Background and objective Dexmedetomidine is characterized with effects of sedation, analgesia, amnesia and lack of respiratory depression. Hence, it should be suitable for awake fibreoptic intubation (AFOI). Methods We enrolled 30 oral cancer patients with limited mouth openings who were undergoing AFOI for elective surgery. Patients were randomly allocated into two groups; the Dex group (nU16) that received dexmedetomidine (1.0mgkg-1) infusion and the Control group (nU14) that received fentanyl (1.0mgkg-1) infusion. Main outcomes were evaluated by grading scores presenting conditions for nasal intubation and postintubation. Other analysed parameters included airway obstruction, haemodynamic changes, consumption time for intubation, amnesia level and satisfaction. Results Intubation score (1-5) representing condition for nasal intubation was significantly better in the Dex group [2(1-3)] than in the Control group [3(2-5)] (PU0.001). Postintubation score (1-3) representing tolerance to intubation also showed more favourable results in the Dex group[1(1-3)] than intheControl group[2(2-3)] (PU0.002). The Dex group showed significantly reduced haemodynamic response to intubation than the Control group. Incidence requiring temporary haemodynamic support was higher in the Dex group but not of significance. Both levels of amnesia and satisfaction score were significant in the Dex group. Other analysed parameters such as consumption time for intubation, airway obstruction score and postoperative adverse events did not differ significantly. Conclusion Combination of dexmedetomidine loading with topical anaesthesia provides significant benefit for AFOI in intubation condition, patient tolerance, haemodynamic response, amnesia and satisfaction. Dexmedetomidine is effective for AFOI in anticipated difficult airway with only minor and temporary haemodynamic adverse effects.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19565号 / 医博第4072号 / 新制||医||1013(附属図書館) / 32601 / 京都大学大学院医学研究科医学専攻 / (主査)教授 江藤 浩之, 教授 前川 平, 教授 髙折 晃史 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Os agonistas alfa 2 adrenérgicos são sedativos empregados na rotina clínica de ruminantes, e têm, entre outras, a vantagem de possuir antagonistas específicos, que aumentam a segurança no uso destes medicamentos. Tendo em vista a escassez de estudos acerca dos parâmetros hemodinâmicos e respiratórios em ovinos em posição quadrupedal e submetidos à sedação com xilazina ou dexmedetomidina com posterior reversão pelo atipamezole, realizou-se o presente estudo. Para tanto, foram utilizados 12 ovinos, machos, com idade entre um e dois anos, peso médio de 37,7kg, distribuídos em dois grupos de seis animais que foram submetidos a dois tratamentos distintos com média de três semanas de intervalo, em estudo do tipo prospectivo, encoberto e aleatório, sendo designados como Grupo XILA (cloridrato de xilazina 0,2 mg/kg IM) e Grupo DEX (cloridrato de dexmedetomidina 15 µg/kg IM). Para a instalação do cateter de artéria pulmonar os animais foram anestesiados com auxílio de máscara facial com isofluorano em oxigênio, e na sequência foram intubados e mantidos sob anestesia com o mesmo agente até o fim da instrumentação. Após a recuperação anestésica foram avaliados os parâmetros hemodinâmicos, hemogasométricos e respiratórios durante os primeiros 60 minutos com os animais em posição quadrupedal, para obtenção dos parâmetros basais. Finalizada esta avaliação, os animais foram submetidos aos protocolos de sedação segundo o seu grupo. Os parâmetros foram verificados e registrados aos cinco (S5), 15 (S15) e 30 minutos (S30) após sedação, e, após a aplicação de 30 µg/kg IM de atipamezole aos cinco (R5) e 15 minutos (R15). Foram avaliados frequência e ritmo cardíaco, pressão arterial sistêmica, parâmetros hemodinâmicos, frequência respiratória, hemogasometria arterial e venosa mista, temperatura central, glicemia e grau de sedação. Os índices ventilatórios e hemodinâmicos foram calculados. O período de latência em XILA e DEX foram 3,9 e 5,2 minutos. A xilazina promoveu sedação mais intensa, com diferença significativa entre os grupos aos 5 e 15min após sedação (momentos S5 e S15). Após a sedação, observou-se redução significativa da frequência cardíaca nos dois grupos, que refletiu no débito cardíaco, índice cardíaco e pressão arterial média. Houve elevação não significativa da resistência vascular sistêmica em ambos os grupos, mas que após o atipamezole ficou significativamente mais baixa no grupo XILA. A xilazina causou taquipneia, que foi inibida após o atipamezole. Não houve alterações clinicamente importantes nos valores de PaCO2, PaO2, SaO2 e nem nos índices de