Abuse of Xylazine by Human and its Emerging Problems: A Review from Forensic Perspective

@#Xylazine is a sedative, analgesic and muscle relaxant widely applied in the veterinary field. However, owing to its depressant effect, xylazine has become a substance of abuse by humans. Misuse of xylazine not only triggers unwanted consequences (death), but also linked with various crimes. Google Scholar, PubMed and SciFinder were used to retrieve articles and case reports in relation to the misuses of xylazine and established analytical methods for forensic investigation until November 2021. Literatures reported the accidental and intended poisoning of xylazine, recreational use of xylazine and as an adulterant in recreational drugs. In addition to being a facilitator of crime and sexual assault, it is administered illegally to food producing animals as a sedative and to sports animals as a doping agent. Problems associated with the abuse of xylazine were highlighted in this review, covering the unknown prevalence of xylazine abuse and the need to revise the regulatory status of xylazine. In addition, limited screening and confirmatory methods that can be readily utilised to detect xylazine either alone or simultaneously with other substances of abuse, particularly useful for forensic toxicology and narcotic section were available in the literature. As a conventionally used veterinary drug, xylazine is undoubtedly a potentially hazardous drug, and the investigations on its potential abuse would enhance routine forensic examination to keep pace with the status of illicit drugs.

New model of Oral Mucositis with 5-Fluorouracil chemo-induced in Wistar rats without the use of anesthesics / Novo modelo de Mucosite Oral quimioinduzida com 5-Fluorouracil em ratos Wistar sem uso de anestésicos

ABSTRACT Introduction: Oral mucositis (OM) is considered the most frequent acute side effect of the antineoplasic treatment, with ulcerative lesions resulting from a painful symptomatology, affecting the oral cavity in response to the Antineoplastic treatment. In order to study these side effects, experiments in animal models are necessary, using antineoplastic drugs for the induction of OM and anesthetics, mainly Ketamine and Xylazine, to perform scarification of the cheeks. Objective: The goal is to report an experimental model of induced OM, without the use of anesthetics for the scarification stage of the animal cheeks. Methods: Fourty five male Wistar rats, 7 weeks old and weighting 220g, were used, divided into 2 groups; with OM induced by 5-Fluorouracil intraperitoneal administration. Two days later, Group I was physically contained, in contrast, Group II were anesthetized with Ketamine and Xylazine, focusing on irritating the cheek mucosa using the tip of a sterile needle, in order to potentialize the development of OM. The animals were euthanized with an anesthetic overdose. Results: Concerning the experiment of 5-Fluorouracil chemo-induced of OM, where the irritation was performed by physical containment, without the use of anesthetics (Ketamine and Xylazine), the animals had a longer survivability and a rapid improvement of the side effects induced by chemotherapy. Conclusion: This new model is promising, considering that the use of anesthetics (Ketamine and Xylazine) showed a high mortality rate. In the absence of anesthesia, all the animals survived until the end of the experiment involving chemotherapy model with 5-Fluorouracil and physical restraint.

RESUMO Introdução: A mucosite oral (MO) é considerada o efeito colateral agudo mais frequente do tratamento antineoplásico, com lesões ulcerativas decorrentes de sintomatologia dolorosa, acometendo a cavidade oral em resposta ao tratamento antineoplásico. Para estudar esses efeitos colaterais, são necessários experimentos em modelos animais, utilizando fármacos antineoplásicas para a indução de MO e anestésicos, principalmente Cetamina e Xilazina, para realizar a escarificação das bochechas Objetivos: Relatar um novo modelo experimental de MO induzida, sem o uso de anestésicos, para a etapa de escarificação das bochechas dos animais. Métodos: Foram utilizados 45 ratos Wistar machos, com 7 semanas de idade e peso de 220g, divididos em 2 grupos com MO induzida pela administração intraperitoneal de 5-fluorouracil. Dois dias depois, o Grupo I foi contido fisicamente, ao contrário, o Grupo II foi anestesiado com Cetamina e Xilazina, com foco em irritar a mucosa da bochecha com a ponta de uma agulha estéril, a fim de potencializar o desenvolvimento de MO. Os animais foram eutanasiados com sobredose de anestésica. Resultados: Em relação ao experimento de 5-Fluorouracil quimioinduzido para MO, onde a irritação foi realizada por contenção física, sem o uso de anestésicos (Cetamina e Xilazina), os animais tiveram maior sobrevida e rápida melhora dos efeitos colaterais induzidos por quimioterapia. Conclusão: Este novo modelo é promissor, visto que o uso de anestésicos (Cetamina e Xilazina) apresentou elevada mortalidade. Porém, na ausência de anestesia, todos os animais sobreviveram até o final do experimento envolvendo este modelo de quimioterapia induzida com 5-fluorouracil e contenção física.

Inmovilización química, hematología y química sanguínea de jaguares (Panthera onca) en zoológicos de Venezuela: estudio retrospectivo, 1996-2009 / Chemical immobilization, hematology, and blood chemistry in jaguars (Panthera onca) in Venezuelan zoos: A retrospective study, 1996-2009 / Imobilização química, hematologia e química sanguínea de onças-pintadas (Panthera onca) em zoológicos de Venezuela: estudo retrospectivo, 1996-2009

Resumen Veintidós jaguares (Panthera onca) (12 machos y 10 hembras) mantenidos en cautiverio entre 1996 y 2009, con edades de entre 3 y 17 años y con una variación de peso entre 40 y 87 kg, fueron inmovilizados químicamente con una combinación de ketamina (100 mg/ml)-xilacina (100 mg/ml) a una dosis constante de 4,0-2,0 mg/kg, respectivamente. El tiempo del efecto inicial varió de 9 a 55 min, y el tiempo de recumbencia lateral o esternal varió de 25 a 155 min. Todos los jaguares inmovilizados mostraron buen relajamiento muscular. Se observó salivación y arqueos en nueve de los jaguares. El vómito se presentó en cuatro animales. Generalmente, la inducción anestésica con la combinación de ketamina-xilacina fue rápida y suave; el tiempo de recuperación osciló de 2 a 35 min. La verificación continua de la frecuencia cardíaca, la frecuencia respiratoria y la temperatura corporal no indica respuestas fisiológicas adversas a esta combinación de fármacos. Todos los jaguares parecían normales y regresaban a sus actividades después de la recuperación.

