Pharmacokinetics, pharmacodynamics and antinociceptive effects of buprenorphine following transdermal administration to horses.

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.

Evaluation of the 4-point regional nerve block using 2% lidocaine in sheep.

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.

Évaluation du bloc nerveux régional en quatre points avec de la lidocaïne à 2 % chez le mouton. OBJECTIF: Déterminer si un seul bloc nerveux régional en quatre points utilisant de la lidocaïne à 2 % administrée distalement du boulet d'un mouton présentant une boiterie d'un seul membre distal entraînera une analgésie des doigts. ANIMAUX: Dix-huit brebis adultes avec une boiterie d'un seul membre provenant de la partie distale de l'articulation métacarpo/métatarsophalangienne ont été incluses dans l'étude. PROCÉDURES: La boiterie digitale a été confirmée et notée sur la base d'un examen clinique. La douleur associée aux lésions digitales a été évaluée en triple à l'aide d'un algomètre à pression pour quantifier le seuil nociceptif mécanique. La même procédure a été répétée sur le membre controlatéral en tant que témoin, et la force maximale et le temps de réponse ont été enregistrés. Un bloc nerveux régional en quatre points a été réalisé avec 8 ml de lidocaïne à 2 %. La nociception mécanique a de nouveau été appliquée en triple exemplaire aux deux membres comme décrit ci-dessus, par un chercheur en aveugle. Suite à un traitement médical approprié, la brebis a été relâchée et le score de boiterie répété.Les valeurs médianes de la pression et du temps de retrait ont été déterminées pour les membres affectés et les membres témoins, et les différences entre les mesures du bloc avant et après le bloc de lidocaïne ont été comparées à l'aide du test ANOVA de Friedman. Le test de Wilcoxon (signed-rank) a été utilisé pour comparer le score de boiterie avant et après le bloc. Le seuil de signification statistique a été fixé à α = 0,05. PRINCIPAUX RÉSULTATS: L'utilisation du bloc à quatre points a entraîné une modification de la pression requise pour déclencher le retrait (valeur F 17,7; P < 0,0001) ainsi que du temps de retrait (valeur F 20,4; P < 0,0001), pour les membres affectées par rapport au membres témoins. Les scores de boiterie ont diminué après le bloc (statistique de Signed-rank 85,5; P < 0,0001). CONCLUSION PRINCIPALE: Le bloc nerveux en quatre points a entraîné une anesthésie du membre distal chez le mouton dans ce modèle clinique.(Traduit par Dr Serge Messier).

Comparison of sedation quality and safety of detomidine and romifidine as a continuous rate infusion for standing elective laparoscopic ovariectomy in mares.

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.

Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs.

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.

EVALUATION OF TWO MEDETOMIDINE-AZAPERONE-ALFAXALONE COMBINATIONS IN CAPTIVE ROCKY MOUNTAIN ELK (CERVUS ELAPHUS NELSONI).

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.

A COMPARISON OF A SINGLE-DART VERSUS STAGED TWO-DART ANESTHESIA INDUCTION PROTOCOL IN PRZEWALSKI'S HORSES (EQUUS FERUS PRZEWALSKII).

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.

REPEATED USE OF A THIAFENTANIL-BASED ANESTHESIA PROTOCOL IN AN OKAPI (OKAPIA JOHNSTONI).

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.

COMPARISON OF ANESTHESIA OF ADULT GIRAFFE (GIRAFFA CAMELOPARDALIS) USING MEDETOMIDINE-KETAMINE WITH AND WITHOUT A POTENT OPIOID.

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.

A COMPARISON OF OPIOID-BASED PROTOCOLS FOR IMMOBILIZATION OF CAPTIVE GREVY'S ZEBRA (EQUUS GREVYI).

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.

Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α2-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. PaCO2 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 α2-adrenergic antagonist to inhalation anesthesia in dogs.

EVALUATION OF BLOOD GAS VALUES IN ANESTHETIZED SOUTHERN WHITE RHINOCEROS ( CERATOTHERIUM SIMUM) VENTILATED WITH A NOVEL DEMAND VENTILATOR IN A ZOOLOGICAL PARK SETTING.

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 (PaO2 and PaCO2), 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 PaO2 and PaCO2 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 PaO2 increased significantly ( P < 0.001) following ventilation from a median value of 58 (range, 38-67) to 123 (range, 42-184) mm Hg. The PaCO2 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.

Pain: Its Diagnosis and Management in the Rehabilitation of Horses.

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.

Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats.

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.

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine.

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.

Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats.

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.

Multicenter clinical evaluation of a multi-dose formulation of propofol in the dog.

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.

Prevalence of dysphoria after fentanyl in dogs undergoing stifle surgery.

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.

Pharmacokinetics of intravenous propofol in southern white rhinoceros (Ceratotherium simum simum) after intramuscular etorphine-butorphanol-medetomidine-azaperone.

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.

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse.

OBJECTIVE: To describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse. STUDY DESIGN: Prospective experimental trial. ANIMALS: Eight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg. METHODS: Medetomidine (10 µg kg(-1) ) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis. RESULTS: Pharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL(-1) ) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg(-1) minute(-1) and a volume of distribution of 1854 ± 565 mL kg(-1). The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL(-1) approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound. CONCLUSION AND CLINICAL RELEVANCE: Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.

Effect of epidural and intravenous use of the neurokinin-1 (NK-1) receptor antagonist maropitant on the sevoflurane minimum alveolar concentration (MAC) in dogs.

OBJECTIVE: To determine the effect of maropitant, an NK-1 receptor antagonist on the minimum alveolar concentration (MAC) of sevoflurane after intravenous and epidural administration to dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Seven, adult, spayed-female dogs (24.8 ± 1.9 kg). METHODS: Each dog was anesthetized twice with sevoflurane in oxygen, with at least 10 days separating the anesthetic events. The minimum alveolar concentration (MAC) of sevoflurane was determined using the tail-clamp technique. During the first anesthetic event, the MAC of sevoflurane was determined initially and again after intravenous administration of maropitant (5 mg kg(-1)) and an infusion (150 µg kg(-1) hour(-1)). During the second anesthetic event, an epidural catheter was advanced to the 4th lumbar vertebra and MAC was determined after administration of saline and maropitant (1 mg kg(-1)) epidurally. All MAC determinations were done in duplicate. The MAC values were adjusted to sea level and compared using student's t-test. RESULTS: The baseline MAC for sevoflurane was 2.08 ± 0.25%. Intravenous maropitant decreased (p < 0.05) MAC by 16% (1.74 ± 0.17%). In contrast, epidural administration of either saline or maropitant did not change (p > 0.05) the MAC (2.17 ± 0.34% and 1.92 ± 0.12%, respectively). CONCLUSION AND CLINICAL RELEVANCE: Maropitant decreased the MAC of sevoflurane when administered intravenously to dogs but not after epidural administration.