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

ObjectiveTo evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.Study designCrossover study (part 1) with observational study (part 2).AnimalsA 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.MethodsCrossover 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.ResultsThe 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 relevancePremedication 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.     

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles

ObjectiveTo evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsA group of six adult Beagles.MethodsDogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with two doses of alfaxalone (0.5 and 1 mg kg^–1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO₂) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran’s Q tests. Significance was p < 0.05.ResultsSedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum–maximum), 43 (35–54) versus 30 (20–47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO₂.Conclusions and clinical relevanceAdding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.     

ED50 and ED95 of rocuronium during alfaxalone anesthesia in dogs

ObjectiveTo determine the median effective dose (ED₅₀) and effective dose required to depress the twitch value by 95% (ED₉₅) of rocuronium during alfaxalone anesthesia in dogs.Study designA randomized, prospective, crossover experimental study.AnimalsA total of eight adult Beagle dogs (four female, four male), weighing 10.3–14.6 kg and aged 6–8 years.MethodsThe dogs were anesthetized three times with 1.25-fold the individual minimum infusion rate of alfaxalone 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) and first twitch of TOF (T1C), a single bolus dose of rocuronium 100, 175 or 250 μg kg^–1 (treatments R100, R175 or R250) was administered intravenously. The maximum suppression of the first twitch of TOF (T1) was recorded and calibrated with T1C to construct the dose–response curve, from which ED₅₀ and ED₉₅ were calculated. Time from rocuronium administration to TOF ratio/TOFRC > 0.9 (duration TOFR0.9) was recorded.ResultsED₅₀ and ED₉₅ of rocuronium during alfaxalone anesthesia were 175 and 232 μg kg^–1, respectively. The median (range) duration TOFR0.9 was longer in treatment R250 [10.1 (9.2–10.9) minutes] than in treatments R100 [3.1 (2.9–4.4) minutes; p < 0.0001] and R175 [7.7 (6.9–8.1) minutes; p < 0.0001]; and longer in treatment R175 than in treatment R100 (p < 0.0001).Conclusions and clinical relevanceThe duration of TOFR0.9 correlated positively with the dosage of rocuronium, indicating that recovery time of rocuronium was also dose-dependent in dogs anesthetized with alfaxalone. The duration TOFR0.9 of rocuronium 250 μg kg^–1 was 10 minutes during alfaxalone anesthesia in dogs.     

Evaluation of xylazine–alfaxalone anesthesia for field castration in donkey foals

ObjectiveTo evaluate the anesthetic and cardiopulmonary effects of xylazine–alfaxalone anesthesia in donkey foals undergoing field castration.Study designProspective clinical study.AnimalsA group of seven standard donkeys aged [median (range)] 12 (10–26) weeks, weighing 47.3 (37.3–68.2) kg.MethodsDonkeys were anesthetized with xylazine (1 mg kg⁻¹) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg⁻¹) IV. Additional doses of xylazine (0.5 mg kg⁻¹) and alfaxalone (0.5 mg kg⁻¹) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute⁻¹. Heart rate (HR), respiratory rate (f_R) and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO₂) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent).ResultsMedian (range) induction score was 5 (1–5), and recovery score 4 (1–5). Overall, two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. f_R was decreased at 5 and 10 minutes but was not considered clinically significant. SpO₂ was <90% at one time point in two animals.Conclusions and clinical relevanceXylazine–alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.     

Effects of intramuscular and intranasal administration of midazolam–dexmedetomidine on sedation and some cardiopulmonary variables in New Zealand White rabbits

