The thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats.

OBJECTIVE: To evaluate the thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats. STUDY DESIGN: Randomized, blinded, placebo-controlled crossover study design. ANIMALS: A total of six purpose-bred, adult female ovariohysterectomized Domestic Short Hair cats. METHODS: Cats were allocated into three treatments each consisting of two injections, subcutaneous then intravenous (IV) administration, 2 hours apart: treatment SS, two injections of 0.9% saline; treatment BS, buprenorphine (0.24 mg kg-1, 1.8 mg mL-1) and saline; and treatment BH, buprenorphine (0.24 mg kg-1) and hydromorphone (0.1 mg kg-1). Skin temperature (ST) and thermal threshold (TT) were recorded before (baseline) and for 24 hours following first injection. TT data were analyzed using mixed linear models and a Benjamini-Hochberg sequential adjustment procedure (p < 0.05). RESULTS: There were no significant differences among treatments for baseline ST and TT values, treatment SS over time and between treatments BS and BH. Compared with baseline, TT was significantly increased at all time points in treatments BH and BS except at 2 hours in treatment BS. TT was significantly higher than SS at 3-18 hours and 4-12 hours for treatments BS and BH, respectively. Maximal increases in TT were 47.5 °C at 2 hours, 53.9 °C at 3 hours and 52.4 °C at 6 hours in treatments SS, BS and BH, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of IV hydromorphone following high-concentration buprenorphine provided no additional antinociception and decreased the duration of effect when compared with high-concentration buprenorphine alone. Alternative analgesics should be considered if additional analgesia is required after administration of high-concentration buprenorphine.

Pain behaviors before and after treatment of oral disease in cats using video assessment: a prospective, blinded, randomized clinical trial.

BACKGROUND: Specific behaviors associated with pain in cats with oral disease have not been consistently studied. The aim of this exploratory study was to identify pain-induced behaviors in cats before and after treatment of oral disease using video assessment. Twenty-four cats (6 ± 3.3 years old; 4.9 ± 1.7 kg) were included in a prospective, blinded, randomized clinical trial. Cats were equally divided into minimal (G1: minimal dental treatment) or severe (G2: multiple dental extractions) oral disease groups. After acclimation at day 0, they underwent oral examination, radiographs, scaling, and dental extractions under general anesthesia (anesthetic protocol: acepromazine, hydromorphone, propofol, isoflurane, meloxicam, and local anesthetic blocks; day 1), and were discharged at day 6. Cats were filmed remotely for 10 min using a wide-angle glass lens camera before surgery (baseline) and throughout the study at different time points (36 h of video recording). The videos consisted of four parts namely general, playing, feeding and post-feeding behaviors. A board-certified behaviorist evaluated the duration/frequency of different behaviors based on an ethogram, which were analyzed using linear mixed models and a generalized linear model, respectively (p < 0.05). RESULTS: In comparison with baseline, duration of "not pawing the face" was significantly shorter at day 3 in G2. These cats spent significantly longer time "standing" and "laying" at days 3 and 6, respectively; G1 spent significantly less time "walking" and "standing" at days 3 and 4, respectively and significantly longer time "immobile" at day 3. Duration of "no/slow tail movement" was significantly longer in G2 than G1 at day 5. Duration of "pawing the ribbon" (playing) was significantly shorter in G2 than G1 at day 1. Feeding and post-feeding behaviors with soft food were not significantly different between groups or over time. Frequency of "difficulty grasping dry food" was significantly higher in G2 than G1 up to day 6. Frequency of post-feeding "head shaking" was significantly higher in both groups at day 6 when compared with baseline. CONCLUSIONS: This study identified pain-induced behaviors in cats undergoing treatment of oral disease. These behaviors may be used to differentiate painful versus pain-free cats in clinical practice.

Pharmacokinetics and analgesic effects of intravenous, intramuscular or subcutaneous buprenorphine in dogs undergoing ovariohysterectomy: a randomized, prospective, masked, clinical trial.

