Sinopsis de revisiones sistemáticas sobre el efecto clínico de la Ketamina en el paciente agitado / Synopsis of systematic reviews on the clinical effect of Ketamine in the agitatedpatient / Sinopse de revisões sistemáticas sobre o efeito clínico da Ketamina no paciente agitado

Introducción:La literatura científica reporta estudios sobre la Ketamina, con alta heterogeneidad en los diseños, poblaciones, desenlaces y especialidades clínicas; sin embargo, no se encontró un documento que consolidara sistemáticamente la evidencia disponible y que oriente decisiones clínicas para el paciente agitado.Objetivo:Analizar la evidencia disponible en revisiones sistemáticas sobre el uso de Ketamina en paciente agitado. Materiales y métodos:Búsqueda sistemática en bases de datos multidisciplinarias. Se garantizó la exhaustividad del protocolo de búsqueda y selección de estudios, reproducibilidad y evaluación de la calidad metodológica según la herramienta Ameasurement Tool to Assess Systematic Reviews-2.Se realizó síntesis cualitativa de variables extraídas y estimación de proporciones con IC=95%.Resultados:Se tamizaron 134 estudios, 10 cumplieron los criterios del protocolo. Las revisiones sistemáticas incluyeron una población de 26.936 pacientes, la evidencia procede de dos series de caso, 7 estudios observacionales y 9 ensayos clínicos controlados. La Ketamina produce múltiples efectos adversos, algunos mayores a los causados por Midazolam.Conclusión:En algunos subgrupos se presentó alta proporción de efectos adversos respiratorios, neuropsiquiátricos y cardiovasculares, pero sin posibilidades de generalización a otros contextos. Es necesario mejorar la evidencia clínica y epidemiológica para la prescripción de Ketamina en el manejo de la agitación.

Introduction:The scientific literature about Ketamine use shows high heterogeneity in terms of design, populations, outcomes, and clinical specialties. Nevertheless, available evidence systematically consolidated to guide clinical decisions for anxious patients was notfound. Objective:To analyze evidence available in systematic reviews about the use of Ketamine in anxious patients. Materials and methods:Systematic search in multidisciplinary databases. The "A measurement Tool to Assess Systematic Reviews-2" was used to guarantee comprehensiveness of the searching protocol and study selection, reproducibility, and analysis of the methodological quality. A quantitative synthesis of the extracted variables and proportion estimation with a 95% CI were performed. Results:10 out of 134 screened studies met the protocol criteria. The systematic reviews included a population of 26,936 patients and the evidence comes mainly from two case series, 7 observational studies, and 9 controlled clinical trials. Ketamine has multiple adverse effects, some of them more critical than those caused by Midazolam. Conclusion:Some patient subgroups showed a high frequency of adverse effects such as respiratory, neuropsychiatric, and cardiovascular dysfunctions, but it was difficult to generalize them to other contexts. It is necessary to improve clinical and epidemiological evidence in order to prescribe Ketamine to manage anxiety.

Introdução:A literatura científica relata estudos sobre Ketamina, com elevada heterogeneidade nos desenhos, populações, resultados e especialidades clínicas; no entanto, não foi encontrado nenhum documento que consolide sistematicamente as evidências disponíveis e que oriente às decisões clínicas para o paciente agitado. Objetivo:Analisar as evidências disponíveis em revisões sistemáticas sobre o uso da Ketaminaem pacientes agitadose/ou agressivos. Materiais e métodos:Pesquisa sistemática em bases de dados multidisciplinares. A exaustividade do protocolo de pesquisae seleção dos estudos, reprodutibilidade e avaliação da qualidade metodológica foram garantidos com a ferramenta Ameasurement Tool to Assess Systematic Reviews-2. Foi realizada uma síntese qualitativa das variáveis extraídas e estimativa de proporções com IC=95 %. Resultados:134 estudos foram selecionados, 10 preencheram os critérios do protocolo. As revisões sistemáticas incluíram uma população de 26.936 pacientes,a evidência vem de duas séries de casos, 7 estudos observacionais e 9 ensaios clínicos controlados. A Ketaminaproduz múltiplos efeitos adversos, alguns maiores que os causados pelo Midazolam. Conclusão:Em alguns subgrupos houve alta proporção de efeitos adversos respiratórios, neuropsiquiátricos e cardiovasculares, mas sem possibilidade de generalização para outros contextos. É necessário melhorar as evidências clínicas e epidemiológicas para a prescriçãoda Ketaminano manejo da agitação.

