Trazodone and dexmedetomidine cause fentanyl to decrease the isoflurane minimum alveolar concentration in cats

Objective: To screen modulators of biogenic amine (BA) neurotransmission for the ability to cause fentanyl to decrease isoflurane minimum alveolar concentration (MAC) in cats, and to test whether fentanyl plus a combination of modulators decreases isoflurane MAC more than fentanyl alone.

Study design: Prospective, crossover

Animals: 6 male domestic shorthair cats

Methods: Each cat was anesthetized 3 times with a 1-week washout period. First, anesthesia was induced and maintained with isoflurane, and MAC was measured in duplicate using a tail clamp stimulus and standard bracketing technique. A 21 ng mL-1 fentanyl target-controlled infusion (TCI) was next administered, and MAC was re-measured. Second, each cat was administered 1 BA modulator drug (buspirone, haloperidol, dexmedetomidine, pregabalin, ramelteon, or trazodone), and isoflurane MAC was measured before and after fentanyl administration. Third, isoflurane MAC was measured in cats administered 50mg oral trazodone plus a 1.05 ng mL-1 intravenous dexmedetomidine TCI before and after fentanyl administration. Isoflurane MAC-sparing by fentanyl alone, trazodone-dexmedetomidine, and trazodone-dexmedetomidine-fentanyl was evaluated using paired t-tests with p < 0.05 denoting significant effects.

Results: MAC of isoflurane was 1.87% ± 0.09 and was not significantly affected by fentanyl administration (p = 0.09). In the BA screen, cats administered trazodone or dexmedetomidine exhibited 26% and 22% fentanyl MAC-sparing, respectively. Trazodone plus dexmedetomidine co-administration reduced isoflurane MAC to 1.50% ± 0.14 (p = 0.0004), and fentanyl further decreased MAC to 0.95% ± 0.16 (p = 0.000004).

Conclusions and clinical relevance: Fentanyl alone does not affect isoflurane MAC in cats, but co-administration of trazodone and dexmedetomidine causes fentanyl to significantly decrease isoflurane requirement.

Methods
Minimum alveolar concentration (MAC) was measured twice (in duplicate) for each cat. Data were collected prior to nociceptive tail clamp stimulation for MAC testing. Physiologic responses measured at bracketing (move and no-move) anesthetic concentrations were averaged. Responses for each animal represent the mean of duplicate physiologic response pairs.