Alfaxalone Anaesthesia Research Articles

Impact of procedural handling on the physiological effects of alfaxalone anaesthesia in the ball python (Python regius)

To describe the cardiovascular changes following intramuscular (handled) and intravascular (undisturbed, via intraarterial catheter) alfaxalone administration, we studied 20 healthy ball pythons (Python regius) in a randomised, prospective study. The pythons were instrumented with occlusive arterial catheters to facilitate undisturbed, continuous monitoring of heart rate and blood pressure. Six pythons were administered intramuscular (IM) saline, followed by 20 mg/kg IM alfaxalone, and were manually restrained for both injections. Six pythons received intraarterial (IA) saline, followed by 10 mg/kg IA alfaxalone, and remained undisturbed for both injections. Arterial blood samples were taken at 0, 12 and 60 min post-injection, and heart rate and blood pressure were recorded for 60 min. The remaining eight snakes received 20 mg/kg IM or 10 mg/kg IA alfaxalone (n = 4 per treatment) and were not handled for intubation 10 min post-injection, to examine the effects of handling during anaesthesia. IM administration of 20 mg/kg alfaxalone or an equivalent volume of saline elicited a profound tachycardia and hypertension, which recovered to resting values after 20 min. However, when 10 mg/kg alfaxalone or saline were injected IA, mild hypotension and a lower magnitude tachycardia occurred. Arterial PCO2 and PO2, pH and lactate concentrations did not change following IA alfaxalone, but an acidosis was observed during IM alfaxalone anaesthesia. There were no significant changes in plasma catecholamines and corticosterone among treatments. Handling for injection and during anaesthesia associated with intubation significantly affects cardiovascular parameters, whereas alfaxalone per se only elicits minor changes in cardiovascular physiology.

Effect of water temperature on the anesthetic effects of alfaxalone in carp (Cyprinus carpio).

To evaluate the effect of water temperature on intramuscular injected alfaxalone anesthesia in carp (Cyprinus carpio). Six healthy adult carp (C. carpio) were intramuscularly injected with alfaxalone (2.5, 5.0, or 7.5 mg/kg) at normal water temperature (25°C) and at low water temperature (2.5 mg/kg, 15°C). The respiratory rate, heart rate (HR), and anesthesia depth (AD) were evaluated every 5 min for 30 min after administration and every 1 h after 60 min after injection. The respiratory and HRs did not change significantly upon alfaxalone injection, regardless of dose. However, a dose-dependent increase in AD scores was observed. Furthermore, 2.5 mg/kg alfaxalone injected in 15°C water showed an almost equal anesthetic effect to that of 5.0 mg/kg alfaxalone in 25°C water. Alfaxalone is readily available, and its anesthetic effect in carp was enhanced by lowering water temperature, illustrating the possibility of intramuscular injection of alfaxalone in fish.

Physiological effects of alfaxalone anesthesia on rhesus monkeys during intravenous glucose tolerance testing.

Laboratory animal research with nonhuman primates (NHPs) requires anesthesia for most procedures to ensure safety and consistency in sample collection. However, anesthesia drugs can have adverse effects on the physiological measures of interest. Alfaxalone, most notably used in dogs and cats, offers rapid onset, short duration of action, and has a high safety margin. Here, we compared our current anesthesia protocol using Telazol, to three different doses of alfaxalone during a one-hour intravenous glucose tolerance test, the standard evaluation of glucose metabolism in NHPs. Results indicate there are no differences in the rate of glucose metabolism, anesthesia depth measurements, or total duration of sedation, but induction, number of supplemental doses required, and recovery time to eating were affected by the different doses of alfaxalone. Cardiovascular measures showed variability between the four protocols in respiratory rate and systolic blood pressure rates only. These results indicate that alfaxalone can produce a reliable state of anesthesia, similar to our current protocol, and confers minimal cardiovascular or metabolic disturbance, as well as enhanced recovery characteristics. As such, alfaxalone is a promising anesthetic for use in laboratory animals and further investigation is warranted.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade during alfaxalone anesthesia in dogs

