Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.

Ketamine ameliorates hypoxia-induced endothelial injury in human umbilical vein endothelial cells

OBJECTIVES: Hypoxia leads to endothelial cell inflammation, apoptosis, and damage, which plays an important role in the complications associated with ischemic cardiovascular disease. As an oxidoreductase, p66Shc plays an important role in the regulation of reactive oxygen species (ROS) production and apoptosis. Ketamine is widely used in clinics. This study was designed to assess the potential protective effect of ketamine against hypoxia-induced injury in human umbilical vein endothelial cells (HUVECs). Moreover, we explored the potential mechanism by which ketamine protected against hypoxia-induced endothelial injury. METHODS: The protective effects of ketamine against hypoxia-induced injury was assessed using cell viability and adhesion assays, quantitative polymerase chain reaction, and western blotting. RESULTS: Our data showed that hypoxia reduced HUVEC viability, increased the adhesion between HUVECs and monocytes, and upregulated the expression of endothelial adhesion molecules at the protein and mRNA levels. Moreover, hypoxia increased ROS accumulation and upregulated p66Shc expression. Furthermore, hypoxia downregulated sirt1 expression in HUVECs. Alternatively, ketamine was shown to reverse the hypoxia-mediated reduction of cell viability and increase in the adhesion between HUVECs and monocytes, ameliorate hypoxia-induced ROS accumulation, and suppress p66Shc expression. Moreover, EX527, a sirt1 inhibitor, reversed the protective effects of ketamine against the hypoxia-mediated reduction of cell viability and increase in adhesion between HUVECs and monocytes. CONCLUSION: Ketamine reduces hypoxia-induced p66Shc expression and attenuates ROS accumulation via upregulating sirt1 in HUVECs, thus attenuating hypoxia-induced endothelial cell inflammation and apoptosis.

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

ABSTRACT Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days) induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

Propofol attenuates cytokine-mediated upregulation of expression of inducible nitric oxide synthase and apoptosis during regeneration post-partial hepatectomy

Abstract Purpose: To determine the effects of propofol and ketamine anesthesia on liver regeneration in rats after partial hepatectomy (PHT). Methods: Male Wistar albino rats were assigned randomly to four groups of 10. Anesthesia was induced and maintained with propofol in groups 1 and 2, and with ketamine in groups 3 and 4. PHT was undertaken in groups 1 and 3. Rats in groups 2 and 4 (control groups) underwent an identical surgical procedure, but without PHT. At postoperative day-5, rats were killed. Regenerated liver was removed, weighed, and evaluated (by immunohistochemical means) for expression of inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), apoptosis protease-activating factor (APAF)-1, and proliferating cell nuclear antigen (PCNA). Also, blood samples were collected for measurement of levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Results: Between groups 2 and 4, there were no differences in tissue levels of iNOS, eNOS, and APAF-1 or plasma levels of TNF-α and IL-6. eNOS expression was similar in group 1 and group 3. Expression of iNOS and APAF-1 was mild-to-moderate in group 1, but significantly higher in group 3. Groups 1 and 3 showed an increase in PCNA expression, but expression in both groups was comparable. Plasma levels of TNF-α and IL-6 increased to a lesser degree in group 1 than in group 3. Conclusion: Propofol, as an anesthetic agent, may attenuate cytokine-mediated upregulation of iNOS expression and apoptosis in an animal model of liver regeneration after partial hepatectomy.

Effect of different anesthetic agents on left ventricular systolic function assessed by echocardiography in hamsters

Determination of left ventricular ejection fraction (LVEF) using in vivo imaging is the cardiac functional parameter most frequently employed in preclinical research. However, there is considerable conflict regarding the effects of anesthetic agents on LVEF. This study aimed at assessing the effects of various anesthetic agents on LVEF in hamsters using transthoracic echocardiography. Twelve female hamsters were submitted to echocardiography imaging separated by 1-week intervals under the following conditions: 1) conscious animals, 2) animals anesthetized with isoflurane (inhaled ISO, 3 L/min), 3) animals anesthetized with thiopental (TP, 50 mg/kg, intraperitoneal), and 4) animals anesthetized with 100 mg/kg ketamine plus 10 mg/kg xylazine injected intramuscularly (K/X). LVEF obtained under the effect of anesthetics (ISO=62.2±3.1%, TP=66.2±2.7% and K/X=75.8±1.6%) was significantly lower than that obtained in conscious animals (87.5±1.7%, P<0.0001). The K/X combination elicited significantly higher LVEF values compared to ISO (P<0.001) and TP (P<0.05). K/X was associated with a lower dispersion of individual LVEF values compared to the other anesthetics. Under K/X, the left ventricular end diastolic diameter (LVdD) was increased (0.60±0.01 cm) compared to conscious animals (0.41±0.02 cm), ISO (0.51±0.02 cm), and TP (0.55±0.01 cm), P<0.0001. The heart rate observed with K/X was significantly lower than in the remaining conditions. These results indicate that the K/X combination may be the best anesthetic option for the in vivo assessment of cardiac systolic function in hamsters, being associated with a lower LVEF reduction compared to the other agents and showing values closer to those of conscious animals with a lower dispersion of results.

Historia de los terrenos del Hospital Clínico y la Facultad de Medicina de la Universidad de Chile / History of the University of Chile Faculty of Medicine and clinical hospital location

The history of the location of the University of Chile Faculty of Medicine North Campus is derived from a farm of Pedro de Valdivia founder of the city of Santiago de la Nueva Extremadura and governor of the “Reyno de Chile”. This work narrates succinctly the history of this particular location from the Spanish Conquest period to present days.

