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Background: While a number of anesthetics has been shown potentially associated with neurotoxicity in the developing brain, dexmedetomidine, a drug that was rather recently introduced into the perioperative setting, is considered beneficial from neurological wellbeing. However, the underlying mechanism of how dexmedetomidine affects brain health remains to be determined. Based on our recent study, we hypothesized that dexmedetomidine would directly bind to and inhibit Toll-like receptor 4 (TLR4), a critical receptor largely expressed in microglia and responsible for neurological insult., Methods: We used TLR4 reporter assays to test if dexmedetomidine attenuates TLR4 activation. Furthermore, a direct binding of dexmedetomidine on TLR4 was tested using photoactivatable medetomidine. Lastly, the effect of dexmedetomidine on ketamine (anesthetic)-induced neurotoxicity was tested in rat pups (P7)., Results: We showed that dexmedetomidine attenuated TLR4 activation using reporter assay (IC 50  = 5.8 µg/mL). Photoactivatable dexmedetomidine delineated its direct binding sites on TLR4. We also showed that dexmedetomidine attenuated microglia activation both in vitro and in vivo., Discussion: We proposed a novel mechanism of dexmedetomidine-mediated neuroprotection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medetomidine is an FDA-approved α 2 -adrenoreceptor (α 2 -AR) agonist used as a veterinary sedative due to its analgesic, sedative, and anxiolytic properties. While it is marketed for veterinary use as a racemic mixture under the brand name Domitor, the pharmacologically active enantiomer, dexmedetomidine, is approved for sedation and analgesia in the hospital setting. Medetomidine has recently been detected in the illicit drug supply alongside fentanyl, xylazine, cocaine, and heroin, producing pronounced sedative effects that are not reversed by naloxone. The pharmacological effects along with the low cost of supply and lack of regulation for medetomidine has made it a target for misuse. Since 2022, medetomidine has been found as an adulterant in samples of seized drugs, as well as in toxicological analyses of patients admitted to the emergency department after suspected overdoses across several U.S. states and Canada. This Review will discuss the history, chemistry, structure-activity relationships, drug metabolism and pharmacokinetics (DMPK), pharmacology, and emergence of medetomidine as an adulterant in drug mixtures in the context of the current opioid drug crisis.

Background: The aim of our study was to test different anesthetic mixtures in order to identify the most suitable one for a surgical cardiac ischemia-reperfusion model in mice., Methods: 1) Sixty four mice were submitted to one of the 6 combinations of ketamine or alfaxalone associated to xylazine, medetomidine or midazolam. Depth and quality of anesthesia were evaluated via 5 reflex scores. 2) Impact of analgesic (buprenorphine or butorphanol), anesthesia reversal (with atipamezole) and surgery (cardiac ischemia-reperfusion surgery) have been tested in the selected protocols. 3) infarction size has been measured with TTC (Triphenyl Tetrazolium Chloride) method in mice anesthetized with best protocols., Results: Protocol involving medetomidine induced the longest surgical anesthesia: (median = 120, {interquartile range = 100-125}) min with ketamine and 53 {25-100} min with alfaxalone. Butorphanol substitution with buprenorphine did not alter time-related anesthesia parameters. Atipamezole reversal considerably reduced both recovery and immobilization time (respectively 22 {18-30} min and 98 {88-99} min vs. 55 {40-70} min and 143 {131-149} min, in groups with no reversal, p = 0.001) with no impact on infarction size measurement., Conclusion: In this study, the combination alfaxalone/medetomidine/buprenorphine (80/0,3/0,075 mg.kg-1, s.c.) associated with reversal by atipamezole was a reliable anesthetic protocol for murine surgery, particularly for the study of ischemia-reperfusion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Leon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anesthesia modifies sensory representations in the thalamo-cortical circuit but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane or ketamine medetomidine anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation under anesthesia is not possible based on awake activity. However, population-level parameters, such as average tuning strength and population decoding accuracy, are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk., (© Wildlife Disease Association 2024.)

Capturing and handling wildlife is a common practice for both management and research. As telemetry use has become common, the need to capture and chemically immobilize wildlife has increased. Understanding how long the effects of immobilizing agents last after releasing the animal is often poorly understood but needed to ensure that analyses use data that reflect natural behavior. Between 2016 and 2021, 60 cougars (Puma concolor) were chemically immobilized with medetomidine, zolazepam, and tiletamine (MZT) and collared across west-central Alberta, Canada, 27 of which were individuals being recollared. We examined the distance an individual traveled per day and compared equivalent periods before and after the recollaring event to determine whether postcapture movement rates were significantly different from precapture rates. Within 1 d of the recollaring, daily movement rates had returned to precapture rates (t20=2.09, P=0.18). Our results provide insight on how MZT used in cougars affects their postcapture movement and thus may be helpful in interpreting movement data after release., (© Wildlife Disease Association 2024.)

Administration of butorphanol, azaperone, and medetomidine (BAM) for immobilization of black howler monkeys ( Alouatta pigra ) has not been previously reported. In this observational study, 0.02 ml/kg of compounded BAM (butorphanol 27.3 mg/ml, azaperone 9.1 mg/ml, medetomidine 10.9 mg/ml) was administered IM in 10 captive black howler monkeys. Time to immobilization was recorded, an arterial blood gas performed, and at 5-min intervals, HR, RR, oscillometric arterial blood pressure, SPO 2, and rectal temperature were measured. Naltrexone and atipamezole were administered IM at procedure completion and recovery times were recorded. If invasive procedures such as surgery were necessary and additional drugs needed, further data from that individual was removed from data analysis. Final BAM dosages were 0.55 ± 0.12 mg/kg butorphanol, 0.19 ± 0.04 mg/kg azaperone, and 0.22 ± 0.05 mg/kg medetomidine. Nine of 10 monkeys achieved sedation allowing for physical exam, venipuncture, and tuberculin skin testing within 4 ± 2 min. No monkeys reached a plane of immobilization allowing for intubation. Physiologic variables were acceptable for this species. Hypoxemia (SPO 2 < 95%) was observed in three monkeys via pulse oximetry, and normoxemia was observed on arterial blood gas. Recovery was smooth and rapid. Therefore, BAM is a viable option for noninvasive procedures or as a premedication prior to induction of anesthesia in black howler monkeys.