ObjectiveTo investigate the reversal effect of sugammadex on neuromuscular blockade induced by a single bolus of rocuronium in dogs under alfaxalone anesthesia. Study designRandomized, prospective, crossover experimental study. AnimalsA group of six adult Beagle dogs (three females and three males), weighing 11.3–15.8 kg and aged 6–8 years, were used. MethodsDogs were anesthetized twice with a 1.25 times minimum infusion rate of alfaxalone, with a washout period of at least 14 days between experiments. Neuromuscular function was monitored using acceleromyography with train-of-four (TOF) stimulation of the peroneal nerve. After recording the control TOF ratio (TOFRC), rocuronium (0.5 mg kg–1) was administered intravenously. Subsequently, sugammadex (4 mg kg–1) or an equal volume of saline (control treatment) was administered intravenously when the TOF count returned from 0 to 1 after neuromuscular blockade. Time from rocuronium injection to TOF count = 0 (onset time), time from TOF count = 0 to TOF count = 1 (maximum blockade period), time of first twitch amplitude recovery from 0.25 to 0.75 (recovery index), and time from sugammadex or saline administration to TOF ratio/TOFRC ≥ 0.9 (recovery time) were recorded. ResultsThe onset time and maximum blockade duration did not differ between sugammadex treatment [1.2 (0.7–1.5) minutes and 9.9 (6.3–10.5) minutes, respectively] and control treatment [median (range); 1.0 (0.7–1.1) minutes and 9.9 (8.8–11.5) minutes, respectively] (p = 0.219 and 0.844, respectively). Recovery index was 0.5 (0.3–0.7) minutes in sugammadex treatment, which was shorter than that in control treatment [4.5 (3.7–4.9) minutes] (p = 0.031). Recovery time was 0.8 (0.5–2.8) minutes in sugammadex treatment, which was shorter than that in control treatment [10.5 (6.8–14.3) minutes] (p = 0.031). Conclusions and clinical relevanceRocuronium-induced neuromuscular blockade was effectively reversed by sugammadex in dogs anesthetized with alfaxalone.

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.

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial

BackgroundAlfaxalone is a fast acting intravenous anaesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid allopregnanolone responsible for maintenance of cognition and neuroprotection by activation of brain pregnane X receptors and consequent increased production of mature brain-derived neurotrophic factor (m-BDNF). Two studies are reported here: an in vitro study investigated whether alfaxalone activates human pregnane X receptors (h-PXR) as effectively as allopregnanolone; and a clinical study that measured postoperative changes in serum m-BDNF and cognition in patients after alfaxalone anaesthesia compared with propofol and sevoflurane.MethodsIn vitro Activation of h-PXR by allopregnanolone and alfaxalone solutions (206 - 50,000 nM) was measured using human embryonic kidney cells expressing h-PXR hybridised and linked to the firefly luciferase gene. Light emission by luciferase stimulated by each ligand binding with h-PXR was measured.Clinical A double blind prospective randomised study of patients undergoing hip arthroplasty anaesthetised with alfaxalone TIVA (n = 8) or propofol TIVA (n = 3) or propofol plus sevoflurane inhalational anaesthesia (n = 4). The doses of anaesthetics were titrated to the same depth of anaesthesia (BIS 40-60). Subjects’ cognitive performance was assessed using the Grooved Pegboard Test, Digit Symbol Substitution Test (DSST) and Mini Mental State examination (MMSE) for 7 days postoperatively. Serum m-BDNF concentrations were measured for 7 postoperative days.ResultsIn vitro Allopregnanolone and alfaxalone both activated h-PXR, alfaxalone being more efficacious than allopregnanolone: 50,000 nM, p = 0.0019; 16,700 nM, p = 0.0472; 5600 nM, p = 0.0031.Clinical Alfaxalone treated subjects scored better than propofol and sevoflurane anaesthetised patients in the cognition tests: (MMSE p = 0.0251; Grooved Pegboard test dominant hand pre v post anaesthesia scores p = 0.8438 for alfaxalone and p = 0.0156 for propofol and propofol/sevoflurane combined). The higher cognition scores were accompanied by higher serum m-BDNF levels in the alfaxalone anaesthetised patients (p < 0.0001).ConclusionsThese results suggest that sedation and anaesthesia induced by the synthetic neuroactive steroid alfaxalone may be accompanied by effects normally caused by physiological actions of allopregnanolone at PXR, namely, increased secretion of m-BDNF and consequent neuroprotection and preservation of cognition.Trial registrationThe clinical trial was registered on 17/01/2018 with the Australian New Zealand Clinical Trials Registry: registration number ACTRN12618000064202 [Universal Trial Number U1111-1198-0412].