Comparison between oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in autism spectrum disorder: double-blind randomized clinical trial

Abstract Background: Conventional dental care is often impossible in patients with Autism Spectrum Disorder (ASD). Non-collaborative behaviors, sometimes associated with aggressiveness, are usual justifications for premedication in this population. Thereby, this research focuses on the effects of oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in ASD. Methods: The sample included 64 persons with ASD, aged 2-59 years, scheduled for dental care under general anesthesia. The primary objective of this study was to compare degrees of sedation between two parallel, double-blinded, equally proportional groups randomized to receive oral midazolam (0.5 mg.kg−1, maximum 15 mg) or oral midazolam (0.5 mg.kg−1) associated with oral S(+)-ketamine (3 mg.kg−1, maximum 300 mg). The secondary outcomes were the need of physical stabilization to obtain intravenous line, awakening time, and occurrence of adverse events. Results: According to the dichotomous analysis of sedation level (Ramsay score 1 and 2 versus Ramsay ≥ 3), oral association of S(+)-ketamine and midazolam improved sedation, with increased probability of Ramsay ≥ 3, Relative Risk (RR) = 3.2 (95% Confidence Interval [95% CI] = 1.32 to 7.76) compared to midazolam alone. Combined treatment also made it easier to obtain venous access without physical stabilization, RR = 2.05 (95% CI = 1.14 to 3.68). There were no differences between groups regarding awakening time and the occurrence of adverse events. Conclusion: The association of oral S(+)-ketamine with midazolam provides better preanesthetic sedation rates than midazolam alone and facilitates intravenous line access in patients with autism.

Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial

Abstract Background Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. Objective We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. Methods Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5 mg.kg-1 bolus then 0.12 mg.kg-1.h-1 infusion for the first 24 hours postoperatively. Group KM: received ketamine 0.5 mg.kg-1 and Mg sulfate 50 mg.kg-1, then ketamine 0.12 mg.kg-1.h-1 and Mg sulfate 8 mg.kg-1.h-1 infusions for the first 24 hours postoperative. The primary outcome was the morphine consumption in the first 24 hours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. Results Group KM had less postoperative opioid consumption (14.12 ± 5.11 mg) than Group K (19.43 ± 6.8 mg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. Conclusion Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.

Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic replacement in oncology: a double-blinded randomized trial

Abstract Background There has been a growing interest in the use of ketamine following orthopedic surgeries. We hypothesized that low dose intravenous ketamine during surgery would help in mobilization following total knee replacement (TKR) in oncology patients as assessed by the timed to up and go (TUG) test at 72 hours post-surgery. Our secondary objectives were to compare the opioid requirement at the end of 72 hours, pain scores, satisfaction with pain management, adverse effects, range of joint movement achieved in the post-operative period and the functional recovery at the end of 1 month. Methods After the ethics commitee approval, registration of the trial with the Clinical Trial Registry - India (CTRI), and informed consent, this double-blinded trial was conducted. Using computer generated randomization chart, an independent team randomized the patients into ketamine group which received at induction, a ketamine bolus dose of 0.5 mg.kg-1 before the incision followed by 10 µg.kg-1min-1 infusion which was maintained intraoperatively till skin closure and the saline group received an equivalent volume of saline. Postoperatively, patient controlled morphine pumps were attached and the pain score with morphine usage were recorded for 72 hours. The TUG tests and range of motion were assessed by the physiotherapists until 72 hours. Results Fifty-two patients were enrolled in the trial. Demographics were comparable. No significant intraoperative hemodynamic changes and post-operative adverse events were noted between the groups. A decrease in the TUG test, along with decreased opioid usage with a better range of movements was noted in the ketamine group, but this was not statistically significant. Day of discharge, patient satisfaction score, and functional recovery assessed by Oxford Knee Score (OKS) were comparable between the groups. Conclusion In conclusion, low dose intraoperative ketamine infusion does not provide clinical benefit in perioperative pain management and postoperative rehabilitation following total knee endoprosthetic replacement in oncology.

