A dose characterization study evaluating the pharmacodynamics and safety of a concentrated alfaxalone solution (4%) as an intramuscular sedative in dogs.

Alfaxalone is a commonly employed veterinary anaesthetic induction and sedation agent. A 4% w/v preserved, aqueous formulation of alfaxalone 'RD0387' (A4%) has recently been developed. To evaluate the sedative effects of A4%, three doses, 5 mg kg-1 (A5); 7.5 mg kg-1 (A7.5) and 10 mg kg-1 (A10) were administered intramuscularly into the epaxial musculature of six healthy adult mixed-breed dogs in an experimental, randomized, blinded, crossover study. Sedation time variables, quality of sedation (including onset of sedation and recovery), physiological variables, response to cephalic vein catheterization and frequency of undesirable events were recorded. Continuous variables were analysed between treatments (one-way ANOVA or restricted maximum likelihood modelling) and within treatments compared with baseline (Tukey's test). Categorical data were analysed between treatments (Kruskal-Wallis' test) and within treatments from baseline (Dunn's test). Significance was set at p < .05. All dogs became sedated (laterally recumbent) and sedation onset was significantly faster in groups A7.5 (9.8 ± 5.3 min) and A10 (9.1 ± 5.6 min) compared to A5 (25.6 ± 16.1 min) (p = .033, p = .027, respectively). Duration of sedation was significantly longer in A10 (168.5 ± 70.6 min) and A7.5 (143.8 ± 58 min) compared to A5 (63.8 ± 28.2 min) (p = .005 and p = .003, respectively). Dogs in A10 had a superior quality of onset of sedation compared to A5 (p = .028). Sedation scores and quality of recovery from sedation were not significantly different between doses. Two dogs (2/6) in A5 were insufficiently sedated for cephalic catheterization. Ataxia was the most frequently observed undesirable event with an overall frequency of 78% (14/18) and 89% (16/18) during sedation onset and recovery, respectively. Overall, A4% administered IM in dogs at 7.5 and 10 mg kg-1 resulted in sufficient sedation for IV catheterization in dogs. To improve the speed and quality of the sedation, it is recommended that future research focuses on combining A4% with other sedative or analgesic drugs.

Echocardiographic and hemodynamic effects of alfaxalone or dexmedetomidine based sedation protocols in cats with hypertrophic cardiomyopathy: a pilot study.

OBJECTIVE: To report the effects of alfaxalone and dexmedetomidine based sedation protocols on echocardiographic and hemodynamic variables in cats with hypertrophic cardiomyopathy (HCM) during sedation and inhalational anesthesia. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: A group of 10 client-owned cats with subclinical HCM. METHODS: Cats were administered one of two sedative intramuscular combinations: protocol ABM (alfaxalone 2 mg kg-1, butorphanol 0.4 mg kg-1, midazolam 0.2 mg kg-1; n = 5) or protocol DBM (dexmedetomidine 8 µg kg-1, butorphanol 0.4 mg kg-1, midazolam 0.2 mg kg-1; n = 5). General anesthesia was induced with intravenous alfaxalone and maintained with isoflurane in oxygen. Echocardiographic variables and noninvasive arterial blood pressures were obtained before sedation, following sedation, and during inhalational anesthesia. Sedation scores and alfaxalone induction dose requirements were recorded. Descriptive statistics are reported for cardiovascular variables. RESULTS: During sedation, echocardiographic and hemodynamic variables remained within normal limits with protocol ABM, whereas protocol DBM was characterized by bradycardia, low cardiac index and elevated blood pressure. During isoflurane anesthesia, both protocols demonstrated similar hemodynamic performance, with heart rates of 98 ± 12 and 89 ± 11 beats min-1, cardiac index values of 68 ± 17 and 47 ± 13 mL min-1 kg-1 and Doppler blood pressures of 72 ± 15 and 79 ± 20 mmHg with protocols ABM and DBM, respectively. A reduction in myocardial velocities were also observed during atrial and ventricular contraction with both protocols during isoflurane anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: An alfaxalone based protocol offered hemodynamic stability during sedation in cats with HCM; however, both dexmedetomidine and alfaxalone based protocols resulted in clinically relevant hemodynamic compromise during isoflurane anesthesia. Further studies are required to determine optimal sedative and anesthetic protocols in cats with HCM.

