Tramadol Administered Intravenously Either as a Bolus or a Slow Injection in Pain Management of Romifidine-Sedated Calves Undergoing Umbilical Hernia Repair.

Umbilical hernias in calves occur with relative frequency. Most abdominal surgeries can be performed in cattle using standing sedation and local blocks. Romifidine is widely used in calves, alone or in combination with opioids. Tramadol administered as an intravenous slow injection provided better analgesia than an IV bolus in cows. The aim of the present study was to compare the response to surgical stimulus, and sedative effects of tramadol administered intravenously either as a bolus or a slow injection in romifidinesedated calves. Twenty Frisian calves undergoing umbilical hernia repair received romifidine (0.08 mg/kg IM; time 0) followed by tramadol (1 mg/kg IV) 5 min later either as a bolus (n = 10, B group) or a slow injection over 10 min (n = 10, SI group). Surgical area was infiltrated with lidocaine (4 mg/kg). Heart rate (HR), respiratory rate (RR), systolic, dyastolic and mean arterial pressure (SAP, DAP, MAP), sedation scores and response to surgical stimulus were recorded for up to 55 min. After the calves recovered a standing position, postoperative pain scores were assessed for up to 50 min. Sedation scores were significantly higher in the SI group than in the B group at 55 min (p < 0.05). HR, RR, SAP and response to surgical stimulus were significantly higher in the B group than in the SI group (p < 0.05). No significant differences were recorded in postoperative pain scores between groups (p > 0.05). Romifidine IM followed by intravenous tramadol, as a bolus or slow injection and local infiltration with lidocaine provided adequate sedation and analgesia in calves undergoing umbilical hernia repair.

Pharmacokinetics of butorphanol following intravenous and intramuscular administration in donkeys: A preliminary study.

The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys (n = 5), aged 6-12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume of distribution, elimination half-life, total body clearance, and area under the plasma concentration time curve from time 0 to infinity (AUC0-∞) were 322 ± 50 mL/kg, 0.83 ± 0.318 h, 400 ± 114 mL/h/kg, 370 ± 131 h·ng/mL, respectively. After IMB administration, a maximum plasma drug concentration of 369 ± 190 ng/mL was reached at 0.48 ± 0.09 h. The IMB AUC0-∞ was 410 ± 60 h·ng/mL. Bioavailability of IMB was 133 ± 45%. The pharmacokinetics of butorphanol in healthy donkeys was characterized by faster elimination half-life compared to values from the equine literature.

The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys (Equus africanus asinus).

The pharmacokinetics and pharmacodynamics of midazolam were studied in eight 1-to-3-year-old healthy gelded donkeys. Blood samples were obtained. Heart rate, respiratory rate, rectal temperature, sedation/excitement, ataxia, and response to tactile and auditory stimuli were recorded at baseline until 48 hours after intravenous (IV) midazolam (0.1 mg/kg) administration. Plasma midazolam and 1-hydroxymidazolam were measured using reversed-phase high-performance liquid chromatography. Pharmacokinetic variables were calculated using non-compartmental analysis. Physiologic data were analyzed using a mixed-effects model followed by Dunnett's test and behavioral data were analyzed using a Friedman test then a Dunn's test; P < 0.05 was considered significant. Midazolam was detectable for up to 60 minutes post-treatment in 7 donkeys. The median total body clearance, volume of distribution at steady state, elimination half-life, and area under concentration-time profile were 1210 mL/kg/h, 359 mL/kg, 0.27 hours, and 82.7 h × ng/mL, respectively. 1-hydroxymidazolam was detected (29 to 105 ng/mL) between 5 to 15 minutes post-treatment in 4 donkeys. Compared to baseline, rectal temperature and ataxia increased from 90 to 720 minutes (P ≤ 0.038) and 3 to 15 minutes (P ≤ 0.024) post-treatment, respectively. No other parameters showed statistically significant differences. Healthy donkeys cleared midazolam rapidly from plasma after IV administration. Transient ataxia and recumbency without sedation were observed.