Association of S(+) ketamine, dexmedetomidine and butorphanol for chemical restraint in scarlet macaws (Ara macao) / Associação cetamina S(+), dexmedetomidina e butorfanol na contenção química de araracangas (Ara macao)

The present study aimed at assessing the effects of combining 20 mg/kg S(+) ketamine with 25 µg/kg dexmedetomidine and 0.4 mg/kg butorphanol on the physiological parameters and anesthetic recovery time and score of eight captive scarlet macaw (Ara macao) specimens. These specimens were captured at the Marabá Zoobotanic Foundation (Fundação Zoobotânica de Marabá), Pará, using butterfly and mist nets, and subsequently subjected to the proposed protocol. The following physiological parameters were evaluated: heart rate (HR), respiratory rate (RR), saturation of peripheral oxygen (SpO2), body temperature (BT), and non-invasive blood pressure 5 min after drug administration (M0) and every 10 min thereafter (M1‒M5), with a total of 55 min of analysis of anesthetic effects. Glycemia was measured 5 min after drug administration and every 30 min thereafter. Anesthetic induction and recovery times were also determined. Among the parameters evaluated in this study, both HR and BT significantly decreased throughout the anesthetic period, with the lowest levels at 55 min after drug administration (M5). In contrast, RR did not significantly differ, and all animals remained stable, maintaining an RR close to a mean of 20 ± 8 cpm. Throughout the anesthetic period, SpO2was 92 ± 5%, with no significant difference. The birds remained under spontaneous ventilation and without oxygen supplementation. Systolic, diastolic, and mean blood pressures remained stable, with no significant differences in any of these measurements. At M0 and M3, the glycemia decreased slightly, albeit with no significant difference justifying an adverse effect or even hypoglycemia. The anesthetic induction time, from M0 to decubitus, was 2.4 ± 0.7 min. The anesthetic recovery time, from M0 to effortless bipedal position and adequate phalangeal flexion, was 99.3 ± 32.4 min. The sedation was assessed as intense, and the anesthetic recovery was rated excellent in 62.5% and good in 37.5% of the animals.(AU)

O presente estudo objetivou avaliar os efeitos do uso da cetamina S(+) 20 mg/kg associada à dexmedetomidina 25 µg/kg e butorfanol 0,4 mg/kg sobre os parâmetros fisiológicos, tempo e qualidade da recuperação anestésica de araracangas (Ara macao). Foram utilizados oito espécimes de Ara macao cativas da Fundação Zoobotânica de Marabá, Pará. A captura foi realizada com o uso de puçá e rede de contenção e em seguida as aves foram submetidas ao protocolo proposto. Foram avaliados: frequência cardíaca, frequência respiratória, saturação parcial da oxihemoglobina (SpO2), temperatura corporal e pressão arterial não-invasiva a partir de 5 minutos após a aplicação dos fármacos (M0) e a cada 10 minutos seguintes (M1, M2, M3, M4 e M5), totalizando 55 minutos de contemplação dos efeitos anestésicos. A glicemia foi avaliada aos 5 minutos da aplicação dos fármacos e repetida após 30 minutos. Também foi determinado o tempo de indução e de recuperação. Dentre os parâmetros avaliados, a frequência cardíaca e a temperatura demonstraram queda estatisticamente significativa ao longo do período anestésico, ambas com os menores valores registrados aos 55 minutos após a aplicação dos fármacos (M5). A frequência respiratória não apresentou diferença estatística e todos os animais se mantiveram estáveis e com a frequência próxima a média de 20±8mpm. A saturação da oxihemoblobina (SpO2) ao longo do período anestésico foi de 92±5%, não houve diferença estatisticamente relevante, as aves permaneceram sob ventilação espontânea e sem suplementação de oxigênio. As pressões arteriais sistólica, diastólica e média, mantiveram-se estáveis e não houve diferença estatística para nenhuma dessas medidas. A glicemia, mensurada em M0 e M3 demonstrou queda discreta, sem diferença significativa capaz de justificar um efeito adverso ou mesmo hipoglicemia. O tempo de indução, desde aplicação dos anestésicos até o decúbito, foi de 2,4±0,7 minutos. O tempo de recuperação, compreendido desde a aplicação dos fármacos (M0) até a constatação da posição bipedal sem esforço e adequada flexão das falanges, foi de 99,3±32,4 minutos. A qualidade de sedação foi considerada intensa e a recuperação anestésica foi classificada como ótima para 62,5% e boa para 37,5% dos animais.(AU)