Effects of ketamine and midazolam on emergence agitation after sevoflurane anaesthesia in children receiving caudal block: a randomized trial / Efeitos de cetamina e midazolam sobre a incidência de agitação pós-anestesia com sevoflurano em crianças submetidas ao bloqueio caudal: estudo randomizado / Efectos de la ketamina y el midazolam sobre la incidencia de agitación postanestesia con sevoflurano en niños sometidos al bloqueo caudal: estudio aleatorizado

Background and objectives: Emergence agitation is a common postanaesthetic problem in children after sevoflurane anaesthesia. We aimed to compare the effects of ketamine and midazolam administered intravenously, before the end of surgery, for prevention of emergence agitation in children who received caudal block for pain relief under sevoflurane anaesthesia. Methods: 62 American Society of Anesthesiologists patient classification status I children, aged 2–7 years, scheduled for inguinal hernia repair, circumcision or orchidopexy were enrolled to the study. Anaesthesia was induced with sevoflurane 8% in a mixture of 50% oxygen and nitrous oxide. After achieving adequate depth of anaesthesia, a laryngeal mask was placed and then caudal block was performed with 0.75 mL kg−1, 0.25% bupivacaine. At the end of the surgery, ketamine 0.25 mg kg−1, midazolam 0.03 mg kg−1 and saline were given to ketamine, midazolam and control groups, respectively. Agitation was assessed using Paediatric Anaesthesia Emergence Delirium scale and postoperative pain was evaluated with modified Children's Hospital of Eastern Ontario Pain Scale. Results and conclusions: Modified Children's Hospital of Eastern Ontario Pain Scale scores were found higher in control group than in ketamine and midazolam groups. Paediatric Anaesthesia Emergence Delirium scores were similar between groups. Modified Children's Hospital of Eastern Ontario Pain Scale and Paediatric Anaesthesia Emergence Delirium scores showed a significant decrease by time in all groups during follow-up in postanaesthesia care unit. The present study resulted in satisfactory Paediatric Anaesthesia Emergence Delirium scores which are below 10 in all groups. As a conclusion, neither ketamine nor midazolam added to caudal block under sevoflurane anaesthesia did show further effect on emergence agitation. In addition, pain relief still seems to be the major factor in preventing emergence ...

Justificativa e objetivos: A incidência de agitação é um problema pós-anestésico comum em crianças após a anestesia com sevoflurano. Nosso objetivo foi comparar os efeitos de cetamina e midazolam administrados por via intravenosa, antes do término da cirurgia, para prevenir a incidência de agitação em crianças submetidas ao bloqueio caudal para alívio da dor sob anestesia com sevoflurano. Métodos: Foram inscritos no estudo 62 pacientes pediátricos, entre 2-7 anos, estado físico classificado de acordo com a Sociedade Americana de Anestesiologistas (ASA: I), programados para correção de hérnia inguinal, circuncisão ou orquidopexia. A anestesia foi induzida com sevoflurano a 8% em uma mistura de oxigênio (50%) e óxido nitroso (50%). Depois de atingir a profundidade adequada da anestesia, uma máscara laríngea foi colocada e, em seguida, o bloqueio caudal foi feito com bupivacaína a 0,25% (0,75 mL kg−1). No fim da cirurgia, cetamina (0,25 mg kg−1), midazolam (0,03 mg kg−1) e solução salina foram administrados aos grupos cetamina, midazolam e controle, respectivamente. A incidência de agitaçio foi avaliada com a escala Paediatric Anaesthesia Emergence Delirium (PAED) e a dor no período pós-operatório avaliada com a escala modificada Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS). Resultados e conclusões: Os escores de dor da escala modificada mCHEOPS foram maiores no grupo controle do que nos grupos cetamina e midazolam. Os escores PAED foram semelhantes entre os grupos. Os escores dessas duas escalas mostraram uma diminuição significativa do tempo em todos os grupos durante o acompanhamento em sala de recuperação pós-anestesia. O presente estudo resultou em escores satisfatórios da escala PAED, que ficaram abaixo ...

Introducción y objetivos La incidencia de agitación es un problema postanestésico frecuente en niños después de la anestesia con sevoflurano. Nuestro objetivo fue comparar los efectos de la ketamina y del midazolam administrados por vía intravenosa antes del término de la cirugía para prevenir la incidencia de agitación en niños sometidos al bloqueo caudal para alivio del dolor bajo anestesia con sevoflurano. Métodos 62 pacientes pediátricos, con edades entre 2 y 7 años, estado físico clasificado de acuerdo con la Sociedad Norteamericana de Anestesiólogos (ASA I), programados para la corrección de hernia inguinal, circuncisión o orquidopexia fueron inscritos en el estudio. La anestesia se indujo con sevoflurano al 8% en una mezcla de oxígeno al 50% y óxido nitroso al 50%. Después de alcanzar la profundidad adecuada de la anestesia, una mascarilla laríngea se colocó y enseguida el bloqueo caudal se realizó con bupivacaína al 0,25% (0,75 ml kg−1). Al final de la cirugía, la ketamina (0,25 mg kg−1), el midazolam (0,03 mg kg−1) y la solución salina fueron administrados a los grupos ketamina, midazolam y control, respectivamente. La incidencia de agitación se evaluó usando la escala Paediatric Anaesthesia Emergence Delirium y el dolor en el período postoperatorio se calculó con la escala modificada Children's Hospital of Eastern Ontario Pain Scale. Resultados y conclusiones Las puntuaciones de dolor de la escala modificada Children's Hospital of Eastern Ontario Pain Scale fueron más elevadas en el grupo control que en los grupos ketamina y midazolam. Las puntuaciones de la Paediatric Anaesthesia Emergence Delirium fueron parecidas entre los grupos. Las puntuaciones de esas 2 escalas arrojaron una reducción significativa del tiempo en todos los grupos durante el ...

