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The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α2-adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half-maximal effect (IC50 ) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data.

Benzodiazepines are purported to inhibit opioid analgesia via GABA receptor binding. The purpose of this study was to determine if diazepam (DZ) inhibits, or flumazenil (FZ) enhances, opioid analgesia in isoflurane (ISO)-anesthetized dogs. Eight healthy, mixed breed, intact female dogs weighing 19.6 ± 2.0 kg (mean ± SD) and aged 1.8 ± 0.4 years were anesthetized with ISO in oxygen three times over a six week period. Dogs were mechanically ventilated to normocapnia and body temperature was maintained at 38.2 ± 0.4 C. After 30 minutes, ISO MAC was determined in triplicate using standard techniques. A single dose of glycopyrrolate (0.015 mg kg[sup -1] IM) was given 5 minutes prior to administration of fentanyl (FEN). FEN was administered as a bolus (10 µg kg[sup -1] IV) followed by an infusion (0.3 µg kg[sup -1]h[sup -1] IV) throughout the rest of the experiment. After determining ISO-FEN MAC, each dog randomly received 0.9% NaCl (SALINE), DZ (0.5 mg kg[sup -1] IV followed by 0.5 mg kg[sup -1]h[sup -1] IV) or FZ (0.1mg kg[sup -1] IV followed by 0.1mg kg[sup -1]h[sup -1] IV). After 30 minutes of treatment infusion, MAC was determined in triplicate. Data were analyzed using ANOVA with posthoc differences identified using Tukey's test. [ABSTRACT FROM AUTHOR]

Electromagnetic field therapy has been used in human and veterinary medicine to promote tissue healing and alleviate a variety of chronic medical conditions. The purpose of this study was to evaluate the effects of PEMF therapy (0.5 Hz delivered in a continuous cycle of 20-minutes on then 20-minutes off) on post-operative pain in dogs. Sixteen healthy dogs weighing 19.8 ± 6.2 kg (mean ± SD) and aged 15.4 ± 10.7 months were evaluated following routine ovariohysterectomy. Anesthesia consisted of atropine (0.04 mg kg[sup -1] SQ), acepromazine (0.02 mg kg[sup -1] SQ), fentanyl (0.01 mg kg[sup -1] SQ), thiopental to effect (10–15 mg kg[sup -1] IV) and maintenance with halothane. Pain score (numeric rating scale, 0–28), heart rate, respiratory rate, indirect mean arterial pressure (MAP) and body temperature were evaluated before anesthetic premedication, at extubation, 30 minutes after extubation and then hourly for 6 hours. Following extubation, dogs were randomly assigned to one of four treatment groups with four dogs per group: (1) PEMF off, 0.9% NaCl IV; (2) PEMF on, 0.9% NaCl IV; (3) PEMF off, morphine 0.25 mg kg[sup -1] IV; (4) PEMF on, morphine 0.25 mg kg[sup -1] IV. One observer, who was unaware of treatment, obtained behavioral observations and physiological data. Due to the small sample size, data were analyzed by Kruskal–Wallis with significance considered with p < 0.05. Pain score in group 4 [1.5, 0–5 (median, range)] was significantly less than group 1 (8, 6–13) at 30 minutes, but not different from group 2 (5.5, 4–7) or 3 (4.5, 2–9). Significant differences in MAP occurred at 300 minutes (groups 3 and 4 less than group 1) and at 360 minutes (group 4 less than groups 1 and 2). These results suggest that PEMF may augment analgesia following ovariohysterectomy in dogs and that further study of the analgesic effects of PEMF is warranted. [ABSTRACT FROM AUTHOR]

As a result of the observed behavioral differences between dogs and horses in response to opioid and α-2 adrenergic agonists, we tested the hypothesis that the distribution, density, and subtype of opiate and α-2 adrenergic receptors within the central nervous system (CNS) are significantly different between the horse and the dog. Brain tissue was obtained following euthanasia as a secondary use of tissue from three dogs (3 years of age) at 126 days post-surgery and from three horses (2–5 years of age) at 72 days post-surgery. Animals were opioid- and α-2 agonist-free at the time of euthanasia. The brains were removed, sectioned coronally into 1 cm slabs, frozen in methylbutane cooled by liquid nitrogen, and stored at -70.5 °C. Receptor autoradiography was performed using established techniques. [3 H]DAMGO, [3 H]U-69593, and [3 H]RX821002 were used for μ-opiate, κ-opiate, and α-2 adrenergic binding assays, respectively. Binding densities (fmol mg-1 protein binding) were not affected by differences in brain size. Species differences were analyzed separately for each major brain region by Repeated Measures anova for subregions followed by Fisher's protected LSD. p < 0.05 was considered significant. Only significant differences were reported. There was higher binding of μ-opiate receptors in the frontal cortex, left somatosensory cortex, colliculus (mid-brain), and granule cell layer of the cerebellum of the horse than that of the dog. There was higher binding to κ-opiate receptors in the frontal cortex of the dogs compared to the horses, whereas binding to κ-opiate receptors in the cerebellum was higher in horses. Binding to α-2 adrenergic receptors in the mid-brain was significantly higher in the dog than the horse. There was higher binding in the dorsomedial and dorsolateral periaqueductal grey matter of the dog as compared to the horse. These results suggest a neuroanatomical basis for the differences in opioid and α-2 adrenergic pharmacodynamics observed between horses and dogs. [ABSTRACT FROM AUTHOR]

