Alfaxalone for total intravenous anaesthesia in horses.

OBJECTIVE: To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period. STUDY DESIGN: Prospective, experimental study. ANIMALS: Eight Standardbred horses. METHODS: Horses were premedicated with IV acepromazine (0.03 mg kg-1) and xylazine (1 mg kg-1) and anaesthesia was induced with guaifenesin (35 mg kg-1) and alfaxalone (1 mg kg-1). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse's response to a supramaximal electrical noxious stimulus. Venous blood samples were regularly collected to determine alfaxalone plasma concentrations and for pharmacokinetic analysis. Cardiopulmonary variables were monitored and the quality of the anaesthetic recovery period scored. RESULTS: The median (range) alfaxalone infusion rate was 3.1 (2.4-4.3) mg kg-1 hour-1. The mean ± standard deviation plasma elimination half-life, plasma clearance and volume of distribution for alfaxalone were 41 minutes, 25 ± 6.3 mL minute-1 kg-1 and 1.6 ± 0.5 L kg-1, respectively. During anaesthesia, mean arterial blood pressure was maintained above 70 mmHg in all horses. Cardiac index reached a minimum value (68% of baseline values) immediately after induction of anaesthesia and was maintained between 74% and 90% of baseline values for the remainder of the anaesthetic protocol. Following the cessation of the alfaxalone infusion, six of eight horses exhibited muscle tremors and paddling. All horses stood without incident on the first or second attempt with a median recovery score of 4.5 (good to excellent). CONCLUSIONS AND CLINICAL RELEVANCE: Anaesthesia in horses can be maintained with an infusion of alfaxalone at approximately 3 mg kg-1 hour-1. The alfaxalone infusion rates used resulted in minimal haemodynamic changes and good recovery quality. Mean alfaxalone plasma concentration was stable over the infusion period and clearance rates were similar to previously published single-dose alfaxalone studies in horses.

Delivery of sevoflurane to dogs using a Stephens anaesthetic machine.

OBJECTIVE: To investigate the sevoflurane concentrations produced within the Stephens anaesthetic machine circuit (vaporizer in-circle system) at different fresh gas flow rates (FGFRs), temperatures, vaporizer settings and vaporizer sleeve positions when used to anaesthetize dogs of different body sizes. STUDY DESIGN: Experimental non-blinded studies. ANIMALS: Eighteen mixed breed dogs, weights 4-39 kg. METHODS: Anaesthetic induction with propofol was followed by maintenance with sevoflurane in oxygen via the Stephens anaesthetic machine. In study 1, the vaporizer setting, temperature and circuit FGFRs were altered with the vaporizer sleeve down (n = 3), or in separate experiments, up (n = 3). Delivered (Fi'SEVO) and expired sevoflurane concentrations were recorded. Study 2 determined the vaporizer settings (sleeve up) required to achieve predetermined multiples of minimal alveolar concentration (MAC) of Fi'SEVO when sevoflurane was delivered to dogs (n = 12) of different bodyweights and at different FGFRs. RESULTS: Delivered concentrations of sevoflurane were sufficient to maintain anaesthesia in all dogs, regardless of bodyweight, FGFR, vaporizer temperature and sleeve position. Fi'SEVO increased with increasing temperature, when the vaporizer sleeve was down, when vaporizer setting was increased and when FGFR was decreased. As the FGFR increased or the dog's bodyweight decreased, higher vaporizer settings were required to produce the same Fi'SEVO. The median Stephens vaporizer settings to achieve an Fi'SEVO of 1.3 MAC ranged from 4.3 to 5.0 for a small dog (1-10 kg), 2.5 to 5.6 for a medium dog (15-25 kg) and 2.5 to 3.5 for a large dog (30-40 kg), depending on the FGFR. CONCLUSION AND CLINICAL RELEVANCE: The Stephens anaesthetic machine can deliver to dogs, weighing 4 kg and above, concentrations of sevoflurane sufficient or in excess of that required to maintain anaesthesia, at temperatures from 10 to 35 °C, FGFRs of 1 to 5 times the patient's estimated metabolic oxygen requirement and at any vaporizer sleeve position.

Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin.