ObjectiveTo compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand White rabbits.Study designA randomized, crossover experimental study.AnimalsA total of eight healthy New Zealand White rabbits, aged 6–12 months, weighing 3.1 ± 0.3 kg (mean ± standard deviation).MethodsThe animals were randomly assigned to administration of dexmedetomidine (0.1 mg kg^–1) with midazolam (2 mg kg^–1) by either IN or IM route separated by 2 weeks. The electrocardiogram, pulse rate (PR), peripheral haemoglobin oxygen saturation (SpO₂), mean noninvasive arterial pressure (MAP), respiratory frequency (f_R) and rectal temperature were measured before drug administration (baseline), T₀ (onset of sedation) and at 5 minute intervals until recovery. The onset of sedation, duration of sedation and sedation score (SS) were also recorded.ResultsThe PR was significantly lower in treatment IM than in treatment IN over time (p = 0.027). MAP < 60 mmHg developed in two and four rabbits in treatments IN and IM, respectively. SpO₂ progressively decreased over time in both treatments. f_R was lower than baseline at several time points in both treatments. Onset of sedation was shorter in treatment IN (90 ± 21 seconds) than in treatment IM (300 ± 68 seconds) (p = 0.036). Duration of sedation was longer in treatment IM (55.2 ± 8.7 minutes) than in treatment IN (39.6 ± 2.1 minutes) (p = 0.047). No significant difference in SS was observed between treatments (p > 0.05).Conclusions and clinical relevanceCombination of dexmedetomidine (0.1 mg kg^–1) and midazolam (2 mg kg^–1) decreased f_R, PR and SpO₂ regardless of the administration route in New Zealand White rabbits. A more rapid action and shorter duration of sedation were observed after treatment IN than after treatment IM administration.     

Comparative evaluation of sedative and clinical effects of dexmedetomidine and xylazine in dromedary calves (Camelus dromedarius)

ObjectiveTo compare the sedative and clinical effects of intravenous (IV) administration of dexmedetomidine and xylazine in dromedary calves.Study designExperimental, crossover, randomized, blinded study.AnimalsA total of seven healthy male dromedary calves aged 14 ± 2 weeks and weighing 95 ± 5.5 kg.MethodsCalves were assigned three IV treatments: treatment XYL, xylazine (0.2 mg kg⁻¹); treatment DEX, dexmedetomidine (5 μg kg⁻¹); and control treatment, normal saline (0.01 mL kg⁻¹). Sedation scores, heart rate (HR), respiratory rate (f_R), rectal temperature (RT) and ruminal motility were recorded before (baseline) and after drug administration. Sedation signs were scored using a 4-point scale. One-way anova and Mann–Whitney U tests were used for data analysis.ResultsCalves in treatments XYL and DEX were sedated at 5–60 minutes. Sedation had waned in XYL calves, but not DEX calves, at 60 minutes (p = 0.037). Sedation was not present in calves of any treatment at 90 minutes. HR decreased from baseline in XYL and DEX at 5–90 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.017). HR was lower in DEX (p = 0.001) and XYL (p = 0.013) than in control treatment at 90 minutes. f_R decreased from baseline in XYL and DEX at 5–60 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.013). RT was unchanged in any treatment over 120 minutes. Ruminal motility was decreased in XYL at 5, 90 and 120 minutes and absent at 10–60 minutes. Motility was decreased in DEX at 5, 10 and 120 minutes and was absent at 15–90 minutes.Conclusion and clinical relevanceThe duration of sedation from dexmedetomidine (5 μg kg^–1) and xylazine (0.2 mg kg^–1) was similar in dromedary calves.     

Intramuscular injection of alfaxalone in combination with butorphanol for sedation in cats

Objective

To assess quality of sedation following intramuscular (IM) injection of two doses of alfaxalone in combination with butorphanol in cats.

Maximum volume of nasal administration using a mucosal atomization device without aspiration in Japanese White rabbits

Recently, a mucosal atomization device (MAD) has been applied in veterinary medicine. In the present study, the maximum volume of nasal atomization without aspiration using MAD was examined in eight healthy female Japanese White (JW) rabbits. Each rabbit had their head and neck examined by computed tomography before and after nasal atomization with four different doses (0.15, 0.3, 0.45, and 0.6 ml per nostril) of diluted contrast medium (1:2 mixture of iohexol and saline). This was done under general anesthesia by an intramuscular administration of alfaxalone 2.5 mg/kg, medetomidine 40 μg/kg, and butorphanol 0.4 mg/kg, with a 7-day washout period between each treatment. The diluted contrast medium was distributed in the nasal cavity, external nares, and/or oral cavity in all rabbits receiving each treatment. The intranasal distribution volumes of the contrast medium were 287 (250–333) mm³ [median (interquartile range)] for 0.15 ml, 433 (243–555) mm³ for 0.3 ml, 552 (356–797) mm³ for 0.45 ml, and 529 (356–722) mm³ for 0.6 ml of treatment. The intranasal distribution volume for 0.15 ml treatment tended to be lower than that for 0.6 ml treatment (P=0.083). The contrast medium was deposited in the trachea in one rabbit (12.5%) and four rabbits (50%) receiving treatments of 0.45 and 0.6 ml per nostril, respectively. The maximum volume of nasal atomization without aspiration into the trachea was 0.3 ml per nostril for the JW rabbits.     

