Evaluation of the thermal antinociceptive effects of subcutaneous administration of butorphanol tartrate or butorphanol tartrate in a sustained-release poloxamer 407 gel formulation to orange-winged Amazon parrots (Amazona amazonica).

OBJECTIVE: To determine the thermal antinociceptive effects of butorphanol tartrate and butorphanol tartrate in a sustained-release 25% poloxamer 407 (P407) gel formulation (But-P407) in parrots. ANIMALS: 13 orange-winged Amazon parrots (Amazona amazonica). PROCEDURES: First, butorphanol tartrate (5 mg/kg) or saline (0.9% NaCl) solution was administered IM to birds in a randomized complete crossover design. The temperature prompting a foot withdrawal response to a thermal stimulus (ie, the thermal threshold) was determined 30 minutes before (baseline) and at various points after treatment administration. Second, But-P407 (12.5 mg/kg) or P407 was administered SC in a similar crossover design. Thermal threshold was determined before and at various points after treatment administration. Third, But-P407 (12.5 mg/kg) or saline solution was administered SC and evaluated as in the second trial. Sedation was scored immediately before each time point in all 3 trials. RESULTS: In the first trial, a significant increase in thermal threshold was noted 30 minutes after butorphanol tartrate (vs saline solution) administration. No sedation was noted. In the second and third trials, no significant difference was identified between results for But-P407 and those for either control treatment (saline solution or P407). Mild sedation was noted in the second trial following But-P407 administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested a small but significant thermal antinociceptive effect of butorphanol tartrate lasting between 30 minutes and 1.5 hours in orange-winged Amazon parrots. No antinociceptive effect of butorphanol tartrate was demonstrated when delivered in P407. Further research is needed to evaluate the potential analgesic effects of But-P407.

Evaluation of a welfare assessment tool to examine practices for preventing, recognizing, and managing pain at companion-animal veterinary clinics.

Successful prevention, recognition, and treatment of pain are integral to ensuring veterinary patient welfare. A canine and feline welfare assessment tool, incorporating verbal interviews with veterinarians using open-ended questions, was developed to assess pain management practices that safeguard and improve patient welfare. The tool was evaluated in 30 companion- and mixed-animal veterinary clinics in Ontario in order to assess its reliability, feasibility, and validity, while also benchmarking current practices. Responses were analyzed according to a scoring scheme developed based on published literature and expert opinion. Based on weighted kappa statistics, interview scoring had substantial inter-observer (Kw = 0.83, 0.73) and near-perfect intra-observer (Kw = 0.92) agreement, which suggests that the tool reliably collects information about pain management practices. Interviews were completed at all recruited clinics, which indicates high feasibility for the methods. Validity could not be assessed, as participants were reluctant to share information about analgesic administration from their clinical records. Descriptive results indicated areas for which many veterinarians are acting in accordance with best practices for pain management, such as pre-emptive and post-surgical analgesia for ovariohysterectomy patients, and post-surgical care instructions. Areas that offer opportunity for enhancement were also highlighted, e.g., training veterinary staff to recognize signs of pain and duration of analgesia in ovariohysterectomy patients after discharge. Overall, based on this limited sample, most veterinarians appear to be effectively managing their patients' pain, although areas with opportunity for enhancement were also identified. Further research is needed to assess trends in a broader sample of participants.

