Remifentanil-ketamine vs. propofol-ketamine for sedation in pediatric patients undergoing colonoscopy: A randomized clinical trial / Remifentanil-cetamina vs. propofol-cetamina para sedação em pacientes pediátricos submetidos à colonoscopia: ensaio clínico randômico

Abstract Background and objectives: Pediatric patients frequently require deep sedation or general anesthesia for colonoscopy. This study was designed to compare the sedative efficacy of remifentanil-ketamine combination with propofol-ketamine combination in children undergoing colonoscopy. Methods: Seventy patients, between 2 and 16 years of age, scheduled for diagnostic colonoscopy were randomly allocated into two groups. Remifentanil-ketamine group received intravenous ketamine 2 mg.kg−1 and remifentanil 0.25 µg.kg−1 combination, followed by 0.1 µg.kg−1.min−1 remifentanil infusion. Propofol-ketamine group received intravenous propofol 1 and 2 mg.kg−1 ketamine combination, followed by 1 mg.kg−1.h−1 propofol infusion. In the case of children discomfort (cry, movement, and cough), remifentanil 0.1 µg.kg−1 in the remifentanil-ketamine group or propofol 0.5 mg.kg−1 in the propofol-ketamine group were administered to improve children discomfort. Despite the therapy given above, if children still experience discomfort, 1 mg.kg−1 of ketamine was administered as a rescue drug, regardless of the group. Ramsay sedation score, hemodynamic variables, drug requirements, gastroenterologists' satisfaction, colonoscopy duration, recovery time, and side effects were recorded throughout the procedure and the recovery period. Results: The percentage of patients with a Ramsay sedation score of 4 or higher during the procedure was 73.5 and 37.1% in remifentanil-ketamine and propofol-ketamine groups, respectively (p = 0.02). Systolic and diastolic blood pressure variables were significantly higher only after induction in the remifentanil-ketamine group than in the propofol-ketamine group (p = 0.015). Conclusion: Coadministration of ketamine with either remifentanil or propofol effectively and safely provides sedation and analgesia in children undergoing colonoscopy. Sedation scores were significantly better in remifentanil-ketamine group than in propofol-ketamine group.

Resumo Justificativa e objetivos: Os pacientes pediátricos com frequência precisam de sedação profunda ou anestesia geral para colonoscopia. Este estudo foi desenhado para comparar a eficácia sedativa da combinação de remifentanil-cetamina e de propofol-cetamina em crianças submetidas à colonoscopia. Métodos: Setenta pacientes, entre 2-16 anos, programados para colonoscopia diagnóstica foram alocados randomicamente em dois grupos. O grupo remifentanil-cetamina recebeu a combinação de 2 mg.kg−1 de cetamina por via intravenosa e 0,25 µg.kg−1 de remifentanil; seguido de infusão de remifentanil (0,1 µg.kg−1.min−1). O grupo propofol-cetamina recebeu a combinação de 1 mg.kg−1 de propofol e 2 mg.kg−1 de cetamina; seguido de infusão de propofol (1 mg.kg−1.h−1). Em caso de desconforto das crianças (choro, movimento e tosse), remifentanil (0,1 µg.kg−1) seria administrado ao grupo remifentanil-cetamina ou propofol (0,5 mg.kg−1) ao grupo propofol-cetamina. A despeito da terapia acima citada, caso as crianças ainda sentissem desconforto, cetamina (1 mg.kg−1) seria administrada como fármaco de resgate, independentemente do grupo. Escore de sedação de Ramsay, variáveis hemodinâmicas, necessidade de medicamentos, satisfação dos gastroenterologistas, duração da colonoscopia, tempo de recuperação e efeitos colaterais foram registrados durante o procedimento e o período de recuperação. Resultados: O percentual de pacientes com escore 4 ou mais na escala de sedação de Ramsay durante o procedimento foi de 73,5% e 37,1% nos grupos remifentanil-cetamina e propofol-cetamina, respectivamente, (p = 0,02). As variáveis, pressão arterial sistólica e diastólica, foram significativamente maiores no grupo remifentanil-cetamina do que no grupo propofol-cetamina, mas somente após a indução (p = 0,015). Conclusão: A coadministração de cetamina com remifentanil ou propofol fornece sedação e analgesia de forma eficaz e segura em crianças submetidas à colonoscopia. Os escores de sedação foram significativamente melhores no grupo remifentanil-cetamina do que no grupo propofol-cetamina.