ventilação, indicando que não ocorreu hipoxemia, hipercapnia ou hipoventilação durante a sedação. A glicemia elevou-se de maneira significativa nos dois grupos mantendo-se elevada mesmo após o antagonista. Após administração do atipamezole os animais levaram 10,0 e 11,7 minutos para ficarem em posição quadrupedal e 19,3 e 30 minutos para reversão dos efeitos da xilazina e da dexmedetomidina, respectivamente. Tanto a xilazina como a dexmedetomidina promoveram sedação segura, com poucos efeitos hemodinâmicos e cardiorrespiratórios, sugerindo que a administração pela via intramuscular seja adequada para sedação de ovinos com xilazina ou dexmedetomidina / Adrenergic alpha 2 agonists are sedatives used in ruminants clinical routine and have, among others, the advantage of specific antagonists which increase the safety of these drugs. Given the scarcity of studies on the hemodynamic and respiratory parameters in sheep in standing position and undergoing sedation with xylazine or dexmedetomidine with subsequent reversal by atipamezol, this study was performed. For this purpose were used 12 male sheep, aged between one and two years, average weight 37,7kg. Sheep were divided into two groups of six animals that were submitted to two different treatments with a mean interval of three weeks, in a study of prospective hidden and random type, being designated as XILA Group (xylazine hydrochloride 0.2 mg/kg) and DEX Group (dexmedetomidine hydrochloride 15 µg/kg) given by intramuscular route. For the installation of pulmonary artery catheter, the animals were anesthetized with facial mask with isofluorane in oxygen, and were intubated and maintained under anesthesia with the same agent until the end of instrumentation. After recovery of anesthesia, we evaluated the hemodynamic, blood gas and respiratory parameters during the first 60 minutes with animals in standing position, to obtain the baseline parameters. Completed this evaluation, the animals were submitted to sedation protocols according to their group. The parameters were checked and registered to 5 (S5), 15 (S15) and 30 minutes (S30) after sedation, and after application of 30 µg/kg atipamezole by intramuscular route to 5 (R5) and 15 minutes (R15). Frequency and heart rate, systemic blood pressure, hemodynamic parameters, respiratory rate, arterial and mixed venous blood gas analysis, core temperature, blood glucose and degree of sedation were evaluated. Ventilatory and hemodynamic indices were calculated. The onset period in XILA and DEX were 3.9 and 5.2 minutes. Xylazine promoted more intense sedation, with a significant difference between the groups at 5 and 15 minutes after alpha 2 administration (S5 and S15). After sedation, significant decrease in heart rate was observed in both groups, which reflected in cardiac output, cardiac index and mean arterial pressure. There was no significant increase in systemic vascular resistance in both groups, but after atipamezol was significantly lower in the XILA group. Xylazine caused tachypnea, which was inhibited after atipamezol. There were no clinically significant changes in PaCO2, PaO2, SaO2 nor in the ventilation indices, indicating that there was no hypoxemia, hypercapnia or hypoventilation during sedation period. Blood glucose rose significantly in both groups, remained higher even after antagonist. After administration of atipamezol sheep needed 10.0 and 11.7 minutes to remain in standing position and 19.3 and 30 minutes to reverse the effects of dexmedetomidine and xylazine, respectively. Xylazine and dexmedetomidine promoted safe sedation with few hemodynamic and cardiorespiratory effects, suggesting that the intramuscularly route is suitable for sedation of sheep with xylazine or dexmedetomidine

Originalmente da Bahia, a espécie Leontopithecus chrysomelas foi introduzida no estado do Rio de Janeiro provavelmente por meio do tráfico e atualmente é encontrado em uma das áreas remanescentes de ocupação natural do mico-leão-dourado (Leontopithecus rosalia) podendo comprometer a sobrevivência do último. Visando mitigar esse problema foi criado um plano de ação, onde se recomenda a captura dos animais introduzidos. Procedimentos de captura e contenção química produzem estresse e afetam diretamente a homeostase, podendo alterar diretamente a saúde e o bem estar dos animais somando-se o fato de os protocolos de capturas atuais gerarem um período de recuperação prolongado. O objetivo deste trabalho consistiu em determinar e comparar os efeitos cardiorrespiratórios da dexmedetomidina, quando associada à cetamina S(+) ou à cetamina racêmica, e do midazolam associado à cetamina S(+), por via intramuscular, na contenção química de