The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg^?1 IV). Twenty minutes later they received xylazine (1 mg kg^?1 IV), then after 5 minutes, guaiphenesin (35 mg kg^?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg^?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t_1/2), plasma clearance (Clp) and volume of distribution (V_d) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute^?1 kg^?1 and 1.6 ± 0.4 L kg^?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.     

Hypoventilation following oxygen administration associated with alfaxalone–dexmedetomidine–midazolam anesthesia in New Zealand White rabbits

ObjectiveTo investigate the relationship between oxygen administration and ventilation in rabbits administered intramuscular alfaxalone–dexmedetomidine–midazolam.Study designProspective, randomized, blinded study.AnimalsA total of 25 New Zealand White rabbits, weighing 3.1–5.9 kg and aged 1 year.MethodsRabbits were anesthetized with intramuscular alfaxalone (4 mg kg^–1), dexmedetomidine (0.1 mg kg^–1) and midazolam (0.2 mg kg^–1) and randomized to wait 5 (n = 8) or 10 (n = 8) minutes between drug injection and oxygen (100%) administration (facemask, 1 L minute^–1). A control group (n = 9) was administered medical air 10 minutes after drug injection. Immediately before (PRE_oxy/air5/10) and 2 minutes after oxygen or medical air (POST_oxy/air5/10), respiratory rate (f_R), pH, PaCO₂, PaO₂, bicarbonate and base excess were recorded by an investigator blinded to treatment allocation. Data [median (range)] were analyzed with Wilcoxon, Mann–Whitney U and Kruskal–Wallis tests and p < 0.05 considered significant.ResultsHypoxemia (PaO₂ < 88 mmHg, 11.7 kPa) was observed at all PRE times: PRE_oxy5 [71 (61–81) mmHg, 9.5 (8.1–10.8) kPa], PRE_oxy10 [58 (36–80) mmHg, 7.7 (4.8–10.7) kPa] and PRE_air10 [48 (32–64) mmHg, 6.4 (4.3–8.5) kPa]. Hypoxemia persisted when breathing air: POST_air10 [49 (33–66) mmHg, 6.5 (4.4–8.8) kPa]. Oxygen administration corrected hypoxemia but was associated with decreased f_R (>70%; p = 0.016, both groups) and hypercapnia (p = 0.016, both groups). Two rabbits (one per oxygen treatment group) were apneic (no thoracic movements for 2.0–2.5 minutes) following oxygen administration. f_R was unchanged when breathing air (p = 0.5). PaCO₂ was higher when breathing oxygen than air (p < 0.001).Conclusions and clinical relevanceEarly oxygen administration resolved anesthesia-induced hypoxemia; however, f_R decreased and PaCO₂ increased indicating that hypoxemic respiratory drive is an important contributor to ventilation using the studied drug combination.     

Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats

ObjectiveTo compare the effects of propofol and alfaxalone on respiration in cats.Study designRandomized, ‘blinded’, prospective clinical trial.AnimalsTwenty cats undergoing ovariohysterectomy.MethodsAfter premedication with medetomidine 0.01 mg kg⁻¹ intramuscularly and meloxicam 0.3 mg kg⁻¹ subcutaneously, the cats were assigned randomly into two groups: group A (n = 10) were administered alfaxalone 5 mg kg⁻¹ minute⁻¹ followed by 10 mg kg⁻¹ hour⁻¹ intravenously (IV) and group P (n = 10) were administered propofol 6 mg kg⁻¹ minute⁻¹ followed by 12 mg kg⁻¹hour⁻¹ IV for induction and maintenance of anaesthesia, respectively. After endotracheal intubation, the tube was connected to a non-rebreathing system delivering 100% oxygen. The anaesthetic maintenance drug rate was adjusted (± 0.5 mg kg⁻¹ hour⁻¹) every 5 minutes according to a scoring sheet based on physiologic variables and clinical signs. If apnoea > 30 seconds, end-tidal carbon dioxide (Pe′CO₂) > 7.3 kPa (55 mmHg) or arterial haemoglobin oxygen saturation (SpO₂) < 90% occurred, manual ventilation was provided. Methadone was administered postoperatively. Data were analyzed using independent-samples t-tests, Fisher's exact test, linear mixed-effects models and binomial test.ResultsManual ventilation was required in two and eight of the cats in group A and P, respectively (p = 0.02). Two cats in both groups showed apnoea. Pe′CO₂ > 7.3 kPa was recorded in zero versus four and SpO₂ < 90% in zero versus six cats in groups A and P respectively. Induction and maintenance dose rates (mean ± SD) were 11.6 ± 0.3 mg kg⁻¹ and 10.7 ± 0.8 mg kg⁻¹ hour⁻¹ for alfaxalone and 11.7 ± 2.7 mg kg⁻¹ and 12.4 ± 0.5 mg kg⁻¹ hour⁻¹ for propofol.Conclusion and clinical relevanceAlfaxalone had less adverse influence on respiration than propofol in cats premedicated with medetomidine. Alfaxalone might be better than propofol for induction and maintenance of anaesthesia when artificial ventilation cannot be provided.     

