A novel needle-free method of lidocaine administration during standing castration of Holstein bulls.

The American Veterinary Medical Association recognizes castration to be important for both human and animal safety. Lidocaine delivered through-the-needle has been shown to be effective at reducing cortisol response to castration, but this method has drawbacks for both animals and caretakers. As such, a study was conducted to examine the potential benefits of lidocaine delivery using a pneumatic needle-free device immediately before standing bovine castration. Twelve Holstein bulls weighing 400.7 ± 39.5 kg (mean ± standard deviation) were enrolled. Bulls were allocated to receive a local anesthetic block of 2% lidocaine for surgical castration by traditional needle injection or by needle-free injection. Outcomes were collected out to 48 h postcastration. Outcome variables included plasma cortisol concentrations, visual analog scale scores for pain, medial canthus temperatures as measured using infrared thermography, pressure mat changes, and chute defense scores. A time effect was observed for cortisol, visual analog scale scores, infrared thermography temperatures, and some pressure mat outcomes. No statistically significant differences between lidocaine delivery methods were observed, but further research is needed to build upon this small dataset.

Veterinarians' perspectives of pain, treatment, and diagnostics for bovine respiratory disease in preweaned dairy calves.

Background: Bovine Respiratory Disease (BRD) is a leading cause of morbidity and mortality in preweaned dairy calves. Early detection and therefore treatment are essential to minimize animal welfare concerns, particularly given that recent research also demonstrates that BRD is painful. Veterinarians are essential to ensuring calves with BRD receive appropriate treatment, but little to no research exists regarding veterinarians' perspectives about BRD detection and treatment in dairy calves. This is a critical step to determine education and outreach needs that can target BRD treatment to improve calf welfare. Thus, the objectives of the current study were to describe US veterinarians' current detection methods and treatment practices for BRD in preweaned dairy calves, understand veterinarians' rationale for treatment decisions, and identify gaps in knowledge regarding treatment and management of calf BRD. Methods: An online survey was sent to two veterinarian-focused list-serves and newsletter. Final responses (n = 47) were analyzed using qualitative and quantitative analyses. Results: On-farm necropsy was the diagnostic tool most considered "extremely important" (26, 55.3%). All veterinarians indicated that BRD was at least mildly painful. However, only 53% of veterinarians (n = 25) assess pain in preweaned calves with BRD in order to make treatment decisions. Furthermore, of the veterinarians that assessed pain, 40% (n = 10) reported that their knowledge of pain assessment and treatment was adequate, but most (n = 24) considered a calf's pain-level at least "moderately important" to make BRD treatment decisions. The most important ancillary therapy for antimicrobials were NSAIDs (21, 44.7%). The ancillary therapy most often considered "extremely important" for treating BRD was NSAIDs. Qualitative analysis identified the following as factors that influenced veterinarians' willingness to provide analgesia: the farm's willingness to administer drugs, clinical signs, perceived severity of pain, the need for anti-inflammatories, and the presence of fever and comorbidities. Discussion: This study included a small sample size and an extremely low response rate; results should therefore be interpreted with caution. Despite this limitation, important gaps in knowledge were identified, including pain assessment and consideration when making treatment decisions, and diagnostic tools. Addressing these needs in future research and outreach efforts could help ensure appropriate and timely treatment of calf BRD, including pain mitigation.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows.