Cetamina, xilazina e atropina, em doses calculadas por extrapolação alométrica interespecífica, para contenção farmacológica da cutia (Dasyprocta azarae) / Allometrically scaled dosages of ketamine, xylazine and atropine for chemical restraint of agouti (Dasyprocta azarae) / Ketamina, xilacina y atropina, en dosis calculadas por extrapolación alométrica interespecífica, para sujeción farmacológica del agutí (Dasyprocta azarae)

A cutia (Dasyprocta azarae) é um roedor neotropical que necessita ser contido por meios farmacológicos para a realização de certos procedimentos médicos e de manejo, em função de características comportamentais de defesa e grande susceptibilidade ao estresse. A combinação de cloridrato de cetamina, cloridrato de xilazina e sulfato de atropina foi administrada, por via intramuscular, a 53 cutias (33 machos e 20 fêmeas) com pesos entre 0,74 e 3,58 kg (2,071±0,678 kg), para possibilitar a realização de procedimentos de campo que incluíam determinação de sexo, biometria, marcação, exame físico e colheita de sangue e urina. Após a pesagem de cada cutia, a dose individual de cada um dos fármacos foi calculada por meio de extrapolação alométrica interespecífica, usando-se como modelo as doses usualmente recomendadas para um cão doméstico de 10 kg (cetamina – 20,00mg/kg, xilazina – 2,00mg/kg e atropina – 0,05mg/kg). Em todos os animais a indução do estado de contenção foi rápida, sendo a reação postural de endireitamento abolida entre 0,5 e 5,0 minutos (2,02±1,21 minutos) após a injeção. A temperatura retal variou de 28,9 a 40,9ºC (36,38±2,04ºC), a frequência cardíaca variou de 72 a 240 b.p.m. (150,93±31,48 b.p.m.) e a frequência respiratória variou de 20 a 192 m.p.m. (80,63±29,09 m.p.m.). Avaliou-se a qualidade da contenção farmacológica com base no miorrelaxamento observado aos dez, 15, 25 e 35 minutos após a injeção. A contenção farmacológica foi excelente em cerca de 90,00% dos casos, e boa em outros 5,00%. A qualidade da analgesia foi avaliada, principalmente, por meio das rea- ções de nocicepção ao pinçamento de um dígito do membro torácico esquerdo aos dez, 15, 25 e 35 minutos após a injeção, e foi ruim em mais de 50,00% dos casos...

The agouti (Dasyprocta azarae) is a neotropical rodent that requires chemical restraint for handling due to its susceptibility to stress and defensive behavior characteristics. Fifty-three agoutis (33 males and 20 females) weighing 0.74 to 3.58 kg (2.071±0.678 kg) were given ketamine hydrochloride, xylazine hydrochloride and atropine sulfate combined by i.m. injection during field procedures that included sexing, measuring, marking, physical examinations and collecting blood and urine. All drug doses were calculated using the respective doses of a 10-kg dog as model. These doses are 20.00 mg/ kg for ketamine, 2.00mg/kg for xylazine and 0.05mg/kg for atropine. In all individuals, immobilization was rapid and uneventful. Righting reflexes were abolished after 0.50 to 5.00 min (2.02±1.21 min). Body temperature fluctuated between 28.9 and 40.9ºC (36.38±2.04ºC), heart rates remained between 72 and 240 beats/min (150.93±31.48); and respiratory rates ranged between 20 and 192 breaths/min (80.63±29.09). Restraint quality was evaluated by measuring muscle relaxation at 10, 15, 25 and 35 min after injection. Chemical restraint was excellent in about 90.00% and good in about 5.00% of the cases. Analgesia quality was evaluated mainly by measuring the reactions to painful stimuli such as pinching of a digit in the left thoracic limb at 10, 15, 25 e 35 min after injection, and was poor in more than 50.00% of the cases. Recovery occurred without psychomotor disturbances, and every animal remained calm until normal ambulation resumed between 105 and 277 min (164.94 ±37.14 min). The proposed method was safe for both animals and the human personnel. It is recommended for routine management and stressful but not painful medical procedures like physical examination, measuring, sexing, and urine and blood collection in D. azarae. This article rescues data obtained in an investigation performed back in 1998...

El agutí (Dasyprocta azarae) es un roedor neo tropical que necesita ser sujetado por medios farmacológicos para ciertos procedimientos médicos y de manejo, debido a características comportamentales de defensa y gran susceptibilidad a el estrés. La combinación de clorhidrato de ketamina, clorhidrato de xilacina y sulfato de atropina fue administrada por vía intramuscular a 53 agutíes (33 machos e 20 hembras) con pesos entre 0,74 e 3,58 kg (2,071±0,678 kg), para posibilitar la realización de procedimientos de campo que incluyan determinación de sexo, biometría, marcación, examen físico y colecta de sangre y orina. Cada animal fue pesado y la dosis individual de cada uno de los fármacos fue calculada por extrapolación alométrica interespecífica, usándose como modelo las dosis usualmente recomendadas para un perro doméstico de 10 kg (ketamina – 20,00mg/kg, xilacina – 2,00mg/kg y atropina – 0,05mg/kg). En todos los animales la inducción del estado de sujeción fue rápida, y la reacción postural de enderechamiento fue abolida entre 0,5 e 5,0 minutos (2,02±1,21 minutos) después de la inyección. La temperatura rectal varió de 28,9 a 40,9ºC (36,38±2,04ºC), la frecuencia cardíaca varió de 72 a 240 b.p.m. (150,93±31,48 b.p.m.) y la frecuencia respiratoria varió de 20 a 192 m.p.m. (80,63±29,09 m.p.m.). Se evaluó la calidad de la sujeción farmacológica, basado en el relajamiento muscular observado a los 10, 15, 25 y 35 minutos después de la inyección. La sujeción farmacológica fue excelente en casi 90,00% de los casos, y buena en otros 5,00%. La calidad de la analgesia fue evaluada principalmente por las reacciones de sensibilidad dolorosa al pinzamiento de un dígito del miembro torácico izquierdo a los 10, 15, 25 e 35 minutos después de la inyección, y fue ruin en más de 50,00% de los casos...

