Comparison of sedative and some cardiopulmonary effects of intramuscular medetomidine or medetomidine–tramadol in dogs

ObjectiveTo evaluate the clinical and physiologic effects of intramuscular (IM) administration of medetomidine with and without tramadol in dogs.Study designProspective experimental study.AnimalsA group of eight mixed breed dogs of both sexes, aged 1–2 years, weighing 16.0 ± 0.6 kg.MethodsEach dog was studied twice at ≥1 week interval. Medetomidine (5 μg kg^–1; treatment M) was administered IM alone or with tramadol (4 mg kg^–1; treatment MT). Sedation was scored by a system that included vocalization, posture, appearance, interactive behaviors, resistance to restraint and response to noise. Times from drug administration to ataxia, impaired walking, head drop, sternal and lateral position and standing were recorded. Sedation score, heart rate, respiratory rate, rectal temperature, end-tidal carbon dioxide (Pe′CO₂), hemoglobin oxygen saturation and mean noninvasive blood pressure were recorded and compared 15 minutes before and 15, 30 and 45 minutes after drug administration.ResultsDogs administered MT had higher sedation scores than dogs administered M at 30 and 45 minutes after drug administration (p < 0.05). Times to ataxia, impaired walking, head drop and sternal recumbency were not different between the treatments. Time to lateral recumbency was longer in M than in MT (21.1 ± 1.0 versus 17.6 ± 0.7 minutes, respectively; p < 0.05). Time to standing was longer in MT than in M (67.9 ± 1.4 versus 54.5 ± 1.9 minutes, respectively; p < 0.001). Measured physiological variables did not differ between the treatments, with the exception of Pe′CO₂, which was higher in MT than in M at all post-treatment evaluation times (p < 0.001).Conclusions and clinical relevanceTramadol combined with medetomidine resulted in greater sedation scores (deeper sedation) than medetomidine alone in dogs, and minimal adverse changes in the physiologic variables were measured.     

Cardiovascular effects of dobutamine,norepinephrine and phenylephrine in isoflurane-anaesthetized dogs administered dexmedetomidine–vatinoxan

ObjectiveTo determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan.Study designBalanced, randomized crossover trial.AnimalsA total of eight healthy Beagle dogs.MethodsEach dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 μg kg^–1) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 μg kg^–1) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used.ResultsMost dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 μg kg^–1 minute^–1 for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute^–1 m^–2, respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute^–1 m^–2).Conclusions and clinical relevanceHypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.     

Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs

Objective

To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs.

Field immobilization using alfaxalone and alfaxalone–medetomidine in free-ranging koalas (Phascolarctos cinereus): a randomized comparative study

ObjectiveTo characterize and compare two intramuscular drug protocols using alfaxalone and alfaxalone–medetomidine combination for the field immobilization of free-ranging koalas.Study designBlinded, randomized, comparative field study.AnimalsA total of 66 free-ranging koalas from the Mount Lofty Ranges, South Australia.MethodsKoalas were randomly allocated into two groups. Group A animals were given alfaxalone alone at 3.5 mg kg^–1. Group AM animals were given alfaxalone 2 mg kg^–1 and medetomidine 40 μg kg^–1, reversed with atipamezole at 0.16 mg kg^–1. Blinded operators recorded heart rate (HR), respiratory rate (f_R), cloacal temperature, depth of sedation and times to: first effect, sedation suitable for clinical interventions, first arousal and full recovery. Data were analysed using independent t test, Mann–Whitney U test, chi-square analysis and log-rank test at 5% level of significance.ResultsSuitable immobilization for clinical examination and sample collection was achieved in all animals. In groups A and AM, median time to working depth was 6.5 minutes (range: 3.4–15) and 8.1 minutes (range: 4.3–24) and time to complete recovery was 66 minutes (range: 12–138) and 34 minutes (range: 4–84), respectively, following reversal. Time to first effect was significantly shorter in group A (p = 0.013), whereas time to full arousal was significantly shorter in group AM (p = 0.007) probably due to the administration of atipamezole. Maximum HR was 117 ± 28 beats minute^–1 in group A, which was a significant increase from baseline values (p < 0.0001), whereas group AM showed a significant tachypnoea of 67 ± 25 (normal f_R 10–15; p < 0.0001).Conclusions and clinical relevanceBoth the protocols produced immobilization, enabling clinical examination and sample collection; however, protocol AM was more suitable for field work due to shorter recovery times.     