The objectives of this descriptive study were to (1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of acetylsalicylic acid (ASA; aspirin), (2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA, and (3) to determine the effect of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg of body weight, 24 h apart. Concentrations of SA in plasma and milk from 0 h through 120 h after ASA administration were analyzed using ultra performance liquid chromatography triple quadrupole mass spectrometry and a milk withdrawal period was estimated using the United States Food and Drug Administration Milk Discard App in R. Two withdrawal periods were estimated: (1) a whole-herd treatment scenario with no dilution factor and (2) an individual animal treatment scenario with a bulk tank factor included in analysis. Plasma PGEM concentrations in samples from 0 h to 24 h after ASA administration were determined using a commercially available competitive ELISA. Milk SA concentrations were undetected in all cows by 48 h after the last ASA treatment. Secondary peaks were observed in plasma at 58 and 82 h after the last treatment and in milk at 87 h after the last treatment. In the absence of a tolerance for SA in milk, the estimated milk withdrawal periods were (1) 156 h for the whole-herd treatment scenario and (2) 120 h for the individual animal treatment scenario. Plasma PGEM concentrations were reduced compared with baseline for up to 12 h after ASA administration, with the greatest reduction observed at 2 h. Results from this study suggest that the current milk withhold recommendation for dairy cattle administered ASA may need revision to 120 h (5 d) and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production for up to 12 h after treatment. Pharmacokinetic and milk withdrawal data from this study will inform future recommendations for extra-label use of aspirin in postpartum dairy cows. Further research is required to determine the basis for the secondary SA peaks and to elucidate the long-term effects of ASA administration on dairy cow health.

Randomized controlled trial comparison of analgesic drugs for control of pain associated with induced lameness in lactating dairy cattle.

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0-2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2-8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0-24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM difference = 187.6 ng·h/mL, 95% CI: 64.9, 310.4 ng·h/mL). Analysis of data from other assessment modalities failed to discern biologically relevant differences between treatment groups. We conclude that meaningful differences were evident for visual lameness assessment and cortisol from MEL and FLU treatment versus the positive control. Further clinical research is needed toward development of a model that will create reproducible events that are more pronounced in severity and duration of lameness which can be validated as a substitute for naturally occurring lameness cases.

Evaluation of a carbon dioxide laser scalpel for disbudding Holstein calves: A pilot study.

Cautery hot-iron disbudding is a painful routine husbandry practice performed on many dairy farms and calf rearing facilities. Refinements to eliminate or reduce the pain associated with disbudding are desired. Carbon dioxide (CO2) laser scalpels cut and ablate tissue using high-power light energy. The objective of this study was to test the utility of a CO2 laser scalpel in bovine disbudding and to compare healing and pain measures with those of cautery hot-iron disbudding. Twelve Holstein bull calves (6-39 d of age) were enrolled in the study. Calves were randomly assigned into groups that were disbudded with a CO2 laser scalpel (n = 6) or cautery hot iron (n = 6). Calves were sedated with xylazine for the procedure and were given oral meloxicam and a local anesthetic block for analgesia. Outcome measures were maximum surface temperature by infrared thermography, mechanical nociception threshold (MNT) tests, and digital images for wound healing. The infrared thermography and MNT measures were collected before disbudding and out to 72 h postprocedure. Images for wound healing were collected before disbudding and at 6, 24, and 72 h and 7, 14, 28, and 42 d postdisbudding. Overall maximum surface temperatures were not different between groups (35.3 ± 0.3°C vs. 36.0 ± 0.3°C for laser and hot iron, respectively). No differences in overall MNT measures were noted between the laser calves (2.28 ± 0.19) and the hot-iron calves (2.42 ± 0.19 kg of force). All 6 calves in the laser group were completely healed by d 42, whereas only 4 out of 6 hot-iron calves were fully healed. These results suggest that disbudding calves using a CO2 laser scalpel may be painful based on the outcomes measured. Further research that focuses on pain associated with time points beyond those used in this study and that performs the procedure in unsedated calves is needed to fully evaluate its utility.

Administration of acetylsalicylic acid after parturition in lactating dairy cows under certified organic management: Part II. Biomarkers of nociception, inflammation, and stress.