OBJECTIVE: To compare anaesthesia induced with either alfaxalone or ketamine in horses following premedication with xylazine and guaifenesin. STUDY DESIGN: Randomized blinded cross-over experimental study. ANIMALS: Six adult horses, five Standardbreds and one Thoroughbred; two mares and four geldings. METHODS: Each horse received, on separate occasions, induction of anaesthesia with either ketamine 2.2 mg kg(-1) or alfaxalone 1 mg kg(-1) . Premedication was with xylazine 0.5 mg kg(-1) and guaifenesin 35 mg kg(-1) . Incidence of tremors/shaking after induction, recovery and ataxia on recovery were scored. Time to recovery was recorded. Partial pressure of arterial blood oxygen (PaO(2) ) and carbon dioxide (PaO(2) ), arterial blood pressures, heart rate (HR) and respiratory rates were recorded before premedication and at intervals during anaesthesia. Data were analyzed using Wilcoxon matched pairs signed rank test and are expressed as median (range). RESULTS: There was no difference in the quality of recovery or in ataxia scores. Horses receiving alfaxalone exhibited a higher incidence of tremors/shaking on induction compared with those receiving ketamine (five and one of six horses respectively). Horses recovered to standing similarly [28 (24-47) minutes for alfaxalone; 22 (18-35) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (38-67) minutes] compared with ketamine [35 (30-47)]. There was no statistical difference between treatments in effect on HR, PaO(2) or PaCO(2) although for both regimens, PaO(2) decreased with respect to before premedication values. There was no difference between treatments in effect on blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE: Both alfaxalone and ketamine were effective at inducing anaesthesia, although at induction there were more muscle tremors after alfaxalone. As there were no differences between treatments in relation to cardiopulmonary responses or quality of recovery, and only minor differences in recovery times, both agents appear suitable for this purpose following the premedication regimen used in this study.

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

OBJECTIVE: To 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 DESIGN: Prospective experimental study. ANIMALS: Ten (five male and five female), adult, healthy, Standardbred horses. METHODS: Horses 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). RESULTS: The 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 RELEVANCE: Alfaxalone, 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.

An updated method for the jugular catheterization of grower pigs for repeated blood sampling following an oral glucose tolerance test.

Jugular catheterization is a common procedure used under experimental conditions. However, there is considerable variation in the reported techniques, particularly for grower pigs (>40 kg and <60 kg) when larger volumes of blood per sample (>10 mL) are required. This paper provides a complete methodology including the use of current equipment and anaesthetic regimen for grower pigs. This surgical jugular catheterization method was carried out in 30 large white grower pigs. Firstly, the pigs were habituated to human handling for at least two weeks prior to surgery. Animals were sedated and anesthetized. Following intubation, an incision was made in the jugular fossa, and the jugular vein was located. A catheter was then inserted and fixated. The wound was stapled and the catheter line secured to the back of the neck. The pigs recovered fully from the surgery and the catheters remained patent for the duration of the blood sampling period (min 72 h). Twenty millilitres of blood were collected every 15 min, taking approximately 2 min per pig. No haemolysis was detected in any samples. Jugular catheterization of pigs using this procedure proved successful both in terms of animal recovery and quality of samples. Catheters remained patent and pigs remained calm during sampling.

A systematic review of the effects of euthanasia and occupational stress in personnel working with animals in animal shelters, veterinary clinics, and biomedical research facilities.

BACKGROUND: The study of occupational stress and compassion fatigue in personnel working in animal-related occupations has gained momentum over the last decade. However, there remains incongruence in understanding what is currently termed compassion fatigue and the associated unique contributory factors. Furthermore, there is minimal established evidence of the likely influence of these conditions on the health and well-being of individuals working in various animal-related occupations. OBJECTIVE: To assess currently available evidence and terminology regarding occupational stress and compassion fatigue in personnel working in animal shelters, veterinary clinics, and biomedical research facilities. DATA SOURCE: Studies were identified by searching the following electronic databases with no publication date restrictions: ProQuest Research Library, ProQuest Social Science Journals, PsycARTICLES, Web of Science, Science Direct, Scopus, PsychINFO databases, and Google Scholar. Search terms included (euthanasia AND animals) OR (compassion fatigue AND animals) OR (occupational stress AND animals). STUDY APPRAISAL AND SYNTHESIS: Only articles published in English in peer-reviewed journals that included use of quantitative or qualitative techniques to investigate the incidence of occupational stress or compassion fatigue in the veterinary profession or animal-related occupations were included. On the basis of predefined criteria, 1 author extracted articles, and the data set was then independently reviewed by the other 2 authors. RESULTS: 12 articles met the selection criteria and included a variety of study designs and methods of data analysis. Seven studies evaluated animal shelter personnel, with the remainder evaluating veterinary nurses and technicians (2), biomedical research technicians (1), and personnel in multiple animal-related occupations (2). There was a lack of consistent terminology and agreed definitions for the articles reviewed. Personnel directly engaged in euthanasia reported significantly higher levels of work stress and lower levels of job satisfaction, which may have resulted in higher employee turnover, psychological distress, and other stress-related conditions. LIMITATIONS AND CONCLUSIONS: Results of this review suggested a high incidence of occupational stress and euthanasia-related strain in animal care personnel. The disparity of nomenclature and heterogeneity of research methods may contribute to general misunderstanding and confusion and impede the ability to generate high-quality evidence regarding the unique stressors experienced by personnel working with animals. The present systematic review provided insufficient foundation from which to identify consistent causal factors and outcomes to use as a basis for development of evidence-based stress management programs, and it highlights the need for further research.