mico-leão-da-cara-dourada. Foram utilizados 45 animais da espécie Leontopithecus chrysomelas, adultos, machos, pesando em média 532 gramas, oriundos do Centro de Primatologia do Rio de Janeiro, em parceria com a ONG PRI-MATAS. Os animais foram distribuídos em três grupos onde receberam aleatoriamente as associações: CSM - cetamina S(+) (15 mg/kg) e midazolam (0,5 mg/kg); CSD - cetamina S(+) (15 mg/kg) e dexmedetomidina (10 µg/kg); e CD - cetamina racêmica (15 mg/kg) e dexmedetomidina (10 µg/kg). Foram avaliados os períodos de latência, hábil e de recuperação. A frequência e ritmo cardíacos, frequência respiratória, saturação da oxihemoglobina periférica, pressão arterial sistólica, temperatura retal, qualidade de indução e de recuperação, sedação, antinocicepção e grau de relaxamento muscular foram monitorados a cada cinco minutos durante 50 minutos. Os dados paramétricos foram avaliados pela análise de variância (ANOVA) seguida do teste de Tukey. Os dados não paramétricos foram avaliados pelo teste de Kruskal-Wallis seguido do teste de Dunn para identificar quais grupos apresentavam diferença estatística significativa. O grau de significância estabelecido para as análises foi de 5% (p<0,05). Os valores referentes aos parâmetros de frequência respiratória, saturação da oxihemoglobina periférica, temperatura, pressão arterial sistólica, início da perda de tônus muscular, latência e os períodos de recuperação parcial e total não apresentaram diferença entre os grupos. Já os valores de frequência cardíaca, relaxamento muscular, antinocicepção, grau de sedação e consumo de lidocaína apresentaram diferença significativa entre os mesmos momentos dos grupos CSM e CSD, e CSM e CD. Conclui-se que as associações de dexmedetomidina com cetamina racêmica e cetamina S(+) apresentaram os melhores índices de relaxamento muscular, sedação e antinocicepção e mostraram-se seguras para a realização de cirurgia de vasectomia em micos-leão-da-cara-dourada. Apesar dos grupos CSD e CD apresentarem bradicardia mais acentuada, os valores mantiveram-se dentro do limite esperado. / The Golden-headed lion tamarin, originally endemic to the southern Bahia region, was introduced in the state of Rio de Janeiro probably by illegal wildlife trade activity. The species is currently found in one of the remaining areas of natural occupation of the golden lion tamarin (Leontopithecus rosalia), which may compromise the survival of the latter. In order to mitigate this problem, an action plan was elaborated and the capture of golden-headed lion tamarins recommended. Both capture and chemical restraint procedures can cause stress and compromise homeostasis with a direct effect on the health and well-being of the animals. Besides that, current chemical immobilization protocols usually result in prolonged recovery times. This study aims to determine and compare the cardiovascular and respiratory effects of three different protocols for chemical immobilization of golden-headed lion tamarins. Thirty-five adult male specimens of Leontopithecus chrysomelas were studied. Animals were randomly separated into three groups: ketamine S(+) and midazolam (15 mg kg-1 and 0.5 mg kg--1-) (KSM group), ketamine S(+) and dexmedetomidine (15 mg kg--1- and 10 µg kg-1) (KSD group) and racemic ketamine and dexmedetomidine (15 mg kg-1 and 10 µg kg-1 ) (KD group). Periods of latency, immobilization and recovery were evaluated. Heart rate and rhythm, respiratory rate, peripheral oxyhemoglobin saturation, systolic blood pressure, rectal temperature, induction and recovery quality, sedation, antinociception, and degree of muscle relaxation were monitored every five minutes for 50 minutes. Parametric data were analyzed by using repeated measures analysis of variance (ANOVA) followed by a Tukey\'s test. Non-parametric data were analyzed by the Kruskal-Wallis test followed by Dunn\'s test. Values of P< 0.05 were considered statistically significant. No significant differences were found in respiratory rate, peripheral oxygen saturation, temperature, systolic blood pressure, onset of muscle tone loss, latency and partial and total recovery periods. Heart rate, sedation and muscle relaxation degrees, antinociception, and lidocaine consumption presented significant difference at the same moments between KSM and KSD and between KSM and KD. Marked bradycardia was presented on KSD and KD groups, with values remaining within the normal range. This study demonstrated that combinations of dexmedetomidine with racemic ketamine and S(+) ketamine presents the best outcomes for muscle relaxation, sedation and antinociception and were safe for vasectomy surgery in golden-headed lion tamarins.