The objective was to assess the effect of oral administration of acetylsalicylic acid after calving on the concentrations of substance P (SP), haptoglobin (HP), and cortisol in lactating dairy cows. Holstein dairy cows (n = 152) from 3 organic herds were included. At parturition, cows were blocked by parity [multiparous (MULT) and primiparous (PRIM)] and calving ease [eutocia (EUT) and dystocia (DYS)] and were randomly assigned to 1 of 2 treatment groups: aspirin (ASP; n = 76), in which within 12 h after parturition cows received 4 treatments with acetylsalicylic acid (100 mg/kg; 2 boluses) at 12-h intervals, or placebo (PLC; n = 76), in which within 12 h after parturition cows received 4 consecutive treatments with gelatin capsules (2 capsules) containing water 12 h apart. Blood samples were collected immediately before treatment and at 12, 24, 36, 48, and 168 h (7 DIM) for assessment of circulating concentration of SP, HP, and cortisol. Based on farm records, cows were classified in the following clinical disease categories: no clinical disease event (NO-EVT), a single clinical disease event (SI-EVT), and more than 1 clinical disease event (MU-EVT). The study data were analyzed as a randomized complete block design using mixed multiple linear and logistic regression models. With regard to HP, there was a tendency for an interaction between treatment and parity, where MULT cows treated with ASP had lower concentration of HP compared with MULT cows treated with PLC (ASP = 124.33 ± 6.83 µg/mL; PLC = 143.9 ± 7.24 µg/mL). Analysis by calving ease showed that cows with DYS had higher concentrations of HP (DYS = 159.17 ± 5.97 µg/mL; EUT = 138.72 ± 6.22 µg/mL) and SP (only at 168 h; DYS = 64.99 pg/mL, 95% confidence interval, CI: 2.68-2.81; EUT = 60.33 pg/mL, 95% CI: 2.91-3.06) after calving compared with EUT cows. Regardless of treatment, PRIM cows had higher concentrations of SP (MULT = 55.11 pg/mL, 95% CI: 1.27-1.30; PRIM = 57.62 pg/mL, 95% CI: 1.99-2.06), HP (MULT = 134.14 ± 4.96 µg/mL; PRIM = 163.75 ± 7.76 µg/mL), and cortisol (MULT = 18.65 µg/mL, 95% CI: 1.02-1.05; PRIM = 21.92 µg/mL, 95% CI: 1.67-1.74) compared with MULT cows. In addition, cows that experienced SI-EVT or MU-EVT had higher concentrations of HP (NO-EVT = 134.13 ± 5.95 µg/mL; SI-EVT = 142.68 ± 7.32 µg/mL; MU-EVT = 170.03 ± 9.42 µg/mL) and cortisol (NO-EVT = 17.86 µg/mL, 95% CI: 1.20-1.24; SI-EVT = 21.01 µg/mL, 95% CI: 1.61-1.67; MU-EVT = 22.01 µg/mL, 95% CI: 2.08-2.18) compared with cows with NO-EVT recorded. Results from this study suggest that a short-duration anti-inflammatory therapy after calving reduced HP in MULT cows but may not have effects on SP and cortisol concentrations. Calving ease and parity affected the concentrations of markers of inflammation, nociception, and stress regardless of treatment. Further research is warranted to assess anti-inflammatory strategies aimed at decreasing inflammation and stress in DYS and PRIM cows and therefore improve welfare and performance of these high-priority groups.

Short communication: Determination of the milk pharmacokinetics and depletion of milk residues of flunixin following transdermal administration to lactating Holstein cows.

