An analysis of oxidative stress indices and clinical parameters in budgerigars (Melopsittacus undulatus) treated with medetomidine-ketamine and midazolam-ketamine.

Various companion birds, including budgerigars, are anesthetized with injectable anesthesia. The current study aimed to evaluate oxidative stress indices including malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) along with clinical parameters such as the time required to induce, maintain and recover from medetomidine-ketamine anesthesia and midazolam-ketamine anesthesia in budgerigars. Among 20 mature and healthy budgerigars, three groups were assigned as follows: Control (n = 4) to determine baseline oxidative stress indices medetomidine + ketamine (n = 8) anesthetized by intramuscular injections of medetomidine (0.04 mg kg-1) and ketamine (30.00 mg kg-1) in the pectoral muscles, midazolam + ketamine (n = 8) anesthetized by intramuscular injections of midazolam (1.00 mg kg-1) and ketamine (50.00 mg kg-1). Half of birds (n = 4) in the second and third groups were euthanized by cervical dislocation 1 hr after anesthesia induction, blood samples were collected directly from the heart, and sera were extracted. Additionally, the remaining birds were euthanized 24 hr later, and their serum was analyzed for oxidative stress indices. Clinical parameters were recorded during the study. Compared to the medetomidine + ketamine group, the midazolam + ketamine group experienced shorter induction, anesthetic, and recovery times. Administering medetomidine and ketamine elevated TOS levels compared with midazolam + ketamine. No significant difference was found between the test groups for TAC, MDA, or OSI. Therefore, the midazolam + ketamine regimen appears superior to medetomidine + ketamine when performing minor surgeries on budgerigars.

Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl.

BACKGROUND: Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. RESULTS: Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1-41.6), range (median) versus 0.9 (0-8.0) mL /kg/min] were significantly higher without vatinoxan. CONCLUSIONS: Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.

Cardiorespiratory effects of intramuscular alfaxalone combined with low-dose medetomidine and butorphanol in dogs anesthetized with sevoflurane.

Background: The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied. Aim: To assess the cardiorespiratory function following the IM co-administration of 5 µg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane. Methods: Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A p < 0.05 was considered statistically significant. Results: The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m2 : p < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm5/m2 : p = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide. Conclusion: The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended.

Effects of alfaxalone, medetomidine, and xylazine on intraocular pressure in domestic pigeons (Columba livia domestica).

OBJECTIVE: To evaluate the effects of alfaxalone, medetomidine, and xylazine on intraocular pressure (IOP) in domestic pigeons (Columba livia domestica). ANIMALS STUDIED: Eight 12-month-old pigeons (16 eyes). PROCEDURES: The pigeons were randomly assigned to three treatment groups (10 mg/kg of alfaxalone, 0.2 mg/kg of medetomidine, or 10 mg/kg of xylazine) with a 7-day washout period. The IOP was measured using a rebound tonometer and calibrated using the formula y = 0.439x + 2.059, where y is the tonometric IOP and x is the actual IOP. RESULTS: All three drugs significantly reduced IOP. Alfaxalone led to the least reduction at 5.2 mm Hg, medetomidine reduced IOP to 12.5 mm Hg, whereas xylazine resulted in the greatest reduction at 15.3 mm Hg. Alfaxalone achieved its maximum IOP reduction in 6 min, whereas medetomidine and xylazine required 95 and 115 min, respectively. Both alpha-2 agonists, medetomidine, and xylazine, showed a prolonged duration of effect and a greater reduction in IOP than those of alfaxalone. All three medications provided adequate sedation without any discernible adverse effects. CONCLUSIONS: The findings revealed the varied effects of these drugs on IOP in pigeons, potentially providing valuable insights that could be useful for broader applications in veterinary medicine.

Effect of Butorphanol-Medetomidine and Butorphanol-Dexmedetomidine on Echocardiographic Parameters during Propofol Anaesthesia in Dogs.

