Administration Of Atipamezole Research Articles

Cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry during continuous intravenous infusion of a combination solution of xylazine, butorphanol, and propofol in calves.

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10μg/kg/min xylazine, 1μg/kg/min butorphanol, 200μg/kg/min propofol) and 9mL/kg/h (G9; 15μg/kg/min xylazine, 1.5μg/kg/min butorphanol 300μg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2mg/kg) and propofol (2mg/kg), followed by a continuous infusion of XBP for 60min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves.

Pharmacological screening of a new valproic acid derivative using the pharmacoencephalography method in rats

Introduction. The naïve Bayes classifier combined with principal component analysis allows to distinguish the effects of antipsychotic agents effectively as well as evaluate their dose-dependency based on their impact on electroencephalogram parameters in rats. Further development of this method requires its validation as an instrument for the screening of new understudied molecules. Valproic acid derivatives appear to be a promising neuropharmacological group as they exhibit not only antiepileptic activity but also mood-stabilizing, antimigraine, neuroprotective and analgesic effects.Aim. This work was carried out to perform the pharmacological screening of a valproic acid aminoester (AVA) that exhibits antidote properties in case of poisoning with anticholinesterase agents.Materials and methods. The experiments were conducted in white outbred rats with chronically implanted electrocorticographic electrodes. AVA was administered at doses of 0,5, 5 and 30 mg/kg. The training set, used as a reference to determine the pharmacological effects of each dose of the investigated substance, included matrixes of effects of 7 drugs: the antiepileptic agent sodium valproate, the D2-dopamine receptor blocker haloperidol, the M-cholinergic receptor blocker tropicamide, the H1-histamine receptor blocker chloropyramine, the acetylcholinesterase inhibitor galantamine, the sedative dexmedetomidine, and the anxiolytic phenazepam.Results and discussion. AVA at the dose of 0,5 mg/kg showed effects similar to those of sodium valproate, while a tenfold dose increase led to the predominance of an atropine-like effect. When administered at the dose of 30 mg/kg, the compound exhibited dexmedetomidine-like action. The central M-anticholinergic effect of AVA was confirmed by an arecoline test in mice, in which the substance at a dose of 88 mg/kg completely abolished the onset of tremor. Dexmedetomidine-like action was cancelled by the administration of atipamezole in equimolar quantities, which may indicate the potential сapability of AVA to activate α2-adrenergic receptors at a high dose. The results of molecular docking suggest that this effect is related specifically to the original aminoester molecule and not to its presumable active metabolites.Сonclusion. The obtained results confirm the effectiveness of the naïve Bayes classifier as an instrument for the prediction of the pharmacological activity of compounds based on their impact on electroencephalogram parameters in rats. Identification of new pharmacological effects of understudied compounds may widen the potential range of their clinical application as well as reveal probable adverse effects.

Evaluation of the use of intranasal atipamezole to reverse the sedative effects of xylazine in dogs.

To assess the ability of intranasal atipamezole to reverse sedative effects of xylazine in dogs. Prospective proof-of-concept study. University research laboratory. Six healthy, staff-owned dogs. Dogs were sedated with 1.1mg/kg of xylazine intravenously. The sedation score of each dog was recorded every 5minutes until they achieved a sedation score of >13/21 for 3 readings. Once achieved, 0.3mg/kg of atipamezole was administered intranasally using a mucosal atomization device. Sedation scores continued to be recorded every 5minutes until successful reversal was achieved (<4/21). Average times to standing and normal wakefulness after administration of intranasal atipamezole were 6minutes, 30seconds and 7minutes, 20seconds, respectively. Intranasal atipamezole successfully reversed the sedation effects of xylazine. The findings of this study provide justification for future controlled prospective studies into the potential use of intranasal atipamezole in a variety of settings including exposure to xylazine in operational canines as well as bioavailability studies for optimal dosing.

Effects of atipamezole on selected physiologic parameters in cynomolgus macaques (Macaca fascicularis).

Atipamezole, an α-2 adrenergic receptor antagonist, reverses the α-2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters. Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure [systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure], body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection. While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min. This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed.

Comparison of sedation with dexmedetomidine/atipamezole administered subcutaneously at GV20 acupuncture point with usual routes of administration in dogs presented for orthopaedic radiographs.

