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Modern veterinary medicine offers numerous options for treatment and clinicians must decide on the best one to use. Interventions causing short-term harm but ultimately benefitting the animal are often justified as being in the animal's best interest. Highly invasive clinical veterinary procedures with high morbidity and low success rates may not be in the animal's best interest. A working party was set up by the European College of Veterinary Anaesthesia and Analgesia to discuss the ethics of clinical veterinary practice and improve the approach to ethically challenging clinical cases. Relevant literature was reviewed. The 'best interest principle' was translated into norms immanent to the clinic by means of the 'open question argument'. Clinical interventions with potential to cause harm need ethical justification, and suggest a comparable structure of ethical reflection to that used in the context of in vivo research should be applied to the clinical setting. To structure the ethical debate, pertinent questions for ethical decision-making were identified. These were incorporated into a prototype ethical tool developed to facilitate clinical ethical decision-making. The ethical question 'Where should the line on treatment be drawn' should be replaced by 'How should the line be drawn?'

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BACKGROUND: The interaction between type 1 diabetes mellitus (T1DM) and attention deficit hyperactivity disorder (ADHD) in children and adolescents has been studied rarely. We aimed to analyse metabolic control in children and adolescents with both T1DM and ADHD compared to T1DM patients without ADHD. PATIENTS AND METHODS: Auxological and treatment data from 56.722 paediatric patients (<20 years) with T1DM in the multicentre DPV (Diabetes Prospective Follow-up Initiative) registry were analysed. T1DM patients with comorbid ADHD were compared to T1DM patients without ADHD using multivariable mixed regression models adjusting for demographic confounders. RESULTS: We identified 1.608 (2.83%) patients with ADHD, 80.8% were male. Patients with comorbid ADHD suffered twice as often from diabetic ketoacidosis compared to patients without ADHD [10.2; 9.7-10.8 vs [5.4; 5.3-5.4] (P < .0001). We also found significant differences in HbA1c [8.6% (7.3-9.4); 66.7 mmol/mol (56.3-79.4) vs 7.8% (7.0-9.0); 62.1 mmol/mol (53.2-74.7)], insulin dose/kg [0.9 IU/kg (0.7-1.1) vs 0.8 IU/kg (0.7-1.0)], body mass index-standard deviation score (BMI-SDS) [0.2 (-0.5 to 0.8) vs 0.3 (-0.3 to 0.9)], body weight-SDS [0.1 (-0.5 to 0.8) vs 0.3 (0.3 - 0.9)]; (all P < 0.0001), and systolic blood pressure after adjustment [mean: 116.3 vs 117.1 mm Hg)]; (P < 0.005). CONCLUSION: Paediatric patients with ADHD and T1DM showed poor metabolic control compared to T1DM patients without ADHD. Closer cooperation between specialized paediatric diabetes teams and paediatric psychiatry/psychology seems to be necessary to improve diabetes care and metabolic control in this group of patients.

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BACKGROUND: To investigate changes in diabetes treatment over the last two decades in three age-groups of children and adolescents with type 1 diabetes (T1D) from Germany and Austria. METHODS: 63,967 subjects (<18yr) with T1D documented between 1995 and 2014 from the DPV-database were included and stratified according to age (0.5-<6, 6-<12, 12-<18yr). Regression models were applied for insulin regimens (<3 and ≥4 injection time points/day, or continuous subcutaneous insulin infusion (CSII)), use of rapid- and long acting insulin analogues, NPH insulin, and frequency of self-monitoring of blood glucose (SMBG)/day. Models were adjusted for sex, diabetes duration, and migration background. P-value for trend was given. FINDINGS: The number of subjects with <3 injection time points/day decreased from 1995 to 2014 to <5% in all age-groups (p<0.0001). Proportion of patients with ≥4 injections/day increased until the early 2000s, and then declined until 2014. This trend was not found in 6-<12yr olds (p = 0.3403). CSII increased in all age-groups (p<0.0001) with the highest increase in children <6 years (from 0.4% to 79.2%), and the lowest increase in 12-<18 year olds (from 1.0% to 38.9%). NPH insulin decreased in all age-groups (p<0.0001). Insulin analogues, especially rapid-acting, became more frequent in all age-groups (p<0.0001), accounting for 78.4% in 2014 for all subjects. The highest use was found in the youngest children (in 2014: 85.6%), the lowest use in 6-<12 year olds (in 2014: 72.9%). The number of SMBG/day increased from 2.2 to 6.4 with a similar rise in all age-groups (p<0.0001). Frequency was highest in subjects <6yr. CONCLUSIONS: In all age-groups, T1D treatment was intensified over the last 20 years. Age-specific differences in trends were particularly observed in the number of patients on CSII, in the number of patients with 4 or more injections/day, and in the frequency of SMBG/day.

