Effects of multimodal pain management strategies on acute physiological and behavioral response to cautery disbudding in neonatal goat kids.

Dairy goat kids are commonly disbudded in the United States without pain relief. Our objective was to identify an efficient pain management strategy by monitoring changes in plasma biomarkers and behavior of disbudded goat kids. A total of 42 kids (5-18 d old at the time of disbudding) were randomly allocated to 1 of 7 treatments (n = 6/treatment): sham treatment; 0.05 mg/kg i.m. xylazine (X); 4 mg/kg subcutaneous buffered lidocaine (L); 1 mg/kg oral meloxicam (M); xylazine and lidocaine (XL); xylazine and meloxicam (XM); and xylazine, meloxicam, and lidocaine together (XML). Treatments were administered 20 min before disbudding. One trained individual, blinded to treatment, disbudded all kids; sham-treated kids were handled similarly except the iron was cold. Jugular blood samples (3 mL) were obtained before (-20, -10, and -1 min) and after (1, 15, and 30 min, and 1, 2, 4, 6, 12, 24, 36, 48 h) disbudding and analyzed for cortisol and prostaglandin E2 (PGE2). Mechanical nociceptive threshold (MNT) testing was performed at 4, 12, 24, and 48 h after disbudding, and kids were weighed daily until 2 d post-disbudding. Vocalizations, tail flicks, and struggle behavior during disbudding were recorded. Cameras were mounted over home pens; continuous and scan observations over 12 periods of 10 min each, in the 48 h after disbudding, captured frequency of locomotion and pain-specific behaviors. Repeated measures and linear mixed models assessed treatment effects on outcome measures during and after disbudding. Models accounted for sex, breed, and age as random effects, and Bonferroni adjustments accounted for multiple comparisons. At 15 min after disbudding, XML kids had lower plasma cortisol concentrations compared with L (50.0 ± 13.2 vs. 132.8 ± 13.6 mmol/L) and M kids (50.0 ± 13.2 vs. 145.4 ± 15.7 mmol/L). Cortisol was also lower in XML kids over the first hour after disbudding compared with L kids (43.4 ± 9 vs. 80.2 ± 9 mmol/L). Change from baseline PGE2 was not affected by treatment. Behaviors observed during disbudding did not differ by treatment group. Treatment affected MNT such that M kids were more sensitive overall compared with sham kids (0.93 ± 0.11 kgf vs. 1.35 ± 0.12 kgf). None of the recorded post-disbudding behaviors were affected by treatment, but study activities did influence behavior over time, with kid activity levels declining in the first day after disbudding but largely recovering thereafter. We conclude that none of the drug combinations investigated here appeared to fully attenuate pain indicators during or after disbudding, but triple modality seems to have offered partial relief compared with some of the single-modality treatments.

Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis.

This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 µg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independently assigned pain scores (at rest, walk and trot) and lameness scores before and up to 48 hr after t-TUCB/LPS. Responses to touching the joint skin to assess tactile allodynia, plasma, and synovial fluid (SF) t-TUCB concentrations were determined before and up to 48 hr after t-TUCB/LPS. Blood and SF were collected for clinical laboratory evaluations before and up to 48 hr after t-TUCB/LPS. Areas under the curves of pain and lameness scores were calculated and compared between control and treatments. Data were analyzed using repeated measures ANOVA with Dunnett or Bonferroni post-test. p < .05 was considered significant. Data are mean ± SEM. Compared to control, pain, lameness, and tactile allodynia were significantly lower with 1 mg/kg t-TUCB, but not the other doses. For 0.1, 0.3, and 1 mg/kg t-TUCB treatments, plasma terminal half-lives were 13 ± 3, 13 ± 0.5, and 24 ± 5 hr, and clearances were 68 ± 15, 48 ± 5, and 14 ± 1 ml hr-1  kg-1 . The 1 mg/kg t-TUCB reached the SF at high concentrations. There were no important anti-inflammatory effects. In conclusion, sEH inhibition with t-TUCB may provide analgesia in horses with inflammatory joint pain.

Equivalence between invasive and oscillometric blood pressures at different anatomic locations in healthy normotensive anaesthetised horses.