Efeitos antimicrobianos de cetamina em combinação com propofol: um estudo in vitro / The antimicrobial effects of ketamine combined with propofol: an in vitro study / Efectos antimicrobianos de la cetamina en combinación con el propofol: un estudio in vitro

EXPERIÊNCIA E OBJETIVOS: Cetamina e propofol são os anestésicos gerais que também exibem efeitos antimicrobianos e promotores do crescimento microbiano, respectivamente. Embora esses agentes sejam frequentemente aplicados em combinação durante o uso clínico, não há dados sobre seu efeito total no crescimento microbiano na administração combinada. Nesse estudo, investigamos o crescimento de alguns microrganismos em uma mistura de cetamina e propofol. MÉTODO: Nesse estudo, utilizamos cepas padronizadas: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Candida albicans. Realizamos uma análise de tempo-crescimento para avaliar as taxas de crescimento microbiano em propofol 1%. A atividade antimicrobiana de cetamina, isoladamente e em propofol, foi estudada pelo método de microdiluição. RESULTADOS: Em propofol, as cepas estudadas cresceram de concentrações de 10³-10(4) ufc/mL para > 10(5) ufc/mL, dentro de 8-16 horas, dependendo do tipo de microrganismo. Foram determinadas a concentração inibitória mínima (CIM) e a concentração bactericida mínima (CBM) (para Candida, concentração fungicida mínima) de cetamina, como se segue (CIM, CBM): E. coli 312,5, 312,5 µg/mL; S.aureus 19,5, 156 µg/mL; P. aeruginosa 312,5, 625 µg/mL; e C. albicans 156, 156 µg/mL. Na mistura cetamina + propofol, cetamina exibiu atividade antimicrobiana para E. coli, P. aeruginosa e C. albicans em CBMs a 1250, 625 e 625 µg/mL, respectivamente. O crescimento de S. aureus não foi inibido nessa mistura (concentração de cetamina = 1250 µg/mL). CONCLUSÃO: Cetamina preservou sua atividade antimicrobiana de maneira dose-dependente contra alguns microrganismos em propofol, que é robusta solução promotora de crescimento microbiano. O uso combinado de cetamina e propofol na aplicação clínica de rotina pode diminuir o risco de infecção causada por contaminação acidental. Entretanto, deve-se ter em mente que cetamina não pode reduzir todas as ameaças patogênicas na mistura com propofol.

BACKGROUND AND OBJECTIVES: Ketamine and propofol are the general anesthetics that also have antimicrobial and microbial growth-promoting effects, respectively. Although these agents are frequently applied together during clinical use, there is no data about their total effect on microbial growth when combined. In this study, we investigated some organisms' growth in a ketamine and propofol mixture. METHOD: We used standard strains including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans in this study. Time-growth analysis was performed to assess microbial growth rates in 1% propofol. Antimicrobial activity of ketamine, alone and in propofol was studied with microdilution method. RESULTS: In propofol, studied strains grew from 10³-10(4) cfu/mL to >10(5) cfu/mL concentrations within 8-16 hours depending on the type of organism. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) (for candida, minimal fungicidal concentration) of ketamine were determined as follows (MIC, MBC): E.coli 312.5, 312.5 µg/mL; S.aureus 19.5, 156 µg/mL; P.aeruginosa 312.5, 625 µg/mL; and C.albicans 156, 156 µg/ml. In ketamine+propofol mixture, ketamine exhibited antimicrobial activity to E.coli, P.aeruginosa and C.albicans as MBCs at 1250, 625 and 625 µg/mL, respectively. Growth of S. aureus was not inhibited in this mixture (ketamine concentration=1250 µg/mL). CONCLUSION: Ketamine has sustained its antimicrobial activity in a dose-dependent manner against some organisms in propofol, which is a strong microbial growth-promoting solution. Combined use of ketamine and propofol in routine clinical application may reduce the risk of infection caused by accidental contamination. However, one must keep in mind that ketamine cannot reduce all pathogenic threats in propofol mixture.

EXPERIENCIA Y OBJETIVOS: La Cetamina y el propofol son los anestésicos generales que también tienen efectos antimicrobianos y son los promotores del crecimiento microbiano, respectivamente. Aunque esos agentes sean frecuentemente aplicados en combinación durante el uso clínico, no hay datos sobre su efecto total en el crecimiento microbiano en la administración combinada. En ese estudio, investigamos el crecimiento de algunos microrganismos en una mezcla de cetamina y propofol. MÉTODO: En este estudio, utilizamos cepas estandarizadas: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa y Candida albicans. Realizamos un análisis de tiempo-crecimiento para evaluar las tasas de crecimiento microbiano en el propofol al 1%. La actividad antimicrobiana de cetamina, aisladamente y en propofol, fue estudiada por el método de microdilución. RESULTADOS: En el propofol, las cepas estudiadas crecieron de concentraciones de 10³-10(4) ufc/mL para #> 10(5) ufc/mL, dentro de 8-16 horas, dependiendo del tipo de microrganismo. Fueron determinadas la concentración inhibitoria mínima (CIM) y la concentración bactericida mínima (CBM) (para Candida, concentración fungicida mínima) de cetamina, como vemos (CIM, CBM): E. coli 312,5, 312,5 µg/mL; S.aureus 19,5, 156 µg/mL; P. aeruginosa 312,5, 625 µg/mL; y C. albicans 156, 156 µg/ml. En la mezcla cetamina + propofol, la cetamina mostró una actividad antimicrobiana para E. coli, P. aeruginosa y C. albicans en CBMs a 1250, 625 y 625 µg/mL, respectivamente. El crecimiento de S. aureus no se inhibió en esa mezcla (concentración de cetamina = 1250 µg/mL). CONCLUSIONES: La cetamina preservó su actividad antimicrobiana de manera dosis-dependiente contra algunos microrganismos en propofol, que es una robusta solución que promueve el crecimiento microbiano. El uso combinado de cetamina y propofol en la aplicación clínica de rutina puede disminuir el riesgo de infección causada por la contaminación accidental. Sin embargo, debemos tener presente que la cetamina no puede reducir todas las amenazas patógenas en la mezcla con el propofol.