Safety evaluation of combination vinblastine and toceranib phosphate (Palladia®) in dogs: a phase I dose-finding study

Combining drugs with known single-agent activity that lack overlapping dose-limiting toxicities (DLT) and exert antitumour activity through different mechanisms could improve clinical outcome. As toceranib and vinblastine meet these requisites, a phase I trial was performed in combination in dogs with mast cell tumours. The DLT for the simultaneous combination was neutropenia and the maximally tolerated dose was vinblastine (1.6 mg m(-2) every other week) concurrent with toceranib (3.25 mg kg(-1) PO, every other day). This represents greater than a 50% reduction in dose intensity for vinblastine (compared with single-agent use) and as such does not support this combination based on current drug combination paradigms. Although a strict adherence to dose paradigms speaks against the combination, evidence of significant activity (71% objective response) and enhanced myelosuppression suggest additive or synergistic activity. A prospective randomized evaluation comparing this combination with standard single-agent treatments would seem prudent to interrogate this potential.     

Concentrations of medetomidine enantiomers and vatinoxan,an α2-adrenoceptor antagonist,in plasma and central nervous tissue after intravenous coadministration in dogs

ObjectiveTo quantify the peripheral selectivity of vatinoxan (L-659,066, MK-467) in dogs by comparing the concentrations of vatinoxan, dexmedetomidine and levomedetomidine in plasma and central nervous system (CNS) tissue after intravenous (IV) coadministration of vatinoxan and medetomidine.Study designExperimental, observational study.AnimalsA group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 ± 0.1 years (mean ± standard deviation).MethodsAll dogs were administered a combination of medetomidine (40 μg kg⁻¹) and vatinoxan (800 μg kg⁻¹) as IV bolus. After 20 minutes, the dogs were euthanized with an IV overdose of pentobarbital (140 mg kg⁻¹) and both venous plasma and CNS tissues (brain, cervical and lumbar spinal cord) were harvested. Concentrations of dexmedetomidine, levomedetomidine and vatinoxan in all samples were quantified by liquid chromatography–tandem mass spectrometry and data were analyzed with nonparametric tests with post hoc corrections where appropriate.ResultsAll dogs became deeply sedated after the treatment. The CNS-to-plasma ratio of vatinoxan concentration was approximately 1:50, whereas the concentrations of dexmedetomidine and levomedetomidine in the CNS were three- to seven-fold of those in plasma.Conclusions and clinical relevanceWith the doses studied, these results confirm the peripheral selectivity of vatinoxan in dogs, when coadministered IV with medetomidine. Thus, it is likely that vatinoxan preferentially antagonizes α₂-adrenoceptors outside the CNS.     

Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine–tiletamine–zolazepam anaesthetised red deer (Cervus elaphus)

ObjectiveTo determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine–tiletamine–zolazepam in red deer (Cervus elaphus).Study design and animalsA total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study.MethodsDeer were administered a combination of 0.1 mg kg^–1 medetomidine hydrochloride and 2.5 mg kg^–1 tiletamine–zolazepam intramuscularly, followed by 0.1 mg kg^–1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (f_R), end-tidal CO₂ (Pe′CO₂), arterial oxygen saturation (SpO₂), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p < 0.05).ResultsMaximal (81 ± 10 beats minute^–1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute^–1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute^–1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. Pe′CO₂, f_R and SpO₂ showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan.Conclusions and clinical relevanceVatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine–tiletamine–zolazepam.     

Evaluation of LHP? (1% hydrogen peroxide) cream versus petrolatum and untreated controls in open wounds in healthy horses: a randomized,blinded control study

Background

Treatment and protection of wounds in horses can be challenging; protecting bandages may be difficult to apply on the proximal extremities and the body. Unprotected wounds carry an increased risk of bacterial contamination and subsequent infection which can lead to delayed wound healing. Topical treatment with antimicrobials is one possibility to prevent bacterial colonization or infection, but the frequent use of antimicrobials ultimately leads to development of bacterial resistance which is an increasing concern in both human and veterinary medicine.

