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_glyco) 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_glyco. 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.