Elizabeth Armitage-Chan

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti-Inflammatory Response, and Regulatory T Cells

Sepsis, the systemic inflammatory response to infection, represents the major cause of death in critically ill veterinary patients. Whereas important advances in our understanding of the pathophysiology of this syndrome have been made, much remains to be elucidated. There is general agreement on the key interaction between pathogen‐associated molecular patterns and cells of the innate immune system, and the amplification of the host response generated by pro‐inflammatory cytokines. More recently, the concept of immunoparalysis in sepsis has also been advanced, together with an increasing recognition of the interplay between regulatory T cells and the innate immune response. However, the heterogeneous nature of this syndrome and the difficulty of modeling it in vitro or in vivo has both frustrated the advancement of new therapies and emphasized the continuing importance of patient‐based clinical research in this area of human and veterinary medicine.

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

OBJECTIVE To evaluate the clinical efficacy and cardiorespiratory effects of alfaxalone as an anaesthetic induction agent in dogs with moderate to severe systemic disease. STUDY DESIGN Randomized prospective clinical study. ANIMALS Forty dogs of physical status ASA III-V referred for various surgical procedures. METHODS Dogs 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). RESULTS Treatment 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 RELEVANCE Induction 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.

Phenotypic and functional characterization of a CD4(+) CD25(high) FOXP3(high) regulatory T-cell population in the dog

Relatively little is known about regulatory T (Treg) cells and their functional responses in dogs. We have used the cross‐reactive anti‐mouse/rat Foxp3 antibody clone FJK‐16s to identify a population of canine CD4+ FOXP3high T cells in both the peripheral blood (PB) and popliteal lymph node (LN). FOXP3+ cells in both PB and LN yielded positive staining with the newly developed anti‐murine/human Helios antibody clone 22F6, consistent with the notion that they were naturally occurring Treg cells. Stimulation of mononuclear cells of LN origin with concanavalin A (Con A) in vitro yielded increased proportions and median fluorescence intensity of FOXP3 expression by both CD4+ and CD8+ T cells. Removal of the Con A and continued culture disclosed a CD4+ FOXP3high population, distinct from the CD4+ FOXP3intermediate T cells; very few CD8+ FOXP3high T cells were observed, though CD8+ FOXP3intermediate cells were present in equal abundance to CD4+ FOXP3intermediate cells. The CD4+ FOXP3high T cells were thought to represent activated Treg cells, in contrast to the FOXP3intermediate cells, which were thought to be a more heterogeneous population comprising predominantly activated conventional T cells. Co‐staining with interferon‐γ (IFN‐γ) supported this notion, because the FOXP3high T cells were almost exclusively IFN‐γ−, whereas the FOXP3intermediate cells expressed a more heterogeneous IFN‐γ phenotype. Following activation of mononuclear cells with Con A and interleukin‐2, the 5% of CD4+ T cells showing the highest CD25 expression (CD4+ CD25high) were enriched in cells expressing FOXP3. These cells were anergic in vitro, in contrast to the 20% of CD4+ T cells with the lowest CD25 expression (CD4+ CD25−), which proliferated readily. The CD4+ CD25high FOXP3high T cells were able to suppress the proliferation of responder CD4+ T cells in vitro, in contrast to the CD4+ CD25− cells, which showed no regulatory properties.

Anaphylaxis and anaesthesia

Anaphylaxis is defined as ‘a severe life-threatening, generalised or systemic hypersensitivity reaction’.1 The recent 6th National Audit Project (NAP6) in the United Kingdom (UK) defined perioperative anaphylaxis as ‘anaphylaxis which occurs in patients undergoing a procedure requiring general or regional anaesthesia or sedation or managed anaesthesia care (anaesthesia monitoring only) under the care of an anaesthetist between the period of first administration of a drug (including premedication) and the post-procedure transfer to a ward, or critical care’.2 This short narrative review will discuss the recent NAP6 results in the context of current knowledge, as relevant to the South African anaesthetist.