Oral preanesthetic medication in children - comparison between midazolam alone and in combination with ketamine: a systematic review and meta-analysis

Abstract Background Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with oral midazolam alone for pediatric preanesthetic medication. Methods The study protocol was registered in PROSPERO as CRD42020172920. A systematic literature search was conducted using Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing oral combinations of midazolam and ketamine with midazolam alone as preanesthetic medication in elective surgical pediatric patients. Meta-analyses included the following outcomes: anxiety and sedation levels, child's behavior during separation from parents, face mask acceptance, and venipuncture. The quality of evidence was assessed using GRADE criteria. Results Twenty studies were included. The following effects (RR (95% CI)) were observed for combinations of ketamine and midazolam relative midazolam alone: anxiolysis (1.2 (0.94-1.52); p= 0.15; I2 = 80%; GRADE = very low); satisfactory sedation (1.2 ( 1.10-1.31); p< 0.001; I2 = 71%; GRADE = very low); behavior during parental separation (1.2 (1.06-1.36); p= 0.003; I2 = 88%; GRADE = very low); facial mask acceptance (1.13 (1.04-1.24); p= 0.007; I2 = 49%; GRADE = very low); behavior during venipuncture (1.32 (1.11-1.57); p= 0.002; I2 = 66%; GRADE = very low). Conclusions While similar probabilities of obtaining anxiolysis were found, adequate sedation, calm behavior during child's separation from parents, low levels of fear during face mask adaptation, and cooperative behavior during peripheral venous cannulation were more likely with midazolam-ketamine combinations.

The effects of repeated doses of xylazine-ketamine and medetomidineketamine anesthesia on DNA damage in the liver and kidney

Purpose: This study evaluated the DNA damage caused by repeated doses of xylazine-ketamine and medetomidine-ketamine anesthesia in the liver and kidneys. Methods: In this study, 60 rats were used. The rats were divided into group 1 (xylazine-ketamine), and group 2 (medetomidine-ketamine), and these anesthetic combinations were administered to the rats at repeated doses with 30-min intervals. The effects of these anesthetic agents on the tumor necrosis factor-alpha gene for DNA damage were investigated. Results: According to the gene expression results, it was observed that a single dose of xylazine-ketamine was 2.9-fold expressed, while first and second repeat doses did not show significant changes in expression levels. However, in the case of the third repetition, it was observed to be 3.8-fold overexpressed. In the case of medetomidine-ketamine administration, it was observed that a single-dose application resulted in a 1.04-fold expression, while the first and the third repeat doses showed a significant down expression. The samples from the second repeat dose administration group were found to have insignificant levels of expression. Conclusions: This study can contribute to understanding the safe anesthetic combination in research and operations in which xylazine-ketamine and medetomidine-ketamine combinations are used.