Uso da S(+) cetamina por via intra-articular em modelo de osteoartrite em ratos: análise da imunoexpressão da ciclooxigenase 2 / Using the S (+) Ketamine in intraarticular osteoarthritis model in rats: analysis of the immunoreactivity cyclooxygenase 2

A osteoartrite (OA) é uma doença degenerativa que afeta grande parte da população e resulta em significativa morbidade e incapacidade. O presente estudo teve como objetivo investigar os efeitos periféricos da S(+) cetamina na expressão da ciclo-oxigenase 2 (COX-2). Foram utilizados modelos experimentais de osteoartrite em ratos. Inicialmente setenta e dois ratos foram utilizados no estudo. Foram divididos em três grupos de 24 animais cada. Em dois grupos foi induzida a OA através de 2mg de MIA (monoiodo acetato de sódio) por via intra-articular (i.a), em um volume máximo de 50μL e em um dos grupos não foi realizada a indução da OA. No sétimo dia após a indução, dois grupos, incluindo o sem OA, receberam injeção i.a de salina 0,9% em volume máximo de 50μL e o terceiro grupo recebeu injeção de S(+) cetamina na dose de 0,5mg/kg. Nos dias 7, 14, 21 e 28 os animais foram anestesiados e sacrificados para coleta da membrana sinovial e análise imuno-histoquímica da ciclo-oxigenase-2. Durante o estudo ocorreram 29 perdas do material a ser analisado, totalizando um n = 43. O protocolo adotado para a interpretação imuno-histoquímica foi a imunomarcação citoplasmática da COX-2 em células da membrana sinovial, tecido conjuntivo e adiposo, conforme a intensidade da coloração. A análise dos resultados foi realizada através do teste do quiquadrado. A reatividade da COX-2 foi positiva em 53,8% dos animais do grupo sem OA, em 60% do grupo OA com salina e em 80% dos animais do grupo OA com cetamina, sem diferença estatisticamente significante entre os grupos (p = 0,3069). Esse estudo sugeriu que a S(+) cetamina por via intra-articular não inibiu a expressão da COX-2 em modelos de osteoartrite em ratos

Osteoarthritis (OA) is a degenerative disease that effects a large population and results in significant morbidity and disability. The objective of the present study was to investigate the peripheral effects of S(+) ketamine on the COX-2 expression. Experimental models of OA in rats were used. At first, 72 rats were used in the study. The animals were divided into three groups of 24 each. In two groups, OA was induced through intra-articular (i.a.) injection of 2mg of monoiodine acetate (MIA), at a maximum volume of 50μL, while one of the groups was not submitted to OA induction. On the seventh day following the induction, the animals of two groups, including those form the not-induced group, received an i.a. injection of saline at 0.9% at a maximum volume of 50μL, while the third group received and injection of S(+) ketamine at 0.5mg/kg. On days 7, 14, 21 and 28 the animals were anesthetized and sacrificed, and the synovial membrane was extracted and submitted to immunohistochemistry analysis of the cyclooxygenase-2. Throughout the study, there were 29 losses of materials that were to be analyzed, totaling an n = 43. The protocol used for the immunohistochemical interpretation was cytoplasmic immunostaining of COX-2 in cells of the synovial membrane, conjunctive and adipose tissue, according to the intensity of the stain. Results were analyzed by the chi-square test. COX-2 reactivity was positive in 53.8% of animals in the group without OA, in 60% of those of the OA group with saline, and in 80% of group OA with ketamine, with no statistically significant difference between the groups (p = 0.3069). Thus, the study implies that intra-articular injections of S(+) ketamine did not inhibit the COX-2 expression in osteoarthritis models in rats

Avaliação da S(+)-cetamina no tratamento da dor neuropática e qualidade de vida em portadores de hanseníase / Assessment of the S (+) ketamine in the treatment of neuropathic pain and quality of life in patients with leprosy

A dor neuropática é uma síndrome dolorosa crônica, que ocorre muito frequentemente em pacientes com hanseníase, de difícil tratamento. Objetivou-se avaliar o efeito terapêutico da S(+)-cetamina na dor neuropática e qualidade de vida em portadores de hanseníase atendidos em ambulatórios em São Luís - MA. Estudo experimental tipo ensaio clínico, prospectivo, aleatório, duplamente cego, controlado por placebo, com 34 pacientes distribuídos aleatoriamente em um dois grupos, cetamina e placebo por três meses e randomizados por numeração sequenciada. A dor foi avaliada por meio de escala analógica visual (EAV) nas seis visitas quinzenais (1, 2, 3, 4, 5 e 6), e pelo inventário DN4, na visita 1 e 6, com distribuição da S(+)-cetamina e o analgésico de resgate e avaliado os efeitos adversos em cada visita. Realizou-se a coleta de 15mL de sangue para exames de segurança na visita 1 e 6 e para quantificação de citocinas plasmáticas IL-1, IL-6 e TNFα, nas visitas 1, 2, 4 e 6. Foi também, avaliada a qualidade de vida por meio do questionário WHOQOL-Bref nas visitas 1 e 6. Os resultados demostraram predominância do sexo feminino, idade de 18 a 29 anos, pardos, solteiros, renda de 2 a 4 salários mínimos; e média de 7,78±2,21 anos de estudo. Na avaliação da dor pela EAV os dois grupos apresentaram uma redução dos escores médios de dor ao longo do tempo, e mostrou significância estatística p < 0,05. Entretanto não foi observada diferença estatística para os escores de dor entre os grupos e também, em relação ao uso do medicamento analgésico (codeína) de resgate. Houve redução significante nos escore de DN4 no grupo placebo em relação às avaliações iniciais e finais comparadas à cetamina, ainda os escores iniciais do DN4 foram significativamente menores no grupo placebo, nas avaliações de antes e depois do uso da S(+)-cetamina. Na avaliação da qualidade de vida nos domínios físico, psicológico, relações sociais e meio ambiente, não se observou diferença estatisticamente ...