Combinations of a low dose of opioid, such as thiafentanil, and a high dose of medetomidine, are increasingly being used for immobilization of African ungulates. Both drugs can have undesirable cardiorespiratory effects. In this study we assessed whether vatinoxan, a peripherally acting alpha 2 -adrenergic receptor antagonist, can be used to alleviate some of these effects without affecting the immobilization quality. Eight healthy, female, boma-confined blesbok ( Damaliscus pygargus phillipsi ), weighing a mean (SDtion) of 56.8 (4.4) kg, were immobilized twice in a randomized cross-over study with a 2-wk washout period using (1) 0.5 mg thiafentanil + 1.5 mg medetomidine (TM), (2) TM + vatinoxan: 0.5 mg thiafentanil + 1.5 mg medetomidine + 15 mg vatinoxan per milligram medetomidine (total of 22.5 mg, administered intramuscularly at 10 min post recumbency). Heart rate, respiratory rate, rectal temperature, oxygen saturation (SpO 2 ), arterial blood pressure, and sedation scores from 1 to 5 (1 = limited effect; 5 = excessively deep) were measured every 5 min. Arterial blood gases (PaO 2 and PaCO 2 ) were measured at 10, 15, 25, and 35 min postrecumbency and the alveolar--arterial oxygen gradient (P[A-a]O 2 ) was calculated. Induction times and immobilization quality did not differ between groups. The heart rate was significantly higher and the mean arterial pressure significantly lower in blesbok after receiving vatinoxan. All animals were hypoxemic and there were no significant differences in the respiratory rates, PaO 2 , PaCO 2 , SpO 2 , or P(A-a)O 2 gradients at any time point. Although vatinoxan did not improve respiratory variables and blood oxygenation in these animals, the change in cardiovascular variables may suggest that it improves tissue perfusion, a positive outcome that requires further investigation.

Twenty lesser chevrotains ( Tragulus sp.), 10 males and 10 females, were anesthetized with a combination of butorphanol-midazolam-medetomidine (BMidM), to assess the efficacy of this protocol for short procedures in this genus. The animals received BMidM (0.32, 0.06, 0.15 mg/kg, respectively) intramuscularly via hand injection. Physiological variables were recorded once the animals reached a working depth of anesthesia that lasted 30 min (range 12-60 min). At the end of the procedure, medetomidine and butorphanol were antagonized with atipamezole (0.75 mg/kg) and naltrexone (0.3 mg/kg) intramuscularly, respectively. Induction and recovery were 9.4 ± 4.0 min and 10.2 ± 4.1 min, respectively. Supplementation with isoflurane via face mask was required in five animals to reach light anesthesia. Times to reach the various stages of anesthesia were compared between sexes. There was no difference between males and females reaching the different stages of anesthesia, except for the time required to reach the ambulatory stage, in which females took a significantly longer time (11.8 min vs 7.8 min for the males) to stand after the injection of the antagonists ( P = 0.02). Heart rate, respiratory rate, rectal temperature, and peripheral hemoglobin oxygen saturation were similar between sexes and stable throughout the procedure. At the dosage tested BMidM was a reliable and safe protocol for short, minimally invasive procedures in lesser chevrotains with a fast induction and smooth recovery without complications.

Background: Electroencephalography (EEG) recording protocols have been standardized for humans. Although the utilization of techniques in veterinary medicine is increasing, a standard protocol has not yet been established., Hypothesis: Assessment of a sedation-awakening EEG protocol in dogs., Animals: Electroencephalography examination was performed in a research colony of 6 nonepileptic dogs (control [C]) and 12 dogs with epilepsy admitted to the clinic because of the epileptic seizures., Methods: It was a prospective study with retrospective control. Dogs with epilepsy were divided into 2 equal groups, wherein EEG acquisition was performed using a "sedation" protocol (IE-S, n = 6) and a "sedation-awakening" protocol (IE-SA, n = 6). All animals were sedated using medetomidine. In IE-SA group, sedation was reversed 5 minutes after commencing the EEG recording by injecting atipamezole IM. Type of background activity (BGA) and presence of EEG-defined epileptiform discharges (EDs) were evaluated blindly. Statistical significance was set at P > 0.05., Results: Epileptiform discharges were found in 1 of 6 of the dogs in group C, 4 of 6 of the dogs in IE-S group, and 5 of 6 of the dogs in IE-SA group. A significantly greater number of EDs (spikes, P = .0109; polyspikes, P = .0109; sharp waves, P = .01) were detected in Phase 2 in animals subjected to the "sedation-awakening" protocol, whereas there was no statistically significant greater number of discharges in sedated animals., Conclusions and Clinical Importance: A "sedation-awakening" EEG protocol could be of value for ambulatory use if repeated EEG recordings and monitoring of epilepsy in dogs is needed., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To determine if sedation with medetomidine-vatinoxan (Zenalpha; Dechra Veterinary Products) and midazolam (Alvogen) (ZM) would cause less cardiovascular depression and maintain similar depth and duration of sedation in pigeons (Columba livia domestica) compared to dexmedetomidine and midazolam (DM)., Methods: In a blinded crossover study, 15 healthy adult domestic pigeons were sedated IM with either dexmedetomidine (0.08 mg/kg) and midazolam (2 mg/kg) or medetomidine (0.16 mg/kg), vatinoxan (3.2 mg/kg), and midazolam (2 mg/kg) from November through December 2023. Each subject was monitored for 60 minutes, then the sedation was reversed with atipamezole (0.8 mg/kg) and flumazenil (0.1 mg/kg) as needed. Sedation scores, heart rates, and respiratory rates were compared., Results: There was no significant difference in the peak sedation score between DM and ZM groups, with both exhibiting median scores of 4 (heavy sedation). Mean heart rate was significantly higher for ZM than DM at 5, 10, 20, 30, 45, 60, and 65 minutes postinjection. Bradycardia occurred in both groups at 5 and 10 minutes postinjection and persisted for DM until reversal with atipamezole. Arrhythmias were auscultated in both groups. Bradypnea was not observed in either group, and all birds resumed normal behavior following recovery and the following day., Conclusions: Medetomidine-vatinoxan-midazolam provides a similar depth of sedation to DM but with less incidence of bradycardia. Further study is needed to determine the clinical applicability of this sedative in birds., Clinical Relevance: Medetomidine-vatinoxan may be considered for short-term sedation and restraint in cardiovascularly stable pigeons.