The use of alfaxalone for short-term anesthesia can confound serum progesterone measurements in the common marmoset: a case report.

Alfaxan® (alfaxalone) is a steroid general anesthetic widely used in veterinary medicine for induction and maintenance of anesthesia in several species. While the use of alfaxalone in veterinary practice has several benefits compared to the use of other anesthetic agents, the fact that it is derived from progesterone may confound the measurement of the latter in the blood of animals under alfaxalone treatment. In the present case study, we report the measurement of serum progesterone in an individual common marmoset (Callithrix jacchus) during five ovarian cycles in which luteolysis was induced by PGF2. Blood samples were usually taken from the awake animal with the exception of the fifth cycle in which the sample was collected under alfaxalone anesthesia in connection with a tooth extraction. In contrast to the previous four cycles in which luteolysis resulted in the expected marked decrease in progesterone concentrations, the – apparent – progesterone level in the cycle under alfaxalone treatment remained unexpectedly high. Cross-reactivity of the non-specific antibody used in the progesterone assay with alfaxalone most likely explains this finding.

Comparison between propofol and alfaxalone anesthesia for the evaluation of laryngeal function in healthy dogs utilizing computerized software.

Laryngeal paralysis is a well-documented cause of upper respiratory tract obstruction in canines. Diagnosis of laryngeal paralysis is usually made by visual evaluation of laryngeal motion whilst patients are under a light-plane of anesthesia. However, in human studies of laryngeal function evaluation, it has been shown that subjective scoring can lead to significant interobserver variance, which may cause false diagnosis. In this study, we propose to introduce a more objective method of assessing laryngeal function using GlotAnTools and Tracker software to directly measure laryngeal motion in anaesthetized patients. Additionally, two anesthetic agents, alfaxalone and propofol, were compared in this study to assess their relative effect on laryngeal motion and thus their suitability for use in this diagnostic process. This study was a two-stage, cross-over, 1:1 randomization, with two active treatment arms. Ten beagles (10–18 months, five males and five females) were exposed to both anesthetic agents and laryngeal motion was recorded using videoendoscopy. GlotAnTools and Tracker software were applied to the recorded images to measure glottal gap area (A) and length (L). A normalized measure of laryngeal function–computed as A/L–was created, representing the "elongatedness" of the rima glottidis. The glottal gap area was significantly reduced in dogs receiving alfaxalone. This study objectively establishes that alfaxalone impacted laryngeal motion significantly more than propofol and confirms the capability of these computational methods to detect differences in laryngeal motion.

Determination of the Minimum Infusion Rate of Alfaxalone Combined with Electroacupuncture in Goats.

