Alfaxalone for total intravenous anaesthesia in horses

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.Prospective, experimental study.Eight Standardbred horses.Horses were premedicated with IV acepromazine (0.03 mg kg) and xylazine (1 mg kg) and anaesthesia was induced with guaifenesin (35 mg kg) and alfaxalone (1 mg kg). 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.The median (range) alfaxalone infusion rate was 3.1 (2.4-4.3) mg kg hour. The mean ± standard deviation plasma elimination half-life, plasma clearance and volume of distribution for alfaxalone were 41 minutes, 25 ± 6.3 mL minute kg and 1.6 ± 0.5 L kg, 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).Anaesthesia in horses can be maintained with an infusion of alfaxalone at approximately 3 mg kg hour. 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

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

An investigation of the prevalence of compassion fatigue, compassion satisfaction and burnout in those working in animal-related occupations using the Professional Quality of Life (ProQoL) Scale

Background: Animal-related occupational stress and compassion fatigue are important issues as they can have a negative impact on employee mental wellbeing, workplace productivity and morale. The impacts of these conditions are notable and have become more recognised by those who are employed in animal-related occupations. Aims: This study aims to investigate the incidence of compassion satisfaction and compassion fatigue (burnout and secondary traumatic stress) in those working in animal-related occupations using the Professional Quality of Life (ProQoL) Scale. Methods: Data were collected from 229 employees from a range of animal-related occupations using an anonymous self-report survey. Results: Most respondents were employed in veterinary practice (either veterinarians or veterinary nurses/ technicians) and 85% of all respondents were female. 42% of participants were between 26 and 35 years of age and, 71% had been working in animal-related occupations between 1 and 10 years. Most participants scored in the mean or top quartile on the compassion satisfaction scale; however, about a quarter reported a score which indicated that they were deriving less satisfaction from their work. Low burnout was reported by 78% of participants; however, 21% of participants had a score which indicated that they were at higher risk of burnout. Low or average symptoms of secondary traumatic stress was reported by 74% of participants; however, 25.8% were at risk of secondary traumatic stress. While most of the surveyed population scored in the mean or top quartile on the compassion satisfaction scale, all of the occupational categories reported experiencing the negative aspects of caring: burnout and secondary traumatic stress. Conclusion: The prevalence of compassion fatigue demonstrated in these results should be a major concern in animal-related occupations and thus, be used as a beneficial, contextualised resource to inform resilience training programmes and preventative strategies specifically targeted towards those working in animal-related occupations

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 Sources—Studies were identified by searching the following electronic databases with no publication date restrictions: ProQuest Research Library, ProQuest Social Science Journals, Psyc ARTICLES, 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

Intraarticular and periarticular opioid binding in inflamed tissue in experimental canine arthritis

Small-dose (1 mg) intraarticular morphine has been used successfully in many studies to provide long-lasting analgesia after arthroscopic knee surgery. We used radioligand binding to determine whether these effects could be mediated by opioid binding sites in the joint, particularly after the induction of inflammation. Inflammation was induced by the injection of oleyl alcohol (20 µL) in sterile peanut oil (0.25 mL) into the left radiocarpal joint of 27 dogs, and the dogs were euthanized at 12 h. The articular and periarticular tissues from both treated and control joints were collected, and membranes were prepared for equilibrium binding assays. The density of specific opioid binding was markedly enhanced (P < 0.05) in homogenates prepared from the treated relative to those from the control joint. The binding affinities (KD values) for morphine and naloxone (mean ± SEM) were approximately one one-hundredth (79 ± 17 nM and 124 ± 5.5 nM, respectively) that of the corresponding published affinities in brain tissue. However, the binding site densities were approximately one hundred times larger (Bmax = 1032 ± 265 and 543 ± 51 fmol/mg of protein) than the respective published values in brain tissue. These findings imply that the opioid binding sites, found in the inflamed articular and periarticular tissues in this study, are similar to those of putative µ3-opioid binding sites that appear to be present on cultured thymocytes and in the airways of rats and humans. Implications: The high density of opioid binding sites found in inflamed canine joint tissue supports the clinical use of intraarticular opioids in the treatment of postoperative and chronic inflammatory joint pain

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 (PaO2) and carbon dioxide (PaO2), 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 (2447) minutes for alfaxalone; 22 (1835) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (3867) minutes] compared with ketamine [35 (3047)]. There was no statistical difference between treatments in effect on HR, PaO2 or PaCO2 although for both regimens, PaO2 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

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

Objective To 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 design Prospective experimental study. Animals Five clinically healthy Australian Stock Horse foals of mean±SD age of 12±3days and weighing 67.3±12.4kg. Methods Foals were premedicated with butorphanol (0.05mgkg IV) and anaesthesia was induced 10minutes later by IV injection with alfaxalone 3mgkg. 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. Results The harmonic, mean±SD plasma elimination half life (t1/2) for alfaxalone was 22.8±5.2minutes. The observed mean plasma clearance (Cl) and volume of distribution (Vd) were 19.9±5.9mLminutekg and 0.6± 0.2Lkg, 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±4.7minutes, respectively. Conclusions The 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 relevance Alfaxalone 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. © 2012 The Authors. Veterinary Anaesthesia and Analgesia

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 (0.03mgkg IV). Twenty minutes later they received xylazine (1mgkg IV), then after 5 minutes, guaiphenesin (35mgkg IV) followed immediately by IV induction of anaesthesia with alfaxalone (1mgkg). 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), plasma clearance (Clp) and volume of distribution (V) for alfaxalone were 33.4minutes, 37.1±11.1mLminutekg and 1.6±0.4 Lkg, 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. © 2011 The Authors. Veterinary Anaesthesia and Analgesia

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

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 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