Neuropathic pain is a chronic pain syndrome of difficult treatment, occurring frequently in patients with leprosy. The objective of this study was to evaluate the therapeutic effect of S(+)-ketamine on neuropathic pain and quality of life in patients with leprosy seen at an outpatient clinic in São Luís - Ma. Experimental study clinical trial, prospective, randomized, double-blind, placebo-controlled trial with 34 patients in a randomized two groups, ketamine and placebo for three months and randomized by sequential numbering. Pain was evaluated using a visual analogue scale (VAS) on six bimonthly visits (1, 2, 3, 4, 5 and 6), and using the DN4 questionnaire on visits 1 and 6, with distribution of S (+)-ketamine and rescue analgesic and adverse effects assessed at each visit. Blood (15ml) was drawn from patients for safety tests on visits 1 and 6, and on visits 1, 2, 4 and 6, to cytokines IL-1, IL-6 and TNFα. Quality of life was also evaluated using WHOQOL-Bref on visits 1 and 6. Results showed most subjects female, age 18 and 29 years of age, pardo ethnicity, single, income between 2 and 4 minimum salaries, and a mean 7.78±2.21 years of education. In the assessment of pain by VAS both groups showed a reduction in mean pain scores over time, and showed statistical significance p <0.05. However there was no statistical difference in pain scores between groups and also in relation to the use of analgesic medication (codeine). There was significant reduction in DN4 score in the placebo group compared to the initial and final evaluations compared to ketamine, although the initial DN4 scores were significantly lower in the placebo group, the assessments before and after the use of S (+)-ketamine. In evaluating the quality of life in the physical, psychological, social relationships and environment, there was no statistically significant difference between groups. The amounts of IL-1, IL-6 and TNF-α in serum of four collections of ketamine and placebo ...

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.

Avaliação do efeito preemptivo da s(+)-cetamina por via peridural para histerectomia: concentrações plasmáticas de interleucinas / Evaluation of preemptive effect of epidural s(+)-ketamine for hysterectomy: plasmatic concentrations of interleukins

JUSTIFICATIVA E OBJETIVOS: Alguns estudos demonstraram que a cetamina inibe a produção de citocinas. O objetivo deste estudo foi avaliar o efeito analgésico preemptivo e citocinas plasmáticas (IL-6, TNF-α e IL-10) de S(+)-cetamina por via peridural em histerectomia. MÉTODO: Foi realizado estudo duplo-encoberto em 29 pacientes. Pacientes do Grupo 1 receberam 13 mL de bupivacaína a 0,25 por cento com 25 mg de S(+)-cetamina 30 minutos antes da incisão cirúrgica, e 15 mL de solução salina fisiológica, 30 minutos após, por via peridural. Pacientes do Grupo 2 receberam 15 mL de salina 30 minutos antes da incisão cirúrgica, seguido por 13 mL de bupivacaína 0,25 por cento, mais 25 mg de S (+)-cetamina 30 minutos após. A analgesia pós-operatória foi feita com bupivacaína e fentanil por via peridural. Quando necessário, foi utilizado 1 g de dipirona. Foram avaliados: concentração de citocinas, intensidade da dor, o tempo da primeira solicitação de analgésico e a quantidade total de analgésico utilizado. RESULTADOS: O tempo para a primeira solicitação de analgésico foi de 61,5 minutos no Grupo 1 e 69,0 no Grupo 2, sem diferença entre os grupos. Não houve diferença entre os grupos para a dose total de fentanil usada no Grupo 1 (221,4 µg) e Grupo 2 (223,3 µg). Foi obtido efeito analgésico semelhante nos grupos, exceto em T12 (Grupo 1 = 2,4 ± 3,2; Grupo 2 = 5,5 ± 3,4). Não foi observada diferença entre os grupos na concentração de citocinas. CONCLUSÕES: A injeção de 25 mg de S(+)-cetamina por via peridural antes da incisão reduziu a intensidade da dor apenas 12 horas após a incisão cirúrgica e não alterou a concentração de citocinas.

BACKGROUND AND OBJECTIVES: Some studies showed that ketamine inhibits the production of cytokines. The objective of this study was to evaluate the preemptive analgesic effect of epidural S(+)-ketamine in hysterectomy and plasmatic cytokines (IL-6, TNF-α and IL-10). METHOD: A double-blinded study with 29 patients was conducted. Patients in Group 1 received 13 mL of 0.25 percent bupivacaine with 25 mg of S(+)ketamine 30 minutes before surgical incision and 15 mL of saline solution via the epidural route 30 minutes after. Patients in Group 2 received 15 mL of saline solution 30 minutes before the surgical incision, followed by 13 mL of 0.25 percent bupivacaine with 25 mg of S(+)-ketamine 30 minutes after. Postoperative analgesia was made with epidural bupivacaine and fentanyl. Dipyrone 1 g was used whenever required. The following paramenters were evaluated: concentration of cytokines, intensity of pain, time of first request of analgesic and total quantity of analgesic used. RESULTS: Time for the first request for analgesics was 61.5 minutes in Group 1 and 69.0 in Group 2, without difference between these groups. There was no difference for total dose of fentanyl used in Group 1 (221.4 µg) and Group 2 (223.3 µg). A similar analgesic effect was obtained in both groups, except in T12 (Group 1 = 2.4 ± 3.2; Group 2 = 5.5 ± 3.4). No differences in concentration of cytokines were observed. CONCLUSIONS: The epidural injection of 25 mg S(+)-ketamine before incision reduced the pain intensity only 12 hours after surgical incision and did not alter concentration of cytokines.

