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.

Validation of a human paper-based blood typing method for use in pet pigs.

BACKGROUND: Evidence-based medical practices for pet pigs are needed. EldonCard is a human blood-typing card shown to be rapid and reliable in identifying blood phenotypes of pet pigs. The objective of this study was to validate EldonCard by determining its reliability, reproducibility, and robustness for its routine use in the clinical setting. KEY FINDINGS: Twenty-four venous blood samples from pet pigs were collected for a prospective in vitro study. Blood genotypes ("EAAA0 " and "EAA00 ") were identified in 15 samples via polymerase chain reaction (PCR). All samples were phenotyped ("A," "Aweak ," and "0" or "-") via EldonCard. Kappa (κ) statistics measured the level of agreement between 2 raters, and between EldonCard and PCR. McNemar's test determined if an association between the blood types and EldonCard or PCR exists, with significance at P < 0.05. Agreement between raters and methods was perfect (60/60 [100%], κ:1, P < 0.001; 15/15 [100%], κ:1, P < 0.001). There was no difference in the proportions of blood groups based on method. SIGNIFICANCE: In conjunction with previous data, EldonCard is a rapid, accurate, reliable, precise, and robust in-clinic blood-typing method for the A0 system of pet pigs. EldonCard is now a validated blood-typing tool for the A0 system of pet pigs and maybe used for pretransfusion screenings and identification of donors and recipients.

The effect of age on the induction dose of propofol for general anesthesia in dogs.

OBJECTIVE: In people, the dose of propofol (DOP) required for procedural sedation and anesthesia decreases significantly with age. The objective of this study was to determine if the DOP required to perform endotracheal intubation decreases with age in dogs. STUDY DESIGN: Retrospective case series. ANIMALS: 1397 dogs. METHODS: Data from dogs anesthetized at referral center (2017-2020) were analyzed with three multivariate linear regression models with backward elimination using a combination of either absolute age, physiologic age, or life expectancy (ratio between age at the time of anesthetic event and expected age of death for each breed obtained from previous literature) as well as other factors as independent variables, and DOP as the dependent variable. The DOP for each quartile of life expectancy (<25%, 25-50%, 50-75%, 75-100%, >100%) was compared using one-way ANOVA. Significance was set at alpha = 0.025. RESULTS: Mean age was 7.2 ± 4.1 years, life expectancy 59.8 ± 33%, weight 19 ± 14 kg, and DOP 3.76 ± 1.8 mg kg-1. Among age models, only life expectancy was a predictor of DOP (-0.37 mg kg-1; P = 0.013) but of minimal clinical importance. The DOP by life age expectancy quartile was 3.9 ± 2.3, 3.8 ± 1.8, 3.6 ± 1.8, 3.7 ± 1.7, and 3.4 ± 1.6 mg kg-1, respectively (P = 0.20). Yorkshire Terrier, Chihuahua, Maltese, mixed breed dogs under 10 kg, and Shih Tzu required higher DOP. Status of neutered male, ASA E, and Boxer, Labrador and Golden Retriever breeds decreased DOP, along with certain premedication drugs. CONCLUSIONS AND CLINICAL RELEVANCE: In contrast to what is observed in people, an age cut-off predictive of DOP does not exist. Percentage of elapsed life expectancy along with other factors such as breed, premedication drug, emergency procedure, and reproductive status significantly alter DOP. In older dogs, the dose of propofol can be adjusted based on their elapsed life expectancy.

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.

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.

Comparison of blind and endoscopic-guided orotracheal intubation on laryngeal and tracheal damage in domestic rabbits (Oryctolagus cuniculus).

OBJECTIVE: To compare blind and endoscopic-guided techniques for orotracheal intubation in rabbits and the number of intubation attempts with laryngeal/tracheal damage. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: A total of 24 healthy, intact female New Zealand White rabbits, weighing 2.2 ± 0.2 kg (mean ± standard deviation). METHODS: Rabbits were randomly assigned to blind (group B) or endoscopic-guided (group E) orotracheal intubation with a 2.0 mm internal diameter uncuffed tube. Intramuscular (IM) alfaxalone (7 mg kg-1), hydromorphone (0.1 mg kg-1) and dexmedetomidine (0.005 mg kg-1) were administered, and additional IM alfaxalone (3-5 mg kg-1) and dexmedetomidine (0.025 mg kg-1) were administered to rabbits with strong jaw tone. An intubation attempt was defined as the advancement of the endotracheal tube from the incisors to the laryngeal entrance. Tracheal intubation was confirmed via capnography and anesthesia was maintained with isoflurane for 2 hours. Following euthanasia, laryngeal and tracheal tissues were submitted for histopathology. Quality of anesthesia for orotracheal intubation, intubation procedure and tissue damage were numerically scored. Data were analyzed using Poisson regression, Spearman's correlation, t test, mixed anova, Mann-Whitney U test, Friedman and Chi square tests as appropriate. RESULTS: Median (range) intubation attempts were 2 (1-8) and 1 (1-3) for groups B and E, respectively. More rabbits in group E (91.6%) required additional alfaxalone and dexmedetomidine than in group B (16.7%). Median (range) cumulative histopathology scores were 6 (3-10) and 6 (2-9) for groups B and E, respectively. Scores were highest in the cranial trachea, but there was no difference between groups and no correlation between laryngeal/tracheal damage and the number of intubation attempts. CONCLUSIONS AND CLINICAL RELEVANCE: Both orotracheal intubation techniques were associated with laryngeal/tracheal damage. Although blind orotracheal intubation was associated with a higher number of attempts, the tissue damage was similar between groups.