To evaluate the efficacy of subcutaneous administration of dexmedetomidine/atipamezole at the Governing Vessel 20 (GV20) acupuncture point compared with other administration routes (intramuscular and intravenous) in dogs presented for orthopaedic radiographs. Prospective, randomised, blinded, controlled clinical study. Sixty-four client-owned dogs were randomly injected with 200 μg/m2 of dexmedetomidine intramuscular (lumbar muscles) (n=20), intravenous (n=23) or subcutaneous at the GV20 point (n=21). Following radiographs, dogs received 2000 μg/m2 of atipamezole intramuscular (n=31), or subcutaneous at the GV20 point (n=27). Degree and time to sedation and recovery were assessed using a sedation scale and a Dynamic and Interactive Visual Analog Scale (DIVAS). Clinical physiological variables and adverse events were used. Statistical linear mixed-effect models (analysis of variance) and Cox models were performed. Significance was set at P-value <0.05. Sedation was insufficient to perform orthopaedic radiographs in six dogs in the intramuscular group. The time to sedation was significantly longer, and sedation scale and DIVAS scores were significantly lower in the intramuscular group. The intravenous group had significantly higher sedation scale and DIVAS scores than the GV20 group. No significant differences were observed between the intramuscular and GV20 recovery groups, although the time effect was significantly more pronounced in the GV20 recovery group. Subcutaneous administration of dexmedetomidine and atipamezole at GV20 provided effective sedation and recovery in dogs undergoing orthopaedic radiographic studies. GV20 administration provided a clinically similar level of sedation to the intravenous route, and greater and faster sedation and similar recovery to intramuscular.

Atipamezole Reverses Cardiovascular Changes Induced by High-Dose Medetomidine in Cats Undergoing Sedation for Semen Collection.

This study aimed at describing the change in echocardiographic variables after high-dose medetomidine and the reversal with atipamezole in six cats undergoing sedation for semen collection. Further cardiac Troponin I (cTnI) concentration and the effect of repeated sedation were assessed. Echocardiography was performed before and 20 min after sedation with 0.1 mg/kg medetomidine intramuscularly (IM) for urethral catheterisation. Prior to epididymectomy, S-ketamine was administered intravenously. Twenty minutes after reversal with 0.5 mg/kg atipamezole IM, the third echocardiography was performed. Sedation with medetomidine and reversal with atipamezole was repeated on day 7, 14, 21 and 28. Heart rate (HR) and rhythm were monitored throughout all sedations. On day 0 and 28 cTnI concentrations were measured before and after the procedure. After normality testing, the values were compared over time. The administration of medetomidine led to a marked reduction in HR, cardiac output and ventricular systolic function and a significant increase in left ventricular dimensions. Rhythm abnormalities, such as ventricular premature complexes and idioventricular rhythm, could be observed. The administration of atipamezole completely reversed sedation and the changes in haemodynamic variables. No significant increase in cTnI concentrations could be detected, although two out of six cats showed values above the reference range.

A comparison of anesthesia induction by two different administration routes and doses of ketamine and medetomidine in red-eared sliders (Trachemys scripta elegans)

This study aimed to assess the efficiency of ketamine and medetomidine by two different doses and routes on anesthesia depth and cardiac stability in red-eared sliders. Each turtle was anesthetized two times, with seven days wash-out period. Induction of anesthesia consisted of a bolus combination of ketamine (10 mg/kg) and medetomidine (0.2 mg/kg) administered in the left brachial biceps in the intramuscular protocol, or a bolus combination of ketamine (20 mg/kg) and medetomidine (0.2 mg/kg) administered in subcarapacial sinus after clear blood presence confirmation in the intravenous protocol. Vital signs, reaction on the skin palpation, manual mouth opening for endotracheal intubation, palpebral and cloacal reflex, and the withdrawal reflex of the front and hind limbs were measured and recorded every 5 minutes for 60 minutes after anesthesia injection. Atipamezole (1 mg/kg) was administered in the right brachial biceps one hour after ketamine and medetomidine administration. Needle insertion and possible painful reactions to drug administration were also evaluated and recorded. Obtained data were analyzed for normality and paired t-tests, Wilcoxon, or McNamar tests were performed where appropriate. The values of P ≤ 0.05 were considered significant. A significantly less pronounced decrease in heart rate was observed with intravenous anesthesia protocol. Both protocols recorded complete anesthesia recovery 60 minutes after intramuscular atipamezole administration. A ketamine-medetomidine dose combination administered intravenously provides a more stable and consistent anesthetic plane in red-eared sliders than ketamine-medetomidine administered intramuscularly.

Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The combination between medetomidine, midazolam, and butorphanol (MMB) is commonly used in different animal models. The possibility of MMB combination to establish the MI model in rats did not study yet which is difficult because of severe respiratory depression and delayed recovery post-surgery, resulting in significant deaths. Atipamezole is used to counter the cardiopulmonary suppressive effect of MMB. The aim of the present study is to establish MI model in rats using a novel anesthetic combination between MMB and Atipamezole. Twenty-five Sprague Dawley (SD) rats were included. Rats were prepared for induction of the Myocardial infarction (MI) model through thoracotomy. Anesthesia was initially induced with a mixture of MMB (0.3/5.0/5.0 mg/kg/SC), respectively. After endotracheal intubation, rats were maintained with isoflurane 1% which gradually reduced after chest closing. MI was induced through the left anterior descending (LAD) artery ligation technique. Atipamezole was administered after finishing all surgical procedures at a dose rate of 1.0 mg/kg/SC. Cardiac function parameters were evaluated using ECG (before and after atipamezole administration) and transthoracic echocardiography (before and 1 month after MI induction) to confirm the successful model. The induction time, operation time, and recovery time were calculated. The success rate of the MI model was also calculated. MI was successfully established with the mentioned anesthetic protocol through the LAD ligation technique and confirmed through changes in ECG and echocardiographic parameters after MI. ECG data was improved after atipamezole administration through a significant increase in heart rate (HR), PR Interval, QRS Interval, and QT correction (QTc) and a significant reduction in RR Interval. Atipamezole enables rats to recover voluntary respiratory movement (VRM), wakefulness, movement, and posture within a very short time after administration. Echocardiographic ally, MI rats showed a significant decrease in the left ventricular wall thickness, EF, FS, and increased left ventricular diastolic and systolic internal diameter. In addition, induction time (3.440 ± 1.044), operation time (29.40 ± 3.663), partial recovery time (10.84 ± 3.313), and complete recovery time (12.36 ± 4.847) were relatively short. Moreover, the success rate of the anesthetic protocol was 100%, and all rats were maintained for 1 month after surgery with a survival rate of 88%. Our protocol produced a more easy anesthetic effect and time-saving procedures with a highly successful rate in MI rats. Subcutaneous injection of Atipamezole efficiently counters the cardiopulmonary side effect of MMB which is necessary for rapid recovery and subsequently enhancing the survival rate during the creation of the MI model in rats.

Dexmedetomidine Ameliorated Cognitive Dysfunction Induced by Intestinal Ischemia Reperfusion in Mice with Possible Relation to the Anti-inflammatory Effect Through the Locus Coeruleus Norepinephrine System

Cognitive impairment is a common central nervous system complication that occurs following surgery or organs damage outside the nervous system. Neuroinflammation plays a key role in the molecular mechanisms of cognitive impairment. Dexmedetomidine alleviates neuroinflammation and reduces cognitive dysfunction incidence; however, the mechanism by which dexmedetomidine alleviates cognitive dysfunction remains unclear. This study evaluated the effect of dexmedetomidine on attenuation of early cognitive impairment induced by intestinal ischemia–reperfusion in mice and examined whether the locus coeruleus norepinephrine (LCNE) system participates in the anti-inflammatory effect of dexmedetomidine. The superior mesenteric artery was clamped for 45 min to induce intestinal ischemia reperfusion injury. Dexmedetomidine alone or combined with DSP-4, a selective locus coeruleus noradrenergic neurotoxin, was used for pretreatment. Postoperative cognition was assessed using the Morris water maze. Serum and hippocampal levels of IL-1β, TNF-α, norepinephrine (NE), and malondialdehyde (MDA) were assessed by enzyme-linked immunosorbent assay. Immunofluorescence, immunohistochemistry, and hematoxylin and eosin staining were used to evaluate the expression of tyrosine hydroxylase (TH) in the locus coeruleus, hippocampal microglia, and intestinal injury. Pretreatment with dexmedetomidine alleviated intestinal injury and decreased the serum and hippocampal levels of NE, IL-1β, TNF-α, and MDA at 24 h after intestinal ischemia reperfusion, decreased TH-positive neurons in the locus coeruleus, and ameliorated cognitive impairment. Similarly, DSP-4 pre-treatment alleviated neuroinflammation and improved cognitive function. Furthermore, α2-adrenergic receptor antagonist atipamezole or yohimbine administration diminished the neuroprotective effects and improved cognitive function with dexmedetomidine. Therefore, dexmedetomidine attenuated early cognitive dysfunction induced by intestinal ischemia–reperfusion injury in mice, which may be related to its anti-inflammatory effects through the LCNE system.

