Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats

To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single‐dose, randomized, two‐period, two‐sequence, cross‐over bioequivalence study with a 7‐day washout period between treatments. Twenty‐four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross‐over design. One‐milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC‐MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUC_last and C_max. Equivalence was achieved if the 90% confidence interval for AUC_last and C_max fell into the asymmetric ±20% interval (0.80–1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. C_max and AUC_last for Reference and Test Products were statistically bioequivalent. No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats.     

Effects of sevoflurane,propofol or alfaxalone on neuromuscular blockade produced by a single intravenous bolus of rocuronium in dogs

ObjectiveTo compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs.Study designA randomized, prospective, crossover experimental study.AnimalsA total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years.MethodsThe dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg^–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded.ResultsThe onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments.Conclusions and clinical relevanceCompared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.     

Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats

Objective

To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L^–1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats.

Determination of the sevoflurane sparing effect of methadone in cats

ObjectiveTo determine the magnitude and duration of sevoflurane minimum alveolar concentration (MAC) reduction following a single intravenous (IV) dose of methadone in cats.Study designProspective experimental study.AnimalsEight (four females and four males) healthy mixed-breed adult (1–2 years) cats weighing 5.82 ± 0.42 kg.MethodsAnesthesia was induced and maintained with sevoflurane. Intravenous catheters facilitated administration of methadone and lactated Ringer’s solution. After baseline MAC determination in triplicate using a tail clamp technique, 0.3 mg kg^?1 of methadone was administered IV. End-tidal sevoflurane concentration (e′SEVO) was reduced and MAC was redetermined. In an effort to determine the duration of MAC reduction, measurements were repeated in a stepwise manner until MAC values returned to baseline. After the last stimulation, the e′SEVO was increased to 1.2 individual MAC for 15 minutes, then sevoflurane was discontinued and cats were allowed to recover from anesthesia.ResultsBaseline sevoflurane MAC was 3.18 ± 0.06%. When compared with baseline the sevoflurane MAC after methadone administration was significantly reduced by 25, 15 and 7% at 26, 76 and 122 minutes, respectively. The final MAC value (3.09 ± 0.07%) determined 156 minutes after methadone administration was not significantly different from baseline.Conclusions and clinical relevanceIntravenous methadone (0.3 mg kg^?1) significantly decreased MAC of sevoflurane in cats but the effect was short-lived.     

Comparison of pain on injection during induction of anaesthesia with alfaxalone and two formulations of propofol in dogs

ObjectiveTo compare the incidence of pain during injection of three intravenous induction agents in dogs.Study designProspective, crossover, randomized, blinded, clinical study.AnimalsThirty dogs requiring anaesthesia for radiotherapy.MethodsDogs were anaesthetized on three occasions at weekly intervals. An IV cephalic catheter was placed, flushed with saline and alfentanil 0.01 mg kg^?1 and atropine 0.02 mg kg^?1 administered. After 30 seconds either: propofol lipid macroemulsion (Drug_P), propofol lipid-free microemulsion (Drug_PC) or alfaxalone (Drug_A) was administered over 60 seconds. Each induction agent was administered once to each dog. Induction was recorded by video and reviewed by an assessor, unaware of treatment. Catheter placement (number of attempts, site, size and recent vein use) were recorded. Behavioural changes associated with pain or excitation, were recorded. Severity of pain on injection was recorded (mild, moderate or severe pain). Incidence of pain was analysed using logistic regression, excitation using McNemar's test (p < 0.05) and association of pain with induction agent and catheter placement using the Akaike Information Criterion (AIC).ResultsNo dogs reacted to saline or Drug_A, thus Drug_A was excluded from analysis. Pain on injection occurred in six dogs (20%) with Drug_PC and one dog (3.3%) with Drug_P. Pain was severe in four dogs with Drug_PC. Drug_P resulted in a trend for reduced risk of pain compared to Drug_PC (p = 0.076, odds ratio [confidence intervals] 0.14 [0.027–0.86]). Both propofol formulations resulted in greater risk of excitation than Drug_A (p = 0.0003, odds ratio 4.5 [1.86–10.90]). Induction agent was associated with pain, whilst catheter placement was not. One dog developed facial oedema and one other dog skin necrosis adjacent to the catheter site following Drug_PC. The study was terminated early due to ethical concerns about the severity of reactions with Drug_PC.Conclusions and Clinical relevanceDrug_PC was associated with clinically relevant moderate to severe pain behaviour whilst Drug_A and Drug_P were not.     

Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs

ObjectiveTo compare the anaesthetic and cardiopulmonary effects of alfaxalone with propofol when used for total intravenous anaesthesia (TIVA) during ovariohysterectomy in dogs.Study designA prospective non-blinded randomized clinical study.AnimalsFourteen healthy female crossbred bitches, aged 0.5–5 years and weight 16–42 kg.MethodsDogs were premedicated with acepromazine 0.01 mg kg^?1 and morphine 0.4 mg kg^?1. Anaesthesia was induced and maintained with either propofol or alfaxalone to effect for tracheal intubation followed by an infusion of the same agent. Dogs breathed spontaneously via a ‘circle’ circuit, with oxygen supplementation. Cardiopulmonary parameters (respiratory and heart rates, end-tidal carbon dioxide, tidal volume, and invasive blood pressures) were measured continuously and recorded at intervals related to the surgical procedure. Arterial blood samples were analysed for blood gas values. Quality of induction and recovery, and recovery times were determined. Non-parametric data were tested for significant differences between groups using the Mann–Whitney U-test and repeatedly measured data (normally distributed) for significant differences between and within groups by anova.ResultsBoth propofol and alphaxalone injection and subsequent infusions resulted in smooth, rapid induction and satisfactory maintenance of anaesthesia. Doses for induction (mean ± SD) were 5.8 ± 0.30 and 1.9 ± 0.07 mg kg^?1 and for the CRIs, 0.37 ± 0.09 and 0.11 ± 0.01 mg kg^?1 per minute for propofol and alfaxalone respectively. Median (IQR) recovery times were to sternal 45 (33–69) and 60 (46–61) and to standing 74 (69–76) and 90 (85–107) for propofol and alphaxalone respectively. Recovery quality was good. Cardiopulmonary effects did not differ between groups. Hypoventilation occurred in both groups.Conclusions and clinical relevanceFollowing premedication with acepromazine and morphine, both propofol and alphaxalone produce good quality anaesthesia adequate for ovariohysterectomy. Hypoventilation occurs suggesting a need for ventilatory support during prolonged infusion periods with either anaesthetic agent.     

Comparison of two formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish (Danio rerio)

ObjectiveTo compare two commercial formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish.Study designProspective, blinded, randomized study.AnimalsA total of 20 adult Danio rerio (Tuebingen strain).MethodsZebrafish were divided into two groups of 10 (five female, five male) and placed in individual immersion baths containing 10 mg L^–1 of unpreserved alfaxalone (group 1) or preserved alfaxalone (group 2). Anaesthetists blinded to treatment used a composite score scale (CSS) (range 0–12) to assess fish every 30 seconds until induction of anaesthesia. Anaesthetic induction occurred when equilibrium and response to stimulus were lost. Fish were then placed in a clean water bath and scored every 60 seconds. Recovery from anaesthesia was defined as a CSS of ≤ 1. Time variables recorded were anaesthetic induction time (AIT), anaesthetic recovery time (ART) and total procedure time (TPT). Fish were observed for evidence of roupgross external pathology during the procedure. Following anaesthesia, four fish from each group were randomly chosen and euthanized for gill histopathology analysis immediately after recovery criteria were met. Data are presented as mean ± standard deviation. An independent t test was used to compare the difference in average anaesthetic time variables between groups (α = 0.05).ResultsThere were no statistical differences between groups in reported variables. TPT, AIT and ART were 10.2 ± 1.2, 1.9 ± 0.9 and 8.3 ± 1.2 minutes for group 1 and 10.8 ± 2.9, 2.4 ± 1.2 and 8.4 ± 2.7 minutes for group 2. No gross external pathology was evident, and no fish died during the experimental period. Histopathology showed normal gill pathology and no difference between the groups.Conclusions and clinical relevanceImmersion anaesthesia using 10 mg L^–1 of either formulation of alfaxalone resulted in anaesthesia of similar quality and duration.     