Être en mesure de prévenir, reconnaitre, et traiter la douleur avec succès est essentiel pour assurer le bien-être des patients vétérinaires. Un outil d'évaluation du bien-être des chiens et des chats, incorporant une entrevue orale avec des vétérinaires avec des questions ouvertes, a été développé pour évaluer les pratiques de gestion de la douleur qui sauvegarde et améliore le bien-être des patients. L'outil a été évalué dans 30 cliniques vétérinaires pour animaux de compagnie et cliniques mixtes en Ontario afin de vérifier la fiabilité, la faisabilité, et la validité, tout en réalisant un étalonnage des pratiques actuelles. Les réponses ont été analysées selon un schéma de pointage basé sur la littérature publiée et l'opinion d'expert. Sur la base des statistiques kappa pondérées, les pointages des entrevues avaient un accord inter-observateur marqué (Kw = 0,83, 0,73) et un accord intra-observateur presque parfait (Kw = 0,92), ce qui suggère que l'outil a permis d'obtenir des informations fiables sur les pratiques de gestion de la douleur. Les entrevues ont été complétées dans toutes les cliniques recrutées, ce qui indiquait une excellente faisabilité pour les méthodes utilisées. La validité n'a pu être vérifiée car les participants étaient réfractaires à partager de l'information sur l'administration d'analgésique à partir de leurs dossiers médicaux. Les résultats indiquent que plusieurs vétérinaires agissent en concordance avec les bonnes pratiques de gestion de la douleur pour l'analgésie préventive et post-chirurgicale des patients subissant une ovariohystérectomie et les instructions pour les soins post-chirurgie. D'autres domaines ont été identifiés comme nécessitant des améliorations, e.g. former le personnel de la clinique à reconnaitre les signes de douleurs et la durée de l'analgésie chez les patients ayant eu une ovariohystérectomie après leur congé. De manière générale, sur la base de cet échantillonnage limité, la plupart des vétérinaires semble gérer la douleur de leurs patients de manière efficace, bien que des améliorations à faire aient été identifiées. De la recherche supplémentaire est requise pour évaluer les tendances dans un échantillonnage plus grand de participants.(Traduit par Docteur Serge Messier).

Induction dose and recovery quality of propofol and alfaxalone with or without midazolam coinduction followed by total intravenous anesthesia in dogs.

OBJECTIVES: To compare propofol and alfaxalone, with or without midazolam, for induction of anesthesia in fentanyl-sedated dogs, and to assess recovery from total intravenous anesthesia (TIVA). STUDY DESIGN: Prospective, incomplete, Latin-square study. ANIMALS: Ten dogs weighing 24.5 ± 3.1 kg (mean ± standard deviation). METHODS: Dogs were randomly assigned to four treatments: treatment P-M, propofol (1 mg kg-1) and midazolam (0.3 mg kg-1); treatment P-S, propofol and saline; treatment A-M, alfaxalone (0.5 mg kg-1) and midazolam; treatment A-S, alfaxalone and saline, administered intravenously (IV) 10 minutes after fentanyl (7 µg kg-1) IV. Additional propofol or alfaxalone were administered as necessary for endotracheal intubation. TIVA was maintained for 35-55 minutes by infusions of propofol or alfaxalone. Scores were assigned for quality of sedation, induction, extubation and recovery. The drug doses required for intubation and TIVA, times from sedation to end of TIVA, end anesthesia to extubation and to standing were recorded. Analysis included a general linear mixed model with post hoc analysis (p < 0.05). RESULTS: Significant differences were detected in the quality of induction, better in A-M than A-S and P-S, and in P-M than P-S; in total intubation dose, lower in P-M (1.5 mg kg-1) than P-S (2.1 mg kg-1), and A-M (0.62 mg kg-1) than A-S (0.98 mg kg-1); and lower TIVA rate in P-M (268 µg kg-1 minute-1) than P-S (310 µg kg-1 minute-1). TIVA rate was similar in A-M and A-S (83 and 87 µg kg-1 minute-1, respectively). Time to standing was longer after alfaxalone than propofol, but was not influenced by midazolam. CONCLUSIONS AND CLINICAL RELEVANCE: Addition of midazolam reduced the induction doses of propofol and alfaxalone and improved the quality of induction in fentanyl-sedated dogs. The dose rate of propofol for TIVA was decreased.

Antihistaminic and cardiorespiratory effects of diphenhydramine hydrochloride in anesthetized dogs undergoing excision of mast cell tumors.