This study compared the effects of butorphanol-medetomidine and butorphanol-dexmedetomidine combinations on echocardiographic parameters during propofol anaesthesia in dogs. The dogs were randomly divided into two groups. In the butorphanol-medetomidine (BM) group, butorphanol (0.2 mg/kg) and medetomidine (15 µg/kg) were intravenously administered; in the butorphanol-dexmedetomidine (BD) group, butorphanol (0.2 mg/kg) and dexmedetomidine (7.5 µg/kg) was used. Anaesthesia was induced with propofol and maintained with a constant-rate infusion of propofol (0.2 mg/kg/min). The echocardiographic parameters were assessed in conscious dogs (T0). Echocardiography was conducted again at 10 min post premedication (T1), followed by assessments at 30 (T2), 60 (T3), and 90 (T4) mins. The dogs were subjected to diagnostic procedures (radiography, computed tomography) under anaesthesia. A significant reduction in heart rate and cardiac output was noted in both groups at T1. There was no significant difference in the stroke volume between the BM and BD groups. The application of butorphanol-dexmedetomidine caused a significant increase in the left ventricular internal diameter in diastole and the diameter of the left atrium compared to that caused by butorphanol-medetomidine. This study documented that butorphanol-medetomidine and butorphanol-dexmedetomidine combinations caused similar reductions in heart rate and cardiac output in both groups. 'New´ valvular regurgitation occurred following their administration.

Effects of ketamine, propofol and isoflurane on electrocardiographic variables in clinically healthy dogs premedicated with medetomidine and midazolam.

The purpose of this study was to investigate the effects of three anesthetic agents, with premedication of medetomidine and midazolam, on electrocardiographic variables in dogs. Ten adult mixed breed dogs were used in a crossover design study, where they received ketamine, propofol and isoflurane treatments with a one-week washout period between them. In all three groups, medetomidine was administered first followed by midazolam after 15 min. Then, after 20 min, group 1 received ketamine intravenously (IV), group 2 received propofol (IV), and group 3 received isoflurane (inhalation). In all dogs, electrocardiographs were taken before and after premedication's, as well as every 15 min during anesthesia. Medetomidine significantly decreased heart rate and P wave amplitude and increased PR interval, R wave amplitude, QT interval, and T wave amplitude. Midazolam increased the amplitude of the R and T waves. Ketamine increased the heart rate and PR interval. Propofol increased the heart rate for up to 15 min, decreased the PR interval for up to 30 min, and the QT interval for up to 45 min. Isoflurane increased the heart rate and decreased the amplitude of R and T waves. The results showed that the drugs used in this study did not have many side effects on electrocardiographic variables and could be used without serious concern. The most important side effects observed were a severe reduction in heart rate and 1st degree atrioventricular (AV) block and, to a lesser extent, 2nd degree AV block caused by medetomidine and midazolam which were masked by the anesthetics.

Comparison between dexmedetomidine and a combination of medetomidine-vatinoxan on muscle tissue saturation in privately-owned adult dogs undergoing intradermal testing.

This double-blinded randomized cross-over study compared the muscle tissue oxygen saturation (StO2) measured at the sartorius muscle after intramuscular (IM) injection of dexmedetomidine hydrochloride (HCl) and co-administration of vatinoxan HCl, a peripheral α2-adrenoceptor antagonist, and medetomidine HCl in healthy privately-owned dogs undergoing intradermal testing (IDAT). After written owner consent, dogs received IM injections of either dexmedetomidine (0.5 mg/m2, DEX) or medetomidine (1 mg/m2) and vatinoxan (20 mg/m2) (MVX). Once sedated, intradermal injections were given on the lateral thorax of each dog, and the study was repeated with the alternative sedation on the opposite side one week later. At the end of the study, sedation was reversed with atipamezole (5 mg/m2). Depth of sedation, cardiopulmonary parameters, StO2, and rectal temperature were recorded and compared using mixed effect linear models (α ≤ 0.05). MVX achieved adequate sedation faster [median (interquartile range), 10 (8, 10) minutes] compared to DEX [18 (15, 22) minutes; hazard ratio = 7.44, p = 0.013), with higher scores at 10- and 15-min post-injection. StO2 was significantly reduced for 30 min after injection (p < 0.001), independently of the treatment (p = 0.68). Cardiopulmonary variables favored MVX. However, higher heart rate did not correlate with improved StO2. There was no difference in either subjective or objective assessment of the wheal size between sedations (p > 0.05). Both sedation protocols, MVX and DEX, were deemed suitable for IDAT in dogs, with mild reductions in StO2 measured at the sartorius muscle that were not significantly different between treatments.

Effect of fentanyl constant-rate infusions with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement in dogs.