Abstract Twenty-two jaguars (Panthera onca) (12 males and 10 females) kept in captivity between 1996 and 2009, between 3 and 17 years of age, and with a weight variation between 40 and 87 kg, were chemically immobilized with a combination of ketamine (100 mg/ml)-xylazine (100 mg/ml) at a constant dose of 4.0-2.0 mg/kg, respectively. Initial effect time varied from 9 to 55 min, and lateral or sternal recumbency time varied from 25 to 155 min. All the immobilized jaguars showed good muscle relaxation. Salivation and arching were observed in nine jaguars. Four animals presented with vomiting. Generally, anesthetic induction with the combination of ketamine-xylazine was quick and smooth; recovery time ranged from 2 to 35 min. The continuous monitoring of heart rate, respiratory rate, and body temperature did not indicate adverse physiological responses to this combination of drugs. All the jaguars seemed normal and returned to their activities after recovery.

Resumo Vinte e duas onças-pintadas (Panthera onca) (12 machos e 10 fêmeas) mantidos em cativeiro entre 1996 e 2009, com idades entre 3 e 17 anos e com variação de peso entre 40 e 87 kg, foram quimicamente imobilizadas com uma combinação de cetamina (100 mg/ml)-xilacina (100 mg/ml) em una dose constante de 4,0-2,0 mg/kg, respetivamente. O tempo de efeito inicial variou de 9 a 55 min, e o tempo de decúbito lateral ou esternal variou de 25 a 155 min. Todas as onças-pintadas imobilizadas mostraram bom relaxamento muscular. Observou-se salivação e arcos em nove dos jaguares. Vómitos ocorreram em quatro animais. Geralmente, a indução anestésica com a combinação de cetamina-xilacina foi rápida e suave. O tempo de recuperação oscilou de 2 a 35 min. A verificação continua da frequência cardíaca, frequência respiratória e temperatura corporal não indica respostas fisiológicas adversas a esta combinação de fármacos. Todos os jaguares pareciam normais e voltaram a suas atividades após da recuperação.

Safety and efficacy of ketamine xylazine along with atropine anesthesia in BALB/c mice

Anesthetics are an indispensable prerequisite for surgical intervention and pharmacological animal studies. The objective of present study was to optimize the dose of ketamine (K) and xylazine (X) along with atropine sulfate (A) in order to achieve surgical tolerance in BALB/c mice. Several doses of ketamine (100, 150, 200 mg/kg) and xylazine (10, 15, 20 mg/kg) were mixed and combination of nine doses (K/X: 100/10, 100/15, 100/20, 150/10, 150/15, 150/20, 200/10,200/15,200/20) were evaluated (n=9 per combination). A constant dose of atropine (0.05 mg/kg) was also used to counter side effect. Time-related parameters were evaluated on the basis of reflexes. KX at dose 200/20 mg/kg produced surgical tolerance in all nine mice with duration 55.00±6.87 minutes. The induction time 0.97±0.09 minutes, sleeping time 90.67±5.81 minutes and immobilization time (102.23±6.83 minutes) were significantly higher than all combination. However, this combination was considered unsafe due to 11 % mortality. While, KX at dose 200/15 mg/kg results in none of the mortality, so was considered as safe. Moreover, this combination produces surgical tolerance in 89 % mice with duration (30.00±7.45 minutes). It was concluded that KX at dose 200/15 mg/kg along with atropine 0.05 mg/kg is safe for performing surgical interventions in BALB/c mice.

Sedative, analgesic, behavioral and clinical effects of intravenous nalbuphine-xylazine combination in camels (Camelus dromedarius)

This study examined the sedative, analgesic, behavioral, and clinical effects of a combination of xylazine (XY) and nalbuphine-xylazine (NA-XY) in camels. A total of five adult camels were used in a prospective randomized cross-over design with a wash out period of two weeks. Camels were allocated randomly to two treatment groups: the XY group (xylazine, 1.1mL/100 kg IV) and the NA-XY group (xylazine, 1.1mL/100 kg IV and nalbuphine, 1 mg/kg IV). The sedative, analgesic, behavioral, and clinical effects of XY and NA-XY combination were evaluated prior to administration (baseline) and at 5, 15, 30, 45, 60, 75, 90, and 120 minutes post-administration. The results showed that the NA-XY combination accelerates the onset of sedation and analgesia and prolongs the durations of both sedation (p < 0.001) and analgesia (p < 0.01). The behavioral parameters showed higher scores with a NA-XY combination than xylazine alone. Although a XY injection resulted in a significant decline in the heart and respiratory rate, the NA-XY combination group revealed a non-significant change in both clinical parameters compared to the baseline. In conclusion, the use of a NA-XY combination in camels improved the sedative and analgesic onset and duration with an improved outcome in the behavioral scores, as well as in both the heart and respiratory rates compared to XY alone.

