Tail-Clamp-Determined End-Tidal Isoflurane Requirement after Midazolam-Propofol or Midazolam-Ketamine Co-Induction in Dogs: A Translational Comparative Medical Model

Background: Reducing volatile anesthetic exposure is an objective of balanced anesthesia. Dogs can provide a model for studying pharmacodynamic interactions between injectable co-induction agents and end-tidal inhalant requirements, although findings should not be directly extrapolated to humans. Objective: To compare the tail-clamp-determined end-tidal isoflurane (EtISO) requirement after midazolam-propofol or midazolam-ketamine co-induction in healthy dogs, using castration as a standardized surgical noxious-stimulus model. Methods: Twelve healthy male dogs were randomized into two equal groups. All dogs received xylazine premedication. Group A received midazolam-propofol co-induction, and Group B received midazolam-ketamine co-induction. Isoflurane was delivered in oxygen. EtISO requirement was determined using a tail-clamp up-and-down approach, and cardiorespiratory variables were monitored. Results: The EtISO required to prevent purposeful movement was significantly lower in Group A (1.05 +/- 0.07%) than in Group B (1.23 +/- 0.08%; p < 0.01). The final vaporizer setting was also lower in Group A (1.10 +/- 0.10%) than in Group B (1.35 +/- 0.10%; p < 0.05). Physiological variables remained clinically acceptable in both groups. Conclusion: Midazolam-propofol produced a greater isoflurane-sparing effect than midazolam-ketamine in this canine comparative model. These findings may support translational hypotheses on balanced anesthesia, while requiring validation in human studies.