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.     

Pharmacokinetics and pharmacodynamics of intramuscular alfaxalone in central bearded dragons (Pogona vitticeps): effect of injection site

ObjectiveTo evaluate the pharmacodynamic effects and pharmacokinetics of a single intramuscular (IM) injection of alfaxalone in central bearded dragons (Pogona vitticeps) when injected at a cranial versus a caudal site.Study designProspective, masked, randomized crossover study.AnimalsA total of 13 healthy bearded dragons weighing 0.48 ± 0.1 kg.MethodsAlfaxalone (10 mg kg^–1) was administered IM to 13 bearded dragons in the triceps muscle (cranial treatment) or the quadriceps muscle (caudal treatment) separated by 4 weeks. Pharmacodynamic variables included movement score, muscle tone score and righting reflex. Blood was obtained from the caudal tail vein using a sparse sampling methodology. Plasma alfaxalone concentrations were determined using liquid chromatography–mass spectrometry, and pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Differences in variables between injection sites were analyzed using a nonparametric Wilcoxon signed-rank test for paired data with significance set at p ≤ 0.05.ResultsTime to loss of righting reflex score was not different, median (interquartile range), between cranial and caudal treatments [8 (5–11) and 8 (4–12) minutes, respectively, p = 0.72]. Time to recovery of righting reflex was also not different between cranial and caudal treatments [80 (44–112) and 64 (56–104) minutes, respectively, p = 0.75]. Plasma alfaxalone concentrations were not significantly different between treatments. The population estimate (95% confidence intervals) for volume of distribution per fraction absorbed was 1.0 (0.79–1.20) L kg^–1, clearance per fraction absorbed was 9.6 (7.6–11.6) mL minute^–1 kg^–1, absorption rate constant was 2.3 (1.9–2.8) minute^–1 and elimination half-life was 71.9 (52.7–91.1) minutes.Conclusions and clinical relevanceRegardless of the injection site, IM alfaxalone (10 mg kg^–1) produced reliable chemical restraint in central bearded dragons, appropriate for nonpainful diagnostic procedures or anesthetic premedication.     

Effects of intracoelomic alfaxalone–dexmedetomidine on righting reflex in common garter snakes (Thamnophis sirtalis): preliminary data

ObjectiveTo evaluate the effect of dexmedetomidine on alfaxalone immobilization in snakes.Study designNonblinded, crossover study.AnimalsA total of eight mature common garter snakes (Thamnophis sirtalis).MethodsSnakes were administered each of three treatments intracoelomically: alfaxalone (30 mg kg^–1; treatment A), alfaxalone (30 mg kg^–1) combined with dexmedetomidine (0.05 mg kg^–1; treatment AD0.05); and alfaxalone (30 mg kg^–1) combined with dexmedetomidine (0.10 mg kg^–1; treatment AD0.10). A minimum of 10 days elapsed between experimental trials. Times to loss of righting reflex (LRR) and return of righting reflex (RRR) were recorded. Heart rate (HR) was recorded every 5 minutes throughout the period of LRR and averaged for each snake. Times to LRR and RRR, and mean HR in snakes that achieved LRR were reported.ResultsLRR occurred in eight (100%), five (63%) and three (38%) snakes in treatments A, AD0.05 and AD0.10, respectively. For all treatments, time to LRR ranged 3–20 minutes. Median (range) times to RRR were 39 (30–46), 89 (62–128) and 77 (30–185) minutes for treatments A, AD0.05 and AD0.10, respectively. In animals where righting reflex was lost, mean HR was lower in all dexmedetomidine treatments compared with treatment A.Conclusions and clinical relevanceIn this pilot study, alfaxalone resulted in reliable immobilization, whereas dexmedetomidine and alfaxalone combinations resulted in highly variable durations of immobilization with low HR in immobilized animals. For snakes that achieved LRR, the addition of dexmedetomidine (0.05 mg kg^–1) to alfaxalone appeared to extend the period of immobilization compared with alfaxalone alone.     