Methods

Standardized wounds were created in 10 Standardbred mares. Three wounds were made in each horse. Two wounds were randomly treated with LHP^® or petrolatum and the third wound served as untreated control. All wounds were assessed daily until complete epithelization. Protocol data were recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for inflammation and healing, photoplanimetry for calculating wound areas and swab cytology to assess bacterial colonization and inflammation. Bacterial cultures were obtained on day 2, 6 and 16.

Results

Mean time to complete healing for LHP^® treated wounds was 32 days (95%CI = 26.9-37.7). Mean time to complete healing for petrolatum and untreated control wounds were 41.6 days (95%CI = 36.2-47.0) and 44.0 days (95%CI = 38.6-49.4) respectively. Wound healing occurred significantly faster in LHP^® wounds compared to both petrolatum (p = 0.0004) and untreated controls (p < 0.0001). There was no significant difference in time for healing between petrolatum and untreated controls. Total scores for bacteria and neutrophils were significantly (p < 0.0001) lower for LHP^® treated wounds compared to petrolatum from day 16 and onwards. Staphylococcus aureus and Streptococcus zooepidemicus were only found in cultures from petrolatum treated wounds and untreated controls.

Conclusions

Treatment with LHP^® reduced bacterial colonization and was associated with earlier complete wound healing. LHP^® cream appears to be safe and effective for topical wound treatment or wound protection.     

Comparison of the effects of butorphanol–midazolam–medetomidine and butorphanol–azaperone–medetomidine in wild common palm civets (Paradoxurus musangus)

ObjectiveTo assess the efficacy of butorphanol–azaperone–medetomidine (BAM) and butorphanol–midazolam–medetomidine (BMM) protocols for immobilization of wild common palm civets (Paradoxurus musangus) with subsequent antagonization with atipamezole.Study designProspective, randomized, blinded clinical trial.AnimalsA total of 40 adult wild common palm civets, 24 female and 16 male, weighing 1.5–3.4 kg.MethodsThe civets were randomly assigned for anesthesia with butorphanol, azaperone and medetomidine (0.6, 0.6 and 0.2 mg kg^–1, respectively; group BAM) or with butorphanol, midazolam and medetomidine (0.3, 0.4 and 0.1 mg kg^–1, respectively; group BMM) intramuscularly (IM) in a squeeze cage. When adequately relaxed, the trachea was intubated for oxygen administration. Physiological variables were recorded every 5 minutes after intubation. Following morphometric measurements, sampling, microchipping and parasite treatment, medetomidine was reversed with atipamezole at 1.0 or 0.5 mg kg^–1 IM to groups BAM and BMM, respectively. Physiological variables and times to reach the different stages of anesthesia were compared between groups.ResultsOnset time of sedation and recumbency was similar in both groups; time to achieve complete relaxation and tracheal intubation was longer in group BAM. Supplementation with isoflurane was required to enable intubation in five civets in group BAM and one civet in group BMM. All civets in group BAM required topical lidocaine to facilitate intubation. End-tidal carbon dioxide partial pressure was lower in group BAM, but heart rate, respiratory rate, rectal temperature, peripheral hemoglobin oxygen saturation and mean arterial blood pressure were not different. All civets in both groups recovered well following administration of atipamezole.Conclusions and clinical relevanceBoth BAM and BMM combinations were effective for immobilizing wild common palm civets. The BMM combination had the advantage of producing complete relaxation that allowed intubation more rapidly.     

Anesthetic effects of ketamine–medetomidine–hydromorphone in dogs during high-quality,high-volume surgical sterilization program under field conditions

ObjectiveTo describe the anesthetic and adverse effects of an injectable anesthetic protocol in dogs as part of a high-volume sterilization program under field conditions in Belize.Study designProspective, observational, field study.AnimalsA total of 23 female and eight male dogs (14.2 ± 7.7 kg; age ≥ 8 weeks).MethodsUsing a volume per kg-based dose chart, dogs were administered ketamine (4.5 mg kg⁻¹), medetomidine (0.04 mg kg⁻¹) and hydromorphone (0.09 mg kg⁻¹) intramuscularly. After induction of anesthesia, an endotracheal tube was inserted and dogs were allowed spontaneous breathing in room air. Monitoring included peripheral oxygen saturation (SpO₂), mean arterial pressure (MAP), heart rate (HR), respiratory rate, rectal temperature and end-tidal carbon dioxide (Pe′CO₂). Meloxicam (0.2 mg kg⁻¹) was administered subcutaneously after surgery. Data were analyzed with linear models and chi-square tests (p < 0.05).ResultsOnset of lateral recumbency (3.4 ± 2 minutes) was rapid. Desaturation (SpO₂ < 90%) was observed at least once in 64.5% of dogs and was more frequent in large dogs (p = 0.019). Hypercapnia (Pe′CO₂ ≥ 50 mmHg; 6.7 kPa) was observed in 48.4% of dogs. MAP was 111 ± 19 mmHg, mean ± standard deviation. Hypertension (MAP ≥ 120 mmHg), bradycardia (HR ≤ 60 beats minute⁻¹) and tachycardia (HR ≥ 140 beats minute⁻¹) were observed in 45.2%, 16.1% and 3.3% of dogs, respectively. Hypotension and hypothermia were not observed. Sex was not significantly associated with any complication. Return of swallowing reflex and time to standing were 71 ± 23 and 152 ± 50 minutes after injection, respectively. Return of swallowing was significantly longer in large dogs.Conclusions and clinical relevanceAt the doses used, ketamine–medetomidine–hydromorphone was effective in dogs for high-volume sterilization. In this field setting, adverse effects included hypoventilation, hypoxemia and prolonged recovery.     

Immobilization,cardiopulmonary and blood gas effects of ketamine–butorphanol–medetomidine versus butorphanol–midazolam–medetomidine in free-ranging serval (Leptailurus serval)

ObjectiveTo compare ketamine–butorphanol–medetomidine (KBM) with butorphanol–midazolam–medetomidine (BMM) immobilization of serval.Study designBlinded, randomized trial.AnimalsA total of 23 captures [KBM: five females, six males; 10.7 kg (mean); BMM: 10 females, two males; 9.6 kg].MethodsServal were cage trapped and immobilized using the assigned drug combination delivered via a blow dart into gluteal muscles. Prior to darting, a stress score was assigned (0: calm; to 3: markedly stressed). Drug combinations were dosed based on estimated body weights: 8.0, 0.4 and 0.08 mg kg^–1 for KBM and 0.4, 0.3 and 0.08 mg kg^–1 for BMM, respectively. Time to first handling, duration of anaesthesia and recovery times were recorded. Physiological variables including blood glucose and body temperature were recorded at 5 minute intervals. Atipamezole (5 mg mg^–1 medetomidine) and naltrexone (2 mg mg^–1 butorphanol) were administered intramuscularly prior to recovery. Data, presented as mean values, were analysed using general linear mixed model and Spearman’s correlation (stress score, glucose, temperature); significance was p < 0.05.ResultsDoses based on actual body weights were 8.7, 0.4 and 0.09 mg kg^–1 for KBM and 0.5, 0.4 and 0.09 mg kg^–1 for BMM, respectively. Time to first handling was 10.2 and 13.3 minutes for KBM and BMM, respectively (p = 0.033). Both combinations provided cardiovascular stability during anaesthesia that lasted a minimum of 35 minutes. Recovery was rapid and calm overall, but ataxia was noted in KBM. Stress score was strongly correlated to blood glucose (r² = 0.788; p = 0.001) and temperature (r² = 0.634; p = 0.015).Conclusions and clinical relevanceBoth combinations produced similar effective immobilization that was cardiovascularly stable in serval. Overall, BMM is recommended because it is fully antagonizable. A calm, quiet environment before drug administration is essential to avoid capture-induced hyperglycaemia and hyperthermia.     

Scrotal tumors in dogs: A retrospective study of 676 cases (1986–2010)

The objective of this study was to determine common tumor types that occur on the canine scrotum in relation to other cutaneous locations and to identify potential risk factors for specific scrotal tumor development. A retrospective study was conducted and the database of pathology reports from the Surgical Pathology Service of the Department of Pathology and Toxicology, School of Veterinary Medicine, University of Pennsylvania from 1986 to 2010 was searched for canine neoplastic scrotal and non-scrotal cutaneous lesions. Neoplastic lesions were evaluated based on diagnosis, breed, age, and number and location of tumors (scrotal versus non-scrotal cutaneous). Mast cell tumor, melanocytoma, malignant melanoma, vascular hamartoma, hemangiosarcoma, hemangioma, and cutaneous histiocytoma were the most common tumor types identified on the canine scrotum. Breed predispositions and mean age at diagnosis were identified for each tumor type and should be considered when planning surgical excision of a canine scrotal tumor.     

Comparison of three continuous positive airway pressure (CPAP) interfaces in healthy Beagle dogs during medetomidine–propofol constant rate infusions

Objective

To compare the efficacy of three continuous positive airway pressure (CPAP) interfaces in dogs on gas exchange, lung volumes, amount of leak during CPAP and rebreathing in case of equipment failure or disconnection.

Comparison between three dosages of intramuscular alfaxalone and a ketamine–dexmedetomidine–midazolam–tramadol combination in golden-headed lion tamarins (Leontopithecus chrysomelas)

ObjectivesTo characterize the cardiopulmonary and anesthetic effects of alfaxalone at three dose rates in comparison with a ketamine–dexmedetomidine–midazolam–tramadol combination (KDMT) for immobilization of golden-headed lion tamarins (GHLTs) (Leontopithecus chrysomelas) undergoing vasectomy.Study designProspective clinical trial.AnimalsA total of 19 healthy, male, wild-caught GHLTs.MethodsTamarins were administered alfaxalone intramuscularly (IM) at 6, 12 or 15 mg kg^–1, or KDMT, ketamine (15 mg kg^–1), dexmedetomidine (0.015 mg kg^–1), midazolam (0.5 mg kg^–1) and tramadol (4 mg kg^–1) IM. Immediately after immobilization, lidocaine (8 mg kg^–1) was infiltrated subcutaneously (SC) at the incision site in all animals. Physiologic variables, anesthetic depth and quality of immobilization were assessed. At the end of the procedure, atipamezole (0.15 mg kg^–1) was administered IM to group KDMT and tramadol (4 mg kg^–1) SC to the other groups; all animals were injected with ketoprofen (2 mg kg^–1) SC.ResultsA dose-dependent increase in sedation, muscle relaxation and immobilization time was noted in the alfaxalone groups. Despite the administration of atipamezole, the recovery time was longer for KDMT than all other groups. Muscle tremors were noted in some animals during induction and recovery with alfaxalone. No significant differences were observed for cardiovascular variables among the alfaxalone groups, whereas an initial decrease in heart rate and systolic arterial blood pressure was recorded in KDMT, which increased after atipamezole administration.Conclusions and clinical relevanceAlfaxalone dose rates of 12 or 15 mg kg^–1 IM with local anesthesia provided good sedation and subjectively adequate pain control for vasectomies in GHLTs. KDMT induced a deeper plane of anesthesia and should be considered for more invasive or painful procedures. All study groups experienced mild to moderate hypothermia and hypoxemia; therefore, the use of more efficient heating devices and oxygen supplementation is strongly recommended when using these protocols.     

Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.     

Replicate effects and test–retest reliability of quantitative sensory threshold testing in dogs with and without chronic pain

Objective

To evaluate replicate effects and test–retest reliability of mechanical and thermal quantitative sensory testing (QST) in normal dogs and dogs with osteoarthritis (OA)-associated pain.

Cardiorespiratory effects of a 7° reverse Trendelenburg position in anaesthetized horses: a randomized clinical trial

Objective

To evaluate the cardiorespiratory effects of a 7° reverse Trendelenburg position (RTP) in anaesthetized horses.