Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate.Study designProspective experimental study.AnimalsFive clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg.MethodsFoals were premedicated with butorphanol (0.05 mg kg^?1 IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg^?1. Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis.ResultsThe harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl_p) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg^?1 and 0.6 ± 0.2 L kg^?1, respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively.ConclusionsThe anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life.Clinical relevanceAlfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended.     

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.     

Effects of ketamine or midazolam continuous rate infusions on alfaxalone total intravenous anaesthesia requirements and recovery quality in healthy dogs: a randomized clinical trial

ObjectiveTo determine the alfaxalone dose reduction during total intravenous anaesthesia (TIVA) when combined with ketamine or midazolam constant rate infusions and to assess recovery quality in healthy dogs.Study designProspective, blinded clinical study.AnimalsA group of 33 healthy, client-owned dogs subjected to dental procedures.MethodsAfter premedication with intramuscular acepromazine 0.05 mg kg^-1 and methadone 0.3 mg kg^-1, anaesthetic induction started with intravenous alfaxalone 0.5 mg kg^-1 followed by either lactated Ringer’s solution (0.04 mL kg^-1, group A), ketamine (2 mg kg^-1, group AK) or midazolam (0.2 mg kg^-1, group AM) and completed with alfaxalone until endotracheal intubation was achieved. Anaesthesia was maintained with alfaxalone (6 mg kg^-1 hour^-1), adjusted (±20%) every 5 minutes to maintain a suitable level of anaesthesia. Ketamine (0.6 mg kg^-1 hour^-1) or midazolam (0.4 mg kg^-1 hour^-1) were employed for anaesthetic maintenance in groups AK and AM, respectively. Physiological variables were monitored during anaesthesia. Times from alfaxalone discontinuation to extubation, sternal recumbency and standing position were calculated. Recovery quality and incidence of adverse events were recorded. Groups were compared using parametric analysis of variance and nonparametric (Kruskal-Wallis, Chi-square, Fisher’s exact) tests as appropriate, p < 0.05.ResultsMidazolam significantly reduced alfaxalone induction and maintenance doses (46%; p = 0.034 and 32%, p = 0.012, respectively), whereas ketamine only reduced the alfaxalone induction dose (30%; p = 0.010). Recovery quality was unacceptable in nine dogs in group A, three dogs in group AK and three dogs in group AM.Conclusions and clinical relevanceMidazolam, but not ketamine, reduced the alfaxalone infusion rate, and both co-adjuvant drugs reduced the alfaxalone induction dose. Alfaxalone TIVA allowed anaesthetic maintenance for dental procedures in dogs, but the quality of anaesthetic recovery remained unacceptable irrespective of its combination with ketamine or midazolam.     

Immersion anaesthesia in goldfish (Carassius auratus) with three concentrations of alfaxalone

Objective

To evaluate the anaesthetic effects of three different alfaxalone doses to induce anaesthesia in goldfish.

Effects of different doses of dexmedetomidine on anaesthetic induction with alfaxalone – a clinical trial

ObjectiveTo document the effects of two doses of dexmedetomidine on the induction characteristics and dose requirements of alfaxalone.Study designRandomized controlled clinical trial.AnimalsSixty one client owned dogs, status ASA I-II.MethodsDogs were allocated randomly into three groups, receiving as pre-anaesthetic medication, no dexmedetomidine (D₀), 1 μg kg^?1 dexmedetomidine (D₁) intramuscularly (IM) or 3 μg kg^?1 dexmedetomidine IM (D₃). All dogs also received 0.2 mg kg^?1 methadone IM. Level of sedation was assessed prior to induction of anaesthesia. Induction of general anaesthesia was performed with alfaxalone administered intravenously to effect at a rate of 1 mg kg^?1 minute^?1; the required dose to achieve tracheal intubation was recorded. Anaesthesia was maintained with isoflurane in oxygen. Cardiopulmonary parameters were recorded throughout the anaesthetic period. Quality of intubation, induction and recovery of anaesthesia were recorded. Quantitative data were compared with one-way anova or Kruskal-Wallis test. Repeated measures were log-transformed and analysed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for categorical data, with exception of sedation level (p < 0.001). The doses (mean ± SD) of alfaxalone required for intubation were D₀ 1.68 ± 0.24, D₁ 1.60 ± 0.36 and D₃ 1.41 ± 0.43, the difference between D₀ and D₃ being statistically significant (p = 0.036). Heart and respiratory rates during the anaesthetic period were significantly different over time and between groups (p < 0.001); systolic arterial blood pressure was significantly different over time (p < 0.001) but not between groups (p = 0.833). Induction quality and recovery scores were similar between groups (p = 1.000 and p = 0.414, respectively).Conclusions and clinical relevanceThe administration of alfaxalone resulted in a good quality anaesthetic induction which was not affected by the dose of dexmedetomidine. Dexmedetomidine at 3 μg kg^?1 IM combined with methadone provides good sedation and enables a reduction of alfaxalone requirements.     

Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine

ObjectiveTo describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy.Study designProspective, randomised, clinical study.AnimalsThirty-eight healthy female dogs.MethodsFollowing intramuscular buprenorphine (20 μg kg^?1) and acepromazine (0.05 mg kg^?1) or dexmedetomidine (approximately 10 μg kg^?1, adjusted for body surface area), anaesthesia was induced and maintained with intravenous alfaxalone. Oxygen was administered via a suitable anaesthetic circuit. Alfaxalone infusion rate (initially 0.07 mg kg^?1 minute^?1) was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Alfaxalone boluses were given if required. Ventilation was assisted if necessary. Alfaxalone dose and physiologic parameters were recorded every 5 minutes. Depth of sedation after premedication, induction quality and recovery duration and quality were scored. A Student's t-test, Mann–Whitney U and Chi-squared tests determined the significance of differences between groups. Data are presented as mean ± SD or median (range). Significance was defined as p < 0.05.ResultsThere were no differences between groups in demographics; induction quality; induction (1.5 ± 0.57 mg kg^?1) and total bolus doses [1.2 (0 – 6.3) mg kg^?1] of alfaxalone; anaesthesia duration (131 ± 18 minutes); or time to extubation [16.6 (3–50) minutes]. DEX dogs were more sedated than ACP dogs. Alfaxalone infusion rate was significantly lower in DEX [0.08 (0.06–0.19) mg kg^?1 minute^?1] than ACP dogs [0.11 (0.07–0.33) mg kg^?1 minute^?1]. Cardiovascular variables increased significantly during ovarian and cervical ligation and wound closure compared to baseline values in both groups. Apnoea and hypoventilation were common and not significantly different between groups. Arterial haemoglobin oxygen saturation remained above 95% in all animals. Recovery quality scores were significantly poorer for DEX than for ACP dogs.Conclusions and clinical relevanceAlfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.     

Alfaxalone anaesthesia in the green iguana (Iguana iguana)

ObjectiveTo characterise the anaesthetic effects of alfaxalone administered intramuscularly (IM) at 10, 20, and 30 mg kg^?1.Study designProspective, randomized cross-over study.AnimalsTen juvenile green iguanas (Iguana iguana) of mean body weight (±SD) 480 ± 134 g.MethodsAlfaxalone was administered IM in the triceps of both thoracic limbs. Times for anaesthetic induction, plateau and recovery periods were recorded. Skeletal muscle tone of the jaw, neck, thoracic limbs, pelvic limbs, and tail was scored. The palpebral, corneal and righting reflexes, and the response to painful stimuli were also assessed. Pulse rate and respiratory rate were recorded. Comparisons between different dosages and over time were made using anova.ResultsTimes are given for 10, 20 and 30 mg kg^?1 dosages respectively: mean time to maximal effect was 7.7 ± 2.2, 5.4 ± 1.7 and 3.9 ± 1.2 minutes; duration of the plateau phase was 11.3 ± 3.8, 22.1 ± 6.5 and 39.1 ± 11.5 minutes; recovery time was 10 ± 2.4, 17.5 ± 8.6 and 25 ± 7.1 minutes; and total anaesthetic duration was 29 ± 35.7, 45 ± 8.2 and 68 ± 9.8 minutes. Endotracheal intubation was possible in 40% of the subjects given 10 mg kg^?1 and in 100% subjects given both 20 and 30 mg kg^?1. Loss of response to a painful stimulus was seen in 0/10, 8/10 and 9/10 animals at 10, 20, and 30 mg kg^?1 respectively. There was an initial dose-dependent depression of respiration followed by a significant increase in frequency over time. In contrast, pulse rates decreased by 20% over the duration of the anaesthetic events.Conclusions and clinical relevanceIntramuscular administration of alfaxalone is a simple, rapid and reliable means of achieving relatively brief sedation or anaesthesia in healthy green iguanas. A dosage of 10 mg kg^?1 provides light sedation, appropriate for examination and venipuncture; 20 mg kg^?1 provides a level suitable for minor procedures or for endotracheal intubation and supplementation with inhalational anaesthesia; 30 mg kg^?1 produces an anaesthetic plane suitable for surgical procedures of limited duration (up to 40 minutes).     