The risk of passive regurgitation during general anaesthesia in a population of referred dogs in the UK.

OBJECTIVE To evaluate the risk of passive regurgitation during anaesthesia, and to identify major factors associated with this in dogs attending the Queen Mother Hospital for Animals (QMHA), the Royal Veterinary College. STUDY DESIGN A case-control study nested within the cohort of dogs undergoing anaesthesia with inhalation agents. ANIMAL POPULATION All dogs undergoing general anaesthesia at the referral hospital between October 2006 and September 2008 (4271 cases). METHODS All dogs anaesthetized at the QMHA during the study period were included. Regurgitating cases were defined as dogs for which reflux material was observed at the external nares or in the mouth, either during anaesthesia or before return to normal consciousness immediately after general anaesthesia. The risk of regurgitation was estimated and risk factors for regurgitation were evaluated with multivariable logistic regression (p < 0.05). RESULTS The overall risk of regurgitation was 0.96% (41 cases out of 4271 anaesthetics, 95% confidence interval [95% CI] 0.67-1.25%). Exclusion of animals where pre-existing disease was considered a contributing factor to regurgitation (n = 14) resulted in a risk of passive regurgitation of 0.63% (27 cases of 4257 anaesthetics, 95% CI 0.40-0.87%). In the multivariable logistic regression model, procedure and patient weight were significantly associated with regurgitation. Dogs undergoing orthopaedic surgery were 26.7 times more likely to regurgitate compared to dogs undergoing only diagnostic procedures. Dogs weighing more than 40 kg were approximately five times more likely to regurgitate than those weighing <20 kg. CONCLUSIONS AND CLINICAL RELEVANCE This study highlights the rare but important occurrence of perioperative regurgitation and identifies that dogs undergoing orthopaedic procedures, and those weighing more than 40 kg, are particularly at risk. Further work is required to evaluate the reasons for these observations.

A comparison of epidural morphine with low dose bupivacaine versus epidural morphine alone on motor and respiratory function in dogs following splenectomy.

OBJECTIVE To compare post-operative motor function in dogs that received epidural morphine and low dose bupivacaine versus epidural morphine alone following splenectomy. STUDY DESIGN Prospective, randomized study. ANIMALS 16 client owned dogs undergoing routine splenectomy. METHODS Following splenectomy dogs were randomly allocated into one of two groups. The morphine group (MOR) was administered epidural morphine (0.1 mg kg(-1)); the morphine-bupivacaine group (MORB) received epidural morphine (0.1 mg kg(-1)) and low dose bupivacaine [0.25 mg kg(-1), (0.167%)]. The adjusted final volume was 0.15 mL kg(-1) in both groups. Motor function and pain assessment were performed at pre-determined times using a simple numerical motor score and the University of Melbourne Pain Scale (UMPS) respectively. An arterial blood gas was performed 2 hours following epidural administration to check for respiratory compromise. If patients scored >7 on the UMPS or were deemed painful by the observer they were administered hydromorphone intravenously and dose and time of rescue analgesia were recorded. RESULTS There were no statistically significant differences in motor scores, pain scores, amount of rescue analgesia administered or PaCO2 between treatment groups. No dogs demonstrated respiratory depression or profound motor dysfunction at any time point during the study. 9/16 (56%) dogs did not require rescue analgesia during the first 18 hours following splenectomy. CONCLUSIONS AND CLINICAL RELEVANCE The combination of low dose bupivacaine (0.25 mg kg(-1)) and morphine (0.1 mg kg(-1)) when administered epidurally has little effect on post-operative motor function. This combination can be used without concern of motor paralysis in healthy animals.

