Dissociative anaesthesia in dogs and cats with use of tiletamine and zolazepam combination. What we already know about it.

This article is an attempt to gather available literature regarding the use of tiletamine and zolazepam combination in anaesthesia in dogs and cats. Although tiletamine and zolazepam mixture has been known in veterinary practice for a long time, the increased interest in these drugs has been observed only recently. Tiletamine, similarly to ketamine, is a drug which belongs to the phencyclidine group. Ketamine has considerable popularity in veterinary practice what suggests that other dissociative anaesthetic drugs, such as tiletamine, could also prove effective in cats' and dogs' anaesthetic care. Zolazepam is a widely used benzodiazepine known for its muscle relaxant and anticonvulsant properties. While conducting an electronic search for articles regarding the use of tiletamine-zolazepam combination in dogs and cats, it has been discovered that the literature on the subject (tiletamine-zolazepam combination in dogs and cats) is quite scarce. Very few articles were published after 2010. Databases used were: Google Scholar, Scopus, PubMed. Most of the adverse effects, including those affecting the cardiovascular, nervous, and respiratory systems, were strictly dose-dependent. Tiletamine-zolazepam combination can be safely used as a premedication agent, induction for inhalation anaesthesia, or an independent anaesthetic for short procedures. Contraindications using tiletamine-zolazepam mixture include central nervous system (CNS) diseases such as epilepsy and seizures, head trauma, penetrative eye trauma, cardiovascular abnormalities (hypertrophy cardiomyopathy in cats, arrythmias or conditions where increase of heart rate is inadvisable), hyperthyroidism, pancreatic deficiencies or kidney failure.

PHYSIOLOGICAL AND ANESTHETIC EFFECTS OF HAND INJECTION VERSUS DARTING TO INDUCE ANESTHESIA IN CHIMPANZEES (PAN TROGLODYTES).

Great ape anesthesia is reported to carry a significant risk. Therefore, techniques aiming to reduce stress and increase welfare, such as hand injection of anesthesia induction agents, have received considerable attention in zoo, laboratory, and captive wildlife environments. However, there is little evidence to support the superiority of such techniques. To investigate this issue, anesthesia records of healthy zoo-housed chimpanzees (Pan troglodytes) between 2012 and 2017 in which the animal was either darted or hand injected were analyzed (n = 50). Sex, age, induction, muscle relaxation, and overall anesthesia quality as well as recovery ratings, heart rate, systolic, mean and diastolic blood pressure, respiratory rate, end-tidal CO2, oxygen saturation (SpO2), and body temperature were analyzed. Chimpanzees that were darted showed statistically significantly higher heart rate, SpO2, and body temperature than those that were hand injected. It was found that darted chimpanzees were also significantly more likely to have poorer perianesthetic muscle relaxation and overall anesthesia rating scores. This study provides further evidence that the use of hand injection can reduce factors associated with stress and improve the quality of chimpanzee anesthesia.

EVALUATION OF A PARTIALLY REVERSIBLE IMMOBILIZATION PROTOCOL USING MEDETOMIDINE, BUTORPHANOL, ZOLAZEPAM-TILETAMINE, AND KETAMINE IN FREE-RANGING WARTHOGS (PHACOCHOERUS AFRICANUS) IN KRUGER NATIONAL PARK, SOUTH AFRICA.