Soluble arabinoxylan alters digesta flow and protein digestion of red meat-containing diets in pigs.

OBJECTIVES: The aim of this study was to investigate how a moderate increase in dietary meat content combined (or not) with soluble fibre would influence protein digestion as well as digesta characteristics and flow. METHODS: Four groups of pigs were fed Western-style diets (high-protein/high-fat) containing two types of barbecued red meat, one with and one without a wheat arabinoxylan-rich fraction. After 4 wk, digesta samples were collected from small and large intestinal sites and analyzed for protein, amino acids, dry matter, and acid-insoluble ash. Tissue samples were also collected from each site. RESULTS: Arabinoxylan consumption led to somewhat lower apparent protein digestibility within the small and large intestines as well as shorter mean retention times. This suggests that the lowered protein digestibility is due, at least partly, to shorter access time to digestive proteases and absorptive surfaces. Additionally, digesta mass was higher in pigs fed arabinoxylan while dry matter (%) was lower, indicating an increased digesta water-holding capacity due to the presence of a soluble dietary fiber. CONCLUSION: Data showed that solubilized wheat arabinoxylan provides potential health benefits through decreased protein digestibility, increased digesta mass, and reduced mean retention time, even for diets with a moderately higher protein content. These factors are associated with efficiency of digestion and satiety, both of which have implications for prevention of obesity and other health disorders.

Elongate microparticles for enhanced drug delivery to ex vivo and in vivo pig skin.

The delivery of therapeutics and cosmaceuticals into and/or through the skin is hindered by epidermal barriers. To overcome the skin's barriers we have developed a novel cutaneous delivery method using high aspect ratio elongate microparticles (EMPs). Using ex vivo and in vivo pig skin we assess the penetration and delivery characteristics of the elongate microparticles. With reflectance confocal microscopy we observed that the elongate microparticles successfully penetrated the epidermis and upper dermis. Delivery was then assessed using two different length populations of EMPs, comparing their delivery profile to topical alone using sodium fluorescein and confocal microscopy. We observed a relatively uniform and continuous delivery profile in the EMP treated area within the upper layers of the skin--up to seven times greater than topical alone. Finally, we delivered two therapeutically relevant compounds (Vitamins A and B3), showing enhanced delivery using the EMPs. To our knowledge this is the first report using high aspect ratio elongate microparticles in this manner for enhanced topical delivery to the skin.

A pig model of the preterm neonate: anthropometric and physiological characteristics.

BACKGROUND: Large animal models are an essential tool in the development of rationally-based new clinical therapies for preterm infants. We provide a description of the newborn pig as a model of the preterm neonate in terms of growth parameters, physiology and the requirement for intensive care over a range of gestational ages. METHODS: Twenty-nine litters of piglets (n = 298) were delivered by caesarean section at six timepoints during gestation from 91d to 113d (term = 115d). Two groups, at 91 and 97d gestation, also received maternal glucocorticoid treatment. At four of these timepoints, piglets (n = 79) were ventilated, sedated and monitored using standard neonatal intensive care techniques for up to 8 h in various experimental protocols. RESULTS: Body weight increased from mean 697 g (SD 193) at 91d gestation to 1331 g (SD 368) at 113d gestation. Piglets delivered at 97d gestation were able to be resuscitated and kept alive for at least 8 h on respiratory support after surfactant administration. Maternal glucocorticoid treatment 48 h and 24 h hours prior to delivery reduced the requirement for ventilator support and improved cardiovascular stability. CONCLUSION: The pig provides a relevant model for the study of human preterm physiology and for investigation of novel therapies to improve outcomes.