Este estudo determinou e comparou os efeitos da administração epidural ou infusão contínua intravenosa de dexmedetomidina em gatas anestesiadas com propofol e isofluorano para realização de ovariossalpingohisterectomia. Vinte e uma gatas (peso: 3.06&plusmn;0.35 kg) foram pré-tratadas com dexmedetomidina (4 mcg.kg-1, IM). Quinze minutos depois, administrou-se propofol para permitir entubação orotraqueal seguido de manutenção anestésica com isofluorano diluído em oxigênio por um circuito Mapleson D com respiração espontânea. As gatas foram distribuídas aleatoriamente, em três grupos, onde receberam, por via epidural, lidocaína (1 mg.kg-1, G1, n=7) ou lidocaína (1 mg.kg-1) + dexmedetomidina (4 mcg.kg-1, G2, n=7) ou lidocaína (1 mg.kg-1) + infusão contínua intravenosa de dexmedetomidina (0,25 mcg.kg-1.min-1, G3, n=7). O volume da solução para administração epidural foi ajustada para 0.3 mL.kg-1 com solução salina. A profundidade anestésica foi realizada por um único avaliador que não possuía conhecimento dos fármacos empregados pela via epidural e intravenosa. Foram mensurados freqüência cardíaca (FC) e respiratória (FR), pressão arterial sistólica (PAS) e temperatura retal (TR) antes e quinze minutos após a medicação pré-anestésica. Durante a anestesia, FC, FR, pressões arteriais, concentração expirada de CO2, concentração expirada de isofluorano (ISOe), TR e grau de relaxamento muscular foram avaliados em intervalos de 15 minutos de 20 até 80 minutos. A hemogasometria foi realizada aos 20 e 80 minutos após a indução anestésica. Os valores de FC, FR, TR, escore de analgesia, qualidade e os tempos de recuperação anestésica foram avaliados por três horas após o término da anestesia. Utilizou-se o teste t pareado para avaliar os efeitos do pré-tratamento e os valores hemogasométricos nos dois momentos. O teste análise de variância seguido de Tukey e Friedmann seguido de Dunn foram realizados para variáveis paramétricas e não paramétricas respectivamente (p&LT;0.05). O pré-tratamento com dexmedetomidina reduziu a FC, FR, PAS e TR. A dose de propofol utilizada para indução anestésica foi 7.4&plusmn;1.4 mg.kg-1. Quando comparado ao G1, a dexmedetomidina, por via epidural, reduziu significativamente a FC dos 20 aos 65 minutos da anestesia e aos 150 e 180 minutos após o término da anestesia, entretanto, por infusão contínua intravenosa reduziu a FC em todos os momentos avaliados da anestesia e recuperação anestésica. Quando comparado ao G2, a infusão contínua intravenosa de dexmedetomidina reduziu a FC aos 60 e 90 minutos da recuperação anestésica. No G1 a média&plusmn;DP ISOe variou de 0.86&plusmn;0.28% a 1.91&plusmn;0.63% de 20 a 80 minutos. Neste período, ISOe foi significativamente menor no G2 (variação de 0.70&plusmn;0.12% a 0.97&plusmn;0.20%) e G3 (variação de 0.69&plusmn;0.12% to 1.17&plusmn;0.25%). Aos 20 minutos, a PaCO2 foi significativamente superior em G3 em relação ao G1. Os tempos de recuperação anestésica foram significativamente menores no G1, exceto o tempo de extubação se comparado ao G2. Não houve diferença significativa nas outras variáveis entre os três grupos. Conclui-se que o pré-tratamento com dexmedetomidina promoveu depressão cardiorrespiratória. A administração epidural e a infusão contínua intravenosa de dexmedetomidina reduziram o consumo do agente inalatório e produziram recuperação de melhor qualidade e mais prolongada. As administrações de dexmedetomidina causaram bradicardia, porém sem afetar a pressão arterial. / This study compared the effects of epidural or continuous intravenous infusion of dexmedetomidine in isoflurane-anesthetized cats undergoing ovariohysterectomy. Twenty-one cats (weight: 3.06±0.35 kg) were premedicated with dexmedetomidine (4 mcg.kg-1, IM). Fifteen minutes later, propofol was titrated to allow endotracheal intubation and anesthesia was maintained in spontaneously breathing cats with isoflurane in oxygen using a Mapleson D system. Cats were randomly allocated to receive either epidural lidocaine (1 mg.kg-1, G1, n=7) or epidural lidocaine (1 mg.kg-1) + dexmedetomidine (4 mcg.kg-1, G2, n=7) or epidural lidocaine (1 mg.kg-1) + continuous intravenous infusion of dexmedetomidine (0,25 mcg.kg-1. min-1, G3, n=7). The volume of either epidural injection was adjusted to 0.3 mL.kg-1 with saline. The individual controlling depth of anesthesia was blinded to the drug being administered epidurally and intravenouslly. Heart (HR) and respiratory (RR) rates, systolic arterial blood pressure (SAP) and rectal temperature (RT) were recorded before and after 15 minutes of premedication. During anesthesia, heart (HR) and respiratory (RR) rates, invasive arterial blood pressures, end-tidal CO2, end-tidal isoflurane (ISOe), RT and muscular relaxation were recorded at 15 minute intervals from 20 until 80 minutes. Arterial blood gases were measured at 20 and 80 min after induction. HR, RR, RT, analgesia score, and recovery quality and times were compared for 3 hours after end of anesthesia. Paired t test were performed to compare the premedication effects and arterial blood gases at differents intervals. ANOVA with Tukey post-test and Friedmann with Dunn post-test were performed to parametric and nonparametric values, respectively (P<0.05). Dexmedetomidine premedication decreased HR, RR, SAP and RT. The induction dose of propofol was 7.4±1.4 mg.kg-1. When compared to the G1, epidural dexmedetomidine significantly decreased HR from 20 to 65 minutes of anesthesia and 150 and 180 minutes after end of anesthesia, however, continuous intravenous infusion decreased HR all times during anesthesia and recovery time. When compared to G2, continuous intravenous infusion of dexmedetomidine decreased HR at 60 and 90 minutes during recovery. In the G1 mean±SD ISOe concentrations ranged form 0.86±0.28% to 1.91±0.63% from 20 to 80 min. At the same time interval, ISOe concentrations were significantly lower in the G2 (ISOe ranged from 0.70±0.12% to 0.97±0.20%) and G3 (ISOe ranged from 0.69±0.12% to 1.17±0.25%). PaCO2 was significantly greater in G3 than G1 at 20 minutes. The recovery times were significantly lower in the G1 except for extubation time when compared with G2. There were no significant differences among groups for the remaining variables. It was concluded that premedication with dexmedetomidine produced cardiorespiratory depression. Epidural administration and continuous intravenous infusion of dexmedetomidine significantly reduced inhalant requirements for maintaining anesthesia and produced a better anesthesia recovery although of longer duration. Dexmedetomidine administration may cause bradycardia, however reduced HR does not affect arterial blood pressure.