Safety and Efficacy of Nalbuphine, Medetomidine, and Azaperone for Immobilizing Aoudad (Ammotragus lervia).

We evaluated the safety and efficacy of nalbuphine (40 mg/mL), plus medetomidine (10 mg/mL), plus azaperone (10 mg/mL) under the premixed label NalMed-A. From January to March 2020, 10 aoudad (Ammotragus lervia) were immobilized via dart-gun for seven separate sampling periods for a total of 45 recorded individual immobilization events. Induction and reversal times with NalMed-A were 5.53±2.61 min and (following atipamezole administration) 5.08±2.43 min while previous studies with alpha-2 agonist-ketamine combinations gave median and average induction times of 4.6 min and 11.2 min using medetomidine-ketamine and xylazine-ketamine, respectively. Overall, NalMed-A adequately immobilized aoudad, with 13% incidence of hyperthermia and 2.22% mortality when delivered via dart.

Effect of dexmedetomidine on cardiorespiratory regulation in spontaneously breathing adult rats.

PurposeWe examined the cardiorespiratory effect of dexmedetomidine, an α2- adrenoceptor/imidazoline 1 (I1) receptor agonist, in spontaneously breathing adult rats.MethodsMale rats (226−301 g, n = 49) under isoflurane anesthesia had their tail vein cannulated for drug administration and their tail artery cannulated for analysis of mean arterial pressure (MAP), pulse rate (PR), and arterial blood gases (PaO2, PaCO2, pH). After recovery, one set of rats received normal saline for control recording and was then divided into three experimental groups, two receiving dexmedetomidine (5 or 50 μg·kg−1) and one receiving normal saline (n = 7 per group). Another set of rats was divided into four groups receiving dexmedetomidine (50 μg·kg−1) followed 5 min later by 0.5 or 1 mg∙kg−1 atipamezole (selective α2-adrenoceptor antagonist) or efaroxan (α2-adrenoceptor/I1 receptor antagonist) (n = 6 or 8 per group). Recordings were performed 15 min after normal saline or dexmedetomidine administration.ResultsCompared with normal saline, dexmedetomidine (5 and 50 μg·kg−1) decreased respiratory frequency (fR, p = 0.04 and < 0.01, respectively), PR (both p < 0.01), and PaO2 (p = 0.04 and < 0.01), and increased tidal volume (both p = 0.049). Dexmedetomidine at 5 μg·kg−1 did not significantly change minute ventilation (V′E) (p = 0.87) or MAP (p = 0.24), whereas dexmedetomidine at 50 μg·kg−1 significantly decreased V′E (p = 0.03) and increased MAP (p < 0.01). Only dexmedetomidine at 50 μg·kg−1 increased PaCO2 (p < 0.01). Dexmedetomidine (5 and 50 μg·kg−1) significantly increased blood glucose (p < 0.01), and dexmedetomidine at 50 μg·kg−1 increased hemoglobin (p = 0.04). Supplemental atipamezole or efaroxan administration similarly prevented the 50 μg·kg−1 dexmedetomidine-related cardiorespiratory changes.Principal conclusionThese results suggest that dexmedetomidine-related hypoventilation and hypertension are observed simultaneously and occur predominantly through activation of α2-adrenoceptors, but not I1 receptors, in spontaneously breathing adult rats.

Partially Reversible Immobilization of Free-Ranging Huemul Deer (Hippocamelus bisulcus) with Medetomidine-Ketamine and Atipamezole.