Intra-articular (IA) opioids have been administered in people and animals with the intent of providing local analgesia while minimizing systemic effects. Studies supporting the analgesic e cacy of IA morphine suggest that opioid receptors are present and functional in joints. The purpose of this study was to determine if opioid receptors are present in synovial tissue of horses. [ABSTRACT FROM AUTHOR]

Objective: This study describes the pharmacokinetics and pharmacodynamics, including antinociceptive effects, of a transdermal buprenorphine solution in horses. It was hypothesized that transdermal application would lead to sustained blood concentrations and antinociceptive effects with fewer adverse effects compared with intravenous (IV) injection., Study Design: Prospective nonrandomized four-part parallel experimental study., Animals: A group of eight horses (three mares and five geldings) aged 6-12 years., Methods: Horses were administered incremental doses of 15, 30 and 45 μg kg -1 of buprenorphine transdermal solution and a single IV dose of 5 μg kg -1 of buprenorphine with a 2 week washout period between treatments. Concentrations of buprenorphine were determined in plasma using liquid chromatography-tandem mass spectrometry and modeled using a nonlinear mixed effects population pharmacokinetic model to determine pharmacokinetic parameters. Pharmacodynamic effects, including changes in locomotor activity, heart rate, body temperature, gastrointestinal borborygmi, thermal and mechanical nociceptive thresholds were recorded. Mixed effects analysis of variance and post hoc comparisons were performed using a Bonferroni multiple comparison adjustment to assess differences in pharmacodynamic parameters between baseline and each time point within each dose group and between dose groups at the same time point., Results: Transdermal application of buprenorphine resulted in low systemic concentrations relative to IV injection. Bioavailability after transdermal application was 11%. Thermal nociceptive thresholds were significantly (p < 0.05) increased (4.3-10.7% relative to baseline) for up to 72 hours in the IV dose group, but only sporadically in the transdermal dose groups (2.5-9.9% relative to baseline). Changes in locomotor activity, heart rate and borborygmi varied over time and with dose., Conclusions and Clinical Relevance: Limited thermal antinociceptive effects were observed at the transdermal doses studied likely owing to limited absorption relative to IV dosing. Future studies may be directed toward investigating antinociceptive effects of higher transdermal doses and different application sites., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the pharmacokinetics of a single bolus of intravenous (IV) propofol after intramuscular administration of etorphine, butorphanol, medetomidine, and azaperone in 5 southern white rhinoceros to facilitate reproductive evaluations. A specific consideration was whether propofol would facilitate timely orotracheal intubation., Animals: 5 adult, female, zoo-maintained southern white rhinoceros., Procedures: Rhinoceros were administered etorphine (0.002 mg/kg), butorphanol (0.02 to 0.026 mg/kg), medetomidine (0.023 to 0.025 mg/kg), and azaperone (0.014 to 0.017 mg/kg) intramuscularly (IM) prior to an IV dose of propofol (0.5 mg/kg). Physiologic parameters (heart rate, blood pressure, respiratory rate, and capnography), timed parameters (eg, time to initial effects and intubation), and quality of induction and intubation were recorded following drug administration. Venous blood was collected for analysis of plasma propofol concentrations using liquid chromatography-tandem mass spectrometry at various time points after propofol administration., Results: All animals were approachable following IM drug administration, and orotracheal intubation was achieved at 9.8 ± 2.0 minutes (mean ±SD) following propofol administration. The mean clearance for propofol was 14.2 ± 7.7 ml/min/kg, the mean terminal half-life was 82.4 ± 74.4 minutes, and the maximum concentration occurred at 2.8 ± 2.9 minutes. Two of 5 rhinoceros experienced apnea after propofol administration. Initial hypertension, which improved without intervention, was observed., Clinical Relevance: This study provides pharmacokinetic data and insight into the effects of propofol in rhinoceros anesthetized using etorphine, butorphanol, medetomidine, and azaperone. While apnea was observed in 2 rhinoceros, propofol administration allowed for rapid control of the airway and facilitated oxygen administration and ventilatory support.

Objective: To evaluate the sedative and cardiopulmonary effects of various combinations of acepromazine, dexmedetomidine, hydromorphone, and glycopyrrolate, followed by anesthetic induction with propofol and maintenance with isoflurane in healthy dogs., Animals: 6 healthy adult female Beagles., Procedures: Dogs were instrumented for hemodynamic measurements while anesthetized with isoflurane. Two hours after recovery, dogs received 1 of 4 IM combinations in a crossover design with 1 week between treatments: hydromorphone (0.1 mg/kg) and acepromazine (0.005 mg/kg; HA); hydromorphone and dexmedetomidine (0.0025 mg/kg; HD); hydromorphone, acepromazine, and dexmedetomidine (HAD); and hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate (0.02 mg/kg; HADG). Sedation was scored after 30 minutes. Physiologic variables and cardiac index were measured after sedation, after anesthetic induction with propofol, and every 15 minutes during maintenance of anesthesia with isoflurane for 60 minutes (target expired concentration at 760 mm Hg, 1.3%)., Results: Sedation scores were not significantly different among treatments. Mean ± SD cardiac index was significantly higher for the HA (202 ± 45 mL/min/kg) and HADG (185 ± 59 mL/min/kg) treatments than for the HD (88 ± 31 mL/min/kg) and HAD (103 ± 25 mL/min/kg) treatments after sedation and through the first 15 minutes of isoflurane anesthesia. No ventricular arrhythmias were noted with any treatment., Clinical Relevance: In healthy dogs, IM administration of HADG before propofol and isoflurane anesthesia provided acceptable cardiopulmonary function with no adverse effects. This combination should be considered for routine anesthetic premedication in healthy dogs.