Simple SummaryGoats have been used as animal models in research and are increasingly kept as pets like dogs and cats. Total intravenous anesthesia (TIVA) is increasingly used in companion animals. Electroacupuncture (EA) has been proven to produce analgesia, therefore, the objective of this study was to investigate the effect of EA on alfaxalone-based TIVA in goats. In this current study, the minimum infusion rate (MIR) of alfaxalone was determined in a combination with EA. The findings found that EA reduces the alfaxalone MIR required to prevent purposeful movement of the extremities in response to standardized noxious. In conclusion, EA provided analgesia, reduced the MIR of alfaxalone-based IV anesthesia, and thereby alleviated the adverse cardiorespiratory effects associated with alfaxalone anesthesia in goats.Total intravenous anesthesia (TIVA) is increasingly used in companion animals. The effect of electroacupuncture (EA) on alfaxalone-based TIVA has not been previously reported in goats. Therefore, the objective of this study was to determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its combination with EA in goats. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups (six goats/group). Alfaxalone alone (ALF group) and alfaxalone combined with EA (EA-ALF group). In the EA-ALF, alfaxalone was administered 30 min after EA stimulation. For induction of anesthesia, a bolus of alfaxalone was given at 3 mg/kg IV, and an infusion dose of 9.6 mg/kg/h was initially set for maintenance. The MIR of alfaxalone in both groups was determined by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) at 10-min intervals after induction of anesthesia till the entire period of the experiment. Cardiopulmonary parameters and nociceptive threshold were measured throughout anesthesia. The median alfaxalone MIR was significantly lower in the EA-ALF group than the ALF group [9 (4.8–9.6) and 12 (11.4–18)], respectively; p = 0.0035). In the ALF group, goats anesthetized with MIR showed a significant increase in heart rate and cardiac output (p < 0.0001 and 0.0312, respectively), and decrease in respiratory rate (p < 0.0001), hemoglobin oxygen saturation (p = 0.0081), and rectal temperature (p = 0.0046) compared with those in the EA-ALF. Additionally, goats in the EA-ALF showed a higher nociceptive threshold than those in the ALF group (p < 0.0001). EA provided analgesia, reduced the MIR of alfaxalone-based IV anesthesia and thereby alleviated the adverse cardiorespiratory effects associated with alfaxalone anesthesia in goats.

Macrocirculatory Parameters and Oxygen Debt Indices in Pigs During Propofol Or Alfaxalone Anesthesia When Subjected to Experimental Stepwise Hemorrhage.

Background: Pigs are anesthetized when used for emergency procedures live tissue training (LTT) of civilian and military medical personnel or for experimental purposes, but there is a paucity in the literature regarding anesthesia of pigs for this purpose.Objective(s): The main goals of the study were to compare oxygen debt, macrocirculatory parameters, and time to cardiac arrest between pigs in hemorrhagic shock and anesthetized with propofol-ketamine-dexmedetomidine or alfaxalone-ketamine-dexmedetomidine.Design: A prospective, non-blinded randomized study design was used. Sixteen pigs were randomized in blocks of four to be anesthetized with either propofol-ketamine-dexmedetomidine (n = 8) or alfaxalone-ketamine-dexmedetomidine (n = 8) as a continuous infusion.Interventions: Premedication with ketamine 15 mg kg−1 and midazolam 1 mg kg−1 was given i.m. Anesthesia was maintained with propofol 8 mg kg−1 h−1 or alfaxalone 5 mg kg−1 h−1 combined with ketamine 5 mg kg−1 h−1 and dexmedetomidine 4 μg kg−1 h−1 i.v. A stepwise, volume-controlled model for hemorrhage was created by exsanguination.Main Outcome Measures: Indices of oxygen debt (lactate, base excess, and oxygen extraction), macrocirculatory (PR, SAP, DAP, MAP, and CI, SVI, and TPR) variables, and time to death was compared between groups.Results: Pigs in the alfaxalone group had significantly higher SAP than pigs given propofol. No difference in other macrocirculatory variables or indices of oxygen debt could be found. A blood loss of 50% of the total blood volume or more was possible in most pigs with both anesthetic regimes.Conclusions: Pigs anesthetized with propofol or alfaxalone combined with ketamine and dexmedetomidine tolerated substantial blood loss.