Twenty-one free-ranging warthogs (Phacochoerus africanus) in the Kruger National Park, South Africa, were immobilized with a combination of medetomidine (0.07 ± 0.01 mg/kg), butorphanol (0.26 ± 0.04 mg/kg), tiletamine-zolazepam (0.69 ± 0.15 mg/kg), and ketamine (1.43 ± 0.21 mg/kg) administered intramuscularly by dart. Induction, immobilization, and recovery characteristics were evaluated using a standardized scoring system. In the immobilized warthogs, physiological variables were measured every 5 min and arterial blood gases were analyzed at 15-min intervals. At 45 min after initial drug administration, atipamezole (0.34 ± 0.050 mg/kg) and naltrexone (0.53 ± 0.079 mg/kg) were administered intravenously. Overall, induction quality after darting was scored as excellent and the mean time to safe handling was 5.9 ± 2.0 min. Based on muscle relaxation, and loss of palpebral and pedal reflexes, most subjects (17 out of 21) reached a plane of surgical anesthesia by 10 and 15 min; 20 out of 21 warthogs were in this plane for the duration of the monitoring period. In the immobilized warthogs the overall mean heart rate was 65 ± 15.3 beats per minute, mean respiratory rate was 14.7 ± 5.6 breaths per minute, and the mean rectal temperature was 37.9 ± 1.4°C during the 40 min. Arterial blood gas results showed hypoxemia (mean PaO2 62.1 ± 16.2 mmHg), hypercapnia (mean PaCO2 47.1 ± 5.1 mmHg), and acidemia (mean pH = 7.36 ± 0.04). Values for PaO2 and pH improved over the immobilization period. After antagonist administration, overall recovery quality from immobilization was scored as good, with animals standing at a mean time of 7.3 ± 4.9 min. The drug combination proved to be effective in the immobilization of free-ranging warthogs with rapid induction, good anesthesia, and limited cardiorespiratory changes. This anesthetic protocol produces effective, safe, and partially reversible immobilization in warthogs.

Use of nalbuphine as a substitute for butorphanol in combination with dexmedetomidine and tiletamine/zolazepam: a randomized non-inferiority trial.

OBJECTIVES: The goal of this study was to determine whether a drug combination using nalbuphine with dexmedetomidine and tiletamine/zolazepam is non-inferior to one that uses butorphanol. METHODS: All healthy cats presenting solely for gonadectomy to two trap-neuter-return mobile clinic days were randomly assigned to induction with a combination of tiletamine/zolazepam 3 mg/kg, dexmedetomidine 7.5 µg/kg and either butorphanol or nalbuphine at 0.15 mg/kg. All participants were blinded to the identity of the combinations. The primary endpoint was clinician satisfaction, comprised of the mean of four satisfaction ratings on a 7-point Likert scale (highly dissatisfied through to highly satisfied) recorded for induction, maintenance of anesthesia, surgery and recovery. Exploratory endpoints included each individual score, number of injections, duration of induction, duration of recovery and need for reversal agent. To assess non-inferiority for the primary endpoint and individual scores, the difference and 95% confidence intervals (CIs) of the difference between the mean clinical scores for the nalbuphine and butorphanol-based combinations were calculated and compared with a prespecified non-inferiority margin of 20% (1.4 points). RESULTS: Seventy-two cats were enrolled, 36 in each group. The mean ± SD composite score for the combination with nalbuphine was 6.06 ± 0.59 (95% CI 5.86-6.25) points, while the combination with butorphanol was 6.22 ± 0.62 (95% CI 6.01-6.43). The difference between mean scores was 0.17 (-0.12 to 0.45), which did not exceed the prespecified boundary of 1.4, establishing the non-inferiority of nalbuphine. No individual clinical score for nalbuphine was inferior to butorphanol, and there were no significant differences for any secondary endpoints. CONCLUSIONS AND RELEVANCE: The clinical experience of the nalbuphine-based combination was non-inferior to the butorphanol-based combination. Nalbuphine is an effective substitute for butorphanol, providing another option if butorphanol is unavailable due to shortage, controlled status or cost, without requiring a change in anesthetic workflow.

Sedative and physiologic effects of tiletamine-zolazepam following buccal administration in cats.

OBJECTIVES: The aim of this study was to describe the sedative and some physiological effects of tiletamine-zolazepam following buccal administration (BA) in cats. METHODS: Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine-zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. RESULTS: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. CONCLUSIONS AND RELEVANCE: BA of tiletamine-zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.

FACTORS AFFECTING TEAR PRODUCTION AND INTRAOCULAR PRESSURE IN ANESTHETIZED CHIMPANZEES (PAN TROGLODYTES).