Purpose: To determine whether a single 4-point regional nerve block using 2% lidocaine administered distal to the fetlock of sheep with a single distal limb lameness will result in analgesia of the digits., Animals: Eighteen adult ewes with a single limb lameness originating from distal to the metacarpo/metatarsophalangeal joint were enrolled in the study., Procedures: Digital lameness was confirmed and scored based on clinical examination. Pain associated with digital lesions was assessed in triplicate using a pressure algometer to quantify mechanical nociceptive threshold. The same procedure was repeated on the contralateral limb as a control, and maximum force and time to response recorded. A 4-point regional nerve block was performed using 8 mL of 2% lidocaine. Mechanical nociception was again applied in triplicate to both limbs as described above, by a blinded investigator. Following appropriate medical treatment, the ewe was released and lameness scoring repeated.Median values for pressure and time to withdrawal were determined for affected and control limbs, and differences between pre- and post-lidocaine block measures were compared using Friedman's ANOVA test. The Wilcoxon Signed-Rank test was used to compare lameness score pre- and post-block. Statistical significance was set at α = 0.05., Main Findings: Application of the 4-point block resulted in a change in pressure required to elicit withdrawal (F-value 17.7; P < 0.0001) as well as time to withdrawal (F-value 20.4; P < 0.0001), for the affected limb as compared to the control limb. Lameness scores decreased following the block (Signed-rank statistic 85.5; P < 0.0001)., Principal Conclusion: The 4-point nerve block resulted in anesthesia of the distal limb in sheep in this clinical model., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Objective: To compare efficacy and safety of a continuous rate infusion of detomidine hydrochloride and romifidine hydrochloride for standing elective bilateral laparoscopic ovariectomy in mares., Study Design: Blinded, randomized prospective clinical study., Animals: Eighteen healthy mares presenting for elective bilateral ovariectomy METHODS: Mares were randomly assigned to one of two sedation protocols. Prior to surgery, baseline head height, heart rate, respiratory rate, and postural sway were recorded. An IV loading dose of α2-agonist (46 μg/kg romifidine or 13.9 μg/kg detomidine) was administered. Standing sedation was maintained with a continuous rate infusion of the respective α2-agonist (126 μg/kg/h romifidine or 37.8 μg/kg/h detomidine). Intraoperative measurements included respiratory rate, heart rate, head height, postural sway, and response to surgical stimulus. Postoperatively, fecal output was recorded, and pain scoring was performed using composite pain score and visual analog scales., Results: Three of 18 horses required additional α-2 agonists: one detomidine and two romifidine and butorphanol. Head height during surgery was lower (p < .001) in mares receiving detomidine. Postural sway around the vertical axis was greater in mares sedated with detomidine rather than romifidine (p = .013). No differences were detected in intraoperative heart rate, postoperative pain scores or postoperative fecal output between sedation techniques., Conclusion: Comparable scores for surgical stimulation and sedation were measured in both sedation groups. No differences in postoperative analgesia or manure production were identified., Clinical Significance: Romifidine appears suitable as an alternative to detomidine and may limit ataxia and head drop in sedated horses., (© 2021 American College of Veterinary Surgeons.)

Przewalski's horses ( Equus ferus przewalskii ) are an endangered equid species. Anesthesia administered by remote delivery is often needed to provide medical care. Behavioral and physiologic parameters were prospectively compared in 14 horses (8 females and 6 males, 3-18 yr) after a single-dart or staged two-dart anesthesia induction protocol with intramuscular medetomidine (0.06 mg/kg), butorphanol (0.05 mg/kg), thiafentanil (0.02 mg/kg), and ketamine (1 mg/kg). Seven horses were randomly assigned to receive all drugs in a single dart, and the other seven to receive medetomidine and butorphanol 10 min prior to thiafentanil and ketamine in a second dart. Induction and recovery quality were scored on a scale from 1 to 5 (worst to best), and video recordings were assessed for frequency of specific behaviors. Need for supplemental propofol was recorded. Median induction score was significantly better ( P = 0.01) after two darts (4/5) compared to a single dart (3/5). Degree of muscle fasciculation (undesirable) during induction was significantly lower ( P = 0.006) with the two-dart protocol. During the transition to recumbency, 71% versus 14% of horses transitioned headfirst (undesirable) after a single dart versus two darts, respectively ( P = 0.07). Supplemental propofol administration was necessary in 43% of horses after two darts and in 100% of horses after a single dart ( P = 0.10) to facilitate intubation and reach a working depth of anesthesia. Physiologic and recovery parameters were not significantly different between groups. Improved induction quality was observed clinically using a staged two-dart versus a single-dart protocol and should be considered when anesthetizing captive Przewalski's horses using this drug combination.

