title: Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl.
abstract: OBJECTIVE
  To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs.
  
  
  METHODS
  8 mixed-breed adult dogs.
  
  
  METHODS
  Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again.
  
  
  RESULTS
  Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups.
  
  
  CONCLUSIONS
  Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80526, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Hellyer
authors.forename: K R
authors.initials: KR
authors.lastname: Mama
authors.forename: H L
authors.initials: HL
authors.lastname: Shafford
authors.forename: A E
authors.initials: AE
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Kollias-Baker
mesh_terms: D000759:Adjuvants, Anesthesia / Q000097:blood / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003975:Diazepam / Q000097:blood / Q000494:pharmacology*; D004285:Dogs / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D005283:Fentanyl / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D005442:Flumazenil / Q000097:blood / Q000494:pharmacology; D018757:GABA Modulators / Q000097:blood / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007530:Isoflurane / Q000493:pharmacokinetics* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000759:Adjuvants, Anesthesia; D018685:Anesthetics, Inhalation; D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D005442:Flumazenil; D007530:Isoflurane; D003975:Diazepam; D005283:Fentanyl