Propofol is a potential injectable anesthetic agent used in total intravenous anesthesia. However, the sparing effect of fentanyl and medetomidine on the required propofol dose in dogs remains unclear. We aimed to investigate the effect of fentanyl constant-rate infusion (CRI) with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement (MIRNM) in dogs. Six healthy purpose-bred dogs were anesthetized on three occasions with propofol alone (loading dose [LD], 8 mg/kg to effect; initial infusion rate [IR], 0.70 mg/kg/min); propofol (LD, 6 mg/kg to effect; IR, 0.35 mg/kg/min) and fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min); or propofol (LD, 4 mg/kg to effect; IR, 0.25 mg/kg/min), fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min), and medetomidine (LD, 2 µg/kg; IR, 0.5 µg/kg/hr) under controlled ventilation. The MIRNM was determined by observing the response to a noxious electrical stimulus. Heart rate, blood pressure, and blood gas analyses were performed at 1, 2, 3, and 4 hr after initiating CRI. The MIRNM (mean [range]) was significantly lower in the propofol-fentanyl-medetomidine group (0.16 [0.10-0.27] mg/kg/min) than that in the propofol-alone group (0.63 [0.47-0.82] mg/kg/min) (P=0.0004). Fentanyl combined with medetomidine did not significantly decrease the mean arterial pressure in dogs receiving propofol CRI 1-3 hr after initiating CRI compared with propofol CRI alone (P>0.9999, P=0.1536, and P=0.0596, respectively), despite inducing a significantly lower heart rate.

Validation of the anesthetic effect of a mixture of remimazolam, medetomidine, and butorphanol in three mouse strains.

Proper administration of anesthesia is indispensable for the ethical treatment of lab animals in biomedical research. Therefore, selecting an effective anesthesia protocol is pivotal for the design and success of experiments. Hence, continuous development and refinement of anesthetic agents are imperative to improve research outcomes and elevate animal welfare. "Balanced anesthesia" involves using multiple drugs to optimize efficacy while minimizing side effects. The medetomidine, midazolam, and butorphanol, called MMB, and medetomidine, alfaxalone, and butorphanol, called MAB, are popular in Japan. However, the drawbacks of midazolam, including its extended recovery time, and the narrow safety margin of MAB, have prompted research for suitable alternatives. This study replaced midazolam in the MMB combination with remimazolam (RMZ), which is noted for its ultra-short half-life. The resulting combination, called MRB, was effective in providing a wider safety margin compared to MAB while maintaining an anesthesia depth equivalent level to that of MMB in mice. Notably, MRB consistently exhibited better recovery scores after antagonist administration in contrast to MMB. Furthermore, the re-sedation phenomenon observed with MMB was not observed with MRB. The rapid metabolism of RMZ enables reliable anesthesia induction, circumventing the complications linked to MAB. Overall, MRB excelled in providing extended surgical anesthesia and swift post-antagonist recovery. These results highlight the potential of RMZ for broader animal research applications.

Comparing the Efficacy of Two Immobilization Drug Combinations for the Chemical Restraint of Bobcats (Lynx rufus).

Chemical immobilization agents that provide rapid induction time, short duration of action, wide margin of safety, and postreversal recovery are important attributes to the handling process of immobilized animals. We evaluated differences in induction, recovery, and physiologic parameters in 23 (13 female, nine adults and four yearlings; 10 male, nine adults and one yearling) free-ranging bobcats (Lynx rufus) chemically immobilized with an intramuscular combination of ketamine (10 mg/kg) and xylazine (KX; 1.5 mg/kg; n=11) or a combination of butorphanol (0.8 mg/kg), azaperone (0.27 mg/kg), and medetomidine (BAM; 0.32 mg/kg; n=12). Induction parameters, time to first effect, hemoglobin oxygen saturation, and anesthesia between bobcats administered KX and BAM were similar. Pulse rate was significantly higher for KX than for BAM. Time to standing and full recovery after reversal were faster for bobcats administered BAM than KX. Six of 11 (55%) bobcats given KX were effectively immobilized with a single injection, and five required additional drugs to allow adequate time for processing. Of 12 bobcats given BAM, six (50%) were effectively immobilized with a single injection, three (25%) individuals were not completely immobilized and required additional doses to allow adequate time for processing, and three (25%) required additional doses after complete arousal during processing. We found that BAM provided reduced sedation and processing times (<30 min), whereas KX provided extended sedation and processing times beyond 30 min. We suggest that researchers increase initial BAM drug volumes for yearling and adult bobcats at time of processing and consider taking appropriate safety precautions when handling free-ranging bobcats.

Butorphanol-Azaperone-Medetomidine Is as Safe and Effective as Nalbuphine-Azaperone-Medetomidine for Immobilization of Juvenile American Black Bears (Ursus americanus).