Objective: To evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs., Study Design: Prospective experimental study., Methods: A total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 μg kg -1 hour -1 ) and after two IV doses of vatinoxan in sequence (90 and 180 μg kg -1 hour -1 ). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p < 0.05 was considered significant., Results: Dexmedetomidine reduced sevoflurane MAC by 67% (0.64 ± 0.1%), mean ± standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 ± 0.1%) and 43% (1.1 ± 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline., Conclusions and Clinical Relevance: IV infusions of 90 and 180 μg kg -1 hour -1 of vatinoxan combined with 4.5 μg kg -1 hour -1 dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 μg kg -1 hour -1 might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Alfaxalone has been successfully used intramuscularly (im) combined with medetomidine and azaperone for immobilization of small ungulates. An experimental 40 mg/ml alfaxalone solution (RD0387) was recently formulated for reduced injection volume. The objective of this study was to assess the efficacy and cardiopulmonary effects of high-concentration alfaxalone combined with medetomidine and azaperone for the intramuscular immobilization of captive Rocky Mountain elk ( Cervus elaphus nelsoni ). Seven adult female elk were used in a crossover design in which they were administered alfaxalone 1 mg/kg, medetomidine 0.05 mg/kg, and azaperone 0.1 mg/kg or alfaxalone 0.5 mg/kg, medetomidine 0.1 mg/kg, and azaperone 0.1 mg/kg im approximately 3 wk apart. Drugs were delivered to each elk in a chute by hand injection. Once recumbent, elk were placed in sternal recumbency for a period of 30 min, during which time level of sedation, response to minor procedures, heart rate, respiratory rate, rectal temperature, oxygen saturation, and direct arterial blood pressures were recorded every 5 min. Arterial blood gases were performed every 15 min. At 30 min, elk were administered atipamezole 0.25 or 0.5 mg/kg im and recovery quality and times were recorded. Statistical comparisons were made by t test, Wilcoxon signed rank test, and repeated measures analysis (significance level P < 0.05). Both drug combinations provided effective immobilization for 30 min, with induction and recovery time and quality similar to other medetomidine-based combinations used in elk. Cardiopulmonary effects included bradycardia, hypertension, and hypoxemia that resolved with oxygen supplementation. The average injection volume in the low-dose alfaxalone combination was approximately 5 ml. These combinations provided deep sedation and the ability to perform minor procedures in captive elk, with acceptable cardiopulmonary parameters as long as supplemental oxygen was provided.

Background: Post-anaesthetic sedation is administered to horses to improve recovery quality from inhalant anaesthesia and reduce the risk of catastrophic injury. A single dose of dexmedetomidine for this purpose has not been evaluated clinically., Objectives: To determine whether dexmedetomidine improves recovery quality from sevoflurane anaesthesia compared to a previously studied dose of romifidine., Study Design: Prospective, randomised, masked clinical trial., Methods: Ninety-nine, adult, client-owned horses anaesthetised for elective procedures completed the trial. Anaesthetic protocol was standardised. Horses were randomly assigned to receive either dexmedetomidine 1 mcg/kg bwt (D) or romifidine 20 mcg/kg bwt (R) intravenously at their first spontaneous breath in recovery. Recoveries were reviewed and independently assigned subjective visual analogue scale (VAS) scores (0-100 mm, worst to best) for overall quality and standing ataxia scores (1-4, none to severe) by two anaesthesiologists blinded to treatment group. Objective anaesthesia and recovery data were also recorded. Comparisons were made using the Chi-square, Wilcoxon rank sum, linear models or Welch-Satterthwaite two-sample t-test (P ≤ .05). Predictors of VAS score were analysed independent of treatment group., Results: There were no significant differences between groups except end-tidal sevoflurane (FE´Sevo) concentration and post-induction extra ketamine dosing. Including FE´Sevo and additional ketamine in the analysis as covariates, VAS scores and time to standing were not significantly different between groups. Increased age, not receiving a nerve block, increased duration of hypotension, and having a nervous temperament were significant predictors of VAS score., Main Limitations: No universal recovery scale exists for inter-study comparisons., Conclusions: After sevoflurane anaesthesia, sedation with dexmedetomidine or romifidine provides clinically similar recovery time and quality., (© 2020 EVJ Ltd.)

Objective: To compare the Element point-of-care (POC) portable blood gas analyzer with a laboratory-based bench-top reference analyzer using whole blood samples obtained from horses presenting to a referral center with various disorders in order to determine agreement between these analyzers., Design: Prospective clinical study., Setting: The study was conducted at a university teaching hospital at moderate altitude., Animals: One hundred paired samples from 80 horses >1 year of age were collected after obtaining informed client consent. Fifty paired samples were from patients admitted for elective procedures and considered to be healthy, and 50 paired samples were emergency admissions and considered to be critically ill., Measurements and Main Results: Paired whole blood samples were evaluated on both the Element POC and Radiometer ABL 800 FLEX analyzers simultaneously, and results were compared. Pearson correlation coefficients between analyzers were calculated. To assess agreement, scatter and Bland-Altman plots were evaluated, and mean difference and 95% limits of agreement were calculated for each analyte. Correlation was either good (0.8-0.92) or excellent (>0.93) for the majority of analytes. All analytes apart from hemoglobin had acceptable agreement, with ≥80% of individual results within agreement targets. Precision targets were acceptable for most analytes, with partial pressure of carbon dioxide (pCO 2 ) and calcium (Ca 2+ ) exceeding precision targets., Conclusions: The portable Element POC system had acceptable agreement with the ABL 800 FLEX bench-top analyzer currently in use at the study center when evaluating the majority of analytes from equine whole blood samples., (© Veterinary Emergency and Critical Care Society 2020.)