A combination of intramuscular medetomidine and ketamine was used to immobilize 46 free-ranging huemul deer (Hippocamelus bisulcus) with a remote drug delivery system in Chilean Patagonia for tagging and biological sampling. Captures occurred in May-October of 2005-09 between fall and early spring in the southern hemisphere. An initial dose of 6.6 mg medetomidine and 185 mg ketamine was adjusted after 17 captures to 3 mg and 200 mg, respectively, in the 29 remaining deer. Mean±SD adjusted dose was 0.042±0.012 mg/kg of medetomidine and 2.929±0.427 mg/kg of ketamine. Inductions were calm and the mean±SD time to sternal recumbency was 10.3±10.1 min. Palpebral reflex and jaw tone were present during immobilization. Atipamezole at 5 mg/mg of medetomidine was administered intramuscularly for reversal after 55.3±18.8 min procedure time. Recoveries were smooth and mean±SD time to standing was 10.2±3.3. All immobilized animals were hypoxemic by pulse oximetry (blood oxygen saturation approximately 81%). Three animals that developed apnea were resuscitated through chest compression and atipamezole administration, another regurgitated during capture, and all developed tachypnea. The combination of medetomidine-ketamine and atipamezole can be used for partially reversible immobilization of huemul, but supplemental oxygen should be administered, blood oxygenation should be monitored, and equipment for intubation and manual ventilation should be available.

Cardiopulmonary (No Ventilation) and Anesthetic Effects of Dexmedetomidine-Tiletamine in Dogs.

The aim of the present study was to evaluate the anesthetic and cardiopulmonary effects of dexmedetomidine in combination with tiletamine (without zolazepam) as a general anesthetic. The study was divided into two phases. In Phase 1, 18 adult healthy mixed-breed dogs were randomly allocated into three groups: Group TD8 (4.5 mg kg−1 tiletamine and 8 μg kg−1 dexmedetomidine), Group TD10 (4.5 mg kg−1 tiletamine and 10 μg kg−1 dexmedetomidine), or Group TD12 (4.5 mg kg−1 tiletamine and 12 μg kg−1 dexmedetomidine). After drug administration, the heart rate (HR), respiratory rate (f R), mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), peripheral hemoglobin oxygen saturation (SpO2), behavioral score, quality of induction and recovery, extent of ataxia, the time taken for induction, and the duration of anesthesia were recorded. The recovery time and quality were recorded after administration of atipamezole (50 μg kg−1) after 60 min. In phase 2, the feasibility of combining dexmedetomidine (10 μg kg−1) and tiletamine (4.5 mg kg−1) as general anesthetics for orchiectomy was evaluated in dogs (n = 6). HR, f R, MAP, SAP, DAP, temperature, SpO2, behavioral scores, and adverse reactions were recorded during each surgical procedure. In phase 1, the dogs were anesthetized for 5 min after administration of drugs and achieved a maximum behavioral score in TD10 and TD12 after 10 min. Although HR, MAP, SAP, DAP, and NIBP decreased in all three groups, they still maintained within the normal range. In phase 2, orchiectomy was completed smoothly in all dogs with little fluctuation in the physiological variables. We found that a combination of tiletamine (4.5 mg kg−1) and dexmedetomidine (10 μg kg−1) intramuscularly induced moderate anesthesia in dogs and could be utilized for short-term anesthesia and minor surgery.

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

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

FIELD ANESTHESIA OF FREE-RANGING NUTRIAS (MYOCASTOR COYPUS) FOR SURGICAL REPRODUCTION CONTROL.

The nutria (Myocastor coypus), a rodent native to South America, has been introduced and has established feral populations at numerous locations in North America, Europe, and Asia. As such, the nutria is subject to research and management programs, including investigation of surgical fertility-control techniques. We evaluated the efficacy of a mixture of ketamine and medetomidine, with additional use of isoflurane and reversal with atipamezole, to provide safe, reliable anesthesia for surgical procedures under field conditions. We anesthetized 40 free-ranging nutrias between December 2018 and March 2019, in Turin, Italy, to perform surgical reproduction control techniques. We administered a ketamine and medetomidine mixture (6 mg/kg and 140 µg/kg, respectively) after trapping the animals and weighing them in the cage traps. After induction, we reweighed the rodents and performed a brief clinical examination. The times of loss of palpebral and pedal reflexes were noted. After induction of anesthesia, heart rate, respiratory rate, and percentage of oxygen saturation were monitored and recorded. Isoflurane was delivered through a face mask to 27 nutrias (70%) to maintain an adequate depth of anesthesia. Upon completion of surgery and other procedures, atipamezole was administered to the animals at doses 2.5 higher than those of medetomidine (actual dose: 366±31 µg/kg). Induction times were short (3±2 min), with the animals completely immobilized. The heart rate and respiratory rate both decreased. After administration of atipamezole, recoveries were smooth and complete. There were two deaths after higher doses of atipamezole and longer surgeries. Carprofen (4 mg/kg) was administered subcutaneously for its analgesic effects. The animals were released at the end of all the procedures. Overall, the medetomidine and ketamine mixture, with supplemental isoflurane in most instances, provided a reliable anesthesia in free-ranging nutrias, adequate for performing surgical procedures under field conditions.