Field immobilization using alfaxalone and alfaxalone–medetomidine in free-ranging koalas (Phascolarctos cinereus): a randomized comparative study

ObjectiveTo characterize and compare two intramuscular drug protocols using alfaxalone and alfaxalone–medetomidine combination for the field immobilization of free-ranging koalas.Study designBlinded, randomized, comparative field study.AnimalsA total of 66 free-ranging koalas from the Mount Lofty Ranges, South Australia.MethodsKoalas were randomly allocated into two groups. Group A animals were given alfaxalone alone at 3.5 mg kg^–1. Group AM animals were given alfaxalone 2 mg kg^–1 and medetomidine 40 μg kg^–1, reversed with atipamezole at 0.16 mg kg^–1. Blinded operators recorded heart rate (HR), respiratory rate (f_R), cloacal temperature, depth of sedation and times to: first effect, sedation suitable for clinical interventions, first arousal and full recovery. Data were analysed using independent t test, Mann–Whitney U test, chi-square analysis and log-rank test at 5% level of significance.ResultsSuitable immobilization for clinical examination and sample collection was achieved in all animals. In groups A and AM, median time to working depth was 6.5 minutes (range: 3.4–15) and 8.1 minutes (range: 4.3–24) and time to complete recovery was 66 minutes (range: 12–138) and 34 minutes (range: 4–84), respectively, following reversal. Time to first effect was significantly shorter in group A (p = 0.013), whereas time to full arousal was significantly shorter in group AM (p = 0.007) probably due to the administration of atipamezole. Maximum HR was 117 ± 28 beats minute^–1 in group A, which was a significant increase from baseline values (p < 0.0001), whereas group AM showed a significant tachypnoea of 67 ± 25 (normal f_R 10–15; p < 0.0001).Conclusions and clinical relevanceBoth the protocols produced immobilization, enabling clinical examination and sample collection; however, protocol AM was more suitable for field work due to shorter recovery times.     

Cardiopulmonary and anesthetic effects of the combination of butorphanol,midazolam and alfaxalone in Beagle dogs

ObjectiveTo evaluate the physiological variables, arterial blood gas values, induction of anesthesia quality, and recovery quality using the combination of butorphanol, midazolam and alfaxalone in dogs.AnimalsTen healthy adult Beagle dogs weighing 8.3 ± 3.1 kg.MethodsRectal temperature (T), pulse rate (PR), respiratory rate (f_R), mean arterial pressure (MAP), and arterial blood gases were measured and recorded prior to intravenous (IV) administration of butorphanol, prior to administration of both midazolam and alfaxalone IV 10 minutes later, then every 5 minutes for 20 minutes. M-mode echocardiographic left ventricular (LV) indices were measured before and 5 minutes after administration of alfaxalone. Qualitative scores for induction of anesthesia and recovery were allocated, duration of anesthesia and recovery were calculated, and adverse events were recorded.ResultsScores for induction and recovery quality were excellent. No significant adverse events were observed. Mean ± SD time from induction to extubation and to standing (full recovery) was 29 ± 6 and 36 ± 8 minutes, respectively. There were statistically significant changes in PR, f_R and MAP after drug administration. Transient hypercarbia developed after alfaxalone injection. The echocardiographic LV indices were reduced after alfaxalone injection, although those changes were not statistically significant.Conclusions and clinical relevanceThe combination of butorphanol, midazolam and alfaxalone provided excellent quality of induction of anesthesia and exerted minimal cardiopulmonary effects in healthy dogs.     

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.