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (Pan troglodytes) were anesthetized using either tiletamine-zolazepam (TZ; 2 mg/kg) combined with medetomidine (TZM; 0.02 mg/kg), or, TZ alone (6mg/kg). Tear production was lower (P = 0.03) with TZM (5.63 ± 6.22 mm/min; n = 16) than with TZ (11.13 ± 4.63 mm/min; n = 8). Mean IOP, measured using rebound tonometry in an upright body position (n = 8) was 18.74 ± 3.01 mm Hg, with no differences between right and left eyes. However, positioning chimpanzees in left lateral recumbency (n = 27) resulted in higher IOP in the dependent (left) eye (24.77 ± 4.49 mm Hg) compared to the nondependent (right) eye (22.27 ± 4.65 mm Hg) of the same animal (P < 0.0001). These data indicate medetomidine anesthesia markedly lowers tear production in chimpanzees, and that body position should be taken into consideration when performing rebound tonometry.

Comparison between total intravenous anesthesia with propofol and intermittent bolus of tiletamine-zolazepam in capuchin monkey (Sapajus apella) / Comparação entre anestesia total intravenosa com propofol e bolus intermitente de tiletamina-zolazepam em macaco-prego (Sapajus apella)

Dissociative anesthesia results in stressful and long recovery periods in monkeys and use of injectable anesthetics in medical research has to be refined. Propofol has promoted more pleasure wake up from anesthesia. The objectives of this study were to investigate the use of intravenous anesthetic propofol, establishing the required infusion rate to maintain surgical anesthetic level and comparing it to tiletamine-zolazepam anesthesia in Sapajus apella. Eight healthy capuchin monkeys, premedicated with midazolam and meperidine, were anesthetized with propofol (PRO) or tiletamine-zolazepam (TZ) during 60 minutes. Propofol was infused continually and rate was titrated to effect and tiletamine-zolazepam was given at 5mg/kg IV bolus initially and repeated at 2.5mg/kg IV bolus as required. Cardiopulmonary parameters, arterial blood gases, cortisol, lactate and quality and times to recovery were determined. Recovery quality was superior in PRO. Ventral recumbency (PRO = 43.0±21.4 vs TZ = 219.3±139.7 min) and normal ambulation (PRO = 93±27.1 vs TZ = 493.7±47.8 min) were faster in PRO (p<0.05). Cardiopulmonary effects did not have marked differences between groups. Median for induction doses of propofol was 5.9mg/kg, varying from 4.7 to 6.7mg/kg, Mean infusion rate was 0.37±0.11mg/kg/min, varying during the one-hour period. In TZ, two animals required three and five extra doses. Compared to tiletamine-zolazepam, minor post-anesthetic adverse events should be expected with propofol anesthesia due to the faster and superior anesthetic recovery. (AU)

A anestesia dissociativa em primatas resulta em recuperação anestésica lenta e estressante, e, portanto, o uso de anestesia injetável em pesquisas médicas precisa ser refinado. Por outro lado, o propofol promove recuperação mais suave. Os objetivos desse estudo foram investigar o uso do anestésico intravenoso propofol, estabelecer a taxa de infusão contínua necessária para manter anestesia cirúrgica, e comparar tal técnica com a dissociativa tiletamina-zolazepam em Sapajus apella. Oito macacos-prego saudáveis foram pré-medicados com midazolam e meperidina, e posteriormente anestesiados com propofol (PRO) ou tiletamina-zolazepam (TZ) durante 60 minutos. O propofol foi administrado em infusão contínua, e a taxa foi titulada ao efeito, já a tiletamina-zolazepam foi administrada em 5mg/kg IV como bolus inicial, e repiques de 2,5mg/kg IV conforme necessário. Os parâmetros cardiopulmonares, hemogasometria arterial, cortisol, e lactato, além da qualidade e duração da recuperação anestésica foram determinados. A qualidade da recuperação anestésica foi superior em PRO. O tempo para atingir decúbito ventral (PRO = 43,0±21,4 vs TZ = 219,3±139,7 min) e ambulação normal (PRO = 93±27,1 vs TZ = 493,7±47,8 min) foram mais rápidos em PRO (p<0,05). As variáveis cardiopulmonares não diferiram entre os grupos. A mediana para dose de indução com propofol foi de 5,9mg/kg, variando de 4,7 a 6,7mg/kg. A taxa de infusão contínua média de propofol foi de 0,37±0,11mg/kg/min, variando ao longo dos 60 minutos. Em TZ, dois animais necessitaram de três e cinco repiques. Comparado à tiletamina-zolazepam, menos efeitos adversos pós-anestésicos devem ser esperados com o propofol, devido à recuperação mais suave e rápida.(AU)

Effects of intravenous administration of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for induction of anesthesia on cardiorespiratory and metabolic variables in healthy dogs before and during anesthesia maintained with isoflurane.