BACKGROUND: Buprenorphine is used for canine postoperative pain management. This study aimed to describe the pharmacokinetics and evaluate the analgesic efficacy of buprenorphine (Simbadol, 1.8 mg/mL) administered by different routes in dogs undergoing ovariohysterectomy. Twenty-four dogs were included in a randomized, prospective, masked, clinical trial. Buprenorphine (0.02 mg/kg) was administered intravenously (IV), intramuscularly (IM) or subcutaneously (SC) (n = 8/group) 0.5 h before general anesthesia with propofol-isoflurane. Carprofen (4.4 mg/kg SC) was administered after anesthetic induction and before ovariohysterectomy. Pain was scored using the short-form Glasgow composite pain scale for dogs (SF-GCPS). Dogs were administered morphine (0.25 mg/kg IV) when SF-GCPS scores were ≥ 5/20. Blood sampling was performed up to 720 min after drug administration. Plasma buprenorphine and norbuprenorphine concentrations were analyzed using liquid chromatography mass spectrometry. Pharmacokinetics of buprenorphine was described using a non-compartmental model (PK Solver 2.0). Statistical analysis was performed using linear mixed models and Fisher's exact test (p < 0.05). RESULTS: Pain scores were significantly higher than baseline after IV (0.5-2 h), IM (0.5-3 h) and SC (0.5-4 h) but not among groups. Prevalence of rescue analgesia was significantly higher in SC (7/8 dogs) than IV (2/8) but not different between IV and IM (3/8) or IM and SC. The frequency of rescue analgesia was not significantly different among groups (IV = 2, IM = 5 and SC = 9). Norbuprenorphine was not detected. For IV, IM and SC administration, clearance was 1.29, 1.65 and 1.40 L/hour/kg, volume of distribution was 6.8, 14.2 and 40.1 L/kg, the elimination half-life was 3.7, 5.7, 22 h, and the area under the plasma concentration-time curved extrapolated to infinity was 15.7, 12.4 and 16.4 ng/mL/hour, respectively. Bioavailability for IM and SC was 62.6 and 40%, respectively. Maximum plasma concentrations of buprenorphine were 6.2 and 1.3 ng/mL at 0.14 and 0.33 h after IM and SC administration, respectively. CONCLUSIONS: The route of administration influences the analgesic efficacy of buprenorphine in dogs. SC administration of buprenorphine failed to provide clinical analgesia due to erratic drug absorption. At the doses administered, the IV and IM routes are preferred for postoperative analgesia.

Anesthetic effects of ketamine-medetomidine-hydromorphone in dogs during high-quality, high-volume surgical sterilization program under field conditions.

OBJECTIVE: To describe the anesthetic and adverse effects of an injectable anesthetic protocol in dogs as part of a high-volume sterilization program under field conditions in Belize. STUDY DESIGN: Prospective, observational, field study. ANIMALS: A total of 23 female and eight male dogs (14.2 ± 7.7 kg; age ≥ 8 weeks). METHODS: Using a volume per kg-based dose chart, dogs were administered ketamine (4.5 mg kg-1), medetomidine (0.04 mg kg-1) and hydromorphone (0.09 mg kg-1) intramuscularly. After induction of anesthesia, an endotracheal tube was inserted and dogs were allowed spontaneous breathing in room air. Monitoring included peripheral oxygen saturation (SpO2), mean arterial pressure (MAP), heart rate (HR), respiratory rate, rectal temperature and end-tidal carbon dioxide (Pe'CO2). Meloxicam (0.2 mg kg-1) was administered subcutaneously after surgery. Data were analyzed with linear models and chi-square tests (p < 0.05). RESULTS: Onset of lateral recumbency (3.4 ± 2 minutes) was rapid. Desaturation (SpO2 < 90%) was observed at least once in 64.5% of dogs and was more frequent in large dogs (p = 0.019). Hypercapnia (Pe'CO2 ≥ 50 mmHg; 6.7 kPa) was observed in 48.4% of dogs. MAP was 111 ± 19 mmHg, mean ± standard deviation. Hypertension (MAP ≥ 120 mmHg), bradycardia (HR ≤ 60 beats minute-1) and tachycardia (HR ≥ 140 beats minute-1) were observed in 45.2%, 16.1% and 3.3% of dogs, respectively. Hypotension and hypothermia were not observed. Sex was not significantly associated with any complication. Return of swallowing reflex and time to standing were 71 ± 23 and 152 ± 50 minutes after injection, respectively. Return of swallowing was significantly longer in large dogs. CONCLUSIONS AND CLINICAL RELEVANCE: At the doses used, ketamine-medetomidine-hydromorphone was effective in dogs for high-volume sterilization. In this field setting, adverse effects included hypoventilation, hypoxemia and prolonged recovery.