Pela sua alta incidência, morbidade, mortalidade e custos ao sistema de saúde, a sepse se destaca entre as diversas indicações de internação em unidade de terapia intensiva (UTI). A disfunção da microcirculação tem papel central na gênese e manutenção da síndrome séptica, sendo um marco fisiopatológico desta síndrome. Pacientes críticos invariavelmente estão ansiosos, agitados, confusos, desconfortáveis e/ou com dor. Neste contexto, drogas sedativas são amplamente utilizadas na medicina intensiva. A dexmedetomidina, um agonista potente e altamente seletivo dos receptores alfa-2 adrenérgicos, vem conquistando espaço como o sedativo de escolha nas UTIs por seus efeitos de sedação consciente, redução da duração e incidência de delirium e preservação da ventilação espontânea. Apesar destas possíveis vantagens, a indicação de uso da dexmedetomidina na síndrome séptica ainda carece de conhecimentos sobre seus efeitos na microcirculação e perfusão orgânica. Com o intuito de caracterizar os efeitos microcirculatórios da dexmedetomidina em um modelo murino de endotoxemia que permite estudos in vivo da inflamação e disfunção da perfusão microvascular, hamsters Sírios dourados submetidos à endotoxemia induzida por administração intravenosa de lipopolissacarídeo de Escherichia coli (LPS, 1,0 mg.kg-1) foram sedados com dexmedetomidina (5,0 &#956;g.kg.h-1). A microscopia intravital da preparação experimental (câmara dorsal) permitiu a realização de uma análise quantitativa das variáveis microvasculares e do rolamento e adesão de leucócitos à parede venular. Também foram analisados os parâmetros macro-hemodinâmicos e gasométricos (arterial e venoso portal), as concentrações de lactato arterial e venoso portal, a água pulmonar total e a sobrevivência do animal. Animais não-endotoxêmicos e/ou tratados com solução salina a 0,9% serviram como controles neste experimento. O LPS aumentou o rolamento e a adesão de leucócitos à parede venular, diminuiu a densidade capilar funcional e a velocidade das hemácias nos capilares e induziu acidose metabólica. O tratamento com dexmedetomidina atenuou significativamente estas respostas patológicas (p < 0,05). A frequência de pulso dos animais foi significativamente reduzida pela droga (p < 0,05). Outros resultados não foram tão expressivos (estatisticamente ou clinicamente). Estes resultados indicam que a utilização de dexmedetomidina produz um efeito protetor sobre a microcirculação da câmara dorsal de hamsters endotoxêmicos. Efeitos anti-inflamatórios da dexmedetomidina sobre os leucócitos e o endotélio poderiam melhorar a perfusão capilar e representar o mecanismo in vivo de ação da droga na microcirculação. / Due to its high incidence, morbidity, mortality and costs to the healthcare system, sepsis stands out among the many indications for intensive care unit (ICU) admission. The microcirculatory dysfunction plays a central role in the genesis and maintenance of the septic syndrome, being a pathophysiologic milestone in this syndrome. Critically ill patients are invariably anxious, agitated, confused, uncomfortable and/or with pain. In this context, sedative drugs are widely used in intensive care medicine. Dexmedetomidine, a potent and highly selective agonist of alpha-2 adrenergic receptors, is gaining ground as the sedative of choice in ICUs due to its effects of "conscious sedation", reducing the duration and incidence of delirium and preservation of spontaneous ventilation. Despite these potential advantages, the indication of dexmedetomidine in sepsis syndrome still lacks knowledge about its effects on microcirculation and perfusion. To characterize microcirculatory actions of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microvascular inflammation and perfusion dysfunction, endotoxemia-submitted Syrian golden hamsters, induced by intravenous Escherichia coli lipopolysaccharide (LPS, 1,0 mg.kg-1) administration, were sedated with dexmedetomidine (5,0 &#956;g.kg.h-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Macro-hemodynamic parameters, arterial and portal venous blood gases and lactate concentrations, pulmonary total water, and animal survival were also analyzed. Non-endotoxemic and/or normal saline treated animals served as controls in this experiment. LPS increased leukocyte rolling and adhesion, decreased functional capillary density and red blood cell velocity, and induced metabolic acidosis. Dexmedetomidine treatment significantly attenuated these pathologic responses (p < 0.05). The pulse rate was significantly reduced by the drug (p < 0.05). Other results were not as expressive (statistically or clinically). These results indicate that the use of dexmedetomidine yields a protective effect on the microcirculation of the dorsal skinfold in endotoxemic hamsters. Anti-inflammatory dexmedetomidine effects on leukocytes and the endothelium, subsequently improving capillary perfusion, could represent the in vivo mechanism of the microcirculatory action of the drug.