OBJECTIVE To compare effects of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for anesthetic induction on cardiorespiratory and acid-base variables before and during isoflurane-maintained anesthesia in healthy dogs. ANIMALS 6 dogs. PROCEDURES Dogs were anesthetized with sevoflurane and instrumented. After dogs recovered from anesthesia, baseline values for cardiorespiratory variables and cardiac output were determined, and arterial and mixed-venous blood samples were obtained. Tiletamine-zolazepam (5 mg/kg), alfaxalone (4 mg/kg), propofol (6 mg/kg), or ketamine-diazepam (7 and 0.3 mg/kg) was administered IV in 25% increments to enable intubation. After induction (M0) and at 10, 20, 40, and 60 minutes of a light anesthetic plane maintained with isoflurane, measurements and sample collections were repeated. Cardiorespiratory and acid-base variables were compared with a repeated-measures ANOVA and post hoc t test and between time points with a pairwise Tukey test. RESULTS Mean ± SD intubation doses were 3.8 ± 0.8 mg/kg for tiletamine-zolazepam, 2.8 ± 0.3 mg/kg for alfaxalone, 6.1 ± 0.9 mg/kg and 0.26 ± 0.04 mg/kg for ketamine-diazepam, and 5.4 ± 1.1 mg/kg for propofol. Anesthetic depth was similar among regimens. At M0, heart rate increased by 94.9%, 74.7%, and 54.3% for tiletamine-zolazepam, ketamine-diazepam, and alfaxalone, respectively. Tiletamine-zolazepam caused higher oxygen delivery than propofol. Postinduction apnea occurred in 3 dogs when receiving alfaxalone. Acid-base variables remained within reference limits. CONCLUSIONS AND CLINICAL RELEVANCE In healthy dogs in which a light plane of anesthesia was maintained with isoflurane, cardiovascular and metabolic effects after induction with tiletamine-zolazepam were comparable to those after induction with alfaxalone and ketamine-diazepam.

Anesthesia effects on the low frequency blood flow oscillations in mouse skin.

BACKGROUND: When laboratory animals are used one needs to anesthetize them before recording. However, the influence of anesthesia on animal blood flow oscillations has not been studied. The effects of two ways of anesthesia, zoletil-xylazine, and zoletil-nitrous oxide mixtures, on mouse skin perfusion using laser Doppler flowmetry (LDF) technique were studied. METHODS: BALB/c mice were used. LDF probe was placed on the ventral surface of the left hind paw. Spectral analysis of LDF signals was performed with continuous adaptive wavelet transform to identify and describe peripheral blood flow oscillations in mouse skin. RESULTS: Low-frequency oscillation interval boundaries (myogenic, neurogenic, and endothelial) for mice were shown to coincide with the boundaries determined for human and rats, that demonstrate their independence from the body size. Zoletil-xylazine anesthesia significantly decreased neurogenic and endothelial oscillation amplitudes by 29% and 50% respectively and increased the amplitude of cardiac oscillations by 23% compared to zoletyl-nitrous oxide anesthesia. There were no significant changes of the amplitudes of myogenic and respiratory oscillations with zoletil-nitrous oxide anesthesia compared to the zoletil-xylazine mixture. CONCLUSION: We suggest that the different influence of anesthesia modes on the amplitudes of skin blood flow oscillations is associated with sympathetic activity suppressed by zoletil-xylazine anesthesia.

A fixed moderate-dose combination of tiletamine+zolazepam outperforms midazolam in induction of short-term immobilization of ball pythons (Python regius).