Clinical Evaluation of Alfaxalone in Cyclodextrin as an Intravenous Anesthetic in the Common Buzzards (Buteo buteo)

There has not been any report about the use of the Alfaxan-CD(R) in common buzzard. The objective of this study was to evaluate the effects of Alfaxan-CD(R) as an intravenous anesthetic agent for inducing anesthesia in the common buzzard and describe some of its clinical pharmacological effects. Eight healthy adult common buzzards (Buteo buteo) of unknown sex, weighing 750–1000 grams, kept in captivity at the Dilek Peninsula National Park located in Aydin, Turkey, and appropriately fed (i.e.: rats, mice, rabbits, and day-old chicks) were included in this study. Birds were given alfaxalone (10 mg/kg, by 2-4 mg/kg boluses) intravenously. Variables measured before, and 5, 10, 15, 20, 30, and 90 minutes after induction were the followings: heart rate (HR, beats/min), respiratory rate (RR, breaths/min), cloacal temperature (CT), hemoglobin concentration (Hb), sodium (Na+), potassium (K+), ionized calcium (iCa++), arterial pH (pHa), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), bicarbonate concentration (HCO3) and base excess (BE). All buzzards survived the alfaxalone anesthesia. In this study, alfaxalone provided excellent muscle relaxation and a moderate level of anesthesia. Buzzards given alfaxalone developed primary respiratory acidosis. Base excess and HCO3 were within the reference range and did not significantly change, indicating a primary respiratory acidosis without metabolic component. All physiologic parameters, except cloacal temperature, returned to approximate baseline values at recovery after anesthesia with alfaxalone. This study indicated that alfaxalone produced good to excellent anesthesia in buzzards, characterized by rapid induction of anesthesia, excellent muscle relaxation, unresponsiveness to noxious stimuli, and smooth, uneventful recovery from anesthesia. Hypoventilation and apnea were uncommon at clinically relevant doses but became the most important adverse effects when larger doses were administered rapidly IV.

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 (fR) 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. fR 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.

A comparison of propofol and alfaxalone in a continuous rate infusion in dogs with mitral valve insufficiency

The aim of this study was to compare alfaxalone and propofol in balanced anaesthesia using midazolam 0.5 mg/kg, xylazine 0.125 mg/kg, butorphanol 0.2 mg/kg intravenously as premedication and the ultrashort acting anaesthetics alfaxalone or propofol for inducing and maintaining in dogs with medically stabilised mitral valve regurgitation. Seven client-owned dogs with a second stage cardiac insufficiency were used in this study. All the dogs suffered from class II cardiac insufficiency according to the classification by the International Small Animal Cardiac Health Council (ISACH). All the dogs were treated with angiotensin converting enzyme inhibitors (enalapril) and diuretics (furosemide), which eliminated the clinical signs of mitral valve regurgitation in all the dogs included in the study. This was a prospective controlled clinical study, 12 months in duration, when the dogs included in the study underwent regular dental prophylaxis. The dogs were monitored electrocardiographically throughout the anaesthesia for the presence of arrhythmias, % oxygen saturation of haemoglobin (%SpO&lt;sub&gt;2&lt;/sub&gt;) measured by pulse oximetry, heart rate, respiratory rate and body temperature. The dogs underwent two anaesthesia procedures with an interval of one year due to the prophylaxis of periodontitis, with the first anaesthesia maintained by propofol and second one by alfaxalone. The respiratory rate was mostly significantly higher in the individuals undergoing alfaxalone anaesthesia (P &amp;lt; 0.05), but neither the slower respiratory frequency in the propofol anaesthesia had any negative impact on the % oxygen saturation of the haemoglobin (%SpO&lt;sub&gt;2&lt;/sub&gt;). The heart frequency was significantly higher in the alfaxalone group (P &amp;lt; 0.005). The arterial blood pressures were comparable, but, on the contrary, the two dogs from propofol group had significantly higher blood pressure. The cardiovascular values in both types of anaesthesia had a tendency to progressively decrease within the physiological range. The level of the analgesia was significantly higher in the case of the propofol anaesthesia (P &amp;lt; 0.01) and the recovery period was also significantly shorter (P &amp;lt; 0.005). It can be concluded that the investigated ultra short acting anaesthetics used in balanced anaesthesia containing subanaesthetic doses of xylazine can be used over one hour of surgical procedures in dogs stabilised for mitral valve regurgitation without a significantly increased risk from the anaesthesia.

