title: The combined effects of sevoflurane and remifentanil on central respiratory activity and nociceptive cardiovascular responses in anesthetized rabbits.
abstract: We studied the effects of sevoflurane and remifentanil, alone and in combination, on phrenic nerve activity (PNA), resting heart rate (HR), arterial pressure (MAP), and changes in HR (delta HR) and MAP (delta MAP) evoked by electrical stimulation of tibial nerves in anesthetized rabbits. The 50% effective dose (95% confidence intervals) for the depressant effects of sevoflurane on delta HR, delta MAP, and PNA were 2.3 (1.8%-2.6%), 2.7 (2.3%-2.9%), and 3.4 (3.1%-3.7%), respectively, and for remifentanil were 0.100 (0.050-0.132), 0.850 (0.720-1.450), and 0.090 (0.080-0.145) microgram.kg-1.min-1, which were reduced to 0.046 (0.021-0.065), 0.110 (0.080-0.200), and 0.030 (0.020-0.040) microgram.kg-1.min-1, respectively, by 1% sevoflurane. Depression of evoked cardiovascular responses relative to PNA was greater for sevoflurane and less for remifentanil both alone and in combination with sevoflurane. Sevoflurane acted synergistically with remifentanil on PNA and delta MAP, but not delta HR, for which their combined effect was additive. Coadministration of 1% sevoflurane with the highest infusion rate of remifentanil (1.6 micrograms.kg-1.min-1) used during combined administration reduced resting HR and MAP by 25% (P < 0.05) and 41% (P < 0.05), respectively, which was greater than the predicted reductions of only 14% and 15% if their combined effects had been additive. We conclude that sevoflurane caused a relatively greater depression of nociceptive cardioaccelerator and pressor responses compared with PNA and vice versa for remifentanil. When coadministered, their combined effects on PNA, resting HR, MAP, and delta MAP were synergistic, whereas they were merely additive for delta HR.
  
  
  CONCLUSIONS
  Although sevoflurane caused relatively greater depression of nociceptive cardiovascular responses compared with phrenic nerve activity, remifentanil either alone or combined with sevoflurane caused a much greater depression of phrenic nerve activity than cardio-accelerator and pressor responses. This could imply that, during major surgery using anesthesia combining sevoflurane and remifentanil, spontaneous ventilation is not acceptable, and depression of the resting circulation may be much greater than anticipated.
authors.affiliation: Department of Anaesthetics and Intensive Care, 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: M K
authors.initials: MK
authors.lastname: Chakrabarti
authors.forename: J G
authors.initials: JG
authors.lastname: Whitwam
mesh_terms: D000200:Action Potentials; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010791:Phrenic Nerve / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D000077208:Remifentanil; D012119:Respiration; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D000077208:Remifentanil