Flunixin is a nonsteroidal anti-inflammatory drug and the most commonly prescribed analgesic in cattle in the United States. Recently, the US Food and Drug Administration (FDA) approved a transdermal formulation of flunixin for control of pyrexia associated with bovine respiratory disease and the control of pain associated with foot rot. The transdermal formulation is not currently approved for use in lactating dairy cattle in the United States, but extra-label use in dairy cattle is permissible under US regulations. The objectives of this study were to determine the pharmacokinetics in milk of dairy cows treated with transdermal flunixin and determine an appropriate withdrawal time for milk. Ten lactating Holstein cows were enrolled into the study in mid lactation. Following treatment, cows were milked 3 times per day through 144 h. Milk samples were collected for drug analysis using ultra-high-pressure liquid chromatography coupled with a triple quadrupole mass spectrometer. The geometric mean maximum concentration for flunixin in milk was 0.010 µg/mL and was 0.061 µg/mL for the active metabolite, 5-hydroxyflunixin. The geometric mean terminal half-life was 20.71 h for flunixin and 22.62 h for 5-hydroxyflunixin. Calculations to approximate a withdrawal time in milk following transdermal flunixin administration were accomplished using a statistical tolerance limit procedure. This analysis indicated that it would be prudent to observe a withdrawal period of 96 h following the last treatment. This is more than twice as long as the labeled withdrawal period of 36 h following use of the injectable formulation. The withdrawal period suggested by this work should be applied carefully, as this study was not conducted under the full quality control practices required by the US FDA for a full drug approval study. Caution should be taken when applying this withdrawal time to diseased animals, animals that are milked with different milking frequencies, and those in different stages of production as these have all been shown to affect drug depletion from milk.

Effects of transdermal flunixin meglumine on experimentally induced lameness in adult dairy cattle.

Lameness is a common animal health condition with significant production and welfare implications. The transdermal formulation of flunixin meglumine is the only approved drug for pain control in cattle in the United States. Thirty adult dairy cows were enrolled in a study to determine the effect of transdermal flunixin on cattle with induced lameness. Cows were allocated to 1 of 3 treatment groups, with 10 cows per group: lameness and flunixin (L+F), lameness and placebo (L+P), or sham induction and placebo (S+P). An arthritis-synovitis was induced in the distal interphalangeal joint of the left hind lateral digit, using 20 mg of amphotericin B, 6 h before the application of treatment. Cows enrolled into the sham induction group had 4 mL of isotonic saline injected into the joint. Cows were dosed with transdermal flunixin at 3.33 mg/kg (1 mL/15 kg), or a placebo at 1 mL/15 kg, every 24 h for 3 d. The first treatment of flunixin or placebo was considered the start of the study, identified as time 0 h. Data were collected from all cows for 120 h following the initial treatment application. Outcome measures included plasma cortisol; substance P; visual lameness assessment; mechanical nociception threshold (MNT), presented as difference between left and right feet; infrared thermography (IRT), presented as difference between left and right feet; and gait analysis using a pressure mat. Cortisol concentrations were lower for the L+F group starting at 1.5 h after drug administration. Substance P levels showed no evidence for treatment differences among groups. Differences between the left hind MNT and right hind MNT were detected, with S+P having the lowest difference at -0.04 kilograms-force (kgf; 95% CI: -1.86 to 1.78 kgf), and L+P having the highest at -2.96 kgf (95% CI: 1.55 to 4.36 kgf). The L+F group was intermediate at -2.08 kgf (95% CI: 0.89 to 3.27 kgf). Similarly, when the difference between the maximum temperatures of the coronary band were examined via IRT, the L+P group had the highest difference at 1.64°C (95% CI: 1.02 to 2.26°C), with the L+F and S+P groups measuring 0.57°C (95% CI: 0.06 to 1.08°C) and 0.53°C (95% CI: -0.2 to 1.25°C) respectively. We found no evidence for differences among treatment groups when analyzing force, contact pressure, step impulse, or stride length. Based on differences in MNT, IRT, and cortisol, transdermal flunixin is an effective analgesic agent for induced lameness. Multiple doses of transdermal flunixin may be required to be clinically effective, based on MNT and IRT data. Further investigation of transdermal flunixin and its analgesic effects is warranted in naturally occurring lameness.

Evaluation of compounded aqueous milbemycin oxime: issues with formulation potency and reproducibility.

