The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study

Abstract Background: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. Methods: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. Results: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. Conclusion: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB approval number: 23115 012030/2009-05.

Application of low dose S-ketamine in analgesia of elderly patients with non-traumatic acute abdomen in emergency / 中华急诊医学杂志

Objective:To investigate the efficacy and safety of low dose S-ketamine in analgesia of elderly patients with non-traumatic acute abdomen (NTAA) in emergency department.Methods:This was a randomized controlled trail. From January to August 2021, elderly patients with NTAA in the Emergency Department of the No. 904 Hospital of the Joint Logistic Support Force were selected. Analgesia was administered intravenously with 0.3 mg/kg S-ketamine or 0.1 mg/kg morphine injection for 15 min. Visual analogue score (VAS), respiratory rate, heart rate, non-invasive blood pressure and pulse oxygen saturation were recorded at 15 min, 30 min, 60 min and 90 min. The mini-mental state examination (MMSE) scores were recorded at 90 min after injection. The incidence of salvage analgesia, incidence of adverse reactions and diagnostic accuracy after analgesia were recorded in the two groups. VAS scores and vital signs were compared between the two groups by two-way repeated measures analysis of variance, and multiple comparisons between and within groups were performed.Results:A total of 137 elderly patients with NTAA were selected and randomly divided into two groups: S-ketamine group (SK group, 68 cases) and morphine group (M group, 69 cases). After the exclusion of patients with abscission, 39 cases were included in the SK group and 45 cases in the M group. VAS score of the SK group was significantly lower than that of the M group in 15 min after administration [(3.1±1.8) vs. (4.8±2.2)], and the difference was statistically significant ( P=0.013). There were no significant differences in vital signs and MMSE score between the two groups or within the group at each time point after medication (all P>0.05). However, the incidence of dizziness in the SK group was significantly higher than that in the M group (61.54% vs. 31.11%, P=0.005). Conclusions:Intravenous administration of low dose S-ketamine is not considered to be more effective than morphine in alleviating acute abdominal pain in elderly patients with NTAA. S-ketamine provides not only satisfactory analgesia but also short recovery time and high controllability. S-ketamine is one of the recommended analgesic alternatives of NTAA for elderly patients in emergency.

Ketamine for depression treatment: past, present, and future / 中国临床药理学与治疗学

Depression has become a serious global public health problem due to its high incidence and great harm, and has aroused the attention of the society. Ketamine, a commonly used intravenous anesthetic and analgesic in clinical practice, has been found to have unique advantages in antidepressant therapy in recent years. With the development of research, the enantiomeric isomers of ketamine, (S)-ketamine and (R)ketamine have entered the research field of antidepressant therapy. In this paper, we reviewed the progress of research on the antidepressant effects and mechanisms of ketamine, (S )-ketamine and (R)-ketamine, and provide a brief overview of the antidepressant effects of metabolites of ketamine, thereby deepening the understanding of the readers in the field of antidepressant effects of ketamine.

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 ...

Efeitos anestésicos da administração intranasal ou intramuscular de cetamina S+ e midazolam em pomba-rola (Streptotelia sp) / Anesthetic effects of intranasal or intramuscular administration of S+ Ketamine and Midazolam in ring necked dove (Streptotelia sp)

A via intranasal é uma boa alternativa por ser indolor e de fácil aplicação em aves. O objetivo deste estudo foi avaliar os efeitos anestésicos da associação de cetamina S+ e midazolam pela via intranasal (IN) em comparação com a via intramuscular (IM) em pombos. Foram utilizados 12 pombos alocados em dois grupos com 15 dias de intervalo, os quais receberam: grupo IM: 20 mg/kg de cetamina S+ associada a 3,5 mg/kg de midazolam pela via intramuscular (musculatura do peito); e grupo IN, mesmo protocolo, porém, pela via intranasal. Os parâmetros avaliados foram: período de latência, tempo de duração em decúbito dorsal, tempo total de anestesia, tempo de recuperação e efeitos adversos. Para a análise estatística, empregou-se o teste de Wilcoxon, com as diferenças consideradas significativas quando P<0,05. O período de latência obtido foi de 30 [30-47,5] e 40 [30-50] segundos para IM e IN, respectivamente. O tempo de duração de decúbito dorsal foi de 59 [53,25-65] e 63 [37-71,25] minutos para IM e IN, respectivamente, sem diferenças significativas entre os grupos. Com relação à duração total de anestesia, foi observada diferença significativa, com 88 [86,25-94,5] e 68 [53,5-93] minutos para os grupos IM e IN, respectivamente. O tempo de recuperação foi mais curto no grupo IN (15 [4,25-19,5]) comparado ao IM (32 [28,25-38,25] minutos). Dois animais de cada grupo apresentaram regurgitação na fase de recuperação. Conclui-se que a administração de cetamina S+ e midazolam pela via intranasal é um método aceitável de administração de fármacos e produz anestesia rápida e eficaz em pombos.