La pharmacocinétique et la pharmacodynamique du midazolam ont été étudiées chez huit ânes hongres en bonne santé âgés de 1 à 3 ans. Des échantillons de sang ont été obtenus. La fréquence cardiaque, la fréquence respiratoire, la température rectale, la sédation/excitation, l'ataxie et la réponse aux stimuli tactiles et auditifs ont été enregistrées au départ jusqu'à 48 heures après l'administration intraveineuse (IV) de midazolam (0,1 mg/kg). Le midazolam plasmatique et le 1-hydroxymidazolam ont été mesurés par chromatographie liquide haute performance en phase inversée. Les variables pharmacocinétiques ont été calculées à l'aide d'une analyse non compartimentale. Les données physiologiques ont été analysées à l'aide d'un modèle à effets mixtes suivi du test de Dunnett et les données comportementales ont été analysées à l'aide d'un test de Friedman puis d'un test de Dunn; P < 0,05 était considéré comme significatif. Le midazolam était détectable jusqu'à 60 minutes après le traitement chez sept ânes. La clairance corporelle totale médiane, le volume de distribution à l'état d'équilibre, la demi-vie d'élimination et l'aire sous le profil concentration-temps étaient respectivement de 1210 mL/kg par heure, 359 mL/kg, 0,27 heure et 82,7 heures × ng/mL. Le 1-hydroxymidazolam a été détecté (29 à 105 ng/mL) entre 5 et 15 minutes après le traitement chez quatre ânes. Par rapport au départ, la température rectale et l'ataxie ont augmenté de 90 à 720 minutes (P ≤ 0,038) et de 3 à 15 minutes (P ≤ 0,024) après le traitement, respectivement. Aucun autre paramètre n'a montré de différences statistiquement significatives. Des ânes en bonne santé ont rapidement éliminé le midazolam du plasma après administration IV. Une ataxie transitoire et un décubitus sans sédation ont été observés.(Traduit par Docteur Serge Messier).

Reference intervals for hematological and biochemical analytes in a single herd of clinically healthy gelding donkeys in Saint Kitts.

There is a large population of donkeys in Saint Kitts; however, hematological and biochemical reference intervals (RIs) are lacking. This study addressed this deficiency by following the American Society for Veterinary Clinical Pathology RI guidelines. Sixty-six healthy, gelding standard donkeys with a median and interquartile range age of 5 years (3.5 - 8 years) and a mean ± standard deviation body weighed of 156 ± 16.7 kg were used to produce a five-part differential complete blood count using an impedance-based analyzer. Clinical chemistry analytes were quantified using a photometric-based analyzer utilizing two reagent rotors that determined 14 and 11 analytes, respectively. An electrochemical-based analyzer quantified chloride, sodium and potassium. Reference intervals were computed using Reference Value Advisor. Results of analytes determined using different rotors/analyzers were assessed using Passing-Bablok regression and Bland-Altman plot analyses. Reference intervals for 43 hematological and biochemical analytes were generated. Reference intervals for hematocrit, red blood cells, white blood cells, total protein, glucose, blood urea nitrogen, and creatinine were 23.67% - 38.08%, 4.08 - 6.42 1012/L, 4.7 - 12.34 109/L, 5.84 - 6.93 g/dL, 64.7 - 130.9 mg/dL, 11.1 - 13.4 mg/dL, and 0.67 - 1.36 mg/dL, respectively. There was good agreement between detection system for albumin, aspartate aminotransferase, gamma glutamyl transferase, total protein, globulin, and potassium, but not for blood urea nitrogen, calcium, creatinine kinase, and sodium. This study is the first to establish hematological and biochemical RIs in donkeys in Saint Kitts. These values will be useful for clinical decision-making.

Heat hypersensitivity at a site proximal to a surgically induced osteochondral fracture in horses.