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

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

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

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

Assessment of the effects of intramuscular administration of alfaxalone with and without medetomidine in Horsfield's tortoises (Agrionemys horsfieldii)

ObjectiveTo characterise four different intramuscular (IM) anaesthetic protocols, two with alfaxalone and two with alfaxalone in combination with medetomidine in terrestrial tortoises.Study designBlinded, randomized, cross‐over experimental study.AnimalsNine healthy adult male Horsfield's tortoises (Agrionemys horsfieldii).MethodsEach tortoise was randomly assigned to one of four different protocols: 1) 10 mg kg^?1 alfaxalone; 2) 10 mg kg^?1 alfaxalone + 0.10 mg kg^?1 medetomidine; 3) 20 mg kg^?1 alfaxalone; and 4) 20 mg kg^?1 alfaxalone + 0.05 mg kg^?1 medetomidine. During the experiment, the following variables were recorded: heart rate; respiratory rate; peripheral nociceptive responses; muscle strength; ability to intubate; palpebral, corneal and tap reflexes; and cloacal temperature.ResultsProtocols 1 and 2 resulted in moderate sedation with no analgesia, and moderate to deep sedation with minimal analgesia, respectively. Protocols 3 and 4 resulted in deep sedation or anaesthesia with variable analgesic effect; these two protocols had the longest total anaesthetic time and allowed intubation in 6/9 and 8/9 tortoises respectively. The total anaesthesia/sedation time produced by alfaxalone was significantly increased (p <0.05) by the addition of medetomidine. There were no significant differences regarding time to plateau phase and duration of plateau phase. Baseline heart rate of 53 ± 6 beats minute^?1 decreased significantly (p <0.05) with all protocols, and was lower (p <0.05) in protocols 3 and 4. Heart rate increased after atipamezole administration, but the increase was transient. In two tortoises, extreme bradycardia with no cardiac activity for 10 minutes was observed with protocols 3 and 4.Conclusion and clinical relevanceAlfaxalone 10 and 20 mg kg^?1 IM can be used for sedation for non‐painful procedures. Alfaxalone in combination with medetomidine can be used for deeper sedation or anaesthesia, but the observed respiratory and cardiovascular depression may limit its use.     

Efficacy of benzocaine as an anaesthetic for Crucian carp (Carassius carassius)

ObjectiveTo investigate the anaesthetic induction time and concentrations of stress markers in Crucian carp (Carassius carassius) subjected to different concentrations of benzocaine.Study designProspective experimental study.AnimalsThirty-six Crucian carp [body weight 368.3 ± 22.7 g and length 28.1 ± 1.9 cm (mean ± SD)].MethodsFish were divided into four groups, initially with nine fish per group. Each group was subjected to one of four final concentrations [0, 25, 50 and 100 parts per million (p.p.m.)] of benzocaine. The times to induction of sedation, to pre-anaesthesia and to anaesthesia were recorded according to the behavioural events observed after exposing the fish to benzocaine. At each stage, blood was collected from the caudal vein of three fish of the group, and these three fish were then euthanized. Plasma cortisol and glucose concentrations in the blood samples were measured as indices of stress response.ResultsInduction times for all stages of anaesthesia decreased significantly with increasing concentrations of benzocaine (1678 ± 103, 475 ± 73 and 251 ± 2 seconds for anaesthesia in 25, 50 and 100 p.p.m., respectively). Plasma cortisol and glucose concentrations were significantly lower in the anaesthetized groups than the control group (p < 0.05), and tended to decrease with an increasing dose of benzocaine. The cortisol concentrations (36.1 ± 5.8 ng dL^?1) at the anaesthetic stage for the 100 p.p.m. group were significantly decreased compared with the other groups (67.3 ± 14.9 ng dL^?1 in 25 p.p.m. and 47.6 ± 2.6 ng dL^?1 in 50 p.p.m.). Differences in glucose concentrations between benzocaine-treated groups were not significant.Conclusions and clinical relevanceIn this study, the fish group exposed to 100 p.p.m. benzocaine had a fast induction time for all monitored stages, low circulating cortisol and glucose concentrations and no immediate mortality.     

