Use of intravenous lidocaine in a patient with refractory chest pain secondary to Takayasu arteritis. Case report / Uso da lidocaína endovenosa em paciente com dor torácica refratária secundária à arterite de Takayasu. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Takayasu's arteritis (TA) is a rare form of chronic inflammatory disease involving large vessels, with uncertain etiology, with chest pain as a common and challenging symptom, resulting from inflammation in the aortic root or arch, pulmonary artery or coronary arteries. The objective of this study was to describe the use of intravenous lidocaine to treat severe and refractory chest pain secondary to TA. CASE REPORT: A 33-year-old female patient diagnosed with TA, with severe chest pain that was difficult to manage, was admitted after consulting an emergency department. The pain was unresponsive to traditional treatment after a week of drug adjustments. As a therapeutic option, a Sympathetic Venous Blockade (SVB) with lidocaine was chosen, achieving a reduction in pain from 10 to 3 on the Visual Analog Scale. Infliximab was administered before discharge. The patient was re-evaluated at an outpatient appointment after 30 days. CONCLUSION: This strategy for the treatment of severe chest pain allowed for pain reduction and relief.

RESUMO JUSTIFICATIVA E OBJETIVOS: A arterite de Takayasu (AT) é uma forma rara de doença inflamatória crônica envolvendo grandes vasos, com etiologia incerta, tendo a dor torácica como um sintoma comum e desafiador, consequente à inflamação na raiz ou arco aórtico, artéria pulmonar ou coronárias. O objetivo deste estudo foi relatar a utilização da lidocaína por via endovenosa na abordagem da dor torácica intensa e refratária secundária à AT. RELATO DO CASO: Paciente do sexo feminino, 33 anos, com diagnóstico de AT, dor torácica intensa de difícil manejo, internada após consulta em serviço de emergência. Dor não responsiva ao tratamento tradicional após uma semana de ajustes em fármacos. Como opção terapêutica, foi escolhido o Bloqueio Simpático Venoso (BSV) com lidocaína, obtendo redução da dor de 10 para 3 na Escala Analógica Visual. Antes da alta hospitalar foi administrado infliximabe. Paciente foi reavaliada em consulta ambulatorial após 30 dias. CONCLUSÃO: Esta estratégia fora tratamento da dor torácica intensa permitiu redução e alívio da dor.

Efecto de la dibucaína sobre la SERCA del músculo pterigoideo interno / Drug action of dibucaine on the SERCA from medial pterygoid muscle

Objetivo: Determinar el efecto del anestésico local di-bucaína sobre las principales isoformas de la SERCA (calcio ATPasa de retículo sarco-endoplásmico) pre-sentes en músculo pterigoideo interno. Métodos: Se aislaron por centrifugación diferencial membranas de retículo sarcoplásmico de pterigoideo interno de conejo neozelandés macho (n=5). Se separaron las isoformas SERCA1a, 2a y 2b por cromatografía de afinidad. Se determinó in vitro la actividad enzimá-tica en presencia de diferentes concentraciones de dibucaína (0-90 mM) por el método de Fiske y Subba-row, realizando 5 experimentos por duplicado y en paralelo para cada isoforma. Se calculó la media y ES de la CI50 (mM) del anestésico para cada isofor-ma y éstas se compararon por ANOVA de una vía (p<0,05), y prueba Student-Newman-Keuls de com-paraciones múltiples. Resultados: Dibucaína inhibió la actividad enzimática en función de su concentra-ción en las tres isoformas en estudio. Las CI50 fueron: SERCA1a 20,02 ± 0,64 mM, SERCA2a 15,03 ± 0,52 mM y SERCA2b 16,00 ± 0,51 mM y resultaron signi-ficativamente diferentes (F2,27 = 11,08, p<0,001). La prueba post hoc identificó diferencias significativas entre SERCA1a y 2a, 1a y 2b. El efecto inhibitorio re-sultó significativamente mayor sobre las isoformas 2a y 2b, cuya presencia es sustancialmente mayor en músculos masticadores. Conclusión: La dibucaína inhibe a la SERCA de pterigoideo interno a concen-traciones menores que las usadas en clínica médica (29 mM). Es un anestésico local con potencial efecto miotóxico derivado de la inhibición de la SERCA (AU)