OBJECTIVE: To evaluate thermal nociceptive thresholds (TNTs) before and after inducing a standardized radiocarpal bone osteochondral fracture (OCF) in horses. STUDY DESIGN: Prospective, controlled, randomized, masked study. ANIMALS: A group of 10 Thoroughbred fillies aged 2 years. METHODS: Skin temperature and TNTs were measured on the skin over the triceps brachii muscle in both the thoracic limbs before (week 0) and weekly (weeks 1-8) after unilateral arthroscopic induction of a radiocarpal OCF (n = 4) or sham surgery (n = 6) followed by a standardized exercise programme. The contralateral, non-operated thoracic limb was used as a control within each horse. Percentage thermal excursion (%TE) defined as %TE = 100 ∗ (TNT - skin temperature)/(cut-off temperature - skin temperature) was calculated. Data were analysed with a mixed-effects model followed by Dunnett's and Tukey's tests for within and between-limbs comparisons, respectively; p < 0.05 was considered significant. RESULTS: Skin temperature in the control limb of OCF horses was significantly higher at week 7 than at week 0 (p = 0.0125). At week 1, TNTs and %TE values in operated limbs of OCF horses were significantly reduced compared with their baseline values at week 0 (p ≤ 0.0153) and their values in contralateral control limbs (p ≤ 0.0024) and operated limbs of sham-operated horses (p ≤ 0.0162). At week 2, TNTs and %TE values in operated limbs of OCF horses remained significantly reduced compared with values in operated limbs of sham-operated horses (p ≤ 0.0248). CONCLUSIONS AND CLINICAL RELEVANCE: Creation of an OCF in a radiocarpal bone induced transitory (<2 weeks) ipsilateral heat hypersensitivity proximal to the surgery site (skin over the triceps brachii muscle) in horses. Surgically induced OCF may cause somatosensory abnormalities consistent with secondary thermal hyperalgesia.

Clinical utility of a targeted smartphone application to aid veterinary students in calculating constant rate infusions and perioperative fluid drip rates.

BACKGROUND: To compare the utility of a targeted smartphone application (TSPA) with a non-programmable calculator (NPC) when calculating fluid drip rates (FDR) and constant rate infusions (CRIs). METHODS: In a prospective randomised clinical study, 48 fourth-year veterinary students entered one of four parallel groups involving two mock scenarios: fentanyl calculation using an NPC followed by lidocaine calculation using a TSPA, fentanyl (TSPA) followed by lidocaine (NPC), lidocaine (NPC) followed by fentanyl (TSPA) or lidocaine (TSPA) followed by fentanyl (NPC). Students calculated volume of drug added to maintenance fluids and drops/second that correctly administered the drug dose and FDR. Time to completion was assessed using an analysis of variance. A Fisher's exact test assessed the effect of study period, scenario and device in the proportion of correct/incorrect answers. RESULTS: Participants took longer to complete the scenarios in period 1 and 2 with the NPC (380.7±195.6 seconds and 488±154.8 seconds, respectively) than the TSPA (247.5±88.8 seconds and 224±94.2 seconds, respectively) (P<0.0031 and P<0.0001). Participants were more likely to complete the scenarios incorrectly with the NPC (n=32) when compared with the TSPA (n=7) (P<0.0001). CONCLUSIONS: TSPAs are more efficient and accurate when calculating CRIs and FDR compared with conventional methods. Medical mathematics must be emphasised during the veterinary curriculum.

Thermal antinociceptive, sedative and cardiovascular effects of Governing Vessel 1 dexmedetomidine pharmacopuncture in healthy cats.