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The electroencephalogram (EEG) Narcotrend index (NI) has been shown to improve anaesthetic depth monitoring in isoflurane-anaesthetised sheep. Data obtained from 13 anaesthetised juvenile female sheep were analysed retrospectively in order to assess the relationship between clinical stages of anaesthesia (CS) and NI during both propofol and isoflurane anaesthesia. Polynomial regression analysis revealed no significant association between CS and NI for propofol (R = 0.374, R(2) = 0.140, P = 0.403) but for isoflurane anaesthesia (R = 0.548, R(2) = 0.301, P = 0.010) there was a significant relationship. Furthermore, a strong correlation existed between end-tidal isoflurane concentration (ISOET) and CS (r = -0.463, P = 0.008). A combination of assessment of clinical signs and analogous EEG patterns is recommended during propofol anaesthesia.

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OBJECTIVE: To review the beneficial and adverse effects of therapeutic hypothermia (TH) applicable to cardiac surgery with cardiopulmonary bypass (CPB) in the contexts of various temperature levels and techniques for achieving TH. DATABASES USED: Multiple electronic literature searches were performed using PubMed and Google for articles published from June 2012 to December 2014. Relevant terms (e.g. 'hypothermia', 'cardiopulmonary bypass', 'cardiac surgery', 'neuroprotection') were used to search for original articles, letters and reviews without species limitation. Reviews were included despite potential publication bias. References from the studies identified were also searched to find other potentially relevant citations. Abstracts, case reports, conference presentations, editorials and expert opinions were excluded. CONCLUSIONS: Therapeutic hypothermia is an essential measure of neuroprotection during cardiac surgery that may be achieved most effectively by intravascular cooling using hypothermic CPB. For most cardiac surgical procedures, mild to modest (32-36 °C) TH will be sufficient to assure neuroprotection and will avoid most of the adverse effects of hypothermia that occur at lower body core temperatures.

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CONTEXT: The predictive value of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR) to define cardiometabolic risk is unclear in childhood obesity. OBJECTIVE: [corrected] The associations between BMI, WtHR, or WC and cardiometabolic risk markers were analyzed in a multicenter data collection of obese youth. DESIGN AND SUBJECTS: BMI, WtHR, and WC were retrospectively evaluated in 1278 patients (11-18 years, 53% boys) from the German/Austrian/Swiss Adiposity Patients Registry. MAIN OUTCOME MEASURES: Parameters were correlated with homeostasis model assessment for insulin resistance, fasting insulin, blood pressure, transaminases, lipids and uric acid, applying adjusted regression models, with age group, pubertal stage and gender as covariates. RESULTS: Homeostasis model assessment for insulin resistance and fasting insulin were most strongly correlated with BMI, independent of age group or gender. Lipids, transaminases, and uric acid were most strongly correlated with WC with stronger associations for boys. Correlations between BMI and WC as well as metabolic markers and systolic blood pressure showed only minor differences. The pattern of relationship changed during the course of pubertal development with the strongest associations for pubertal children. None of the parameters showed a dependency on WtHR that was superior to BMI or WC. CONCLUSIONS: There is only small additional benefit in using WC measurements for routine pediatric care in addition to BMI for predicting metabolic risk. For all parameters, the relationship is strongest during midpuberty, emphasizing that among obese pubertal adolescents, anthropometric measures (BMI and WC) best predict cardiometabolic comorbidities. WtHR does not seem to be superior to BMI or WC in predicting metabolic or cardiovascular risk related to childhood obesity.

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OBJECTIVE: To evaluate the influence of various anesthetic protocols and 3 multiples of isoflurane minimum alveolar concentration (MAC) before and after supramaximal stimulation on electroencephalographic (EEG) variables in dogs. ANIMALS: 6 healthy adult Beagles (mean ± SD body weight, 16.3 ± 1.0 kg). PROCEDURES: All dogs underwent 3 anesthesia sessions with a minimum of 1 week separating sessions: isoflurane alone, isoflurane and a constant rate infusion of dexmedetomidine (3 µg/kg/h, IV; ID), and isoflurane and a constant rate infusion of remifentanil (18 µg/kg/h, IV; IR). The MAC of isoflurane was determined via supramaximal electrical stimulation. Quantitative variables (frequency bands and their ratios, median frequency, 95% spectral edge frequency [SEF], and an EEG index) were determined directly before and after supramaximal stimulation at 0.75, 1.0, and 1.5 times the MAC for each session of 20-second epochs. RESULTS: Mean ± SD isoflurane MACs for isoflurane alone, ID, and IR were 1.7 ± 0.3%, 1.0 ± 0.1%, and 1.0 ± 0.1%, respectively. Prestimulation 95% SEF decreased significantly with increasing MAC during the isoflurane alone and ID sessions. Significant decreases in δ frequency band (0.5 to 3.5 Hz) presence and significant increases in ß frequency band (> 12.5 Hz) presence, median frequency, and 95% SEF after stimulation were dependent on the MAC and anesthetic protocol. The EEG index had the strongest correlation with increasing MAC during the isoflurane-alone session (ρ = -0.89) and the least in the IR session (ρ = -0.15). CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia with isoflurane alone resulted in the greatest overall EEG depression of all protocols. Use of remifentanil depressed the EEG response to nociceptive stimulation more strongly than did dexmedetomidine. The EEG variables evaluated did not appear useful when used alone as indicators of anesthetic depth in dogs.