Immobilization kits including butorphanol-azaperone-medetomidine (BAM) and nalbuphine-azaperone-medetomidine can provide effective, safe, and easy-to-use protocols in bears. Nalbuphine-azaperone-medetomidine is not commercially available but may be useful for wildlife agencies because it does not contain controlled substances. This study directly compared BAM to nalbuphine-azaperone-medetomidine immobilization in 10 juvenile healthy black bears (10 mo old; four females, six males) undergoing prerelease examinations after rehabilitation. Bears were immobilized via remote delivery of 1 mL of BAM (n=5) or nalbuphine-azaperone-medetomidine (n=5) intramuscularly in the shoulder during December (randomized, blinded trial). Bears were intubated, monitored with an electrocardiogram, pulse oximeter, capnograph, noninvasive blood pressure cuff, and rectal thermometer, and underwent physical examination, sample collection, morphometrics, and ear-tag placement. Induction, physiologic, and recovery parameters were recorded, including arterial blood gas analysis. The anesthetic agents were antagonized with atipamezole and naltrexone. There were no differences between protocols in induction or recovery times. There were no differences between protocols in heart rate, respiratory rate, temperature, oxygen saturation, end-tidal CO2, mean arterial pressure, or blood gas analysis or any differences between male and female bears in any parameters. Bears were hypertensive and normoxemic with low oxygen saturation via pulse oximeter, but all recovered smoothly and were released within 2 h of recovery. This study supports that nalbuphine-azaperone-medetomidine is clini-cally as safe and effective as BAM in American black bears.

Optimal clinical dose of medetomidine for sedation of young cows during dehorning surgery.

The present paper reports on the clinical efficacy and optimal clinical dose of medetomidine for sedation of young cows during dehorning surgery. Medical records of 24 female Holstein cows that underwent dehorning surgery were used in this study. In four groups, the sedation of animals was carried out by one of the four intravenous treatments: 0.1 mg kg-1 xylazine (Xyl group, n = 6), 5.0 µg kg-1 medetomidine (5.0 Med group, n = 6), 10.0 µg kg-1 medetomidine (10.0 Med group, n = 6) or 20.0 µg kg-1 medetomidine (20.0 Med group, n = 6). The clinical sedation score (CSS) and heart rate (HR) were recorded. The CSSs after intravenous administration of each α2-adrenergic receptor agonist increased rapidly and peaked at 12.5 (10.0-16.0) at t = 20 min in the Xyl group, 11.5 (10.0-15.0) at t = 10 min in the 5.0 Med group, 16.0 (14.0-16.0) at t = 20 min in the 10.0 Med group and 16.0 (14.0 - 16.0) at t = 20 min in the 20.0 Med group. A similar degree of bradycardia was observed after every sedative treatment. We conclude that the intravenous administration of 10.0-20.0 µg kg-1 medetomidine is appropriate for sedation of young cows without severe side effects.

Comparison of Ketamine-Xylazine, Butorphanol-Azaperone-Medetomidine, and Nalbuphine-Medetomidine-Azaperone for Raccoon (Procyon lotor) Immobilization.

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine-medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint.

Validity and Repeatability Characteristics of a Non-Invasive, Infrared-Based Method Estimating Plasma Indocyanine Green Decay in Healthy Dogs.

Plasma clearance of indocyanine green (ICG-CL) is an invasive method to evaluate liver dysfunction. We aimed to investigate the practicality of a noninvasive, transcutaneous, infrared-based method estimating the disappearance rate of indocyanine green (ICG-PDR). In a randomized, cross-over study, both ICG-CL and ICG-PDR were determined in eight healthy dogs while conscious and when sedated with medetomidine and medetomidine-vatinoxan. ICG-PDR was further repeated in six of the dogs to assess its repeatability. Differences were tested with repeated-measures analysis of variance and post hoc t-tests with Bonferroni corrections, while associations were evaluated by both Spearman and Pearson correlation analyses. Furthermore, repeatability was assessed by examining calculated coefficients of variation (CV). A significant decrease in ICG-CL was observed in dogs sedated with medetomidine, while no difference between conscious and sedated states was detected with ICG-PDR. Overall, correlations between ICG-CL and ICG-PDR were poor, as was the intrasubject repeatability of ICG-PDR in conscious dogs with CV consistently above 20%. While some of the results may be explained by poor signal quality for the non-invasive method, we conclude that in healthy dogs ICG-PDR performed poorly.

A MIXTURE OF NALBUPHINE, AZAPERONE, AND MEDETOMIDINE FOR IMMOBILIZING RINGTAILS (BASSARISCUS ASTUTUS).

