title: Synergism between sevoflurane and intravenous fentanyl on A delta and C somatosympathetic reflexes in dogs.
abstract: In this study, we defined the nature of the interactions between sevoflurane and fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes, evoked by electrical stimulation of radial nerves, and HR and MAP were recorded in anesthetized dogs. In one group, the effects of incremental doses of 2-64 micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on C than on A delta reflexes, which were abolished by mean cumulative doses of 64 micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5% sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it reduced the total doses of fentanyl required for their abolition to 32 micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%, 11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively, which indicates a less than additive effect. These results indicate that sevoflurane interacts synergistically with fentanyl to depress A delta and C somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were less than the additive.
  
  
  CONCLUSIONS
  Although fentanyl caused a greater depression of C than of A delta reflexes to the point of abolition, the maximal depression of spontaneous sympathetic activity, heart rate, and arterial pressure occurred at smaller doses. The combined depressant effects of sevoflurane and fentanyl were synergistic on somatosympathetic reflexes but were less than additive on spontaneous sympathetic activity, heart rate, and arterial pressure.
authors.affiliation: Department of Anaesthetics, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom. dma@rpms.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.forename: S M
authors.initials: SM
authors.lastname: Sapsed-Byrne
authors.forename: M K
authors.initials: MK
authors.lastname: Chakrabarti
authors.forename: D
authors.initials: D
authors.lastname: Ridout
authors.forename: J G
authors.initials: JG
authors.lastname: Whitwam
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005283:Fentanyl / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D000077149:Sevoflurane; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D005283:Fentanyl