Evaluation of a noncontrolled, pre-euthanasia, intramuscular sedation drug protocol including alfaxalone 4%, medetomidine, and acepromazine for injured or ill raccoons.

Background: As a major animal control service provider in the city of Guelph and Wellington County in Ontario, the Guelph Humane Society transports and presents injured or ill raccoons requiring humane euthanasia to the Ontario Veterinary College Health Sciences Centre (OVC-HSC). Issues around handling, transportation, and delays before euthanasia have recently raised some concerns for welfare and the need for means of improving this process. Objective: Investigation of a noncontrolled sedation and analgesia protocol for injured or ill raccoons intended to improve animal welfare by allowing humane handling, transport, and euthanasia following administration by an animal protection officer (APO). Animals and procedure: Twenty-seven injured or ill raccoons requiring transport and euthanasia, as determined by the Guelph Humane Society APOs, were included in the study. Each raccoon was administered acepromazine (0.05 mg/kg), alfaxalone (4 mg/kg), and medetomidine (0.15 mg/kg), intramuscularly, before being transported to the OVC-HSC for humane euthanasia. Results: The combination of acepromazine, alfaxalone, and medetomidine was suitable for administration by APOs and provided the desired sedation depth to allow transport and humane euthanasia. Transit time was the only predictor of sedation depth upon arrival at the OVC-HSC. Two raccoons showed mild physical response to intracardiac injection for euthanasia. Numerical cutoff points of an in-hospital visual analog score of sedation of ≥ 70/100 and duration of sedation of < 62 min showed zero probability of response to euthanasia. Conclusion and clinical relevance: Administration of acepromazine, alfaxalone, and medetomidine at the stated doses provided acceptable sedation and analgesia to improve animal welfare during transport and eventual euthanasia of raccoons.

Évaluation d'un protocole médicamenteux sans groupe témoin de sédation intramusculaire, pré-euthanasie, comprenant de l'alfaxalone 4 %, de la médétomidine et de l'acépromazine pour les ratons laveurs blessés ou malades. Contexte: En tant que fournisseur majeur de services de contrôle des animaux dans la ville de Guelph et dans le comté de Wellington en Ontario, la Guelph Humane Society transporte et présente les ratons laveurs blessés ou malades nécessitant une euthanasie sans cruauté au Ontario Veterinary College Health Sciences Centre (OVC-HSC). Les problèmes liés à la manutention, au transport et aux délais avant l'euthanasie ont récemment soulevé des inquiétudes quant au bien-être et à la nécessité de trouver des moyens d'améliorer ce processus. Objectif: Enquête sur un protocole de sédation et d'analgésie sans groupe témoin pour les ratons laveurs blessés ou malades destiné à améliorer le bien-être des animaux en permettant une manipulation, un transport et une euthanasie sans cruauté après administration par un agent de protection des animaux (APO). Animaux et procédure: Vingt-sept ratons laveurs blessés ou malades nécessitant un transport et une euthanasie, tel que déterminé par les APO de la Guelph Humane Society, ont été inclus dans l'étude. Chaque raton laveur a reçu de l'acépromazine (0,05 mg/kg), de l'alfaxalone (4 mg/kg) et de la médétomidine (0,15 mg/kg), par voie intramusculaire, avant d'être transporté à l'OVC-HSC pour une euthanasie sans cruauté. Résultats: La combinaison d'acépromazine, d'alfaxalone et de médétomidine convenait à l'administration par un APO et fournissait la profondeur de sédation souhaitée pour permettre le transport et l'euthanasie sans cruauté. Le temps de transit était le seul prédicteur de la profondeur de la sédation à l'arrivée à l'OVC-HSC. Deux ratons laveurs ont montré une légère réponse physique à une injection intracardiaque pour l'euthanasie. Les seuils numériques d'un score analogique visuel de sédation à l'hôpital ≥ 70/100 et d'une durée de sédation < 62 min ont montré une probabilité nulle de réponse à l'euthanasie. Conclusion et pertinence clinique: L'administration d'acépromazine, d'alfaxalone et de médétomidine aux doses indiquées a fourni une sédation et une analgésie acceptables pour améliorer le bien-être des animaux pendant le transport et l'euthanasie éventuelle des ratons laveurs.(Traduit par Dr Serge Messier).