Laboratory animals are commonly anesthetized to prevent pain and distress and to provide safe handling. Anesthesia procedures are well-developed for common laboratory mammals, but not as well established in reptiles. We assessed the performance of intramuscularly injected tiletamine (dissociative anesthetic) and zolazepam (benzodiazepine sedative) in fixed combination (2 mg/kg and 3 mg/kg) in comparison to 2 mg/kg of midazolam (benzodiazepine sedative) in ball pythons (Python regius). We measured heart and respiratory rates and quantified induction parameters (i.e., time to loss of righting reflex, time to loss of withdrawal reflex) and recovery parameters (i.e., time to regain righting reflex, withdrawal reflex, normal behavior). Mild decreases in heart and respiratory rates (median decrease of <10 beats per minute and <5 breaths per minute) were observed for most time points among all three anesthetic dose groups. No statistically significant difference between the median time to loss of righting reflex was observed among animals of any group (p = 0.783). However, the withdrawal reflex was lost in all snakes receiving 3mg/kg of tiletamine+zolazepam but not in all animals of the other two groups (p = 0.0004). In addition, the time for animals to regain the righting reflex and resume normal behavior was longer in the drug combination dose groups compared to the midazolam group (p = 0.0055). Our results indicate that midazolam is an adequate sedative for ball pythons but does not suffice to achieve reliable immobilization or anesthesia, whereas tiletamine+zolazepam achieves short-term anesthesia in a dose-dependent manner.

Inductive effect of Zoletil on cystathionine ß-synthase expression in the rat brain.

Zoletil is an anesthetic and immobilizing drug that has been used in the veterinary field for over 50 years; however, the effect of Zoletil, or its constituents, on brain cystathionine ß-synthase (CBS) remains unknown. Here, we aimed to determine the effect of Zoletil on rat brain CBS by administering a single intraperitoneal injection of the drug and examining hydrogen sulfide (H2S) and CBS levels in the cerebral cortex, hippocampus, and thalamus following three distinct behavioral phenotypes associated with the sedation procedure (e.g., loss of the righting reflex, return of the righting reflex, and return of walking). Zoletil administration resulted in significant decreases of endogenous H2S in the cerebral cortex, hippocampus, and thalamus, and H2S was observed to increase in these brain regions when rats recovered from the anesthesia. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry revealed that CBS expression in the cerebral cortex and hippocampus exhibited the same trend as endogenous H2S following Zoletil administration. In summary, our results demonstrated that Zoletil induced the expression of CBS which could exert region-specific regulation of H2S in the cerebral cortex and hippocampus.

Chemical immobilization of free-ranging and captive Sunda clouded leopards (Neofelis diardi) with two anesthetic protocols: medetomidine-ketamine and tiletamine-zolazepam.

There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.

Prediction of arterial blood gas values from venous blood gas values in Asiatic black bears (Ursus thibetanus) anesthetized with intramuscular medetomidine and zolazepam-tiletamine.

The objective of this study was to measure differences between arterial and venous blood gas parameters and to evaluate whether arterial blood gas values can be estimated from venous blood in Asiatic black bears (ABBs). Twelve healthy captive ABBs (8 males and 4 females; 8-16 years; 76.8-220 kg) were included in this study. The bears were immobilized with medetomidine and zolazepam-tiletamine using a dart gun. Arterial and venous samples were collected simultaneously at 5 and 35 min after recumbency (5- and 35-min points). Partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), pH, bicarbonate (HCO3-), total carbon dioxide (TCO2), oxygen saturation of hemoglobin (SO2) and base excess (BEecf) were analyzed using a portable blood gas analyzer. There was no marked difference in measured and calculated variables over time in both venous and arterial blood except for PO2. However, arterial PO2, SO2 and pH were significantly higher and arterial PCO2, TCO2 and HCO3- were lower than those of venous samples at both 5- and 35-min points. In the regression analysis to estimate arterial values from venous values, PCO2, TCO2, HCO3-, BEecf and pH significantly showed over 0.45 in coefficient of determination value (R2), and there were little differences between actual and predicted arterial values. Although there were limits in venous gas values replaced those of arterial blood, if we could not get the arterial samples, the regression formulas for arterial values from venous blood in this study would be useful clinically, except for PO2 and SO2.