REASONS FOR PERFORMING STUDY: Accurate blood pressure measurement is essential for effective clinical assessment and appropriate interventions in anaesthetised horses. Information on the accuracy of oscillometry for blood pressure measurement on the appendages of mature horses is limited. OBJECTIVES: To assess equivalence between invasive and oscillometric blood pressures at different anatomic locations in horses. STUDY DESIGN: Prospective experimental study using 6 healthy mature horses. METHODS: Blood pressure was measured invasively in the right transverse facial artery and noninvasively by oscillometry in nondependent limbs and tail of laterally recumbent sevoflurane- or desflurane-anaesthetised horses. Cuff widths of 5-12 cm were tested on the tail, metatarsus, metacarpus and distal radius/ulna. Equivalence between mean arterial pressure (MAP) oscillometric and MAP invasive was assessed using a linear mixed effects model with a significance level of P≤0.05. RESULTS: Twenty paired measurements were obtained for each cuff size in each of the locations, totalling 340 measurements. There was only one location (tail) and one cuff width (6 cm; cuff width-to-tail circumference ratio of 0.25) that resulted in equivalence between MAP measured with the oscillometric and the invasive methods (P = 0.8). All other locations (metacarpus, radius/ulna, metatarsus) and cuff widths were not equivalent (P≤0.01). CONCLUSIONS: A cuff width-to-tail circumference ratio of 0.25 is recommended for accurate oscillometric blood pressure measurement in mature, laterally recumbent anaesthetised normotensive horses. Studies with variable haemodynamics are warranted. Oscillometric measurements at other extremities and/or with other cuff sizes cannot be recommended for clinical use.

Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses.

This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10 mg/kg orally every 12 h for 5 days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored and adverse events were recorded. Data were analysed with two-way repeated measures anova or Kruskal-Wallis one-way anova on ranks with P < 0.05 considered statistically significant. There were no significant effects of tramadol on the physiological variables. One horse receiving 10 mg/kg tramadol developed mild colic. Following tramadol at 5 and 10 mg/kg, respectively, maximum plasma concentrations (Cmax ) of tramadol ranged from 82-587 and 127-1280 ng/mL, nonconjugated M1 ranged from 2.51-26.7 and 4.88-34.3 ng/mL, and nonconjugated M2 from 12.5-356 and 35.4-486 ng/mL. Corresponding minimum plasma concentrations (Cmin ) of tramadol at 12 h following each dose ranged from 0.8-24 and 3-117 ng/mL. Tramadol accumulated considerably over time, more markedly when given at 10 mg/kg than at 5 mg/kg (accumulation indexes of 3.51 and 1.73 respectively). There was no accumulation of M1 but substantial accumulation of M2. In conclusion, there was accumulation and increase in exposure to tramadol and M2, but not M1, during repeated oral administrations in horses.

Evaluation and clinical use of an intraoral inferior alveolar nerve block in the horse.

REASONS FOR PERFORMING STUDY: Local anaesthesia is often required to facilitate invasive procedures in equine dental patients under standing sedation. OBJECTIVES: To show that an intraoral approach can be used to desensitise the inferior alveolar nerve in horses and report complications seen with this technique. METHODS: The distance of the mandibular foramen from the distal (caudal) edge of the mandibular third molar tooth, rostral edge of the mandibular ramus and ventral margin of the mandible were measured in 26 adult equine skulls of various ages and breeds. Computed tomography (CT) was used to verify the placement of the local anaesthetic with a custom-made device on 4 equine cadaver heads. The technique was applied in 43 clinical cases having procedures performed on the mandibular quadrants using the delivery device. RESULTS: Computed tomography demonstrated that the intraoral approach provided deposition of the local anaesthetic at the mandibular foramen and anatomical localisation of mandibular foramen indicated that anaesthetic solution could be delivered with a 38 mm needle. Clinical patients to lerated invasive dental procedures following the inferior alveolar nerve block with a 5 ml dose of local anaesthetic, without evidence of self-inflicted lingual trauma. CONCLUSIONS: The inferior alveolar nerve was successfully desensitised with the intraoral approach with minimal complications. The reduced volume of local anaesthetic and ability to deposit the local anaesthetic in close proximity to the nerve compared with an extraoral technique may decrease the complication of self-inflicted lingual trauma.

