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The aim of this study was to determine the efficacy and pharmacokinetics of bupivacaine in combination with epinephrine or dexmedetomidine after intraperitoneal administration in cats undergoing ovariohysterectomy. Sixteen healthy adult cats (3.3 ± 0.6 kg) were included in a prospective, randomized, masked clinical trial after obtaining owners' consent. Anesthetic protocol included buprenorphine-propofol-isoflurane. Meloxicam [0.2 mg/kg body weight (BW)] was administered subcutaneously before surgery. Cats were randomly divided into 2 groups to receive 1 of 2 treatments. Intraperitoneal bupivacaine 0.25% (2 mg/kg BW) was administered with epinephrine (BE group; 2 μg/kg BW) or dexmedetomidine (BD group; 1 μg/kg BW) before ovariohysterectomy ( n = 8/group). A catheter was placed in the jugular vein for blood sampling. Blood samples were collected for up to 8 h after bupivacaine was administered. Plasma concentrations and pharmacokinetics of bupivacaine were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS) and non-compartmental model, respectively. Pain was evaluated using the UNESP-Botucatu multidimensional composite pain scale (MCPS), the Glasgow composite feline pain scale (GPS), and a dynamic visual analog scale up to 8 h after extubation. Rescue analgesia was provided with buprenorphine if MCPS was ≥ 6. Repeated measures linear models were used for analysis of pain and sedation scores ( P < 0.05). Maximum bupivacaine plasma concentrations (Cmax) for BE and BD were 1155 ± 168 ng/mL and 1678 ± 364 ng/mL ( P = 0.29) at 67 ± 13 min (Tmax) and 123 ± 59 min ( P = 0.17), respectively. Pharmacokinetic parameters and pain scores were not different between treatments ( P > 0.05). One cat in the BE group received rescue analgesia ( P = 0.30). Intraperitoneal bupivacaine with epinephrine or dexmedetomidine produced concentrations below toxic levels and similar analgesic effects. It is therefore safe to administer these drug combinations in cats undergoing ovariohysterectomy.

OBJECTIVE To evaluate agreement between observers with different training and experience for assessment of postoperative pain and sedation in cats by use of a dynamic and interactive visual analog scale (DIVAS) and for assessment of postoperative pain in the same cats with a multidimensional composite pain scale (MCPS). DESIGN Randomized, controlled, blinded study. ANIMALS 45 adult cats undergoing ovariohysterectomy. PROCEDURES Cats received 1 of 3 preoperative treatments: bupivacaine, IP; meloxicam, SC with saline (0.9% NaCl) solution, IP, (positive control); or saline solution only, IP (negative control). All cats received premedication with buprenorphine prior to general anesthesia. An experienced observer (observer 1; male; native language, Spanish) used scales in English, and an inexperienced observer (observer 2; female; native language, French) used scales in French to assess signs of sedation and pain. Rescue analgesia was administered according to MCPS scoring by observer 1. Mean pain and sedation scores per treatment and time point, proportions of cats in each group with MCPS scores necessitating rescue analgesia, and mean MCPS scores assigned at the time of rescue analgesia were compared between observers. Agreement was assessed by intraclass correlation coefficient determination. Percentage disagreement between observers on the need for rescue analgesia was calculated. RESULTS Interobserver agreements for pain scores were good, and that for sedation scores was fair. On the basis of observer 1's MCPS scores, a greater proportion of cats in the negative control group received rescue analgesia than in the bupivacaine or positive control groups. Scores from observer 2 indicated a greater proportion of cats in the negative control group than in the positive control group required rescue analgesia but identified no significant difference between the negative control and bupivacaine groups for this variable. Overall, disagreement regarding need for rescue analgesia was identified for 22 of 360 (6.1%) paired observations. CONCLUSIONS AND CLINICAL RELEVANCE Interobserver differences in assessing pain can lead to different conclusions regarding treatment effectiveness.

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.