Anesthetic and analgesic effects of an opioid-free, injectable protocol in cats undergoing ovariohysterectomy: A prospective, blinded, randomized clinical trial.

This study evaluated the effects of ketamine-dexmedetomidine-midazolam as part of an opioid-free, multimodal protocol in cats undergoing ovariohysterectomy. In a prospective, blinded, randomized clinical trial, cats received either 1 of 2 doses of ketamine [5 mg/kg body weight (BW), n = 10, K5 or 7 mg/kg BW, n = 13, K7] with midazolam (0.25 mg/kg BW) and dexmedetomidine (40 µg/kg BW) intramuscularly, intraperitoneal bupivacaine (2 mg/kg BW) and subcutaneous meloxicam (0.2 mg/kg BW) after surgery. Buprenorphine (0.02 mg/kg BW, intravenously) was administered if pain scores exceeded intervention scores with 2 pain scoring systems. Similar prevalence of rescue analgesia was observed (K5 = 6/10; K7 = 7/13) with significantly lower requirements in kittens (2/8) than adults (11/15). Tachypnea (K5 = 7/10 and K7 = 9/13) and desaturation (K5 = 3/10 and K7 = 4/13) were the 2 most common complications. Age influenced the prevalence of rescue analgesia. Most adult cats required opioids for postoperative pain relief.

Effets anesthésiants et analgésiques d'un protocole injectable sans opioïde chez des chats soumis à une ovario-hystérectomie : essai clinique prospectif, randomisé, à l'aveugle. Lors de la présente étude nous avons évalué les effets de la combinaison kétamine-dexmedetomidine-midazolam comme élément d'un protocole multimodal sans opioïde chez des chats soumis à une ovario-hystérectomie. Dans un essai clinique prospectif, randomisé, à l'aveugle, des chats reçurent une des deux doses de kétamine [5 mg/kg poids corporel (BW), n = 10, K5 ou 7 mg/kg BW, n = 13, K7] avec du midazolam (0,25 mg/kg BW) et du dexmedetomidine (40 µg/kg BW) par voie intramusculaire, de la bupivacaine par voie intrapéritonéale (2 mg/kg BW) et du meloxicam sous-cutané (0,2 mg/kg BW) après la chirurgie. De la buprenorphine (0,02 mg/kg BW, par voie intraveineuse) fut administrée si les pointages de douleur excédaient les pointages d'intervention avec deux systèmes de pointage de la douleur. Une prévalence similaire d'analgésie de secours fut observée (K5 = 6/10; K7 = 7/13) avec des demandes significativement moindres chez les chatons (2/8) que chez les adultes (11/15). De la tachypnée (K5 = 7/10 et K7 = 9/13) et de la désaturation (K5 = 3/10 et K7 = 4/13) étaient les deux complications les plus fréquentes. L'âge influençait la prévalence de l'analgésie de secours. La plupart des chats adultes ont requis des opioïdes pour soulager la douleur post-opératoire.(Traduit par Dr Serge Messier).

The analgesic effects of buprenorphine (Vetergesic or Simbadol) in combination with carprofen in dogs undergoing ovariohysterectomy: a randomized, blinded, clinical trial.