COMPARISON OF SUBCUTANEOUS ALFAXALONE AND SUBCUTANEOUS ALFAXALONE-DEXMEDETOMIDINE FOR SEDATION IN THE HOUSTON TOAD (ANAXYRUS HOUSTONENSIS).

The Houston toad (Anaxyrus houstonensis), a primarily terrestrial amphibian of south-central Texas, has been listed as federally endangered since 1970. Sedation is an important tool for obtaining diagnostics and providing treatment in this species. This prospective, randomized, and blinded study compared the sedative effects of SC alfaxalone (Protocol A) at approximately 12 mg/kg (median [range] = 12.70 [12.09-13.95] mg/kg] to SC alfaxalone-dexmedetomidine (Protocol AD) at approximately 12 mg/kg (median [range] = 12.68 [12.16-13.56] mg/kg) and 0.1 mg/kg (median [range] = 0.1 [0.07-0.13] mg/kg), respectively, in adult Houston toads (n = 26). Toads from Protocol AD received atipamezole SC at approximately 1 mg/kg (median [range] = 0.96 [0.75-1.25] mg/kg) 45 min postinduction, whereas toads from Protocol A received the equivalent volume of SC sterile saline at the same time point. Heart rate, gular rate, and times to first effect, loss of righting reflex, ability to position for radiographs, loss of nociception, return of righting reflex, and full recovery were recorded. A significantly greater number of toads lost righting reflex, positioned for radiographs, and lost nociception with Protocol AD compared with Protocol A. Additionally, time to return of righting reflex and time to full recovery were significantly longer with Protocol AD than with Protocol A. The protocols did not differ significantly in time to first effect, time to radiographic positioning, or time to loss of nociception. Histologic examination of four toads euthanized during the study revealed acute injection site reactions from all administered drugs, including saline. No clinical adverse reactions were observed. This study demonstrates that the combination of SC alfaxalone and dexmedetomidine results in deeper sedation than SC alfaxalone alone, but also correlates with longer recovery times despite antagonist administration.

Comparison of alfaxalone and propofol on haematological and serum biochemical variables in cats undergoing radiotherapy with sevoflurane maintenance.

OBJECTIVE: To evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy. STUDY DESIGN: Prospective, block-randomized, clinical trial. ANIMALS: A group of 39 client-owned cats. METHODS: After butorphanol (0.2 mg kg-1) and midazolam (0.1 mg kg-1) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10-12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05. RESULTS: At baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 µL-1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 µL-1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg-1 ± 5.3 and 43.4 mg kg-1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Haematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes.

Effect of anesthetic induction with propofol, alfaxalone or ketamine on intraocular pressure in cats: a randomized masked clinical investigation.

OBJECTIVE: To compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats. STUDY DESIGN: Prospective, masked, randomized clinical trial. ANIMALS: A total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures. METHODS: Following baseline IOP measurements using applanation tonometry, anesthesia was induced with propofol (n = 15), alfaxalone (n = 14) or ketamine (n = 14) administered intravenously to effect. Then, midazolam (0.3 mg kg-1) was administered intravenously and endotracheal intubation was performed without application of topical anesthesia. The IOP was measured following each intervention. Data was analyzed using one-way anova and repeated-measures mixed design with post hoc analysis. A p-value <0.05 was considered significant. RESULTS: Mean ± standard error IOP at baseline was not different among groups (propofol, 18 ± 0.6; alfaxalone, 18 ± 0.7; ketamine, 17 ± 0.5 mmHg). Following induction of anesthesia, IOP increased significantly compared with baseline in the propofol (20 ± 0.7 mmHg), but not in the alfaxalone (19 ± 0.8 mmHg) or ketamine (16 ± 0.7 mmHg) groups. Midazolam administration resulted in significant decrease from the previous measurement in the alfaxalone group (16 ± 0.7 mmHg), but not in the propofol group (19 ± 0.7 mmHg) or the ketamine (16 ± 0.8 mmHg) group. A further decrease was measured after intubation in the alfaxalone group (15 ± 0.9 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: Propofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided.

Sedative and cardiorespiratory effects of intranasal atomized alfaxalone in Japanese White rabbits.

OBJECTIVE: To investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits. STUDY DESIGN: Randomized, prospective, crossover study. ANIMALS: A total of eight healthy female rabbits, weighing 3.6-4.3 kg and aged 12-24 months. METHODS: Each rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0-13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (fR), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO2) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO2 <90% or PaO2 <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05). RESULTS: No rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10-20) minutes [median (25th-75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1-4) and 9 (9-9), respectively. fR decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP. CONCLUSIONS AND CLINICAL RELEVANCE: INA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted.