Hemodynamic Changes in Response to Hyperacute Spinal Trauma in a Swine Model.

Acute spinal cord injury (ASCI) is a devastating event that can have severe hemodynamic consequences, depending on location and severity of the lesion. Knowledge of hyperacute hemodynamic changes is important for researchers using porcine models of thoracic ASCI. The goal of this study was to determine the hyperacute hemodynamic changes observed after ASCI when using pigs as their own controls. Five Yucatan gilts were anesthetized, and a dorsal laminectomy performed at T10-T12. Standardized blunt trauma was applied for 5 consecutive min, and hemodynamic variables were collected 5 min before ASCI, and at 2, 4, 6, 8, 10, 20, 30, 60, 80 and 120 min after ASCI. Arterial blood gas samples were collected at 60 min and 10 min before, and at 30 min and between 120 and 240 min after ASCI. Parametric data were analyzed using a mixed effects model with time point as the fixed factor and subject as the random factor. We found no effect on heart rate, pulse pressure, SpO2, EtCO2, and respiratory rate between baseline and timepoints after ASCI. Diastolic arterial pressure, mean arterial pressure, and systolic arterial pressure fell significantly by 18%, 16%, and 15%, respectively, at 2 min after ASCI. However, none of the decrements in arterial pressures resulted in hypotension at any time point. Heart rate did not change significantly after ASCI. Blood glucose progressively increased to 50% above baseline between 120 and 240 minutes after ASCI. Low thoracic ASCI caused a consistent and statistically significant but clinically minor hyperacute decrease in arterial pressures (-15%) that did not produce hypotension or metabolic changes suggestive of tissue hypoperfusion. Our findings using this model suggest that mean arterial pressures should be maintained above 85 mm Hg prior to spinal trauma in order to avoid hypotensive states after ASCI.

Assessment of intramuscular administration of three doses of alfaxalone combined with hydromorphone and dexmedetomidine for endoscopic-guided orotracheal intubation in domestic rabbits (Oryctolagus cuniculus).

OBJECTIVE: To determine the dose of alfaxalone for IM administration combined with dexmedetomidine and hydromorphone that would allow endoscopic-guided orotracheal intubation in rabbits without causing a decrease in respiratory rate or apnea. ANIMALS: 15 sexually intact (9 females and 6 males) healthy Miniature Lop rabbits weighing a mean ± SD of 2.3 ± 0.3 kg and ranging in age from 4 to 9 months. PROCEDURES: In a randomized, controlled clinical trial, rabbits received 0.1 mg of hydro-morphone/kg and 0.005 mg of dexmedetomidine/kg, plus alfaxalone at either 2 mg/kg (5 rabbits), 5 mg/kg (5 rabbits), or 7 mg/kg (5 rabbits). Drugs were mixed in a single syringe and administered IM. Semiquantitative rating scales were used to evaluate quality of anesthesia and intubation. Orotracheal intubation was attempted with endoscopy and confirmed by capnography. RESULTS: The number of successful intubations was 0, 3, and 4 in rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. Median (range) anesthesia quality scores (scale, 0 to 12; 12 = deepest anesthesia) were 3 (2 to 5), 6 (5 to 6), and 6 (4 to 9) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. The median (range) intubation quality scores (scale, 0 to 3 [ie, intubation not possible to easiest intubation]) were 0 (0 to 0), 2 (0 to 3), and 2 (0 to 3) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. None of the rabbits experienced a decrease in respiratory rate or apnea. CONCLUSIONS AND CLINICAL RELEVANCE: Increasing doses of alfaxalone combined with hydromorphone and dexmedetomidine increased the success rate of endoscopic-guided orotracheal intubation. Increasing the dose of alfaxalone had no effect on respiratory rate.