Effects of midazolam before or after alfaxalone for co-induction of anaesthesia in healthy dogs

Objective

To study the effect of alternating the order of midazolam and alfaxalone administration on the incidence of behavioural changes, alfaxalone induction dose and some cardiorespiratory variables in healthy dogs.

Neuromuscular blocking properties of atracurium during sevoflurane or propofol anaesthesia in dogs

OBJECTIVE: To quantify the neuromuscular blockade (NMB) produced by atracurium in either sevoflurane or propofol-anaesthetized dogs. ANIMALS: Twelve healthy, female adult mixed-breed dogs weighing 13 +/- 3 kg (range 10-22 kg). MATERIALS AND METHODS: Three doses of atracurium (0.1, 0.2 and 0.3 mg kg(-1)) were tested at 1-week intervals. Anaesthesia was induced with inhaled sevoflurane or intravenous propofol and maintained with end-tidal sevoflurane concentrations of 1.95% (1.25 x MAC) or propofol 0.6 mg kg(-1) minute(-1) respectively. Acceleromyography and train-of-four stimulation of the fibular nerve were used for the assessment of NMB. The percentage depression of the first twitch (T1) and the fourth to the first twitch ratio (T4/T1), the maximum degree of neuromuscular block achieved and surgical muscle relaxation were recorded. Before and during neuro muscular blockade (at 10 minute intervals) body temperature, ECG, arterial blood pressure, inspired and expired CO2 concentrations and SpO2 were recorded. RESULTS: Atracurium produced a dose-dependent duration of NMB in both propofol and sevoflurane-anaesthetized dogs. Duration of block was longer in dogs anaesthetized with sevoflurane. All studied doses of atracurium caused twitch depression > or =95% with little or no cardiovascular changes. CONCLUSIONS: Sevoflurane produces a clinically relevant potentiation of atracurium-induced NMB in dogs compared with propofol. CLINICAL RELEVANCE: Significant differences in the potentiation of NMB drugs are encountered with commonly used anaesthetics in the dog.     

Endocrine, haematological and metabolic responses to sevoflurane anaesthesia in lambs

Objective To compare the magnitude and duration of the peri‐operative haematological, endocrine and metabolic effects of surgery performed under sevoflurane anaesthesia. Study Design Prospective randomized study. Animals Ten, 55‐day‐old lambs of both sexes, mean weight 20.8 ± 0.3 kg (range 18.5–23.6 kg). Methods Animals were randomly allocated to two equal groups. All were anaesthetized with sevoflurane for 3 hours. Surgery (end‐to‐end anastomosis of the right carotid artery and right jugular vein) was performed in animals of Group 1 only. The electrocardiogram, pulse oximetry, cardiac output and noninvasive arterial blood pressure (NIBP) were monitored. Venous blood samples (5 mL) were taken 30 minutes before induction of anaesthesia (T = 0) and 1 (T1), 24 (T2), 48 hours (T3) and 7 days (T4) after anaesthesia in order to measure plasma cortisol, ACTH, insulin, cyclic adenosine monophosphate (cAMP), glucose, protein concentrations and haematological variables. Results Sevoflurane decreased NIBP (minimum mean value: 64 ± 3 mm Hg) in both groups. Plasma cortisol and ACTH concentration increased in Group 1 (maximum mean values: cortisol: 136.2 nmol L^?1, ACTH: 54.5 pmol L^?1) and Group 2 (maximum mean values: cortisol: 128.7 nmol L^?1, ACTH: 44.0 pmol L^?1). Cyclic AMP increased only in Group 1 (9.3 nmol) 1 hour after anaesthesia. Neutrophilia, lymphopaenia and a decreased PCV were observed in both groups 1 hour after anaesthesia. Plasma protein and glucose concentrations did not change. Conclusions Increased ACTH and cortisol concentrations recorded 1 hour after anaesthesia suggest that sevoflurane induces a stress response in lambs. Clinical relevance The study did not identify the mechanism by which sevoflurane induces a stress response although hypotension is implicated.     