Seven anesthesia events were performed over 6 wk on a 1.5-yr-old female okapi ( Okapia johnstoni ) being managed for a fetlock injury. A combination of butorphanol (B) (median; range) (0.045; 0.031-0.046 mg/kg), medetomidine (M) (0.037; 0.031-0.037 mg/kg), ketamine (K) (0.553; 0.536-1.071 mg/kg), and thiafentanil (T) (0.0045; 0.0040-0.0046 mg/kg) was administered in a padded stall. One dart containing all drugs was used for the first two anesthesias. Subsequently, BM was administered 10 min prior to KT using two darts. Time (median; range) from initial injection to first effects (6; 3-7 min) and recumbency (14; 4-20 min) were recorded. Induction quality with the one-dart protocol was poor or fair and was good or excellent with the two-dart protocol. Following recumbency, the okapi was intubated and ventilated, and physiological parameters were recorded. Anesthesia was consistently achieved with BMKT, but induction was smoother with the staged two-dart approach. Neither resedation nor renarcotization was observed post-reversal.

Objective: To compare IV doses of alfaxalone and ketamine needed to facilitate orotracheal intubation and assess effects of each treatment on selected physiologic variables in goats undergoing orthopedic surgery with isoflurane anesthesia., Animals: 18 healthy adult goats., Procedures: Behavior was assessed before and after sedation with midazolam (0.1 mg/kg, IV) for IV catheter placement. Anesthesia was induced with additional midazolam (0.1 mg/kg, IV) and alfaxalone (n = 9) or ketamine (9) at 2 mg/kg, IV, over 30 seconds. An additional dose of alfaxalone or ketamine (1 mg/kg) was given IV if needed for intubation; anesthesia was maintained with isoflurane in oxygen and IV fluids with ketamine (0.5 to 1 mg/kg/h). Direct systolic (SAP), diastolic (DAP), and mean (MAP) arterial blood pressures; heart rate; and respiratory rate were recorded before induction, immediately after intubation, and during surgery. Qualitative anesthetic induction and recovery characteristics were assessed. Variables were compared within and between groups by statistical methods., Results: No preinduction variables differed significantly between groups. Postintubation and 30-minute intraoperative SAP, DAP, and MAP were higher for the ketamine group than for the alfaxalone group; within the alfaxalone group, postintubation SAP, MAP, and respiratory rate prior to mechanical ventilation were lower than respective preinduction values. All alfaxalone-group goats were intubated after 1 dose of the induction agent; 5 of 9 ketamine-group goats required an additional (1-mg/kg) dose. Postoperative recovery was good to excellent for all animals., Conclusions and Clinical Relevance: Both drugs were suitable for induction of anesthesia after sedation with midazolam, but most goats required higher doses of ketamine to allow intubation. For situations in which alfaxalone administration is appropriate, the potential for decreased arterial blood pressures and respiratory rate should be considered.

Two anesthetic protocols in adult giraffe were compared by retrospective study. Thirteen anesthesia records for medetomidine-ketamine (MK) and seven for medetomidine-ketamine with a potent opioid (MKO) were evaluated for differences in demographic, behavioral, drug, and respiratory parameters. Giraffe stood significantly more quickly with MKO vs MK though MK animals were physically restrained to preclude premature standing as part of normal recovery practices (5.5 min vs 21.4 min, P = 0.01). Regurgitation was recorded in 5/13 and resedation in 4/13 MK animals. The range of values for blood lactate was higher in MKO (5.18-11.25 mM/L) than in MK giraffe (0.78-6.08 mM/L). Despite limitations of a retrospective study, both MK and MKO giraffe anesthesia protocols exhibit benefits and side effects. Awareness and management of these factors will improve outcomes until standardized, prospective studies of giraffe immobilization offer more comprehensive guidance on protocol selection.

Case Description: A 36-kg (79-lb) castrated male Greyhound (dog 1) and a 25-kg (55 lb) spayed female Greyhound (dog 2) underwent general anesthesia for dental care with similar perianesthetic protocols on multiple occasions from 2013 to 2016. Both dogs had periodontal disease but were otherwise deemed healthy. Both dogs developed clinically relevant hyperkalemia, with signs including loss of P waves on ECG tracings, during multiple anesthetic events., Clinical Findings: Dog 1 developed hyperkalemia during 2 of 2 anesthetic events, with ECG changes noted during the first event. Dog 2 developed hyperkalemia during 3 of 4 anesthetic events, with ECG changes identified during the second and third events. Serum potassium concentration for both dogs was within the reference range prior to and between anesthetic events. No underlying etiopathogenesis for hyperkalemia was identified for either dog., Treatment and Outcome: In each hyperkalemic event, the clinician stopped the dental procedure and continued to provide supportive care and monitoring while the dog recovered from anesthesia. The ECG changes resolved, and serum potassium concentration returned to the reference range rapidly after inhalant anesthetic administration was discontinued. The dogs were discharged from the hospital without further complications., Clinical Relevance: Hyperkalemia in anesthetized Greyhounds resulted in serious cardiac conduction abnormalities, which could be potentially fatal if not recognized and promptly treated. Further investigation into the etiopathogenesis, prevention and treatment strategies, and genetic or familial components of this condition is indicated.