Dos concentraciones de ketofol en anestesia total intravenosa para cirugía mínimamente invasiva / Tow concentrations of ketofol in total intravenous anesthesia for minimally invasive surgery

Introducción: En los últimos años se ha iniciado un interés especial por la combinación de ketamina/propofol para pacientes intervenidos por procedimientos mínimamente invasivos. Objetivo: Evaluar la efectividad y seguridad de la anestesia intravenosa total con ketofol en concentración 1:4 contra la concentración 1:2 en pacientes intervenidos por cirugía mínimamente invasiva. Métodos: Estudio analítico, cuasiexperimental, prospectivo y longitudinal, en el Hospital Universitario General Calixto García entre diciembre de 2019 a diciembre de 2020, en 30 pacientes divididos en dos grupos de 15 pacientes: grupo estudio (GE): Ketofol 1:4 y grupo control (GC): Ketofol 1:2. Se analizaron: tensión arterial media y frecuencia cardiaca intra operatoria, grado de hipnosis, grado de nocicepción, necesidad de rescate para hipnosis y analgesia, tiempo de recuperación anestésica, analgesia posoperatoria y efectos adversos. Resultados: Entre los grupos fueron similares la edad, el sexo, el peso, estado físico y tipo de intervención quirúrgica. La frecuencia cardiaca no mostró diferencias entre los grupos. En relación a la tensión arterial mediapos-incisión, fue mayor en el grupo control con diferencias significativas (p=0,03). La necesidad de rescate intraoperatorio para la hipnosis y analgesia fue significativamente mayor en el grupo control. Con respecto a la recuperación anestésica, analgesia posoperatoria y efectos adversos no hubo diferencias significativas. Conclusiones: La combinación ketofol resultó segura y efectiva para proveer una adecuada anestesia en procedimientos quirúrgicos mínimamente invasivos con tiempos quirúrgicos menores a 30 min. La concentración de 1:4 brindó mejor estabilidad hemodinámica, adecuada hipnosis y analgesia intraoperatoria, con menor incidencia de efectos adversos(AU)

Introduction: In recent years, a special interest has appeared in the ketamine/propofol combination for patients intervened by minimally invasive procedures. Objective: To evaluate the effectiveness and safety of total intravenous anesthesia with ketofol at 1:4 concentration versus 1:2 concentration in patients undergoing minimally invasive surgery. Methods: An analytical, quasiexperimental, prospective and longitudinal study was carried out at General Calixto García University Hospital, between December 2019 and December 2020, with thirty patients divided into two groups of fifteen patients each: study group (SG; ketofol 1:4) and control group (CG; ketofol 1:2). The following aspects were analyzed: mean blood pressure and intraoperative cardiac frequency, degree of hypnosis, degree of nociception, necessity of rescue for hypnosis and analgesia, anesthetic recovery time, postoperative analgesia and adverse effects. Results: Age, sex, weight, physical condition and type of surgery were similar between groups. Heart rate showed no differences between groups. Mean blood pressure after incision was higher in the control group, with significant differences (P=0.03). The necessity of intraoperative rescue for hypnosis and analgesia was significantly higher in the control group. Regarding anesthetic recovery, postoperative analgesia and adverse effects, there were no significant differences. Conclusion: The ketofol combination was safe and effective for providing adequate anesthesia in minimally invasive surgical procedures with surgical times of less than thirty minutes. The 1:4 concentration provided better hemodynamic stability, adequate hypnosis and intraoperative analgesia, with lower incidence of adverse effects(AU)

Efficacy of opioids and non-opioid analgesics in the treatment of post procedure pain of burned patients: a narrative review

Abstract Introduction Burns are a common trauma that cause acute severe pain in up to 80% of patients. The objective of this narrative review is to evaluate the efficacy of opioids, non-steroidal anti-inflammatory drugs, paracetamol, gabapentinoids, ketamine, and lidocaine in the treatment of acute pain in burn victims. Methodology The databases explored were PubMed, Embase, ClinicalTrials, and OpenGrey. The included randomized, controlled clinical trials assessed the analgesic efficacy of these drugs on hospitalized patients, had no age limit, patients were in the acute phase of the burn injury and were compared to placebo or other analgesic drugs. Studies describing deep sedation, chronic opioid use, chronic pain, and patients taken to reconstructive surgeries were excluded. The Jadad scale was used to evaluate quality. Results Six randomized controlled clinical trials (397 patients) that evaluated the analgesic efficacy of fentanyl (n = 2), nalbuphine (n = 1), ketamine (n = 1), gabapentin (n = 1), and lidocaine (n = 1) to treat post-procedural pain were included. Fentanyl, nalbuphine, and ketamine were effective, while lidocaine was associated with a slight increase in reported pain and gabapentin showed no significant differences. Two studies were of high quality, one was of medium high quality, and three were of low quality. No studies on the efficacy of NSAIDs or paracetamol were found. Conclusion Evidence of efficacy is very limited. Fentanyl, nalbuphine, and ketamine seem to be effective for controlling acute pain in burn patients, whereas gabapentin and lidocaine did not show any efficacy.

Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

Guia Prático de Atualização no tratamento da exacerbação de asma na criança e no adolescente ­ Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical Update Guide on the treatment of asthma exacerbation in children and adolescents ­ Joint position of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Exacerbação aguda de asma é uma condição frequente na criança e no adolescente e uma das causas mais comuns de procura aos pronto atendimentos e de internações. Pode ocorrer em pacientes que ainda não foram diagnosticados como asmáticos, e mesmo naqueles cujo controle da doença não se encontre adequado. Reconhecer a exacerbação e iniciar seu tratamento desde o domicílio até o adequado manejo inicial em ambiente hospitalar é fundamental para evitar sua evolução para complicações que coloquem o paciente em risco de vida. O tratamento compreende o reconhecimento e tratamento da hipoxemia, da obstrução e do processo inflamatório, além de fornecer orientações na alta hospitalar e encaminhamentos para continuidade do tratamento.

Acute exacerbation of asthma is a frequent condition in children and adolescents and one of the most common causes of seeking emergency care and hospitalization. It can occur in patients who have not yet been diagnosed with asthma, and even in those whose disease control is not adequate. Recognizing the exacerbation and starting its treatment from home until proper initial management in a hospital environment is essential to avoid its evolution to complications that put the patient at risk of life. Treatment comprises the recognition and treatment of hypoxemia, obstruction, and the inflammatory process, in addition to providing guidance at hospital discharge and referrals for continued treatment.

Anestesia intravenosa contínua com cetamina racêmica ou dextrocetamina e detomidina em cadelas / [Continuous intravenous anesthesia with racemic ketamine or dextroketamine and detomidine in female dogs]

Objetivou-se com este estudo comparar a associação de detomidina e cetamina ou dextrocetamina, por via intravenosa contínua, em oito cadelas submetidas a dois protocolos: GCD - indução anestésica com 5mg/kg e infusão intravenosa contínua de 20mg/kg/h de cetamina; e GDD - indução com 3,5mg/kg e infusão de 14mg/kg/h de dextrocetamina. Associou-se detomidina, 30µg/kg/h, em ambos os grupos. Registraram-se frequência cardíaca (FC), pressão arterial (PA), frequência respiratória (f), temperatura (TC), miorrelaxamento, analgesia, hemogasometria e eletrocardiograma, antes e 15 minutos após a MPA (Mbasal e Mmpa); após o início da infusão (Mic); a cada 10 minutos até 90 minutos (M10, M20, M30, M40, M50, M60, M70, M80 e M90); e 30 minutos após o fim da infusão (M120). Foi observada bradicardia em Mmpa no GCD e de Mmpa a M10 no GDD. Ocorreu hipotensão em Mmpa e hipertensão a partir de Mic. A f diminuiu de M10 a M30. Foram observados: onda T de alta amplitude, bloqueios atrioventriculares e parada sinusal. Ocorreu acidose respiratória. O período de recuperação foi de 219,6±72,3 minutos no GCD e de 234,1±96,8 minutos no GDD. A cetamina e a dextrocetamina, associadas à detomidina por infusão contínua, causam efeitos cardiorrespiratórios e anestésicos similares.(AU)