OBJECTIVES: To determine the potency and reproducibility of milbemycin oxime when compounded as an aqueous suspension (20 mg/mL). MATERIALS AND METHODS: Preparation choice reflected current prescribing practices. Samples were acquired by prescription from two national veterinary compounding pharmacies at three time points. Two different storage conditions were evaluated and sampled at four time points from the order date (day 7, 14, 21 and 28). Milbemycin oxime recovery was performed by solid-phase extraction and concentration strength measured via high-performance liquid chromatography. RESULTS: The average concentration on day 7 for Pharmacy A samples was 16.29 mg/mL [confidence interval (CI): 15.66 to 16.92] with a coefficient of variation (CV) = 11%, while for Pharmacy B it was 20.46 mg/mL (CI: 19.83 to 21.08) with CV = 22%. The mean decrease in concentration over 28 days for Pharmacy A was 22% (CI: 9% to 34%) while Pharmacy B was 18% (CI: 2% to 35%). CLINICAL SIGNIFICANCE: The compounded milbemycin oxime suspensions evaluated in this study deviated by more than 10% from their labelled strength in five of the six lots. Clinical efficacy of compounded milbemycin oxime suspensions remains unknown and the use of these products should be discouraged at this time.

Induction of anaesthesia with propofol according to the adjusted ideal body mass in obese and non-obese patients: an observational study

Background: Obesity changes body composition including fat free mass (FFM), regarded as the "pharmacologically active mass". Scaling drug doses to obese patients by total body mass (TBM) results in overdose. We aimed to determine the success rate of inducing anaesthesia in normal, overweight and obese patients with propofol, using an adjusted body mass scalar (ABM), which embodies the increased FFM of obese patients. Methods: Ninety-six patients were divided into three groups according to body mass index (BMI): normal, overweight and obese. Propofol 2 mg/kg ABM was administered according to the equation: ABM = IBM + 0.4(TBM ­ IBM), where IBM = ideal body mass. Induction success was assessed clinically and by electroencephalographic spectral entropy. Results: The groups were similar regarding gender, age, height and IBM. One patient was morbidly obese (BMI = 44). State entropy (SE) decreased to < 60 in 33/33, 28/29 and 33/34 patients in the normal-weight, overweight and obese groups respectively, an overall success rate of 97.5% (95% confidence interval 92.7% to 99.4%). Median lowest achieved SE values and median times that SE remained < 60 did not differ between groups, however the individual values ranged widely in allthree groups. Induction failed in the two patients whose SE did not decrease to < 60 (one overweight and one obese). Conclusions: The ABM-based propofol induction dose has a high success rate in normal, overweight and obese patients. Further studies are required to determine the feasibility among morbidly obese patients

Effects of transportation on cattle health and production: a review.

The goal of this review is to present a concise and critical assessment of the literature related to physiologic responses in cattle that are subjected to transportation. Over two-thirds of US cattle are transported. Understanding trends in circulating physiologic parameters is an important part of mitigating the negative effects of transportation. For the producer, linking these effects after transportation to morbidity outcomes within the first 45 days on feed (i.e. especially development of bovine respiratory disease) is critical. Physiologic parameters in circulation are of primary importance and may have value for prediction of bovine respiratory disease on arrival and for the understanding of disease pathogenesis. The results of our literature survey indicated that post-transportation immune function, increased acute phase proteins, glucocorticoids, and inflammation are a pivotal starting point for understanding disease. These potential biomarkers may have utility in identifying disease for targeted therapeutics so that traditional protocols that rely heavily on metaphylaxis can be avoided. Additional research is needed to develop strategies for physiological marker identification, treatment methods, or predictive behaviors to prevent respiratory disease before and after transport. This review examines the significant deleterious effects of transportation handling and stress, and current immune system translation and non-antimicrobial mitigation strategies.

Pharmacokinetics of fentanyl citrate and norfentanyl in Holstein calves and effect of analytical performances on fentanyl parameter estimation.