Clinical measurements performed during alfaxalone total intravenous anaesthesia for radiography and neurophysiological investigations in dogs

ObjectiveTo describe clinically relevant, physiological measurements collected during a 3 hour duration of alfaxalone total intravenous anaesthesia. Study designCase series. AnimalsA total of 112 client-owned middle-aged or older dogs. MethodsDogs were premedicated with intramuscular acepromazine (0.03 mg kg–1). Anaesthesia was induced and subsequently maintained for up to 3 hours with alfaxalone administered intravenously. Dogs breathed 100% oxygen via an endotracheal tube. Heart rate, respiratory rate and blood pressure were evaluated 30 minutes after administration of acepromazine and used as baseline values for comparisons of intra-anaesthetic data. Blood glucose was measured 1 week prior to anaesthesia and every hour during alfaxalone anaesthesia. Quality and duration of recovery were recorded. Mean data for physiological variables were compared over three time points—before induction of anaesthesia, for the first hour of anaesthesia and from 60 minutes to discontinuation of anaesthesia. ResultsMean induction dose of alfaxalone was 1.4 mg kg–1 [95% confidence interval (CI) 1.3–1.5). Post induction apnoea for >60 seconds occurred in 13 (11.6%) dogs. Mean alfaxalone infusion rate during the first 60 minutes of anaesthesia was 0.099 mg kg–1 minute–1; mean infusion rate was 0.092 mg kg–1 minute–1 from 60 minutes until discontinuation of anaesthesia. Heart rate was well maintained; hypotension (mean arterial blood pressure < 60 mmHg) was encountered in 23 (21%) dogs. Blood glucose levels did not alter during anaesthesia. Median time between discontinuation of alfaxalone infusion and extubation was 17 (7–35 minutes), time to assuming sternal recumbency was 75 (58–110 minutes), and time to standing was 109 (88–140 minutes). Conclusions and clinical relevanceAlfaxalone infusion provided effective anaesthesia in this population. In a minority of cases, respiratory and haemodynamic support of the patient was required.

Electrophysiological characterisation of central sensitisation in canine spontaneous osteoarthritis.

In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC.

A COMPARISON OF ALFAXALONE AND TRICAINE METHANESULPHONATE (MS-222) IN TWO FISH SPECIES

The purpose of this study was to evaluate the effectiveness of the alfaxalone formulation Alfaxan™ as an immersion anesthetic in tropical fish species compared to that of tricaine methanesulfonate (MS-222). 22 black spot barbs (Puntius filamentosis) measuring (mean±SD) 11.4 ±1.4 cm in body length and 22 peacock cichlids (Aulonocara spp.) (measuring 8.4 ± 1.6cm were anesthetized in water baths containing 100 mg/L of MS-222 buffered with 200 mg/L of bicarbonate or 5 mg/L of alfaxalone following a 2-week washout period. Time to maximum effect, recovery periods, self-righting, spontaneous swimming movements, opercular movements, and response to noxious stimuli were recorded. The following results are for the black spot barbs following MS-222 and alfaxalone anesthesia, respectively: mean times (±SD) to surgical anesthesia were 5.5 ± 2.11 and 3.27 ± 1.72 minutes and mean recovery times were 2.95 ± 0.9 and 9.14 ± 3.15 minutes. The peacock cichlid anesthetic protocols for MS-222 (20 of 22 cichlids) and alfaxalone (20 of 21 cichlids) produced the following results, respectively: mean times (±SD) to surgical anesthesia were 14.75 ±5.43 and 11.1 ± 9.84 minutes and mean recovery times were 3.6 ±0.82 and 22.4 ±11.3 minutes. Median recovery time from 5 mg/L alfaxalone was significantly longer (P < 0.001) in both species, by 5 minutes for black spot barbs and by 17 minutes for peacock cichlids. Variation in induction and recovery times between species was observed, with black spot barbs having significantly (P < 0.0001) faster induction times when treated with both drugs, and a faster recovery time from 5 mg/L alfaxalone.

