases after 75 min of anesthesia did not differ from those after 32 min. Increases in plasma epinephrine with the second and third increases in desflurane concentration were attenuated. Subjects who did not responded to the second or third increase in desflurane always responded to tetanic electrical stimulation with substantial increases in HR and MAP (P < 0.05). Addition of nitrous oxide did not change results except for a smaller increase in MAP (P < 0.05). Ulnar nerve stimulation increased HR and MAP but not epinephrine or norepinephrine concentrations.
  
  
  CONCLUSIONS
  An initial rapid increase in desflurane to 1.1 MAC produces much more stimulation than do subsequent increases, regardless of the presence of nitrous oxide. The decreased response is consistent with the hypothesis that stimulation of rapidly-adapting airway receptors produce the initial response.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0648.
authors.forename: R B
authors.initials: RB
authors.lastname: Weiskopf
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: M
authors.initials: M
authors.lastname: Noorani
authors.forename: M
authors.initials: M
authors.lastname: Daniel
mesh_terms: D000328:Adult; D000777:Anesthetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009609:Nitrous Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011650:Pulmonary Alveoli / Q000737:chemistry; D012121:Respiration, Artificial; D013997:Time Factors
chemical_list: D000777:Anesthetics; D000077335:Desflurane; D007530:Isoflurane; D009609:Nitrous Oxide; D009638:Norepinephrine; D004837:Epinephrine