Efecto de la premeditación de Fentanilo-acepromacina y Fentanilo-xilacina sobre la presentación de vómito posoperatorio en perros / Effect of premedication with fentanyl-acepromazine and fentanyl-xylazine over postsurgical vomiting in dogs / Efeito da pré-medicação com fentanil-acepromazina e fentanil-xilazina sobre o vômito pós-cirúrgico em cães

Resumen La inclusión de opioides durante la preanestesia y anestesia, potencialmente puede incrementar la presentación de vómito y náuseas posoperatorias, acrecentando el riesgo de presentación de sangrado, dehiscencias, neumonía por aspiración o esofagitis. En éste estudio se evaluó la presentación de vómito, salivación excesiva y anorexia durante 24 horas del periodo posanestésico en 100 perros ASA I y II. El grupo A (n: 40) fue premedicado con una mezcla de acepromacina a 0.08 mg/kg i.v. y fentanilo a 5 μg/kg i.v. y el grupo X (n: 60) con xilacina a 0.3 mg/kg i.v. más fentanilo a 5 μg/kg i.v. La inducción anestésica para ambos grupos se realizó con propofol a 4 mg/kg y el mantenimiento con isoflurano a 1,5-3%. La presentación general de vómito post-anestesia fue del 12%. Entre ambos grupos no se encontraron diferencias significativas en la incidencia de vómito a las 2 (p= 0,837), a las 6 (p= 0,439) y a las 24 horas (p= 0,639). No hubo diferencias significativas entre grupos para la presentación de salivación excesiva o anorexia. Se encontró una asociación entre vómito post-anestésico y cirugía del aparato reproductivo en hembras (p= 0,02). Se concluye que un único bolo de fentanilo a 5 μg/kg con acepromacina a 0,08 mg/kg o xilacina 0,3 mg/kg durante la premedicación anestésica, no incrementa la presentación de vómito en las primeras 24 horas del postquirúrgico en perros.

Abstract Opioid inclusion in pre-anesthesia and anesthesia may increase postperative vomiting and nausea, increasing the risk of bleeding, dehiscence, aspiration pneumonia or esophagitis. Therefore, the purpose of this study was to monitor vomiting, excessive salivation and anorexia during 24 hours of the post-surgical period on 100 dogs ASA I and II. Group A (n: 40) was pre-medicated with acepromazine at 0.08 mg/kg with fentanyl at 5 μg/kg i.v; group X (n: 60) with xylazine at 0.3 mg/kg i.v. with fentanyl at 5 μg/kg i.v. Anesthesia induction was made with propofol at 4 mg/kg and maintained with isofluorane at 1.5-3% for both groups. The overall vomiting produced was 12% and there were no significant differences in vomiting manifestation at 2 (p=0.837), 6 (p=0.439) and 24 hours (p= 0.639) between the groups. In the same way, there were no major differences neither for excessive salivation nor anorexia. There was a significant association between postanesthesia vomiting and reproductive surgery in female dogs (p=0.02). As a conclusion, a single bolus of fentanyl at 5 μg/kg with acepromazine at 0.08 mg/kg or xylazine 0.3 mg/kg in pre-anesthesia does not increase post-surgery vomiting in dogs in the first 24 hours.

Resumo A inclusão de opioides durante a pré-anestesia e anestesia, potencialmente podem incrementar a apresentação de vomito e náuseas pós-operatórias, acrescentando o risco de apresentação de sangrado, deiscências, pneumonia por aspiração e esofagites. Neste estudo se avalio a apresentação de vomito, salivação excessiva e anorexia durante 24 horas do período pós-anestésico em 100 cães ASA I e II. O grupo A (n: 40) foi medicado com uma mistura de acepromazina 0.08 mg/kg IV e fentanilo 5 μg/kg IV e no grupo X (n: 60), xilacina 0.3 mg/kg IV e fentanilo 5 μg/kg IV. A indução anestésica para ambos grupos se realizou com propofol 4 mg/kg e manutenção com isoflurano 1,5-3%. A apresentação geral de vomito pós-anestésico foi do 12%. Entre ambos grupos não se encontraram diferencias significativas na incidência de vomito nas 2 (p= 0,837), 6 (p= 0,439) e 24 horas (p= 0,639). Não teve diferenças significativas entre grupos na apresentação de salivação excessiva ou anorexia. Se achou uma associação entre vomito pós-anestésico e cirurgia do trato reprodutivo em fêmeas (p= 0,02). Como conclusão uma única doses de fentanilo 5 μg/kg com acepromacina 0,08 mg/kg ou xilacina 0,3 mg/kg durante a pré-medicação anestésica, não incrementa a apresentação de vomito nas primeiras 24 horas do pós-cirúrgico em cães.

Comparison of two injectable anesthetic combinations used to perform midline laparotomy for embryo recovery in Colombian creole ewes / Comparación de dos combinaciones de anestésicos inyectables utilizados en laparotomía medial para recuperación de embriones en ovejas criollas colombianas / Comparação de duas combinações de anestésicos injetáveis utilizados na laparatomia medial para recuperação de embriões em ovelhas nativas colombianas

Abstract: In the countryside, the use of halogenated anesthetics is difficult, therefore the use of injectable agents is an essential tool in anesthetic practice. This study aimed to compare two multimodal injectable anesthesia protocols and to determine the appropriate protocol to perform a medial laparotomy and embryo recovery in sheep. 16 healthy adult creole sheep were used. Animals were randomized to receive xylazine 0.2 mg/kg PC IM and ketamine 10 mg/kg PC IV (XK group), or a continuous infusion of 5% solution of xylazine (50 mg), ketamine (500 mg), and guaifenesin (500 mL) at a rate of 2.2 mL/kg/h IV (XKG group). Heart and respiratory frequency, rumen motility, and body temperature were evaluated before anesthesia, after induction, and during recovery. Induction was assessed by muscle spasms, nystagmus, and limb movement. Anesthesia was evaluated based on time, mandibular relaxation, skin sensitivity, and reflexes. Recovery was evaluated on a scale for anesthetic agent (0-10). Cardiorespiratory parameters decreased below baseline after induction of anesthesia in both groups. Between the groups, there was a significant difference in decubitus time (XK: 9.06 ± 0.73 min; XKG: 7.81 ± 0.53 min) and recovery (XK: 53.13 ± 5.3 min; XKG: 98.38 ± 5.71 min). Changes in the cardiopulmonary system were similar in both anesthetic regimens, and they were within acceptable clinical range. It is concluded that, in short surgical procedures, xylazine-ketamine anesthesia provides rapid induction, maintenance of physiological parameters within optimum limits, and rapid recovery.

