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

Peter W. Hellyer Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80526.

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Khursheed R. Mama Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80526.

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Heidi L. Shafford Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80526.

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Ann E. Wagner Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80526.

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Cynthia Kollias-Baker Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616.

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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.

Animals—8 mixed-breed adult dogs.

Procedure—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 µg/kg of body weight, IV) that was followed by a constant infusion (0.3 µg/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-fentanylsaline MAC (0.79 ± 0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyldiazepam (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.

Conclusion and Clinical Relevance—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. (Am J Vet Res 2001;62:555–560)

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.

Animals—8 mixed-breed adult dogs.

Procedure—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 µg/kg of body weight, IV) that was followed by a constant infusion (0.3 µg/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-fentanylsaline MAC (0.79 ± 0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyldiazepam (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.

Conclusion and Clinical Relevance—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. (Am J Vet Res 2001;62:555–560)

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