This study describes the pharmacokinetics of intravenously administered (i.v.) fentanyl citrate, and its primary metabolite norfentanyl in Holstein calves. Eight calves (58.6 ± 2.2 kg), aged 3-4 weeks, were administered fentanyl citrate at a single dose of 5.0 µg/kg i.v. Blood samples were collected from 0 to 24 hr. Plasma (nor)fentanyl concentrations were determined using liquid chromatography with mass spectrometry and a lower limit of quantification (LLOQ) of 0.03 ng/ml. To explore the effect of analytical performance on fentanyl parameter estimation, the noncompartmental pharmacokinetic analysis was then repeated with a hypothetical LLOQ value of 0.05 ng/ml. Terminal elimination half-life was estimated at 12.7 and 3.6 hr for fentanyl and norfentanyl, respectively. For fentanyl, systemic clearance was estimated at 2.0 L hr-1  kg-1 , volume of distribution at steady-state was 24.8 L/kg and extraction ratio was 0.42. At a hypothetical LLOQ of 0.05 ng/ml fentanyl half-life, volume of distribution at steady-state and clearance were, respectively, of 3.0 hr, 8.8 L/kg and 3.4 L kg-1  hr-1 . Fentanyl citrate administered i.v. at 5.0 µg/kg can reach levels associated with analgesia in other species. Pharmacokinetic parameters should be interpreted with respect to LLOQ, as lower limits can influence estimated parameters, such as elimination half-life or systemic clearance and have significant impact on dosage regimen selection in clinical practice.

Comparison of milk and plasma pharmacokinetics of meloxicam in postpartum versus mid-lactation Holstein cows.

The objective of this study reported here was determine whether differences occurred in meloxicam pharmacokinetics between postpartum cows and mid-lactation cows. Preliminary data from a separate study (P. J. Gorden, unpublished data) in postpartum cows demonstrated elevated plasma and milk concentration profiles compared to previously published data (Malreddy, Coetzee, KuKanich, & Gehring, ). Two different groups were enrolled, each with 10 cows. The treatment group (TRT) was postpartum cows treated with meloxicam, and the positive control (PC) group was cows in mid-lactation treated with meloxicam. Plasma and milk meloxicam concentrations between the TRT and PC group were compared. Significant differences in meloxicam concentration in plasma were determined at all time points from 8 hr to 120 hr post-treatment. In milk, there was a treatment (p = .003), time (p < .001), and treatment by time interaction (p < .001). Significant differences in milk meloxicam concentration were determined at all time points from 8 hr to 96 hr post-treatment, except for the 16-hr time point. The time needed for meloxicam to no longer be detected in milk of the TRT group was longer compared to the PC group, indicating that a longer milk withdrawal is needed. These data suggest higher bioavailability as the underlying mechanism. Further research is needed to determine the mechanisms underlying differences this outcome.

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows.

A transdermal formulation of the nonsteroidal anti-inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single-dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (Tmax) was 2.81 hr, and the maximum drug concentration was 1.08 µg/ml. The mean terminal half-life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg-1 , and volume of distribution of fraction (Vz/F) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.

Pharmacokinetics of chlortetracycline in maternal plasma and in fetal tissues following oral administration to pregnant ewes.

The purpose of this study was to determine if concentrations of chlortetracycline could be detected in fetal plasma or tissues after administering an oral dose of chlortetracycline (CTC; 500 mg/head/day) reported to be effective in controlling Campylobacter spp. abortions. Five pregnant ewes were administered 250 mg/head twice a day (total dose 500 mg/hd/d) for 7 days. On the beginning of day 7, intravenous catheters were surgically implanted or inserted into the fetus and dam. Plasma samples were collected from the ewe and fetus at various time points before and up to 36 hr after the last dose of CTC. All ewes were then sacrificed, and tissues were harvested from the fetus for drug analysis. Concentrations of CTC in maternal plasma were consistent with our previous study and below the minimum inhibitory concentration of Campylobacter abortion isolates. Concentrations of CTC were below the limit of detection in three of five fetal plasma samples and all of the placenta, amniotic fluid, and fetal stomach contents. Low concentrations were detectable in fetal kidney and liver, suggesting that CTC reaches the fetus, although at a variable and low ratio when compared to maternal concentrations.