HEART RATE AND INDIRECT BLOOD PRESSURE RESPONSES TO FOUR DIFFERENT FIELD ANESTHETIC PROTOCOLS IN WILD-BORN CAPTIVE CHIMPANZEES (PAN TROGLODYTES).

Limited data are available on hemodynamic responses to anesthetic protocols in wild-born chimpanzees (Pan troglodytes). Accordingly, this study characterized the heart rate (HR) and blood pressure responses to four anesthetic protocols in 176 clinically healthy, wild-born chimpanzees undergoing routine health assessments. Animals were anesthetized with medetomidine-ketamine (MK) (n = 101), tiletamine-zolazepam (TZ) (n = 30), tiletamine-zolazepam-medetomidine (TZM) (n = 24), or medetomidine-ketamine (maintained with isoflurane) (MKI) (n = 21). During each procedure, HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were regularly recorded. Data were grouped according to anesthetic protocol, and mean HR, SBP, and DBP were calculated. Differences between mean HR, SBP, and DBP for each anesthetic protocol were assessed using the Kruskall-Wallis test and a Dunn multiple comparisons post hoc analysis. To assess the hemodynamic time course response to each anesthetic protocol, group mean data (±95% confidence interval [CI]) were plotted against time postanesthetic induction. Mean HR (beats/min [CI]) was significantly higher in TZ (86 [80-92]) compared to MKI (69 [61-78]) and MK (62 [60-64]) and in TZM (73 [68-78]) compared to MK. The average SBP and DBP values (mm Hg [CI]) were significantly higher in MK (130 [126-134] and 94 [91-97]) compared to TZ (104 [96-112] and 58 [53-93]) and MKI (113 [103-123] and 78 [69-87]) and in TZM (128 [120-135] and 88 [83-93]) compared to TZ. Time course data were markedly different between protocols, with MKI showing the greatest decline over time. Both the anesthetic protocol adopted and the timing of measurement after injection influence hemodynamic recordings in wild-born chimpanzees and need to be considered when monitoring or assessing cardiovascular health.

Development of a sedation protocol using orally administered tiletamine-zolazepam-acepromazine in free-roaming dogs.

OBJECTIVE: To investigate the sedative effects in dogs of tiletamine-zolazepam-acepromazine (TZA) or ketamine-flunitrazepam (KF) administered orally and to evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs. STUDY DESIGN: Experimental study followed by a field trial. ANIMALS: Six research dogs and 27 free-roaming dogs. METHODS: In a pilot study, six research dogs were administered liquid TZA (20 mg kg-1 tiletamine-zolazepam and 2 mg kg-1 acepromazine) or liquid KF (50 mg kg-1 ketamine and 2 mg kg-1 flunitrazepam) orally: treatment 1, forcefully squirting liquid medication into the mouth; treatment 2, encapsulating liquid medication for administration in canned food; treatment 3, administering liquid medication mixed with gravy. Sedation was scored. A follow-up field trial attempted capture of 27 free-roaming dogs. RESULTS: In the pilot study, the median time (range) to lateral recumbency (% dogs) after TZA administration was: treatment 1, 47.5 (35-80) minutes (67%); treatment 2, 30 (15-65) minutes (83%); and treatment 3, 75 (45-110) minutes (100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on these results, 20 free-roaming dogs were offered encapsulated TZA in canned food: TZ (20 mg kg-1) and acepromazine (2 mg kg-1). Of these, no further drugs to four dogs (one dog captured), 10 dogs were administered a second dose within 30 minutes (five dogs captured) and six dogs were administered TZ (5 mg kg-1) and xylazine (1.1-2.2 mg kg-1) intramuscularly by blow dart (six dogs captured). Seven dogs were initially offered twice the TZA dose (five dogs captured). In total, 63% free-roaming dogs were captured after administration of encapsulated TZA in canned food. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs, but additional drugs may be required. The sedation onset time and medication palatability influenced the capture rate.

Contenção farmacológica do rato-do-bambu (Dactylomys dactylinus Desmarest, 1817) e relato de ocorrência da espécie na região Sul do Brasil / Chemical restraint of the Amazon Bamboo Rat (Dactylomys dactylinus Desmarest, 1817) and of the occurrence of the species in southern Brazil

Um exemplar de rato-do-bambu (Dactylomys dactylinus) subadulto saudável do sexo feminino, de vida livre, com massa corporal de 0,32 kg, recebeu por via intramuscular, em uma única injeção, doses de tiletamina, zolazepam, xilazina e atropina calculadas por meio de extrapolação alométrica interespecífica, a partir das recomendações usuais para o cão doméstico de 10,0 kg (tiletamina/zolazepam - 5,0mg/kg, xilazina - 1,0mg/kg) e atropina - 0,05mg/kg). O rato perdeu a reação postural de endireitamento em 2,3 minutos pós-injeção (MPI) e recuperou a capacidade de deambular normalmente em 135 MPI. A frequência cardíaca variou de 360 a 188 bpm (226±62), a frequência respiratória de 128 a 112mpm (120±5), e a temperatura retal de 36,2 a 33,5°C (34,4±1,0). A analgesia e o miorrelaxamento foram considerados bons para a realização de procedimentos indolores ou pouco dolorosos de curta duração, como exame físico, colheita de material biológico, biometria, exames de imagem e marcação. A associação de fármacos permitiu a manipulação segura do animal por 63 MPI. A recuperação foi considerada satisfatória, porém prolongada. Destaca-se que este é primeiro registro de ocorrência da espécie na Região Sul do Brasil, e o primeiro relato de contenção farmacológica desse roedor neotropical.(AU)

One subadult healthy free-living female Amazon Bamboo Rat (Dactylomys dactylinus), weighting 0.32 kg, received tiletamine HCl, zolazepam HCl, xilazine HCl and atropine sulfate, combined in a single intramuscular injection. All doses were calculated by interspecific allometric scaling, using as model a 10.0 kg domestic dog (tiletamine/zolazepam -5.0mg/kg), xylazine -1.0mg/kg), and atropine - 0.05mg/kg). Immobilization occurred in 2.3 minutes after injection (MAI) and returno to normal ambulation was observed in 135 MAI. Heart rate remained between 360 and 188 beats/minute (226±62), respiratory rate between 128 and 112 breaths/minute (120±5), and body temperature ranged from 36.2 to 33.5°C (34.4±1.0). Analgesia and myorelaxation were considered good for painless or mild painful fast procedures as physical examination, biological sampling, biometrics, imaging tests and tagging. The proposed anesthetic protocol was safe and effective, allowing safe manipulation of the animal during 63 MAI. The recovery was satisfactory, but prolonged. This is the first record of the species in Southern Brazil and the first report on its chemical restraint.(AU)

Hyaluronidase administered with xylazine-tiletamine-zolazepam into adipose tissue shortens recovery from anesthesia in pigs.

OBJECTIVE: To evaluate the effect of hyaluronidase on uptake, duration and speed of elimination of xylazine-tiletamine-zolazepam administered in the subcutaneous fat over the dorsal lumbar region of swine. STUDY DESIGN: Blinded, randomized, crossover study. ANIMALS: Six healthy Landrace/Large White pigs weighing 132±24 kg (mean±standard deviation). METHODS: Animals were administered xylazine (1 mg kg-1) and tiletamine-zolazepam (8 mg kg-1) (control treatment, CON), or xylazine-tiletamine-zolazepam at the same doses with hyaluronidase (400 IU) (treatment HYA). The treatments were administered into the dorsal lumbar adipose tissue, 2.5-3.0 cm laterally from the spinous process of the second lumbar vertebra. The latency, anesthesia and recovery periods were measured. Heart rate, noninvasive systolic, diastolic, and mean arterial pressures, respiratory rate, hemoglobin oxygen saturation and rectal temperature were recorded every 10 minutes for up to 50 minutes. RESULTS: One animal in CON and one animal in HYA were responsive to stimulation and did not allow safe handling. No significant difference was found between treatments for latency (CON 11.3±5.9 minutes, HYA 7.4±5.1 minutes) and anesthesia (CON 53±53 minutes, HYA 49±38 minutes) periods. Recovery period was shorter in HYA (9±6 minutes) than in CON (32±16 minutes) (p < 0.05). Physiological variables were not significantly changed over time and were within accepted normal clinical limits for the species in both treatments. CONCLUSION AND CLINICAL RELEVANCE: Hyaluronidase (400 IU) administered into adipose tissue in pigs did not reduce the latency and duration of dissociative anesthesia, but was associated with faster recovery.