Resumen: En el campo, el uso de anestésicos halogenados es difícil, por lo que el uso de agentes inyectables es una herramienta esencial de la práctica anestésica. El objetivo del presente estudio fue comparar dos protocolos de anestésicos inyectables multimodales y determinar el adecuado protocolo para realizar una laparatomía medial y recuperar embriones en ovejas. Se utilizaron 16 ovejas criollas adultas y sanas. Los animales se asignaron al azar para recibir xilazine 0,2 mg/kg PC IM y de ketamina 10 mg/kg PC IV (XK grupo) o una infusión continua de solución al 5 % de xilazine (50 mg), ketamina (500 mg) y de guaifenesina (500 mL) a una tasa de 2,2 mL/kg/h IV (grupo XKG). Frecuencia cardiaca y respiratoria, motilidad del rumen y temperatura corporal se evaluaron antes de la anestesia, después de la inducción y durante la recuperación. La inducción se evaluó según los espasmos musculares, nistagmo y movimiento de las extremidades. La anestesia se valora en función del tiempo, relajación mandibular, sensibilidad cutánea y reflejos. La recuperación se evaluó a una escala de agente anestésico (0-10). Los parámetros cardiorrespiratorios disminuyeron por debajo de los valores basales después de la inducción de anestesia en ambos grupos. Entre los grupos, hubo una diferencia significativa en el tiempo de decúbito (XK: 9,06 ± 0,73 min; XKG: 7,81 ± 0,53 min) y la recuperación (XK: 53,13 ± 5,3 min; XKG: 98,38 ± 5,71 min). Los cambios en el sistema cardiopulmonar fueron similares en ambos regímenes anestésicos, y estaban dentro de rangos clínicos aceptables. Se concluye que, en intervenciones quirúrgicas cortas, la anestesia xilacina-ketamina proporciona una rápida inducción, el mantenimiento de los parámetros fisiológicos dentro de los límites óptimos y una recuperación rápida.

Resumo: O uso de anestésicos halogenetos é difícil em campo, razão pela qual o uso de agentes injetáveis é uma ferramenta essencial da prática anestésica. O objetivo do presente estudo foi comparar dois protocolos de anestésicos injetáveis multimodais e determinar o protocolo adequado para realizar uma laparatomia medial e recuperar embriões em ovelhas. Se utilizaram 16 ovelhas domésticas adultas e saudáveis. Os animais foram designados aleatoriamente ao azar para receber 0,2 mg/kg PC IM de xilazina e 10 mg/kg PC IV de cetamina (XK grupo) ou uma infusão contínua de solução ao 5 % de xilazina (50 mg), cetamina (500 mg) e de guaifenesin (500 mL) a um índice de 2,2 mL/kg/h IV (grupo XKG). A frequência cardíaca e respiratória, motilidade do rumem e temperatura corporal foram avaliaram antes da anestesia, após a indução e durante a recuperação. A indução é avaliada se avaliou segundo os espasmos musculares, nistagmo e movimento das extremidades. A anestesia foi medida em função do tempo, relaxamento mandibular, sensibilidade cutânea e dos reflexos. A recuperação se avaliou com uma escala do agente anestésico (0-10). Os parâmetros cardiorrespiratórios diminuíram abaixo dos valores basais apósa indução do anestesia em ambos os grupos. Entre os grupos, houve uma diferença significativa no tempo de decúbito (XK: 9,06 ± 0,73 min; XKG: 7,81 ± 0,53 min) e a recuperação (XK: 53,13 ± 5,3 min; XKG: 98,38 ± 5,71 min). As mudanças no sistema cardiopulmonar foram similares em ambos os regimes anestésicos, e estavam dentro de rangos clínicos aceitáveis. Conclui-se que, em intervenções cirúrgicas curtas, a anestesia xilazina-cetamina proporciona uma rápida indução, a manutenção dos parâmetros fisiológicos dentro dos limites ótimos e uma recuperação rápida.

Detection of xylazine and 2,6-xylidine in blood and urine by SPE-HPLC/MS/MS / 中国法医学杂志

Objective To develop an HPLC-MS/MS method for simultaneous determination of xylazine and 2,6-xylidine in body fluid samples.Methods The samples were extracted by HLB SPE,separated by Waters Atlantis dC18 chromatographiccolumn,and then detected in the MRM scan ion mode under positive ionization condition.Results The recoveryrates of this method were between 70.5％ and 79.8％ with the range of RSD rfrom8.2％ to 10.5％.The limits of detection ofxylazine and 2,6-xylidine in blood and urine samples were 0.4 and 0.3 ng/mL,and the limits of quantitation were 1.2 and 1.0 ng/mL,respectively.Conclusion This method is of high sensitivity,good specificity and good reproducibility,and thus could besuitable for accurate quantification of xylazine in blood and urine samples.