OBJECTIVE: To compare the antinociceptive, sedative and cardiovascular effects of dexmedetomidine pharmacopuncture at Governing Vessel 1 (GV 1) with dexmedetomidine intramuscular (IM) administration. STUDY DESIGN: Randomized, masked crossover design. ANIMALS: A group of eight healthy female cats. METHODS: Cats were randomly administered either dexmedetomidine (0.005 mg kg-1; Dex-IM) IM or at acupuncture point GV 1 (Dex-P) separated by 1 week. Prior to and up to 120 minutes posttreatment, skin temperature (ST), thermal threshold (TT), heart rate (HR), respiratory rate (fR), sedation, muscle relaxation and auditory response scores were recorded. Parametric data were analyzed using a two-way repeated measures anova followed by Tukey's test for multiple comparisons. Nonparametric data were analyzed using a Friedman test followed by Dunn's multiple comparisons test, and Wilcoxon signed-rank test with Bonferroni correction for multiple comparisons. Significance was set at p ≤ 0.05. RESULTS: There were no differences within or between treatments for ST, fR and auditory response. TT was significantly higher at 30-90 minutes in Dex-P (p ≤ 0.0285) than baseline. TT was significantly higher at 60-90 minutes for Dex-P than for Dex-IM (p ≤ 0.0252). HR was significantly lower at 10-75 minutes in Dex-P (p ≤ 0.0378) and at 5-75 minutes in Dex-IM (p ≤ 0.0132) than baseline. Compared with baseline, sedation scores were higher at 25 minutes (p = 0.0327) and 30 minutes (p = 0.0327), and muscle relaxation scores were higher at 25 minutes (p = 0.0151) and 35 minutes (p = 0.0151) in Dex-P. There were no differences in HR, sedation and muscle relaxation scores between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Dex-P increased thermal antinociception compared with Dex-IM at the same dose of dexmedetomidine in cats. This antinociceptive effect must be evaluated under clinical situations.

The antinociceptive effects of intravenous administration of three doses of butorphanol tartrate or naloxone hydrochloride following hydromorphone hydrochloride to healthy conscious cats.

OBJECTIVE: To evaluate thermal antinociception from intravenous (IV) administration of hydromorphone alone or followed by butorphanol or naloxone in cats. STUDY DESIGN: Randomized, controlled, masked, crossover design. ANIMALS: A group of eight adult female cats. METHODS: Cats were administered six treatments of two IV injections 30 minutes apart: treatments S-S, two 0.9% saline; H-S, hydromorphone (0.1 mg kg-1) and saline; H-LB, hydromorphone and butorphanol (0.02 mg kg-1); H-MB, hydromorphone and butorphanol (0.1 mg kg-1); H-HB, hydromorphone and butorphanol (0.2 mg kg-1); H-N, hydromorphone and naloxone (0.04 mg kg-1). Skin temperature (ST), thermal threshold (TT) and sedation score (SS) were recorded before (baseline) and for 8 hours after the first injection. Percentage maximum possible effect (%MPE), thermal excursion (TE), TT, SS and ST were compared using two-way repeated measures anova or Friedman test followed by Tukey's or Dunn's multiple comparisons test when appropriate. Significance was set at p ≤ 0.05. RESULTS: Data from seven cats were analyzed. There were no significant differences among treatments in baseline values, SS and within S-S over time. Compared with respective 0.5 hour values following hydromorphone administration, %MPE was significantly lower at 4-8 hours for H-S; at 3-8 hours for H-LB; at 4-8 hours for H-MB; at 6-8 hours for H-HB and at 1-8 hours for H-N. Compared with respective 0.5 hour values, TE was significantly lower at 4-8 hours for H-S; at 3-8 hours for H-LB; at 2 and 4-8 hours for H-MB; at 6 and 8 hours for H-HB and at 1-8 hours for H-N. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol and naloxone reduced hydromorphone-induced thermal antinociception. Butorphanol preserved hydromorphone antinociceptive properties better than naloxone. Butorphanol is recommended during non-life-threatening scenarios as a partial reversal agent for hydromorphone in cats.

Pharmacokinetics and pharmacodynamics of midazolam following intravenous and intramuscular administration to sheep.

OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult rams. PROCEDURES Sheep were administered midazolam (0.5 mg/kg) by the IV route and then by the IM route 7 days later in a crossover study. Physiologic and behavioral variables were assessed and blood samples collected for determination of plasma midazolam and 1-hydroxymidazolam (primary midazolam metabolite) concentrations immediately before (baseline) and at predetermined times for 1,440 minutes after midazolam administration. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods. RESULTS Following IV administration, midazolam was rapidly and extensively distributed and rapidly eliminated; mean ± SD apparent volume of distribution, elimination half-life, clearance, and area under the concentration-time curve were 838 ± 330 mL/kg, 0.79 ± 0.44 hours, 1,272 ± 310 mL/h/kg, and 423 ± 143 h·ng/mL, respectively. Following IM administration, midazolam was rapidly absorbed and bioavailability was high; mean ± SD maximum plasma concentration, time to maximum plasma concentration, area under the concentration-time curve, and bioavailability were 820 ± 268 ng/mL, 0.46 ± 0.26 hours, 1,396 ± 463 h·ng/mL, and 352 ± 148%, respectively. Respiratory rate was transiently decreased from baseline for 15 minutes after IV administration. Times to peak sedation and ataxia after IV administration were less than those after IM administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated midazolam was a suitable short-duration sedative for sheep, and IM administration may be a viable alternative when IV administration is not possible.

Comparison of sedation and mechanical antinociception induced by intravenous administration of acepromazine and four dose rates of dexmedetomidine in donkeys.

OBJECTIVE: To assess and compare the sedative and antinociceptive effects of four dosages of dexmedetomidine in donkeys. STUDY DESIGN: Randomized, controlled, crossover, Latin-square, blinded study. ANIMALS: Six healthy, castrated, adult, standard donkeys. METHODS: Dexmedetomidine (2, 3, 4 and 5 µg kg-1; D2, D3, D4 and D5), acepromazine (0.1 mg kg-1) and saline were administered intravenously to each donkey and a 1 week interval was allowed between successive trials on each animal. Sedation scores (SS) and head heights above ground (HHAG) were used to assess sedation and mechanical nociceptive threshold (MNT) testing to assess antinociception over 120 minutes post-treatment. Areas under the curve (AUC) for 0-30, 30-60 and 60-120 minutes were computed to compare the effect of treatments. RESULTS: SS-AUC0-30 values were larger for D4 and D5, and SS-AUC30-60 values were larger for D5 than for saline. All dexmedetomidine treatments produced lower HHAG-AUC0-30 and HHAG-AUC30-60 values, and acepromazine produced lower HHAG AUC60-120 values than did saline. For MNT, D3, D4 and D5 increased AUC0-30 and AUC30-60 values compared with saline and also AUC0-30 values compared with D2 and acepromazine. Smaller MNT-AUC30-60 values were obtained with D2 than with D4 and D5, with D3 than with D5, and with acepromazine than with D4 and D5. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine induced sedation and dosage-dependent mechanical antinociception. Larger dexmedetomidine dose rates were required to induce antinociception than sedation. Furthermore, the antinociception induced by dexmedetomidine was of shorter duration than its sedation. For minor painful procedures on standing donkeys, D5 may be clinically useful to provide sedation and analgesia.

Sedative and mechanical antinociceptive effects of four dosages of romifidine administered intravenously to donkeys.

Although romifidine is commonly used to provide sedation and analgesia for the facilitation of clinical procedures in donkeys, limited scientific information is available for this drug in this species. This randomized, controlled, crossover, Latin-square, blinded study compared the sedative and antinociceptive effects of four dosages of romifidine (40, 60, 80, and 100µg/kg IV; R40, R60, R80, and R100, respectively), acepromazine (0.1mg/kg IV; ACE) and saline (0.9%, 5mL IV) by assigning sedation scores (SS) and measuring head heights above ground (HHAG) and mechanical nociceptive thresholds (MNT) in donkeys. Areas under the curve (AUC) from 0 to 30, 30-60, 60-120, and 120-180min after administration were computed for SS, HHAG, and MNT and compared among treatments. Romifidine and ACE, but not saline, induced clinical signs of sedation. SS-AUC0-30 for R60, R80 and R100, and SS-AUC30-60 for R100 were higher than corresponding values for saline. HHAG-AUC30-60 for R40 and R80, and HHAG-AUC60-120 for R40, R60, R80 and R100 were smaller than for saline. HHAG-AUC60-120 for R100 were also smaller than those for ACE. Romifidine, but not saline or ACE, increased MNT. MNT-AUC0-30 and MNT-AUC30-60 for R40, R60, R80 and R100, and MNT-AUC60-120 for R80 and R100 were higher than corresponding values for saline and ACE. MNT-AUC60-120 for R100 were higher than for all other romifidine treatments. In donkeys, the degree of sedation was similar for the four dosages of romifidine, but antinociception was dose-dependent.