Comparative plasma and interstitial fluid pharmacokinetics of flunixin meglumine and ceftiofur hydrochloride following individual and co-administration in dairy cows.

Ceftiofur (CEF) and flunixin meglumine (FLU) are two drugs approved for use in beef and dairy cattle that are frequently used in combination for many diseases. These two drugs are the most commonly used drugs in dairy cattle in their respective drug classes. Two research groups have recently published manuscripts demonstrating altered pharmacokinetics of FLU and CEF in cows affected with naturally occurring mastitis. The objective of this study was to determine whether pharmacokinetics of flunixin meglumine administered intravenously or intramuscularly administered ceftiofur hydrochloride would be altered when co-administered versus individual administration to healthy dairy cattle. Ten cows were utilized in a three-period, three-treatment crossover design, with all cows receiving each treatment one time with a 10-day washout period between treatments. Following treatment, plasma and interstitial fluid samples were collected and stored for later analysis. Additionally, plasma ultrafiltrate was collected using microcentrifugation to determine plasma protein binding of each drug. Drug concentrations in plasma, plasma ultrafiltrate, and interstitial fluid were determined using high-pressure liquid chromatography coupled with mass spectrometry. The results of this trial indicate that drug interactions between FLU and CEF do not occur when the two drugs are administered simultaneously in healthy cattle. Further work is needed to determine whether this relationship is maintained in the presence of severe disease.

Blood pressure measurement in obese patients: non-invasive proximal forearm versus direct intra-arterial measurements

Background: In obesity, accurate perioperative blood pressure measurement using upper arm, non-invasive blood pressure (NIBP) is technically challenging. Proximal forearm NIBP may be an acceptable substitute. Mean arterial blood pressures (MAP) estimated by proximal forearm NIBP were compared with direct intra-arterial measurements. It was hypothesised that the measurement techniques would be interchangeable if between-technique MAP differed ≤ 20% and MAP ratios were < 1.2 and > 0.8. Method: A total of 30 adults with body mass index ≥ 30 kg/m2 in whom perioperative intra-arterial blood pressure measurement was considered mandatory were enrolled. MAP measurements using the two techniques were obtained at three random intervals in each patient. Bland­Altman analyses were employed. Results: Forearm mean NIBP MAP overestimated mean intra-arterial MAP by 2.2 (SD 8.1; range from 23.8 to ­19.4 mmHg; p = 0.011, 95% CI 3.9 to 0.5). However, Bland­Altman analyses revealed a wide dispersion with several MAP differences and MAP ratios exceeding the pre-specified bounds for interchangeability. Conclusion: Forearm NIBP could not be considered interchangeable with direct intra-arterial MAP measurements in obese patients

Effects of transdermal flunixin meglumine on pain biomarkers at dehorning in calves.

The objective of this study was to evaluate the analgesic properties of transdermal flunixin meglumine when given at the time of dehorning on pain biomarkers. Twenty-four weaned male Holstein calves, 6 to 8 wk of age were enrolled into the study. The calves were randomly assigned to 1 of 3 treatment groups: 1) transdermal flunixin and dehorn (DH-FLU); 2) transdermal flunixin and sham dehorn (SHAM-FLU); and 3) placebo and dehorn (DH-PLBO). Transdermal flunixin at a label dose of 3.33 mg/kg (or placebo at an equivalent volume) was administered as a pour-on along the top-line of the calves in each treatment group concurrently with electrocautery dehorning or sham dehorning. Biomarker parameters collected and analyzed included: infrared thermography (IRT), mechanical nociception threshold (MNT), plasma cortisol, and substance P (SP). There were no differences in maximal temperatures detected for the IRT measurements of the medial canthus of the eye for the DH groups. Mean control point MNT measurements at 48 h were 3.14 kgF, 3.46 kgF, and 1.43 kgF for the DH-FLU, Sham-FLU, and DH-PLBO groups, respectively (P = 0.0001). No other differences of MNT were detected between the dehorned groups for the other test sites and time points. Plasma cortisol reached peak concentration at 20 min postdehorning for the DH-FLU and DH-PLBO groups and 10 min for SHAM-FLU group. Peak plasma cortisol concentrations were 32.0 ng/mL, 12.7 ng/mL, and 28.8 ng/mL for the DH-FLU, SHAM-FLU, and DH-PLBO groups, respectively. Cortisol concentrations were lower for the DH-FLU group at 90 min postdehorning compared to the SHAM-FLU and DH-PLBO groups ( = 0.04). Area under the effect curve (AUEC) were similar for all groups ( = 0.93). No statistical differences in SP concentrations between groups were detected for any of the time points. In conclusion, transdermal flunixin meglumine given at the time of dehorning did not provide substantial analgesia based on the pain biomarkers investigated. Further investigation into its role as part of a multimodal analgesic plan is warranted.

