Influence of Ketamine-Xylazine Anaesthesia on Cubic and Quadratic High-Frequency Distortion-Product Otoacoustic Emissions

Ketamine is a dissociative anaesthetic, analgesic drug as well as an N-methyl-d-aspartate receptor antagonist and has been reported to influence otoacoustic emission amplitudes. In the present study, we assess the effect of ketamine-xylazine on high-frequency distortion-product otoacoustic emissions (DPOAE) in the bat species Carollia perspicillata, which serves as model for sensitive high-frequency hearing. Cubic DPOAE provide information about the nonlinear gain of the cochlear amplifier, whereas quadratic DPOAE are used to assess the symmetry of cochlear amplification and potential efferent influence on the operating state of the cochlear amplifier. During anaesthesia, maximum cubic DPOAE levels can increase by up to 35 dB within a medium stimulus level range from 35 to 60 dB SPL. Close to the -10 dB SPL threshold, at stimulus levels below about 20-30 dB SPL, anaesthesia reduces cubic DPOAE amplitudes and raises cubic DPOAE thresholds. This makes DPOAE growth functions steeper. Additionally, ketamine increases the optimum stimulus frequency ratio which is indicative of a reduction of cochlear tuning sharpness. The effect of ketamine on cubic DPOAE thresholds becomes stronger at higher stimulus frequencies and is highly significant for f2 frequencies above 40 kHz. Quadratic DPOAE levels are increased by up to 25 dB by ketamine at medium stimulus levels. In contrast to cubic DPOAEs, quadratic DPOAE threshold changes are variable and there is no significant loss of sensitivity during anaesthesia. We discuss that ketamine effects could be caused by modulation of middle ear function or a release from ipsilateral efferent modulation that mainly affects the gain of cochlear amplification.