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.     

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.     

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.     

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.     

Evaluation of butorphanol–azaperone–medetomidine (BAM) in captive blesbok immobilization (Damaliscus pygargus phillipsi)

Objective

The fixed-dose combination of butorphanol, azaperone and medetomidine (BAM; 30, 12 and 12 mg mL^?1, respectively) with subsequent antagonism by naltrexone–atipamezole was evaluated for reversible immobilization of captive blesbok (Damaliscus pygargus phillipsi).

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.     

A comparison of cardiopulmonary and anesthetic effects of an induction dose of alfaxalone or propofol in dogs

ObjectiveTo compare the physiological parameters, arterial blood gas values, induction quality, and recovery quality after IV injection of alfaxalone or propofol in dogs.Study designProspective, randomized, blinded crossover.AnimalsEight random-source adult female mixed-breed dogs weighing 18.7 ± 4.5 kg.MethodsDogs were assigned to receive up to 8 mg kg^?1 propofol or 4 mg kg^?1 alfaxalone, administered to effect, at 10% of the calculated dose every 10 seconds. They then received the alternate drug after a 6-day washout. Temperature, pulse rate, respiratory rate, direct blood pressure, and arterial blood gases were measured before induction, immediately post-induction, and at 5-minute intervals until extubation. Quality of induction, recovery, and ataxia were scored by a single blinded investigator. Duration of anesthesia and recovery, and adverse events were recorded.ResultsThe mean doses required for induction were 2.6 ± 0.4 mg kg^?1 alfaxalone and 5.2 ± 0.8 mg kg^?1 propofol. After alfaxalone, temperature, respiration, and pH were significantly lower, and PaCO₂ significantly higher post-induction compared to baseline (p < 0.03). After propofol, pH, PaO₂, and SaO₂ were significantly lower, and PaCO₂, HCO₃, and PA-aO₂ gradient significantly higher post-induction compared to baseline (p < 0.03). Post-induction and 5-minute physiologic and blood gas values were not significantly different between alfaxalone and propofol. Alfaxalone resulted in significantly longer times to achieve sternal recumbency (p = 0.0003) and standing (p = 0.0004) compared to propofol. Subjective scores for induction, recovery, and ataxia were not significantly different between treatments; however, dogs undergoing alfaxalone anesthesia were more likely to have ≥1 adverse event (p = 0.041). There were no serious adverse events in either treatment.Conclusions and clinical relevanceThere were no clinically significant differences in cardiopulmonary effects between propofol and alfaxalone. A single bolus of propofol resulted in shorter recovery times and fewer adverse events than a single bolus of alfaxalone.     

Evaluation of butorphanol, medetomidine and midazolam as a reversible narcotic combination in free-ranging African lions (Panthera leo)

ObjectiveTo evaluate the effects of the combination butorphanol, medetomidine and midazolam (BMM) and its reversibility in lions.Study designProspective clinical trial.AnimalsThirty free-ranging lions, 10 male and 20 female, weighing 81-210 kg.MethodsLions were immobilised with butorphanol mean 0.31 ± SD 0.034 mg kg^?1, medetomidine 0.052 ± 0.006 mg kg^?1, midazolam 0.21 ± 0.024 mg kg^?1 and hyaluronidase 1250 IU administered intramuscularly with a dart gun. Upon recumbency, physiological parameters and anaesthetic depth were monitored 10-15 minutes after darting (T1) and repeated every 10 minutes for a further 30 minutes (T2, T3, T4). Arterial blood gas analyses were performed at T1 and T4. At the end of the procedure, 45-60 minutes after initial darting, immobilisation was reversed with naltrexone 0.68 ± 0.082 mg kg^?1, atipamezole 0.26 ± 0.031 mg kg^?1, and flumazenil 0.0032 ± 0.0007 mg kg^?1 administered intravenously and subcutaneously.ResultsThe BMM combination rapidly induced immobilisation and lateral recumbency was reached within 7.25 ± 2.3 minutes. Median induction score [scored 1 (excellent) to 4 (poor)] was 1.4 (range 1-2). Cardio-respiratory parameters were stable. Heart rate varied from 32 to 72 beats per minute, respiratory rate from 14 to 32 breaths minute^?1 and rectal temperature from 36.6 to 40.3 °C. No sudden arousals were observed. Arterial blood gas analyses revealed a mean pH of 7.33, PaCO₂ of 33 mmHg and PaO₂ of 87 mmHg. Mild to moderate hypoxemia was seen in four lions. Recovery was smooth and lions were walking within 4.4 ± 4.25 minutes. Median recovery score [scored 1 (excellent) to 4 (poor)] was 1.3 (range 1-2).Conclusion and clinical relevanceThe drug combination proved to be effective in immobilising free-ranging healthy lions of both sexes with minimal cardio-respiratory changes.     

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

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

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.     

Accelerated induction of etorphine immobilization in blue wildebeest (Connochaetes taurinus) through the addition of hyaluronidase