The objectives of this study were to determine the cardiopulmonary effects and pharmacokinetics of fentanyl in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine sedation. This was investigated in 7 healthy dogs using a randomized cross over study design. Dogs were given fentanyl as an initial IV loading dose (5 μg/kg) followed by an infusion (5 μg/kg/hr) for 120 minutes during isoflurane anesthesia and for 60 minutes following isoflurane discontinuation. Dogs received IV dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg) or saline at the time of isoflurane discontinuation. Cardiopulmonary variables were measured and blood samples were obtained at multiple time points during the anesthetic maintenance and recovery phases. Plasma concentrations of fentanyl were measured using HPLC-MS, and subsequent population pharmacokinetic analysis was performed. During isoflurane anesthesia, fentanyl bolus administration resulted in significant changes in measured cardiopulmonary variables, however, many returned to baseline values during the maintenance of anesthesia. During anesthetic recovery, dexmedetomidine administration resulted in significant increases in PaCO2, and decreases in PvO2 and CI. Systemic arterial blood pressures were significantly lower in dogs receiving acepromazine, however CI and PvO2 were significantly higher compared to the other treatments. Analysis of fentanyl plasma concentrations showed that fentanyl pharmacokinetics best fit a 2-compartmental model, with average concentrations in the treatment groups ranging from 1.6 to 4.5 ng/mL during isoflurane anesthesia, and from 1.6 to 2.0 ng/mL during anesthetic recovery. Plasma concentrations of fentanyl were significantly higher with dexmedetomidine administration compared to the other treatments during the recovery period. Compared to the maintenance phase of anesthesia, anesthetic recovery with dexmedetomidine administration did not significantly change fentanyl pharmacokinetics, while acepromazine administration increased systemic and intercompartmental clearance, and recovery without sedation increased the central volume of distribution and systemic clearance. In conclusion, recovery from anesthesia with concurrent fentanyl administration, with or without sedation, caused clinically significant alterations in cardiopulmonary function that influenced fentanyl disposition in healthy dogs. / Ontario Veterinary College Pet Trust Fund

Made available in DSpace on 2016-09-27T13:40:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-09-21. Added 1 bitstream(s) on 2016-09-27T13:45:11Z : No. of bitstreams: 1 000870504.pdf: 2094890 bytes, checksum: 4efcd5daececceda5488d900500bc29b (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / The study aimed to evaluate the effects of administration of ropivacaine 0.75% combined with dexmedetomidine on the sciatic and femoral nerves in dogs. Seven adult and healthy Beagle dogs were submitted to three experimental groups. In GCON, animals received perineural ropivacaine 0,75% (0.1mL/kg/nerve); GDPN received perineural dexmedetomidine diluted (1μg/mL) in ropivacaine 0,75% (0.1mL/kg/nerve); and GDIM received perineural ropivacaine 0,75% (0.1mL/kg/nerve) and dexmedetomidine diluted in saline (1μg/mL) via intramuscular administration (0,2mL/kg). The perineural administrations were carried out under general inhalation anesthesia and guided by ultrasound and nerve stimulation. Onset time and duration of sensory and motor blocks were evaluated, as well as patellar, gastrocnemius and cranial tibial reflexes, heart (FC) and respiratory rate (f), systolic arterial pressure (PAS), rectal temperature (TR), lactate (LACT), blood glucose (GLIC), sedation (SED) and blood gas analysis during 240 minutes. No differences were observed between groups with regards to FC, f, PAS, LACT, GLIC, TR, SED, blood gas, reflexes and sensory and motor block latency. However, the duration of the tibial sensory block was significantly longer in GDPN compared with GDIM (p=0,0302). Administration of perineural or intramuscular dexmedetomidine did not cause changes in physiologic parameters or the onset time and duration of motor block. The perineural administration of dexmedetomidine prolonged the duration of the sensory block only for the tibial nerve.