Sedation and mechanical hypoalgesia after sublingual administration of detomidine hydrochloride gel to donkeys.

OBJECTIVE To compare sedative and mechanical hypoalgesic effects of sublingual administration of 2 doses of detomidine gel to donkeys. DESIGN Randomized blinded controlled trial. ANIMALS 6 healthy castrated male donkeys. PROCEDURES In a crossover study design, donkeys received each of the following sublingual treatments 1 week apart in a randomly assigned order: 1 mL of molasses (D0) or detomidine hydrochloride gel at 20 µg/kg (9 µg/lb; D20) or 40 µg/kg (18 µg/lb; D40). Sedation score (SS), head height above the ground (HHAG), and mechanical nociceptive threshold (MNT) were assessed before and for 180 minutes after treatment. Areas under the effect change-versus-time curves (AUCs) from 0 to 30, 30 to 60, 60 to 120, and 120 to 180 minutes after administration were computed for SS, HHAG, and MNT and compared among treatments. RESULTS D20 and D40 resulted in greater SS AUCs from 60 to 120 minutes and smaller HHAG AUCs from 30 through 180 minutes than did D0. The D40 resulted in smaller HHAG AUCs from 60 to 120 minutes than did D20. Compared with D0 values, MNT AUCs from 60 to 120 minutes were higher for D20, whereas MNT AUCs from 30 through 180 minutes were higher for D40. CONCLUSIONS AND CLINICAL RELEVANCE D20 and D40 induced sedation and mechanical hypoalgesia in donkeys by > 30 minutes after administration, but only sedation was dose dependent. Sublingual administration of detomidine gel at 40 µg/kg may be useful for sedation of standing donkeys prior to potentially painful minor procedures.

Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats.

OBJECTIVE: To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats. ANIMALS: 6 healthy adult cats. PROCEDURES: In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points. RESULTS: Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation.

Sedation and mechanical antinociception after intravenous administration of detomidine in donkeys: a dosage-effect study.

There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 µg/kg) and acepromazine (50 µg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 µg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 µg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 µg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 µg/kg detomidine, and AUC60-120 for 10 µg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 µg/kg than for 17 and 20 µg/kg detomidine. MNT AUC60-120 values were larger for 20 µg/kg detomidine than for saline, 10 µg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia.

Comparing lidocaine, bupivacaine and a lidocaine-bupivacaine mixture as a metacarpal block in sheep.

Mechanical sensory blocking effects in the metacarpi of rams were compared following perineural injection of saline, 2% lidocaine (LIDO), 0.5% bupivacaine (BUPI), and a 1:1 (volume/volume) mixture of LIDO-BUPI. Saline was also administered in the contralateral metacarpi. Compared with the saline treatment and contralateral controls, the various treatments induced larger area under the curve (AUC) values 0-60 min post-treatment (AUC0-60). Administration of BUPI and LIDO-BUPI also induced larger AUC60-120 values (P<0.01). The AUC0-60 and AUC60-120 values with LIDO were less than those achieved with LIDO-BUPI and BUPI (P<0.001), and AUC60-120 values with LIDO-BUPI were less than those obtained with BUPI (P<0.05). Anaesthesia occurred within 5 min following the administration of all local anaesthetics and lasted longer in the case of BUPI (110.0 ± 47.3 min) than with LIDO (40.0 ± 13.2 min) (P<0.01). The duration of anaesthesia was 86.9 ± 66.0 min with the LIDO-BUPI combination. Thus this combination offered no apparent advantages over the use of BUPI alone.

