Correlation of Sedline-generated variables and clinical signs with anaesthetic depth in experimental pigs receiving propofol.

Most of currently available electroencephalographic (EEG)-based tools to assess depth of anaesthesia have not been studied or have been judged unreliable in pigs. Our primary aim was to investigate the dose-effect relationship between increasing propofol dose and variables generated by the EEG-based depth of anaesthesia monitor Sedline in pigs. A secondary aim was to compare the anaesthetic doses with clinical outcomes commonly used to assess depth of anaesthesia in this species. Sixteen juvenile pigs were included. Propofol infusion was administered at 10 mg kg-1 h-1, increased by 10 mg kg-1 h-1 every 15 minutes, and stopped when an EEG Suppression ratio >80% was reached. Patient state index, suppression ratio, left and right spectral edge frequency 95%, and outcomes from commonly used clinical methods to assess depth of anaesthesia in pigs were recorded. The best pharmacodynamic model was assessed for Patient state index, suppression ratio, left and right spectral edge frequency 95% in response to propofol administration. The decrease of Patient state index best fitted to an inhibitory double-sigmoid model (including a plateau phase). The increase of suppression ratio fitted a typical sigmoid Emax model. No relevant relationship could be identified between spectral edge frequency 95% values and propofol administration. A large variability in clinical outcomes was observed among pigs, such that they did not provide a reliable evaluation of propofol dose. The relationship between propofol dose and Patient state index/suppression ratio described in the present study can be used for prediction in future investigations. The evaluation of depth of anaesthesia based on common clinical outcomes was not reliable

Management of pain induced by surgical procedures in veterinary medicine: ethical and practical aspects in the canine species

Treatment methods and drugs used to alleviate pain in animals have been developed, as well as the ethical considerations regarding veterinary analgesia. Especially considering surgical interventions, knowledge is growing about pain treatment. Alleviation of perioperative pain becomes an essential duty. Dogs probably benefit most of it. We learn to evaluate perioperative signs of pain, and their treatment become individualized and multimodal. The efficacy of such perioperative analgesia is scrutinized by numerous clinical trials. Intravenous continuous infusions of analgesics and loco-regional anaesthesia are exemples of these advancements which are not anymore rare and luxurious options. The combination of anti-inflammatory drugs with reduced toxicity, opioids, N-Methyl-D-Aspartate-antagonists (ketamine), and alpha-2 agonists, is better controlled and more effective, reducing the potential for undesirable side effects which long hindered their use.Les protocoles thérapeutiques et les produits pharmaceutiques permettant de traiter la douleur chez les animaux se sont développés, ainsi que la déontologie vétérinaire à cet égard et particulièrement dans le domaine de la chirurgie. Des progrès considérables ont été effectués au niveau de la prise en charge de la douleur : le traitement de la douleur peropératoire s’avère un devoir essentiel. Le chien est probablement l’animal qui en bénéficie le plus. Nous perfectionnons l’évaluation de la douleur peropératoire et son traitement devient individualisé et multimodal. L’efficacité des analgésiques peropératoires font l’objet de nombreuses études cliniques. L’administration d’analgésiques par perfusion intraveineuse continue et les techniques d’anesthésie loco-régionale sont des exemples de ces progrès qui ne sont plus des options de luxe à discrétion. L’association thérapeutique d’anti-inflammatoires plus spécifiques et à toxicité réduite, de dérivés morphiniques, d’inhibiteurs du récepteur du N-Méthyl-D-Aspartate (kétamine), et d’alpha-2 agonistes, est mieux contrôlée et plus efficace, réduisant les craintes d’effets indésirables qui ont longtemps retenues leur utilisation

A Survey on the Use of Spirometry in Small Animal Anaesthesia and Critical Care

The objective was to document the use of spirometry and ventilation settings in small animal anaesthesia and intensive care through a descriptive, open, online, anonymous survey. The survey was advertised on social media and via email. Participation was voluntary. The google forms platform was used. It consisted of eight sections in English: demographic information, use of spirometry in spontaneously ventilating/mechanically ventilated dogs, need for spirometry, equipment available and calibration status, ventilation modes, spirometry displays, compliance (CRS) and resistance (RRS) of the respiratory system. Simple descriptive analyses were applied. There were 128 respondents. Respondents used spirometry more in ventilated dogs than during spontaneous breathing. Over 3/4 of the respondents considered spirometry essential in “selected” (43%) or “most” cases (33%). Multiple devices and technologies were used. The majority of the respondents were not directly involved in or informed about the calibration of their equipment. Of all displays, pressure-volume loops were the most common. Values of CRS and RRS were specifically monitored in more than 50% of cases by 44% of the respondents only. A variety of ventilation modes was used. Intensivists tend to use smaller VT than anaesthetists. More information on reference intervals of CRS and RRS and technical background on spirometers is required