Immobilization of Asiatic Black Bears ( Ursus thibetanus ) with Medetomidine-Zolazepam-Tiletamine in South Korea.

The Asiatic black bear ( Ursus thibetanus ; ABB) is a globally endangered species for which a restoration program has been ongoing in South Korea since 2001. However, there is little information on immobilization protocols for ABBs. We evaluated the use of medetomidine-zolazepam-tiletamine for their immobilization. During 2005-13, we anesthetized 60 ABBs (32 males, 28 females; 7 mo to 12 yr old) with medetomidine 0.03-0.045 mg/kg and zolazepam-tiletamine 1.54-2.3 mg/kg; reversal of anesthesia was done with atipamezole 0.15-0.225 mg/kg administered intravenously alone or intravenously and intramuscularly (50:50). Mean (and SD) for physiologic collected for 373 immobilizations of at least 60 min were: time to sedation, 7.8 (5.4) min; anesthesia induction time, 13.7 (8.1) min; complete recovery time, 14.8 (12.4) min; respiratory rate, 14 (7) breaths/min; heart rate, 51 (16) beats/min; rectal temperature, 37.3 (1.3) C; and hemoglobin oxygen saturation, 88% (6%). Few cardiopulmonary side effects occurred during immobilization and adequate depth of anesthesia was maintained for >60 min without need for supplementation. The dosage and drug combination used was effective for immobilization of ABBs with minimal adverse effects on vital signs and can be recommended in most clinical applications.

Using Tiletamine-Zolazepam-Xylazine Anesthesia Compared to CO2-inhalation for Terminal Clinical Chemistry, Hematology, and Coagulation Analysis in Mice.

INTRODUCTION: It is important that the method of anesthesia of mice does not considerably alter the animal's physiological and metabolic status before terminal blood sampling taken in order to analyze clinical pathology parameters. METHODS: Hematology, hemostasis, and clinical chemistry parameters were compared in male and female BALB/c mice exposed to either tiletamine-zolazepam-xylazine (TZX) anesthesia or euthanasia in carbon dioxide (CO2) chamber to reveal an alternative method of anesthesia vs. the recommended CO2 inhalation. Blood samples were taken from the inferior vena cava. RESULTS: Clinical blood parameters in mice exposed to CO2 inhalation or TZX anesthesia proved to be substantially different. The TZX group had lower activated partial thromboplastin time (APTT) and fibrinogen (statistically in males and tending in females) and lower platelets (PLT), red blood cells (RBC), hemoglobin (HGB), and white blood cells (WBC) in both sexes. TZX anesthesia resulted in lower blood serum concentrations of total protein, albumin and globulins, creatinine in males (higher in females); cholesterol, triglycerides, alanine aminotransferase (АLT) and alkaline phosphatase (AP) in both sexes, and bilirubin in males. The calcium level decreased in TZX-anesthetized males and females while the phosphates decreased only in females. The volume of serum obtained from females of TZX group was approximately two times higher than in the CO2-anesthetized group, with the degree of hemolysis tending to decrease. DISCUSSION: The studied method of mouse anesthesia, followed by terminal blood sampling and analysis of clinical pathology parameters, suggests that TZX is a good alternative to CO2 inhalation in toxicological and other nonclinical studies. The differences in hemostasis, hematology, and clinical chemistry parameters between these groups are supposedly associated with alterations in physiological and metabolic status of mice under conditions of increasing hypoxia, respiratory standstill, and circulatory arrest after CO2 inhalation.