Efectividad de la ketamina en depresión bipolar: revisión sistemática de la literatura

Introducción: Aunque el hallazgo clínico más distintivo del Trastorno Afectivo Bipolar es el ánimo patológicamente elevado, este no suele ser el estado de ánimo prevalente de la enfermedad. La fase depresiva del trastorno o depresión bipolar es más crónica, conlleva a un mayor deterioro de la funcionalidad y representa un reto terapéutico habitual. En la actualidad, el manejo farmacológico de la depresión bipolar suele consistir en combinaciones de al menos dos medicamentos distintos, incluyendo estabilizadores del afecto (litio y anticonvulsivantes), antipsicóticos atípicos y antidepresivos. El objetivo central de este trabajo es evaluar la efectividad de la Ketamina en la depresión bipolar. Métodos: Revisión sistemática de la literatura de artículos que proporcionen información sobre la eficacia de la Ketamina en la fase depresiva del Trastorno Bipolar. Resultados: De los 147 artículos arrojados por la búsqueda, dos cumplieron los criterios de selección (n=33). En comparación con placebo, ketamina tiene un efecto antidepresivo rápido y duradero, incluso en pacientes que han recibido más de 3 medicamentos previamente. No se reportaron efectos adversos severos durante los estudios. Discusión. La evidencia actual apunta a que la ketamina es útil para el manejo de la depresión bipolar, incluso cuando es resistente al tratamiento, es segura y puede tener cierto efecto antisuicida. Es necesario ampliar la evidencia existente.

Parâmetros eletrocardiográficos de felideos selvagens da Amazônia (Panthera onca, Leopardus pardalis, Leopardus wiedii, Herpailurus yaguarondi) criados em cativeiro no estado do Pará, tranquilizados com ketamina e cloridrato de xilazina

Pretendeu-se estabelecer os parâmetros eletrocardiográficos (ECG) para felinos selvagens da Amazônia - Panthera onca (onça pintada), Leopardus pardalis (jaguatirica), Leopardus wiedii (gato-maracajá) e Herpailurus yaguarondi (gato-mourisco). Dentre estes felinos, 17 animais pertenciam ao Parque Zoobotânico Dr. Adhemar Monteiro (Capitão Poço/PA) e 2 animais ao 2° Batalhão de Infantaria de Selva (Belém/PA). Embora, o exame eletrocardiográfico não cause dor aos animas, é necessária a realização de contenção química, visto que os animais são perigosos e estressados. Dessa forma, instaurou-se um protocolo de contenção química, visando evitar fugas, estresse excessivo e proteger a integridade física dos animais e do examinador/auxiliares. Antes de serem sedados os animais passaram por jejum alimentar de 24 horas e hídrico de 12 horas. Posteriormente, foram contidos quimicamente, através do uso associativo entre os anestésicos cloridrato de ketamina (10mg/Kg) e cloridrato de xilazina (1mg/Kg), utilizando dardos com auxílio de uma zarabatana ou aplicação intra-muscular após contenção física com puçá. Na realização do eletrocardiograma utilizou-se o mesmo protocolo usado para os animais domésticos. A média de batimentos cardíacos foram os seguintes: 90 bpm para jaguatiricas, 106 bpm gato-maracajá, 166 bpm gato-mourisco e 91 bpm onças pintadas. A maioria das espécies apresentaram ritmo sinusal normal. O eixo elétrico médio variou de 90° a 120°. Os complexos QRS foram predominantemente positivos em DI, DII, DIII e AVF, e negativos em AVR e AVL. As derivações pré-cordiais apresentaram resultados semelhantes aos esperados para o gato doméstico. Os parâmetros observados durantes este estudo, correlacionados com os animais domésticos, apresentaram algumas diferenças, que se devem em função das diferenças fisiológicas associadas ao maior tamanho corporal dos felinos selvagens. Este é um estudo pioneiro visando solucionar problemas com relação ao ECG de felinos selvagens da Amazônia. Portanto, investigações mais amplas sobre o mesmo tema são necessárias para estabelecer critérios a respeito de anormalidades nessas espécies, devendo incluir outras drogas anestésicas e relatórios para combinações de características eletrocardiográficas de animais com doença cardíaca e com distúrbios eletrolíticos.

Efeitos da nicotina no complexo do septo medial na via septo hipocampal em camundongos anestesiados por Ketamina

Nicotine administration in humans and rodents enhances memory and attention, and also has a positive effect in Alzheimer's Disease. The Medial Septum / Diagonal Band of Broca complex (MS/DBB) – a main cholinergic system – massively projects to the hippocampus through the fimbria-fornix, and this pathway is called the septohippocampal pathway. It has been demonstrated that the MS/DBB acts directly on the local field potential (LFP) rhythmic organization of the hippocampus, especially in the rhythmogenesis of Theta (4-8Hz) – an oscillation intrinsically linked to hippocampus mnemonic function. In vitro experiments gave evidence that nicotine applied to the MS/DBB generates a local network Theta rhythm within the MS/DBB. Thus, the present study proposes to elucidate the function of nicotine in the MS/DBB on the septo-hippocampal pathway. In vivo experiments compared the effect of MS/DBB microinfusion of saline (n=5) and nicotine (n=8) on Ketamine/Xylazine anaesthetized mice. We observed power spectrum density in the Gamma range (35 to 55 Hz) increasing in both structures (Wilcoxon Rank-Sum test, p=0.038) but with no change in coherence between these structures in the same range (Wilcoxon Rank-Sum test, p=0.60). There was also a decrease in power of the ketamineinduced Delta oscillation (1 to 3 Hz). We also performed in vitro experiments on the effect of nicotine on membrane voltage and action potential. We patch-clamped 22 neurons in current-clamp mode; 12 neurons were responsive to nicotine, half of them increased firing rate and other 6 decreased, and they significantly differed in action potential threshold (-47.3±0.9 mV vs. -41±1.9 mV, respectively, p=0.007) and halfwidth time (1.6±0.08 ms vs. 2±0.12 ms, respectively, p=0.01). Furthermore, we performed another set of in vitro experiments concerning the connectivity of the three major neuronal populations of MS/DBB that use acetylcholine, GABA or glutamate as neurotransmitter. Paired patch-clamp recordings found that glutamatergic and GABAergic neurons realize intra-septal connections that produce sizable currents in MS/DBB postsynaptic neurons. The probability of connectivity between different neuronal populations gave rise to a MS/DBB topology that was implemented in a realistic model, which corroborates that the network is highly sensitive to the generation of Gamma rhythm. Together, the data available in the full set of experiments suggests that nicotine may act as a cognitive enhancer, by inducing gamma oscillation in the local circuitry of the MS/DBB.

Efectos de la ketamina o la alfaxalona y su combinación con diazepam o dexmedetomidina en el cerdo

La especie porcina constituye hoy en día la de elección en muchos modelos experimentales utilizados en investigación, debido principalmente, a sus similitudes anatómicas y fisiológicas y a su reactividad farmacológica con el hombre; sin embargo son animales de difícil manejo que se estresan con facilidad, por lo que la vía intramuscular constituye la vía más cómoda y fácil de utilizar. Tradicionalmente se ha utilizado, para la tranquilización y anestesia de la especie porcina la ketamina, combinada con benzodiacepinas o con agonistas de los receptores adrenérgicos α2 habituales; sin embargo, recientemente se están empleando nuevos y potentes fármacos para la tranquilización y anestesia de esta especie, entre los que se encuentran la dexmedetomidina, un agonista potente, eficaz y selectivo de los receptores adrenérgicos α2 sobre el sistema nervioso central y periférico. La bradicardia e hipotensión se encuentran entre sus efectos adversos más comunes, sin embargo ejerce un efecto leve sobre la ventilación y produce un excelente efecto sedante y antinociceptivo, disminuyendo los requerimientos de otros fármacos anestésicos intravenosos, con la ventaja de poder ser antagonizada, por lo que viene siendo utilizada en medicina veterinaria tanto en el campo de la anestesiología clínica como en la captura y manejo de animales exóticos. La dexmedetomidina se ha empleado tanto en medicina humana como en veterinaria de forma parenteral sola y/o combinada con ketamina o alfaxalona...

Evaluación intraoperatoria y postoperatoria del efecto analgésico de infusiones intravenosas de tramadol, ketamina, lidocaína y su combinación, en hembras caninas sometidas a ovariohisterectomía

Tesis (Médico Veterinario). -- Universidad de La Salle. Facultad de Ciencias Agropecuarias. Programa de Medicina Veterinaria, 2014

Ketamina para el tratamiento de la hiperalgesia causada por remifentanil en cirugía: revisión sistemática de literatura

La hiperalgesia secundaria a la administración de remifentanil se ha documentado tanto en estudios animales como en estudios experimentales en humanos y ha aumentado su incidencia dado su uso cada vez más frecuente para el mantenimiento durante diferentes procedimientos anestésicos, anestesia general balanceada, anestesia total intravenosa y sedaciones. La hiperalgesia secundaria al uso de remifentanil es un proceso pro-nociceptivo relacionado pero que difiere de la tolerancia aguda, en el que los neurotransmisores excitatorios de N- metil D aspartato (NMDA) juegan un rol central. Por tanto la ketamina se ha utilizado en diferentes dosis para la prevención de dicha hiperalgesia sin que se haya establecido su efectividad para la prevención y tratamiento de esta condición. Se encontraron 8 estudios publicados en los últimos 10 años que proponen a la ketamina como una estrategia útil y efectiva el tratamiento de la hiperalgesia inducida por el uso de remifentanil. Los resultados demuestran que la ketamina es un tratamiento costo efectivo para el tratamiento de la hiperalgesia en diferentes poblaciones sometidas a diversos procedimientos quirúrgicos y anestésicos que incluyan la administración de remifentanil tanto en la inducción como en el mantenimiento anestésico sin generar efectos secundarios adicionales, así como que logra disminuir el consumo de opioides y la EVA en el posoperatorio.

Impacto en la calidad de la Inducción anestésica con premedicación en pacientes pediatricos

La inducción anestésica en niños es uno de los mayores retos para los anestesiólogos ya que es la fase más estresante del período perioperatorio para el paciente pediátrico. Existen diferentes intervenciones para minimizar la ansiedad perioperatoria y aumentar la cooperación del paciente pediátrico con la inducción anestésica. Entre las intervenciones exitosas la premedicación farmacológica con midazolam ha mostrado grandes beneficios en pacientes pediátricos. Metodología: Se realizó un estudio de casos y controles en pacientes pediátricos llevados a cirugía en la Fundación Cardioinfantil entre 2011-2014. Por medio de muestreo aleatorio por conveniencia se tomaron como casos pacientes con premedicación y controles pacientes sin premedicación. El éxito en la inducción se midió por medio de la escala ICC, usada a nivel mundial. Resultados: El promedio de edad fue 4.9 σ 3.01 años para los casos y 5.02σ3.2 años para controles, presentaron la misma distribución por género, 40.6% femenino, 59.3% masculino. El éxito de la inducción anestésica con midazolam mostró resultados significativos (OR 7.3 IC95% 4.3 – 12.5 p0,000), en hombres (OR 9.44 IC95%4.5 – 19.8 p0,000), en menores de 5 años (OR 10.33 IC95% 5.07 – 21.04 p0,000), en pacientes con antecedentes quirúrgicos (OR 12.2 IC95% 5.28 – 27.8 p0.000) o anestesias previas (OR 7.9 IC95% 4.4 – 14.4 p0,000). Discusión: El midazolam como agente farmacológico usado para premedicación en pacientes pediátricos presenta resultados exitosos contundentes, por lo cual debe usarse en todos los casos.

Avaliação de efeitos toxicológicos e comportamentais de ginseng panax em ratos

Panax ginseng CA Meyer (Araliaceae) is a herbaceous plant widely used in China, South Korea, Japan and other Asian countries for the treatment of various diseases micro circulatory, cerebrovascular, among others, representing one of the drugs used by older man. It has over 30 biologically active ginsenosides with different pharmacological and behavioral effects and inhibitory effect on the NMDA receptor. The amino acid glycine is a co-agonist of the NMDA receptor, activating this receptor. At the cellular level, ketamine is widely known to be NMDA receptor antagonist. The aim of this study was to evaluate the general activity in the open field, and anxiety in elevated plus maze, mice treated with P. ginseng compared with the action of ketamine and glycine, to better understand the action of this herbal medicine at the NMDA receptor. We used 66 adult male rats were divided into six groups: a positive control, treated for 30 days with water by gavage, who received glycine (500mg/kg; po) on days 7, 14, 21 and 28 of treatment, one hour before of behavioral assessment, a negative control was treated for 30 days with water by gavage received ketamine (5mg/kg, ip) on days 7, 14, 21 and 28 of treatment, one hour prior to behavioral evaluation, three experimental groups, receiving 100, 200 or 300 mg / kg P. ginseng by gavage for 30 days and one group treated solely with white water, and is also administered 1 ml of water by gavage one hour prior to behavioral evaluation. Animal behavior in these three groups was also examined on days 7, 14, 21 and 28 of treatment. On day 30 of treatment, the animals were anesthetized with thiopental (70mg/kg) for blood collection and after euthanasia, withdrawal of various organs. There were no changes in weight and body weight gain and weight reasons in organ / body weight. However the consumption of water and food values showed a significant increase. Serum levels of AST was increased in a dose-dependently in the animals treated with doses of P. ginseng, glycine and ketamine as compared to the blank group. Unlike creatinine levels proved to be decreased in all treated groups when compared with white. However, the level of urea in these groups was reduced and no changes were observed in the ALT parameter. Histopathological examination revealed no changes in cell morphology in different tissues. There were no behavioral changes in the elevated plus maze and few changes were observed in the open field, animals treated with P. ginseng, glycine and ketamine when compared to white. These data suggest that the doses of P. ginseng employed were unable to induce general toxicity in rats treated for 30 days and also shows that the general behavior of mice treated with P. ginseng was slightly different from that observed in animals treated with ketamine and glycine. Finally, the study on the elevated plus maze showed that the extract of P. ginseng showed no anxiolytic or anxiogenic action

Pre-emptive epidural ketamine or S(+)-ketamine in post-incisional pain in dogs: A comparative study

Objective-To compare the pre-emptive analgesic effects of epidural ketamine or S(+)-ketamine on post-incisional hyperalgesia.Study Design-Prospective randomized study.Animals-Twenty-four mongrel dogs (1-5 years, weighing 11.9 +/- 1.8 kg).Methods-Dogs were anesthetized with propofol (5 mg/kg intravenously) and a lumbosacral epidural catheter was placed. Dogs were randomly allocated to 3 groups, each with 8 dogs. The control group (CG) was administered saline solution (0.3 mL/kg); the ketamine group (KG) ketamine (0.6 mg/kg); and the S(+)-ketamine group (SG) S(+)-ketamine (0.6 mg/kg). The final volume was adjusted to 0.3 mL/kg in all groups. Five minutes after the epidural injection a surgical incision was made in the common pad of the right hind limb and was immediately closed with simple interrupted nylon suture. Respiratory (RR) and heart (HR) rates, rectal temperature (7, sedation (S), lameness score, and mechanical nociceptive threshold by von Frey filaments were evaluated before the propofol anesthesia and at 15, 30, 45, 60, 75, and 90 minutes and then at 2, 4, 6, 8, 12, and 24 hours after epidural injection.Results-There were no differences in RR, HR, T, or S between groups. Motor blockade of the hind limbs was observed during 20 +/- 3.6 minutes in KG and during 30.6 +/- 7.5 minutes in SG (mean SD). Mechanical force applied to obtain an aversive response was higher from 45 minutes to 12 hours in KG and from 60 to 90 minutes in SG, when compared with CG.Conclusions-Pre-emptive epidural ketamine induced no alterations in RR and FIR, and reduced post-incisional hyperalgesia for a longer time than did S(+) ketamine.Clinical Relevance-Although anesthetic and analgesic potency of S(+) ketamine is twice that of ketamine, the racemic form is seemingly better for post-incisional hyperalgesia. (C) Copyright 2004 by the American College of Veterinary Surgeons.

Topical (S)-ketamine for pain management of postherpetic neuralgia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Romifidine or xylazine combined with ketamine in dogs premedicated with methotrimeprazine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Association of midazolam with ketamine in giant Amazon river turtles Podocnemis expansa breed in captivity

OBJETIVO: Avaliar os efeitos de duas associações anestésicas em tartarugas da Amazônia em (Podocnemis expansa). MÉTODOS: Vinte P. expansa, hígidas, de ambos os sexos, com massa corporal entre 1,0 e 1,5 kg, de um criatório comercial localizado no vale do rio Araguaia, Goiás, Brasil, foram distribuídas em dois grupos (G1 n=10 e G2 n=10). Cada grupo recebeu um protocolo sendo: P1 = midazolam (2 mg/kg IM) com cetamina (20 mg/kg IM) e P2 = midazolam (2 mg/kg IM) com cetamina (60 mg/kg IM), aplicados nos grupos G1 e G2, respectivamente. Os fármacos foram aplicados no membro torácico esquerdo. Os parâmetros clínicos avaliados foram: locomoção, relaxamento muscular, resposta aos estímulos dolorosos nos membros torácico direito e pelvinos e freqüência cardíaca. Essas avaliações foram feitas no tempo 0 (imediatamente após a injeção) e nos tempos 5, 10, 20, 30, 45, 60, 90, 120, 150 e 180 minutos após as injeções. RESULTADOS: O G2 apresentou maior freqüência cardíaca que o G1 e imobilização mais rápida e prolongada. CONCLUSÃO: As sedações obtidas por esses protocolos (P1 e P2) foram satisfatórias, sendo possível a contenção farmacológica para a coleta de amostras biológicas e exame físico em P. expansa.

The pre-emptive effect of epidural ketamine on wound sensitivity in horses tested by using von Frey filaments

Objective To evaluate the pre-emptive analgesic effect of pre-incisional epidural ketamine.Study Design A blinded, randomized experimental study.Animals Sixteen mixed breed mares, 17.6 +/- 2.8 years old, weighing 352 +/- 32 kg.Methods In a pilot study, an incision was made on one lateral thigh using a lidocaine block and no further analgesics, and it was verified that the nociceptive threshold was lower on the incised side than nonincised side (p < 0.05), and that von Frey filaments evoked a pain response. The 16 animals were divided into group A (ketamine, n = 9) and B (saline, n = 7). An epidural catheter was inserted 24 hours before the trials, the thigh was shaved bilaterally, and the right side was blocked (incised side) using lidocaine. Twenty-five minutes later, ketamine (A) or saline (B) was administered epidurally. Five minutes later, a 10-cm. skin incision was made on the right side, and then sutured. Nociceptive threshold was determined with von Frey filaments at 1, 3, and 5 cm. around the incision at 15-minute intervals for 2 hours, then at 4, 6, and 8 hours. Behavioral alterations, heart and respiratory rates were recorded. Nociceptive thresholds from these points were averaged to obtain mean values at each time, converted to a logarithmic scale, and submitted to a nonparametric analysis (Mann-Whitney and one-way repeated measures anova test,p less than or equal to 0.05).Results After 8 hours, the global range score revealed reduced hyperalgesia (p < 0.01) around the incision in 92% (4.65-4.27) of evaluated intervals in group A (ketamine). There were no significant changes in behavior, heart and respiratory rates,Conclusions It was concluded that pre-emptive epidural ketamine reduced post-incisional pain in the horse, and that von Frey filaments were able to quantify cutaneous sensitivity after tissue damage.Clinical relevance Epidural ketamine injection can reduce post-incisional sensitivity in the horse.

Dopplerfluxometria renal em macao-prego (Sapajus apella) de cativeiro

Pós-graduação em Medicina Veterinária - FMVZ

Consumo de extrato hidrossolúvel de soja diminui a qualidade do tecido ósseo de ratos machos jovens: Bruna Rezende Silva Martins de Oliveira. -

Pós-graduação em Ciência Animal - FMVA