The intranasal route is a good alternative because is painless and easy to perform in birds. The objective of this study was to evaluate the anesthetic effects of S+ ketamine and midazolam administered by intranasal or intramuscular route in pigeons. Twelve animals were used in a randomized and crossover design. Animals received two treatments with 2-weeks interval. IM group: animals received 20mg/kg of S+ ketamine and 3.5mg/kg of midazolam by intramuscular route (pectoral muscles); IN group: animals received the same protocol by intranasal route. Parameters evaluated were: onset of action, time of duration in dorsal recumbency; total time of anesthesia and side effects. Statistical analysis was performed using Wilcoxon test and the differences were considered significant when P<0.05. Onset of action was 30 [30-47.5] and 40 [30-50] seconds for IM and IN respectively. Time of duration in dorsal recumbency was 59 [53.25-65] and 63 [37-71.25] minutes for IM and IN respectively, without significant differences between treatments. Total time of anesthesia was 88 [86.25-94.5] and 68 [53.5-93] minutes for IM and IN, respectively, with significant difference between groups. The recovery time was lower for IN (15[4.25-19.5] minutes) compared with IM (32 [28.25-38.25] minutes). Two animals of each group presented regurgitation in the recovery period. It was concluded that S+ ketamine and midazolam administered intranasal is an acceptable method of drug delivery and can be used to promote anesthesia in pigeons.

Associação de cetamina S(+) e midazolam pelo método convencional de cálculo e pela extrapolação alométrica em bugios-ruivo (Alouatta guariba clamitans): resposta clínica e cardiorrespiratória / S(+) ketamine and midazolam association by the conventional method of calculation and allometric extrapolation in red howler monkeys (Alouatta guariba clamitans): clinical and cardiopulmonary response

O objetivo deste estudo foi avaliar o protocolo de contenção química com cetamina S(+) e midazolam em bugios-ruivos, comparando o cálculo de doses pelo método convencional e o método de extrapolação alométrica. Foram utilizados 12 macacos bugios (Alouatta guariba clamitans) hígidos, com peso médio de 4,84±0,97kg, de ambos os sexos. Após jejum alimentar de 12 horas e hídrico de seis horas, realizou-se contenção física manual e aferiram-se os seguintes parâmetros: frequência cardíaca (FC), frequência respiratória (f), tempo de preenchimento capilar (TPC), temperatura retal (TR), pressão arterial sistólica não invasiva (PANI) e valores de hemogasometria arterial. Posteriormente, os animais foram alocados em dois grupos: GC (Grupo Convencional, n=06), os quais receberam cetamina S(+) (5mg kg-1) e midazolam (0,5mg kg-1), pela via intramuscular, com doses calculadas pelo método convencional; e GA (Grupo Alometria, n=06), os quais receberam o mesmo protocolo, pela mesma via, utilizando-se as doses calculadas pelo método de extrapolação alométrica. Os parâmetros descritos foram mensurados novamente nos seguintes momentos: M5, M10, M20 e M30 (cinco, 10, 20 e 30 minutos após a administração dos fármacos, respectivamente). Também foram avaliados: qualidade de miorrelaxamento, reflexo podal e caudal, pinçamento interdigital, tempo para indução de decúbito, tempo hábil de sedação, qualidade de sedação, e tempo e qualidade de recuperação. O GA apresentou menor tempo para indução ao decúbito, maior grau e tempo de sedação, bem como redução significativa da FC e PANI de M5 até M30, quando comparado ao GC. Conclui-se que o grupo no qual o cálculo de dose foi realizado por meio da alometria (GA) apresentou melhor grau de relaxamento muscular e sedação, sem produzir depressão cardiorrespiratória significativa.

The aim of this study was to evaluate a protocol of chemical restraint comparing the conventional method of calculation (weight dose) and allometric extrapolation. Twelve healthy red howler monkeys (Alouatta guariba clamitans), average weight 4.84±0.97kg, male and female, were used for this study. After a 12-hour period of food restriction and 6 hours of water restriction, the animals were physically restraint and the following parameters were measured: heart rate (HR), respiratory rate (RR), capillary refill time (CRT), rectal temperature (RT), non invasive systolic arterial pressure (NISAP) and arterial blood gases analysis. The animals were distributed into two groups: CG (Conventional Group, n=6), in which the animals received S(+) ketamine (5mg kg-1) and midazolam (0.5mg kg-1), by intramuscular (IM) injection; and AG (Allometry Group, n=6), in which the animals also received S(+) ketamine and midazolan IM, but the doses were calculated by allometric extrapolation. Parameters were evaluated at the following moments: M5, M10, M20 and M30 (5, 10, 20 and 30 minutes after IM injection, respectively). Muscle relaxation, pedal and caudal reflexes, interdigital pinch, recumbency time, sedation's quality and duration, and recovery time and its quality were also evaluated. The AG had a faster time for recumbency, higher period and quality of sedation, and a significantly reduction on HR and SAP from M5 to M30 when compared to CG. It was concluded that allometric extrapolation presented a better muscle relaxation and sedation without significant cardiorespiratory depression.

Propofol-cetamina racêmica e propofol-cetamina levógira em cadelas: parâmetros eletrocardiográficos e outras variáveis fisiológicas / Propofol-racemic ketamine or propofol-levogire ketamine in dogs: effects on electrocardiography and other physiological parameters

Estudaram-se os efeitos da infusão contínua da associação propofol e cetamina sobre variáveis fisiológicas e eletrocardiográficas e sua possível analgesia em 12 cadelas. Após indução com propofol, os animais receberam 0,4mg/kg/min de propofol + 0,2mg/kg/min de cetamina racêmica (n = 6, grupo PC) ou 0,4mg/kg/min de propofol + 0,1mg/kg/min de cetamina S+ (n = 6, grupo PCS). Avaliaram-se: teste álgico, freqüência cardíaca (FC), parâmetros eletrocardiográficos, freqüência respiratória (FR), pressão arterial sistólica, média e diastólica (PAS, PAM, PAD), saturação da oxiemoglobina (SpO2) e temperatura retal (TR). Houve elevação da FC sem alterações eletrocardiográficas, com exceção de aumento na amplitude da onda T em um animal de cada grupo. A FR diminuiu, e os valores de SpO2 ficaram abaixo de 90 por cento em alguns momentos nos dois grupos. PAS, PAM e PAD diminuíram, mas não houve diferença entre os protocolos. Não se observou analgesia em sete animais, três cadelas apresentaram analgesia discreta, e apenas duas demonstraram analgesia favorável. Conclui-se que os protocolos são seguros em cadelas, contudo não há analgesia suficiente para procedimento cirúrgico. As alterações eletrocardiográficas foram relacionadas à FC e à amplitude de onda T, sendo esta sugestiva de hipóxia do miocárdio.

The effects of propofol and ketamine on physiological parameters, electrocardiography, and analgesia were evaluated in twelve dogs that received propofol-ketamine (0.4mg/kg/min + 0.2mg/kg/min, n=6, PK group) or propofol-S+ketamine (0.4mg/kg/min + 0.1mg/kg/min, n=6, PKS group) after induction of anesthesia with propofol (8.0mg/kg). Assessments of pain; heart rate (HR); electrocardiography (ECG); respiratory rate (RR); systolic, medium, and diastolic arterial pressures (SAP, MAP, DAP); saturation of hemoglobin (SpO2); and rectal temperature (RT) were conducted. There was a rise in HR with no electrocardiographically changes, but an increase in amplitude of T wave in one animal of each group. RR decreased and SpO2 were lower than 90 percent in two moments of both groups. SAP, MAP, and DAP were reduced during the experimental period, but with no statistical difference between the protocols. There was no analgesia in seven bitches, mild analgesia was observed in three, and satisfactory analgesia in only two animals tested. It was concluded that the protocols are safe for dogs, but there is no analgesia for surgical procedures. The changes in ECG are related to HR and amplitude of T wave, which may be due to myocardial hypoxia.