Effects of tail docking and tail biting on performance and welfare of growing-finishing pigs in a confinement housing system.

A study was conducted to evaluate the effect of tail docking on the welfare and performance of victimized pigs by tail biting and tail biters. Pigs ( = 240; 25.7 ± 2.9 kg average weight), including 120 pigs that were tail docked at birth and 120 pigs that remained with intact tails, were used. Pigs were housed in 8 pens of 30 pigs in a confinement barn for 16 wk, with 4 pens each housing pigs of both sexes with docked or intact tails. Tail biters and victimized pigs with damaged tails were identified during outbreaks of tail biting. Growth performance was monitored, and skin lesions on the tail, ears, and body were assessed. Blood samples were collected from focal tail biters, victimized pigs, and nonvictimized pigs for analysis of total serum protein, IgG, and substance P concentrations. When pigs were marketed, carcass weights and the number of pigs with carcass trim loss were recorded. During the growing-finishing period, 48% of pigs with docked tails and 89% of pigs with intact tails experienced lesions on their tails, including 5% of docked pigs and 30% of intact pigs identified as victimized pigs that experienced puncture wounds with signs of infection on their tails or loss of tails ( < 0.001). Victimized pigs tended to gain less weight ( = 0.07) between 17 and 21 wk of age than other pigs when tail biting prevailed in this study. Victimized pigs were more frequently ( = 0.04) sold for less than full value and had a lower dressing percentage ( < 0.001) compared with nonvictimized pigs. For victimized pigs, total serum protein and IgG concentrations were elevated 5 d after tails were injured, suggesting that tail damage can cause inflammation, which may lead to carcass abscesses and trim loss. Compared with victimized pigs and nonvictimized pigs, tail biters had lower total serum protein ( = 0.01) and IgG ( = 0.01) concentrations, indicating that tail biters may experience poor immune functions. Results of this study demonstrated that tail docking reduced tail damage in pigs kept in a confinement system. Tail damage can cause inflammation and reduce the value of market pigs. More research is needed to test whether compromised immune functions predispose pigs to tail biting.

Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline-free acid in pigs.

The pharmacokinetics of intramuscularly administered ceftiofur crystalline-free acid (CCFA) were determined in pigs that were clinically healthy (n = 8), vaccinated with a Porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) (n = 10), challenged with wild-type porcine reproductive and respiratory syndrome virus (PRRSv) VR-2385 (n = 10), or vaccinated with PRRS MLV and later challenged with wild-type PRRSv VR-2385 (n = 10). Animals were given a single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h postinjection. Plasma was analyzed using liquid chromatography-mass spectrometry. Plasma concentration-time curves for each group were evaluated with noncompartmental modeling. When compared to control animals, those receiving the PRRSv wild-type challenge only had a lower AUC0-last , higher Cl/F, and higher Vz/F. The PRRSv wild-type challenge only group had the longest T1/2λ . The Cmax did not differ among all four treatments. Control animals had no statistically significant differences from animals vaccinated with PRRS MLV alone or animals vaccinated with PRRS MLV and later challenged with wild-type PRRSv. Our results suggest that PRRSv wild-type infection has the potential to alter CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes.