Evaluation of cardiovascular effects of intramuscular medetomidine and a medetomidine–vatinoxan combination in Beagle dogs: A randomized blinded crossover laboratory study

ObjectiveTo compare the cardiovascular effects of a combination of medetomidine and vatinoxan (MVX) versus medetomidine (MED) alone administered intramuscularly (IM) and to determine whether heart rate (HR) can be used as a surrogate for cardiac output (CO) after the use of medetomidine with or without vatinoxan.Study designA randomized, blinded, experimental, crossover study.AnimalsA group of eight healthy Beagle dogs aged 4.6 (2.3–9.4) years and weighing 12.9 (9–14.7) kg, median (range).MethodsEach dog was injected with 1 mg m^–2 medetomidine with or without 20 mg m^–2 vatinoxan IM with a washout period of 7 days. Cardiovascular data and arterial and mixed venous blood gas samples were collected at baseline, 5, 10, 15, 20, 35, 45, 60, 90 and 120 minutes after treatment administration. CO was measured at all time points via thermodilution. Differences between treatments, period and sequence were evaluated with repeated measures analysis of covariance and the relationship between HR and CO was assessed with a repeated measures analysis of variance; p values < 0.05 were deemed significant.ResultsThe CO was 47–96% lower after MED than after MVX (p < 0.0001). Increases in systemic, pulmonary arterial and right atrial pressures and oxygen extraction ratio were significantly higher after MED than after MVX (all p < 0.0001). HR was significantly lower after MED and the linear relationship to CO was significant (p < 0.0001).Conclusions and clinical relevanceOverall, MED affected the cardiovascular system more negatively than MVX, and the difference in cardiovascular function between the treatments can be considered clinically relevant. HR was linearly related to CO, and decreases in HR reflected cardiac performance for dogs sedated with medetomidine with or without vatinoxan.     

Comparison of anesthetic effects of tiletamine–zolazepam–medetomidine or ketamine–medetomidine in captive Amur leopard cats (Prionailurus bengalensis euptailurus)

ObjectiveTo evaluate the effects and utility of tiletamine–zolazepam–medetomidine (TZM) and ketamine–medetomidine (KM) for anesthesia of Amur leopard cats (Prionailurus bengalensis euptailurus).Study designProspective, randomized experimental trial.AnimalsA total of six female (3.70 ± 0.49 kg) and six male (5.03 ± 0.44 kg; mean ± standard deviation) Amur leopard cats aged 2–6 years.MethodsEach animal was administered four protocols separated by ≥3 weeks. Each protocol included medetomidine (0.05 mg kg^–1) combined with tiletamine–zolazepam (1 mg kg^–1; protocol MTZ_LO); tiletamine–zolazepam (2 mg kg^–1; protocol MTZ_HI); ketamine (2 mg kg^–1; protocol MK_LO); or ketamine (4 mg kg^–1; MK_HI) administered intramuscularly. At time 0 (onset of lateral recumbency) and 30 minutes, heart rate (HR), respiratory rate (f_R), rectal temperature, noninvasive mean arterial pressure (MAP) and hemoglobin oxygen saturation (SpO₂) were recorded. Times to onset of lateral recumbency, duration of anesthesia and time to standing were recorded.ResultsOverall, animals were anesthetized with all protocols within 10 minutes, anesthesia was maintained ≥57 minutes, and recovery (time from the first head lift to standing) was completed within 5 minutes. During anesthesia with all protocols, HR, f_R, rectal temperature, SpO₂ and MAP were 99–125 beats minute^–1, 33–44 breaths minute^–1, 37.6–39.4 °C, 90–95% and 152–177 mmHg, respectively. No adverse event was observed.Conclusions and clinical relevanceTZM and KM at various dosages resulted in rapid onset of anesthesia, duration of >57 minutes and rapid recovery without administration of an antagonist. Accordingly, all these combinations are useful for anesthetizing Amur leopard cats and for performing simple procedures. However, the low doses of the anesthetic agents are recommended because there was no difference in duration of anesthesia between the dose rates studied.     

Comparison of medetomidine—morphine and medetomidine—methadone for sedation,isoflurane requirement and postoperative analgesia in dogs undergoing laparoscopy

Objective

To compare the effects of intravenous (IV) medetomidine-morphine and medetomidine-methadone on preoperative sedation, isoflurane requirements and postoperative analgesia in dogs undergoing laparoscopic surgery.

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.     

Clinical evaluation of intranasal medetomidine–ketamine and medetomidine–S(+)-ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques

Objective

The aim was to compare efficacy and side effects of induction with medetomidine–ketamine or medetomidine–S(+)-ketamine by intranasal (IN) instillation in rabbits and to evaluate both protocols during subsequent isoflurane anaesthesia.