Therapeutic effects of xylazine and dexmedetomidine in establishing the model of spinal cord inj ury in beagle dogs / 西安交通大学学报(医学版)

ABSTRACT:Objective To observe the anesthetic effects of xylazine and dexmedetomidine in establishing the model of spinal cord injury in beagle dogs.Methods Thirty female beagle dogs were randomly divided into 3 groups with 1 0 in each:xylazine group (group S ), dexmedetomidine group (group D ), and xylazine +dexmedetomidine group (group S+D).Basal anesthesia with ketamine was performed in all the dogs.Then group S was intramuscularly injected with xylazine discontinuously, group D was intravenously injected with dexmedetomidine 2μg/(kg·h)continuously,but group S+D was injected with xylazine and dexmedetomidine in combination.The heart rate (HR),respiratory frequency (RR),Ramsay score and spasm index (SI)were observed at the time of skin incision (T1),after the beginning of the operation 30 min (T2),before the end of the operation 30 min (T3),and the end of the operation(T4);and the usage of anesthetics was recorded.Results Compared with that in groups S and D,the usage of xylazine and dexmedetomidine in group S+D was decreased by 1/2 and 1/4,respectively (P<0.01),but HR and RR did not change significantly;the sedative effect was superior to that in S.No obvious increase in muscular tensility in the foreleg was observed before operation.Conclusion Xylazine and dexmedetomidine used in combination to establish the model of spinal cord injury in beagle dogs have advantages of better sedative effect,less respiratory depression and lower dosage of anesthetic drugs.

Echocardiography analysis of bama minipigs anesthesia by xylazine hydrochloride / 中国比较医学杂志

Objective To explore effect of Xylazine hydrochloride on Bama minipigs under general anesthesia. To emphasize safety consciousness of general anesthesia. To research cardiac main function and structure of normal Bama minipigs in preparation for the subsequent comparative medicine research. Methods 43 Bama minipigs, inject in post aurem muscles of neck with 5 mL of mixed drug conclude Xylazine hydrochloride (2 mL), Atropine Sulfate(1 mL) and Droperidol(2 mL) on each one. Echocardiography after general anesthesia. Observe induction and recovery time of anesthesia, anesthesia maintaining time, total check time and the others. Introduce the method of simple endotracheal intubation. Results Anesthesia, induction period (18 ±3)min, maintaining period (40 ±5)min, recovery period (60 ± 10)min. Echocardiography, LAD (2?54 ± 0?20) cm, LVDd (3?41 ± 0?25) cm, LVDs (2?28 ± 0?23) cm, IVSTd (0?60 ± 0?07) cm, LVPWTd (0?59 ± 0?07) cm, AoD (1?77 ± 0?18) cm, EDV (48?59 ± 8?31) cm, ESV (18?28 ± 4?46) mL, SV ( 39?30 ± 5?16 ) mL, LVEF ( 62?76 ± 5?01 )%. Conclusions Intramuscular injection of xylazine hydrochloride with droperidol and atropine sulfate on bama minipigs for general anesthesia is a highly conserved specie in cardiovascular system and safe. We obtained some information of cardiac main function and structure of normal Bama minipigs which could provide reference for scientific research and veterinarian clinic.

Intraperitoneal co-administration of low dose urethane with xylazine and ketamine for extended duration of surgical anesthesia in rats / 한국실험동물학회지

Procedures involving complex surgical techniques in rats, such as placement of abdominal aortic graft require extended duration of surgical anesthesia, which often can be achieved by repeated administrations of xylazine-ketamine combination. However such repeated anesthetic administration, in addition to being technically challenging, may be associated with potential adverse events due to cumulative effects of anesthesia. We report here the feasibility of using urethane at low dose (~1/10 the recommended anesthetic dose) in combination with a xylazine-ketamine mix to achieve an extended duration of surgical anesthesia in rats. The anesthesia induction phase was quick and smooth with an optimal phase of surgical anesthesia achieved for up to 90 minutes, which was significantly higher compared to that achieved with use of only xylazine-ketamine combination. The rectal temperature, heart rate and respiratory rate were within the physiological range with an uneventful recovery phase. Post surgery the rats were followed up to 3 months without any evidence of tumor or any other adverse effects related to the use of the urethane anesthetic combination. We conclude that low dose urethane can be effectively used in combination with xylazine and ketamine to achieve extended duration of surgical anesthesia up to 90 minutes in rats.

Comparação da contenção farmacológica com cetamina e xilazina, administradas pela via intramuscular no membro torácico ou pélvico, em jacarés-do-papo-amarelo juvenis / Comparison of pharmacological restraint with ketamine and xylazine, administered intramuscularly in the forelimb or hindlimb, in broad-snouted caiman juveniles

Os répteis possuem um sistema porta-renal, o qual pode desviar parte do sangue proveniente das porções caudais do corpo aos rins antes que a mesma atinja a circulação sistêmica. Em vista disto, vem sendo aconselhada a administração de medicamentos injetáveis nos membros torácicos, para que se evite a filtração imediata pelo parênquima renal, causando redução do efeito esperado. O objetivo do presente estudo foi comparar aspectos qualitativos e quantitativos da associação de cetamina (30 mg/kg) e xilazina (1 mg/kg), injetada no membro torácico ou pélvico, em jacarés-do-papo-amarelo (Caiman latirostris) juvenis. Oito animais machos com peso médio (±DP) de 1,3 (±0,3) kg e, aproximadamente, dois anos de idade foram anestesiados em duas ocasiões distintas com intervalo de sete dias. Em cada ocasião, os animais receberam, de forma aleatória, a associação anestésica por via intramuscular em membro torácico (tratamento MT) ou pélvico (tratamento MP). Foram avaliados os intervalos de tempo entre a administração do tratamento e a perda do reflexo de endireitamento (período de indução), entre a perda e o retorno desse reflexo (duração do efeito clínico importante) e entre o retorno do reflexo de endireitamento e os primeiros movimentos de deambulação (duração do efeito residual), as frequências cardíaca e respiratória e as temperaturas ambiental e cloacal. Os escores de sedação/anestesia foram avaliados através de uma escala com variação de 0 (alerta/consciente) a 10 (anestesia profunda/sobredosagem). No tratamento MP, dois animais não apresentaram perda de reflexo de endireitamento. Considerando somente aqueles que apresentaram a perda desse reflexo, o tempo de indução (21±9 e 17±5 minutos) e a duração do efeito clínico importante (35±19 e 43±21 minutos) e residual (28±31 e 12±11 minutos) foram similares entre os tratamentos MT e MP (média±desvio padrão)...

