Effect of Fentanyl, with or Without Treatment of Bradycardia, on the Minimum Alveolar Concentration of Isoflurane and Cardiovascular Function in Dogs.

Objective To determine the effect of fentanyl on the minimum alveolar concentration of isoflurane (MAC(ISO)) and cardiovascular variables in dogs, and how the treatment of bradycardia affects them. Study design Prospective, randomized crossover-controlled trial. Animals A total of six male Beagle dogs weighing 9.9 +/- 0.7 kg (mean +/- standard deviation) and aged 13 months. Methods To each dog, two treatments were assigned on different days: fentanyl (FENTA) or fentanyl plus glycopyrrolate (FENTA(gl)(yco)) to maintain heart rate (HR) between 100 and 132 beats minute(-1). Determinations of MAC(ISO) were performed with 10 plasma fentanyl target concentrations ([Fenta](Target) ( 0, 0.16, 0.32, 0.64, 1.25, 2.5, 5.0, 10.0, 20.0 and 40.0 ng mL(-1)) for FENTA and 5 [Fenta](Target) (0, 1.25, 2.5, 5.0, 10.0 ng mL(-1))) for FENTA(gl)(yco). During each MAC(ISO) determination, cardiovascular variables [mean arterial pressure (MAP), HR and cardiac index (CI)] were measured, and systemic vascular resistance index (SVRI) calculated. Pharmacodynamic models were used to describe the plasma fentanyl concentration [Fenta]-response relationship for the effect on MAC(ISO) and cardiovascular variables. A mixed-model analysis of variance followed by Dunnett's or Tukey's test, and the Bonferroni adjustment were used for comparisons within and between each treatment, respectively. Significance was set as p < 0.05. Results Fentanyl decreased MAC(ISO) by a maximum of 84%. The [Fenta] producing 50% decrease in MAC, HR and CI were 2.64, 3.65 and 4.30 ng mL(-1) (typical values of population model), respectively. The prevention of fentanyl-mediated bradycardia caused no significant effect on MAC(ISO), but increased HR, MAP and CI, and decreased SVRI when compared with isoflurane alone. Conclusions and clinical relevance Fentanyl caused a plasma concentration-dependent decrease in MAC(ISO), HR and CI and an increase in SVRI. Cardiovascular improvements associated with fentanyl in isoflurane-anesthetized dogs only occurred when the fentanyl-mediated bradycardia was prevented.