Introduction/objective: The purpose of this study was to investigate the echocardiographic effects of intravenous medetomidine and vatinoxan in dogs with stage B1 mitral valve disease. We hypothesised medetomidine-vatinoxan would reduce the need for manual restraint during echocardiography without producing detrimental cardiovascular effects or echocardiographic changes., Animals: Twelve client-owned dogs with stage B1 mitral valve disease., Methods: A transthoracic echocardiographic examination was performed before and after sedation with intravenous medetomidine (10 μg/kg) and vatinoxan (200 μg/kg). Vital parameters were also recorded, and the level of sedation was assessed subjectively. The data were analysed with Student's t-tests with an alpha level of <0.05., Results: End-systolic volume and left ventricular systolic diameter increased (from 0.89 ± 0.19 mL/kg to 1.13 ± 0.29 mL/kg and 0.96 ± 0.12 cm to 1.10 ± 0.10 cm, respectively) and ejection fraction (from 66.33 ± 4.0% to 56.23 ± 9.54%) and fractional shortening (from 36.13 ± 5.42% to 27.24 ± 5.6%) decreased significantly after sedation. End diastolic volume, left ventricular diastolic diameter, and left atrial size remained statistically unchanged, while aortic (from 1.34 ± 0.2 m/s to 0.99 ± 0.14 m/s) and pulmonic (from 0.94 ± 0.16 m/s to 0.66 ± 0.15 m/s) velocities decreased significantly. No dogs had a mean arterial pressure below 65 mmHg. Sedation enabled echocardiographic examination without manual restraint. No adverse effects were observed with the dose studied., Conclusions: Echocardiographic parameters were not completely comparable with the baseline values, which should be taken into consideration when evaluating dogs sedated with intravenous medetomidine-vatinoxan., Competing Interests: Conflict of Interest Statement Dr. Turunen is an employee of Vetcare Ltd (Mäntsälä, Finland), which produces the veterinary medicinal product that was the subject of this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl., Study Design: Prospective, randomized, blind clinical study., Animals: A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg., Methods: Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg -1 ), MF group with medetomidine (0.005 mg kg -1 ) and fentanyl (0.01 mg kg -1 ) and AF group with acepromazine (0.01 mg kg -1 ) and fentanyl (0.01 mg kg -1 ). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg -1 hour -1 ). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05)., Results: Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60)., Conclusions and Clinical Relevance: Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

We combined electrical perforant pathway stimulation with electrophysiological and fMRI recordings in the hippocampus to investigate the effects of neuronal afterdischarges (nAD) on subsequent fMRI BOLD signals in the presence of isoflurane and medetomidine. These two drugs already alter basal hemodynamics in the hippocampus, with isoflurane being mildly vasodilatory and medetomidine being mildly vasoconstrictive. The perforant pathway was stimulated once for 8 seconds with either continuous 20 Hz pulses ( continuous stimulation ) or 8 bursts of 20 high-frequency pulses ( burst stimulation ). Burst stimulation in the presence of medetomidine elicited long-lasting nAD that coincided with a brief positive BOLD response and a subsequent long-lasting decrease in BOLD signals. Under isoflurane, this stimulation elicited only short-lasting nAD and only a short-lasting decline in BOLD signals. In contrast, continuous stimulation under isoflurane and medetomidine caused a similar duration of nAD. Under isoflurane, this caused only a sharp and prolonged decline in BOLD signals, whereas under medetomidine, again, only a brief positive BOLD response was elicited, followed by a shorter and moderate decline in BOLD signals. Our results suggest that nAD simultaneously activate different neurovascular coupling mechanisms that then independently alter local hemodynamics in the hippocampus, resulting in an even more complex neurovascular coupling mechanism., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Alpha2-adrenoceptor agonists (α 2 -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, α 2 -agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α 2 -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 α 2 -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., (© 2024. The Author(s).)

Objective: Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates., Animals: 98 hamadryas baboons (Papio hamadryas) held in a German zoological institution., Methods: A group of 12 veterinarians, 2 zookeepers, and 6 volunteers anesthetized all animals within 2 days. The baboons were orally premedicated with midazolam (0.1 to 0.5 mg/kg) and anesthetized with medetomidine (40 to 60 µg/kg, IM) and ketamine (2 to 4 mg/kg, IM); isoflurane at rates of 1.5% to 2% was used for maintaining anesthesia if necessary. All animals received a physical examination, prophylactic medication, and tuberculin testing. For population management, the animals received a contraceptive implant (adult females), orchiectomy (young males), or vasectomy (breeding males). Young males received intratesticular blocks with lidocaine. All animals received atipamezole (125 to 150 µg/kg) before recovery., Results: Premedication resulted in anxiolysis, which facilitated separating and darting. Median time from darting to access to the animal was 10 minutes. Mean anesthetic times were 25 minutes for females and 55 minutes for males. The depth of anesthesia was appropriate for the procedures. No fatalities were recorded. One animal was injured by other baboons but recovered after treatment., Clinical Relevance: Health management and birth control measures are necessary in baboon troops under human care. Anesthesia and/or contraception of individual animals often leads to intraspecific aggression. This case series describes how to provide anesthesia and contraception to an entire troop as an alternative approach that can be adopted to future similar interventions.

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.

This double-blinded randomized cross-over study compared the muscle tissue oxygen saturation (StO 2 ) 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/m 2 , DEX) or medetomidine (1 mg/m 2 ) and vatinoxan (20 mg/m 2 ) (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/m 2 ). Depth of sedation, cardiopulmonary parameters, StO 2 , 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. StO 2 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 StO 2 . 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 StO 2 measured at the sartorius muscle that were not significantly different between treatments., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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/m 2 : 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/cm 5 /m 2 : 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., Competing Interests: The authors declare that there is no conflict of interest.