Reptiles possess a renal portal system which can divert part of the blood from the caudal portions of the body to the kidney before it reaches the systemic circulation. In view of this, it has been recommended the administration of injectable medications in the forelimbs, in order to avoid immediate glomerular filtration, which might result in a reduction of the expected effect. The aim of this study was to compare qualitative and quantitative aspects of the pharmacological restraint provided by the combination of ketamine (30mg/kg) and xylazine (1mg/kg), injected into the forelimb or hindlimb, in broad-snouted caiman juveniles (Caiman latirostris). Eight male animals, with a mean weight (±SD) of 1.3 (±0.3) kg, and aged about 2 years old, were anesthetized on two separate occasions with an interval of 7 days. On each occasion, the animals were randomly assigned to receive the anesthetic combination intramuscularly into the forelimb (FL treatment) or hindlimb (HL treatment). The time intervals between administration of treatment and loss of the righting reflex (induction time), between the loss and return of this reflex (duration of important clinical effect), and between the return of the righting reflex and first movements of ambulation (duration of residual effect) were measured as well as heart and respiratory rates and cloacal and environmental temperatures. Sedation/anesthesia scores were evaluated using a scale ranging from 0 (alert/conscious) to 10 (deep anesthesia/overdose). In the HL treatment, loss of righting reflex was not observed in two animals. Considering only those animals whose loss of righting reflex was observed, the induction time (21±9 and 17±5 minutes), the duration of important clinical effect (35±19 and 43±21 minutes), and the duration of residual effect (28±31 and 12±11 minutes) were similar between the FL and HL treatments, respectively (mean±SD). Sedation/anesthesia scores were significantly higher than at baseline...

Sedative and clinical effects of the pharmacopuncture with xylazine in dogs

To investigate the sedative and clinical effects of the pharmacopuncture with xylazine, compared to the conventional dose of a intramuscular injection in dogs. METHODS: Twelve dogs were randomly distributed in two groups of six animals and treated as follows: control group (X-IM): 1mg kg-1 of xylazine given intramuscularly (IM); pharmacopuncture group (X-Yintang): 0.1mg kg-1 of xylazine diluted to 0.5 mL of saline injected into the Yin Tang acupoint. Heart rate, cardiac rhythm (ECG), systolic arterial blood pressure (SABP), respiratory rate (RR), rectal temperature (RT), blood glucose concentration, degree of sedation and adverse effects were evaluated. RESULTS: Sedative effect was observed in both groups. The degree of sedation was greater in X-IM only at 15 min when compared with X-Yintang group. Cardiovascular established was observed in X-Yintang group, while marked reduction in the HR and increased incidence of ECG abnormalities were detected in X-IM. In both treatment groups, minimal changes were observed in relation to SABP, RR, RT and blood glucose. High incidence (66%) of vomiting was observed in X-IM, while this adverse effect was absent in X-Yintang. CONCLUSION: Pharmacopuncture with xylazine induced clinically relevant sedative effects in dogs, with the advantage of reduction of undesirable side effects associated with α2-agonists, including bradycardia, cardiac arrhythmias, and emesis.

Clinical observation of anesthesia using xylazine hydrochloride injection in Beagle dogs / 中国比较医学杂志

Objective The aim of this study was to observe the anesthetic effect of xylazine hydrochloride Injection on Beagle dogs.Methods Anaesthetizing 30 healthy Beagles with xylazine hydrochloride injection, some physiological indexes of the dogs, such as body temperature (T), respiration (R), heart rate (P), and blood pressure (systolic pressure SBP, diastolic pressure DBP), were monitored.Results After using xylazine hydrochloride injection, the body temperature, respiration, heart rate, blood pressure, and peripheral vascular resistance were decreased in the Beagles.Conclusion Xylazine hydrochloride injection can keep a stable induction period, and has advantages including powerful and quick effect, simple method and operation, safe and insignificant toxicity and side effects,and has a better effect of anaesthesia.

Recovery effect of moxibustion at Nei Guan (PC-6) in xylazine induced bradycardia in dogs / 대한수의학회지

This study was performed to investigate the effect of Nei Guan (PC-6) moxibustion stimulation on artificial bradycardia of dogs. Xylazine was injected for inducing bradycardia. Rectal temperature, systolic blood pressure, respiratory rate, heart rate were recorded every 10 minutes for 120 minutes. Systolic blood pressure significantly increased on 40 min (p < 0.05) after xylazine injection, compared with those of control group. Heart rate significantly increased on 40 min (p < 0.01), 50 min (p < 0.01), 60 min (p < 0.01), 70 min (p < 0.01), 80 min (p < 0.01), 100 min (p < 0.01), 120min (p < 0.01) after xylazine injection, compared with those of control group. In conclusion, moxibustion of Nei Guan (PC-6) showed recovery effect in xylazine induced bradycardia in dogs.