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.

Desarrollo de un modelo experimental de osteonecrosis de maxilar asociada al tratamiento crónico con aminobisfosfonatos / Experimental model of osteonecrosis of the jaw associated to chronic treatment with aminobisphosphonates

La osteonecrosis de maxilar asociada a aminobisfosfonatos (BRONJ) constituye un efecto secundario del tratamiento crónico con los más potentes. Un modelo experimental permitiría determinar la patogenia de dicha alteración. La oveja presenta características orales y del metabolismo óseo similar al humano y permite realizar manipulaciones bucales. Se evaluaron cambios clínicos, remodelación ósea y masa ósea maxilar en ovejas hembras adultas tratadas con zolendronato (ZOL), durante 22 meses y utilizando dosis equivalente al tratamiento de neoplasias. Seis ovariectomizadas (OVX) recibieron ZOL; 5 OVX y 4 SHAM (control) recibieron solución fisiológica. Al inicio, 4 y 22 meses se evaluó calcemia, fosfatemia, crosslaps (CTX) y fosfatasa alcalina ósea. Al final, se evaluó contenido mineral óseo de la hemimandíbula superior (CMO: mg/cm2). Al final del estudio, CTX disminuyó significativamente en ZOL (p<0,05) sin diferencias entre SHAM y OVX. En maxilar, los contenidos de Ca y P (g/g tejido) y CMO (g/cm2 ) disminuyeron en OVX vs. SHAM (p<0,05) y solo Ca y CMO respecto de ZOL (p<0,05). ZOL incrementó el contenido de Ca y CMO, mientras que el de P permaneció significativamente disminuido respecto de SHAM. La sobrevida en SHAM y OVX fue del 100% y en ZOL 77% (2 muertes); 2 ovejas del grupo ZOL presentaron necrosis de maxilar. Conclusiones: fue posible obtener desarrollo de BRONJ por tratamiento crónico con ZOL, el cual redujo notablemente la resorción y, según la relación Ca/P, posiblemente haya afectado la mineralización ósea. (AU)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of chronic treatment with the most powerful aminobisphosphonates (BPs). An experimental animal model would allow to determine the pathogenesis of this complication. Ewes exhibit similar oral cavity characteristics and bone metabolism as humans, and they are suitable for oral cavity interventions. We examined herein the clinical manifestations, bone remodeling status, and maxillary bone mass in adult female ewes treated with zoledronate (ZOL) for 22 months. Six ovariectomized (OVX) ewes received ZOL; and 5 OVX and 4 SHAM animals received saline solution. At the start of the experiment, and at the 4 and 22 month-time points serum Ca, P, crosslaps (CTX), and bone alkaline phosphatase were measured. Bone mineral content (BMC) of the superior hemimandible was measured at the end of the experiment. At this time point, CTX was significantly decreased only in the ZOL group (p<0.05). Ca and P content (g/g tissue) and BMC in the mandible were significantly decreased in the OVX group compared to SHAM animals (p<0.05) and only Ca content and BMC were decreased when compared to ZOL (p<0.05). ZOL treatment increased the Ca content and BMC, whereas the P content remained low compared to the SHAM group (p<0.05). All ewes from the SHAM and OVX groups and 77% of the animals from the ZOL group survived until the end of the experiment, whereas two ewes of ZOL group exhibited BRONJ. Conclusion: under our experimental conditions, it was possible to induce BRONJ by the chronic ZOL administration, which in turn induced a high reduction in bone resorption as well as possibly impaired bone mineralization, based on the Ca/P ratio in the mandible. (AU)

Tourniquet-induced ischaemia-reperfusion injury: the comparison of antioxidative effects of small-dose propofol and ketamine / Lesão de isquemia-reperfusão induzida por torniquete: comparação dos efeitos antioxidantes de propofol e cetamina em doses baixas