We evaluated a combination of nalbuphine HCl (40 mg/mL), azaperone tartrate (10 mg/mL), and medetomidine HCl (10 mg/mL), a combination known as NAM or NalMed-A, in 23 ringtails (Bassariscus astutus) during 29 handling events for a radio-collaring study in southern Oregon, US, from August 2020 to March 2022. The combination was delivered to ringtails by hand injection at 0.075 mL NAM per estimated 1 kg body mass. The mean (± standard deviation, SD) dosage calculated post hoc was 3.366 (±0.724) mg/kg nalbuphine, 0.841 (±0.181) mg/kg medetomidine, and 0.841 (±0.181) mg/kg azaperone. All captured ringtails were effectively immobilized with a mean (SD) induction time of 13.24 (±3.57) min. The medetomidine and nalbuphine components were antagonized with a combination of atipamezole and naltrexone HCl with a mean (SD) recovery time of 2.48 (±1.94) min. This combination appeared to be safe and effective for immobilizing ringtails with a low volume dose, smooth antagonism, and rapid recovery. In addition, NAM does not contain any drugs that are US Drug Enforcement scheduled, which makes it useful for immobilization procedures by wildlife professionals in the US.

Investigation of the effect and availability of ketamine on electroencephalography in cats with temporal lobe epilepsy.

In recent years, electroencephalography (EEG) in veterinary medicine has become important not only in the diagnosis of epilepsy, but also in determining the epileptogenic focus. In cats, sedation and immobilization, usually with medetomidine or dexmedetomidine, are necessary to place the electrodes and to obtain stable scalp EEG recordings. In this study, we hypothesized that, for cats with temporal lobe epilepsy (TLE), ketamine, a sedative/anesthetic and N-methyl-D-aspartate (NMDA) antagonist that activates the limbic system and is also used to treat refractory status epilepticus in dogs, would induce sufficient sedation and immobilization for EEG, as well as induce interictal epileptiform discharges (IEDs) that are more pronounced than those induced with medetomidine. We obtained EEG recordings from TLE cats and healthy cats administered either ketamine or medetomidine alone (study 1) or ketamine after medetomidine sedation (study 2). In study 1, the frequency of IEDs showed no statistically significant difference between ketamine and medetomidine in both TLE and healthy cats. Seizures were observed in 75% (9/12) cats of the TLE group with ketamine alone. When ketamine was administered after sedation with medetomidine (study 2), 3/18 cats in the TLE group developed generalized tonic-clonic seizure and 1/18 cats showed subclinical seizure activity. However, no seizures were observed in all healthy cats in both study 1 and study 2. Slow wave activity at 2-4 Hz was observed in many individuals after ketamine administration regardless studies and groups, and quantitative analysis in study 2 showed a trend toward increased delta band activities in both groups. While there was no significant difference in the count of IEDs between medetomidine and ketamine, ketamine caused seizures in cats with TLE similar to their habitual seizure type and with a higher seizure frequency. Our results suggest that ketamine may activate epileptiform discharges during EEG recordings. However, caution should be used for cats with TLE.

Effects of three immobilizing drug combinations on ventilation, gas exchange and metabolism in free-living African lions (Panthera leo).

Free-living lions (12 per group) were immobilized with tiletamine-zolazepam-medetomidine (TZM), ketamine-medetomidine (KM), or ketamine-butorphanol-medetomidine (KBM). During immobilization, respiratory, blood gas and acid-base variables were monitored for 30 minutes. Respiratory rates were within expected ranges and remained constant throughout the immobilizations. Ventilation increased in lions over the immobilization period from 27.2 ± 9.5 to 35.1 ± 25.4 L/min (TZM), 26.1 ± 14.3 to 28.4 ± 18.4 L/min (KM) and 23.2 ± 10.8 to 26.7 ± 14.2 L/min (KBM). Tidal volume increased over the immobilization period from 1800 ± 710 to 2380 ± 1930 mL/breath (TZM), 1580 ± 470 to 1640 ± 500 mL/breath (KM) and 1600 ± 730 to 1820 ± 880 mL/breath (KBM). Carbon dioxide production was initially lower in KBM (0.4 ± 0.2 L/min) than in TZM (0.5 ± 0.2 L/min) lions but increased over time in all groups. Oxygen consumption was 0.6 ± 0.2 L/min (TZM), 0.5 ± 0.2 L/min (KM) and 0.5 ± 0.2 L/min (KBM) and remained constant throughout the immobilization period. Initially the partial pressure of arterial oxygen was lower in KBM (74.0 ± 7.8 mmHg) than in TZM (78.5 ± 4.7 mmHg) lions, but increased to within expected range in all groups over time. The partial pressure of arterial carbon dioxide was higher throughout the immobilizations in KBM (34.5 ± 4.2 mmHg) than in TZM (32.6 ± 2.2 mmHg) and KM (32.6 ± 3.8 mmHg) lions. Alveolar-arterial gradients were initially elevated, but decreased over time for all groups, although in KM lions it remained elevated (26.9 ± 10.4 mmHg) above the expected normal. Overall, all three drug combinations caused minor respiratory and metabolic side-effects in the immobilized lions. However, initially hypoxaemia occurred as the drug combinations, and possibly the stress induced by the immobilization procedure, hinder alveoli oxygen gas exchange.