Sedación y analeesia con bolos de xilazina y mofina en infusión continua en unna yegua criolla Colombiana sometida a ovarioectomía en estación / Sedation and analgesia with xylazine bolus and morphine in continuous infusion in a mare standing subjected to ovariectomy: case report

En el acto quirúrgico la anestesia es un proceso que siempre conlleva riesgos. Un procedimiento común en equinos es realizar cirugías en estación para disminuir el riesgo de la anestesia general. Para los procedimientos anestésicos en estación en equinos se han utilizado las combinaciones de bolos de xilazina y anestesia local; sin embargo, la analgesia irregular y la marcada ataxia son complicaciones frecuentes. En el presente caso clínico se evaluó un protocolo de bolos de xilazina 0,6 mg/kg I.V. y morfina en infusión I.V. continua a 30 µg/kg/hora, con aplicación de anestesia local para la extraccción de un tumor de células de la granulosa en una yegua. Durante el procedimiento quirúrgico se observó una buena analgesia, sedación moderada y ataxia leve, sin alteraciones cardiovasculares o respiratorias, lo que favoreció el procedimiento quirúrgico; solamente se observó un corto periodo de amotilidad intestinal el cual fue superado espontáneamente. La yegua se recuperó totalmente del procedimiento quirúrgico y presentó evidencia de estro en dos ocasiones dentro del año siguiente a la intervención. Los procedimeintos anestésico y quirúrgico empleados en esta yegua fueron apropiados y la llevaron a su normalidad reproductiva.

Anesthesia is always a procedure that leads many risks in the quirurgical act. A common procedure in horses is to make standing surgeries to decrease the general anesthesia risks. For standing anesthetic procedures in horses there have been used combinations of xilazine bolus and local anesthesia; however, irregular analgesia and marked ataxia are frequent complications. In this clinical case it was evaluate a protocol of xilazine bolus 0,6 mg/kg I.V. and a constant rate infusion of morphine 30 µg/kg/h I.V., with local anesthesia for the extraction of a granulosa cell tumor in one mare. In general, during the surgical procedure it was observed good analgesia, moderate sedation and slight ataxia, without cardiovascular or respiratory problems which favored the surgical procedure; it was observed only a short period without intestinal motility that returned to normality spontaneously. The mare recovered fully from the surgical procedure and presented evidence of estrus twice within one year after the intervention. The anesthetic and surgical procedures used in this case were appropriate and lead recovery of the normal reproductive behavior of this mare.

Efeitos de detomidina e xilazina intravenosa sobre as variáveis basais e respostas comportamentais em bovinos / Effects of intravenous detomidine and xilazine on basal parameters and behavioral responses in bovine

Avaliaram-se, durante 60 minutos, 10 bovinos após administração intravenosa de 0,1mg.kg-1 de xilazina ou 10μg.kg-1 de detomidina, quanto às frequências cardíaca e respiratória, movimentos ruminais, pressão arterial média, temperatura retal e respostas comportamentais como ataxia ou decúbito, ptose palpebral, estado de alerta ou sedação e redução da altura da cabeça em relação ao solo, além da presença de salivação, micção e concentração sanguínea de glicose. Observou-se que a xilazina, via intravenosa, em bovinos, ao mesmo tempo que promove sedação mais intensa e prolongada que a detomidina, induz a uma maior quantidade de efeitos indesejáveis, como salivação e decúbito, e redução das frequências cardíaca e respiratória, da pressão arterial média, da motilidade ruminal e da temperatura, sendo estas alterações mais prolongadas. Conclui-se que a detomidina pode ser utilizada com segurança em bovinos na dose de 10μg.kg-1, promovendo sedação e permanência do animal em posição quadrupedal.

Ten bovine were evaluated after intravenous injection of 0,1mg.kg-1 of xylazine or 10μg.kg-1 of detomidine during 60 minutes for heart and respiratory rate, ruminal motility, mean arterial pressure, rectal temperature and behavioral responses like ataxia or recumbency, palpebral ptoses, state of sedation or alert and head drop, besides the measurement of salivation, urination and blood glucose concentration. It was observed that intravenous xylazine in bovine promotes more intense and prolonged sedation than detomidine, and at the same time induces a larger and more prolonged quantity of unwanted side effects such as salivation, recumbency, decrease of cardiac and respiratory rate, mean arterial pressure, ruminal motility and temperature. We concluded that detomidine can be used safely in bovines at 10μg.kg-1 dose, promoting sedation with standing position.

Infusão contínua intravenosa de midazolam isolado ou associado ao fentanil para realização de endoscopia em suínos / Continuous infusion rate of midazolam alone or in combination with fentanyl for endoscopy in swine