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In order to provide objective measures of anaesthetic depth for periods without clinical signs (e.g., cardiopulmonary bypass [CPB]), the correlation between the electroencephalographic Narcotrend index (NI), 95% spectral edge frequency (SEF95), median power frequency (MPF) and clinical stages of anaesthesia was investigated in 16 juvenile sheep. Data were recorded during recovery from anaesthesia for pulmonary or aortic valve replacement. A significant (P<0.05) negative correlation was found between clinical stages of anaesthesia and NI (r(s) = -0.534) and SEF95 (r(s) = -0.543). No significant correlation existed between anaesthetic stages and MPF (r(s) = -0.292, P>0.05). The sensitivity of NI, SEF95 and MPF to assure an adequate level of anaesthesia was 71.43%, 66.67% and 44.44%, respectively, while the specificity of the descriptors ranged between 97.44 and 92.31%. No significant age-related effect on EEG data and stages of anaesthesia was detected when data from sheep between 4 and 6 months of age were compared with data obtained from 8- to 12-month old sheep. In conclusion, NI seems to be the most appropriate EEG descriptor to assure adequate depth of anaesthesia in juvenile, isoflurane-anaesthetized sheep.

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OBJECTIVE: To estimate the prevalence of epilepsy and possible risk factors in children and adolescents with diabetes mellitus. STUDY DESIGN: We conducted an observational cohort study based on the Diabetes Patienten Verlaufsdokumentation database including data from 45 851 patients (52% male) with type 1 diabetes mellitus, age 13.9 ± 4.3 years (mean ± SD) and duration of diabetes mellitus 5.4 ± 4.2 years. The database was searched for the concomitant diagnosis of epilepsy or epileptic convulsions and for antiepileptic medication. RESULTS: A total of 705 patients with epilepsy were identified, giving a prevalence of 15.5 of 1000. A total of 375 patients were treated with antiepileptic medication, and 330 patients were without anticonvulsive therapy. Patients with epilepsy were younger at onset of diabetes mellitus and shorter than patients without epilepsy, and their weight and body mass index were comparable. No difference could be demonstrated for metabolic control, type of insulin treatment, insulin dose, and prevalence of B-cell specific autoantibodies. The frequency of severe hypoglycemia was lower in patients treated with antiepileptic medication. The risk for diabetic ketoacidosis was almost double in patients with epilepsy compared with patients with type 1 diabetes mellitus alone (P < .01). CONCLUSION: Children and adolescents with diabetes mellitus show an increased prevalence of epileptic seizures. For unknown reasons, there is an association between epilepsy and diabetic ketoacidosis in children with type 1 diabetes mellitus.

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Isolation of lungs from the circulation during cardiopulmonary bypass (CPB) results in the loss of end-tidal anaesthetic measurement as a monitor of anaesthetic depth. The objective of our study was to test whether the isoflurane concentration measured at the oxygenator exhaust (ISO(PO-OX)) could be used as an alternative. Five juvenile ewes were anaesthetised for experimental aortic valve replacement during hypothermic CPB. One sheep recovered from anaesthesia with signs of CNS excitement and was excluded from electroencephalogram (EEG) data analysis. ISO(PO-OX) was similar to the end-tidal anaesthetic concentration measured before start of CPB (ISO(ET(PRE-CPB))) and was positively correlated (P<0.001; R=0.431) to the bypass temperature (T(CPB)). EEG burst suppression ratio was negatively correlated with the oesophageal temperature (T(ESO)) (P=0.002; R=0.433) whilst data analysis revealed only a weak association between EEG variables and ISO(PO-OX). Therefore, EEG monitoring may be the only valuable quantitative measure of adequate anaesthetic depth during hypothermic CPB.