OBJECTIVE To evaluate the effects of IV diphenhydramine hydrochloride administration on cardiorespiratory variables in anesthetized dogs undergoing mast cell tumor (MCT) excision. DESIGN Randomized, blinded clinical trial. ANIMALS 16 client-owned dogs with MCTs. PROCEDURES In a standardized isoflurane anesthesia session that included mechanical ventilation, dogs received diphenhydramine hydrochloride (1 mg/kg [0.45 mg/lb], IV; n = 8) or an equivalent volume of saline (0.9% NaCl) solution (IV; control treatment; 8) 10 minutes after induction. Cardiorespiratory variables were recorded throughout anesthesia and MCT excision, and blood samples for determination of plasma diphenhydramine and histamine concentrations were collected prior to premedication (baseline), throughout anesthesia, and 2 hours after extubation. RESULTS Cardiorespiratory values in both treatment groups were acceptable for anesthetized dogs. Mean ± SD diastolic arterial blood pressure was significantly lower in the diphenhydramine versus control group during tumor dissection (52 ± 10 mm Hg vs 62 ± 9 mm Hg) and surgical closure (51 ± 10 mm Hg vs 65 ± 9 mm Hg). Mean arterial blood pressure was significantly lower in the diphenhydramine versus control group during surgical closure (65 ± 12 mm Hg vs 78 ± 11 mm Hg), despite a higher cardiac index value. Plasma histamine concentrations were nonsignificantly higher than baseline during maximal manipulation of the tumor and surgical preparation in the diphenhydramine group and during surgical dissection in the control group. CONCLUSIONS AND CLINICAL RELEVANCE IV administration of diphenhydramine prior to MCT excision had no clear clinical cardiorespiratory benefits over placebo in isoflurane-anesthetized dogs.

In vitro characterization of a formulation of butorphanol tartrate in a poloxamer 407 base intended for use as a parenterally administered slow-release analgesic agent.

OBJECTIVE To assess rheological properties and in vitro diffusion of poloxamer 407 (P407) and butorphanol-P407 (But-P407) hydrogels and to develop a sustained-release opioid formulation for use in birds. SAMPLE P407 powder and a commercially available injectable butorphanol tartrate formulation (10 mg/mL). PROCEDURES P407 and But-P407 gels were compounded by adding water or butorphanol to P407 powder. Effects of various concentrations of P407 (20%, 25% and 30% [{weight of P407/weight of diluent} × 100]), addition of butorphanol, and sterilization through a microfilter on rheological properties of P407 were measured by use of a rheometer. In vitro diffusion of butorphanol from But-P407 25% through a biological membrane was compared with that of a butorphanol solution. RESULTS P407 20% and 25% formulations were easily compounded, whereas it was difficult to obtain a homogenous P407 30% formulation. The P407 was a gel at avian body temperature, although its viscosity was lower than that at mammalian body temperature. The But-P407 25% formulation (butorphanol concentration, 8.3 mg/mL) was used for subsequent experiments. Addition of butorphanol to P407 as well as microfiltration did not significantly affect viscosity. Butorphanol diffused in vitro from But-P407, and its diffusion was slower than that from a butorphanol solution. CONCLUSIONS AND CLINICAL RELEVANCE But-P407 25% had in vitro characteristics that would make it a good candidate for use as a sustained-release analgesic medication. Further studies are needed to characterize the pharmacokinetic and pharmacodynamic properties of But-P407 25% in vivo before it can be recommended for use in birds.

Pharmacokinetics of butorphanol tartrate in a long-acting poloxamer 407 gel formulation administered to Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE To determine pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after SC administration to Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS 11 adult Hispaniolan Amazon parrots (6 males and 5 females; 11 to 27 years old). PROCEDURES A sterile formulation of butorphanol in P407 (But-P407) 25% (percentage determined as [weight of P407/weight of diluent] × 100]) was created (8.3 mg/mL). Five preliminary experiments (2 birds/experiment) were performed to determine the ideal dose for this species. The formulation then was administered (12.5 mg/kg, SC) to 8 birds. Blood samples were collected before (time 0) and 0.08, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Some birds were used more than once, with a washout period of ≥ 3 months between subsequent treatments. Butorphanol concentrations were quantitated by use of liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed by use of noncompartmental analysis. RESULTS Maximal plasma butorphanol concentration was reached at 1.31 hours. Plasma concentrations of butorphanol remained > 100 ng/mL for > 3 hours (all birds) or > 4 hours (5/8 birds) but < 8 hours (all birds). Half-life of the terminal slope was 3.41 hours. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE Butorphanol was absorbed well from the But-P407 25% by Hispaniolan Amazon parrots, and absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would theoretically provide analgesia for 4 to 8 hours. No adverse effects were detected. Studies on the pharmacodynamics of this formulation are necessary to confirm the degree and duration of analgesia.