Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl

Objective-To determine the effect of a constant-rate infusion of fentanyl o n minimum alveolar concentration (MAC) of isoflurane and to determine the i nteraction between fentanyl and a benzodiazepine agonist (diazepam) and ant agonist (flumazenil) in isoflurane-anesthetized dogs. Animals-8 mixed-breed adult dogs. Procedure-Dogs were anesthetized with iso flurane 3 times during a 6-week period. After a 30-minute equilibration per iod, each MAC determination was performed in triplicate, using standard tec hniques. Fentanyl was administered as a bolus 110 mug/kg of body weight, IV ) that was followed by a constant infusion (0.3 mug/kg per min, IV) through out 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 bar ometric pressure of 760 mm Hg) from 1.80 +/- 0.21 to 0.85 +/- 0.14%, a redu ction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48 +/- 0.29%) was signifi cantly less than isoflurane-fentanyl-saline MAC (0.79 +/- 0.21%). Percentag e reduction in isoflurane MAC was significantly greater for fentanyl-diazep am (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 g roups. Conclusions and Clinical Relevance-Fentanyl markedly decreased isoflurane M AC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fent anyl MAC. Our results indicate that diazepam enhances, whereas flumazenil d oes not affect, opioid-induced CNS depression and, possibly, analgesia in d ogs.