Comparison of two formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish (Daniorerio).

OBJECTIVE: To compare two commercial formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish. STUDY DESIGN: Prospective, blinded, randomized study. ANIMALS: A total of 20 adult Danio rerio (Tuebingen strain). METHODS: Zebrafish 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). RESULTS: There 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 RELEVANCE: Immersion anaesthesia using 10 mg L-1 of either formulation of alfaxalone resulted in anaesthesia of similar quality and duration.

Evaluation of alfaxalone total intravenous anesthesia in rabbits (Oryctolagus cuniculus) premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.

OBJECTIVE: To evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine. STUDY DESIGN: Crossover study (part 1) with observational study (part 2). ANIMALS: A total of eight New Zealand White rabbits (Oryctolagus cuniculus), four female and four male, aged 12-16 weeks and weighing 2.8-3.5 kg in part 1. Separately, four additional rabbits in part 2. METHODS: Crossover study design with eight rabbits per treatment. Rabbits were administered treatment D, dexmedetomidine (0.2 mg kg-1), or treatment DB, dexmedetomidine (0.1 mg kg-1) and buprenorphine (0.05 mg kg-1) intramuscularly. Anesthesia was induced with alfaxalone intravenously until a supraglottic airway device was placed to deliver 100% oxygen. Anesthesia was maintained with alfaxalone (TIVA). Infusion rates were adjusted to achieve an absent pedal withdrawal reflex. Heart rate, respiratory rate, noninvasive blood pressure, end-tidal carbon dioxide partial pressure and peripheral hemoglobin oxygen saturation (SpO2) were recorded every 5 minutes. Subsequently, four rabbits underwent ovariohysterectomy using treatment DB and alfaxalone TIVA. RESULTS: The mean ± standard deviation alfaxalone infusion rate was 9.6 ± 2.6 and 4.5 ± 1.3 mg kg-1 hour-1 for treatments D and DB, respectively. In both treatments, blood pressure remained within acceptable range and SpO2 was > 95%. Postinduction apnea and respiratory depression were observed in both treatments and managed with manual positive pressure ventilation. Four separate rabbits underwent successful ovariohysterectomy with treatment DB and alfaxalone TIVA. One rabbit required supplementation with inhalant anesthesia; three rabbits were successfully maintained using alfaxalone TIVA alone. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with dexmedetomidine-buprenorphine combined with alfaxalone TIVA may be a viable alternative for performing abdominal surgery in the rabbit. The use of supplemental oxygen and ability to provide respiratory support are advised.

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

OBJECTIVE: To compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. STUDY DESIGN: A randomized, prospective, crossover experimental study. ANIMALS: A total of eight adult Beagle dogs (four female, four male), weighing 8.9-15.3 kg and aged 5-7 years. METHODS: The 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. RESULTS: The 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 RELEVANCE: Compared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.

PLASMA CONCENTRATION AND PHARMACODYNAMICS OF INTRAMUSCULAR ADMINISTRATION OF ALFAXALONE IN INDIAN PEAFOWL (PAVO CRISTATUS).

Alfaxalone, a neuroactive steroid with anesthetic properties, is considered safe when used alone or in combination with other drugs for anesthesia at recommended species doses, and its use has been studied in numerous species. The objective of this study was to assess the pharmacokinetics and pharmacodynamics of IM alfaxalone in Indian peafowl (Pavo cristatus; hereafter peafowl). Eight female peafowl from one zoological institution were used. A control blood sample was obtained before administration of either 10 mg/kg (n = 4) or 20 mg/kg (n = 4) alfaxalone. Blood was collected at 5, 10, 15, 30, and 60 min after alfaxalone injection, with monitoring of sedation score, heart rate, and respiratory rate at each time point. Four peahens receiving a 10 mg/ kg dose had subjectively smoother inductions and recoveries, although sedation level was generally scored as low, with no adverse reactions noted. They were considered fully recovered by the 60-min postinjection time point, although measurable alfaxalone plasma concentrations remained present. Four peahens receiving 20 mg/kg IM experienced adverse effects including seizure-like episodes and hypersensitivity to stimuli throughout the study. This dosing group experienced prolonged recoveries consistent with high plasma concentrations (>3,000 ng/ml). Based on these results, use of 20 mg/kg IM alfaxalone as the sole anesthetic agent is not recommended in this species. Further studies should determine whether alfaxalone in conjunction with other anesthetic or analgesic agents could provide better sedation and smoother induction and recovery for peafowl and to assess the pharmacokinetics and pharmacodynamics of alfaxalone in other avian species.