Sensory processing in the auditory brainstem can be studied with auditory brainstem responses (ABRs) across species. There is, however, a limited understanding of ABRs as tools to assess the effect of pharmacological interventions. Therefore, we set out to understand how pharmacological agents that target key transmitter systems of the auditory brainstem circuitry affect ABRs in rats. Given previous studies, demonstrating that Nrxn1α KO Sprague Dawley rats show substantial auditory processing deficits and altered sensitivity to GABAergic modulators, we used both Nrxn1α KO and wild-type littermates in our study. First, we probed how different commonly used anesthetics (isoflurane, ketamine/xylazine, medetomidine) affect ABRs. In the next step, we assessed the effects of different pharmacological compounds (diazepam, gaboxadol, retigabine, nicotine, baclofen, and bitopertin) either under isoflurane or medetomidine anesthesia. We found that under our experimental conditions, ABRs are largely unaffected by diverse pharmacological modulation. Significant modulation was observed with (i) nicotine, affecting the late ABRs components at 90 dB stimulus intensity under isoflurane anesthesia in both genotypes and (ii) retigabine, showing a slight decrease in late ABRs deflections at 80 dB stimulus intensity, mainly in isoflurane anesthetized Nrxn1α KO rats. Our study suggests that ABRs in anesthetized rats are resistant to a wide range of pharmacological modulators, which has important implications for the applicability of ABRs to study auditory brainstem physiology., (© 2024. The Author(s).)

The maned sloth ( Bradypus torquatus ) is an endemic and endangered species of two Brazilian states, with much unknown biological information needed to direct conservation actions. Other sloth species have been studied regarding anesthesia; however, there is a lack of anesthesia research for the maned sloth. Anesthetic data were collected from 12 free-range maned sloths that were immobilized for a field examination. Individuals were anesthetized using a combination of ketamine (4.0 mg/kg) and medetomidine (0.03 mg/kg), and antagonized with atipamezole (0.1 mg/kg). Time to induction and recovery were recorded and compared with sex and age classes. After the induction and until antagonist administration, physiological parameters (rectal temperature, heart rate, respiratory rate, and oxygen saturation) were recorded every 10 min during anesthesia and were statistically evaluated over time. Induction was fast (3.21 ± 0.76), but recovery was longer (113.3 ± 18) when compared to other studies. Induction and recovery times were not different across sex or age classes. Rectal temperature, heart rate, and oxygen saturation remained stable throughout the procedure. Respiratory rate significantly decreased over time, from 18.25 ± 7.03 to 13.17 ± 3.66 movements per minute. Our results indicate that the described combination of ketamine and medetomidine is a safe and effective choice for anesthesia of maned sloths.

Sedation, recovery response, and physiologic outcomes were evaluated in five captive reindeer ( Rangifer tarandus ) in Minnesota using a completely reversible immobilization protocol. Reindeer were immobilized with butorphanol (0.23-0.32 mg/kg), midazolam (0.23-0.32 mg/kg), and medetomidine (0.15 mg/kg) (BMM) via IM dart. Induction time (IT), recumbency time (DT), and recovery time (RT) were recorded. Temperature (T), respiratory rate (RR), pulse rate (PR), pulse oximetry (SpO 2 ), arterial blood gas values including oxygen (PaO 2 ), and carbon dioxide (PaCO 2 ) tensions and lactate (Lac) were recorded preoxygen supplementation and 15 min postoxygen supplementation. Reversal was done using naltrexone (2.3-3.0 mg/kg), flumazenil (0.008-0.01 mg/kg) and atipamezole (0.62-0.78 mg/kg) (NFA) IM, limiting recumbency to 1 h. Median IT, DT, and RT were 5 min, 46 min, and 7 min, respectively. SpO 2 (92 to 99%, P = 0.125), PaO 2 (45.5 to 97 mmHg, P = 0.25), and PaCO 2 (46.5 to 54.6 mmHg, P = 0.25) all increased, whereas Lac (3.02 to 1.93 mmol/L, P = 0.25) decreased between baseline and 15 min postoxygen supplementation, without statistical significance. BMM immobilization, and reversal with NFA provided rapid and effective immobilization and recovery, respectively. Oxygen supplementation mitigated hypoxemia in all reindeer.

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 (MIR NM ) 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 MIR NM 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 MIR NM (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.

This randomized, crossover study evaluated three sedation protocols administered subcutaneously in nine budgerigars ( Melopsittacus undulatus ) and nine black-cheeked lovebirds ( Agapornis nigrigenis ). All protocols included midazolam (5 mg/kg), combined with butorphanol (5 mg/kg) (BM), medetomidine (20 lg/kg) (MM), or alfaxalone (13 mg/kg) (AM). Mortalities from suspected cardiorespiratory arrest were observed when AM was used in lovebirds, even after reduction of alfaxalone dosage to 3 mg/kg, and therefore this protocol was excluded from further use in this species. Induction and recovery times were recorded and their quality assessed. Sedation depth and heart and respiratory rates were measured every 5 min and radiographic positioning was attempted at 10 and 20 min. At 30 min, midazolam and medetomidine were reversed with flumazenil (0.05 mg/kg, SC), and atipamezole (0.2 mg/kg, SC), respectively. MM consistently provided deep sedation in both species, with successful radiographic positioning at every attempt. As expected, heart rate was often lower with MM than with other protocols, but no associated complications were noted. In budgerigars, BM had the lowest radiographic positioning success rate (10 min: 5/9, 20 min: 3/9), whereas in lovebirds it provided significantly deeper sedation ( P < 0.001), allowing radiographic positioning in all subjects. In both species, BM provided the shortest recovery times. AM resulted in reliable radiographic positioning of all budgerigars at 10 min, but not at 20 min (5/ 9), and provided consistently poor recoveries. This study highlights how differently two psittacine species of similar size may react to the same sedation protocols. AM sedation cannot be fully reversed and produced significant undesirable effects, several of which have been previously reported with alfaxalone administration to avian species. The authors therefore caution against using alfaxalone-midazolam combinations in budgerigars and black-cheeked lovebirds. Both BM and MM provided reliable sedation in these species, and appear to be suitable alternatives to AM.