The combination of detomidine and ketamine or dextrocetamine for continuous intravenous infusion was compared in eight female dogs submitted to two protocols: GCD - 5mg/kg of anesthetic induction and continuous intravenous infusion of ketamine 20mg/kg/h; and GDD - induction with 3.5mg/kg and infusion of 14mg/kg/h of dextrocetamine. Detomidine, 30µg/kg/h was associated in both groups. Heart rate (HR), blood pressure (BP), respiratory rate (RR), temperature (CT), myorelaxation, analgesia, blood gas analysis and electrocardiogram were recorded before and 15 minutes after MPA (Mbasal and Mmpa); after the start of infusion (Mic); every 10 minutes to 90 minutes (M10, M20, M30, M40, M50, M60, M70, M80 and M90); and 30 minutes after the end of infusion (M120). Bradycardia was observed in Mmpa in GCD and from Mmpa to M10 in GDD. There was hypotension in Mmpa and hypertension from Mic. The RR decreased from M10 to M30. High amplitude T wave, atrioventricular blocks and sinus arrest were observed. Respiratory acidosis occurred. The recovery period was 219.6±72.3 minutes in GCD and 234.1±96.8 minutes in GDD. Ketamine and S+ ketamine associated with detomidine for continuous infusion cause cardiorespiratory and similar anesthetic effects.(AU)

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.

A new anesthetic protocol to medullary nerve roots access in rats

ABSTRACT Purpose: To describe a new anesthetic protocol medullary and nerve roots access and in Rattus norvegicus. Methods: Seventy female Wistar rats (n=70) were used. The animals were randomly divided into two laminectomy groups: cervical (n=40) and thoracic (n=30). In cervical group, a right posterior hemilaminectomy was performed to access the nerve roots. In thoracic group, a laminectomy of the eighth thoracic vertebra was accomplished. Thirty-five rats (20 cervical and 15 thoracic) were submitted to old anesthetic protocol (ketamine 70 mg/kg plus xylazine 10 mg/kg); and the 35 other animals (20 cervical and 15 thoracic) were submitted to a new anesthetic protocol (ketamine 60 mg/kg,xylazine 8 mg/kg and fentanyl 0.03 mg/kg). Results: The time to complete induction was 4.15 ±1.20 minin ketamine, xylazine and fentanyl group, and it was 4.09 ±1.47 min in the ketamine and xylazine group. There was no correlation in the time required to perform the cervical laminectomy in the old anesthetic protocol. In all groups, the animals submitted to the old anesthetic protocol had a higher level of pain on the first and third postoperative days than the animals submitted to the new anesthetic protocol. Conclusions: The new anesthetic protocol reduces the surgical time, allows better maintenance of the anesthetic plan, and brings more satisfactory postoperative recovery.

Histomorphometric comparison of the corpus cavernosum of rats submitted to euthanasia with ketamine and xylazine or isoflurane

ABSTRACT Purpose: To compare the penile histoarchitecture of rats euthanized with isoflurane or with ketamine and xylazine. Methods: Fourteen male rats were divided into two groups: ISO, with animals euthanized with isoflurane; and K+X, with animals euthanized with ketamine (150 mg/kg) associated with xylazine (15 mg/kg). Immediately after the death, the penises were dissected, fixed in a 4% buffered formalin solution, and processed for histomorphometric analysis. The surface densities (Sv) of the corpus cavernosum structures (connective tissue, smooth muscle, sinusoidal space, and elastic fibers) were evaluated using Image J software. The distribution of collagen types I and III was qualitatively assessed. Statistical analyses were performed using the Student's t test for data comparison, considering it statistically significant when p < 0.05. Results: Regarding the Sv of connective tissue, smooth muscle and sinusoidal space, there were no differences between animals in both groups. On the other hand, the animals euthanized with the association of ketamine and xylazine showed the Sv of elastic fibers 24.8% higher in relation to animals euthanized with isoflurane. Conclusions: The euthanasia method affected one of the morphological parameters of the rat penises. The choice of euthanasia method must be standardized to reduce bias and to obtain reliable and reproducible results.