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.     

The impact of vatinoxan on medetomidine–ketamine–midazolam immobilization in Patagonian maras (Dolichotis patagonum)

ObjectiveTo compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine–ketamine–midazolam combination with or without vatinoxan (MK-467), a peripherally acting α₂-adrenoceptor antagonist.Study designRandomized, blinded, crossover study.AnimalsA group of nine healthy Patagonian maras (Dolichotis patagonum).MethodsMaras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg^–1) + ketamine (5 mg kg^–1) + midazolam (0.1 mg kg^–1) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg^–1), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO₂, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p < 0.05).ResultsVatinoxan significantly reduced systolic (p = 0.0002), mean (MAP; p < 0.0001) and diastolic (p < 0.0001) arterial blood pressures between 20 and 40 minutes. MAPs at 30 minutes (mean ± standard deviation) with MKM and MKM + vatinoxan were 105 ± 12 and 71 ± 14 mmHg, respectively. Without vatinoxan, four animals were hypertensive (MAP > 120 mmHg), whereas with vatinoxan, four animals were hypotensive (MAP < 60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols.Conclusions and clinical relevanceIn Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.     

Evaluation of butorphanol–azaperone–medetomidine (BAM) in captive blesbok immobilization (Damaliscus pygargus phillipsi)

Objective

The fixed-dose combination of butorphanol, azaperone and medetomidine (BAM; 30, 12 and 12 mg mL^?1, respectively) with subsequent antagonism by naltrexone–atipamezole was evaluated for reversible immobilization of captive blesbok (Damaliscus pygargus phillipsi).

Evaluation of BAM (butorphanol–azaperone–medetomidine) in captive African lion (Panthera leo) immobilization

Objective

The combination of butorphanol, azaperone and medetomidine (BAM) with subsequent antagonism by naltrexone–yohimbine or naltrexone–atipamezole was evaluated for reversible immobilization of captive African lions (Panthea leo).

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.     

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.     

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.

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.     

Propofol–medetomidine–ketamine total intravenous anaesthesia in thiafentanil–medetomidine-immobilized impala (Aepyceros melampus)

Objective

To characterize a propofol–medetomidine-ketamine total intravenous anaesthetic in impala (Aepyceros melampus).

Ketamine–propofol for total intravenous anaesthesia in rabbits: a comparison of premedication with acepromazine–medetomidine,acepromazine–midazolam or acepromazine–morphine

ObjectiveTo describe ketamine–propofol total intravenous anaesthesia (TIVA) following premedication with acepromazine and either medetomidine, midazolam or morphine in rabbits.Study designRandomized, crossover experimental study.AnimalsA total of six healthy female New Zealand White rabbits (2.2 ± 0.3 kg).MethodsRabbits were anaesthetized on four occasions, each separated by 7 days: an intramuscular injection of saline alone (treatment Saline) or acepromazine (0.5 mg kg^–1) in combination with medetomidine (0.1 mg kg^–1), midazolam (1 mg kg^–1) or morphine (1 mg kg^–1), treatments AME, AMI or AMO, respectively, in random order. Anaesthesia was induced and maintained with a mixture containing ketamine (5 mg mL^–1) and propofol (5 mg mL^–1) (ketofol). Each trachea was intubated and the rabbit administered oxygen during spontaneous ventilation. Ketofol infusion rate was initially 0.4 mg kg^–1 minute^–1 (0.2 mg kg^–1 minute^–1 of each drug) and was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Ketofol dose and physiological variables were recorded every 5 minutes. Quality of sedation, intubation and recovery times were recorded.ResultsKetofol induction doses decreased significantly in treatments AME (7.9 ± 2.3) and AMI (8.9 ± 4.0) compared with treatment Saline (16.8 ± 3.2 mg kg^–1) (p < 0.05). The total ketofol dose to maintain anaesthesia was significantly lower in treatments AME, AMI and AMO (0.6 ± 0.1, 0.6 ± 0.2 and 0.6 ± 0.1 mg kg^–1 minute^–1, respectively) than in treatment Saline (1.2 ± 0.2 mg kg^–1 minute^–1) (p < 0.05). Cardiovascular variables remained at clinically acceptable values, but all treatments caused some degree of hypoventilation.Conclusions and clinical relevancePremedication with AME, AMI and AMO, at the doses studied, significantly decreased the maintenance dose of ketofol infusion in rabbits. Ketofol was determined to be a clinically acceptable combination for TIVA in premedicated rabbits.     

Intratesticular and incisional line infiltration with ropivacaine for castration in medetomidine–butorphanol–midazolam sedated dogs

Objective

To evaluate whether intratesticular and incisional ropivacaine infiltration produces sufficient intra- and postoperative analgesia for castrating dogs under sedation.

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.