A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses.

OBJECTIVE: To compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses. STUDY DESIGN: Randomized, controlled, crossover, Latin-square, operator-blinded design. ANIMALS: Six 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg. METHODS: Each animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg(-1) ), or acepromazine (0.05 mg kg(-1) ) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold change versus time curve values for 60 minutes (AUC(0-60) ) post-drug administration were used to compare the effect of treatment. A 1-week interval was allowed between successive trials on each animal. RESULTS: All doses of xylazine, but not acepromazine or saline, increased mechanical thresholds for up to 60 minutes. Xylazine-induced hypoalgesia was dose-dependent and corresponding AUC(0-60) values for each treatment were not significantly different between donkeys and horses (p ≥ 0.0697). CONCLUSION: The hypoalgesic effects of xylazine at four different doses were not different between donkeys and horses. CLINICAL RELEVANCE: Xylazine induced a similar degree of mechanical hypoalgesia in donkeys and horses suggesting that similar doses are needed for both species with regard to analgesia.

Prevention of N-methyl-D-aspartate-induced mechanical nociception by intrathecal administration of ketoprofen and ketamine in sheep.

BACKGROUND: Nonsteroidal antiinflammatory drugs and N-methyl-D-aspartate (NMDA) receptor antagonists reduce pain hypersensitivity when given by the intrathecal (i.t.) route, but their combined effects have hardly been studied. We assessed the effects of the nonsteroidal antiinflammatory drug ketoprofen and the NMDA receptor channel blocker ketamine, given alone and in combination, on mechanical nociceptive thresholds in sheep implanted with indwelling cervical i.t. catheters. METHODS: Sheep were given, by i.t. catheter, ketoprofen (200-3200 microM; 100 microL) and ketamine (25-400 microM; 100 microL) alone or in combination (837.95-3350.78 microM; 100 microL; 0.955:0.045 proportion). They also received NMDA (2 mM; 100 microL) preceded by the highest concentration of ketoprofen and ketamine alone or in combination. Saline solution (0.9%; 100 microL) and xylazine (1.95 mM; 100 microL) were used as negative and positive controls, respectively. RESULTS: Xylazine significantly increased the area under the nociceptive threshold versus time curve values (AUC) for 30, 60, and 180 min posttreatment. Ketoprofen and ketamine, alone and in combination, produced no significant effect on AUC values. NMDA alone decreased the AUC value for 30 min posttreatment. This pain hypersensitivity was prevented by preadministering ketoprofen and ketamine alone and in combination. CONCLUSIONS: In sheep, i.t. administration of ketoprofen and ketamine, alone or together, produced no hypoalgesia; however, they prevented NMDA-induced mechanical hypersensitivity. Ketoprofen and ketamine may have therapeutic potential in conditions associated with persistent pain.

Involvement of opioidergic and alpha2-adrenergic mechanisms in the central analgesic effects of non-steroidal anti-inflammatory drugs in sheep.

The level within the central nervous system where non-steroidal anti-inflammatory drugs (NSAIDs) produce analgesia and the mechanisms by which they mediate this effect are still uncertain. This study assessed the central analgesic effects of ketoprofen, phenylbutazone, salicylic acid and tolfenamic acid in sheep implanted with indwelling intrathecal (i.t.) catheters and submitted to mechanical noxious stimulation. The sheep received i.t. cumulative concentrations (0.375-200 microM; 100 microL) as well as a single intravenous (i.v.) dose (3, 8, 10 and 2 mg/kg, respectively) of each NSAID. The sheep were also given i.t. naloxone (5.49 mM; 100 microL) and atipamezole (4.03 mM; 100 microL) prior to i.v. ketoprofen. None of the i.t. NSAIDs increased mechanical thresholds. Intravenously, only ketoprofen and tolfenamic acid raised the pain thresholds. The hypoalgesic effect of i.v. ketoprofen was prevented by i.t. naloxone or atipamezole. Although NSAIDs had no direct effect on the spinal cord, their analgesic action appeared to be spinally mediated.