Pharmacokinetics of alfaxalone infusions, context-sensitive half-time and recovery times in male neutered cats

ObjectivesTo determine the context-sensitive half-time of alfaxalone following intravenous infusions of various durations. To estimate the time necessary for plasma concentration to decrease by up to 95%. Study designProspective randomized and simulation studies. AnimalsA group of six 1-year-old male castrated research cats. MethodsCats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered using a target-controlled infusion system, to target a plasma alfaxalone concentration of 7.6 mg L–1. The infusion lasted 30 (n = 2), 60 (n = 2) or 240 (n = 2) minutes. Blood samples were collected prior to drug administration, and at several times during and up to 8 hours after the infusion, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to each time–concentration profile, and a population model was fitted to data from all individuals. The context-sensitive half-time was determined from each individual model. In addition, times for plasma alfaxalone concentration to decrease by 50–95% following bolus administration and target-controlled infusions or continuous rate infusions of 0.5–8 hours were estimated by simulation using the population model. ResultsContext-sensitive half-times were 2 and 8, 6 and 9, and 18 and 20 minutes for the 30, 60 and 240 minutes, respectively. Time for plasma alfaxalone concentration to decrease by 90% was predicted to range from 7 to 120 or 113 minutes following a bolus to an 8 hour target-controlled or continuous rate infusion, respectively. Conclusion and clinical relevanceRecovery time from alfaxalone anesthesia in cats is predicted to be influenced by the duration of target-controlled infusion.

Alfaxalone anaesthesia in Lemur catta following dexmedetomidine–butorphanol–midazolam sedation

ObjectiveTo evaluate the clinical effects and quality of sedation, induction, maintenance and recovery in Lemur catta after dexmedetomidine–butorphanol–midazolam sedation and alfaxalone anaesthesia. Study designProspective, observational study. AnimalsSix male L. catta weighing 3.0 ± 0.6 kg undergoing surgical castration. MethodsLemurs were sedated with intramuscular dexmedetomidine (0.015 mg kg−1), butorphanol (0.2 mg kg−1) and midazolam (0.2 mg kg−1). Anaesthesia was induced with intravenous alfaxalone 0.5 mg kg−1 over 60 seconds; further boluses were administered until tracheal intubation was feasible and final dose recorded. Alfaxalone continuous infusion was used to maintain anaesthesia. Atipamezole (0.15 mg kg−1) was administered during recovery. The quality of sedation, induction, intubation, maintenance and recovery was assessed using a scoring system. Physiological parameters were recorded during sedation, maintenance and recovery. ResultsSedation was achieved in 13.6 ± 5.6 minutes and no reactions were observed during handling or venepuncture. The mean dose of alfaxalone required for induction and maintenance was 2.09 ± 0.65 and 0.08 ± 0.02 mg kg−1 minute−1, respectively. Quality of induction, intubation and maintenance was good in almost all animals. Mild self-limiting muscle twitching was observed after alfaxalone administration in three animals. Cardiorespiratory function was stable in all animals but one. One lemur showed respiratory depression and required oxygen administration and manual ventilation. The mean maintenance time was 29.2 ± 7.4 minutes. The mean times from the end of alfaxalone administration to extubation, atipamezole administration and full recovery were: 15.3 ± 8.0, 22.2 ± 4.6 and 60.0 ± 8.4 minutes, respectively. Recovery was considered good in all animals. Conclusions and clinical relevanceDexmedetomidine–butorphanol–midazolam combination provided reliable sedation and adequate muscle relaxation in L. catta. Alfaxalone proved to be a useful drug for induction and maintenance of anaesthesia and might be considered an option for injectable anaesthesia in lemurs.

Immersıon Anesthesia with Alfaxalone in a Goldfısh (Carassius auratus)

An alfaxalone anesthesia protocol was used to perform a coeliotomy in a goldfish diagnosed with multiple ovarian cysts. The 7-year-old, 460g, female goldfish presented for severe coelomic distension and anorexia. Full-body radiographic images were unremarkable, but coelomic ultrasound revealed multiple ovarian cysts. Ultrasound-guided aspiration of a large cyst was performed. Cytology revealed lysed leukocytes that contained numerous intracellular bacilli suggestive of septic suppurative inflammation. An exploratory coeliotomy was performed and 90mL of semi-clear fluid was aspirated from the largest cysts. For anesthesia, three plastic fish tanks were prepared for induction (10mg/L of alfaxalone), maintenance (5mg/L alfaxalone), and recovery (no anesthetic agent). Water in the fish tanks was saturated with oxygen. The goldfish was immersed in the induction tank and once the labyrinthine-righting reflex was lost (5 minutes), the fish was placed in the maintenance tank. The goldfish was then placed on a platform and supported in a supine position on wet Perlon wool. The head of the goldfish was submerged in water while the coelomic area of the surgical field was maintained out of water. During surgery, the respiratory rate (32 to 53 opercula movements per minute) and heart rate (35 to 45beats per minute) were monitored. Butorphanol (0.4mg/kg IM) was administered for analgesia. The anesthetic event was 60 minutes, with the recovery period being 35 minutes. There were no complications associated with recovery and the goldfish returned to its normal position 12 hours after surgery. Immersion anesthesia with alfaxalone permitted deep anesthesia for surgery with an uncomplicated recovery. The anesthetic protocol described appears to be a safe and easy protocol for general practitioners and, furthermore, uses anesthetic agent commonly available to veterinarians.

Comparison of the brainstem auditory evoked responses during sevoflurane or alfaxalone anaesthesia in adult cats

ObjectiveTo compare the effects of general anaesthesia using sevoflurane or alfaxalone on the brainstem auditory evoked response (BAER) test in adult healthy cats. Study designProspective, clinical, ‘blinded’, crossover study. AnimalsTen feral adult healthy cats. MethodsPremedication consisted of dexmedetomidine (0.01 mg kg–1) intramuscularly (IM). The first general anaesthesia was induced and maintained with sevoflurane (treatment S) for physical examination, BAER test, complete blood tests, thoracic radiographs and abdominal ultrasound. The second general anaesthesia was induced with alfaxalone (treatment A) IM (2 mg kg–1) and maintained with alfaxalone (10 mg kg–1 hour–1) for the BAER test, followed by neutering surgery.The BAER recordings were compared for differences in latencies, amplitudes and waveform morphology. Data were analysed using Student's t test and Wilcoxon rank test for paired samples for parametric and non-parametric data, respectively. Statistical significance was set at p < 0.05. ResultsGeneral anaesthesia was uneventful; normal BAER comprising five peaks could be identified in both treatments. Mean ± SD latencies were 1.05 ± 0.09, 1.83 ± 0.11, 2.52 ± 0.19, 3.43 ± 0.17 and 4.39 ± 0.15 ms and 1.03 ± 0.04, 1.81 ± 0.73, 2.53 ± 0.15, 3.37 ± 0.13 and 4.33 ± 0.13 ms in treatments S and A, respectively. Median (interquartile range) amplitudes were 2.83 (0.67), 1.27 (0.41), 0.30 (0.40), 1.05 (0.82), 0.61 (0.38) microvolts and 2.84 (1.21), 1.49 (1.18), 0.26 (0.32), 0.91 (0.50) and 0.92 (0.64) microvolts in treatments S and A, respectively. There were no statistically significant differences in mean latencies or median amplitudes between both the anaesthetics. Conclusions and clinical relevanceThis study demonstrates that there were no statistically significant differences between both the anaesthetics on the BAER test in adult healthy cats. Moreover, two possible anaesthetic protocols are described for cats undergoing this electrodiagnostic test.