JUSTIFICATIVA Y OBJETIVOS: Algunos estudios han demostrado que la cetamina inhibe la producción de citocinas. El objetivo de este estudio, fue evaluar el efecto analgésico de prevención y citocinas plasmáticas (IL-6, TNF-α y IL-10) de S(+)-cetamina por vía epidural en la histerectomía. MÉTODO: Fue realizado un estudio doble ciego en 29 pacientes. Pacientes del Grupo 1 recibieron 13 mL de bupivacaína al 0,25 por ciento con 25 mg de S(+)-cetamina 30 minutos antes de la incisión quirúrgica, y 15 mL de solución salina fisiológica 30 minutos después de la incisión por vía epidural. Pacientes del Grupo 2, recibieron 15 mL de salina 30 minutos antes de la incisión quirúrgica, seguido de 13 mL de bupivacaína al 0,25 por ciento, más 25 mg de S (+)-cetamina 30 minutos después. La analgesia postoperatoria se realizó con bupivacaína y fentanil por vía epidural. Cuando fue necesario, se usó 1 g de dipirona. Se evaluaron: la concentración de citocinas, la intensidad del dolor, el tiempo de la primera solicitación del analgésico, y la cantidad total de analgésico utilizado. RESULTADOS: El tiempo para la primera solicitación de analgésico fue de 61,5 minutos en el Grupo 1 y 69,0 en el Grupo 2, sin haber diferencias entre los grupos. No hubo diferencias entre los grupos para la dosis total de fentanil usada en el Grupo 1 (221,4 µg) y en el Grupo 2 (223,3 µg). Se obtuvo un efecto analgésico parecido en los grupos, con excepción en T12 (Grupo 1 = 2,4 ± 3,2; Grupo 2 = 5,5 ± 3,4). No fue observada diferencia entre los grupos en la concentración de citocinas. CONCLUSIONES: La inyección de 25 mg de S(+)-cetamina por vía epidural antes de la incisión, redujo la intensidad del dolor solamente 12 horas después de la incisión quirúrgica y no alteró la concentración de citocinas.

Association of midazolam with ketamine in giant Amazon river turtles Podocnemis expansa breed in captivity / Associação de midazolam com cetamina em tartarugas da Amazônia Podocnemis expansa de cativeiro

PURPOSE: Evaluate the effects of two anesthetic associations in giant Amazon river turtles (P. expansa). METHODS: Twenty P. expansa, healthy, of both sexes, with weights between 1.0 and 1.5 kg of a commercial breeding facility located in the valley of the Araguaia River, Goiás, Brazil, were divided into two groups ( G1 n = 10 and G2 n = 10). Each group received a protocol being: P1 = midazolam (2 mg/kg IM) and ketamine (20 mg/kg IM) and P2 = midazolam (2 mg/kg IM) and ketamine (60 mg/kg IM), applied on G1 and G2, respectively. The drugs were applied in the left forelimb. The clinical parameters evaluated were: locomotion, muscle relaxation, response to pain stimuli in the right thoracic and pelvic members and heart rate. These assessments were made at time 0 (immediately after injection) and times of 5, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes after the injections. RESULTS: Group 2 showed a higher heart rate than G1 and more rapid and prolonged immobilization. CONCLUSION: The sedation scores obtained by these protocols (P1 and P2) were satisfactory, with possible pharmacological contention for collecting biological samples and physical examination in P. expansa.

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.

Effects of ketamine and alcohol on learning and memory impairment in mice / 法医学杂志

OBJECTIVE@#To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism.@*METHODS@#Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism.@*RESULTS@#(1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group.@*CONCLUSION@#Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.

[Comparing the efficacy of low dose ketamine versus pethidine in controlling shivering after tonsillectomy surgery]

Postoperative shivering is one of the most common problems after general and local anesthesia. We compared the efficacy of low dose ketamine versus pethidine in controlling shivering after surgery. In a double-blind randomized Clinical trial, 132 ASA I,II patients candidate for tonsillectomy were randomized to receive either pethidine and ketamine. At the time of arrival to the recovery and after 30 minutes, the occurrence of chills and possible complications were evaluated and compared between the two groups. Two patients in the ketamin group [3%] experienced shivering while none of the patients in the pethidine group reported shivering [p>0.05]. Other complications were more in the ketamin group [p<0.05]. Ketamin and pethidine are equally effective in controlling postoperative shivering, but regarding the lower incidence of other complications, pethidine is still the first choice of treatment

Efeitos da sedação produzida pela associação midazolam e cetamina S(+) sobre as variáveis eletroencefalográficas / Effects of sedation produced by the association of midazolam and ketamine S(+) on encephalographic variables / Efectos de la sedación producida por la asociación del midazolam y la cetamina S(+) sobre las variables electroencefalográficas

JUSTIFICATIVA E OBJETIVOS: A cetamina S(+) é importante na modulação da dor em pacientes cirúrgicos. Este trabalho teve por objetivo avaliar a relação entre os níveis de sedação produzidos por baixas doses de cetamina S(+), bem como as variáveis do EEG: BIS, SEF 95 por cento, pEMG, taxa de supressão e presença de surto-supressão. MÉTODO: Trinta pacientes, de ambos os sexos, faixa etária entre 25 e 50 anos, foram distribuídos aleatoriamente em três grupos. O grupo G1 (10) recebeu cetamina S(+) - 0,050 mg.kg-1; o grupo G2 (10), cetamina S(+) - 0,125 mg.kg-1 e o grupo G3(10), cetamina S(+) - 0,250 mg.kg-1; em todos os grupos, a cetamina S(+) foi administrada por via venosa. Todos os pacientes receberam 0,08 mg.kg-1 de midazolam por via venosa 10 minutos antes da administração de cetamina S(+). Em cada grupo, avaliaram-se dois momentos: M1, antes da administração da cetamina S(+); e M2, após a administração da cetamina S(+). Nos três grupos, foram avaliados os níveis de sedação e as variáveis do EEG: BIS, SEF 95 por cento, pEMG, taxa de supressão e presença de surto-supressão, antes e após a injeção de cetamina S(+). Utilizou-se ANOVA para medidas repetidas e valor de p ajustado para comparações múltiplas pelo teste de Tukey. RESULTADOS: Houve diminuição nos escores da escala de alerta sedação nos três grupos nos momentos M2. As variáveis do EEG mostraram variação significante nos três grupos, comparando-se os momentos M1 e M2 tanto na pEMG como no BIS (p < 0,05). CONCLUSÕES: Os níveis de sedação correlacionam-se, de maneira significativa, com o aumento da dose de cetamina S(+). Entretanto, os valores elevados do BIS podem ter refletido aumento da pEMG induzida pela cetamina S(+).

BACKGROUND AND OBJECTIVES: Ketamine S(+) is important in pain modulation in surgical patients. The objective of the present study was to evaluate the relationship between the levels of sedation produced by low doses of ketamine S(+), as well as encephalographic variables: BIS, SEF 95 percent, pEMG, suppression rate, and presence of burst-suppression. METHODS: Thirty patients of both sexes, aged 25-50 years, were randomized into three groups. Group G1 (10) received intravenous ketamine S(+) 0.050 mg,kg-1; group G2 (10) intravenous ketamine S(+) 0.125 mg.kg-1; and group G3 (10) intravenous ketamine S(+) 0.250 mg.kg-1. All patients received 0.08 mg.kg-1 of intravenous midazolam 10 minutes before administration of ketamine S(+). In each group, two moments were evaluated: M1, before ketamine S(+) administration; and M2, after ketamine S(+) administration. Sedation levels and encephalographic variables: BIS, SEF 95 percent, pEMG, suppression rate, and the presence of burst-suppression were evaluated in all patients before and after ketamine S(+) administration. ANOVA was used for repeated measurements and the p-value was adjusted for multiple comparisons by Tukey's test. RESULTS: A decrease in alertness-sedation scale scores was observed in all three groups in moment M2. Electroencephalographic variables showed significant variation in all three groups when moments M1 and M2 were compared, both in pEMG and BIS (p < 0.05). CONCLUSIONS: Sedation levels showed significant correlation with the increase in ketamine S(+) dosage. However, increased BIS levels may have reflected increased pEMG induced by ketamine S(+).

JUSTIFICATIVA Y OBJETIVOS: La cetamina S(+) es importante en la modulación del dolor en pacientes quirúrgicos. Este trabajo tuvo el objetivo de evaluar la relación entre los niveles de sedación producidos por la bajas dosis de cetamina S(+), como también las variables del EEG: BIS, SEF 95 por ciento, pEMG, tasa de supresión y presencia de brote-supresión. MÉTODO: Treinta pacientes de los dos sexos, con una franja etaria entre los 25 y los 50 años, que fueron distribuidos aleatoriamente en tres grupos. El grupo G1 (10) recibió cetamina S(+) - 0,050 mg.kg-1; el grupo G2 (10), cetamina S(+) - 0,125 mg.kg-1 y el grupo G3(10), cetamina S(+) - 0,250 mg.kg-1. En todos los grupos, la cetamina S(+) fue administrada por vía venosa. Todos los pacientes recibieron 0,08 mg.kg-1 de midazolam por vía venosa 10 minutos antes de la administración de cetamina S(+). En cada grupo fueron evaluados dos momentos: M1: antes de la administración de la cetamina S(+); y M2: después de la administración de la cetamina S(+). En los tres grupos, se evaluaron los niveles de sedación y las variables del EEG: BIS, SEF 95 por ciento, pEMG, la tasa de supresión y la presencia de brote-supresión, antes y después de la inyección de cetamina S(+). Se utilizó ANOVA para medidas repetidas y valor de p ajustado para comparaciones múltiples por el test de Tukey. RESULTADOS: Se registró una disminución en las puntuaciones de la escala de alerta sedación en los tres grupos en los momentos M2. Las variables del EEG arrojaron una variación significativa en los tres grupos al comparar los momentos M1 y M2 tanto en la pEMG como en el BIS (p < 0,05). CONCLUSIONES: Los niveles de sedación se correlacionan de manera significativa con el aumento de la dosis de cetamina S(+). Sin embargo, los valores elevados del BIS pueden haberse reflejado en el aumento de la pEMG inducida por la cetamina S(+).

Ketamine has no effect on oxygenation indices following elective coronary artery bypass grafting under cardiopulmonary bypass.

Cardiopulmonary bypass is known to elicit systemic inflammatory response syndrome and organ dysfunction. This can result in pulmonary dysfunction and deterioration of oxygenation after cardiac surgery and cardiopulmonary bypass. Previous studies have reported varying results on anti-inflammatory strategies and oxygenation after cardiopulmonary bypass. Ketamine administered as a single dose at induction has been shown to reduce the pro-inflammatory serum markers in patients undergoing cardiopulmonary bypass. Therefore we investigated if ketamine can result in better oxygenation in these patients. This was a prospective randomized blinded study. Eighty consecutive adult patients undergoing elective coronary artery bypass grafting under cardiopulmonary bypass were included in the study. Patients were divided into two groups. Patients in ketamine group received 1mg/kg of ketamine intravenously at induction of anesthesia. Control group patients received an equal volume of saline. All patients received standard anesthesia, operative and postoperative care.Paired t test and independent sample t test were used to compare the inter-group and between group oxygenation indices respectively. Oxygenation index and duration of ventilation were analyzed. Deterioration of oxygenation index was noted in both the groups after cardiopulmonary bypass. However, there was no significant difference in the oxygenation index at various time points after cardiopulmonary bypass or the duration of ventilation between the two groups. This study shows that the administered as a single dose at induction does not result in better oxygenation after cardiopulmonary bypass.

Effects of ketamine on proliferation and apoptosis of pheochromocytoma cell / 法医学杂志

OBJECTIVE@#To explore the effect of ketamine on adrenal pheochromocytoma (PC12) cell proliferation inhibition and induction of apoptosis and its mechanism.@*METHODS@#PC12 cells of rats were models for dopaminergic neuron. PC12 cells were cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L, respectively. The cell viability was measured by MTT method after incubation at 12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes of apoptosis. PC12 cells cultured after 48 h with different concentrations of ketamine were selected to detect apoptotic rate using flow cytometry and detect the expression of bax and bcl-2 proteins using Western blotting.@*RESULTS@#For different concentrations of ketamine, vitality of PC12 cells significantly decreased with increase of the incubation time. Apoptosis was obviously observed using Hoechst staining. Flow cytometry showed that apoptosis rates significantly increased with increasing ketamine concentrations.@*CONCLUSION@#Ketamine can inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in a concentrations-dependent manner. The underlying mechanism may be related to promoting the expression of bax and inhibiting the expression of bcl-2 in the cells.