Comparison of electroencephalogram activity and auditory evoked responses during isoflurane and halothane anaesthesia in the rat

Objectives To compare the second differential index (SDI) calculated from the auditory evoked potential (AEP) and electroencephalogram (EEG) parameters: median frequency (MF), spectral edge frequency (SEF) and burst suppression rate (BSR) determined at four equivalent minimum alveolar concentrations (MAC) of isoflurane or halothane. Animals Twelve male Wistar rats weighing 418 g (SD ± 18.4 g). Methods Auditory evoked potentials and EEG responses were recorded in animals implanted with electrodes at established anaesthetic concentrations. Depth of anaesthesia was assessed using the strength of the pedal withdrawal reflex (PWR), and data were analysed using repeated measures anova and paired t‐tests. Results The SEF tended to decrease with increasing depth of halothane anaesthesia (F = 4.198, p = 0.05), but not with isoflurane. The MF and SDI were significantly higher during halothane than with isoflurane (F = 5.82, p = 0.036 and F = 5.263, p = 0.045, respectively) at equivalent depths of anaesthesia, and EEG burst suppression occurred at deeper planes of isoflurane but not halothane anaesthesia. Conclusions The study demonstrated that EEG and AEP characteristics recorded at MAC equivalent concentrations were suppressed to a greater degree by isoflurane than by halothane. These findings have strong implications for research projects where EEG recordings are collected, and also cast more general doubts upon the value of such parameters for evaluating depth of isoflurane anaesthesia in rats.     

The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats

ObjectiveTo determine the cardiorespiratory and anesthetic effects of 0, 5, 15, and 50 mg kg^?1 intravenous (IV) alfaxalone in hydroxypropyl beta cyclodextrin (Alfaxan; Jurox Pty Ltd, Rutherford, NSW, Australia) in cats.Study designFour treatments of alfaxalone were administered in sequential order.AnimalsEight healthy adult cats (four male; four female) weighing between 3.71 and 5.91 kg.MethodsCats were instrumented for hemodynamic measurements. Four (0, 5, 15, and 50 mg kg^?1) IV doses of alfaxalone were administered over one minute, with a 3-hour washout period between doses 0, 5, and 15 mg kg^?1 on Day 0. The 50 mg kg^?1 treatment was administered 24 hours later. Measurements of heart rate, aortic systolic, mean, and diastolic blood pressures, pulmonary arterial and right atrial mean pressures, cardiac output, respiratory rate, tidal and minute volumes, and arterial blood pH and blood gases (PaO₂, PaCO₂) were performed at pre-determined intervals. Systemic vascular resistance and rate pressure product were calculated. The quality of induction, maintenance, and recovery from anesthesia and the response to noxious stimulation were categorically scored.ResultsAlfaxalone administration resulted in dose-dependent cardiorespiratory depression. Decreases in arterial blood pressure and increases in heart rate occurred at higher doses. Most variables returned to baseline by 15-30 minutes. Respiratory rate, minute volume, and PaO₂ decreased. Apnea was the most common side effect. Induction and maintenance quality were judged to be good to excellent at all doses and quality of recovery good to excellent at all but the 50 mg kg^?1 dose. The duration of anesthesia and unresponsiveness to noxious stimulation increased with dose. The administration of the 50 mg kg^?1 dose produced marked cardiorespiratory depression and apnea.Conclusions and clinical relevanceAlfaxalone produced dose-dependent anesthesia, cardiorespiratory depression and unresponsiveness to noxious stimulation in unpremedicated cats. Hypoventilation and apnea were the most common side effects.     