Objectives The aim of this study was to evaluate the analgesic efficacy of intraperitoneal (IP) bupivacaine in cats undergoing ovariohysterectomy (OVH). Methods Forty-five cats were included in a randomized, prospective, blinded study after owners' written consent was obtained. The anesthetic protocol included acepromazine-buprenorphine-propofol-isoflurane. A ventral midline incision was made and cats (n = 15/group) were administered either IP saline 0.9% (negative and positive control groups; NG and PG, respectively) or IP bupivacaine (2 mg/kg; bupivacaine group; BG). Cats in the PG received meloxicam (0.2 mg/kg SC). An OVH was performed and postoperative pain was evaluated using a dynamic interactive visual analog scale (DIVAS), the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociceptive thresholds (MNT) for up to 8 h after the end of surgery. Postoperative sedation was evaluated using DIVAS. Rescue analgesia was provided with buprenorphine and/or meloxicam. Repeated measures linear models and a Cochran-Mantel-Haenszel test were used for statistical analysis ( P <0.05). Results There was a significant effect of treatment on the number of times rescue analgesia was administered ( P = 0.002) (PG, n = 2, 13%; NG, n = 12, 80%; BG, n = 4, 27%) with the number of rescues being higher in the NG group than in the PG ( P = 0.0004) and BG ( P = 0.02) groups. The DIVAS, MCPS and MNT were significantly different when compared with baseline values at different time points; however, data were not significantly different among groups. Conclusions and relevance Treatments PG and BG produced similar analgesia in terms of pain scores, number of times rescue analgesia was administered and MNT. Based on rescue analgesia, IP administration of bupivacaine provides analgesia in cats after OVH.

OBJECTIVE To evaluate pharmacokinetics of bupivacaine after IP administration to cats undergoing ovariohysterectomy. ANIMALS 8 healthy cats. PROCEDURES Anesthesia was induced with propofol and maintained with isoflurane. Buprenorphine (0.02 mg/kg, IV) and meloxicam (0.2 mg/kg, SC) were administered. A 20-gauge catheter was inserted into a jugular vein for blood sample collection. A ventral midline incision was made, and a solution of 0.5% bupivacaine (2 mg/kg) diluted with an equal volume of saline (0.9% NaCl) solution (final concentration, 0.25% bupivacaine) was injected into the peritoneal space over the right and left ovarian pedicles and caudal aspect of the uterus before ovariohysterectomy. Cats were monitored for signs of bupivacaine toxicosis. Venous blood samples (2 mL) were collected before (time 0) and 2, 5, 10, 15, 20, 30, 60, 120, and 240 minutes after bupivacaine administration. Plasma bupivacaine concentrations were determined with a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined by data plotting followed by analysis with a noncompartmental model. RESULTS No signs of bupivacaine toxicosis were observed. Maximum bupivacaine plasma concentration was 1,030 ± 497.5 ng/mL at a mean ± SD value of 30 ± 24 minutes after administration. Mean elimination half-life was 4.79 ± 2.7 hours. Mean clearance indexed by bioavailability and volume of distribution indexed by bioavailability were 0.35 ± 0.18 L•h/kg and 2.10 ± 0.84 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Intraperitoneal administration of bupivacaine resulted in concentrations that did not cause observable toxicosis. Studies to investigate analgesic effects for this technique in cats are warranted.

Objective: To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats., Animals: 6 healthy adult cats., Procedures: In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points., Results: Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection., Conclusions and Clinical Relevance: Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation.

Objective: To evaluate the effects of a constant rate infusion of remifentanil, alone or in combination with ketamine, in healthy cats anesthetized with isoflurane., Design: Randomized, controlled, clinical trial., Animals: 23 cats undergoing elective ovariohysterectomy., Procedures: Cats were premedicated with acepromazine and morphine; anesthesia was induced with propofol and maintained with isoflurane. Cats were given constant rate infusions of remifentanil (20 μg/kg/h [9 μg/lb/h], IV; n = 8), remifentanil and ketamine (0.5 mg/kg [0.23 mg/lb], then 1.8 mg/kg/h [0.82 mg/lb/h], IV; 7), or crystalloid fluids (8). The anesthesiologist was blinded to treatment group, end-tidal isoflurane concentration, and vaporizer setting. Heart rate, systolic arterial blood pressure, respiratory rate, end-tidal partial pressure of CO2, temperature, and end-tidal isoflurane concentration were monitored; recovery scores were assigned., Results: There were no significant differences among treatment groups with respect to age, body weight, surgery time, anesthesia time, time to extubation, recovery score, or cardiorespiratory variables. End-tidal isoflurane concentration was significantly reduced in cats given remifentanil and ketamine (mean ± SD, 0.63 ± 0.4%), compared with concentration in cats given crystalloid fluids (1.22 ± 0.5%) but not compared with concentration in cats given remifentanil alone (1.03 ± 0.4%). Compared with cats given crystalloid fluids, mean isoflurane requirement was reduced by 48.3% in cats given remifentanil-ketamine and 15.6% in cats given remifentanil alone., Conclusions and Clinical Relevance: At the dosages administered, a constant rate infusion of remifentanil-ketamine resulted in a significant decrease in the isoflurane requirement in healthy cats undergoing ovariohysterectomy. However, significant differences in cardiovascular variables were not observed among treatment groups.

Simple Summary: A pain assessment is essential to provide appropriate pain relief. The Feline Grimace Scale© (FGS) is a facial expression-based acute pain scale used in feline medicine; increased FGS scores could indicate acute pain in cats requiring analgesia. However, it is unknown if some sedatives and/or anesthetics can bias pain assessment using the FGS. This study aimed to investigate the effects of sedation with dexmedetomidine-butorphanol followed by anesthesia with propofol-isoflurane on the FGS scores of healthy cats. The cats were video-recorded before and up to 24 h after sedation and general anesthesia. Images collected from the videos were randomized and scored independently by four raters who were masked to the treatments. Dexmedetomidine and butorphanol significantly increased the FGS scores at 20 min after administration. General anesthesia with propofol and isoflurane significantly increased the FGS scores at 0.5 h post-anesthesia, but not after. There were no other statistically significant findings. In conclusion, sedation with dexmedetomidine and butorphanol and general anesthesia with propofol and isoflurane increase FGS scores and may bias clinical pain assessment. Although the effects were short-lived, they should be taken into account during acute pain assessment. This study aimed to evaluate the effects of sedation and anesthesia on Feline Grimace Scale© (FGS) scores. Twelve healthy cats were included in a prospective, blinded and randomized, cross-over study with a 14 day wash-out. Saline or dexmedetomidine-butorphanol (Dex-But) was administered intramuscularly before an anesthetic induction with propofol and maintenance with isoflurane. Saline or atipamezole (Dex-But) was administered at the end of the general anesthesia. Video-filming/image capturing was performed before and up to 24 h post-anesthesia. A total of 125 images were evaluated by four raters blinded to the treatment groups using the FGS (ear position/orbital tightening/muzzle tension/whiskers change/head position; action units (AU); scores 0–2 for each AU). The effects of the sedation/anesthesia were analyzed (p < 0.05). The total FGS and each AU scores were significantly higher with Dex-But than with saline 20 min post-sedation. In the saline group, the total FGS, orbital tightening, and whiskers and head position scores were significantly higher than baseline at 0.5 h post-anesthesia. In the Dex-But group, the total FGS and each AU scores were significantly higher after sedation, whereas the orbital tightening scores were significantly higher at 0.5 h post-anesthesia when compared with the baseline. None of the other comparisons between or within the groups was significantly different. The sedation with dexmedetomidine-butorphanol and anesthesia with propofol-isoflurane changed the FGS scores on a short-term basis; consequently, they may bias acute pain assessment. [ABSTRACT FROM AUTHOR]

Bupivacaine is commonly used for peripheral nerve block in veterinary medicine. This study described the pharmacokinetics of two doses of bupivacaine following administration by an ultrasound-guided transversus abdominis plane (TAP) block in cats undergoing ovariohysterectomy. Twelve healthy female adult cats were included in a randomized, prospective, blinded clinical trial. Anaesthetic protocol included acepromazine–buprenorphine–propofol–isoflurane–meloxicam. Each cat received 1 mL/kg of bupivacaine 0.2% or 0.25% (BUPI-2 and BUPI-2.5, respectively) via bilateral two-point TAP block before surgery (n = 6/group). Plasma concentrations of bupivacaine were detected using liquid chromatography-mass spectrometry. A one-compartment model and non-compartmental analysis described the pharmacokinetic parameters. Bupivacaine was detected up to 480 min (335 ± 76 in BUPI-2 and 485 ± 198 ng/mL in BUPI-2.5). For BUPI-2 and BUPI-2.5, maximum plasma concentrations were 1166 ± 511 and 1810 ± 536 ng/mL at 33 ± 14 and 47 ± 22 min, clearance was 5.3 ± 1.8 and 4.9 ± 1.5 mL/min/kg, and elimination half-life were 253 ± 55 and 217 ± 52 min, respectively. The two doses of bupivacaine via TAP block produced concentrations below toxic levels in cats. A dose of 2.5 mg/kg bupivacaine was safe to be administered using this block in healthy cats. [ABSTRACT FROM AUTHOR]

Abstract: Facial expressions of pain have been identified in several animal species. The aim of this systematic review was to provide evidence on the measurement properties of grimace scales for pain assessment. The protocol was registered (SyRF#21-November-2019), and the study is reported according to the PRISMA guidelines. Studies reporting the development, validation, and the assessment of measurement properties of grimace scales were included. Data extraction and assessment were performed by 2 investigators, following the COnsensus-based Standards for the Selection of Health Measurement INstruments guidelines. Six categories of measurement properties were assessed: internal consistency, reliability, measurement error, criterion and construct validity, and responsiveness. Overall strength of evidence (high, moderate, and low) of each instrument was based on methodological quality, number of studies, and studies' findings. Twelve scales for 9 species were included (mice, rats, rabbits, horses, piglets, sheep or lamb, ferrets, cats, and donkeys). Considerable variability regarding their development and measurement properties was observed. The Mouse, Rat, Horse and Feline Grimace Scales exhibited high level of evidence. The Rabbit, Lamb, Piglet and Ferret Grimace Scales and Sheep Pain Facial Expression Scale exhibited moderate level of evidence. The Sheep Grimace Scale, EQUUS-FAP, and EQUUS-Donkey-FAP exhibited low level of evidence for measurement properties. Construct validity was the most reported measurement property. Reliability and other forms of validity have been understudied. This systematic review identified gaps in knowledge on the measurement properties of grimace scales. Further studies should focus on improving psychometric testing, instrument refinement, and the use of grimace scales for pain assessment in nonhuman mammals. [ABSTRACT FROM AUTHOR]

Background. Pain is the leading cause of animal suffering, hence the importance of validated tools to ensure its appropriate evaluation and treatment. We aimed to test the psychometric properties of the short form of the Unesp-Botucatu Feline Pain Scale (UFEPS-SF) in eight languages. Methods. The original scale was condensed from ten to four items. The content validation was performed by five specialists in veterinary anesthesia and analgesia. The English version of the scale was translated and back-translated into Chinese, French, German, Italian, Japanese, Portuguese and Spanish by fluent English and native speaker translators. Videos of the perioperative period of 30 cats submitted to ovariohysterectomy (preoperative, after surgery, after rescue analgesia and 24 h after surgery) were randomly evaluated twice (one-month interval) by one evaluator for each language unaware of the pain condition. After watching each video, the evaluators scored the unidimensional, UFEPS-SF and Glasgow composite multidimensional feline pain scales. Statistical analyses were carried out using R software for intra and interobserver reliability, principal component analysis, criteria concurrent and predictive validities, construct validity, item-total correlation, internal consistency, specificity, sensitivity, the definition of the intervention score for rescue analgesia and diagnostic uncertainty zone, according to the receiver operating characteristic (ROC) curve. Results. UFEPS-SF intra- and inter-observer reliability were -0.92 and 0.84, respectively, for all observers. According to the principal component analysis, UFEPS-SF is a unidimensional scale. Concurrent criterion validity was confirmed by the high correlation between UFEPS-SF and all other scales (-0.9). The total score and all items of UFEPS-SF increased after surgery (pain), decreased to baseline after analgesia and were intermediate at 24 h after surgery (moderate pain), confirming responsiveness and construct validity. Item total correlation of each item (0.68-0.83) confirmed that the items contributed homogeneously to the total score. Internal consistency was excellent (-0.9) for all items. Both specificity (baseline) and sensitivity (after surgery) based on the Youden index was 99% (97-100%). The suggestive cut-off score for the administration of analgesia according to the ROC curve was -4 out of 12. The diagnostic uncertainty zone ranged from 3 to 4. The area under the curve of 0.99 indicated excellent discriminatory capacity of UFEPS-SF. Conclusions. The UFEPS-SF and its items, assessed by experienced evaluators, demonstrated very good repeatability and reproducibility, content, criterion and construct validities, item-total correlation, internal consistency, excellent sensitivity and specificity and a cut-off point indicating the need for rescue analgesia in Chinese, French, English, German, Italian, Japanese, Portuguese and Spanish. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. The Feline Grimace Scale (FGS) is a facial expression-based scoring system for acute pain assessment in cats with reported validity using image assessment. The aims of this study were to investigate the clinical applicability of the FGS in real-time when compared with image assessment, and to evaluate the influence of sedation and surgery on FGS scores in cats. Methods. Sixty-five female cats (age: 1.37 ± 0.9 years and body weight: 2.85 ± 0.76 kg) were included in a prospective, randomized, clinical trial. Cats were sedated with intramuscular acepromazine and buprenorphine. Following induction with propofol, anesthesia was maintained with isoflurane and cats underwent ovariohysterectomy (OVH). Pain was evaluated at baseline, 15 min after sedation, and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h after extubation using the FGS in real-time (FGS-RT). Cats were video-recorded simultaneously at baseline, 15 min after sedation, and at 2, 6, 12, and 24 h after extubation for subsequent image assessment (FGS-IMG), which was performed six months later by the same observer. The agreement between FGS-RT and FGS-IMG scores was calculated using the Bland & Altman method for repeated measures. The effects of sedation (baseline versus 15 min) and OVH (baseline versus 24 h) were assessed using linear mixed models. Responsiveness to the administration of rescue analgesia (FGS scores before versus one hour after) was assessed using paired t-tests. Results. Minimal bias (−0.057) and narrow limits of agreement (−0.351 to 0.237) were observed between the FGS-IMG and FGS-RT. Scores at baseline (FGS-RT: 0.16 ± 0.13 and FGS-IMG: 0.14 ± 0.13) were not different after sedation (FGS-RT: 0.2 ± 0.15, p = 0.39 and FGS-IMG: 0.16 ± 0.15, p = 0.99) nor at 24 h after extubation (FGS-RT: 0.16 ± 0.12, p = 0.99 and FGS-IMG: 0.12 ± 0.12, p = 0.96). Thirteen cats required rescue analgesia; their FGS scores were lower one hour after analgesic administration (FGS-RT: 0.21 ± 0.18 and FGS-IMG: 0.18 ± 0.17) than before (FGS-RT: 0.47 ± 0.24, p = 0.0005 and FGS-IMG: 0.45 ± 0.19, p = 0.015). Conclusions. Real-time assessment slightly overestimates image scoring; however, with minimal clinical impact. Sedation with acepromazine-buprenorphine and ovariohysterectomy using a balanced anesthetic protocol did not influence the FGS scores. Responsiveness to analgesic administration was observed with both the FGS-RT and FGS-IMG. [ABSTRACT FROM AUTHOR]

Grimace scales have been used for pain assessment in different species. This study aimed to develop and validate the Feline Grimace Scale (FGS) to detect naturally-occurring acute pain. Thirty-five client-owned and twenty control cats were video-recorded undisturbed in their cages in a prospective, case-control study. Painful cats received analgesic treatment and videos were repeated one hour later. Five action units (AU) were identified: ear position, orbital tightening, muzzle tension, whiskers change and head position. Four observers independently scored (0–2 for each AU) 110 images of control and painful cats. The FGS scores were higher in painful than in control cats; a very strong correlation with another validated instrument for pain assessment in cats was observed (rho = 0.86, p < 0.001) as well as good overall inter-rater reliability [ICC = 0.89 (95% CI: 0.85–0.92)], excellent intra-rater reliability (ICC > 0.91), and excellent internal consistency (Cronbach's alpha = 0.89). The FGS detected response to analgesic treatment (scores after analgesia were lower than before) and a cut-off score was determined (total pain score > 0.39 out of 1.0). The FGS is a valid and reliable tool for acute pain assessment in cats. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate pain scores, analgesic requirements, food intake and serum inflammatory cytokines in cats before and after clinically recommended dental treatment. Twenty-four cats were included in a prospective, blinded clinical trial. Cats were equally divided into minimal (minimal dental treatment) or severe (multiple dental extractions) oral disease groups. They were admitted (day 0) and underwent oral examination/radiographs/treatment under general anesthesia (day 1; acepromazine-hydromorphone-propofol-isoflurane-meloxicam-local anesthetic blocks). Serum inflammatory cytokines were measured on days 0 and 6. Pain was scored using the Glasgow composite measure pain scale-feline (CMPS-F). Rescue analgesia was administered with hydromorphone if CMPS-F ≥ 5/20. Dry and soft food intake (%) during 3 minutes and 2 hours, and daily soft food were calculated. The Cochran-Mantel-Haenszel and Chi-square tests, Spearman’s rank correlation and linear mixed models were used for statistical analysis (alpha = 0.05). Pain scores were significantly increased in cats with severe disease when compared with baseline (up to day 4) and minimal disease (all postoperative time points). Prevalence of rescue analgesia was significantly higher in severe (91.7%) than minimal disease (0%); analgesics were required up to day 3. Pain scores and frequency of rescue analgesia were significantly correlated with the number of tooth extractions, gingival and calculus index. Prevalence of rescue analgesia was significantly correlated with the number of missing teeth, teeth extractions and gingival index. Dry and soft food intake during 3 minutes, and dry food intake during 2 hours were significantly lower in the severe than minimal disease group throughout the study. Some cytokines differed between groups between day 0 and day 6 and were associated with the presence of tooth resorption and number of missing tooth and tooth fractures. Long-term analgesia is required after dental extractions in cats with severe oral disease. This condition reduces food intake and influences serum inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats. Methods: Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL). Thermal threshold testing and blood sampling were performed at predetermined time points up to 72 hours including a placebo group. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic model simultaneously fitted data from two analytes/three routes of administration. Temporal changes in TT were analyzed using one-way ANOVA followed by Dunnett’s test and treatment comparisons using two-way ANOVA with Bonferroni’s correction (P < 0.05). Results: Thermal thresholds were significantly increased after SC, IV and OTM from 1–24 hours (except 2 hours), 0.5–8 hours (except 6 hours), and 1–8 hours (except 6 hours), respectively, when compared with baseline. Thermal thresholds were significantly increased after SC (1–30 hours), IV (1–8 hours) and OTM (1–12 hours) when compared with SAL, but not different among buprenorphine-treated cats. The absolute buprenorphine clearance was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94% and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak acceleration at 2.8 hours) uptake. Conclusion: The SC administration of Simbadol™ was characterized by prolonged absorption half-life and sustained plasma concentrations yielding long-lasting antinociception (≥ 24 hours) when compared with the IV and OTM routes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Methods: Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Results: Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5–30)] than in OA cats [14 (8.5–28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Conclusion: Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment. [ABSTRACT FROM AUTHOR]

To evaluate the thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats. Randomized, blinded, placebo-controlled crossover study design. A total of six purpose-bred, adult female ovariohysterectomized Domestic Short Hair cats. 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). 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. 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. [ABSTRACT FROM AUTHOR]