What is the veterinary professional identity? Preliminary findings from web-based continuing professional development in veterinary professionalism

Professionalism and professional skills are increasingly being incorporated into veterinary curricula; however, lack of clarity in defining veterinary professionalism presents a potential challenge for directing course outcomes that are of benefit to the veterinary professional. An online continuing education course in veterinary professionalism was designed to address a deficit in postgraduate support in this area; as part of this course, delegates of varying practice backgrounds participated in online discussions reflecting on the implications of professional skills for their clinical practice. The discussions surrounding the role of the veterinary professional and reflecting on strengths and weaknesses in professional skills were analysed using narrative methodology, which provided an understanding of the defining skills and attributes of the veterinary professional, from the perspectives of those involved (i.e. how vets understood their own career identity). The veterinary surgeon was understood to be an interprofessional team member, who makes clinical decisions in the face of competing stakeholder needs and works in a complex environment comprising multiple and diverse challenges (stress, high emotions, financial issues, work–life balance). It was identified that strategies for accepting fallibility, and those necessary for establishing reasonable expectations of professional behaviour and clinical ability, are poorly developed.

Uterine rupture and septic peritonitis following dystocia and assisted delivery in a Great Dane bitch.

A Great Dane bitch was treated for presumed primary uterine inertia with repeated doses of oxytocin and manually assisted whelping. She was diagnosed with uterine rupture and septic peritonitis the following day. The uterine rupture is hypothesized to have occurred as a result of the management strategy used to treat dystocia. The dog underwent ovariohysterectomy, and the septic peritonitis was managed with open peritoneal drainage. The dog recovered well and was discharged 5 days later. No previous reports of canine uterine rupture associated with manual intervention appear to have been published. This report highlights the potential dangers involved in such an approach.

Career aspiration in UK veterinary students: the influences of gender, self-esteem and year of study

It is widely reported that the veterinary profession is becoming increasingly female-dominated, but there are concerns that this is not represented in positions of leadership. Although there are well-documented data describing the under-representation of women in various senior veterinary positions (academic deans, practice owners, positions on professional councils and corporate boards), it is less clear why this occurs. Although likely multifactorial, the relative contributions from a gender divide in intent to pursue leadership positions, women being dissuaded from considering senior roles, or differences in success rate (e.g. in leadership appointments), are unknown. This study was performed to investigate whether there is a gender divide among veterinary students in intent to pursue a leadership role and also to explore other influencing factors in career aspiration in veterinary students. Students from five UK veterinary schools were surveyed using an electronically distributed questionnaire. Career aspiration and leadership ambition were identified as being influenced by gender, with a greater proportion of male students (83 per cent) than female students (73 per cent) indicating they aspired to owning a practice. Career aspiration was also positively influenced by self-esteem, confidence and previously holding a position in the students’ union or other club or society; however, all of these were also more apparent in male students than female students. Career aspiration also appeared to be influenced by year of study, with a decline seen at each increasing student year group, and this was unrelated to gender or self-esteem.

Identity, environment and mental wellbeing in the veterinary profession

Mental health and career dissatisfaction are of increasing concern to the veterinary profession. The influence of identity on the psychological wellbeing of veterinarians has not been widely explored. Twelve recent veterinary graduates were enrolled in a private social media discussion group, and their identities investigated through narrative inquiry: a methodology which enables identity priorities to be extrapolated from stories of experience. Two distinct variants of the veterinary identity were identified: an academic, ‘diagnosis-focused’ identity, which prioritised definitive diagnosis and best-evidence treatment; and a broader ‘challenge-focused’ identity, where priorities additionally included engaging with the client, challenging environment or veterinary business. Contextual challenges (such as a client with limited finances or difficult interpersonal interactions) were seen as a source of frustration for those with a diagnosis-focused identity, as they obstructed the realisation of identity goals. Overcoming these challenges provided satisfaction to those with a challenge-focused identity. The employment environment of the graduates (general veterinary practice) provided more opportunities for those with a challenge-focused identity to realise identity goals, and more markers of emotional wellbeing were apparent in their stories. Markers of poor emotional health were evident in the stories of those with a diagnosis-focused identity.