Comparison of Sedative Effects of Alfaxalone-Ketamine and Alfaxalone-Midazolam Administered Intramuscularly in Chickens.

The objective of this study was to compare the sedative effects of intramuscular alfaxalone combined with either ketamine or midazolam in chickens (Gallus gallus domesticus). A prospective, randomized blinded crossover study design with a 7-day washout period was used. Nine adult layer hens received alfaxalone 15 mg/kg with ketamine 5 mg/kg IM (treatment AK) or alfaxalone 15 mg/kg with midazolam 1 mg/kg IM (treatment AM). Time to lateral recumbency, time to loss of righting reflex, induction quality, duration of loss of righting reflex, time to sternal recumbency or vigorous response to stimulation, and time to standing were recorded. Muscle tone, response to noxious stimulation, heart rate, respiratory rate, and oxygen saturation were monitored once the righting reflex was absent. Induction and recovery times were not different between treatments. Lateral recumbency was induced in 8 of 9 birds receiving AK compared to 6 of 9 birds receiving AM. Righting reflex was absent in 7 of 9 and 5 of 9 chickens administered AK and AM, respectively. Median time to loss of righting reflex for AK and AM were 5.5 (4.3-9.3) minutes and 9.1 (4.8-15.0) minutes, respectively (P = .88). Median duration of loss of righting reflex was 21.6 (16.0-36.9) minutes for AK and 21.1 (11.9-26.4) minutes for AM (P = .38). Alfaxalone-ketamine resulted in moderate excitation during induction. Further investigations are warranted to investigate the effects of alfaxalone and midazolam or ketamine at different doses.

Pharmacodynamics of propofol and alfaxalone in rattlesnakes (Crotalus durissus).

To characterise the effect of two common induction agents, propofol and alfaxalone, on mean arterial blood pressure (MAP) and heart rate (HR), we equipped 19 adult South American rattlesnakes (Crotalus durissus) with an indwelling arterial catheter approximately 24 h prior to recording of baseline resting values. Then, seven snakes received alfaxalone (15 mg kg-1) intravascularly (IV) through the catheter, while groups two and three (both n = 6) received propofol (15 mg kg-1 IV). The first two groups were not handled, while the group 3 was manually restrained for 2 min for a mock injection of 0.2 ml saline into the ventral tail vein. Baseline HR was similar in all groups and handling caused a significant tachycardia (p = 0.031) in group three. When given IV to undisturbed animals, both propofol and alfaxalone induced a significant increase in HR (p = 0.0022 and p = 0.0045, respectively) lasting approximately 30 min, but with values only significantly exceeding baseline for the first 5 min for propofol and the first 10 min with alfaxalone. Handling caused a significant increase in MAP (p = 0.0313). Propofol did not affect MAP (p = 0.1064), while alfaxalone caused a marked hypertension (although only significant at 2 min; p = 0.031). Manual restraint significantly increases both HR and MAP, which may lead to a masking of true cardiovascular effects of anaesthetic agents.

Laryngeal function in normal dogs administered isoflurane following partial clearance of alfaxalone or propofol.

