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Abstract

Objective—To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep.

Animals—6 healthy adult Dorset cross sheep (5 males and 1 female).

Procedures—Meloxicam (0.5 mg/kg, IV, or 1.0 mg/kg, PO) was administered in a randomized crossover design with a 10-day washout period. Blood samples were collected at predetermined times over 96 hours. Serum drug concentrations were determined by high-pressure liquid chromatography with mass spectrometry. Computer software was used to estimate values of pharmacokinetic parameters through noncompartmental methods.

Results—Following IV administration (n = 5), the geometric mean (range) elimination half-life was 14.0 hours (10.5 to 17.0 hours), volume of distribution was 0.204 L/kg (0.171 to 0.272 L/kg), and clearance was 0.17 mL/min/kg (0.12 to 0.27 mL/min/kg). Following oral administration (n = 6), maximum serum concentration was 1.72 μg/mL (1.45 to 1.93 μg/mL), time to maximum serum concentration was 19.0 hours (12.0 to 24.0 hours), clearance per bioavailability was 0.22 mL/min/kg (0.16 to 0.30 mL/min/kg), and terminal half-life was 15.4 hours (13.2 to 17.7 hours). Bioavailability of orally administered meloxicam was calculated as 72% (40% to 125%; n = 5). No adverse effects were evident following meloxicam administration via either route.

Conclusions and Clinical Relevance—Meloxicam administered PO at 1.0 mg/kg has good bioavailability with slow elimination kinetics in sheep. These data suggested that meloxicam may be clinically useful, provided the safety and analgesic efficacy of meloxicam as well as feed-related influences on its pharmacokinetics are established in ruminants.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To survey cattle producers and veterinarians about the use of analgesia on US cattle operations.

SAMPLE

1,187 members of the following database, electronic mailing lists, and social media groups: FarmProgress master file, American Association of Bovine Practitioners, Academy of Veterinary Consultants, National Milk Producers Federation Farm Evaluators, Dairy Moms Facebook group, and Dairy Girl Network Facebook group.

PROCEDURES

An online survey was developed to gather information about the frequency of local and systemic analgesia use for common painful procedures and diseases in cattle < 2, 2 to 12, and > 12 months old. Respondents also rated their extent of agreement with each of 10 statements related to pain management in cattle. The survey was available from June 11 to August 10, 2018. Descriptive data were generated. Logistic regression was used for comparisons among cattle age groups and respondents on the basis of their industry role.

RESULTS

In general, frequency of analgesia use increased as cattle age increased, regardless of the procedure or disease. The odds of analgesia use were lower for men, compared with women, and greater for veterinarians, compared with producers. Many respondents indicated they were cognizant of the benefits of analgesia use in cattle but perceived federal regulations and drug costs as impediments to the implementation of pain mitigation protocols on cattle operations.

CONCLUSIONS AND CLINICAL RELEVANCE

Results provided insight into current perceptions and use of analgesia in cattle, which can be used to guide implementation of pain mitigation protocols on US beef and dairy cattle operations.

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To evaluate the effects of meloxicam on movement, feeding, and drinking behaviors of transported and nontransported cattle.

ANIMALS 100 crossbred beef steers.

PROCEDURES During experiment 1 of a 2-experiment study, calves from a livestock auction received meloxicam (1 mg/kg, PO; n = 50) or a lactose placebo (1 capsule/calf; 50; control), then calves were transported approximately 1,000 km overnight to a feedlot, where they were instrumented with a real-time location-monitoring ear tag, placed in randomly assigned pens (n = 5 pens/treatment), and monitored for 21 days. During experiment 2, calves in pens were administered the treatment opposite that of experiment 1, returned to their pens without undergoing transportation, and monitored for another 21 days. For each experiment, mean daily distance traveled and percentage time spent near feed (PNF) and water (PNW) were calculated on a pen basis and compared between treatments.

RESULTS During experiment 1, mean daily distance traveled, PNF, and PNW did not differ significantly between meloxicam-treated and control calves; however, all 3 behaviors varied significantly by day. During experiment 2, although mean distance traveled was significantly associated with the interaction between day and treatment, it did not differ significantly between meloxicam-treated and control calves within any specific day. Mean PNF and PNW were significantly associated with day only, although no pattern in that effect was evident.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a single dose of meloxicam prior to transportation did not significantly affect the behaviors of transported and nontransported calves.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the impact of oxytetracycline exposure on horizontal transfer of an antimicrobial resistance plasmid.

Sample—Populations of Salmonella enterica subsp enterica serovar Typhimurium and Escherichia coli.

Procedures—Mixed populations of plasmid donor (Salmonella Typhimurium) and recipient (E coli) bacteria were assigned to 1 of 2 simulated oxytetracycline dosing regimens (high peak concentration-short elimination half-life [HC-SHL] or low peak concentration—long elimination half-life [LC-LHL]) or served as untreated control replicates. Donor, recipient, and transconjugant (E coli that acquired the plasmid) bacteria populations were quantified at 12, 24, and 36 hours after oxytetracycline administration by use of culture on selective bacterial growth media.