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The first attempts to introduce computerized power spectrum analysis of the electroencephalogram (EEG) as an intraoperative anaesthesia monitoring device started approximately 30 years ago. Since that time, the effects of various anaesthetic agents, sedative and analgesic drugs on the EEG pattern have been addressed in numerous studies in human patients and different animal species. These studies revealed dose-dependent changes in the EEG power spectrum for many intravenous and volatile anaesthetics. Moreover, EEG responses evoked by surgical stimuli during relative light levels of surgical anaesthesia have been classified as 'arousal' and 'paradoxical arousal' reaction, previously referred to as 'desynchronization' and 'synchronization', respectively. Contrasting reports on the correlation between quantitative EEG (QEEG) variables derived from power spectrum analysis (i.e. spectral edge frequency, median frequency) and simultaneously recorded clinical signs such as movement and haemodynamic responses, however, limited the routine use of intraoperative EEG monitoring. In addition, the appearance of EEG burst suppression pattern and isoelectricity at clinically relevant concentrations/doses of newer general anaesthetics (i.e. isoflurane, sevoflurane, propofol) may have weakened the dose-related EEG changes previously reported. Despite these findings, the EEG power spectrum analysis may still provide valuable information during intraoperative monitoring in the individual subject. The information obtained from EEG power spectrum analysis may be further supplemented by newer EEG indices such as bispectral index and approximate entropy or other neurophysiological monitors including auditory evoked potentials or somatosensory evoked potentials.

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The effects of averaging epochs on electroencephalographic (EEG) responses to visceral stimulation has been determined in seven isoflurane-anaesthetized dogs. Quantitative EEG variables including 80% spectral edge frequency (SEF80), median frequency (MF), relative power in the delta, theta, alpha, beta band and power band ratios (theta/delta, alpha/delta, beta/delta) were recorded over 1min before stimulation and during a 1-minute stimulation period. During off-line analysis EEG variables were derived from either single 2-second EEG epochs or as an average from 5, 10, 15 and 30 consecutive 2-second epochs. Noxious stimulation resulted in significant increases in SEF80, MF, alpha power, beta power, alpha/delta ratio and beta/delta ratio. The number of variables that were significantly affected as well as the strength of changes as indicated by p-values, however, varied with the number of epochs subjected to averaging. The data suggest that stimulation-induced EEG changes may be more pronounced at lower rather than at higher averaging rates.

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Murine listeriosis is a paradigm to understand host pathogen interactions. Airway infections with Listeria monocytogenes, although representing a serious problem in early onset neonatal listeriosis, has not been investigated in detail in animal models so far. Here, the susceptibility of BALB/c, DBA/2 and C57BL/6 mice towards an intratracheal (i.t.) infection with virulent L. monocytogenes EGDe and the attenuated variant L. monocytogenes EGD hlyW491A(pERL3-CMVGFP) is reported. The course of infection was characterized by determination of bacterial numbers in the organs and assessment of the health condition of the mice. The distribution and cellular localization of Listeria in the airways was assessed by immunocytochemistry and confocal and electron microscopy. The differential susceptibility of inbred mouse strains to airway infections with L. monocytogenes could be assigned to the major virulence factor listeriolysin O. Resistant C57BL/6 mice were not affected by the two listerial strains. In contrast, BALB/c and DBA/2 mice showed differential susceptibility towards L. monocytogenes EGDe and attenuated bacteria, with all the mice being killed by the wild-type bacteria but rarely by the variant that secretes a listeriolysin of only 10% activity of that of the wild-type toxin. Thus, listeriolysin is a decisive factor for differential susceptibility against Listeria. After i.t. application, bacteria were predominantly localized in the peribronchiolar space and invaded alveolar macrophages but rarely lung epithelial cells. Dissemination from the lung into the deep organs started almost immediately after application, although a pulmonary bacterial reservoir remained during the first 4 days.

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The effects of surgical stimuli on haemodynamic and electroencephalographic (EEG) variables were determined in 25 adult ewes undergoing an experimental orthopaedic procedure in isoflurane anaesthesia. Data were recorded after 15 min of constant end-tidal concentration of approximately 2.2% isoflurane (SS: steady state=baseline), during skin disinfection (DIS), incision (INC), drilling of the first hole through the tibia (DRI) and insertion of a threaded pin (PIN) for external fixation. Stimulation resulted in a significant increase in systolic and mean arterial pressure above SS at INC, DRI and PIN. Haemodynamic changes were accompanied by either significant increases or decreases in EEG median frequency (MF) and 80% spectral edge frequency (SEF80) above or below SS at all four stimulation time points suggesting 'arousal' or 'paradoxical arousal' reaction, respectively. We conclude, that either type of EEG activation pattern could be elicited dependent on stimulation intensity and level of anaesthetic depth.

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Resection and end-to-end anastomosis of the trachea are the preferred treatments for various benign and malignant diseases involving the trachea. Various suture techniques and suture materials have been reported; however, some basic questions are still unsolved. Most basic work has been done in dogs, but they are expensive to acquire and keep. Therefore, we evaluated the sheep as an experimental animal for tracheal surgery. We report on our results with sheep regarding anaesthesia, surgical procedure, and tracheal cross-sectional area. Sheep proved to be excellent experimental animals for surgical research regarding tracheal resections and end-to-end anastomosis.

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