ObjectiveTo study the effects of the addition of hyaluronidase (HA) to an etorphine/azaperone drug combination on induction times of immobilization.Study designExperimental part-randomized ‘blinded’ cross-over study.AnimalsEight wild managed blue wildebeest (Connochaetes taurinus).MethodsAnimals were immobilized, on separate occasions separated by two weeks, with one of four treatments. Treatments were; ‘Control drugs (CD), etorphine 0.01 mg kg⁻¹ + azaperone at 0.1 mg kg⁻¹; treatment 1 CD + 5000IU HA; treatment 2 CD + 7500 IU HA; and treatment 3 etorphine 0.007 mg kg⁻¹ + azaperone at 0.07 mg kg⁻¹ + 7500 IU HA. Times to first effect and to immobilization (from darting to possible to approach and blindfold) were measured. anova was used to compare treatments. Results are given in means ± SD (range).ResultsFor control, and treatments 1–3 respectively, times (in minutes) to first effect were 1.58 ± 0.42 (1.02–2.10), 1.64 ± 0.42 (0.95–2.17), 1.12 ± 0.24 (0.80–1.48) and 1.60 ± 0.21 (1.13–1.88) and to immobilization were 5.38 ± 1.53 (3.82–8.07), 3.80 ± 1.14 (2.02–5.50), 3.51 ± 1.08 (2.28–5.52) and 4.46 ± 0.67 (3.30–5.40). Compared to control, time to first effect for treatment 2 was significantly shorter. Time to immobilization was significantly quicker in all three treatments containing HA than that for control.Conclusion and clinical relevanceHyaluronidase can reduce the time to immobilization when used in the immobilizing dart, and might be usefully incorporated into etorphine combinations for darting wildlife.     

Alfaxalone or ketamine‐medetomidine in cats undergoing ovariohysterectomy: a comparison of intra‐operative parameters and post‐operative pain

ObjectiveTo compare post-operative pain in cats after alfaxalone or ketamine- medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters during and after surgery.Study designProspective ‘blinded’ randomized clinical study.AnimalsTwenty-one healthy cats.MethodsCats were assigned randomly into two groups: Group A, anaesthesia was induced and maintained with alfaxalone [5 mg kg^?1 intravenously (IV) followed by boli (2 mg kg^?1 IV); Group MK, induction with ketamine (5 mg kg^?1 IV) after medetomidine (30 μg kg^?1 intramuscularly (IM)], and maintenance with ketamine (2 mg kg^?1 IV). Meloxicam (0.2 mg kg^?1 IV) was administered after surgery. Basic physiological data were collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post-operatively pain was assessed by three methods, a composite pain scale (CPS; 0–24 points), a visual analogue scale (VAS 0–100 mm), and a mechanical wound threshold (MWT) device. Butorphanol (0.2 mg kg^?1 IM) was administered if CPS was scored =13. Data were analyzed using a general linear model, Kruskal–Wallis analyses, Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant. Significance was set at p < 0.05.ResultsVASs were significantly higher at 0.5, 1, 2, 4, and 20 hours in group A; MWT values were significantly higher at 8 and 12 hours in group MK. Post-operative MWT decreased significantly compared to baseline in both groups. There was no difference in CPS at any time point. Five cats required rescue analgesia (four in A; one in MK).Conclusion and clinical relevanceAnaesthesia with ketamine-medetomidine was found to provide better post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary hyperalgesia developed in both groups. Alfaxalone is suitable for induction and maintenance of anaesthesia in cats undergoing OHE, but administration of additional sedative and analgesic drugs is highly recommended.     

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.     

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.     

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.     

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study

ObjectiveTo investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration.Study designA randomized, controlled, blinded, clinical trial.AnimalsA total of 28 client-owned dogs.MethodsDogs were premedicated with medetomidine (0.125 mg m^?2) and butorphanol (0.2 mg kg^?1) (group MB; n = 14), or medetomidine (0.25 mg m^?2), butorphanol (0.2 mg kg^?1) and vatinoxan (5 mg m^?2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg^?1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg^?1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f_R), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe′Sevo) and carbon dioxide (Pe′CO₂) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations.ResultsAt the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute^?1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f_R, Pe′CO₂, Fe′Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups.Conclusions and clinical relevanceIn group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.     

Intramuscular administration of alfaxalone in red‐eared sliders (Trachemys scripta elegans) – effects of dose and body temperature

ObjectiveTo characterise the effects of alfaxalone by intramuscular (IM) injection in red-eared slider turtles and the influence of body temperature on anaesthetic duration and depth.Study designProspective, randomised part-blinded experimental trial.AnimalsTen healthy adult female red-eared sliders.MethodsEach turtle was anaesthetized four times with 10 and 20 mg kg^?1 alfaxalone at 20 and 35 °C respectively. Time to maximal effect and plateau and recovery periods were recorded. Skeletal muscle tone, presence of various reflexes, response to noxious stimuli, and heart rate were assessed.ResultsResults are given for protocols 10 mg kg^?1 20 °C; 20 mg kg^?1 20 °C; 10 mg kg^?1 35 °C and 20 mg kg^?1 35 °C, respectively: mean time (±SD) to maximal effect was 16 ± 8, 19 ± 6, 5 ± 2 and 7 ± 5 minutes; duration of the plateau phase was 13 ± 12, 28 ± 13, 8 ± 5 and 8 ± 5 minutes and recovery time was 76 ± 20, 126 ± 17, 28 ± 9 and 41 ± 20 minutes. Endotracheal intubation was successful in 80%, 100%, 0% and 30% of turtles, respectively. At 35 °C, all animals retained nociceptive sensation in the front limbs, hind limbs and vent, whereas at 20 °C a few turtles lost peripheral nociceptive sensation. Corneal and tap reflexes were retained in all trials. Mean heart rates were 30 ± 2 and 66 ± 4 beats minute^?1 at 20 and 35 °C, respectively.Conclusions and clinical relevanceAlfaxalone administered IM in red-eared sliders provided smooth, rapid induction and uneventful recovery. At 35 °C either dosage provided only short (5–10 minutes) and light sedation. At 20 °C, 10 mg kg^?1 provided sedation suitable for short non-invasive procedures. About 20 mg kg^?1 provided anaesthesia of approximately 20 minutes duration, appropriate for induction of inhalational anaesthesia or for brief surgical procedures with supplemental analgesia.     

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.