Abstract Objectives: The aim of the present study was to investigate the preventive effects of propofol and ketamine as small dose sedation during spinal anaesthesia on tourniquet-induced ischaemia-reperfusion injury. Methods: 30 patients were randomly assigned into two groups of 15 patients. In the propofol group, sedation was performed with propofol 0.2 mg·kg-1 followed by infusion at a rate of 2 mg·kg-1·h-1. In the ketamine group, a continuous infusion of ketamine 0.5 mg·kg-1·h-1 was used until the end of surgery. Intravenous administration of midazolam was not used in any patients. Ramsay sedation scale was used for assessing the sedation level. Venous blood samples were obtained before propofol and ketamine infusion (T1), at 30 minutes (min) of tourniquet ischaemia (T2), and 5 min after tourniquet deflation (T3) for malondialdehyde (MDA) measurements. Results: No differences were noted between the groups in haemodynamic (p > 0.05) and demographic data (p > 0.05). There was no statistically significant difference between the two groups in terms of T1, T2 and T3 periods (p > 0.05). There was a statistically increase observed in MDA values respectively both in Group P and Group K between the reperfusion period (1.95 ± 0.59, 2.31 ± 0.48) and pre-ischaemia (1.41 ± 0.38, 1.54 ± 0.45), and ischaemia (1.76 ± 0.70, 1.71 ± 0.38) (µmoL-1) periods (p < 0.05). Conclusions: Small-dose propofol and ketamine has similar potential to reduce the oxidative stress caused by tourniquet-induced ischaemia-reperfusion injury in patients undergoing arthroscopic knee surgery under spinal anaesthesia.

Resumo Objetivos: O objetivo do presente estudo foi investigar os efeitos preventivos de propofol e cetamina em sedação com doses baixas durante a raquianestesia sobre lesão de isquemia-reperfusão induzida por torniquete. Métodos: 30 pacientes foram randomicamente alocados em dois grupos de 15 pacientes cada. No grupo propofol, a sedação foi feita com 0,2 mg.kg-1 de propofol seguida por infusão a uma taxa de 2 mg.kg-1.h-1. No grupo cetamina, uma infusão contínua de 0,5 mg.kg-1.h-1 de cetamina foi usada até o final da cirurgia. Midazolam intravenoso não foi administrado em nenhum dos pacientes. A Escala de Sedação de Ramsay (ESR) foi usada para avaliar o nível de sedação. Amostras de sangue venoso foram colhidas antes da administração de propofol e infusão de cetamina (T1), aos 30 minutos (min) de isquemia do torniquete (T2) e 5 min após a desinsuflação do torniquete (T3), para medir os valores de malondialdeído (MDA). Resultados: Não observamos diferenças entre os grupos em relação à hemodinâmica (p > 0,05) e dados demográficos (p > 0,05). Não houve diferença estatisticamente significativa entre os dois grupos nos períodos T1, T2 e T3 (p > 0,05). Um aumento estatisticamente significativo foi observado nos valores de MDA, respectivamente, no Grupo P e Grupo C entre os períodos de reperfusão (1,95 ± 0,59, 2,31 ± 0,48) e pré-isquemia (1,41 ± 0,38, 1,54 ± 0,45) e isquemia (1,76 ± 0,70, 1,71 ± 0,38) (µmoL-1) (p < 0,05). Conclusões: Propofol e cetamina em doses baixas apresentam potencial semelhante para reduzir o estresse oxidativo causado pela lesão de isquemia-reperfusão induzida por torniquete em pacientes submetidos à artroscopia de joelho sob raquianestesia.

Moderate sedation helps improve future behavior in pediatric dental patients - a prospective study

Abstract There is little evidence on the long-term effects of pharmacological management in children undergoing dental treatment. This study aimed to assess children's behavior in consecutive dental sessions following oral rehabilitation using different pharmacological regimens for behavioral control. Participants were preschoolers who were previously treated for caries under one of the following: no sedative, oral sedation with midazolam, oral sedation with midazolam/ketamine, or general anesthesia. The children's behavior in the follow-up sessions was assessed using the Ohio State University Behavioral Rating Scale (OSUBRS); higher scores represented less cooperative behavior (range 5-20). Follow-up assessments were conducted on 50 children under four years old for up to 29 months. Data were analyzed by the Friedman/Wilcoxon tests and Cox regression model. OSUBRS mean (standard deviation) scores for the whole sample decreased from 11.9 (5.4) before treatment to 6.8 (3.2) at the final recall session (p < 0.001). Moderate sedation with midazolam (OR 2.9, 95%CI 1.2-6.9) or midazolam/ketamine (OR 4.3, 95%CI 1.6-11.4) improved children's future behavior. The general anesthesia group (n = 4) had a small sample size and the results should be considered with caution. Although invasive dental treatment negatively affected the child's behavior in the dental chair, they became more cooperative over time. Moderately sedated children showed better prospective behavior than those in the non-sedation group.