Acute hyperkalaemia in a captive Persian leopard (Panthera pardus saxicolor) immobilised with a ketamine-medetomidine combination

A 12-year-old captive male Persian leopard (Panthera pardus saxicolor) required general anaesthesia for examination and treatment of a recurrent oral fistula. Medetomidine (0.065 mg/kg) and ketamine (3.6 mg/kg) administered intramuscularly by blowpipe darting effectively immobilised the animal that was maintained under general anaesthesia with inhaled isoflurane. In absence of clinical signs, acute hyperkalaemia (7.26 mmol/l) was incidentally recognised by the end of anaesthesia. Factors that might have played a role in hyperkalaemia development, such as the use of α2-adrenoceptor agonists, stress response, acidosis or dopamine administration, are discussed. Hyperkalaemia should be considered as a potential complication while anaesthetising large non-domestic felids

Sedline® Miscalculation of Depth of Anaesthesia Variables in Two Pigs Due to Electrocardiographic Signal Contamination.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression ratio, raw EEG traces, and its spectrogram were assessed. Physiological parameters and electrocardiographic activity were continuously monitored. In one pig (Case 1), during the administration of high doses of propofol, the Sedline-generated variables suddenly indicated an increased EEG activity while this was not confirmed by observation of either the raw EEG or its spectrogram. In the second pig (Case 2), a similar event was recorded during euthanasia with systemic pentobarbital. Both events happened while the EEG activity was isoelectric except for signal interferences and synchronous in rhythm and shape with the electrocardiographic activity. The suggestion of increased brain activity based on the interpretation of the Sedline variables was suspected wrong; most probably due to electrocardiographic interferences. In pigs, the patient state index and suppression ratio, as calculated by the Sedline monitor, could be influenced by the electrocardiographic activity contaminating the EEG trace, especially during otherwise isoelectric periods (strong EEG depression). Visual interpretation of the raw EEG and of the spectrogram remains necessary to identify such artefacts

Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses

OBJECTIVE To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. STUDY DESIGN Prospective, experimental, nonrandomized trial. ANIMALS A total of 10 healthy adult warmblood horses. METHODS Romifidine (loading dose: 0.08 mg kg-1, infusion: 0.03 mg kg-1 hour-1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic-pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested. RESULTS A two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33). CONCLUSIONS AND CLINICAL RELEVANCE Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration

Do the Manual or Computer-Controlled Flowmeters Generate Similar Isoflurane Concentrations in Tafonius?

Introduction: Tafonius is an anesthesia machine with computer-controlled monitor and ventilator. We compared the isoflurane fluctuations in the circuit with manual (MF) or computer-driven (CF) flowmeters, investigated the origin of the differences and assessed whether isoflurane concentration time course followed a one-compartment model.Material and Methods: A calibrated TEC-3 isoflurane vaporizer was used. Gas composition and flows were measured using a multiparametric monitor and a digital flowmeter. Measurements included: (1) Effects of various FiO2 with MF/CF on the isoflurane fraction changes in the breathing system during mechanical ventilation of a lung model; wash-in kinetic was fitted to a compartmental model; (2) Gas outflow at the common gas outlet (CGO) with MF/CF at different FiO2; (3) Isoflurane output of the vaporizer at various dial settings with MF/CF set at different flows without and with reduction of the CGO diameter.Results: (1) The 3% targeted isoflurane concentration was not reached; additional time was required to reach specific concentrations with CF (lowest FiO2, longer time). The exponential course fitted a two-compartment model; (2) Set and measured flows were identical with MF. With CF at 0.21 FiO2, flow was intermittently 7.6 L min−1 or zero (mean total: 38% of the set flow); with CF at 1.00 FiO2, flow was 10.6 L min−1 or zero (mean: 4–5.3 L min−1); with 0.21 &lt; FiO2 &lt; 1.00, combined flow was intermittent (maximum output: 15.6 L min−1); (3) With MF, isoflurane output was matching dial setting at 5 L min−1 but was lower at higher flows; with CF generating intermittent flows, isoflurane output was fluctuating. With the 4 mm diameter CGO, isoflurane concentration was close to dial setting with both MF and CF. With a 14 G CGO, isoflurane concentration was lower than dial setting with MF, higher with CF.Conclusions and Clinical Relevance: Using MF or CF led to different isoflurane fraction time course in Tafonius. Flows were lower than set with CF; the TEC-3 did not compensate for high/intermittent flows and pressures; the CGO diameter influenced isoflurane output

Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles.

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%-56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1 ) and central and peripheral volumes of distribution (V1 , V2 ). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs

Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity

Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.Animal science