BACKGROUND: Buprenorphine is a potent lipophilic opioid analgesic that is largely used in the multimodal treatment of acute pain. Simbadol (buprenorphine hydrochloride) is the first and only FDA-approved high-concentration formulation of buprenorphine for use in cats. The aim of this study was to evaluate the analgesic efficacy of carprofen in combination with one of two commercial formulations of buprenorphine (Simbadol and Vetergesic, 1.8 mg/mL and 0.3 mg/mL, respectively) in dogs undergoing ovariohysterectomy. Twenty-four dogs were included in a randomized, prospective, controlled, clinical trial. Patients were randomly divided into 2 groups as follows. Dogs were premedicated with acepromazine (0.02 mg/kg) and either 0.02 mg/kg of Vetergesic or Simbadol intramuscularly (Vetergesic group - VG; Simbadol group - SG, respectively; n = 12/group). General anesthesia was induced with propofol and maintained with isoflurane in 100% oxygen. Carprofen (4.4 mg/kg SC) was administered after induction of anesthesia. Heart rate, respiratory rate, blood pressure, pulse oximetry, pain scores using the Glasgow Composite Pain Scale Short Form (CMPS-SF), sedation scores using a dynamic interactive visual analogue scale and adverse events were evaluated before and after ovariohysterectomy by an observer who was unaware of treatment administration. If CMPS-SF scores were ≥ 5/20, dogs were administered rescue analgesia (morphine 0.5 mg/kg IM). Statistical analysis was performed using linear mixed models and Fisher's exact test (p < 0.05). RESULTS: Pain and sedation scores and physiological parameters were not significantly different between treatments. Three dogs in VG (25%) and none in SG (0%) required rescue analgesia (p = 0.109). Adverse effects (i.e. vomiting and melena) were observed in two dogs in SG and were thought to be related to stress and/or nonsteroidal anti-inflammatory drug toxicity. CONCLUSIONS: The administration of buprenorphine with carprofen preoperatively provided adequate postoperative analgesia for the majority of dogs undergoing OVH without serious adverse events. Prevalence of rescue analgesia was not significantly different between groups; however, it could be clinically relevant and explained by a type II error (i.e. small sample size). Future studies are necessary to determine if analgesic efficacy after Simbadol and Vetergesic is related to individual variability or pharmacokinetic differences.

Perceptions and opinions of pet owners in the United Sates about surgery, pain management, and anesthesia in dogs and cats.

OBJECTIVE: To evaluate pet owners' perceptions and understanding of surgical pain, perioperative pain management, and anesthesia. STUDY DESIGN: Prospective owner survey. SAMPLE POPULATION: Eight veterinary hospitals each provided 200 surveys for distribution to pet owners. METHODS: A survey evaluated owners' perceptions and opinions related to surgical pain, perioperative pain management, anesthesia in dogs and cats, and owner demographics (sex, age, education, employment, previous surgical experience, and pet ownership) in 8 regions of the United States (Alaska, Florida, Hawaii, Massachusetts, Oregon, Ohio, Texas, Washington, DC). Effects of demographics on survey questions were analyzed by using a Cochran-Mantel-Haenszel test. Descriptive statistics and frequency distributions were calculated when applicable. RESULTS: 948/1600 (59.25%) of distributed questionnaires were completed. Owners reported that analgesics were "always needed" more often for surgical procedures than medical conditions. Knowing what to expect during recovery (99%), being informed of procedures and risks (98%), adequate pain management (98%), and having a board-certified anesthesiologist perform anesthesia (94%) were considered "important" or "very important" by owners. The majority of owners agreed that pain affects quality of life (81%), interactions with family and pets (73%), and that declawing is a painful procedure (59%). Older respondents (>46 years), women, owners who have had previous surgery or who have pets that have had previous surgery, and those in health care professions have a better understanding of pain but also expect effective client communication. CONCLUSION: Improving our understanding of pet owners' perceptions and knowledge related to anesthesia, surgery, and pain may lead to improved client education, satisfaction, and compliance with administration of analgesics.

Thermal antinociception following oral administration of tapentadol in conscious cats.

OBJECTIVE: To evaluate the onset, magnitude and duration of thermal antinociception after oral administration of two doses of tapentadol in cats. STUDY DESIGN: Prospective, randomized, blinded, experimental study. ANIMALS: Six healthy adult cats weighing 4.4 ± 0.4 kg. METHODS: Skin temperature (ST) and thermal threshold (TT) were evaluated using a wireless TT device up to 12 hours after treatment. Treatments included placebo (PBO, 50 mg dextrose anhydrase orally), buprenorphine (BUP, 0.02 mg kg-1) administered intramuscularly, low-dose tapentadol (LowTAP, 25 mg orally; mean 5.7 mg kg-1) and high-dose tapentadol (HighTAP, 50 mg orally; mean 11.4 mg kg-1) in a blinded crossover design with 7 day intervals. Statistical analysis was performed using anova with appropriate post hoc test (p ≤ 0.05). RESULTS: Salivation was observed immediately following 11 out of 12 treatments with tapentadol. The ST was significantly increased at various time points in the opioid treatments. Hyperthermia (≥ 39.5 °C) was not observed. Baseline TT was 45.4 ± 1.4 °C for all treatments. Maximum TT values were 48.8 ± 4.8 °C at 1 hour in LowTAP, 48.5 ± 3.0 °C at 2 hours in HighTAP and 50.2 ± 5.3 °C at 1 hour in BUP. TT significantly increased after LowTAP at 1 hour, after HighTAP at 1-2 hours, and after BUP at 1-2 hours compared with baseline values. TTs were significantly increased in BUP at 1-2 hours compared with PBO. CONCLUSION AND CLINICAL RELEVANCE: Oral administration of tapentadol increased ST and TT in cats. The durations of thermal antinociception were similar between HighTAP and BUP, both of which were twice as long as that in LowTAP. Studies of different formulations may be necessary before tapentadol can be accepted into feline practice.

Validation of a thermal threshold nociceptive model in bearded dragons (Pogona vitticeps).

OBJECTIVES: To validate a thermal threshold (TT) nociceptive model in bearded dragons (Pogona vitticeps) and to document TT changes after administration of morphine. STUDY DESIGN: A two-part randomized, blinded, controlled, experimental study. ANIMALS: Five adult bearded dragons (242-396 g). METHODS: A TT device delivered a ramped nociceptive stimulus (0.6 °C second-1) to the medial thigh until a response (leg kick/escape behavior) was observed or maximum (cut-off) temperature of 62 °C was reached. In phase I, period 1, six TT readings were determined at 20 minute intervals for evaluation of repeatability. Two of these readings were randomly assigned to be sham to assess specificity of the behavioral response. The same experiment was repeated 2 weeks later (period 2) to test reproducibility. In phase II, animals were administered either intramuscular morphine (10 mg kg-1) or saline 0.9%. TTs (maximum 68 °C) were determined before and 2, 4, 8, 12 and 24 hours after treatment administration. Data were analyzed using one-way anova (temporal changes and repeatability) and paired t tests (reproducibility and treatment comparisons) using Bonferroni correction (p < 0.05). RESULTS: Mean TT values were 57.4 ± 3.8 °C and 57.3 ± 4.3 °C for periods 1 and 2, respectively. Data were repeatable within each period (p = 0.83 and p = 0.07, respectively). Reproducibility between periods was remarkable (p = 0.86). False-positive responses during sham testing were 10%. TTs were significantly increased after morphine administration at 2, 4 and 8 hours compared with baseline, and at 2 and 4 hours compared with saline 0.9%. The highest TT was 67.7 ± 0.7 °C at 4 hours after morphine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Testing was repeatable, reproducible and well tolerated in bearded dragons. TT nociceptive testing detected morphine administration and may be suitable for studying opioid regimens in bearded dragons.

Agreement among undergraduate and graduate veterinary students and veterinary anesthesiologists on pain assessment in cats and dogs: A preliminary study.

This study investigated agreement among undergraduate and graduate veterinary students and veterinary anesthesiologists on video pain assessment at the University of Montreal. Pain assessment in dogs and cats appeared to be affected by gender, previous experience, and degree of training despite a small population of observers.

Accord entre étudiants de premier cycle, diplômés en médicine vétérinaire et anesthésistes pour l'évaluation de la douleur chez les chats et les chiens : étude préliminaire. Cette étude a évalué l'accord entre les étudiants de premier cycle, les étudiants diplômés en médicine vétérinaire et les anesthésiologistes vétérinaires pour l'évaluation de la douleur sur vidéo, à l'Université de Montréal. L'évaluation de la douleur chez les chiens et les chats était influencée par le sexe, l'expérience antérieure et le niveau de formation, malgré une population d'observateurs limitée.(Traduit par les auteurs).

Validation de la version francophone d'une échelle composite multidimensionnelle pour l'évaluation de la douleur postopératoire chez les chats.

Validation of the French version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats. The aim of this study was to validate the French version of the UNESP-Botucatu multidimensional composite pain scale (MCPS-Fr) to assess postoperative pain in cats. Two veterinarians and one DVM student identified three domains of behavior based on video analyses: "psychomotor change", "protection of the painful area" and "physiological variables". Internal consistency was excellent (Cronbach's alpha coefficient of 0.94, 0.90 and 0.61, respectively). Criterion validity was good to very good when evaluations from the three observers were compared with a "gold standard". Inter- and intra-rater reliability for each scale item were good to very good. The optimal cut-off point identified with a ROC curve was > 7 (scale range 0-30 points), with a sensitivity of 97.8% and specificity of 99.1%. The MCPS-Fr is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy.(Translated by Dr. Beatriz Monteiro).

Preliminary study on attitudes, opinions and knowledge of Italian veterinarians with regard to abdominal visceral pain in dogs.

OBJECTIVE: To determine the attitudes, opinions and knowledge of Italian veterinarians regarding abdominal visceral pain in canine practice. STUDY DESIGN: Prospective online survey. METHODS: An online questionnaire was created on a Google Form spreadsheet and the weblink was circulated to Italian veterinarians on several mailing lists. The questionnaire, which was available between November 2012 and July 2013, comprised 18 closed, semi-closed and open questions divided into five sections (aetiology, recognition and assessment, drug choices for canine visceral pain, general knowledge about pain management and desire for further education, and demographic information). RESULTS: A total of 527 responses to the questionnaire were completed. Pancreatitis (19%), gastroenteritis (17%) and gastrointestinal obstructions or foreign bodies (9%) were highlighted as the most frequent causes of abdominal visceral pain. Posture, gait and movement changes (32%) and physiological changes (31%) were commonly quoted for pain recognition and assessment. Most respondents (74%) did not use pain scoring systems. Pancreatitis and peritonitis were considered the most painful abdominal conditions. Opioids (40%), nonsteroidal anti-inflammatory drugs (21%) and tramadol (20%) were cited as drugs for the management of visceral pain. A large percentage of respondents (97%) believed that their knowledge regarding pain management required improvement. There is practitioner interest for more continuing education in the subject. Most respondents were women (66%), aged between 25 and 40 years (57%). Internal medicine (56%), surgery (34%) and anaesthesiology (29%) were the main three speciality areas of interest in this study. CONCLUSIONS AND CLINICAL RELEVANCE: This online survey represents the opinion of a small number of Italian veterinarians regarding the assessment and treatment of canine abdominal visceral pain. The results show that Italian veterinarians are aware of the main causes and clinical signs of canine visceral pain. Pain-scoring systems are not often used for the recognition and assessment of pain; however, according to these veterinarians, visceral pain is commonly diagnosed.

Analgesic efficacy of an oral transmucosal spray formulation of meloxicam alone or in combination with tramadol in cats with naturally occurring osteoarthritis.

OBJECTIVE: To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). STUDY DESIGN: Randomized, blinded study. ANIMALS: Fifteen geriatric cats weighing 4.5 ± 1.0 kg. METHODS: Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg-1 every 24 hours) (group M, n = 7), or tramadol (3 mg kg-1 every 12 hours orally) and meloxicam OTMS (group TM, n = 8) for 25 days. Evaluations performed before treatment (D0) and at week 3 (W3) consisted of peak vertical force, motor activity and response to mechanical temporal summation of pain (RMTS). Data were analyzed with mixed models and Fisher's exact test. RESULTS: Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.

Assessment of tandem mass spectrometry and high-resolution mass spectrometry for the analysis of bupivacaine in plasma.

Triple quadrupole mass spectrometers coupled with high performance liquid chromatography are workhorses in quantitative bioanalyses. They provide substantial benefits including reproducibility, sensitivity and selectivity for trace analysis. Selected reaction monitoring allows targeted assay development but datasets generated contain very limited information. Data mining and analysis of nontargeted high-resolution mass spectrometry profiles of biological samples offer the opportunity to perform more exhaustive assessments, including quantitative and qualitative analysis. The objectives of this study were to test method precision and accuracy, to statistically compare bupivacaine drug concentration in real study samples and to verify if high-resolution and accurate mass data collected in scan mode can actually permit retrospective data analysis, more specifically, extract metabolite related information. The precision and accuracy data presented using both instruments provided equivalent results. Overall, the accuracy ranged from 106.2 to 113.2% and the precision observed was from 1.0 to 3.7%. Statistical comparisons using a linear regression between both methods revealed a coefficient of determination (R(2)) of 0.9996 and a slope of 1.02, demonstrating a very strong correlation between the two methods. Individual sample comparison showed differences from -4.5 to 1.6%, well within the accepted analytical error. Moreover, post-acquisition extracted ion chromatograms at m/z 233.1648 ± 5 ppm (M - 56) and m/z 305.2224 ± 5 ppm (M + 16) revealed the presence of desbutyl-bupivacaine and three distinct hydroxylated bupivacaine metabolites. Post-acquisition analysis allowed us to produce semi-quantitative evaluations of the concentration-time profiles for bupicavaine metabolites.

Postoperative analgesic effects of either a constant rate infusion of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine after ovariohysterectomy in dogs.

OBJECTIVE: To evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs. STUDY DESIGN: Randomized, prospective, blinded, clinical study. ANIMALS: Fifty-four dogs. METHODS: Anesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg(-1), infusion rate of saline 0.9% 2 mLkg(-1) hour(-1)); FENT (5 µg kg(-1), 10 µg kg(-1) hour(-1), then 2.5 µg kg(-1) hour(-1)); KET (1 mgkg(-1) , 40 µg kg(-1) minute(-1), then 10 µg kg(-1) minute(-1) ; LIDO (2 mg kg(-1), 100 µg kg(-1) minute(-1), then 25 µg kg(-1) minute(-1)); DEX (1 µgkg(-1), 3 µg kg(-1) hour(-1), then 1 µg kg(-1) hour(-1)); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal-Wallis test with appropriate post-hoc testing (p < 0.05). RESULTS: Animals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour. CONCLUSIONS AND CLINICAL RELEVANCE: LKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.

Perceptions and opinions of pet caregivers in mainland and Hong Kong China about surgery, pain management, and anesthesia in dogs and cats.

Small animal caregivers' perceptions and previous life experiences play a pivotal role in patient care, making effective communication fundamental within the veterinary business. Despite the large and growing scale of the pet industry, data on small animal client-centered information about veterinary services in Mainland China (MC) and the Hong Kong Special Administrative Region (HKSAR) China are lacking. The objective of this study was to investigate the perceptions and opinions of small animal caregivers about surgery, pain management, and anesthesia in dogs and cats in these geographical regions through a validated online survey using content validity index. A total of 2080 valid answers were collected by convenience sampling over 45 days. Descriptive statistics were used to summarize data; the chi-square test and generalized linear models were used to test the associations between demographics and responses. Overall, caregivers appeared favorable toward the use of analgesia in their pets, with concerns over the potential adverse effects produced by analgesic drugs. Joint pain and ear infections were generally rated as conditions that would be less prone to require analgesia. Significant associations were observed for demographic factors such as gender, age, and geographical area, whether participants were healthcare providers, and whether their pets had undergone surgery before. Although many respondents expressed uncertainty in recognizing pain in their pets and administering analgesics, they also expressed a desire to learn and to be informed. This study highlights areas and factors that may determine the perceptions and opinions of small animal caregivers that form a unique human-animal bond in China. Client communication should be addressed on a case-by-case basis and adapted to the geographical area, as the individual background and demographics may have an ultimate impact on treatment goals and patient care.

2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats.

PRACTICAL RELEVANCE: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and are effective for the management of pain in cats. These Guidelines will support veterinarians in decision-making around prescribing NSAIDs in situations of chronic pain, to minimise adverse effects and optimise pain management. Information is provided on mechanism of action, indications for use, screening prior to prescription, use in the presence of comorbidities, monitoring of efficacy, and avoidance and management of adverse effects. CLINICAL CHALLENGES: The cat's unique metabolism should be considered when prescribing any medications, including NSAIDs. Chronic pain may be challenging to detect in this species and comorbidities, particularly chronic kidney disease, are common in senior cats. Management of chronic pain may be complicated by prescription of other drugs with the potential for interactions with NSAIDs. EVIDENCE BASE: These Guidelines have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM) and American Association of Feline Practitioners (AAFP). Information is based on the available literature, expert opinion and the panel members' experience.

Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats.

OBJECTIVE: To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (SC) buprenorphine in cats. STUDY DESIGN: Randomized, prospective, blinded, three period crossover experiment. ANIMALS: Six healthy adult cats weighing 4.1±0.5 kg. METHODS: Buprenorphine (0.02 mg kg(-1)) was administered i.v., i.m. or s.c.. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p<0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the i.v. data was described using a model combining biophase equilibration and receptor association-dissociation kinetics. RESULTS: TT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after i.v. and i.m. administration, respectively (p<0.05). Maximum increase in TT (mean±SD) was 9.3±4.9°C at 60 minutes (i.v.), 4.6±2.8°C at 45 minutes (i.m.) and 1.9±1.9°C at 60 minutes (s.c.). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after i.v. administration compared to i.m. and s.c., respectively. I.v. and i.m. buprenorphine concentration-time data decreased curvilinearly. S.c. PK could not be modeled due to erratic absorption and disposition. I.v. buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t(1/2) k(e0)=47.4 minutes) and receptor binding (k(on)=0.011 mL ng(-1) minute(-1)). Persistence of thermal antinociception was due to slow receptor dissociation (t(1/2) k(off)=18.2 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: I.v. and i.m. data followed classical disposition and elimination in most cats. Plasma concentrations after i.v. administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the i.v. route should be preferred over the i.m. and s.c. routes when buprenorphine is administered to cats.

Evaluation of the isoflurane-sparing effects of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine during ovariohysterectomy in dogs.

OBJECTIVE: To evaluate the isoflurane-sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine-ketamine-dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy. STUDY DESIGN: Randomized, prospective, blinded, clinical study. ANIMALS: Fifty four dogs. METHODS: Anesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg(-1), saline 0.9% CRI, CONTROL/BUT); fentanyl (5 µg kg(-1), 10 µg kg(-1) hour(-1), FENT); ketamine (1 mg kg(-1), 40 µg kg(-1) minute(-1), KET), lidocaine (2 mg kg(-1), 100 µg kg(-1) minute(-1), LIDO); dexmedetomidine (1 µg kg(-1), 3 µg kg(-1) hour(-1), DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end-tidal isoflurane concentration (Fe'Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe'Iso concentrations were monitored. Data were analyzed using anova (p < 0.05). RESULTS: At most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe'Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe'Iso. CONCLUSIONS AND CLINICAL RELEVANCE: At the doses administered, FENT and LKD had greater isoflurane-sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe'Iso.