Wildlife professionals routinely use potent sedatives and anesthetics when chemically immobilizing wildlife and zoo species in remote environments. Accidental exposure to these prescription veterinary drugs is rare but could be rapidly fatal. Commonly used agents include opioids and α 2 adrenoreceptor agonists. These drugs can be reversed with specific antagonists; however, they are often not approved for human use. The protocol created here can be used by wildlife health professionals in a field setting with basic human emergency medical response training in coordination with local Emergency Medical Services (EMS). Key components include, building local relationships between EMS and wildlife professionals, focused EMS training, administering opioid and α 2 adrenergic antagonists off label, and local evacuation procedures. This framework could allow wildlife management agencies or zoos to mitigate the risk of human exposures to these commonly used drugs, significantly improving occupational safety in an otherwise high-risk environment.

One male and one female giant panda ( Ailuropoda melanoleuca ) from a Belgian zoo were anesthetized on eight different occasions over a course of 4 yr for electro-ejaculation ( n = 3) or artificial insemination ( n = 5). Medetomidine (0.03-0.04 mg/kg) and ketamine (2.5-3 mg/kg) were administered by intramuscular remote injection. Animals gained sternal recumbency with the loss of response to external stimuli after 4.9 ± 1.6 min (mean ± SD). The trachea was intubated with a 14-mm-internal diameter endotracheal tube; anesthesia was maintained with isoflurane in oxygen adjusted according to the required depth of anesthesia with a small-animal circle system. Physiological variables (heart rate, respiratory rate, oxygenation, end tidal carbon dioxide partial pressure and non-invasive blood pressure) were measured and remained within an acceptable range throughout anesthesia. Atipamezole (0.17-0.25 mg/kg) was administered intramuscularly after anesthesia. Recoveries were rapid and uneventful. Medetomidine 0.03 mg/kg and ketamine 2.5 mg/kg IM appeared to be the preferred doses for giant pandas.

Background: According to the findings of several studies, sedatives and anaesthetics have different effects on the functioning of the cardiovascular system and intraocular pressure (IOP). For accurate diagnosis, treatment and surgery with minimal complications, it is necessary to be aware of the effects of sedatives and anaesthetics on the cardiovascular system and IOP., Objectives: The aim of this study was to evaluate the effects of sedatives (medetomidine and midazolam) and anaesthetics (ketamine, propofol and isoflurane) on IOP, heart rate (HR) and blood pressure in dogs., Methods: In this study, 10 dogs participated in three treatments using a randomised cross-over design, with a 1-week washout period between each treatment. Dogs in all treatments were premedicated with medetomidine and midazolam. Anaesthesia was induced using ketamine, propofol, or isoflurane and maintained for 60 min with the appropriate doses of each drug. The cardiovascular variables (heart rate, and systolic, diastolic and mean arterial pressures) and IOP were measured at different timepoints: before premedication (baseline values, T-Bas), 15 min after medetomidine administration (T-Med), 20 min after midazolam administration (T-Mid) and at 15 (T-15), 30 (T-30), 45 (T-45) and 60 (T-60) min after anaesthesia induction., Results: Medetomidine significantly reduced the IOP and HR and did not significantly change the mean arterial pressure (MAP). Midazolam significantly reduced the IOP while did not significantly change the HR and MAP. Ketamine and isoflurane significantly increased the IOP and HR while did not significantly change the MAP. Propofol significantly increased the HR, but did not cause significant changes in IOP and MAP., Conclusions: Considering that anaesthetics are typically administered in conjunction with pre-anaesthetic drugs, the increases in IOP induced by ketamine and isoflurane are not important, as the IOP did not exceed the baseline values. However, further studies are required to investigate these effects in patients with elevated IOP., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

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., (© Wildlife Disease Association 2024.)

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., (© Wildlife Disease Association 2024.)

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., (© Wildlife Disease Association 2024.)

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.

Purpose: This study evaluated the DNA damage caused by repeated doses of xylazine-ketamine and medetomidine-ketamine anesthesia in the liver and kidneys., Methods: In this study, 60 rats were used. The rats were divided into group 1 (xylazine-ketamine), and group 2 (medetomidine-ketamine), and these anesthetic combinations were administered to the rats at repeated doses with 30-min intervals. The effects of these anesthetic agents on the tumor necrosis factor-alpha gene for DNA damage were investigated., Results: According to the gene expression results, it was observed that a single dose of xylazine-ketamine was 2.9-fold expressed, while first and second repeat doses did not show significant changes in expression levels. However, in the case of the third repetition, it was observed to be 3.8-fold overexpressed. In the case of medetomidine-ketamine administration, it was observed that a single-dose application resulted in a 1.04-fold expression, while the first and the third repeat doses showed a significant down expression. The samples from the second repeat dose administration group were found to have insignificant levels of expression., Conclusions: This study can contribute to understanding the safe anesthetic combination in research and operations in which xylazine-ketamine and medetomidine-ketamine combinations are used.

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., (© Wildlife Disease Association 2023.)

Sable antelope ( Hippotragus niger ), a large, dominant species, often require chemical immobilization for captive management. Despite several recorded protocols, limited objective or subjective data are available to guide chemical immobilization of this species. This study retrospectively compared immobilization drug combinations of carfentanil-xylazine (CX), thiafentanil-xylazine (TX), etorphine-xylazine (EX), carfentanil-acepromazine (CA), and butorphanol-azaperone-medetomidine (BAM) for healthy sable antelope at one institution. Clinically applicable physiologic measures, subjective ratings, and timing of anesthetic milestones of 161 events for 107 individuals revealed the following statistically significant findings ( P < 0.05). Induction ratings were best for TX, highest degree of muscle relaxation occurred with BAM and TX, and anesthetic ratings were best for TX and EX. Time to recovery was longest and complications 2.56 times more likely with CX. Time to recumbency was shortest in TX. Heart rate was highest in CA and lowest in BAM. For immobilization procedures, this study suggests TX would be the preferred combination for H. niger . However, all drug combinations evaluated can be used successfully to immobilize H. niger, and certain combinations may be situationally preferred based on desired muscle relaxation, expected induction or recovery times, or anticipated procedure length.

