Hemodynamic effects of subclinical, clinical and supraclinical plasma alfaxalone concentrations in cats

Objective: To characterize the hemodynamic effects of subclinical, clinical and supraclinical plasma alfaxalone concentrations in cats. Study design: Experimental study. Animals: A group of six adult healthy male neutered cats. Methods: Cats were anesthetized with desflurane in oxygen for instrumentation. Catheters were placed in a medial saphenous vein for drug administration and in a carotid artery for arterial blood pressure measurement and blood collection. A thermodilution catheter was placed in the pulmonary artery via an introducer placed in a jugular vein for measurement of central venous pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac output and core body temperature, and for sampling mixed venous blood. A lead II electrocardiogram was connected. Desflurane administration was discontinued and a target-controlled infusion system was used to administer alfaxalone to reach six plasma alfaxalone concentrations ranging from 1.0 to 30.4 mg L⁻¹, with 7.6 mg L⁻¹ considered a clinical concentration for anesthesia. Cardiovascular measurements were recorded, and arterial and mixed-venous blood samples were collected for blood-gas analysis and plasma alfaxalone concentration measurement at each target concentration. Data were analyzed using a repeated-measures analysis of variance and Dunnett's test for comparisons to the lowest target concentration. Significance was set at p < 0.05. Results: Mean ± standard deviation plasma alfaxalone concentrations were 0.73 ± 0.32, 1.42 ± 0.41, 3.44 ± 0.40, 6.56 ± 0.43, 18.88 ± 6.81 and 49.47 ± 5.50 mg L⁻¹ for the 1, 1.9, 3.8, 7.6, 15.2, and 30.4 mg L⁻¹ target concentrations, respectively. PaCO₂ increased with increasing target plasma alfaxalone concentrations and was 69.4 ± 14.2 mmHg (9.3 ± 1.9 kPa) at the 30.4 mg L⁻¹ target. Some cardiovascular variables were statistically significantly affected by increasing target plasma alfaxalone concentrations. Conclusion and clinical relevance: Within the plasma concentration range studied, alfaxalone caused hypoventilation, but the cardiovascular effects were of small clinical significance.