OBJECTIVE: To assess laryngeal function in normal dogs administered isoflurane following partial clearance of alfaxalone or propofol. STUDY DESIGN: Randomized experimental crossover study. ANIMALS: A group of 12 purpose-bred, male Beagle dogs. METHODS: Dogs were randomly assigned to one of two treatments: alfaxalone-isoflurane (ALF-ISO) or propofol-isoflurane (PRO-ISO) and anesthetized for three video laryngoscopy examinations. The alternate treatment occurred after ≥ 14 days interval. Examinations were performed after induction of anesthesia (LS-A), after 20 minutes of breathing isoflurane via a facemask (LS-B) and after a further 20 minutes of isoflurane (LS-C). Parameters of objective laryngeal function included inspiratory rima glottidis surface area (RGSA-I), expiratory rima glottidis surface area (RGSA-E) and % RGSA increase, calculated from three consecutive respiratory cycles in the final 15 seconds of each video laryngoscopy examination. The % RGSA increase was calculated using [(RGSA-I - RGSA-E)/RGSA-E] × 100. Subjective laryngeal function was evaluated independently by two experienced surgeons blinded to treatment. RESULTS: The % RGSA increase within each treatment was greater for LS-B and LS-C than for LS-A (ALF-ISO: p = 0.03, PRO-ISO: p = < 0.001). There was no difference within each treatment from LS-B compared with LS-C. RGSA-I increased within each treatment from LS-A to both LS-B and LS-C (ALF-ISO: p = 0.002) and to LS-C (PRO-ISO: p = 0.006). Subjective laryngeal function scores improved from LS-A to LS-C. CONCLUSIONS AND CLINICAL RELEVANCE: Laryngeal function improved from postinduction examination following either 20 or 40 minutes of anesthesia with isoflurane via facemask. This study demonstrates that isoflurane may have a lesser effect on arytenoid abduction activity compared with more commonly used intravenous induction anesthetics (alfaxalone and propofol).

Evaluating the efficacy of alfaxalone in corn snakes (Pantherophis guttatus).

OBJECTIVE: Alfaxalone is a popular veterinary anesthetic; however, research on this anesthetic in snakes has been limited to ball pythons, garter snakes and several Australian species. The objective was to evaluate the anesthetic effects of alfaxalone in corn snakes (Pantherophis guttatus), a popular pet snake. STUDY DESIGN: Prospective, randomized crossover study. ANIMALS: A total of eight corn snakes. METHODS: In phase I, snakes were subcutaneously administered three doses of alfaxalone (5, 10 and 15 mg kg-1) in the cranial third of the body to determine the most effective dose. In phase II, a dose of 15 mg kg-1 was administered in the cranial and caudal thirds of the snakes to determine if injection site affected anesthesia duration. Heart rate (HR), respiratory rate (fR), righting reflex, escape response, tail pinch, needle prick and tongue flick were monitored at baseline and 5 minute intervals until the snakes fully recovered. RESULTS: Duration of anesthesia differed significantly, with higher doses lasting longer than lower doses: 5 mg kg-1 [23.8 ± 4.4 (15-30) minutes]; 10 mg kg-1 [40.6 ± 9.4 (25-55) minutes]; and 15 mg kg-1 [56.9 ± 8.4 (50-70) minutes], mean ± standard deviation (range). The tail pinch reflex was not completely lost in phase 1. There was a significant change in fR over time, but this was not related to dose. HR was not different by time or dose. Duration of anesthesia was not different after administration of alfaxalone (15 mg kg-1) in the cranial third versus the caudal third of the body; however, there was a significant decrease in HR and fR at this dose, regardless of injection site. CONCLUSIONS AND CLINICAL RELEVANCE: Based on these results, alfaxalone (15 mg kg-1) provides adequate anesthesia for brief procedures or intubation; however, additional analgesia is required for painful procedures.

Evaluation of alfaxalone and midazolam with or without flumazenil reversal in Egyptian fruit bats (Rousettus aegyptiacus).

OBJECTIVES: To evaluate alfaxalone-midazolam anesthesia in Egyptian fruit bats (Rousettus aegyptiacus) and the effect of flumazenil administration on recovery time and quality. STUDY DESIGN: Randomized, blinded, crossover and controlled, experimental trial. ANIMALS: A total of 10 male Egyptian fruit bats. METHODS: Bats were anesthetized with alfaxalone (15 mg kg-1) and midazolam (2 mg kg-1) administered subcutaneously. During anesthesia, vital signs, muscle tone and reflexes were monitored every 10 minutes. Flumazenil (0.3 mg kg-1) or saline at an equal volume was administered subcutaneously 60 minutes after anesthetic administration. Time to induction, time to first movement and recovery time (flying) were measured. Quality of induction, anesthesia and recovery were assessed on a 1-3 scale (1, poor; 2, good; 3, excellent). RESULTS: Time to induction was 4.2 ± 1.9 minutes (mean ± standard deviation), with median quality score of 2 (range, 1-3). Anesthesia quality score was 3 (1-3). During anesthesia, heart rate and respiratory frequency decreased significantly and penis relaxation, indicating muscle tone, increased significantly. Administration of flumazenil significantly reduced mean recovery time compared with saline (10 ± 5 versus 45 ± 17 minutes, respectively), and significantly improved the quality of recovery [2.5 (2-3) versus 1 (1-2), respectively]. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone-midazolam anesthesia resulted in good induction, muscle relaxation and sufficient anesthesia to perform routine diagnostic and therapeutic procedures for approximately 40 minutes. Reversal of midazolam with flumazenil is recommended, resulting in quicker and better recovery.