Esketamine may be an ideal substitute for ketamine during cochlear function measurement

The mixture of ketamine and xylazine is widely used for the auditory brainstem response (ABR) measurement. Esketamine is twice as potent as ketamine. Our objective was to assess the influence of esketamine in mice undergoing cochlear function measurement including ABR and distortion product otoacoustic emission (DPOAE) measurement. C57Bl/6J mice were treated with an equivalent dose of analgesia and received either a single intraperitoneal (ip) injection of 100 mg/kg ketamine and 25 mg/kg xylazine or 50 mg/kg esketamine and 25 mg/kg xylazine. Hearing thresholds, peak latencies of waves I and V, and DPOAE thresholds were recorded. Time to loss of righting and time to regain righting were also assessed. We found that hearing thresholds, the peak latencies of waves I and V, and DPOAE thresholds were similar between the two groups (all P>0.05). Time to regain righting was significantly shorter in the esketamine group (P<0.001) than in the ketamine group. We concluded that when using equivalent doses of analgesia, esketamine may be an ideal substitute for ketamine during cochlear function test.

Infusión intravenosa de ketamina a bajas dosis durante cirugía de artrodesis de columna. Una estrategia en el manejo del dolor agudo posoperatorio / Intravenous ketamine infusión at low doses during spinal arthodesis surgery. A strategy in acute postoperative pain management

INTRODUCTION: Acute postoperative pain is a complex problem given the pathophysiological characteristics, increasing health costs and complications and hindering recovery[1],[2]. Spinal arthrodesis is one of the most painful surgical procedures, presenting intense and disabling pain[3],[4]. Multimodal analgesia has been the tool with the best results, based on opioids; however, the combined use of drugs and dependence on opiates are important consequences. Therefore, the analgesic behavior during the use of subanesthetic doses of ketamine is described in the patients undergoing this procedure. METHODOLOGY: A prospective case series study was conducted from January-December 2019, with patients undergoing spinal arthrodesis who met the inclusion criteria, at the Hernando Moncaleano Perdomo University Hospital, Neiva. A univariate statistical analysis of all the variables is performed, with a joint interpretation of the results. RESULTS: A total of 17 patients underwent surgery, one of whom was excluded due to complications related to the surgical material. 88% of the patients showed evaluations of mild or absent pain in at least 4 times, with a number of morphine rescues in 24 hours of 1-2 per patient and patient ambulation in 90% on the first day. CONCLUSIONS. Postoperative spinal arthrodesis patients receiving intravenous ketamine infusion-based analgesia at subanesthetic doses showed mild or absent pain scores at almost all times.

INTRODUCCIÓN: El dolor agudo postoperatorio es un problema complejo dada las características fisiopatológicas, aumentando los costos en salud y las complicaciones y dificultando la recuperación[1],[2]. La artrodesis de columna, es uno de los procedimientos quirúrgicos más dolorosos, presentando un dolor intenso e incapacitante[3],[4]. La analgesia multimodal ha sido la herramienta con mejores resultados, tomando como base los opioides; sin embargo, el uso combinado de fármacos y la dependencia a opiáceos son consecuencias importantes. Por lo anterior, se describe el comportamiento analgésico durante el uso de dosis subanestésicas de ketamina en los pacientes llevados a dicho procedimiento. METODOLOGÍA: Se realiza un estudio tipo serie de casos, prospectivo de enero-diciembre de 2019, con los pacientes llevados a artrodesis de columna que cumplieron con los criterios de inclusión en el Hospital Universitario Hernando Moncaleano Perdomo, Neiva. Se realiza un análisis estadístico univariado de la totalidad de las variables, con una interpretación conjunta de los resultados. RESULTADOS: Se intervinieron un total de 17 pacientes, uno de los cuales fue excluido por complicaciones relacionadas con el material quirúrgico. El 88% de los pacientes mostraron valoraciones de dolor leve o ausente en al menos 4 tiempos, con número de rescates de morfina en 24 h de 1-2 por paciente y deambulación de los pacientes en el 90% en el primer día. CONCLUSIONES: Los pacientes posoperatorios de artrodesis de columna que recibieron analgesia basada en infusión endovenosa de ketamina a dosis subanestésicas mostraron valoraciones de dolor leve o ausente, en casi todos los tiempos.