Background: The use of intra-articular (IA) local anaesthetics has proven to be an effective means to treat post-operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra- and peri-articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long-term analgesic effects) has not been evaluated in horses., Objectives: Describe bupivacaine concentrations following IA administration and assess biomarkers as indicators of the effects of liposomal bupivacaine on chondrocytes in vivo., Study Design: Parallel design., Methods: Sixteen exercised horses received a single IA administration of 0.12 mg/kg liposomal bupivacaine or 0.9% saline. Blood and urine samples were collected for 96 h post-drug administration. Six horses treated with bupivacaine and those receiving saline, underwent daily arthrocentesis. Six additional bupivacaine treated horses underwent arthrocentesis at 96 h. Drug concentrations were measured using LC-MS/MS and pharmacokinetic analyses performed. Immunoassays were used to measure markers of collagen degradation (C2C, C12C) and cartilage matrix synthesis (CPII, CS846) in synovial fluid., Results: The bupivacaine plasma elimination half-life was 17.8 ± 5.42 and 11.9 ± 5.17 h for horses from which synovial fluid was collected daily and at 96 h respectively. Bupivacaine concentrations in the joint were still detectable at 96 h. Significant increases in C12C and C2C were noted at 96 h in horses undergoing arthrocentesis at 96 h only. CPII was increased at 48 h and CS846 at 24 and 48 h in horses sampled daily., Main Limitations: Limited number of animals and absence of liposome control group., Conclusions: Sustained concentrations of IA bupivacaine suggest viability of this medication as an intra-articular analgesic. Effects on equine chondrocytes need further study., (© 2018 EVJ Ltd.)

Many drugs and non-drug modalities are used to manage pain in horses, but evidence regarding efficacy and safety remains limited. This manuscript will first briefly review tried and tested techniques, e.g. the use of non-steroidal anti-inflammatory drugs, in the management of pain. Newer approaches to administering medications such as oral use of detomidine, which was previously only administered by injection, will also be discussed. Finally, introductory information on newer therapies, for example acupuncture and chiropractic manipulation, that the veterinarian may consider for the management of equine pain will be presented., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Grevy's zebra ( Equus grevyi ) is an endangered species often found in zoological collections. Veterinary care for this species often requires immobilization. This study retrospectively evaluated behavioral and physiological parameters from Grevy's zebra records after three immobilization protocols: etorphine and alpha-2 agonist (EA2; n = 11); etorphine, alpha-2 agonist, and ketamine (EA2K; n = 16); and thiafentanil, alpha-2 agonist, and ketamine (TA2K; n = 6). Median time to working depth was statistically different ( P = 0.03; EA2 = 6.5 min, EA2K = 6.3 min, TA2K = 14.5 min) by the Kruskal-Wallis test. When EA2 + EA2K were combined and compared with TA2K (Wilcoxon rank sum test), median recumbency time ( P = 0.02) was also significantly longer (15 min compared with 6 min) for TA2K. There were no significant differences between the groups for physiological parameters or recovery time after reversal. Although all protocols produced anesthesia in Grevy's zebra, increased time to achieve working depth was observed with the alpha-2 and thiafentanil combinations., (© 2019 by American Association of Zoo Veterinarians.)

This study investigated the influence of changing recumbency and mode of ventilation over repeated anesthesias on the alveolar to arterial oxygen tension gradient (P A-a O 2 ) and laboratory analytes in eight horses during a year-long imaging study. Anesthesia was induced with xylazine, diazepam or guaifenesin, and ketamine and maintained with isoflurane. Horses were positioned in right or left lateral recumbency for computed tomography. Ventilation was controlled during 47% of the anesthetics. Blood was sampled from an arterial catheter prior to (30 ± 5 min from connection to anesthetic circuit), within 5 min of changing lateral recumbency, and prior to circuit disconnection (24 ± 6 min after second sample) for measurement of pH, partial pressure of arterial oxygen (PaO 2 ) and partial pressure of arterial carbon dioxide, blood glucose and electrolytes. P A-a O 2 was calculated. Data from five anesthetic episodes for each horse were summarized as mean ± standard error and analyzed using a mixed-model ANOVA. t tests were used for pairwise comparisons (P<0.05). PaO 2 decreased after turning (198 vs. 347 mmHg), then increased to 291 mmHg prior to disconnection. Correspondingly, P A-a O 2 was wider (252 vs.120 mmHg), and improved before disconnection (190 mmHg). Body temperature, ionized-Ca 2+ and blood glucose were lower, and Na + was higher at the last time point. In conclusion, turning anesthetized horses decreases PaO 2 and results in a widening P A-a O 2 suggesting a cautious approach in animals with pre-existing hypoxemia.

Rhinoceros conservation efforts are essential to the survival of the species. One such effort is focused on using advanced reproductive technologies to produce viable northern white rhinoceros ( Ceratotherium simum cottoni) embryos for implantation into southern white rhinoceros ( Ceratotherium simum simum) surrogates. Anesthesia may be required to facilitate necessary procedures in these surrogate rhinoceros, but commonly reported side effects including hypercapnia and hypoxemia limit anesthetic recumbency time due to animal safety concerns. Although many interventions have been attempted, success in improving these physiologic parameters to date is mixed. The objective of this report is to describe arterial pH (pHa), blood gas (PaO 2 and PaCO 2 ), bicarbonate, base excess, lactate, and cardiovascular (heart rate, direct arterial blood pressure) values recorded in seven intubated and ventilated female southern white rhinoceros anesthetized for reproductive examinations in a zoological park setting. Anesthetic induction was accomplished using etorphine, medetomidine, butorphanol, and midazolam. The primary hypotheses were that PaO 2 and PaCO 2 would improve after intubation and mechanical ventilation. Induction and recovery observations were also summarized. Physiologic and laboratory data were analyzed using a mixed linear regression model using ranks. Statistical significance was set at P < 0.05. The PaO 2 increased significantly ( P < 0.001) following ventilation from a median value of 58 (range, 38-67) to 123 (range, 42-184) mm Hg. The PaCO 2 significantly ( P = 0.003) decreased from 63 (range, 55-73) to 52 (range, 30-75) mm Hg, with a corresponding improvement ( P = 0.068) in pHa from 7.33 (7.25-7.34) to 7.37 (7.24-7.58) units. Intubation and ventilation improve respiratory parameters and may facilitate safe prolongation of anesthetic duration in white rhinoceros.