Results—The ratio of transconjugant to donor bacteria was significantly reduced in the oxytetracycline-exposed replicates, compared with the ratio for the control replicates, at 12 hours. At 24 and 36 hours, results for the HC-SHL regimens were not significantly different from results for the respective control replicates, and results for the LC-LHL regimens also were not significantly different from results for the respective control replicates. The oxytetracycline concentration at these time points (12 hours in the HC-SHL regimen and all 3 time points in the LC-LHL regimen) were in excess of the minimum inhibitory concentration of the recipient bacteria.

Conclusions and Clinical Relevance—Transfer of antimicrobial resistance plasmids may be suppressed in vitro by oxytetracycline exposure at concentrations greater than the minimum inhibitory concentration of the recipient bacteria.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the accuracy of accelerometers for measuring behavior changes in calves and to determine differences in beef calf behavior from before to after castration.

Animals—3 healthy Holstein calves and 12 healthy beef calves.

Procedures—2-dimensional accelerometers were placed on 3 calves, and data were logged simultaneous to video recording of animal behavior. Resulting data were used to generate and validate predictive models to classify posture (standing or lying) and type of activity (standing in place, walking, eating, getting up, lying awake, or lying sleeping). The algorithms developed were used to conduct a prospective trial to compare calf behavior in the first 24 hours after castration (n = 6) with behavior of noncastrated control calves (6) and with presurgical readings from the same castrated calves.

Results—On the basis of the analysis of the 2-dimensional accelerometer signal, posture was classified with a high degree of accuracy (98.3%) and the specific activity was estimated with a reasonably low misclassification rate (23.5%). Use of the system to compare behavior after castration revealed that castrated calves spent a significantly larger amount of time standing (82.2%), compared with presurgical readings (46.2%).

Conclusions and Clinical Relevance—2-dimensional accelerometers provided accurate classification of posture and reasonable classification of activity. Applying the system in a castration trial illustrated the usefulness of accelerometers for measuring behavioral changes in individual calves.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy.

ANIMALS

20 weaned Holstein calves with umbilical hernias.

PROCEDURES

Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group.

RESULTS

During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•μg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To assess the analgesic efficacy of an IV constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination in calves undergoing umbilical herniorrhaphy.

ANIMALS

20 weaned Holstein calves with umbilical hernias.

PROCEDURES

Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). The assigned CRI was begun after anesthesia induction. A pain-scoring system and incisional algometry were used to assess pain, and blood samples were obtained to measure serum cortisol concentration at predetermined times for 120 hours after CRI initiation.

RESULTS

Mean pain scores did not differ significantly between the MLK and control groups at any time. Mean algometry score for the MLK group was significantly greater (calves were less responsive to pressure) than that for the control group at 4 hours after CRI initiation. Mean cortisol concentration decreased over time for both groups and was significantly greater for the MLK group than the control group at 1, 4, and 18 hours after CRI initiation.

CONCLUSIONS AND CLINICAL RELEVANCE

A CRI of MLK provided adequate postoperative analgesia to calves that underwent umbilical herniorrhaphy. However, the technical support required for CRI administration limits its use to hospital settings. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols and withdrawal intervals.

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning.

Animals—40 Holstein bull calves from 3 farms.

Procedures—Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated.

Results—ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods.

Conclusions and Clinical Relevance—SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize amphotericin B–induced lameness in cattle and to ascertain the analgesic effects of flunixin meglumine by use of multimodal assessment.

Animals—10 healthy Holstein steers free from musculoskeletal disease.

Procedures—Steers were randomly allocated to a treatment or negative control group. Amphotericin B was injected into the distal interphalangeal joint of the lateral claw of the left hind limb of all steers. Treatment steers received flunixin meglumine at the time of synovitis-arthritis induction and at 12 hours after induction. Control steers received no medication. Multimodal analysis included vital parameters, visual lameness score, behavioral monitoring with accelerometers, pressure mat analysis, and plasma cortisol determination before and after induction. Data were analyzed by use of linear mixed models with treatment and time designated as fixed effects, accounting for repeated measures on individual calves.

Results—Amphotericin B injection induced moderate, transient lameness. Control steers were more than twice as likely to be lame as treatment steers (mean ± SD lameness score, 92.2 ± 8.1 % vs 40.7 ± 2.5%). Treatment steers placed significantly greater force and contact area on the affected foot and greater force, impulse, and contact area on the paired claw, compared with control steers. Furthermore, treatment steers spent considerably less time in recumbency than controls.

Conclusions and Clinical Relevance—Amphotericin B successfully induced synovitis-arthritis in dairy steers that was transient in nature. Flunixin meglumine was efficacious in providing analgesia for these steers.

Full access
in American Journal of Veterinary Research