The use of α2-adrenergic agonists in association with urethral catheterization has been used as a technique for pharmacological semen collection in cats. The mechanism of action of this drug is the stimulation of adrenoreceptors in the vas deferens, which results in ejaculation. While medetomidine is the α2-agonist most commonly used in studies, ejaculation with the use of dexmedetomidine associated with ketamine has been effective, but with variable results. Therefore, further studies regarding the methodology of use are required to obtain better seminal quality. This study aimed to compare two pharmacological semen collection times after the association of dexmedetomidine (30 μg/kg, IM; Dormitor®, Zoetis), ketamine (5 mg/kg, IM; ketamine, Vetnil) and urethral catheterization using a tomcat probe (0.8 mm × 1.00 mm × 11 cm). The collections were divided into two experimental groups: G10 (N = 8; urethral catheterization after 10 min of anaesthesia) and G15 (N = 8; urethral catheterization after 15 min of anaesthesia). The ejaculates were evaluated for ejaculate volume, sperm concentration, morphology and kinetics using the CASA system. To compare the groups, the t-test and the Mann-Whitney U-test were used with a significance level of 5%. It was identified that ejaculate volume (G10: 22.62 ± 2.13 vs. G15: 26.81 ± 1.55; p < .001) and sperm concentration (G10: 48.10 × 10 6  ± 17.84 vs. G15: 90.18 × 10 6  ± 19.35; p < .001) was higher in G15 than in G10 and had a lower percentage of minor defects than G10 (G10: 3.12 ± 2.41 vs. G15: 1.00 ± 1.19; p = .043). Regarding the kinetic parameters, the results of G15 were better for total motility-TM (G10: 67.00 ± 10.33 vs. G15: 81.87 ± 7.99; p = .006) and faster cells-RAPID: (G10: 55.00 ± 16.63 vs. G15: 74.25 ± 11.94; p = .019); whereas a higher proportion of cells with slow speed-SLOW were seen in G10 (G10: 31.00 ± 12.07 vs. 17.12 ± 7.53; p = .015). Based on these findings, we suggest that collection via urethral catheterization should be performed 15 min after the application of ketamine-associated dexmedetomidine to obtain a better-quality ejaculate., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 (T MR ), tracheal tube insertion (T TTI ) and stage of surgical anaesthesia (T ADS≤3 ) were recorded and compared between groups using a Welch's t test after logarithmic transformation., Results: Median values of T MR , T TTI and T ADS≤3 were 4, 9.5 and 25 minutes in group A, respectively, and 14, 20 and 35 minutes in group MK (T MR , T TTI p ≤ 0.0001; T ADS≤3 p = 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., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Chemical immobilization is widely used by wildlife and veterinary professionals for the safe handling of animals. A combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL), known as NAM, is a low-volume combination with field immobilization practicality and fewer regulations restricting its use in the US than some other drug combinations. We evaluated the safety and effectiveness of NAM as an immobilizing agent for raccoons (Procyon lotor). From May 2021 to February 2022, 16 adult raccoons were captured in cage traps and immobilized with 0.3 mL NAM intramuscularly (12 mg nalbuphine, 3 mg medetomidine, and 3 mg azaperone, regardless of body weight). After administration, time to sedation was measured; body temperature, heart rate, respiratory rate, and oxygen saturation were monitored and recorded every 5 min for 20 min. Each raccoon was weighed; the dose administered was calculated (range 2.2-4.1 mg/kg, mean 3 mg/kg). Mean induction time was 6 min (4-17 min); time to recovery following administration of 15 mg atipamezole, 7.5 mg naltrexone for reversal, was 10 min (6-18 min). Heart rate, oxygen saturation, and respiration rate remained steady during immobilization. Rectal temperature steadily declined. Overall, NAM appeared to be a practical option for raccoon immobilization, providing rapid induction and reversal as well as adequate sedation for short-term handling and minimally invasive sampling., (© Wildlife Disease Association 2023.)

To prevent aspiration in Japanese White (JW) rabbits, the maximum single volume of medetomidine administered intranasally is 0.3 mL per nostril using a mucosal atomization device (MAD). This study aimed to examine the sedative effect of intranasal administration of medetomidine using MAD in eight healthy female JW rabbits. Each rabbit received intranasal atomization (INA) of saline (Control treatment) along with three doses of 1 mg/mL medetomidine (0.3 mL to one nostril [MED0.3 treatment]; 0.3 mL each to both nostrils [MED0.6 treatment]; 0.3 mL twice to both nostrils [MED1.2 treatment]), with a washout period of at least 7 days between treatments. The actual doses of medetomidine were 82 (75-84) μg/kg (median [25th-75th percentile]), 163 (156-168) μg/kg, and 323 (295-343) μg/kg for the MED0.3, MED0.6, and MED1.2 treatments, respectively. A medetomidine-dose dependent sedative effect was detected, and the loss of righting reflex (LRR) was achieved in one rabbit at 18 min, seven rabbits at 11 (9-18) min, and eight rabbits at 7 (4-18) min after the MED0.3, MED0.6, and MED1.2 treatments, respectively. The LRR was maintained for 63 (29-71) min and 83 (68-101) min after the MED0.6 and MED1.2 treatments, respectively. Additionally, the INA of medetomidine produced a significant dose-dependent cardiorespiratory depression including a decrease in pulse rate, respiratory rate, percutaneous oxygen saturation, and arterial partial pressure of oxygen, and an increase in arterial partial pressure of carbon dioxide in the rabbits.