Ketamine promotes inflammation through increasing TLR4 expression in RAW264.7 cells / 华中科技大学学报（医学）（英德文版）

Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.

Premedication with dexmedetomidine in pediatric patients: a systematic review and meta-analysis

Premedication is important in pediatric anesthesia. This meta-analysis aimed to investigate the role of dexmedetomidine as a premedicant for pediatric patients. A systematic literature search was conducted to identify randomized controlled trials comparing dexmedetomidine premedication with midazolam or ketamine premedication or placebo in children. Two reviewers independently performed the study selection, quality assessment and data extraction. The original data were pooled for the meta-analysis with Review Manager 5. The main parameters investigated included satisfactory separation from parents, satisfactory mask induction, postoperative rescue analgesia, emergence agitation and postoperative nausea and vomiting. Thirteen randomized controlled trials involving 1190 patients were included. When compared with midazolam, premedication with dexmedetomidine resulted in an increase in satisfactory separation from parents (RD = 0.18, 95% CI: 0.06 to 0.30, p = 0.003) and a decrease in the use of postoperative rescue analgesia (RD = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003). Children treated with dexmedetomidine had a lower heart rate before induction. The incidence of satisfactory mask induction, emergence agitation and PONV did not differ between the groups. Dexmedetomidine was superior in providing satisfactory intravenous cannulation compared to placebo. This meta-analysis suggests that dexmedetomidine is superior to midazolam premedication because it resulted in enhanced preoperative sedation and decreased postoperative pain. Additional studies are needed to evaluate the dosing schemes and long-term outcomes of dexmedetomidine premedication in pediatric anesthesia.

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

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

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

Sympathetic activity of S-(+)-ketamine low doses in the epidural space / Atividade simpática de cetamina S-(+) em doses baixas no espaço epidural / Actividad simpática de la ketamina S(+)-en dosis bajas en el espacio epidural

BACKGROUND AND OBJECTIVES: S-(+)-ketamine is an intravenous anaesthetic and sympathomimetic with properties of local anaesthetic. It has an effect of an analgetic and local anaesthetic when administered epidurally, but there are no data whether low doses of S-(+)-ketamine have sympathomimetic effects. The aim of this study was to determine whether low doses of S-(+)-ketamine, given epidurally together with local anaesthetic, have any effect on sympathetic nervous system, both systemic and below the level of anaesthetic block. METHODS: The study was conducted on two groups of patients to whom epidural anaesthesia was administered to. Local anaesthesia (0.5% bupivacaine) was given to one group (control group) while local anaesthesia and S-(+)-ketamine were given to other group. Age, height, weight, systolic, diastolic and mean arterial blood pressure were measured. Non-competitive enzyme immunochemistry method (Cat Combi ELISA) was used to determine the concentrations of catecholamines (adrenaline and noradrenaline). Immunoenzymometric determination with luminescent substrate on a machine called Vitros Eci was used to determine the concentration of cortisol. Pulse transit time was measured using photoplethysmography. Mann-Whitney U-test, Wilcoxon test and Friedman ANOVA were the statistical tests. Blood pressure, pulse, adrenaline, noradrenaline and cortisol concentrations were measured in order to estimate systemic sympathetic effects. RESULTS: 40 patients in the control group were given 0.5% bupivacaine and 40 patients in the test group were given 0.5% bupivacaine with S-(+)-ketamine. Value p < 0.05 has been taken as a limit of statistical significance. CONCLUSIONS: Low dose of S-(+)-ketamine administered epidurally had no sympathomimetic effects; it did not change blood pressure, pulse, serum hormones or pulse transit time. Low dose of S-(+)-ketamine administered epidurally did not deepen sympathetic block. Adding 25 ...

JUSTIFICATIVA E OBJETIVOS: cetamina S-(+) é um anestésico intravenoso e simpaticomimético com propriedades de anestésico local. Tem efeito analgésico e de anestésico local quando administrada por via epidural, mas não há dados que relatem se cetamina S-(+) em doses baixas tem efeitos simpaticomiméticos. O objetivo deste estudo foi determinar se cetamina S-(+) em doses baixas, administrada por via epidural em combinação com anestésico local, tem algum efeito sobre o sistema nervoso simpático, tanto sistêmico quanto abaixo do nível do bloqueio anestésico. MÉTODOS: o estudo foi conduzido com dois grupos de pacientes submetidos à anestesia epidural. Anestesia local (bupivacaína a 0,5) foi administrada a um grupo (controle), enquanto anestesia local em combinação com cetamina S-(+) foi administrada ao outro grupo (teste). Idade, altura, peso, pressão arterial sistólica e diastólica e pressão arterial média foram medidos. O método imunoquímico de inibição enzimática não competitiva (Cat Combi Elisa) foi usado para determinar as concentrações de catecolaminas (adrenalina e noradrenalina). O ensaio imunoenzimométrico com substrato luminescente em uma máquina chamada Vitros Eci foi usado para determinar a concentração de cortisol. O tempo de transição do pulso foi medido com fotopletismografia. Para análise estatística, os testes de Wilcoxon, U de Mann-Whitney e Anova de Friedman foram usados. Pressão arterial, pulso e concentrações de adrenalina, noradrenalina e cortisol foram medidos para estimar os efeitos simpáticos sistêmicos. RESULTADOS: receberam bupivacaína a 5% 40 pacientes do grupo controle e 40 do grupo teste receberam bupivacaína a 0,5% com cetamina S-(+). Um valor de p < 0,05 foi ...

JUSTIFICACIÓN Y OBJETIVOS: la ketamina S(+) es un anestésico intravenoso y simpaticomimético con propiedades de anestésico local. Posee un efecto analgésico y de anestésico local cuando se administra por vía epidural, pero no existen datos que informen si la ketamina S(+) en bajas dosis tiene efectos simpaticomiméticos. El objetivo de este estudio fue determinar si la ketamina S(+) en bajas dosis y administrada por vía epidural en combinación con el anestésico local tiene algún efecto sobre el sistema nervioso simpático, tanto sistémico como por debajo del nivel del bloqueo anestésico. MÉTODOS: el estudio fue realizado con 2 grupos de pacientes sometidos a anestesia epidural. A un grupo (grupo control) se le administró la anestesia local (bupivacaína al 0,5), mientras que a otro se le administró la anestesia local en combinación con la ketamina S(+). La edad, altura, peso, presión arterial sistólica y diastólica y la presión arterial media se midieron. El método inmunoquímico de inhibición enzimática no competitiva (Cat Combi ELISA) se usó para determinar las concentraciones de catecolaminas (adrenalina y noradrenalina). El ensayo inmunoenzimométrico con sustrato lumínico en una máquina llamada Vitros Eci fue usado para determinar la concentración de cortisol. El tiempo de transición del pulso fue medido usando la fotopletismografía. Para el análisis estadístico se usaron los test de Wilcoxon, U de Mann-Whitney y ANOVA de Friedman. La presión arterial, pulso y concentraciones de adrenalina, noradrenalina y cortisol fueron medidos para estimar los efectos simpáticos sistémicos. RESULTADOS: cuarenta pacientes del grupo control recibieron bupivacaína al 5% y 40 pacientes del grupo test recibieron bupivacaína al 0,5% con ketamina ...

Effects caused by the spinal administration of ketamine S (+) 5% with no preservatives, using a single puncture, and located on the spinal cord and meninges in rabbits

PURPOSE: To evaluate the effect of ketamine S (+) 5% with no preservatives and administered as a subarachnoid single puncture on the spinal cord and meninges of rabbits. METHODS: Twenty young adult female rabbits, each weighing 3500-5000 g and having a spine length between 34 and 38 cm, were divided by lot into two groups (G): 0.9% saline in G1 and ketamine S (+) 5% in G2, by volume of 5 μg per cm column (0.18 mL). After intravenous anaesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random solution was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: No histological lesions were found in the nervous tissue (roots and cord) or meninges in either group. CONCLUSION: The ketamine S (+) 5% unpreserved triggered no neurological or histological lesions in the spinal cord or meninges of rabbits. .

Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF) levels in rats subjected to ketamine administration (25 mg/kg) for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug. .

Club drugs: review of the ‘rave’ with a note of concern for the Indian scenario.

'Club drugs’ which include Ecstasy, gamma-hydroxybutyrate (GHB), ketamine, and Rohypnol (flunitrazepam) have become popular with participants in ‘raves’, because they are perceived to enhance energy, endurance, sociability and sexual arousal. These drugs vary in their pharmacologic properties, physiological and psychological effects, and potential consequences. The use of club drugs by young people has increased in the last decade, and continue to get modified and evolve, making them very difficult to monitor. Further, these drugs are not picked up by routine drugs screening procedures, thereby making these popular with the criminals. India, which is in a phase of social transition, also faces this rising menace. Despite the nature and extent of this problem, this area has been under-researched. Data from India are sparse barring a few newspaper and police reports. Keeping abreast of current trends in club drug use prepares the clinician to recognize the clinical effects of club drug use, to manage club drug related emergencies, and to generate social awareness.

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.

Electro-acupuncture reduces the need for additional anesthetics in experimental studies / Eletroacupuntura reduz a necessidade de doses adicionais de anestésicos em estudos experimentais

PURPOSE: To evaluate the possible beneficial effects of electro-acupuncture in rats subjected to ketamine/xylazine (KX) intra-peritoneal (i.p.) anesthesia. METHODS: Forty-eight male Wistar rats were distributed in four equal groups. All rats received i.p. injections of ketamine (90 mg/kg) +xylazine (10 mg/kg) anesthesia. Basal values group (control) rats (BV) received no additional treatment. The equivalent of the human right ST36 (Zusanli) and CV-12(Zhongwan) acupoints were chosen for needling and electrical stimulation. AC rats were needled with sterilized disposable stainless steel needles at right ST36 and CV12 acupoints; needles were retained for 30 minutes. EAC10 rats, after needle insertion as described, had electrodes connected to both needles and to an electro stimulator model NKL EL-608; pulsed square waves, 10 Hz, 10 mA, was applied for 30 minutes. EAC100 rats were submitted to EA as described. However, a greater frequency (100 Hz) was used. RESULTS: Thirty-seven rats remained under adequate anesthetic level during the experiment. However, maintenance anesthesia was required by 11 rats. Need for additional anesthesia decreased to 9.1 percent in EAC100 rats compared to BV (36.3 percent). CONCLUSION: Both the AC and the EAC10/100 prolong the anesthetic effect of the combination Ketamine-xylazine in rats, allowing longer duration of anesthesia with a lower dose of anesthetic, thereby reducing the occurrence of complications.

OBJETIVO: Avaliar os possíveis efeitos benéficos da eletroacupuntura em ratos submetidos à anestesia intraperitoneal (i.p.) com ketamina / xilazina. MÉTODOS: Quarenta e oito ratos Wistar foram randomizados em quatro grupos iguais. Todos os ratos receberam injeções i.p. de ketamina (90 mg / kg) + xilazina (10 mg / kg). Os ratos do grupo Valores Basais (controle - BV) não receberam nenhum tratamento adicional. Os acupontos equivalentes aos humanos E-36 (Zusanli) e VC-12 (Zhongwan) foram escolhidos para inserção de agulhas e estimulação elétrica. Os ratos do grupo AC foram estimulados com agulhas esterilizadas descartáveis, de aço inoxidável, nos acupontos E-36 direito e VC12. As agulhas foram mantidas por 30 minutos. Nos ratos do grupo EAC10, após agulhamento, como descrito, eletrodos foram conectados às agulhas e ao eletro-estimulador modelo NKL EL-608 e aplicadas ondas quadradas pulsantes, 10 Hz, 10 mA, por 30 minutos. Os ratos do grupo EAC100 foram submetidos à EA como descrito. No entanto, uma maior freqüência (100 Hz) foi utilizada. RESULTADOS: Trinta e sete ratos permaneceram no nível anestésico adequado durante o experimento. No entanto, a manutenção da anestesia foi se fez necessária em 11 animais. Nos ratos do grupo EAC100 a necessidade de anestesia complementar diminuiu para 9,1 por cento em comparação com ratos do grupo BV (36,3 por cento). CONCLUSÃO: Tanto a AC como a EAC10/100 prolongam o efeito anestésico da combinação ketamina-xilazina em ratos, permitindo maior duração da anestesia com menor dose de anestésico, reduzindo assim a ocorrência de complicações.

Toxicokinetics of ketamine in rabbits / 法医学杂志

OBJECTIVE@#To investigate the toxicokinetics profiles of ketamine and its main metabolite norketamine in rabbits.@*METHODS@#The rabbits were administered orally the hydrochloride of ketamine with a dose of 0.15 g/kg. The serum and urine samples were collected before administration and at different time points after drug administration. The concentrations of ketamine and norketamine were determined by GC-NPD and GC-MS. Compartment model and toxicokinetics parameters were simulated and calculated by WinNorLin program. Changes of important vital signs of rabbits were recorded during the experiment.@*RESULTS@#The mean serum concentration-time profile of ketamine and norketamine were fitted to a two-compartment open model with first order kinetics. The kinetic equation of ketamine and norketamine were p(t) = 121.760 e(-0.0025t) +0.980 e(-0.002t) +4.579 e(-0.021 t) and p(t) = 640.919 e(-0.03 t) +1.023 e(-0.001 t) +9.784 e (-0.031 t), respectively. The peak time and the peak concentration of ketamine in serum were (40.950 +/- 12.098) min and (9.015 +/- 1.344) microg/mL, respectively. The elimination half-time of ketamine in rabbits was (430.370 +/- 28.436) min. The serum and urine showed a middle relation in concentrations of ketamine during 30-240 min after drug administration. After oral administration ketamine to rabbits, the toxic symptom on the rabbits occurred at 30 min and disappeared after 120 min.@*CONCLUSION@#The toxicokinetics parameters and kinetic equation of ketamine and norketamine in rabbits may provide the theoretical basis for forensic identification of reasonable specimen collection and inferring the time of oral administration ketamine from the ketamine concentration in serum.

Effect of ketamine on transient outward potassium current of isolated human atrial myocytes / 药学学报

The effects of ketamine on transient outward potassium current (I(to)) of isolated human atrial myocytes were investigated to understand the mechanism of part of its effects by whole-cell patch-clamp. Atrial myocytes were enzymatically isolated from specimens of human atrial appendage obtained from patients under going cardiac valve displacing. Ito is recorded in voltage-clamp modes using the patch-clamp technique at room temperature. Currents signals were recorded by an Axopatch 200B amplifier with the Digidata 1322A-pClamp 9.0 data acquisition system. Ketamine decreased I(to) of human atrial myocytes in a dose-dependent manner. The current-voltage curve was significantly lowered, 30, 100, 300, and 1000 micromol x L(-1) ketamine decreased respectively I(to) current density about (13.62 +/- 0.04)%, (38.92 +/- 0.05)%, (72.24 +/- 0.10)% and (83.84 +/- 0.05)% at the potential of 50 mV, with an IC50 of 121 micromol x L(-1). The I(to) activation curve, inactivation curve and the recovery curve were not altered by ketamine. So, ketamine concentration-dependently decreased I(to) of human atrial myocytes.

Clorhidrato de ketamina: técnicas analíticas necesarias para el desarrollo tecnológico / Ketamine hydrochloride: analytical techniques needed for technological development

El desarrollo tecnológico requiere de métodos analíticos confiables que permitan la cuantificación del fármaco en diferentes etapas de la investigación. El objetivo de este trabajo fue las validaciones prospectivas de 2 métodos analíticos, uno por UV-VIS y otro por cromatografía líquida de alta eficiencia, desarrolladas para el control del proceso de fabricación, de la calidad y para el estudio de estabilidad de ketamina. A las técnicas se le determinaron los parámetros de desempeño, especificidad, linealidad, exactitud, rango y precisión. Los resultados alcanzados permiten concluir que ambos métodos cumplen con los requisitos establecidos como aceptables para cada uno de los casos en el rango de concentraciones establecido. El método espectrofotométrico puede utilizarse en el control del proceso de producción y el control de calidad del producto terminado al igual que el método cromatográfico; el primero, es de elección para el control de proceso de fabricación por su sencillez y rapidez, y el segundo, para el estudio de estabilidad del producto por su elevada especificidad.

Technological development requires of reliable and analytical methods to quantify drugs in different stages of research. Aim of present paper was the prospective validations of two analytical methods, one by UV-VIS, and the other by high performance liquid chromatography, developed to control of manufacture process, quality, and to study of Ketamine stability. Techniques included the following parameters: performance, specificity, linearity, accuracy, rank, and precision. Results achieved allow concluding that both methods fulfill the criteria established as fair to each of the cases in rank of concentrations stetted. Spectrophotometry method may be used in control of production process and in control of quality of end product just like the chromatography method, the first one, is the choice to control of manufacture process due to its simplicity and speed, and the second one, to study of product stability due to its high specificity.