Pharmacokinetics of oral and compounded intravenous gabapentin in Duroc swine (Sus Scrofa).

The objective of this study was to determine the pharmacokinetics (PK) of oral (OS; 20 mg/kg) and compounded intravenous (IV; 5.5 mg/kg) gabapentin in 6 healthy, adult, Duroc pigs. Subjects were randomized to receive IV and OS gabapentin in a cross-over design, with at least 14 days of wash-out period between the two rounds of drug administrations. Blood samples were obtained before gabapentin administration and at various times up to 24 h, and harvested plasma was stored at -80°C until analysis. Concentration of gabapentin was quantified using a previously validated liquid chromatography/tandem mass spectrometry method, and compartment models were fitted to time-concentration data using non-linear mixed effect (population) analysis. A two-compartment model best fitted the data following IV administration. Typical values for volume of the central compartment and clearance and calculated volume of distribution at steady-state and terminal half-life were 170 ml/kg, 1.2 ml/(kg*min), and 594 ml/kg and 360 min, respectively. For the oral route, absorption half-life, estimated maximal plasma concentration and time to reach maximal plasma concentration were 58 min, 9155 ng/ml, and 194 min, respectively. Estimated oral bioavailability was 47%. Short-lived sedation (approximately 15 min) with sternal or lateral recumbency after IV administration was observed in all subjects without adverse clinical effects. Simulation based on the results of this study suggests that a first oral gabapentin dose of 15 mg/kg and subsequent doses of 8.5 mg/kg every 8 h would achieve and maintain plasma concentrations between 5 and 8 µg/ml in pigs.

Sedation Characteristics of Intranasal Alfaxalone in Adult Yucatan Swine.

Compared with intravenous and intramuscular methods, intranasal administration of sedatives is a less invasive and nonpainful technique. In this prospective, randomized, crossover study, we evaluated the sedative characteristics of 2 doses (1 and 2 mg/kg) of alfaxalone administered intranasally to 7 adult Yucatan swine. We compared sedation scores before and after administration of alfaxalone and between groups by using a composite sedation scoring system (range, 0 to 12, with 12 being the highest level of sedation)). Pigs were randomly assigned to receive 2 doses of intranasal alfaxalone (1 mg/kg [A1]); 2 mg/kg [A2]) as 2 separate events in a crossover design with a 60-d washout period. Categories scored were posture, palpebral droop, uninhibited behavior, drowsiness, and acceptance of anesthetic facemask. Sedation scores were collected before sedation was administered and then every 3 min for 30 min afterward. Instilled volumes (mean ± 1 SD) were 5.7 ± 0.5 and 11.3 ± 0.8 mL for A1 and A2, respectively. Both alfaxalone doses produced significant increases in sedation scores compared with baseline. Median sedation scores for A1 (6; range, 4-12) were not different from those for A2 (6; range, 6 to 12). Intranasal administration of alfaxalone as the sole sedative agent increased sedation scores from baseline, achieving peak sedation at 6 to 9 min after instillation of A2. However, sedation scores were similar between the 2 groups, and neither dose produced sufficient sedation to facilitate handling or the performance of any clinical procedures. Given the concentration of alfaxalone solution currently available, volume is the major limiting factor regarding testing higher doses of this drug for its use as a sole sedative agent in swine.

Effect of Cranial Flexion of Pelvic Limbs on Interlaminar Length of the Lumbosacral Space in Sternally and Laterally Recumbent Juvenile Duroc and Adult Yucatan Pigs.

Epidural puncture in swine is technically challenging. Several combinations of limb and body positions have been suggested to increase lumbosacral interlaminar space (LSS) and lumbosacral angle (LSA). This study investigated whether cranial hyperflexion of pelvic limbs increased LSS and LSA in laterally and sternally recumbent juvenile Duroc and adult Yucatan pigs and assessed which position produced the largest LSS. Juvenile Duroc (n = 7) and adult Yucatan (n = 7) pigs were euthanized and randomly placed in 4 positions: sternal with neutral limbs, sternal with cranially hyperflexed limbs, lateral with neutral limbs, and lateral with hyperflexed limbs. LSS and LSA were measured on transverse axial CT images of the spine and compared by using multivariate ANOVA and the Student t test. In both age groups, LSS was greater in lateral flexed (juvenile, 7.0 ± 0.7 mm; adult, 15.9 ± 1.1 mm) and sternal flexed (juvenile, 7.5 ± 1 mm; adult, 17.1 ± 1.1 mm) positions than in lateral neutral (juvenile, 5.4 ± 0.9 mm; adult, 9.6 ± 1.6 mm) position. In addition, in both age groups, LSS and LSA in lateral neutral position were smaller than lateral flexed, sternal neutral, and sternal flexed positions. In adults, LSS was greater in lateral flexed and sternal flexed than in sternal neutral position. Hyperflexion of pelvic limbs increases LSS and LSA in sternally recumbent adult Yucatan pigs and laterally recumbent adult Yucatan and juvenile Duroc swine. Increased LSS from positioning pigs with pelvic limbs flexed in sternal or lateral recumbence may facilitate epidural puncture compared with neutral limb positioning.

