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.     

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.

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.     

The effects of repeated intravenous iohexol administration on renal function in healthy beagles – a preliminary report

Background

Contrast induced nephrotoxicity (CIN) is a well described syndrome in humans undergoing contrast medium examinations. To date CIN has received minimal attention in the veterinary literature despite increasing use of contrast medium examinations in computed tomographic studies.

Methods

This prospective study evaluated the effect of 1290 mg/kg iohexol given intravenously to 5 normal beagle dogs in a divided dose at an interval of 6–8 weeks. Renal function was evaluated by means of scintigraphically determined glomerular filtration rate (GFR) and a variety of laboratory assays.

Results

Only GFR showed a significant decrease (17%) after the second injection but not to a clinically or pathologically significant level.

Conclusions

No clinically significant effect of repeated contrast medium administration was determined in this limited study. However in dogs with reduced renal function the risk of CIN is likely to increase dramatically post contrast administration.     

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.     

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).

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.

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.     

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.     

Pharmacokinetic study of rhizoma Curcumae oil and rhizoma Curcumae oil-β-cyclodextrin inclusion complex in pigs after oral administration

Pharmacokinetics of rhizoma Curcumae oil-pure drug (RCO-PD) and its β-cyclodextrin inclusion complex (RCO-βCD) were studied in a randomized two-way crossover design following a single oral administration of the two formulations. Germacrone concentrations in plasma were determined by high-performance liquid chromatography with UV detector. The concentrations vs. time data were analyzed by a noncompartmental pharmacokinetic method. The result showed that germacrone in both groups was rapidly absorbed followed by a slow elimination. The main parameters in RCO-PD group were as follows: t(1/2λz) 6.63±1.08 h, C(max) 2.50±0.34 μg/mL, MRT 7.19±0.93 h, and AUC(0-∞) 13.92±2.75 mg/L·h, while in RCO-βCD group, t(1/2λz) 6.77 ± 0.67 h, C(max) 2.98±0.24 μg/mL, MRT 8.87±0.76 h, and AUC(0-∞) 21.60 ± 1.95 mg/L·h, respectively. The above results indicated that C(max), T(max), AUC(0-t), AUC(0-∞), and MRT in RCO-βCD group were significantly different from RCO-PD group, and the relative bioavailability of RCO-βCD group is significantly higher while compared to RCO-PD group (F=156%, with its 90% confidence interval of 145-169%).