A combination of tiletamine-zolazepam, medetomidine, and azaperone was used to immobilize captive Chacoan peccaries (Catagonus wagneri) for health assessments and biological sample collection at the Centro Chaqueño para la Conservación e Investigación (CCCI) in the Paraguayan Chaco during July in 2017 and 2018. In total, 83 peccaries kept in 0.25-1.50 hectare enclosures were immobilized via dart-administered anesthetic. Mean animal weight was 33.89±3.74 kg (standard deviation; n=77). The mean intramuscular (IM) anesthetic drug and dosages were 0.03±0.00 mg/kg of medetomidine, 0.91±0.10 mg/kg of Zoletil 50 (tiletamine-zolazepam), and 0.30±0.03 mg/kg azaperone. The mean time to recumbency after darting was 6.07±2.65 min. The mean time to reach the anesthetic plane postdarting was 10.00±2.00 min. Muscle relaxation was adequate to allow minor veterinary procedures. A mean dosage of 0.15±0.02 mg/kg of atipamezole was given IM to reverse the medetomidine. Recoveries were smooth and animals were standing by 59.17±30.18 min postreversal. Full recovery and release back to enclosures occurred 90±30 min postreversal. A single dose of this drug combination provided adequate anesthesia for 88% of adult Chacoan peccaries; 12% needed a supplemental dose of tiletamine-zolazepam because of failure to receive the full dose from the anesthetic dart. Sex and age did not impact the dosage required to achieve immobilization. Confinement during recovery from anesthesia is required with this protocol. Aside from mild hypoxemia, no adverse effects from anesthesia were observed. However, oxygen supplementation as a part of this protocol is recommended to support circulatory and respiratory capacity., (© Wildlife Disease Association 2023.)

We chemically immobilized a free-ranging moose subspecies, Shiras moose (Alces alces shirasi), using a combination of butorphanol (27.3 mg/mL), azaperone (9.1 mg/mL), and medetomidine (10.9 mg/mL). Ground and helicopter darting with fixed doses of 2 mL and 3 mL, respectively, safely immobilized 13 individuals in Wyoming, USA., (© Wildlife Disease Association 2023.)

Objective: To determine the sedative effects and characteristics of cardiac rhythm with intravenous (IV) premedication of medetomidine, butorphanol and ketamine in dogs., Study Design: Prospective, blinded, randomized clinical trial., Animals: A total of 116 client-owned healthy dogs undergoing elective surgery., Methods: Dogs were randomly allocated one of four groups: group M, medetomidine 5 μg kg -1 ; group B, butorphanol 0.2 mg kg -1 ; group MB, medetomidine 5 μg kg -1 and butorphanol 0.2 mg kg -1 ; or group MBK, medetomidine 5 μg kg -1 , butorphanol 0.2 mg kg -1 and ketamine 1 mg kg -1 IV. Sedation was assessed using a numerical descriptive scale. Heart rate (HR) and rhythm were monitored; propofol dose (mg kg -1 IV) to allow orotracheal intubation was documented. Data were analysed using anova, accounting for multiple testing with the Tukey honest significant difference test., Results: Sedation scores varied significantly between all groups at all time points, except between groups MB and MBK at four time points. HR decreased in all groups: most in groups M and MB, least in group B. HR was initially higher in group MBK than in groups M and MB. Arrhythmias occurred in all groups: group B showed second-degree atrioventricular blocks occasionally, all other groups showed additionally ventricular escape complexes and bundle branch blocks. Dose of propofol required for orotracheal intubation was significantly higher in group B (5.0 ± 2.0 mg kg -1 ) than in group M (2.6 ± 0.6 mg kg -1 ). Although no difference could be demonstrated between groups MB (1.4 ± 0.6 mg kg -1 ) and MBK (0.9 ± 0.8 mg kg -1 ), both groups required significantly less propofol than group M., Conclusion and Clinical Relevance: Medetomidine-based premedication protocols led to various bradyarrhythmias. Addition of subanaesthetic doses of ketamine to medetomidine-based protocols resulted in higher HRs, fewer bradyarrhythmias and fewer animals that required propofol for intubation without causing side effects in healthy dogs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the pharmacokinetics of a single bolus of intravenous (IV) propofol after intramuscular administration of etorphine, butorphanol, medetomidine, and azaperone in 5 southern white rhinoceros to facilitate reproductive evaluations. A specific consideration was whether propofol would facilitate timely orotracheal intubation., Animals: 5 adult, female, zoo-maintained southern white rhinoceros., Procedures: Rhinoceros were administered etorphine (0.002 mg/kg), butorphanol (0.02 to 0.026 mg/kg), medetomidine (0.023 to 0.025 mg/kg), and azaperone (0.014 to 0.017 mg/kg) intramuscularly (IM) prior to an IV dose of propofol (0.5 mg/kg). Physiologic parameters (heart rate, blood pressure, respiratory rate, and capnography), timed parameters (eg, time to initial effects and intubation), and quality of induction and intubation were recorded following drug administration. Venous blood was collected for analysis of plasma propofol concentrations using liquid chromatography-tandem mass spectrometry at various time points after propofol administration., Results: All animals were approachable following IM drug administration, and orotracheal intubation was achieved at 9.8 ± 2.0 minutes (mean ±SD) following propofol administration. The mean clearance for propofol was 14.2 ± 7.7 ml/min/kg, the mean terminal half-life was 82.4 ± 74.4 minutes, and the maximum concentration occurred at 2.8 ± 2.9 minutes. Two of 5 rhinoceros experienced apnea after propofol administration. Initial hypertension, which improved without intervention, was observed., Clinical Relevance: This study provides pharmacokinetic data and insight into the effects of propofol in rhinoceros anesthetized using etorphine, butorphanol, medetomidine, and azaperone. While apnea was observed in 2 rhinoceros, propofol administration allowed for rapid control of the airway and facilitated oxygen administration and ventilatory support.