Made available in DSpace on 2014-06-11T19:29:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-27Bitstream added on 2014-06-13T18:38:43Z : No. of bitstreams: 1 campagnol_d_me_botfm.pdf: 1816065 bytes, checksum: eea006d91fee7f915efbe5633c51ab40 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A administracao intravenosa de dexmedetomidina reduz significativamente a concentracao alveolar minima (CAM) dos agentes halogenados. No entanto, esse beneficio e frequentemente acompanhado por efeitos colaterais tipicos dos agonistas 2, como hipertensao, bradicardia e reducao do debito cardiaco. Ha indicios de que a administracao epidural de doses reduzidas de dexmedetomidina pode potencializar e prolongar seu efeito analgesico. Hipotetizou-se que a administracao epidural de dexmedetomidina reduziria a CAM do isofluorano de forma dose e tempo-dependente, sem ocasionar depressao cardiovascular significativa. Objetivou-se tambem caracterizar as alteracoes do indice bispectral (BIS) induzidas pela estimulacao nociceptiva empregada na mensuracao da CAM, bem como o efeito da dexmedetomidina epidural sobre essas alteracoes. Seis caes higidos (18,8}4,0 kg) foram anestesiados com isofluorano em 4 ocasioes distintas, com intervalo de 7 dias. Em cada anestesia, os animais receberam aleatoriamente 1 de 4 tratamentos pela via epidural. No tratamento controle, administrou-se solucao salina, enquanto nos tratamentos DEX1.5, DEX3 e DEX6, administrou-se dexmedetomidina nas doses de 1,5 . 3,0 e 6,0 Êg/kg, respectivamente. A CAM do isofluorano foi mensurada as 2 e 4,5 horas apos os tratamentos epidurais, por meio de estimulacao nociceptiva supramaxima (50V, 50 Hz e 10 ms) no membro pelvico. O valor medio de CAM (} desvio padrao) no tratamento controle foi de 1,57}0,23% e 1,55}0,25% as 2 e 4,5 horas, respectivamente. Quando comparado ao tratamento controle, o valor de CAM observado no tratamento DEX1,5 foi reduzido em 13% as 2 horas (1,35}0,11%), enquanto que a reducao as 4,5 horas (7% de reducao, CAM: 1,43}0,23%) nao foi significativa. No tratamento DEX3, a CAM foi significativamente reduzida em 29% (1,12}0,18%) e 13% (1,33}0,16%) as 2 e 4,5 horas, respectivamente. Reducoes de maior magnitude foram observadas... / Intravenous administration of dexmedetomidine significantly reduces the minimum alveolar concentration (MAC) of inhalant anesthetics. However, this beneficial effect is often associated with side effects such as hypertension, bradycardia, and a decrease in cardiac output. There are evidences epidural administration of relatively low doses of dexmedetomidine may result in more prolonged analgesia than intravenous administration of higher doses. The hypothesis of the present study is that epidural administration of dexmedetomidine would reduce isoflurane MAC in a dose and time-related fashion, without causing marked cardiovascular changes. This study aimed also to characterize the changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determinations and the effects of epidural dexmedetomidine on these changes. Six healthy dogs (18.8 8l4,0 kg) were anesthetized with isoflurane at 4 different occasions with at least 1-week intervals. On each anesthetic procedure, animals received 1 of 4 epidural treatments. Physiologic saline solution was administered in the control treatment, while for the treatments DEX1.5, DEX3, and DEX6, dexmedetomidine was administered at the doses of 1.5, 3.0, and 6.0 ìg/kg, respectively. Isoflurane MAC was assessed at 2 and 4.5 hours after epidural injections by means of supramaximal nociceptive stimulation (50V, 50 Hz e 10 ms) administered to the pelvic limb. Mean (l SD) isoflurane MAC in the control treatment was 1.57l0.23% and 1.55l0.25% at 2 e 4,5 hours, respectively. When compared to controls, mean MAC values observed in the DEX1.5 treatment were significantly reduced by 13% at 2 hours (1.35l0.11%), while the reduction observed at 4.5 hours (7% reduction, MAC: 1.43l0.23%) was not statistically significant... (Complete abstract click electronic access below)