Com este estudo objetivou-se avaliar o efeito cardiorrespiratório e a qualidade da anestesia e da recuperação pós-anestésica decorrentes da associação cetamina e xilazina seguida da infusão contínua intravenosa (IV) de midazolam isolado ou associado ao fentanil, em suínos. Foram avaliadas 10 porcas adultas, da raça Landrace, com peso médio de 170±4kg, submetidas à endoscopia. Todos os animais foram medicados pela via intramuscular com cetamina (4mg kg-1) associada à xilazina (2mg kg-1). Vinte minutos após, foi realizado um bolus IV de cetamina (2mg kg-1), seguida da infusão contínua IV de midazolam (0,5mg kg-1h-1 GM, n=5), ou midazolam (0,25mg kg-1h-1) associado ao fentanil (4µg kg-1 h-1 GMF, n=5). Foram avaliados: frequência cardíaca (FC) e ritmo cardíaco, pressão arterial sistólica (PAS), temperatura retal (T), frequência respiratória (f), variáveis hemogasométricas (PaO2, PaCO2, pH, HCO3-, SaO2), qualidade da anestesia e qualidade e tempo da recuperação anestésica (RA). A análise estatística foi realizada por meio de análise de variância, teste de Tukey e o teste não paramétrico de Mann-Whitney (P<0,05). A qualidade da anestesia foi semelhante entre os tratamentos, sendo possível a realização da endoscopia em ambos os grupos. Os parâmetros cardiorrespiratórios, bem como os gases sanguíneos, o pH, o bicarbonato e a saturação da oxihemoglobina não variaram entre os diferentes tratamentos. O tempo de recuperação anestésica foi de 98±15 e 79±17 minutos no GM e GMF, respectivamente, sem diferença entre os grupos. A qualidade da RA não diferiu significativamente entre os grupos. Conclui-se que ambos os tratamentos determinaram estabilidade cardiorrespiratória e foram satisfatórios para a realização de endoscopia em suínos. No entanto, apesar da ausência de diferença estatística, menor tempo de RA foi observado nos animais tratados com a infusão contínua de midazolam associado ao fentanil.

The aim of this study was to evaluate the cardiopulmonary effects, the quality of anesthesia and the post-anesthetic recovery of ketamine and xylazine premedication following intravenous (IV) continuous rate infusion of midazolam alone or in combination with fentanyl, in swine. Ten Landrace adult pigs that underwent endoscopy were evaluated. All pigs were premedicated with ketamine (4mg kg-1) and xylazine (2mg kg-1) by intramuscular administration. After twenty minutes, intravenous ketamine (2mg kg-1) was injected, following IV continuous rate infusion of midazolam (0.5mg kg-1 h-1 GM, n=5) or midazolam (0.25mg kg-1 h-1) plus fentanyl (4µg kg-1 h¹ GMF, n=5). Heart and respiratory rates, systolic arterial blood pressure, rectal temperature, arterial blood gases, quality of anesthesia and recovery, and time for recovery were investigated. Statistical analysis was performed with One-Way ANOVA, Tukey test and Mann-Whitney test (P<0.05). The quality of anesthesia was similar between treatments, and endoscopy was able to be performed in both groups. Cardiopulmonary variables and blood gases did not differ between groups. The recovery time was 98±15 and 79±17 minutes in GM and GMF, respectively, without significant difference between treatments. The quality of recovery did not differ between groups. The results allowed us to conclude that both treatments provide cardiopulmonary stability and were satisfactory to swine endoscopy. However, despite of absence of significant difference, shorter time of recovery was observed with midazolam/fentanyl infusion.

Effect of the ketamine/xylazine anesthetic on the auditory brainstem response of adult gerbils

The auditory brainstem response (ABR) is a test widely used to assess the integrity of the brain stem. Although it is considered to be an auditory-evoked potential that is influenced by the physical characteristics of the stimulus, such as rate, polarity and type of stimulus, it may also be influenced by the change in several parameters. The use of anesthetics may adversely influence the value of the ABR wave latency. One of the anesthetics used for e ABR assessment, especially in animal research, is the ketamine/xylazine combination. Our objective was to determine the influence of the ketamine/xylazine anesthetic on the ABR latency values in adult gerbils. The ABRs of 12 adult gerbils injected with the anesthetic were collected on three consecutive days, or a total of six collections, namely: pre-collection and A, B, C, D, and E collections. Before each collection the gerbil was injected with a dose of ketamine (100 mg/kg)/xylazine (4 mg/kg). For the capture of the ABR, 2000 click stimuli were used with rarefaction polarity and 13 stimuli per second, 80 dBnHL intensity and in-ear phones. A statistically significant difference was observed in the latency of the V wave in the ABR of gerbils in the C and D collections compared to the pre-, A and E collections, and no difference was observed between the pre-, A, B, and E collections. We conclude that the use of ketamine/xylazine increases the latency of the V wave of the ABR after several doses injected into adult gerbils; thus clinicians should consider the use of this substance in the assessment of ABR.

The effects of anesthetic regimen in 90% hepatectomy in rats / Os efeitos do regime anestésico na hepatectomia de 90% em ratos

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63±31.7 mg/dL) than in the isoflurane group (98±21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

OBJETIVO: Avaliar a influência do regime anestésico sobre a recuperação anestésica, a sobrevida em 72 horas e a glicemia após hepatectomia parcial de 90% em ratos. MÉTODOS: Trinta ratos Wistar machos adultos foram distribuídos em dois grupos conforme o regime anestésico: combinação de ketamina e xilazina intraperitoneal ou isoflurano inalatório. Para prevenção de hipoglicemia foi administrada glicose intraperitoneal e adicionado glicose (20%) na água de beber. RESULTADOS: A recuperação anestésica no grupo ketamina e xilazina foi mais prolongada. Durante primeira hora após hepatectomia, nenhum rato anestesiado com ketamina e xilazina despertou. Todos do grupo isoflurano estavam ativos minutos após final da cirurgia. A sobrevida em 72 horas foi menor (Log rank=0,0001) no grupo ketamina e xilazina (0,0%) que no grupo isoflurano (26,7%). Glicemia em 6 horas do grupo ketamina e xilazina (63±31,7 mg/dL) foi menor (p=0,017) que no grupo isoflurano (98 ±21,2 mg/dL). Prolongado tempo de recuperação anestésica com ketamina e xilazina diminuiu sobrevida e glicemia após hepatectomia 90%. CONCLUSÃO: Anestesia com isoflurano reduziu tempo de recuperação e hipoglicemia, além de aumentar a sobrevida nas primeiras horas, possibilitando uma janela terapêutica adequada para estudos experimentais.