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

Objective: To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α 2 -adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs., Study Design: Crossover experimental study., Animals: Six healthy, adult Beagle dogs weighing 12.6±0.9 kg (mean±standard deviation)., Methods: Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique. PaCO 2 and temperature were maintained at 40±5 mmHg (5.3±0.7 kPa) and 38±0.5 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 μg kg -1 then 1.5 μg kg -1  hour -1 and 4.5 μg kg -1 then 4.5 μg kg -1  hour -1 ) or MK-467 (90 μg kg -1 then 90 μg kg -1  hour -1 and 180 μg kg -1 then 180 μg kg -1  hour -1 ); loading doses were administered over 10 minutes. MAC was redetermined in duplicate starting 30 minutes after the start of drug administration at each dose. End-tidal sevoflurane concentrations were corrected for calibration and adjusted to sea level. A repeated-measures analysis was performed and comparisons between doses were conducted using Tukey's method. Statistical significance was considered at p<0.05., Results: Sevoflurane MAC decreased significantly from 1.86±0.3% to 1.04±0.1% and 0.57±0.1% with incremental doses of dexmedetomidine. Sevoflurane MAC significantly increased with high dose MK-467, from 1.93±0.3% to 2.29±0.5%., Conclusions and Clinical Relevance: Dexmedetomidine caused a dose-dependent decrease in sevoflurane MAC, whereas MK-467 caused an increase in MAC at the higher infusion dose. Further studies evaluating the combined effects of dexmedetomidine and MK-467 on MAC and cardiovascular function may elucidate potential benefits of the addition of a peripheral α 2 -adrenergic antagonist to inhalation anesthesia in dogs., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

OBJECTIVE To evaluate agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scores determined by use of a simple descriptive scale (SDS) or a composite grading scale (CGS) for quality of recovery of horses from anesthesia and to investigate use of 3-axis accelerometry (3AA) for objective evaluation of recovery. ANIMALS 12 healthy adult horses. PROCEDURES Horses were fitted with a 3AA device and then were anesthetized. Eight diplomates evaluated recovery by use of an SDS, and 7 other diplomates evaluated recovery by use of a CGS. Agreement was tested with κ and AC1 statistics for the SDS and an ANOVA for the CGS. A library of mathematical models was used to map 3AA data against CGS scores. RESULTS Agreement among diplomates using the SDS was slight (κ = 0.19; AC1 = 0.22). The CGS scores differed significantly among diplomates. Best fit of 3AA data against CGS scores yielded the following equation: RS = 9.998 × SG 0.633 × ∑UG 0.174 , where RS is a horse's recovery score determined with 3AA, SG is acceleration of the successful attempt to stand, and ∑UG is the sum of accelerations of unsuccessful attempts to stand. CONCLUSIONS AND CLINICAL RELEVANCE Subjective scoring of recovery of horses from anesthesia resulted in poor agreement among diplomates. Subjective scoring may lead to differences in conclusions about recovery quality; thus, there is a need for an objective scoring method. The 3AA system removed subjective bias in evaluations of recovery of horses and warrants further study.

This article provides a brief overview of pain physiology and its relevance to equine patients. Objective and subjective techniques for assessing pain in the horse are described in depth. Pharmacologic and interventional pain modulation treatments are discussed with a focus on the rehabilitating horse., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats., Study Design: Prospective experimental study., Animals: Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg., Methods: Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05)., Results: Plasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1)  minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration., Conclusions and Clinical Relevance: The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT-116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT-116. Results showed a half-life of 6.9 h, k(el) of 0.1/h, AUC of 56.5 μg·h/mL, T(max) of 3.7 h, and C(max) of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT-116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24-h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT-116 following oral delivery in dogs., (© 2014 John Wiley & Sons Ltd.)

The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half-life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration., (© 2014 John Wiley & Sons Ltd.)

Background: Propofol is a widely used injectable anesthetic agent for induction and short-term maintenance in dogs. A multi-dose formulation of propofol (MDP) has been developed which includes 2% benzyl alcohol as a preservative. In order to document the use of the product under clinical conditions, MDP was tested in a prospective clinical trial conducted at six sites within the United States. One hundred thirty-eight healthy, client-owned dogs were assigned to one of six treatment groups based on premedicants (none, acepromazine/buprenorphine, midazolam/buprenorphine, medetomidine/buprenorphine) and maintenance agents (MDP, inhaled anesthetic). Anesthesia was induced by the intravenous administration of MDP given to effect. Physiological indices including heart rate, respiratory rate and blood pressure were monitored prior to and during anesthesia induction, maintenance and recovery. Adverse events, defined for severity by pre-established limits of these physiological values, as well as side effects, defined as any observation outside the normal range, were noted., Results: The mean intubation dose was 7.6 ± 2.1 mg/kg for MDP alone and 4.7 ± 1.3, 4.0 ± 1.0 mg/kg and 3.2 ± 1.4 mg/kg when buprenorphine was used in combination with midazolam, acepromazine and medetomidine, respectively. Of the 32 adverse events, apnea (12 incidents), bradycardia (9 incidents) and hypotension (7 incidents) were most frequently recorded. Emesis, cyanosis and second degree heart block were each noted once and successfully resolved. The cause of a single death 2 days post-anesthesia was assessed as a surgical complication., Conclusions: MDP was found to be acceptable for use in healthy dogs for induction and short term maintenance of anesthesia when used alone and in combination with premedicants and inhaled anesthetics.