Clinical efficacy and cardiorespiratory effects of alfaxalone, or diazepam/fentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk

ObjectiveTo evaluate the clinical efficacy and cardiorespiratory effects of alfaxalone as an anaesthetic induction agent in dogs with moderate to severe systemic disease.Study designRandomized prospective clinical study.AnimalsForty dogs of physical status ASA III-V referred for various surgical procedures.MethodsDogs were pre-medicated with intramuscular methadone (0.2 mg kg^?1) and allocated randomly to one of two treatment groups for induction of anaesthesia: alfaxalone (ALF) 1–2 mg kg^?1 administered intravenously (IV) over 60 seconds or fentanyl 5 μg kg^?1 with diazepam 0.2 mg kg^?1± propofol 1–2 mg kg^?1 (FDP) IV to allow endotracheal intubation. Anaesthesia was maintained with isoflurane in oxygen and fentanyl infusion following both treatments. All dogs were mechanically ventilated to maintain normocapnia. Systolic blood pressure (SAP) was measured by Doppler ultrasound before and immediately after anaesthetic induction, but before isoflurane administration. Parameters recorded every 5 minutes throughout subsequent anaesthesia were heart and respiratory rates, end-tidal partial pressure of carbon dioxide and isoflurane, oxygen saturation of haemoglobin and invasive systolic, diastolic and mean arterial blood pressure. Quality of anaesthetic induction and recovery were recorded. Continuous variables were assessed for normality and analyzed with the Mann Whitney U test. Repeated measures were log transformed and analyzed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for continuous and categorical data. Anaesthetic induction quality was good following both treatments. Pre-induction and post-induction systolic blood pressure did not differ between treatments and there was no significant change after induction. The parameters measured throughout the subsequent anaesthetic procedures did not differ between treatments. Quality of recovery was very, quite or moderately smooth.Conclusions and clinical relevanceInduction of anaesthesia with alfaxalone resulted in similar cardiorespiratory effects when compared to the fentanyl-diazepam-propofol combination and is a clinically acceptable induction agent in sick dogs.     

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.     

Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog

ObjectiveTo determine in dogs the effects of medetomidine and butorphanol, alone and in combination, on the induction dose of alfaxalone and to describe the induction and intubation conditions.Study designProspective, randomized, blinded clinical trial.AnimalsEighty-five client-owned dogs (ASA 1 or 2).MethodsSubjects were block randomized to treatment group according to temperament. The treatment groups were: medetomidine 4 μg kg^?1 (M), butorphanol 0.1 mg kg^?1 (B), or a combination of both (MB), all administered intramuscularly. After 30 minutes, a sedation score was assigned, and alfaxalone 0.5 mg kg^?1 was administered intravenously over 60 seconds by an observer who was unaware of treatment group. Tracheal intubation conditions were assessed and, if tracheal intubation was not possible after 20 seconds, further boluses of 0.2 mg kg^?1 were given every 20 seconds until intubation was achieved. Induction dose and adverse events (sneezing, twitching, paddling, excitement, apnoea and cyanosis) were recorded; induction quality and intubation conditions were scored and recorded.ResultsThe mean dose of alfaxalone required for induction was similar for groups M and B: 1.2 ± 0.4 mg kg^?1. The mean dose requirement for group MB (0.8 ± 0.3 mg kg^?1) was lower than groups M and B (p < 0.0001). Induction dose was not influenced by temperament or level of sedation. Induction and intubation scores did not differ between treatment groups. Adverse events were noted in 16 dogs; there was no association with treatment group, temperament or level of sedation.Conclusions and clinical relevanceMedetomidine and butorphanol administered in combination reduce the anaesthetic induction dose of alfaxalone compared to either agent alone. This difference should be taken into account when using this combination of drugs in a clinical setting.     

Effects of intramuscular alfaxalone alone or in combination with diazepam in swine

ObjectiveTo describe the use of intramuscular (IM) premedication with alfaxalone alone or in combination with diazepam in pigs.Study designRandomised‐controlled trial.AnimalsTwelve healthy 2 month‐old Landrace x Large White pigs weighing 21.3 ± 2.4 kg.MethodsAnimals were distributed randomly into two groups: group A (n = 6) 5 mg kg^?1 of IM alfaxalone; and group AD (n = 6) 5 mg kg^?1 of IM alfaxalone + 0.5 mg kg^?1 of IM diazepam mixed in the same syringe. The total volume of injectate was standardized at 14 mL by dilution in 0.9% sodium chloride. Pain on injection, the degree of sedation and the quality of and time to induction of recumbency were evaluated. Once pigs were recumbent, reflexes were evaluated. Pulse and respiratory rates and arterial oxygen saturation were recorded at 5 and 10 minutes after drug administration. Pigs were then moved to another room for subsequent anaesthesia.ResultsTwo animals of group A and one of group AD showed slight pain on drug injection. Time to lateral recumbency (in seconds) was shorter in group AD (mean 203 ± SD 45 range 140–260) than group A (302 ± 75, range 220–420; p < 0.05). In group AD sedation was deeper, and on recumbency there was better muscle relaxation. When moved for anaesthesia, two pigs in Group A showed slight resistance but did not vocalize. There were no differences in physiologic measurements between groups, although in both groups, respiratory rate was significantly lower at ten compared with five minutes post drug injection. There was no apneoa.Conclusions and clinical relevanceIM administration of alfaxalone combined with diazepam resulted in a rapid onset of recumbency and deep sedation, with minimal side effects. The combination might be useful for premedication, but volume of injectate will limit its use to small pigs.     

Immersion and branchial/transcutaneous irrigation anaesthesia with alfaxalone in a Mexican axolotl

IntroductionImmersion anaesthetic techniques are commonly used in amphibian species. Alfaxalone has been reported as an immersion anaesthetic in fish but not amphibians.Case history and examinationA Mexican 56 g axolotl was presented with a 3 day history of anorexia. Anaesthesia was required for the surgical retrieval of two gastric foreign bodies. Prior to anaesthesia, on visual inspection the axolotl was bright and active. Branchial and gular respiratory movements occurred at approximately 24 respirations minute^?1 and heart rate was approximately 52 beats minute^?1.ManagementThe axolotl was exposed to increasing concentrations (up to 5 mg L^?1) of alfaxalone (Alfaxan; Vetóquinol, UK) in a water bath. After becoming sedated the axolotl was removed from the water bath. Anaesthesia was induced and maintained with alfaxalone (5 mg L^?1) via continuous irrigation of the gills (branchial) and skin (cutaneous) with additional 30 μL drops of alfaxalone (10 mg mL^?1) administered branchially as required. Endoscopy and surgery were performed to remove two gastric foreign bodies. Branchial and gular respiratory movements persisted at what was considered an appropriate anaesthetic depth. Anaesthetic depth could be rapidly deepened by branchial irrigation of alfaxalone solutions and lightened by irrigation using fresh water. Anaesthesia lasted approximately 1 hour and recovery was rapid (within 15 minutes). Recovery was assisted through branchial and cutaneous irrigation with fresh water.Follow-upNo obvious adverse effects of anaesthesia were observed immediately post-anaesthesia or, according to the owner, in the following week.ConclusionsAxolotls can be anaesthetized using alfaxalone administered via immersion and branchial/transcutaneous irrigation offering an alternative technique for anaesthetising axolotls for clinical and research purposes.     

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

ObjectiveTo evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy.Study designProspective, block-randomized, clinical trial.AnimalsA group of 39 client-owned cats.MethodsAfter 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.ResultsAt 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 relevanceHaematocrit 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

ObjectiveTo compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats.Study designProspective, masked, randomized clinical trial.AnimalsA total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures.MethodsFollowing 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.ResultsMean ± 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 relevancePropofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided.