Pharmacokinetics of oral clonazepam in growing commercial pigs (Sus scrofa domestica).

Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild-to-moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse-phase high-performance liquid chromatography, and compartment models were fit to time-concentration data. A one-compartment first-order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half-life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted.

Evaluation of the analgesic efficacy of grapiprant compared with robenacoxib in cats undergoing elective ovariohysterectomy in a prospective, randomized, masked, non-inferiority clinical trial.

OBJECTIVES: The main objective of this study was to compare the postoperative analgesic effects of grapiprant with those of robenacoxib in cats undergoing ovariohysterectomy (OVH). METHODS: In total, 37 female cats (age range 4 months-10 years, weighing ⩾2.5 kg) were enrolled in a prospective, randomized, masked, non-inferiority (NI) clinical trial. Cats received oral robenacoxib (1 mg/kg) or grapiprant (2 mg/kg) 2 h before OVH. Analgesia was assessed via the Feline Grimace Scale (FGS), the Glasgow Composite Measure Pain Scale-Feline (CMPS-F), von Frey monofilaments (vFFs) and pressure algometry (ALG) 2 h before treatment administration, at extubation, and 2, 4, 6, 8, 18 and 24 hours after extubation. Hydromorphone (<8 h postoperatively) or buprenorphine (>18 h postoperatively) were administered to cats with scores of ⩾5/20 on CMPS-F and/or ⩾4/10 on FGS. NI margins for CMPS-F and vFFs were set at 3 and -0.2, respectively. A mixed-effect ANOVA was used for FGS scores (P <0.05). Data are reported as mean ± SEM. RESULTS: The data from 33 cats were analyzed. The upper limit of the 95% confidence interval (CI) (0.35) was less than the NI margin of 3 for CMPS-F, and the lower limit of the 95% CI (0.055) was greater than the NI margin of -0.2 for vFFs, indicating NI of grapiprant. The FGS scores were greater than baseline at extubation for both treatments (1.65 ± 0.63; P = 0.001); however, there was no difference between treatments. There was no difference between treatments, nor treatment by time interaction, for vFFs (P <0.001). The CMPS-F scores for both treatments were higher at extubation but returned to baseline after 4 h (P <0.001). For ALG, there was no difference in treatment or treatment by time interaction. The robenacoxib group had lower pressure readings at extubation and 6 h compared with baseline. CONCLUSIONS AND RELEVANCE: These results indicate that grapiprant was non-inferior to robenacoxib for mitigating postsurgical pain in cats after OVH performed via ventral celiotomy. The impact of grapiprant for analgesia in OVH via the flank is unknown.

Delayed Urethral Obstruction after Migration of a Ballistic Pellet in an Alpine Wether.

A one-year-old alpine wether was presented for emergency evaluation of stranguria. Diagnostics identified a moderately distended bladder and mild dehydration. Preliminary lateral radiographs identified two metallic structures consistent with projectile pellets in the pelvic and perineal regions and no evidence of radiopaque uroliths. A tube cystostomy was performed, and a contrast urethrogram revealed one of the pellets in the perineal region was in proximity to the urethral obstruction. Subsequent radiography and ultrasound identified the pellet as being within the lumen of the urethra. Examination of the trichotomized skin revealed two scars, including a scar over the paralumbar fossa in the region of the urinary bladder suggestive of a projectile injury. The pellet was removed by a perineal urethrotomy. The patient was able to spontaneously urinate after urethrotomy, passed a tube cystostomy challenge two weeks after surgery, and was discharged. No complications were reported. While uncommon in the veterinary and comparative medical literature, clinicians should consider the potential for projectile pellets to migrate into the urinary tract after initial injury.

Pharmacokinetics of a single oral dose of grapiprant in juvenile pigs (Sus scrofa domestica).

Both pet and research pigs can suffer from some degree of pain from surgery, injuries, or osteoarthritis (OA). Despite this, there is a paucity of data on safe and effective analgesia agents in pigs. Grapiprant is an EP4 antagonist that blocks the action of the pro-inflammatory prostanoid, PGE2 . It has shown efficacy in attenuating pain associated with ovariohysterectomy and OA in dogs. However, there are no data regarding grapiprant in pigs. Therefore, the pharmacokinetic profile of orally administered grapiprant to juvenile pigs (Sus scrofa domestica) was evaluated in this study. Seven juvenile pigs received 12 mg/kg grapiprant orally. Blood was collected from an indwelling jugular catheter using the push-pull method at set timepoints up to 48 hours. Sample analysis was performed with high-performance liquid chromatography. Mean grapiprant plasma concentration was 164.3 ± 104.7 ng/mL which occurred at 0.8 ± 0.3 h. This study demonstrated that grapiprant concentrations consistent with analgesia in dogs were reached at this dosage in pigs. Further studies are needed to evaluate the efficacy of grapiprant in pigs.

In vitro analysis and in vivo assessment of fracture complications associated with use of locking plate constructs for stabilization of caprine tibial segmental defects.

PURPOSE: Locking plate fixation of caprine tibial segmental defects is widely utilized for translational modeling of human osteopathology, and it is a useful research model in tissue engineering and orthopedic biomaterials research due to its inherent stability while maintaining unobstructed visualization of the gap defect and associated healing. However, research regarding surgical technique and long-term complications associated with this fixation method are lacking. The goal of this study was to assess the effects of surgeon-selected factors including locking plate length, plate positioning, and relative extent of tibial coverage on fixation failure, in the form of postoperative fracture. METHODS: In vitro, the effect of plate length was evaluated using single cycle compressive load to failure mechanical testing of locking plate fixations of caprine tibial gap defects. In vivo, effects of plate length, positioning, and relative tibial coverage were evaluated using data from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over 3, 6, 9, and 12 months. RESULTS: In vitro, no significant differences in maximum compressive load or total strain were noted between fixations using 14 cm locking plates and 18 cm locking plates. In vivo, both plate length and tibial coverage ratio were significantly associated with postoperative fixation failure. The incidence of any cortical fracture in goats stabilized with a 14 cm plate was 57%, as compared with 3% in goats stabilized with an 18 cm plate. Craniocaudal and mediolateral angular positioning variables were not significantly associated with fixation failure. Decreasing distance between the gap defect and the proximal screw of the distal bone segment was associated with increased incidence of fracture, suggesting an effect on proximodistal positioning on overall fixation stability. CONCLUSIONS: This study emphasizes the differences between in vitro modeling and in vivo application of surgical fixation methods, and, based on the in vivo results, maximization of plate-to-tibia coverage is recommended when using locking plate fixation of the goat tibial segmental defect as a model in orthopedic research.

Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

Evaluation of the perioperative analgesic effects of grapiprant compared with carprofen in dogs undergoing elective ovariohysterectomy.

OBJECTIVE: To evaluate and compare postoperative analgesic effects of grapiprant and carprofen in dogs undergoing ovariohysterectomy. ANIMALS: 42 sexually intact female healthy dogs (< 35 kg and 0.5 to 7 years old) were enrolled. PROCEDURES: In a masked, randomized, noninferiority clinical trial, dogs received either 2 mg/kg of grapiprant or 4.4 mg/kg of carprofen orally 2 hours prior to ovariohysterectomy. Postoperative pain was assessed using the Glasgow Composite Pain Scale-Short Form (GCPS-SF) at extubation and 2, 4, 6, 8, 18, and 24 hours postextubation and compared to baseline. After each pain scoring, mechanical nociceptive testing with von Frey monofilaments (vF) was performed to assess hyperalgesia. Hydromorphone (0.05 mg/kg, IM) was administered to any dog with a GCPS-SF of ≥ 5/24. The noninferiority limit (NI) for the GCPS-SF was Δ = 3. The NI for vF was Δ = -0.2. Following noninferiority, a mixed-effect ANOVA and post hoc comparisons were made with the Tukey correction method (P < .05). RESULTS: 3 dogs required rescue analgesia and were excluded from statistical analysis. Of the remaining 39 dogs, the upper CI for GCPS-SF was below the NI of 3 and the lower CI for vF was greater than the NI of -0.2, indicating noninferiority of grapiprant as compared to carprofen. There was no difference between treatment (P = .89) nor treatment by time (P = .62) for GCPS-SF. There was no difference between groups at any time point or over time when vF were used. CLINICAL RELEVANCE: Our study results support the use of grapiprant as an analgesic alternative to carprofen in dogs undergoing ovariohysterectomy.

Effects of intravenous acepromazine and butorphanol on propofol dosage for induction of anesthesia in healthy Beagle dogs.

OBJECTIVE: To determine the effects of intravenous (IV) premedication with acepromazine, butorphanol or their combination, on the propofol anesthetic induction dosage in dogs. STUDY DESIGN: Prospective, blinded, Latin square design. ANIMALS: A total of three male and three female, healthy Beagle dogs, aged 3.79 ± 0.02 years, weighing 10.6 ± 1.1 kg, mean ± standard deviation. METHODS: Each dog was assigned to one of six IV treatments weekly: 0.9% saline (treatment SAL), low-dose acepromazine (0.02 mg kg-1; treatment LDA), high-dose acepromazine (0.04 mg kg-1; treatment HDA), low-dose butorphanol (0.2 mg kg-1; treatment LDB), high-dose butorphanol (0.4 mg kg-1; treatment HDB); and a combination of acepromazine (0.02 mg kg-1) with butorphanol (0.2 mg kg-1; treatment ABC). Physiologic variables and sedation scores were collected at baseline and 10 minutes after premedication. Then propofol was administered at 1 mg kg-1 IV over 15 seconds, followed by boluses (0.5 mg kg-1 over 5 seconds) every 15 seconds until intubation. Propofol dose, physiologic variables, recovery time, recovery score and adverse effects were monitored and recorded. Data were analyzed using mixed-effects anova (p < 0.05). RESULTS: Propofol dosage was lower in all treatments than in treatment SAL (4.4 ± 0.5 mg kg-1); the largest decrease was recorded in treatment ABC (1.7 ± 0.3 mg kg-1). Post induction mean arterial pressures (MAPs) were lower than baseline values of treatments LDA, HDA and ABC. Apnea and hypotension (MAP < 60 mmHg) developed in some dogs in all treatments with the greatest incidence of hypotension in treatment ABC (4/6 dogs). CONCLUSIONS AND CLINICAL RELEVANCE: Although the largest decrease in propofol dosage required for intubation was after IV premedication with acepromazine and butorphanol, hypotension and apnea still occurred.

Arterial oxygenation in anesthetized horses placed in a 5-degree reverse Trendelenburg position.

Low arterial oxygen is a common complication in anesthetized horses and placing the animal in reverse Trendelenburg (RT) position may treat hypoxemia. The objective of this study was to assess the arterial partial pressure of oxygen (PaO2) in horses placed in a 5-degree RT compared to horizontal (H) position. Client-owned healthy horses (n = 60) undergoing elective surgeries were enrolled in a randomized controlled clinical study. Horses were sedated with butorphanol, an α2-adrenoceptor agonist, ± acepromazine and induced with ketamine combined with a benzodiazepine, propofol, or guaifenesin. Anesthesia was maintained with isoflurane in oxygen with mechanical ventilation. Each group (RT and H) included 30 horses, 10 in each recumbency (dorsal, right and left lateral). Arterial blood gas analyses (aBG) were performed following arterial catheter placement then hourly. Time first-to-last aBG, changes in PaO2, dynamic compliance (Cdyn), estimated pulmonary shunt fraction (F-shunt), and alveolar dead space to tidal volume ratio (VD/VT) were evaluated with a 2-way analysis of variance. Statistical significance was set at p < .05. Overall, PaO2 increased in all groups; however no significant difference was found between recumbencies (dorsal, right and left lateral) and RT versus H in changes over time for PaO2 (p = .064 and p = .070, respectively), Cdyn (p = .721 and p = .672, respectively), F-shunt (p = .055 and p = .054, respectively), or VD/VT (p = .616 and p = .064, respectively). In healthy anesthetized horses, 5-degree RT did not affect changes in PaO2 as compared to H position.

Comparison of the effects on lameness of orally administered acetaminophen-codeine and carprofen in dogs with experimentally induced synovitis.

OBJECTIVE: To compare the ability of acetaminophen-codeine (AC; 15.5 to 18.5 mg/kg and 1.6 to 2.0 mg/kg, respectively) or carprofen (4.2 to 4.5 mg/kg) administered PO to attenuate experimentally induced lameness in dogs. ANIMALS: 7 purpose-bred dogs. PROCEDURES: A blinded crossover study was performed. Dogs were randomly assigned to receive AC or carprofen treatment first and then the alternate treatment a minimum of 21 days later. Synovitis was induced in 1 stifle joint during each treatment by intra-articular injection of sodium urate (SU). Ground reaction forces were assessed, and clinical lameness was scored at baseline (before lameness induction) and 3, 6, 9, 12, 24, 36, and 48 hours after SU injection. Plasma concentrations of acetaminophen, carprofen, codeine, and morphine were measured at various points. Data were compared between and within treatments by repeated-measures ANOVA. RESULTS: During AC treatment, dogs had significantly higher lameness scores than during carprofen treatment at 3, 6, and 9 hours after SU injection. Peak vertical force and vertical impulse during AC treatment were significantly lower than values during carprofen treatment at 3, 6, and 9 hours. Plasma concentrations of carprofen (R)- and (S)-enantiomers ranged from 2.5 to 19.2 µg/mL and 4.6 to 25.0 µg/mL, respectively, over a 24-hour period. Plasma acetaminophen concentrations ranged from 0.14 to 4.6 µg/mL and codeine concentrations from 7.0 to 26.8 ng/mL, whereas plasma morphine concentrations ranged from 4.0 to 58.6 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen as administered was more effective than AC at attenuating SU-induced lameness in dogs.

Resistin concentrations in serum and stifle synovial fluid from normal and cruciate deficient dogs with osteoarthritis.

OBJECTIVE: To compare synovial fluid (SF) resistin concentrations in healthy dogs to dogs with osteoarthritis (OA) secondary to cranial cruciate ligament (CrCL) injury and to correlate resistin concentrations with body condition score (BCS) and evaluate resistin release from peripheral blood mononuclear cells (PBMC) and adipocytes. STUDY DESIGN: Controlled, prospective, clinical study ANIMALS: Thirty-nine client-owned dogs, 13 healthy and 26 with secondary OA, were enrolled. Blood was collected from six healthy purpose-bred dogs for PBMC culture. An additional six mixed-breed dogs were used for adipocyte collection and culture. METHODS: Resistin concentrations were measured with a canine-specific enzyme-linked immunoabsorbent assay. Resistin was compared between healthy SF and OA SF with Student's t test. Correlation of resistin concentrations to BCS was performed. Peripheral blood mononuclear cells and adipocytes were cultured under three conditions: negative control, lipopolysaccharide, and concanavalin A (Con A). A linear mixed model was used to determine differences in resistin concentrations among treatments. RESULTS: Resistin concentrations in OA SF were comparable to healthy SF. Neither serum nor SF resistin was correlated with BCS. Cultured PBMC stimulated with Con A released resistin, while adipocytes did not. CONCLUSION: Neither serum nor SF resistin were altered in dogs with OA secondary to CrCL insufficiency. In addition, resistin was not correlated with canine body fat and did not appear to function as adipocytokine in the dog. CLINICAL SIGNIFICANCE: Resistin may not be involved in the pathogenesis of OA. However, resistin may be important in inflammation because it is released from inflammatory cells.

Elevated Synovial Fluid Concentration of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Dogs with Osteoarthritis of the Stifle.

Chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) have been shown to cause monocyte and natural killer cell chemotaxis and polymorphonuclear cell chemotaxis, respectively. Additionally, MCP-1 signalling has been implicated in modulating pain. Elevated synovial fluid concentrations of MCP-1 and IL-8 have been demonstrated in humans with osteoarthritis, but currently there are no studies evaluating synovial MCP-1 or IL-8 concentrations in dogs. Additionally, there are no canine studies evaluating the correlation between these chemokines and caregiver perceived pain and mobility, as measured by the clinical metrology instrument, Liverpool Osteoarthritis in Dogs. This study documented elevated synovial fluid concentrations of IL-8 and MCP-1 in the stifle of dogs with secondary osteoarthritis compared with normal stifles. However, this study found no correlation between MCP-1 or IL-8 and Liverpool Osteoarthritis in Dogs or radiographic severity of osteoarthritis.

Comparison of two inhibitors of E-type prostanoid receptor four and carprofen in dogs with experimentally induced acute synovitis.

OBJECTIVE: To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs. ANIMALS: 5 purpose-bred hound-cross dogs. PROCEDURES: A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA. RESULTS: Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant. CONCLUSIONS AND CLINICAL RELEVANCE: In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.

Immunomodulatory effects of dietary IMUNO-2865 in mice, pre-and post-vaccine challenge with parainfluenza virus 5.

Herbal remedies and nutraceuticals continue to be used as treatments for a variety of maladies ranging from joint disease to obesity. IMUNO-2865 is a natural nutraceutical supplement that has been advertised to modulate inflammation, boost cytokine activity promoting a robust immunity, but has yet to be evaluated as an adjuvant. In the present study, 4-week-old C57BL/6 female mice (n = 45) were fed 0, 5 or 50 mg/5 g tablet IMUNO-2865 (I-2865) in a tablet formulated feed. One group of mice (n = 15, 5 mice/diet) were placed on a feed diet for 14 days, while the other group of 30 mice (10 mice/diet) were placed on the diet for 28 days. Five mice from each diet group in the 28-day feeding trial were vaccinated on day 7 with a mouse recombinant parainfluenza virus to mimic viral challenge. On days 0, 14 and 28 blood samples were collected. Mice were humanely euthanized on days 14 and 28. Spleens were collected to analyze organ weight/body weight ratios, cell recovery, T cell and B cell phenotype, cell proliferation, antibody titers and cytokine production. Administration of dietary I-2865 for 14 days had no effect on murine immunity. In the 28-day dietary vaccine trial, I-2865 supplementation did not enhance vaccine response, based on vaccine antigen-specific IgG titers, nor did it alter T cell and B cell phenotype, function or cytokine response, but it did decrease splenocyte numbers in the vaccinated mice.

Correlation of serum and synovial leptin concentrations with body condition scores in healthy and osteoarthritic dogs.

OBJECTIVE: To evaluate the relationship between serum and synovial fluid (SF) leptin concentrations and body condition score (BCS) in healthy and osteoarthritic dogs. STUDY DESIGN: Controlled, prospective, clinical study. ANIMALS: Nineteen healthy dogs and 29 dogs with osteoarthritis (OA) secondary to cranial cruciate ligament injury. METHODS: Synovial fluid was obtained from the femorotibial joint under sedation (healthy dogs) or during surgery (OA dogs). Serum and SF leptin and interleukin (IL)-1ß concentrations were measured via enzyme-linked immunosorbent assay. Dogs were classified as optimal weight (BCS 4-5/9) or overweight (BCS >5/9). Radiographs were scored for OA severity by a radiologist. Owners completed the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire. RESULTS: Mean (± SD) SF leptin (4.09 ± 4 ng/mL) was lower than serum leptin (6.88 ± 5.52 ng/mL, P < .0001). Synovial fluid leptin was higher in overweight (5.28 ± 4.21) than in optimal body weight dogs (1.54 ± 1.72 ng/mL, P < .0001). Serum (P < .001) and SF leptin (P = .004) concentrations were associated with BCS. Concentration of SF leptin did not differ between healthy (2.4 ± 2.04 ng/mL) and OA (4.9 ± 4.3 ng/mL, P = .25) dogs. Synovial fluid leptin and LOAD scores were weakly associated (P = .03). No association was detected between SF leptin and radiographic score or IL-1ß (P = .73). CONCLUSION: Serum and SF leptin correlated with BCS in this population. Synovial fluid leptin was weakly associated with LOAD scores but not with radiographic severity of OA or IL-1ß. CLINICAL SIGNIFICANCE: Serum and SF leptin concentrations do not predict radiographic severity of canine OA but contribute to joint pain and dysfunction.

Effect of routine pre-anesthetic laboratory screening on pre-operative anesthesia-related decision-making in healthy dogs.

The usefulness of pre-anesthetic laboratory screening of healthy veterinary patients is controversial and clear evidence-based guidelines do not exist. The purpose of our study was to determine the influence of preanesthetic laboratory screening on peri-anesthetic plans in canine patients undergoing elective surgery. One hundred medical records were randomly selected between the years 2008 and 2013 and patient information was presented to 5 Diplomates of the American College of Veterinary Anesthesia and Analgesia (ACVAA) for review. They were given pre-anesthetic laboratory screening test results for each patient and asked whether the results would change the way they managed the case from an anesthesia perspective. Peri-operative anesthetic management was altered in 79% of patients based on pre-anesthetic screening results; however, the overall agreement among anesthesiologists was weak with 64% of changes made by only a single anesthesiologist. Pre-anesthetic laboratory screening test results may influence pre-operative anesthesia case management but major discrepancies can occur among ACVAA diplomates.

Effet du dépistage de laboratoire pré-anesthésique de routine sur la prise de décisions préopératoires liées à l'anesthésie chez des chiens en santé. L'utilité du dépistage de laboratoire pré-anesthésique des patients vétérinaires en santé est controversée et des lignes directrices claires basées sur des données probantes n'existent pas. Le but de notre étude consistait à déterminer l'influence du dépistage de laboratoire pré-anesthésique pour la péri-anesthésie chez les patients canins subissant une chirurgie non urgente. Cent dossiers médicaux choisis au hasard entre les années 2008 et 2013 et des données sur les patients ont été présentés à cinq diplomates de l'American College of Veterinary Anesthesia and Analgesia (ACVAA) aux fins d'examen. On leur a donné les résultats des tests de dépistage de laboratoire pré-anesthésiques pour chaque patient et on leur a demandé d'évaluer si les résultats auraient modifié la façon dont ils auraient géré le cas du point de vue de l'anesthésie. La gestion anesthésique péri-opératoire a été modifiée chez 79 % des patients en se basant sur les résultats du dépistage préanesthésique. Cependant, le consensus général parmi les anesthésiologistes était faible avec 64 % des changements apportés par seulement un seul anesthésiologiste. Les résultats des tests de dépistage de laboratoire pré-anesthésiques peuvent influencer la gestion des cas d'anesthésie préopératoire mais des écarts majeurs peuvent se produire parmi les diplomates de l'ACVAA.(Traduit par Isabelle Vallières).

Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis.

OBJECTIVE To investigate the effectiveness of tramadol for treatment of osteoarthritis in dogs. DESIGN Randomized, blinded, placebo-controlled crossover study. ANIMALS 40 dogs with clinical osteoarthritis of the elbow or stifle joint. PROCEDURES Dogs orally received 3 times/d (morning, midday, and night) for a 10-day period each of 3 identically appearing treatments (placebo; carprofen at 2.2 mg/kg [1 mg/lb], q 12 h [morning and night], with placebo at midday; or tramadol hydrochloride at 5 mg/kg [2.3 mg/lb], q 8 h) in random order, with treatment sessions separated by a minimum 7-day washout period. Vertical ground reaction forces (vertical impulse [VI] and peak vertical force [PVF]) were measured and Canine Brief Pain Inventory (CBPI) scores assigned prior to (baseline) and at the end of each treatment period. Repeated-measures ANOVA was performed to compare VI and PVF data among and within treatments, and the χ2 test was used to compare proportions of dogs with a CBPI-defined positive response to treatment. RESULTS 35 dogs completed the study. No significant changes from baseline in VI and PVF were identified for placebo and tramadol treatments; however, these values increased significantly with carprofen treatment. Changes from baseline in VI and PVF values were significantly greater with carprofen versus placebo or tramadol treatment. A significant improvement from baseline in CBPI scores was identified with carprofen treatment but not placebo or tramadol treatment. CONCLUSIONS AND CLINICAL RELEVANCE 10 days of treatment with tramadol as administered (5 mg/kg, PO, q 8 h) provided no clinical benefit for dogs with osteoarthritis of the elbow or stifle joint.

Synovial membrane receptors as therapeutic targets: A review of receptor localization, structure, and function.

Joint pathology and degeneration is a significant cause of pain. The synovial membrane plays an important role in maintenance of the joint, contributes to the pathology of many arthropathies and may be adversely affected in joint disease. Improving knowledge of the receptors present within the synovium will aid in a better understanding of joint pathology and the development of new treatments for diseases such as osteoarthritis and rheumatoid arthritis. Knowledge of the location and function of synovial membrane receptors (both in healthy and diseased synovium) may provide important targets in the treatment of various arthropathies. Classic pain receptors such as opioid receptors in the synovium are a mainstay in local and systemic management of chronic pain in many species. In addition to these, many other receptors such as bradykinin, neurokinin, transient receptor potential vanilloid, and inflammatory receptors, such as prostanoid and interleukin receptors have been discovered within the synovial membrane. These receptors are important in pain, inflammation, and in maintenance of normal joint function and may serve as targets for pharmacologic intervention in pathologic states. The goal of this review is to outline synovial membrane receptor localization and local therapeutic modulation of these receptors, in order to stimulate further research into pharmacological management of arthropathies at the local level. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1589-1605, 2017.

Determination of the minimum alveolar concentration of isoflurane that blunts adrenergic responses in sheep and evaluation of the effects of fentanyl.

OBJECTIVE: To determine the minimum alveolar concentration that blunts adrenergic responses (MACBAR) for isoflurane and evaluate effects of fentanyl on isoflurane MACBAR in sheep. ANIMALS 13 healthy adult Dorset-cross adult ewes. PROCEDURES: In a crossover design, each ewe was anesthetized 2 times for determination of isoflurane MACBAR. Anesthesia was induced with propofol administered IV. Sheep initially received fentanyl (5 µg/kg, IV, followed by a constant rate infusion of 5 µg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment). After a washout period of at least 8 days, the other treatment was administered. For MACBAR determination, a mechanical nociceptive stimulus (ie, sponge forceps) was applied at the coronary band for 1 minute. The MACBAR values of the 2 treatments were compared by means of a paired t test. During MACBAR determination, blood samples were collected for measurement of plasma fentanyl concentration. RESULTS: Mean ± SD isoflurane MACBAR of the fentanyl and control treatments was 1.70 ± 0.28% and 1.79 ± 0.35%, respectively; no significant difference was found between the 2 treatments. Plasma concentration of fentanyl reached a median steady-state concentration of 1.69 ng/mL (interquartile range [25th to 75th percentile], 1.47 to 1.79 ng/mL), which was maintained throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of fentanyl at 5 µg/kg, IV, followed by a constant rate infusion of the drug at 5 µg/kg/h did not decrease isoflurane MACBAR. Further studies to determine the effect of higher doses of fentanyl on inhalation anesthetic agents and their potential adverse effects are warranted.