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

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

Anesthetic Management of a Brown Bear (Ursus arctos) Captive Undergoing Incisional Biopsy of a Skin Nodule

Background: The brown bear (Ursus arctos) is considered one of the largest terrestrial carnivores, native from temperate forest regions of North America, Europe and Asia. In Brazil, they are founded in captivity and their safe capture and immobilization are obtained with one effective anesthesia for management and surgical and diagnostic procedures. Some anesthetic protocols are described for these purposes, however, there is a lack for data on the anesthetic and adverse effects they have on bears when used. The aim of this case is to report the use and effects of the association of dexmedetomidine with tiletamine and zolazepam in the chemical containment of a captive adult brown bear.Case: A 33-year-old female brown bear, weighing 100 kg, belonging to the Zoobotanic Park of Teresina, Piauí, Brazil, was chemically immobilized for an incisional biopsy of a cutaneous nodule with 1.0 cm diameter in the right face region. The anesthetic protocol included 6 μg/kg of dexmedetomidine associated with 3 mg/kg of tiletamine and zolazepam, administered intramuscularly by dart into the gluteal region of the right pelvic limb. The animal showed moderate ataxia at 5 min and assumed sternal decubitus 7 min after anesthetic administration. The bear's degree of sedation was considered adequate and safe to perform the biopsy at 10 min after administration. Heart rate (47 ± 3 bpm), respiratory rate (17 ± 2 mpm) and rectal temperature (38.7 ± 0.1ºC) were monitored. The bear remained immobile and unconscious throughout the procedure, with intense muscle relaxation, bilateral eyeball rotation, absent lateral palpebral reflex and mild medial reflex and without nystagmus. Complementary sedative doses were not necessary. At the beginning of anesthetic recovery, the bear received 6 µg/kg of atipamezole, intramuscularly. After 25 min of administration of atipamezole, the animal showed signs of recovery in the level of consciousness and reactivity to external stimuli, and assumed the quadrupedal position at 60 min after reverser application.Discussion: Even in captivity, the bears behavior is unpredictable and attack can occur, causing trauma or death to people. For this, the chemical immobilization is important to keep safety of everyone. This procedure was performed using blowgun-assisted darts thrown by a staff member who had experience in using this method, who darted accurately and effectively. The latency time observed after administration of the anesthetic protocol used is similar to reported in other studies with bears that also received intramuscular dexmedetomidine and tiletamine and zolazepam and showed intense muscle relaxation and immobility. The doses used contributed to the absence of bradycardia and hypoventilation and, performing the procedure in the morning, when the temperature is milder in the city, minimized the chance of hyperthermia and thermal stress in the animal, not requiring body cooling. The use of dexmedetomidine in chemical containment protocols for short and minimally invasive procedures allows the subsequent use of its antagonist, atipamezole, contributing to a shorter recovery time, return of the animal’s degree of consciousness and lower incidence of ataxia after assuming a quadrupedal position. The anesthetic protocol used was considered efficient, providing a quick and gentle chemical containment, adequate anesthetic plan and good anesthetic recovery in an adult brown bear from captivity.Keywords:atipamezole, dexmedetomidine, wildlife.Título: Manejo anestésico de um urso pardo (Ursus arctos) cativo submetido a biópsia incisional de nódulo cutâneoDescritores: atipamezole, dexmedetomidine, animais selvagens.

Effect of Different Doses of Atipamezole on Reversal of Medetomidine-Induced Tear-Flow Decrease in Rats.