Aim: To test the effect of the local anesthetic dibu-caine on the main isoforms of the SERCA (sarco-endosplasmic reticulum calcium-ATPase) in medial pterygoid muscle. Methods: Sarcoplasmic reticulum membranes from male New Zealand rabbits (n=5) were isolated from medial pterygoid muscle by ul-tracentrifugation. The isoforms SERCA1a, 2a and 2b were separated using high affinity chromatography. In vitro enzymatic activity determinations were per-formed in the presence of different dibucaine con-centrations (0-90 mM) using the colorimetric method described by Fiske & Subbarow. Five assays in dupli-cate and run in parallel were performed for each of the isoforms. Mean and SEM of the IC50 (mM) for the effect of the anesthetic on each isoform were calcu-lated and compared by one-way ANOVA (p<0.05), and Student-Newman-Keuls multiple comparisons test. Results: Dibucaine inhibited the enzymatic activity in a concentration-dependent manner for the three studied isoforms. The IC50 values were: SERCA1a 20.02 ± 0.64 mM, SERCA2a 15.03 ± 0.52 mM and SER-CA2b 16.00 ± 0.51 mM. The values were significantly different (F2.27 = 11.08, p<0.001). The post hoc test revealed significant differences between SERCA1a and 2a, 1a and 2b. The inhibitory effect was signifi-cantly higher on 2a and 2b isoforms, whose presence is substantially higher in masticatory muscles. Con-clusion: Dibucaine inhibits SERCA in medial pterygoid muscle at concentrations lower than those used in clinical medicine (29 mM). It is a potentially myotoxic local anesthetic whose toxic effect may derive from SERCA inhibition (AU)

Effect of continuous intra-incisional bupivacaine on postoperative pain in non-traumatic spinal fixation surgeries: a randomized controlled trial

Abstract Background Continuous injection of local anesthetics by using surgical wound catheters for postoperative pain relief has gained acceptance in recent years. However, whether this method can be alternatively used instead of systemic opioids in different surgical procedures has not yet been elucidated. Objectives The aim was to investigate the effect of continuous injection of bupivacaine through a catheter inside the surgical wound on reducing the postoperative pain of lumbar spine fusion surgeries. Methods In this clinical trial, 31 patients undergoing non-traumatic lumbar spine stabilization surgery were randomly assigned to receive (n = 15) or do not receive (n = 16) bupivacaine through a catheter inside the surgical wound, postoperatively. Pain intensity (NRS), dose of required morphine, and drug-related complications within 24 hours of intervention were assessed and compared by the Mann-Whitney and independent t-test. Results Mean pain intensity was significantly lower in the case group over the first postoperative hour in the recovery room (p < 0.001), which continued for the first 2 hours after entering the ward. The mean morphine intake was lower in the bupivacaine group during the first postoperative 24 hours (16 ± 0.88 vs. 7.33 ± 0.93 mg, p < 0.001). The two groups were not significantly different regarding drug-related complications. Conclusion Continuous intra-incisional infusion of bupivacaine helped better pain reduction during the early postoperative hours while sparing morphine consumption in the first postoperative day.

Avaliação dos padrões cardiovasculares e da concentração sérica de catecolaminas em pacientes submetidos à exodontias por via alveolar, sob anestesia local com epinefrina: um ensaio clínico controlado, cego e randomizado / Assessment of cardiovascular patterns and serum catecholamine concentration in patients undergoing alveolar extraction under local anesthesia with epinephrine: a controlled, blind and randomized clinical trial

Objetivos: Um ensaio clínico controlado, cego e randomizado foi desenvolvido para avaliar os efeitos cardiovasculares em pacientes saudáveis e com hipertensão submetidos à exodontia por via alveolar utilizando lidocaína com epinefrina 1:100.000. Materiais e métodos: Vinte pacientes foram divididos em grupos experimental (GE ­ pacientes hipertensos) e controle (GC ­ pacientes normotensos). As variáveis analisadas foram a frequência cardíaca (FC), saturação de oxigênio (SO2), pressão arterial sistólica e diastólica (PAsis e PAdias), concentração sérica de catecolaminas (dopamina, epinefrina e norepinefrina), extrassístoles ventriculares e supraventriculares (ESV e ESSV respectivamente) e depressão do segmento do ST. Os dados foram colhidos em três momentos distintos: inicial, transoperatório (trans) e final. Amostras de sangue foram coletadas para a mensuração das catecolaminas, e um aparelho de Holter foi utilizado para coleta de dados do eletrocardiograma incluindo um período de avaliação de 24 horas pós-operatório. Foram utilizados o teste de Mann-Whitney para identificar diferenças entre os grupos e o teste de Friedman com o pós-teste de Wilcoxon ajustado para a avaliação intragrupos das amostras repetidas. Resultados: O GE apresentou menor SO2 no momento inicial (p = 0,001) enquanto a PAsis apresentou diferença estatística para os três momentos de avaliação com o GE apresentando os maiores valores. As ESV foram maiores para o GE no período de avaliação pós-operatória de 24 horas (p = 0,041). As ESSV e as catecolaminas séricas foram similares nos dois grupos. A análise intragrupo revelou diferença significativa na avaliação da PAsis para o GE com o período trans operatório apresentando os maiores valores. Já avaliação das extrassístoles demonstrou que o período pós-operatório de 24 horas teve a maioria dos eventos sendo que apenas o GC não apresentou diferença significativa para a variável ESV durante esse período (p = 0,112). Não houve depressão do segmento ST para nenhum dos grupos, ou seja, a isquemia do miocárdio não foi observada durante o estudo. Conclusões: As exodontias por via alveolar, com o uso de ALVC com epinefrina podem ser realizadas de forma segura em pacientes hipertensos. A pressão arterial sistêmica deve ser monitorada durante todo o procedimento, sobretudo nos pacientes hipertensos, devido à tendência de aumento da pressão arterial nesses pacientes. Já o nível sérico de catecolaminas não sofre alteração nas condições estudadas assim como o uso de ALVC parecem não influenciar os padrões cardiovasculares nesse tipo de cirurgia (AU).

Objectives: A blind, randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) containing epinephrine in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100.000. Materials and methods: 20 patients were divided into control (CG ­ normotensive patients) and experimental groups (EG ­ hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (O2S), systolic and diastolic blood pressure (sysBP and diasBP), serum catecholamines concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans and final). Blood samples were taken to measure the catecholamines and a Holter device was used to measure data from the electrocardiogram including a 24-hour postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups and the Friedman test with the adjusted Wilcoxon post-test were used for intragroup evaluation for repeated measures. Results: The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES where higher for the EG during the 24-hour postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystoles evaluation showed that the 24- hour postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups, ie, Myocardial ischemia was not observed. Conclusions: Teeth extraction with LAVC containing epinephrine can be safely executed in hypertensive patients. Blood pressure should be monitored during the entire procedure, especially in hypertensive patients due to a tendency to high blood pressure within these patients. Serum catecholamines concentration levels are not altered in the conditions seen in this study and the use of LAVC seem not to influence cardiovascular changes in this type of surgery (AU).

Atualização em reações de hipersensibilidade aos anestésicos locais / Update on local anesthetics hypersensitivity reactions

Os anestésicos locais são essenciais em diversos procedimentos médicos e odontológicos. Funcionam estabilizando as membranas neuronais e inibindo a transmissão de impulsos neurais, o que permite a realização desses procedimentos com mais segurança e sem dor. As reações adversas a drogas são definidas pela Organização Mundial da Saúde como todos os efeitos nocivos, não intencionais e indesejáveis de uma medicação, que ocorrem em doses usadas para prevenção, diagnóstico e tratamento. As reações de hipersensibilidade são reações adversas do tipo B, imprevisíveis, que clinicamente se assemelham a reações alérgicas e podem ou não envolver um mecanismo imune. As reações de hipersensibilidade verdadeiras aos anestésicos locais são raras, apesar de superestimadas. Nesta revisão destacamos a necessidade de uma avaliação completa dos pacientes com suspeita de reação alérgica aos anestésicos locais, incluindo a investigação de outros possíveis alérgenos que tenham sido utilizados no procedimento, como analgésicos, antibióticos e látex. A estratégia de investigação e seleção de pacientes para testes deve se basear na história clínica. Dessa forma, poderemos fornecer orientações mais assertivas e seguras aos pacientes.

Local anesthetics are essential in many medical and dental procedures. They work by stabilizing neuronal membranes and inhibiting the transmission of neural impulses, which allows these procedures to be performed more safely and without pain. Adverse drug reactions are defined by the World Health Organization as all harmful, unintended and undesirable effects of a medication, which occur at doses used for prevention, diagnosis and treatment. Hypersensitivity reactions are unpredictable type B adverse reactions that clinically resemble allergic reactions and may or may not involve an immune mechanism. True hypersensitivity reactions to local anesthetics are rare, although overestimated. In this review, we highlight the need for a thorough evaluation of patients with suspected allergic reaction to local anesthetics, including investigation of other possible allergens that may have been used in the procedure, such as analgesics, antibiotics and latex. The investigation strategy and patient selection for testing should be based on clinical history. In this way, we will be able to provide more assertive and safe guidelines to patients.

Juan Evangelista Manrique, the true pioneer of spinal anesthesia in Colombia / El verdadero pionero de la raquianestesia en Colombia: Juan Evangelista Manrique

Abstract Several findings paved the way to the use of the spinal approach for anesthesia. Information about the originators and dates of their discoveries is controversial. According to personal communications, doctors Juan Bautista Montoya y Flórez, in Medellín, and Lisandro Leyva, in Bogotá, in 1904 and 1905 respectively, would appear to be the pioneers of spinal anesthesia in Colombia. Pioneering cases of this procedure carried out in 1901 by doctor Juan Evangelista Manrique and which continued to be performed by his colleagues and assistants of the medical community at the time are documented in the Corporis Fabrica dissertation collection of the National University of Colombia.

Resumen Son varios los hallazgos que contribuyeron al abordaje de la columna vertebral como vía para la administración de anestesia. Los autores y las fechas de tales descubrimientos han sido controvertidos. En Colombia, según fuentes orales, los doctores Juan Bautista Montoya y Flórez, en Medellín, y Lisandro Leyva, en Bogotá, en 1904 y 1905 respectivamente, serían los pioneros de la anestesia raquídea en Colombia. En las tesis de la Facultad de Medicina de la Universidad Nacional, Colección Corporis Fabrica, se documentan los casos pioneros de este procedimiento realizados en 1901, por el doctor Juan Evangelista Manrique y continuados enseguida por sus colegas y ayudantes de la comunidad médica de ese entonces.

Analgesia posoperatoria en la videolaparascopía de urgencia mediante irrigación de bupivacaína intraperitoneal / Posoperative analgesia in emergency videolaparoscopy through intraperitoneal bupivacaine irrigation

Introducción: La videolaparascopía es un procedimiento frecuente en los servicios de urgencias de cirugía general. El dolor agudo después de estas intervenciones es de naturaleza compleja y requiere un tratamiento analgésico efectivo. Objetivo: Determinar la utilidad del empleo de bupivacaína intraperitoneal en el alivio del dolor posoperatorio en la videolaparascopía de urgencia. Métodos: Se realizó un estudio longitudinal prospectivo y analítico en 80 pacientes mayores de 18 años, anunciados para videolaparoscopía bajo anestesia general orotraqueal en el servicio de urgencias del HMC: Dr. Luis Díaz Soto, desde septiembre de 2016 hasta septiembre de 2018. Los pacientes fueron divididos aleatoriamente en dos grupos de 40 cada uno. Al grupo 1 se aplicó lidocaína transdérmica preincisional en las incisiones de piel y, al término de la cirugía, se irrigaron ambos hemidiafragmas con bupivacaína al 0,25 por ciento. Al grupo 2 se le administró dosis preincisional de analgésicos endovenosos solamente. Resultados: Predominó significativamente el sexo femenino sin diferencia entre grupos. La analgesia posoperatoria fue mejor en el grupo 1 estadísticamente significativa a las 4, 8 y 12 horas. Los requerimientos de analgesia de rescate fueron menores en el grupo 1 (p=0,0024). No se reportaron efectos adversos. Conclusiones: La administración de lidocaína transdérmica preincisional y la instilación de bupivacaína intraperitoneal al final de la videolaparoscopía de urgencia, reduce significativamente el dolor en las primeras horas de posoperatorio. Su aplicación es sencilla, fácil y segura sin evidencias de efectos adversos(AU)

Introduction: Videolaparoscopy is a frequent general surgery procedure in emergency services. Acute pain after these interventions is complex in nature and requires effective analgesic treatment. Objective: To determine the usefulness of intraperitoneal bupivacaine in the relief of postoperative pain in emergency videolaparoscopy. Methods: A prospective, analytical and longitudinal study was carried out in eighty patients older than eighteen years old, announced for videolaparoscopy under orotracheal general anesthesia in the emergency department of Hospital Militar Central Dr. Luis Díaz Soto, from September 2016 to September 2018. The patients were randomly divided into two groups of forty individuals each. Group 1 was applied pre-incisional transdermal lidocaine on skin incisions and, at the end of surgery, both hemidiaphragms were irrigated with bupivacaine 0.25 percent. Group 2 received pre-incisional doses of intravenous analgesics only. Results: The female sex predominated significantly, without difference between the two groups. Postoperative analgesia was better in group 1, insofar it was statistically significant at four, eight and twelve hours. Rescue analgesia requirements were lower in group 1 (p=0.0024). No adverse effects were reported. Conclusions: The administration of pre-incisional transdermal lidocaine and the instillation of intraperitoneal bupivacaine at the end of emergency videolaparoscopy significantly reduces pain during the first hours after surgery. Its application is simple, easy and safe, without evidence of adverse effects(AU)

Effect of neural therapy on NGF and BDNF serum levels in patients with chronic pain. A pilot study / Efecto de la terapia neural sobre los niveles séricos del NGF y el BDNF en pacientes con dolor crónico. Estudio piloto

