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.
To survey cattle producers and veterinarians about the use of analgesia on US cattle operations.
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.
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.
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.
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.
During a large animal clinical rotation at the College of Veterinary Medicine, Iowa State University, veterinary students commented on observing variability in the route by which perioperative antimicrobials were being administered to prevent surgical site infections in cattle. The clinicians indicated that preoperative parenteral administration of antimicrobials was likely the preferred route, as suggested by the literature available on antimicrobial use in other veterinary species; however, such use results in drug residues that prevent immediate slaughter of the affected cattle for use in the food supply when surgical findings suggest a poor prognosis. Consequently, veterinarians are often under pressure
To assess the analgesic efficacy of an IV constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination in calves undergoing umbilical herniorrhaphy.
20 weaned Holstein calves with umbilical hernias.
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.
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.
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.
Objective—To compare sensitivity of a complement fixation (CF) test and competitive ELISA (cELISA) for detection of Anaplasma marginale in experimentally infected steers.
Animals—40 crossbred (Angus-Simmental) steers.
Procedures—Steers were inoculated with 2.6 × 109A marginale–infected erythrocytes (day 0). Blood samples were collected on days 9, 13, 20, 28, 34, 41, 61, 96, 126, and 156 days after inoculation. The percentage of parasitized erythrocytes (PPE) was determined by microscopic examination of stained blood films, and sera were evaluated with the CF test and cELISA by use of USDA-approved methods. Sensitivity and agreement (κ statistic) between the 2 methods were determined. Persistent infections were confirmed by inoculation of blood obtained from infected steers into susceptible, splenectomized calves.
Results—9 days after inoculation, sensitivity of the cELISA was 47.5%, whereas the CF test failed to identify seropositive steers. After day 13, sensitivity of the cELISA and CF test was 100% and 20%, respectively. During peak parasitemia (day 20), sensitivity of the cELISA and CF test was 100%. Thereafter, sensitivity of the CF test fluctuated between 7.5% and 37.5%, whereas sensitivity of the cELISA remained at 100%. Overall sensitivity of the cELISA and CF test was 94.8% and 26.5%, respectively (κ statistic, 0.039).
Conclusions and Clinical Relevance—The cELISA had superior sensitivity for serologic detection of A marginale.The CF test and cELISA each had a high percentage of false-negative results during the prepatent period. These findings are relevant for export certification and anaplasmosis prevention or eradication programs.
Objective—To determine the effects of protease inhibitors and holding times and temperatures before processing on the stability of substance P in bovine blood samples.
Samples—Blood samples obtained from a healthy 6-month-old calf.
Procedures—Blood samples were dispensed into tubes containing exogenous substance P and 1 of 6 degradative enzyme inhibitor treatments: heparin, EDTA, EDTA with 1 of 2 concentrations of aprotinin, or EDTA with 1 of 2 concentrations of a commercially available protease inhibitor cocktail. Plasma was harvested immediately following collection or after 1, 3, 6, 12, or 24 hours of holding at ambient (20.3° to 25.4°C) or ice bath temperatures. Total substance P immunoreactivity was determined with an ELISA; concentrations of the substance P parent molecule, a metabolite composed of the 9 terminal amino acids, and a metabolite composed of the 5 terminal amino acids were determined with liquid chromatography–tandem mass spectrometry.
Results—Regarding blood samples processed immediately, no significant differences in substance P concentrations or immunoreactivity were detected among enzyme inhibitor treatments. In blood samples processed at 1 hour of holding, substance P parent molecule concentration was significantly lower for ambient temperature versus ice bath temperature holding conditions; aprotinin was the most effective inhibitor of substance P degradation at the ice bath temperature. The ELISA substance P immunoreactivity was typically lower for blood samples with heparin versus samples with other inhibitors processed at 1 hour of holding in either temperature condition.
Conclusions and Clinical Relevance—Results suggested that blood samples should be chilled and plasma harvested within 1 hour after collection to prevent substance P degradation.
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.
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.
20 weaned Holstein calves with umbilical hernias.
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.
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.