Orientador: Antonio José de Araújo Aguiar / Banca: Stelio Pacca Loureiro Luna / Banca: Susane Lilian Beier / Resumo: A dexmedetomidina e o butorfanol, administrados por infusão intravenosa contínua, podem ser úteis para sedação contínua em equinos mantidos na posição quadrupedal. Os efeitos hemodinâmicos, respiratórios e sedativos da infusão intravenosa contínua da dexmedetomidina, associada ou não ao butorfanol, foram avaliados em seis equinos adultos (432±25 kg). Os animais foram submetidos a dois tratamentos aleatoriamente: dexmedetomidina (DEX) e dexmedetomidina e butorfanol (DEX+BUT), com intervalo mínimo de sete dias entre eles. Após preparação, os equinos ainda conscientes receberam o tratamento DEX: dexmedetomidina (bolus 3,5 mcg.kg-1 IV e taxa de infusão 5 mcg.kg-1.h-1) ou DEX+BUT: dexmedetomidina (bolus 3,5 mcg.kg-1 IV e taxa de infusão 3,5 mcg.kg-1.h-1) e butorfanol (bolus 0,02 mg.kg-1 IV e taxa de infusão 0,024 mg.kg-1.h-1). Os escores de sedação e as variáveis hemodinâmicas (método de termodiluição) e respiratórias foram registradas antes da sedação (momento basal), durante as infusões (5, 15, 30, 60 e 90 minutos) e após a interrupção das mesmas (15, 30 e 60 minutos). O teste T-pareado e ANOVA seguida do teste Tukey-Kramer foram utilizados para comparação dos valores cardiorrespiratórios (média±DP). Friedman seguido do teste de Dunn foram utilizados para análise de sedação (p < 0,05). A redução significativa do índice cardíaco (DEX (-37%; 60±9 para 38±4 mL.min-1.kg-1) e DEX+BUT (-41%; 63±6 para 37±4 mL.min-1.kg-1)), frequência cardíaca (DEX (-34%; 44±3 para 29±4 bpm) e DEX+BUT (-30%; 43±5 para 30±4 bpm)), índice de transporte de oxigênio (DEX (-47%; 1166±339 para 613±136 dL.min-1.kg-1) e DEX+BUT (-48%; 1075±204 para 555±73 dL.min-1.kg-1)) e frequência respiratória (DEX (-63%; 16±3 para 10±2 mpm) e DEX+BUT (-63%; 16±1 para 10±2 mpm)) foram acompanhados pelo aumento significativo do índice de resistência vascular ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Dexmedetomidine and butorphanol, administered by constant rate infusion (CRI) might be useful for continuous sedation in standing horses. The hemodynamic, respiratory and sedative effects of the CRI dexmedetomidine associated with butorphanol and CRI dexmedetomidine were evaluated in six adults horses (432±25 kg). The animals underwent 2 treatments in random order: dexmedetomidine (DEX) and dexmedetomidine and butorphanol (DEX+BUT) in a minimum 7-day interval. After instrumentation while unsedated all horses received treatment DEX: dexmedetomidine (3.5 mcg/kg bwt bolus IV, followed by 5 mcg/kg/hour bwt CRI) or treatment DEX+BUT: dexmedetomidine (3.5 mcg/kg bwt bolus IV, and 3.5 mcg/kg/hour bwt CRI) and butorphanol (0.02 mg/kg bwt bolus IV, and 0.024 mg/kg/hour bwt CRI). Sedative scores and hemodynamic (thermodilution method) and respiratory variables were recorded before sedation (baseline), during infusions (5, 15, 30, 60 and 90 minutes) and after infusions (15, 30 and 60 minutes). T-test and ANOVA followed by Tukey-Kramer's test were used to compare cardiorespiratory values (mean±SD), and Friedman followed by Dunn's test were used for sedation analysis (p < 0.05). The decreased from baseline in cardiac index (DEX (-37%; 60±9 to 38±4 mL/minute/kg) and DEX+BUT (-41%; 63±6 to 37±4 mL/minute/kg)), heart rate (DEX (-34%; 44±3 to 29±4 bpm) and DEX+BUT (-30%; 43±5 to 30±4 bpm)), delivery oxygen index (DEX (-47%; 1166±339 to 613±136 dL/minute/kg) and DEX+BUT (-48%; 1075±204 to 555±73 dL/minute/kg)) and respiratory rate (DEX (-63%; 16±3 to 10±2 mpm) and DEX+BUT (-63%; 16±1 to 10±2 mpm)), were accompanied by an increase from baseline in systemic vascular resistance index (DEX (+61%; 129±15 to 210±14 dynas/s/cm-5/kg) and DEX+BUT (+61%; 132±19 to 218±25 dynas/s/cm-5/kg)). The infusions induced head drop (DEX 51% and DEX+BUT 55%), decreased from baseline in sedation ... (Complete abstract click electronic access below) / Mestre