The utility of a novel formulation of alfaxalone in a remote delivery system.

OBJECTIVE: To quantify induction time, reliability, physiological effects, recovery quality and dart volume of a novel formulation of alfaxalone (40 mg mL-1) used in combination with medetomidine and azaperone for the capture and handling of wild bighorn sheep. STUDY DESIGN: Prospective clinical study. ANIMALS: A total of 23 wild bighorn sheep (Ovis canadensis) in Sheep River Provincial Park, AB, Canada. METHODS: Free-ranging bighorn sheep were immobilized using medetomidine, azaperone and alfaxalone delivered with a remote delivery system. Arterial blood was collected for measurement of blood gases, physiologic variables (temperature, heart and respiratory rates) were recorded and induction and recovery length and quality were scored. RESULTS: Data from 20 animals were included. Administered dose rates were alfaxalone (0.99 ± 0.20 mg kg-1; 40 mg mL-1), azaperone (0.2 ± 0.04 mg kg-1; 10 mg mL-1) and medetomidine (0.16 ± 0.03 mg kg-1; 30 mg mL-1). The mean drug volume injected was 1.51 mL. The median (range) induction time was 7.7 (5.8-9.7) minutes, and recovery was qualitatively smooth. CONCLUSIONS AND CLINICAL RELEVANCE: An increased concentration formulation of alfaxalone was administered in combination with medetomidine and azaperone, and resulted in appropriate anesthesia for the capture and handling of bighorn sheep. The dart volume was small, with potential for reducing capture-related morbidity.

A comparison of the pharmacodynamic effects of intravenous ketamine-xylazine with alfaxalone in mute swans (Cygnus olor) presenting at a wildlife veterinary hospital.

OBJECTIVE: To compare effects of intravenous (IV) alfaxalone with ketamine-xylazine combination on anaesthetic induction, recovery and cardiopulmonary variables in mute swans. STUDY DESIGN: Randomized, controlled, clinical study. ANIMALS: A group of 58 mute swans. METHODS: Swans were given either alfaxalone (10 mg kg-1; group A) or a combination of ketamine (12.5 mg kg-1) and xylazine (0.28 mg kg-1) (group KX) IV. Heart and respiratory rates, end-tidal carbon dioxide and peripheral haemoglobin oxygen saturation were recorded at 5 minute intervals during anaesthesia. Time from anaesthetic induction to intubation, from cessation of isoflurane to extubation, to lifting head, sternal recumbency and absence of head/neck ataxia were recorded. Anaesthetic and recovery quality were scored (1 = very poor; 5 = excellent). Data are presented as median (interquartile range). Significance was set at p < 0.05. RESULTS: In group A, 44% (12/27) of swans required mechanical ventilation for 2-14 minutes versus 3.2% (1/31) of swans in group KX (p = 0.0002). Heart rate was higher in group A than in group KX [146 (127-168) versus 65.5 (56-78) beats minute-1, respectively; p < 0.0001]. The isoflurane concentration required to maintain anaesthesia was higher in group A than in group KX [2.5% (2.0-3.0%) versus 1.5% (1.0-2.0%), respectively; p = 0.0001]. Time from cessation of isoflurane administration to lifting head was significantly longer in group A than in group KX [12 (9-17) versus 6 (4-7.75) minutes, respectively; p < 0.0001]. Anaesthesia quality scores were significantly better in group KX than in group A [4 (4-5) versus 4 (3-4), respectively; p = 0.0011], as were recovery scores [4 (3-5) versus 2 (2-3), respectively; p = 0.0005]. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone is a suitable anaesthetic induction agent for use in mute swans. There is a greater incidence of postinduction apnoea and a higher incidence of agitation on recovery with alfaxalone than with ketamine-xylazine.

Comparison between three dosages of intramuscular alfaxalone and a ketamine-dexmedetomidine-midazolam-tramadol combination in golden-headed lion tamarins (Leontopithecus chrysomelas).