Intramuscular alfaxalone and methadone with or without ketamine in healthy cats: effects on sedation and echocardiographic measurements

ObjectiveTo evaluate the effect of alfaxalone and methadone administered intramuscularly (IM), with or without ketamine, on sedation and echocardiographic measurements in healthy cats.Study designA randomized, blinded, clinical study.AnimalsA group of 24 client-owned cats.MethodsBaseline echocardiographic evaluation (bEchoCG) was performed. Cats were given IM alfaxalone (2 mg kg^–1) and methadone (0.3 mg kg^–1) with (AMK group) or without (AM group) ketamine (1 mg kg^–1). A sedation score (0–5, indicating none to good sedation) was assigned at 5 (T5), 10 (T10) and 15 (T15) minutes after IM injection. At T15, a second echocardiographic evaluation (sEchoCG) was performed. Data are shown as median (range). Significance was p < 0.05.ResultsFinally, 21 cats were included. Sedation score was significantly higher in the AMK (11 cats) than in the AM group (10 cats): 4 (1–5) versus 0.5 (0–4) at T5 (p = 0.003); 4 (1–5) versus 1.5 (0–5) at T10 (p = 0.043); and 4 (1–5) versus 2 (0–5) at T15 (p = 0.024). All echocardiographic measurements obtained were within reference ranges. Between the groups, aortic root area (p = 0.009) and end-diastolic aortic dimension (p = 0.011) were significantly higher in the AM group at bEchoCG and sEchoCG, respectively. Within each group, values at bEchoCG and sEchoCG showed no significant differences, except for pulmonary peak velocity (0.85 m second^–1; p = 0.028) in the AMK group and ejection time (154 m second; p = 0.03) in the AM group; both variables decreased after sedation.Conclusions and clinical relevanceIn this population of healthy cats, neither protocol produced clinically meaningful effects on the echocardiographic variables evaluated. Alfaxalone with methadone produced mild sedation, whereas the addition of 1 mg kg^–1 ketamine induced adequate sedation for diagnostic procedures.     

Effects of aging on brainstem responses to toneburst auditory stimuli: a cross-sectional and longitudinal study in dogs

BACKGROUND: It is assumed that the hearing of dogs becomes impaired with advancing age, but little is known about the prevalence and electrophysiologic characteristics of presbycusis in this species. HYPOTHESIS: As in humans, hearing in dogs becomes impaired with aging across the entire frequency range, but primarily in the high-frequency area. This change can be assessed quantitatively by brainstem-evoked response audiometry (BERA). ANIMALS: Three groups of 10 mixed-breed dogs with similar body weights but different mean ages were used. At the start of the study, the mean age was 1.9 years (range, 0.9-3.4) in group I, 5.7 years (3.5-7) in group II, and 12.7 years (11-14) in group III. METHODS: In a cross-sectional study, the BERA audiograms obtained with toneburst stimuli were compared among the 3 groups. In a longitudinal study, changes in auditory thresholds of group II dogs were followed for 7 years. RESULTS: Thresholds were significantly higher in group III than in groups I and II at all frequencies tested, and higher in group II than in group I at 4 kHz. The audiograms in group II indicated a progressive increase in thresholds associated with aging starting around 8-10 years of age and most pronounced in the middle- to high-frequency region (8-32 kHz). CONCLUSIONS AND CLINICAL IMPORTANCE: Age-related hearing loss in these dogs started around 8-10 years of age and encompassed the entire frequency range, but started and progressed most rapidly in the middle- to high-frequency area. Its progression can be followed by BERA with frequency-specific stimulation.