Pharmacokinetics and physiological effects of intravenous hydromorphone in conscious dogs.

This study evaluated the pharmacokinetics, the sedative and anti-nociceptive effects of intravenous hydromorphone in dogs. Five adult dogs were administered hydromorphone (0.1 mg/kg and 0.2 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) at weekly intervals. Blood samples were drawn before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma hydromorphone only was measured by high pressure liquid chromatography (HPLC) with electrochemical detection and pharmacokinetic parameters calculated. Anti-nociceptive and sedation scores were submitted to Kruskal-Wallis one-way anova on ranks and post-hoc Bonferroni test with 5% significance level. The data fitted a two-compartment model with a fast distribution (<1 min for both doses) and slower elimination rate. Mean elimination half-life was 80 +/- 52.7 and 57.7 +/- 30.4 min for the high and low dose, respectively. The apparent mean volumes of distribution at steady-state were 7.2 +/- 3 and 4.5 +/- 2.4 L/kg, while the clearance was 74.7 +/- 19 and 68.1 +/- 20 mL/kg/min for the high and low doses, respectively. Compared to saline, hydromorphone and morphine produced significant anti-nociception and sedation of similar magnitude for 120 min. In conclusion, intravenous hydromorphone has a large volume of distribution, and high clearance rate that exceeds hepatic blood flow. In dogs, it produced mechanical anti-nociception and sedation of a magnitude similar to morphine.

Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs.

This study compared plasma histamine concentrations, behavioral and cardiovascular parameters following intravenous administration of hydromorphone and morphine in conscious dogs. Five adult female dogs received a 15-sec bolus injection of saline, hydromorphone (0.1 and 0.2 mg/kg) or morphine (0.5 and 1.0 mg/kg) randomly at weekly intervals. Blood samples were collected from the jugular vein before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma histamine concentration, noninvasive oscillometric blood pressure, heart rate and rhythm were evaluated. Data were analyzed with repeated measures anova and Tukey-Kramer post hoc test with a 5% significance level. Median plasma histamine increased significantly only after the higher dose of morphine. Maximum plasma histamine measured was 0.8 ng/mL after saline and, after the lower and higher doses, respectively, 10.2 and 9.7 ng/mL for hydromorphone, and 440 and 589 ng/mL for morphine. One dog became hypotensive immediately after receiving the highest dose of morphine. Occasional ventricular premature contractions occurred in one dog after both opioids and dosages. No dogs vomited or defecated, but all salivated profusely with both opioids. Neuroexcitation occurred in four dogs following each opioid. In conclusion, intravenous hydromorphone induced minimal histamine release and was well tolerated by these conscious healthy dogs.

Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs.

This study examined the pharmacokinetics and physiologic effects of two infusions rates of morphine in conscious dogs. Five adult dogs were randomly studied at weekly intervals. An initial dose of either 0.3 or 0.6 mg/kg were each followed by infusions of 0.17 and 0.34 mg/kg/h. Plasma morphine concentrations, physiological parameters, sedation and mechanical antinociception were evaluated during each infusion. Morphine was assayed by high pressure liquid chromatography (HPLC) with electrochemical coulometric detection and pharmacokinetic parameters were calculated. Data were fitted to a bi-compartment model with a rapid distribution (<1 min for both doses) and slower termination rate. For the high and low doses, respectively, mean+/-SD terminal half-life was 38+/-5 and 27+/-14 min, apparent volumes of distribution at steady-state were 1.9+/-0.5 and 1.3+/-0.8 L/kg, with clearances of 50+/-15 and 67+/-20 mL/kg/min. Steady-state plasma concentrations ranged from 93 to 180 ng/mL and 45 to 80 ng/mL in the high and low doses, respectively. Respiratory rate increased significantly, pulse oximetry remained>95% and body temperature decreased significantly during both infusions. No vomition or neuroexcitation occurred. Sedation and mechanical antinociception were both mild during the lower infusion rate, and mild to moderate during the higher infusion rate. In conclusion, morphine pharmacokinetics was not altered by increasing infusion rates, producing stable, long-lasting plasma concentrations.