It has been reported that α2-adrenoceptor agonists such as medetomidine decrease tear flow in many species, including rats. Few studies have investigated the involvement of α2-adrenoceptor in decreased tear flow; the issue has not been illustrated sufficiently. Therefore, we aimed to investigate the effect of different doses of atipamezole on the reversal of medetomidine-induced tear-flow decrease to reveal the specific involvement of α2-adrenoceptor. Treatment with 400, 800, or 1600 µg/kg atipamezole (or saline as the control) was intramuscularly administered to rats 15 min following intramuscular administration of 200 µg/kg medetomidine. After medetomidine administration, tear flow was measured using a phenol red thread test (PRTT). PRTT values decreased significantly after 200 µg/kg medetomidine administration. The PRTT values after 800 (optimal dose to reverse) and 1600 µg/kg atipamezole administration reached baseline, but never exceeded it significantly. Treatment with 400 µg/kg atipamezole also reversed the decrease in PRTT value but the PRTT remained lower than baseline. The optimal dose and the higher dose of atipamezole fully reversed the medetomidine-induced decrease in tear flow to the baseline level in rats, while the lower dose of atipamezole partially recovered tear flow.

THE EFFECTS OF PROCEDURE DURATION AND ATIPAMEZOLE ADMINISTRATION ON HYPERKALEMIA IN TIGERS (PANTHERA TIGRIS) AND LIONS (PANTHERA LEO) ANESTHETIZED WITH α-2 AGONISTS.

A retrospective analysis of 40 extended (>2 hr) anesthetic events in eight lions (Panthera leo) and 32 tigers (Panthera tigris) was performed using a hierarchical linear growth curve model to assess the effects of anesthetic time, α-2 adrenoreceptor agonist dosages, administration of atipamezole, and biochemical parameters on rising plasma K+ concentrations. Hyperkalemia was first noted at a mean time of 187 min (range: 131-226 min), with time under anesthesia as a statistically significant predictor of K+ concentration (P < 0.0001). A significant two-way interaction between time and atipamezole administration (P = 0.0082) for rising K+ concentrations was demonstrated, indicating that administration of atipamezole can mitigate the rise in K+ concentrations. Administration of atipamezole beyond 150 min of anesthetic time was less effective in reducing K+ concentrations than if administered earlier. Electrocardiographic abnormalities were noted in eight animals, including three hyperkalemic individuals. Lions developed significantly greater plasma K+ concentrations than tigers (P = 0.0009) during anesthesia. No biochemical parameter was identified as a significant indicator of which individuals will develop hyperkalemia. Clinicians anesthetizing any large nondomestic felid should monitor electrolytes regularly during anesthetic events; consider early, partial- to full-dose reversal of α-2 agonists; and be prepared to correct potentially life-threatening electrocardiographic abnormalities resulting from hyperkalemia.

EVALUATION OF TWO DOSES OF BUTORPHANOL-MEDETOMIDINE-MIDAZOLAM FOR THE IMMOBILIZATION OF WILD VERSUS CAPTIVE BLACK-FOOTED CATS (FELIS NIGRIPES).

The efficacy, safety, physiologic effects, and reversibility of butorphanol-medetomidine-midazolam (BMM) immobilization were evaluated in black-footed cats (Felis nigripes) and compared between captive and wild animals. Nine captive and 14 wild black-footed cats were hand injected into an accessible hind limb muscle group with the BMM combination. The captive cats (captive group) received a lower dose of the combination (butorphanol, 0.25 ± 0.03 mg/kg; medetomidine, 0.06 ± 0.01 mg/kg; midazolam, 0.13 ± 0.02 mg/kg), whereas the wild cats received a higher dose (butorphanol, 0.53 ± 0.11 mg/kg, medetomidine, 0.13 ± 0.03 mg/kg, midazolam, 0.27 ± 0.05 mg/kg). Two capture methods were required to restrain the wild cats; previously collared cats were tracked and excavated out of their burrows during daylight hours (excavated group), whereas uncollared cats were randomly located using spotlights and pursued by a vehicle at night (pursued group). Inductions were rapid and no spontaneous arousals occurred. Mean arterial blood pressure in all cats was within normal limits for domestic cats. Initial rectal temperatures varied greatly among the groups, but decreased in all groups as the immobilization progressed. In the pursued animals, heart rates and respiratory rates were initially elevated. All cats had moderate hypoxemia, hypocapnia, and metabolic acidosis. Intramuscular administration of naltrexone, atipamezole, and flumazenil resulted in rapid, uncomplicated recoveries. BMM is thus a safe, effective immobilizing drug combination for both captive and wild black-footed cats, but higher doses are required in wild animals. The capture methods exerted a greater influence on the physiology of the immobilized animals than did the doses of the drugs used. Although this drug combination can be used safely to immobilize black-footed cats, supplemental oxygen should always be available for use, especially in pursued animals due to hypoxia.