OBJECTIVES: To characterize the cardiopulmonary and anesthetic effects of alfaxalone at three dose rates in comparison with a ketamine-dexmedetomidine-midazolam-tramadol combination (KDMT) for immobilization of golden-headed lion tamarins (GHLTs) (Leontopithecus chrysomelas) undergoing vasectomy. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 19 healthy, male, wild-caught GHLTs. METHODS: Tamarins were administered alfaxalone intramuscularly (IM) at 6, 12 or 15 mg kg-1, or KDMT, ketamine (15 mg kg-1), dexmedetomidine (0.015 mg kg-1), midazolam (0.5 mg kg-1) and tramadol (4 mg kg-1) IM. Immediately after immobilization, lidocaine (8 mg kg-1) was infiltrated subcutaneously (SC) at the incision site in all animals. Physiologic variables, anesthetic depth and quality of immobilization were assessed. At the end of the procedure, atipamezole (0.15 mg kg-1) was administered IM to group KDMT and tramadol (4 mg kg-1) SC to the other groups; all animals were injected with ketoprofen (2 mg kg-1) SC. RESULTS: A dose-dependent increase in sedation, muscle relaxation and immobilization time was noted in the alfaxalone groups. Despite the administration of atipamezole, the recovery time was longer for KDMT than all other groups. Muscle tremors were noted in some animals during induction and recovery with alfaxalone. No significant differences were observed for cardiovascular variables among the alfaxalone groups, whereas an initial decrease in heart rate and systolic arterial blood pressure was recorded in KDMT, which increased after atipamezole administration. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone dose rates of 12 or 15 mg kg-1 IM with local anesthesia provided good sedation and subjectively adequate pain control for vasectomies in GHLTs. KDMT induced a deeper plane of anesthesia and should be considered for more invasive or painful procedures. All study groups experienced mild to moderate hypothermia and hypoxemia; therefore, the use of more efficient heating devices and oxygen supplementation is strongly recommended when using these protocols.

Evaluation of intramuscular sodium nitroprusside injection to improve oxygenation in white-tailed deer (Odocoileus virginianus) anesthetized with medetomidine-alfaxalone-azaperone.

OBJECTIVE: In ungulates, α2-adrenergic agonists can decrease oxygenation possibly through alteration of pulmonary perfusion. Sodium nitroprusside can decrease pulmonary vascular resistance (PVR) and increase cardiac output (Q˙t) through vasodilation. The objective was to determine if sodium nitroprusside would improve pulmonary perfusion and attenuate the increased alveolar-arterial (a-a) gradient resulting from medetomidine-azaperone-alfaxalone (MAA) administration. STUDY DESIGN: Prospective, randomized, crossover study with a 2 week rest period. ANIMALS: A group of eight adult female captive white-tailed deer (Odocoileus virginianus). METHODS: Deer were administered MAA intramuscularly (IM), and auricular artery and pulmonary artery balloon catheters were placed. Deer spontaneously breathed air. Saline or sodium nitroprusside (0.07 mg kg-1) were administered IM 40 minutes after MAA injection. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary artery occlusion pressure (PAOP), right atrial pressure (RAP), Q˙t, arterial pH, PaCO2 and PaO2 were obtained immediately before nitroprusside injection (baseline) and 5, 10 and 15 minutes afterwards. Mixed venous blood samples were obtained at baseline and at 5 minutes. Systemic vascular resistance (SVR), PVR, intrapulmonary shunt fraction (Q˙s/Q˙t), a-a gradient, oxygen delivery (D˙O2) and oxygen extraction ratio (O2ER) were calculated. Statistical analysis was performed with repeated measures analysis of variance with correction factors. A p value < 0.05 was considered significant. RESULTS: With nitroprusside, MAP, MPAP, PAOP, RAP, SVR and O2ER significantly decreased and HR, Q˙t and D˙O2 increased compared with baseline and between treatments. There was a significant decrease in PVR and a-a gradient and increase in PaO2 compared with baseline and saline treatment. Changes were not sustained. CONCLUSIONS AND CLINICAL RELEVANCE: Nitroprusside temporarily changed hemodynamic variables, increased PaO2 and decreased a-a gradient. Nitroprusside possibly led to better pulmonary perfusion of ventilated alveoli. However, IM nitroprusside at this dose is not recommended because of severe systemic hypotension and short action.