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

OBJECTIVE: To 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 DESIGN: A randomized, blinded, experimental, crossover study. ANIMALS: A group of eight healthy Beagle dogs aged 4.6 (2.3-9.4) years and weighing 12.9 (9-14.7) kg, median (range). METHODS: Each 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. RESULTS: The 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 RELEVANCE: Overall, 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.

Intranasal Atomization of Ketamine, Medetomidine and Butorphanol in Pet Rabbits Using a Mucosal Atomization Device.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to intramuscular administration, of a mix of anesthetic drugs in pet rabbits. In total, 104 mixed-breed pet rabbits, undergoing various types of surgery, received a combination of ketamine, medetomidine, and butorphanol (20, 0.4, and 0.2 mg/kg) by intranasal atomization using a Mucosal Atomization Device (Group MAD) or intramuscular administration (Group IM). When required, isoflurane was dispensed through a face mask. At the end of the procedures, atipamezole was administered using the same routes in the respective Groups. There were no differences in time to loss of righting reflex between the groups, while differences were found for the need for isoflurane (higher in Group MAD) and recovery time, occurring earlier in Group MAD. The results suggest that intranasal atomization of a combination of ketamine, medetomidine, and butorphanol produces a lighter depth of anesthesia in pet rabbits, compared to intramuscular administration. Intranasal atomization can be performed to administer sedative and anesthetic drugs, avoiding the algic stimulus related to the intramuscular inoculation of drugs.

Comparison of intramuscular alfaxalone with medetomidine-ketamine for inducing anaesthesia in Trachemys scripta spp. undergoing sterilization.

OBJECTIVE: To compare the effect of two anaesthetic protocols on heart rate (HR), time to muscle relaxation and tracheal intubation and time to surgical plane of anaesthesia, in Trachemys scripta spp. undergoing oophorectomy. STUDY DESIGN: Prospective randomized clinical study. ANIMALS: A total of 43 healthy female turtles. METHODS: Morphine (1.5 mg kg-1) was injected subcutaneously 2 hours before anaesthesia induction. The turtles were randomly administered either medetomidine (0.2 mg kg-1) and ketamine (10 mg kg-1) (group MK; n = 23) or alfaxalone (20 mg kg-1) (group A; n = 20) intramuscularly followed by bupivacaine (2 mg kg-1) administered subcutaneously along the incision site. Anaesthesia was maintained with isoflurane delivered in oxygen (100%). HR and the anaesthetic depth score (ADS) were recorded every 5 minutes from induction to recovery. A Friedman test followed by Wilcoxon tests with Bonferroni adjustment were used to compare these non-parametric data (HR and ADS) between groups and over time. Time to muscle relaxation of neck and limbs (TMR), tracheal tube insertion (TTTI) and stage of surgical anaesthesia (TADS≤3) were recorded and compared between groups using a Welch's t test after logarithmic transformation. RESULTS: Median values of TMR, TTTI and TADS≤3 were 4, 9.5 and 25 minutes in group A, respectively, and 14, 20 and 35 minutes in group MK (TMR, TTTIp ≤ 0.0001; TADS≤3p = 0.001). Plane of anaesthesia was significantly deeper in group A than in group MK for the first 20 minutes (p < 0.01). HR at 10 and 15 minutes post injection was significantly lower in group MK (28 beats minute-1) than in group A (36 and 34 beats minute-1) (p < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: After intramuscular injection in Trachemys scripta spp., tracheal intubation, muscle relaxation and a surgical plane of anaesthesia developed faster with alfaxalone than medetomidine-ketamine.