Background: Cardiovascular disease is a significant cause of mortality in captive great apes. However, data from bonobos are lacking due to a paucity of collections in Europe. Comprehensive preventive screening is required to understand the aetiopathogenesis of cardiovascular disease, but the provision of a stable and predictable anaesthetic protocol with minimal cardiovascular effects is challenging., Methods: This prospective, observational case series reports anaesthesia of 12 bonobos using hand-injected medetomidine and tiletamine-zolazepam followed by maintenance with isoflurane in oxygen. Comprehensive clinical examinations, including arterial blood gases and echocardiography were undertaken., Results: Induction of anaesthesia with hand injection was successful in all but one individual. Respiratory acidosis with metabolic alkalosis and respiratory alkalosis with metabolic acidosis were documented. Hypochloraemia may have contributed to non-respiratory alkalosis in one individual. Ten bonobos experienced hypotension and required haemodynamic support. Both N-terminal pro b-type natriuretic peptide and troponin I cardiac biomarkers correlated with left ventricular ejection fraction (percentage). Recovery was smooth, rapid and uneventful in all animals., Limitations: The effects of the anaesthetic must be considered during echocardiographical interpretation., Conclusions: The anaesthesia protocol provided a safe, predictable induction and recovery, facilitating diagnostics (including echocardiography) and minor surgical procedures. Comprehensive monitoring, including invasive blood pressure monitoring and haemodynamic support, is highly recommended., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Objective: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration., Study Design: A randomized, controlled, blinded, clinical trial., Animals: A total of 28 client-owned dogs., Methods: Dogs were premedicated with medetomidine (0.125 mg m -2 ) and butorphanol (0.2 mg kg -1 ) (group MB; n = 14), or medetomidine (0.25 mg m -2 ), butorphanol (0.2 mg kg -1 ) and vatinoxan (5 mg m -2 ) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg -1 ) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg -1 ) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f R ), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe'Sevo) and carbon dioxide (Pe'CO 2 ) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations., Results: At the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute -1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f R , Pe'CO 2 , Fe'Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups., Conclusions and Clinical Relevance: In group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to measure the effects of detomidine and medetomidine alone or in combination with ketamine on Schirmer tear test I (STT I) results and intraocular pressures (IOPs) in the common buzzard ( Buteo buteo ). Fourteen ophthalmologically healthy common buzzards were randomly assigned to 1 of 2 α-2 adrenoreceptor agonist groups: a detomidine group (group 1) and a medetomidine group (group 2). The detomidine group had 2 subgroups, detomidine alone or in combination with ketamine. Similarly, the medetomidine group had 2 subgroups, medetomidine alone or in combination with ketamine. Five minutes after α-2 adrenoreceptor agonist administration, the first measurements of STT I and IOP were collected. Ketamine was injected intramuscularly immediately after the first measurements were recorded. Schirmer tear test I and IOP measurements were repeated 5 minutes after ketamine administration. Measurements were obtained for 3 subgroups per agonist grouping: baseline 1, detomidine alone and detomidine with ketamine for group 1, and baseline 2, medetomidine alone and medetomidine with ketamine for group 2. Both IOP and STT I decreased significantly after sedation, anesthesia, or both. Intraocular pressure was significantly lower in the detomidine-ketamine group compared with the detomidine alone group. The IOP and STT I significantly decreased in both the medetomidine alone and medetomidine-ketamine groups when compared with those for all 14 unanesthetized animals before administering the α-2 adrenoreceptor agonist and ketamine. When α-2 adrenoreceptor agonists were considered as a single group (groups 1 and 2 combined), IOP also showed a significant decrease in the α-2 adrenoreceptor agonist-ketamine groups compared with the α-2 adrenoreceptor agonists alone, but STT I did not. According to the results obtained from these common buzzards, no statistical differences were found between the detomidine and medetomidine (alone) groups or detomidine-ketamine and medetomidine-ketamine groups in terms of STT I and IOP.

Background: Sometimes it is necessary to use sedatives or even general anaesthetics to examine animals with spinal cord injuries. These drugs may affect spinal reflexes, alter the outcome of neurological examinations, and make it difficult to diagnose location of the lesion., Objectives: The aim of this study was to evaluate the effects of five pre-anaesthetic and anaesthetic agents commonly used in clinics on spinal reflexes in dogs., Methods: Ten native adult dogs were participated in three groups. In all groups, the dogs were premedicated with medetomidine and midazolam; then, in the first group, ketamine, in the second group, propofol and in the third group, isoflurane were used for induction of anaesthesia. The spinal reflexes were evaluated before injection, 15 min after medetomidine, 20 min after midazolam, and at 15, 30, 45 and 60 min after induction of anaesthesia., Results: Medetomidine did not reduce monosynaptic reflexes (patellar and cranial tibial reflexes) but increased them while it had no effect on the polysynaptic limb withdrawal reflexes. Midazolam had no effect on the spinal reflexes; Ketamine did not affect the patellar, cranial tibial and extensor carpi radialis reflexes, but reduced polysynaptic pain-related reflexes; and propofol and isoflurane abolished the all spinal reflexes., Conclusions: Medetomidine, midazolam and ketamine have no effect on reducing monosynaptic reflexes (patellar and cranial tibial reflexes) and may be used for neurological examination of restless animals in the clinic. Propofol and isoflurane eliminated all spinal reflex responses and are not suitable for neurological examinations., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The use of anaesthesia is a fundamental tool in the investigation of consciousness. Anesthesia procedures allow to investigate different states of consciousness from sedation to deep anesthesia within controlled scenarios. In this study we use information quantifiers to measure the complexity of electrocorticogram recordings in monkeys. We apply these metrics to compare different stages of general anesthesia for evaluating consciousness in several anesthesia protocols. We find that the complexity of brain activity can be used as a correlate of consciousness. For two of the anaesthetics used, propofol and medetomidine, we find that the anaesthetised state is accompanied by a reduction in the complexity of brain activity. On the other hand we observe that use of ketamine produces an increase in complexity measurements. We relate this observation with increase activity within certain brain regions associated with the ketamine used doses. Our measurements indicate that complexity of brain activity is a good indicator for a general evaluation of different levels of consciousness awareness, both in anesthetized and non anesthetizes states., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We unsuccessfully attempted to safely chemically immobilize a roan antelope (Hippotragus equinus) with a premixed combination of medetomidine (5 mg/mL) and ketamine (150 mg/mL) for injury treatment. This dose (0.066 mg/kg medetomidine and 1.96 mg/kg ketamine) produced poor quality of immobilization, probably exacerbated by stimulation before completing induction., (© Wildlife Disease Association 2022.)