Application of Dixon's Up-and-Down Design to Estimate the Minimum Alveolar Concentration of Sevoflurane in Rats with Refined Movement Classification

Our research focuses on the need for a personalized management of drug combinations in anesthesiology to ensure the optimal anesthetic depth considering complex interactions among different drugs. Our previously published studies showed significant reductions in propofol and sevoflurane requirements following THC, ethanol, and pregabalin administration highlighting notable and clinically relevant drug anesthetic interactions. Basic animal studies on hypnotic vasopressor interactions date back to the 1970s, often using just a few subjects and focusing on outdated agents like halothane leaving limited data on modern anesthetics such as sevoflurane.

[Narrator] To begin, use an airtight transparent chamber for placing the rat. Connect the inflow and outflows line to sevoflurane and monitor sevoflurane concentrations. Ensure a constant oxygen flow of three liters per minute. Now, identify the distal third of the tail and lock the clamp in place. Apply the pain stimulus until the rat shows a positive movement response. Classify as rolling when the behavioral response involves an axial rotation of the body, typically along the longitudinal axis, or is stretching when the behavioral response is characterized by a bilateral symmetric outward extension of the limbs and body. Classify as saltatory movement when the behavioral response consists of sudden hind limb-focused kicks or jerks resembling short, hopping like bursts of the whole body. And as curling when the behavioral response involves uncoordinated inward-directed movement of varying intensity causing the body to bend toward its center. The MAC was significantly reduced in the 10 milligram per kilogram THC group compared to the THC control group and in both one gram per kilogram and two gram per kilogram ethanol groups compared to the ethanol control group. Curling was the most frequently observed movement in the THC study, whereas rolling predominated in the ethanol study. In the THC study, movement types such as curling, rolling, stretching, and saltatory appeared at similar sevoflurane concentrations with no evident pattern linking them to anesthetic depth. In the ethanol study, no clear separation between movement types and sevoflurane concentration was observed indicating no obvious relationship with anesthetic depth.