Recovery characteristics of dogs following anesthesia induced with tiletamine-zolazepam, alfaxalone, ketamine-diazepam, or propofol and maintained with isoflurane.

OBJECTIVE To compare characteristics of recovery from isoflurane anesthesia in healthy nonpremedicated dogs after anesthetic induction by IV administration of tiletamine-zolazepam with those observed after induction by IV administration of alfaxalone, ketamine-diazepam, or propofol. DESIGN Prospective, randomized crossover study. ANIMALS 6 healthy adult hounds. PROCEDURES Each dog underwent the 4 treatments in random order with a ≥ 7-day washout period between anesthetic episodes. Anesthesia was induced by IV administration of the assigned induction drug or combination (each to effect in 25% increments of calculated dose) and maintained with isoflurane in oxygen for 60 minutes. Cardiorespiratory variables and end-tidal isoflurane concentration (ETISO) were measured just before isoflurane administration was discontinued. Dogs were observed and video recorded during recovery. Recovery characteristics were retrospectively scored from recordings by 3 raters. Interrater and intrarater reliability of scoring was assessed by intraclass correlation coefficient calculation. Linear and mixed ANOVAs were used to compare extubation times, recovery scores, and body temperature among treatments. RESULTS Most cardiorespiratory variables, body temperature, ETISO, and time to extubation did not differ between tiletamine-zolazepam and other induction treatments. Recovery scores were lower (indicating better recovery characteristics) with propofol or alfaxalone than with tiletamine-zolazepam but did not differ between tiletamine-zolazepam and ketamine-diazepam treatments. Anesthetic episode number and ETISO had no effect on extubation time or recovery score. Intrarater and interrater correlations for recovery scores were excellent. CONCLUSIONS AND CLINICAL RELEVANCE Recovery of healthy dogs from anesthesia with isoflurane after induction with tiletamine-zolazepam was uncomplicated and had characteristics comparable to those observed following induction with ketamine-diazepam. However, recovery characteristics were improved when anesthesia was induced with propofol or alfaxalone.

Effects of intravenous administration of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for induction of anesthesia on cardiorespiratory and metabolic variables in healthy dogs before and during anesthesia maintained with isoflurane.

OBJECTIVE To compare effects of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for anesthetic induction on cardiorespiratory and acid-base variables before and during isoflurane-maintained anesthesia in healthy dogs. ANIMALS 6 dogs. PROCEDURES Dogs were anesthetized with sevoflurane and instrumented. After dogs recovered from anesthesia, baseline values for cardiorespiratory variables and cardiac output were determined, and arterial and mixed-venous blood samples were obtained. Tiletamine-zolazepam (5 mg/kg), alfaxalone (4 mg/kg), propofol (6 mg/kg), or ketamine-diazepam (7 and 0.3 mg/kg) was administered IV in 25% increments to enable intubation. After induction (M0) and at 10, 20, 40, and 60 minutes of a light anesthetic plane maintained with isoflurane, measurements and sample collections were repeated. Cardiorespiratory and acid-base variables were compared with a repeated-measures ANOVA and post hoc t test and between time points with a pairwise Tukey test. RESULTS Mean ± SD intubation doses were 3.8 ± 0.8 mg/kg for tiletamine-zolazepam, 2.8 ± 0.3 mg/kg for alfaxalone, 6.1 ± 0.9 mg/kg and 0.26 ± 0.04 mg/kg for ketamine-diazepam, and 5.4 ± 1.1 mg/kg for propofol. Anesthetic depth was similar among regimens. At M0, heart rate increased by 94.9%, 74.7%, and 54.3% for tiletamine-zolazepam, ketamine-diazepam, and alfaxalone, respectively. Tiletamine-zolazepam caused higher oxygen delivery than propofol. Postinduction apnea occurred in 3 dogs when receiving alfaxalone. Acid-base variables remained within reference limits. CONCLUSIONS AND CLINICAL RELEVANCE In healthy dogs in which a light plane of anesthesia was maintained with isoflurane, cardiovascular and metabolic effects after induction with tiletamine-zolazepam were comparable to those after induction with alfaxalone and ketamine-diazepam.