Background: This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320-400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively., Results: Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively)., Conclusions: At the highest dose administered (THL) lidocaine CRI during xylazine/ketamine anesthesia decreased BIS and motor response to noxious stimulation, and prolonged recovery time without significant added cardiorespiratory depression.

Objective: To evaluate antioxidant capacity and inflammatory cytokine gene expression in horses fed silibinin complexed with phospholipid., Animals: 5 healthy horses., Procedures: Horses consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week). Dose-related changes in plasma antioxidant capacity, peripheral blood cell glutathione concentration and antioxidant enzyme activities, and blood cytokine gene expression were evaluated., Results: Plasma antioxidant capacity increased throughout the study period with increasing dose. Red blood cell nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase I activity decreased significantly with increasing doses of silibinin phospholipid. No significant differences were identified in glutathione peroxidase activity, reduced glutathione or oxidized glutathione concentrations, or expression of tumor necrosis factor α, interleukin-1, or interleukin-2., Conclusions and Clinical Relevance: Minor alterations in antioxidant capacity of healthy horses that consumed silibinin phospholipid occurred and suggest that further study in horses with liver disease is indicated.

Objective: To determine the oral bioavailability, single and multidose pharmacokinetics, and safety of silibinin, a milk thistle derivative, in healthy horses., Animals: 9 healthy horses., Procedures: Horses were initially administered silibinin IV and silibinin phospholipid orally in feed and via nasogastric tube. Five horses then consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week)., Results: Bioavailability of orally administered silibinin phospholipid was 0.6% PO in feed and 2.9% via nasogastric tube. During the multidose phase, silibinin had nonlinear pharmacokinetics. Despite this, silibinin did not accumulate when given twice daily for 7 days at the evaluated doses. Dose-limiting toxicosis was not observed., Conclusions and Clinical Relevance: Silibinin phospholipid was safe, although poorly bio-available, in horses. Further study is indicated in horses with hepatic disease.

Background: A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed., Results: Of the three domains identified by factor analysis, the internal consistency was excellent for 'pain expression' and 'psychomotor change' (0.86 and 0.87) but not for 'physiological variables' (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and 'gold standard' evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0-30 points) with 96.5% sensitivity and 99.5% specificity., Conclusions: The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy.

Objective: To describe the prevalence of dysphoria after intraoperative administration of fentanyl by infusion and identify other risk factors influencing this in dogs undergoing stifle surgery., Study Design: Prospective, randomized clinical study., Animals: Dogs (n = 92) that had tibial plateau leveling osteotomy (TPLO) or tibial tuberosity advancement (TTA)., Methods: Dogs were anesthetized using a standardized anesthetic protocol, and randomly assigned to receive a loading dose followed by 1 of 3 infusions of fentanyl perioperatively: 2 μg/kg/h, 10 μg/kg/h, or 20 μg/kg/h. Dog characteristics and all additional medications were recorded and included as part of the statistical analysis. Dog behavior was scored before anesthesia and during recovery using a scale of 1-4 (Appendices A and B). If no improvement in behavior was seen in 3-5 minutes postextubation, dogs with a score of 3 or 4 during recovery were administered fentanyl (2 μg/kg intravenously [IV]) in the event that the behaviors associated with the higher scores were related to pain. If they did not respond favorably to the administration of additional fentanyl and wound palpation did not elicit a response, but the untoward behaviors continued, dogs were administered either a tranquilizer, sedative, or opioid antagonist, and were considered dysphoric., Results: Of 92 dogs, 22 (23.9%) were considered dysphoric using aforementioned criteria., Conclusions: About one-fourth of dogs enrolled in this study were dysphoric based on study criteria., (© Copyright 2012 by The American College of Veterinary Surgeons.)

The occupational external radiation dose to human medical personnel from positron emission tomography (PET) radiopharmaceuticals has been documented, but to date no corresponding veterinary staff dose data are available. Electronic personal dosimeters (EPDs) were used in this study to measure the per-patient external radiation doses to veterinary staff using a PET/CT (PET combined with computed tomography) protocol in which the patient radiopharmaceutical dose was injected after anesthetic induction. Radiation doses were recorded for the nuclear medicine technologists, the on-duty anesthesiology technologist, and an occasional observer from 19 veterinary (18) F-fluorodeoxyglucose PET/CT studies. Patient mass range was 2.8 to 61.0 kg (22.3 kg mean) and injected activity averaged 6 MBq kg(-1) . The dose range received by nuclear medicine technologists per procedure was 0-30 μSv (9.1 μSv mean), by anesthetists 1-22 μSv (8.2 μSv mean), and by the observer 0-2 μSv (0.5 μSv mean). In both feline and canine studies, placement of the EPD on staff was a significant predictor of radiation dose. Additional significant predictors of staff radiation dose from canine studies included job position and injected activity. The per-patient occupational radiation doses to veterinary PET/CT technologists were slightly greater than those reported for human nuclear medicine PET/CT technologists, but were comparable to estimated radiation doses for nurses caring for nonambulatory human PET/CT patients. Efforts toward maintaining staff radiation doses as low as reasonably achievable (ALARA) will be important as veterinary PET/CT caseload increases., (© 2012 Veterinary Radiology & Ultrasound.)