Abstract Introduction: Neurotrophins (NT) are a family of proteins consisting of the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF) and NT-3 and NT-4/5. These proteins play an essential role in neuronal survival, differentiation, and proliferation. Objectives: To analyze the variations of NGF and BDNF serum levels in patients with chronic pain after undergoing neural therapy and to establish the effects of this type of intervention on their quality of life. Materials and methods: Prospective pilot study conducted in 10 patients with chronic pain treated with neural therapy between July 2017 and April 2018 in Bogotá D.C., Colombia. Three consultations were performed (one in which the intervention was initiated, and two follow-up visits every three weeks). During each consultation, the patients' quality of life was assessed using the SF-12 scale and their NGF and BDNF serum levels were measured. Data were analyzed by means of descriptive statistics, using medians and interquartile ranges for quantitative variables, and absolute frequencies and percentages for qualitative variables. Results: The median score on the SF-12 scale tended to improve in the first and second follow-up visits compared with the baseline score (pre-intervention), particularly during the first follow-up visit (consultation No. 1: 34.5; follow-up No. 1: 39.5, and follow-up No. 2: 38). Median NGF serum levels had a downward trend after the intervention, particularly in the first follow-up visit (157.6, 42.95, and 237.8, respectively), and in the case of BNDF, an overall downward trend was also found (29.96, 19.24 and 20.43, respectively). An improvement in quality of life related to the decrease in the serum levels of both neurotrophins was observed. Conclusion: Neural therapy intervention reduced NGF and BDNF serum levels and improved the quality of life of the participants. Therefore, the behavior of these neurotrophins could become a biomarker for the diagnosis, treatment, and follow-up of patients with chronic pain.

Resumen Introducción. Las neurotrofinas (NT) son una familia de proteínas conformada por el factor de crecimiento nervioso (NGF), el factor neurotrófico derivado del cerebro (BDNF) y las neurotrofinas NT-3 y NT-4/5; estas proteínas tienen un papel esencial en la supervivencia, diferenciación y proliferación neuronal. Objetivos. Analizar las variaciones de los niveles séricos del NGF y el BDNF en pacientes con dolor crónico luego de recibir terapia neural y establecer los efectos de este tipo de intervención en su calidad de vida. Materiales y métodos. Estudio piloto prospectivo realizado en 10 pacientes con dolor crónico tratados con terapia neural entre julio de 2017 y abril de 2018 en Bogotá D.C., Colombia. Se realizaron 3 consultas (una en la que se inició la intervención y dos de control cada tres semanas) y en cada una se evaluó la calidad de vida mediante el cuestionario de salud SF-12 y se midieron los niveles séricos del NGF y el BDNF. Los datos se analizaron mediante estadística descriptiva, utilizando medianas y rangos intercuartiles para las variables cuantitativas, y frecuencias absolutas y porcentajes para las cualitativas. Resultados. La mediana de puntaje del cuestionario SF-12 tendió a mejorar en el primer y segundo control comparada con la puntuación inicial (antes de la intervención), en particular en el primer control (consulta 1: 34.5; control 1: 39.5, y control 2: 38). La mediana de los niveles séricos del NGF tendió a disminuir luego de la intervención, en particular en el primer control (157.6, 42.95 y 62.2, respectivamente), y en el caso del BNDF, la tendencia global también fue hacia la disminución (29.96, 19.24 y 20.43, respectivamente). Se observó una mejora en la calidad de vida relacionada con la disminución de los niveles séricos de ambas neurotrofinas. Conclusión. La intervención de terapia neural produjo una reducción en los niveles séricos del NGF y el BDNF y mejoró la calidad de vida de los participantes; por tanto, el comportamiento de estas neurotro-finas podría convertirse en un biomarcador para el diagnóstico, tratamiento y seguimiento de pacientes con dolor crónico.

Autophagy activation attenuates the neurotoxicity of local anesthetics by decreasing caspase-3 activity in rats / A ativação autofágica atenua a neurotoxicidade dos anestésicos locais ao diminuir a atividade da caspase‐ 3 em ratos

Abstract Background and objectives The mechanisms by which local anesthetics cause neurotoxicity are very complicated. Apoptosis and autophagy are highly coordinated mechanisms that maintain cellular homeostasis against stress. Studies have shown that autophagy activation serves as a protective mechanism in vitro. However, whether it also plays the same role in vivo is unclear. The aim of this study was to explore the role of autophagy in local anesthetic-induced neurotoxicity and to elucidate the mechanism of neurotoxicity in an intrathecally injected rat model. Methods Eighteen healthy adult male Sprague-Dawley rats were randomly divided into three groups. Before receiving an intrathecal injection of 1% bupivacaine, each rat received an intraperitoneal injection of vehicle or rapamycin (1 mg.kg-1) once a day for 3 days. The pathological changes were examined by Haematoxylin and Eosin (HE) staining. Apoptosis was analysed by TdT-mediated dUTP Nick-End Labelling (TUNEL) staining. Caspase-3, Beclin1 and LC3 expression was examined by Immunohistochemical (IHC) staining. Beclin1 and LC3 expression and the LC3-II/LC3-I ratio were detected by western blot analysis. Results After bupivacaine was injected intrathecally, pathological damage occurred in spinal cord neurons, and the levels of apoptosis and caspase-3 increased. Enhancement of autophagy with rapamycin markedly alleviated the pathological changes and decreased the levels of apoptosis and caspase-3 while increasing the expression of LC3 and Beclin1 and the ratio of LC3-II to LC3-I. Conclusions Enhancement of autophagy decreases caspase-3-dependent apoptosis and improves neuronal survivalin vivo. Activation of autophagy may be a potential therapeutic strategy for local anaesthetic-induced neurotoxicity.

Resumo Introdução e objetivos Os mecanismos de neurotoxicidade dos anestésicos locais são complexos. A apoptose e a autofagia são mecanismos altamente organizados que mantêm a homeostase celular durante o estresse. Estudos revelam que a ativação da autofagia atua como mecanismo de proteção in vitro. Não está claro se a autofagia também desempenha essa função in vivo. O objetivo deste estudo foi analisar o papel da autofagia na neurotoxicidade induzida por anestésico local e esclarecer o mecanismo dessa neurotoxicidade utilizando um modelo de injeção intratecal em ratos. Métodos Dezoito ratos Sprague‐Dawley machos adultos saudáveis foram divididos aleatoriamente em três grupos. Antes de receber a injeção intratecal de bupivacaína a 1%, cada rato recebeu injeção intraperitoneal de veículo ou rapamicina (1 mg.kg‐1) uma vez ao dia durante 3 dias. As alterações patológicas foram examinadas por coloração com Hematoxilina e Eosina (HE). A apoptose foi analisada por coloração com o método dUTP Nick‐End Labeling (TUNEL) mediado por TdT. A expressão de caspase‐3, Beclin1 e LC3 foram examinadas por coloração Imunohistoquímica (IHQ). A expressão de Beclin1 e LC3 e a razão LC3‐II/LC3‐I foram detectadas por análise de western blot. Resultados Após a injeção intratecal de bupivacaína, ocorreu lesão patológica nos neurônios da medula espinhal e os níveis de apoptose e caspase‐3 aumentaram. A ativação da autofagia causada pela rapamicina mitigou de forma expressiva as alterações patológicas e diminuiu os níveis de apoptose e caspase‐3, aumentando a expressão de LC3 e Beclin1 e a razão LC3‐II/LC3‐I. Conclusões O aumento da autofagia diminui a apoptose dependente da caspase‐3 e melhora a sobrevivência neuronal in vivo. A ativação da autofagia pode ser uma estratégia terapêutica potencial para a neurotoxicidade induzida por anestésicos locais.

A study of effect of topical anaesthetics on injection pain during immunization in infants

Background: Immunization is a necessary aspect of health care of children and injections are there for unavoidable. Many factors affect injection pain during immunization in infants. This study aims to see the effect of use of local anesthetics delivered by various modes for attenuation of vaccine related injection pain in infants and to compare them.Methods: An Open Label Four-Arm Randomized Control Trial of 300 healthy infants of age group 6 weeks to 6 months reported to immunization clinic for immunization with DPT-HiB-Hepatitis B combination vaccine were taken for study. The enrolled subjects were allocated into control group and intervention group (who were applied some form of local anesthesia).Results: Among the four groups of the patients studied we observed a statistical difference in the mean pain scores of the patients recorded at 15 second, 60 second and 5 min after vaccine injection (p value 0.0024 - 0.000). Group A (Infants with topical occlusive LA cream) showed minimum pain scores values at 15 second, 60 second and 5 min after vaccine injection, followed by Group C (Infants with topical LA spray with vapocoolant) whereas Control group (Infants not received any local anaesthesia) and Group B (Infants with topical LA spray without vapocoolant) exhibited the maximum pain scores.Conclusions: Topical occlusive local anesthetic cream and topical LA spray with vapocoolent, were found to be better than topical LA spray without vapocoolant or no topical anesthetic. Use of topical occlusive LA cream led to a lowest pain score. There was no significant difference in the profile of side effects following injection in the four group.

Influence of different local anesthetics on atracurium neuromuscular blockade on rats / Influência de diferentes anestésicos locais no bloqueio neuromuscular produzido pelo atracúrio em ratos

Abstract Introduction: The association between local anesthetics (LA) and neuromuscular blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. Objective: The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. Methods: Male Wistar rats, weighing from 250 to 300 g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 µg.mL−1 (Group I); racemic bupivacaine 5 µg.mL−1 (Group II); atracurium 20 µg.mL−1 (Group III); atracurium 20 µg.mL−1 in a preparation previously exposed to lidocaine 20 µg.mL−1 and racemic bupivacaine 5 µg.mL−1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane potentials (MP) and miniature endplate potentials (MEPPs). Results: Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. Conclusions: Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

Resumo Introdução: A associação de anestésicos locais (AL) com bloqueadores neuromusculares (BNM) na prática clínica e a possibilidade de interação entre esses fármacos têm sido investigadas. Objetivo: Avaliar, em modelo experimental, o efeito da lidocaína e da bupivacaína racêmica na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido pelo atracúrio. Método: Ratos machos da linhagem Wistar, peso entre 250 e 300 g. A preparação foi feita de acordo com a técnica proposta por Bulbring. Grupos (n = 5) de acordo com o fármaco em estudo: lidocaína 20 µg.mL-1 (Grupo I); bupivacaína racêmica 5 µg.mL-1 (Grupo II); atracúrio 20 µg.mL-1 (Grupo III); atracúrio 20 µg.mL-1 em preparação previamente exposta a lidocaína 20 µg.mL-1 e bupivacaína racêmica 5 µg.mL-1, Grupos IV e V, respectivamente. Foram avaliados: 1) A amplitude das respostas do hemidiafragma à estimulação indireta antes e 60 minutos após a adição dos fármacos; 2) Os potenciais de membrana (PM) e os potenciais de placa terminal em miniatura (PPTM). Resultados: Os AL, isoladamente, não alteraram a amplitude das respostas musculares. Com o uso prévio dos AL, o bloqueio neuromuscular (%) do atracúrio foi 86,66 ± 12,48 e 100, respectivamente, com diferença significante (p= 0,003) em relação ao produzido pelo atracúrio isoladamente (55,7 ± 11,22). Não alteraram o PM. A lidocaína inicialmente aumentou a frequência dos PPTM, seguido de bloqueio; com a bupivacaína, o bloqueio foi progressivo. Conclusão: A lidocaína e a bupivacaína racêmica apresentaram efeito pré-sináptico expresso por alterações nos PPTM, podem justificar a potencialização do bloqueio neuromuscular produzido pelo atracúrio.

General anesthesia combined with erector spinae plane block for ductus arteriosus closure: two case reports / Anestesia geral associada a bloqueio do plano do músculo eretor da espinha para encerramento de persistência de canal arterial: dois relatos de caso

Abstract Background: Failure of ductus arteriosus closure in preterm neonates results in a left-to-right shunt that leads to variable severities of hemodynamic and respiratory distress. When medical therapy fails, surgical ligation via left lateral thoracotomy remains an alternative approach and can be performed in the operating room or at the bedside with a low mortality rate. Opioid-based anesthesia is a frequent choice among anesthesiologists who manage patent ductus arteriosus cases based on the suppression of the stress response and maintenance of hemodynamic stability. This rationale suggests that regional anesthesia may also be an advantageous technique and may benefit earlier weaning from ventilation. Blocking afferent signals before incision may also modulate the long-term consequences of altered sensory perception and pain responses. Case report: We present two cases of general anesthesia combined with erector spinae plane block as part of multimodal anesthesia in premature twins undergoing patent ductus arteriosus closure. Discussion: In these cases, the use of erector spine plane block combined with general anesthesia was efficient to minimize the negative impact of surgery and allowed a reduction in the amount of intraoperative opioid use for patent ductus arteriosus closure.

Resumo Justificativa: A persistência do canal arterial em neonatos prematuros resulta em shunt esquerdo-direito com alterações hemodinâmicas e desconforto respiratório de gravidade variável. Quando o tratamento clínico não é bem sucedido, o fechamento cirúrgico via toracotomia lateral esquerda continua sendo a abordagem alternativa, e pode ser realizado no centro cirúrgico ou à beira leito com baixa taxa de mortalidade. A anestesia baseada em opioides é frequentemente escolhida pelos anestesiologistas nos casos de fechamento de canal arterial devido à supressão de resposta ao estresse e manutenção da estabilidade hemodinâmica. Essa justificativa sugere que a anestesia regional também pode ser uma técnica vantajosa e que promove desmame mais precoce do ventilador. O bloqueio dos estímulos aferentes antes da incisão também pode modular os efeitos no longo-prazo, tanto da percepção sensorial quanto das respostas à dor. Relato de caso: Apresentamos dois casos de anestesia geral associada a bloqueio do plano do músculo eretor da espinha como parte de anestesia multimodal em gêmeos prematuros submetidos a fechamento de canal arterial persistente. Discussão: Nos dois casos descritos, o bloqueio do plano do músculo eretor da espinha associado à anestesia geral foi eficiente para minimizar o impacto negativo da cirurgia, e possibilitou a redução na quantidade de opioide usado durante cirurgia para fechamento de persistência canal arterial.

Unintended Formalin Injection instead of Local Anesthetic Agent: Its Causes & Management

Mistakes do happen in every profession instead of properprecautions. Mishaps are those unfortunate accidents thatoccur during treatment, some owing to inattention to detail,others being very unpredictable and some are due to thenegligence of the employee. Dental negligence may lead tosevere complications and may threaten one's life. This casereport presents an unconventional case of administeringformalin in lieu of local anesthesia in a dental clinic leading tochemical cellulitis and its management.

Toxicidad sistémica por anestésicos locales en paciente con hipoalbuminemia severa. Reporte de un caso / Case report Local anesthetic toxicity due to hypoalbuminemia

Local anesthetics are drugs widely used to perform peripheral nerve blocks. Signs and symptoms of toxicity may vary from mild to severe, including neuro and cardiotoxicity, with seizures and cardiac arrest. We present the case of an 85-year-old patient in total left knee replacement plan due to tibial saucer fracture, where systemic toxicity was observed by local anesthetics (LAST) after performing a femoral nerve block guided by neurostimulation and ultrasound with a solution of 20 ml of 0.525% ropivacaine + 0.6% lidocaine. As a positive data, the patient presented severe hypoalbuminemia

Los anestésicos locales son fármacos ampliamente utilizados para realizar bloqueos nerviosos periféricos. Los signos y síntomas de toxicidad pueden variar de leves a severos, incluidas la neuro y cardiotoxicidad, con convulsiones y paro cardíaco. Presentamos el caso de una paciente de 85 años de edad en plan de reemplazo total de rodilla izquierda debido a fractura de platillo tibial, donde se observó toxicidad sistémica por anestésicos locales (LAST por su sigla en inglés) después de realizar un bloqueo del nervio femoral guiado por neuroestimulación y ultrasonido con una solución de 20 ml de ropivacaína al 0,525% + lidocaína al 0,6%. Su único antecedente médico era presentar hipoalbuminemia severa.

Comparative analyses of response surface methodology and artificial neural networks on incorporating tetracaine into liposomes

This study evaluated the incorporation of tetracaine into liposomes by RSM (Response Surface Methodology) and ANN (Artificial Neural Networks) based models. RCCD (rotational central composite design) and ANN were performed to optimize the sonication conditions of particles containing 100 % lipid. Laser light scattering was used to perform measure hydrodynamic radius and size distribution of vesicles. The liposomal formulations were analyzed by incorporating the drug into the hydrophilic phase or the lipophilic phase. RCCD and ANN were conducted, having the lipid/cholesterol ratio and concentration of tetracaine as variables investigated and, the encapsulation efficiency and mean diameter of the vesicles as response variables. The optimum sonication condition set at a power of 16 kHz and 3 minutes, resulting in sizes smaller than 800 nm. Maximum encapsulation efficiency (39.7 %) was obtained in the hydrophilic phase to a tetracaine concentration of 8.37 mg/mL and 79.5:20.5% lipid/cholesterol ratio. Liposomes were stable for about 30 days (at 4 ºC), and the drug encapsulation efficiency was higher in the hydrophilic phase. The experimental results of RCCD-RSM and ANN techniques show ANN obtained more refined prediction errors that RCCD-RSM technique, therefore, ANN can be considered as an efficient mathematical method to characterize the incorporation of tetracaine into liposomes.

Bloqueos de tronco / Truncal blocks

Truncal blocks have recently been positioned as an alternative to neuraxial analgesia. The injection of local anesthetics in interfascial planes was initially guided by anatomical landmarks, to later evolve towards a more selective administration when guided by ultrasound. Successful execution of truncal blocks requires detailed knowledge of the chest and abdominal walls anatomy. The same logic allows us to understand its potential benefits concerning perioperative analgesia, as well as its limitations and therapeutic margins. Secondary to a growing interest in less invasive techniques and analgesic techniques with a more favorable risk-benefit profile, the available evidence in this field is in continuous development. Thus, in the present review, the technical aspects of these blocks will be evaluated, emphasizing the sonoanatomy, and assessing the best evidence to support the use of each technique.

Los bloqueos de tronco se han posicionado recientemente como una alternativa frente a la analgesia neuroaxial. La inyección de anestésicos locales en planos interfasciales inicialmente fue guiado por referencias anatómicas, para posteriormente evolucionar hacia una administración más selectiva al ser guiada por el ultrasonido. La ejecución exitosa de los bloqueos de tronco requiere un conocimiento detallado de la anatomía de las paredes del tórax y abdomen. Esta misma lógica nos permite entender sus potenciales beneficios en relación con la analgesia perioperatoria, como también sus limitaciones y margen terapéutico. La evidencia disponible está en continuo desarrollo, dado el creciente interés que concitan técnicas menos invasivas y con un perfil de riesgo-beneficio potencialmente más favorable. En la presente revisión se evaluarán los aspectos técnicos de cada bloqueo, poniendo énfasis en la sonoanatomía, y evaluando la mejor evidencia que sustente el uso de cada técnica.

Progress in Development of Long-acting Delivery Systems for Local Anesthetics and Its Application in Postoperative Analgesia / 中国药学杂志

Patients require proper pain relief after surgery. Local anesthetics are widely used to control postoperative pain, but their clinical application is limited due to short duration of action. In decades of research, the long-acting delivery systems have been applied to local anesthetics, with the purpose of locally and continuously release drugs to prolong the action of drugs and reduce the side effects. The study of local anesthetics long-acting delivery systems has laid foundation for clinical postoperative analgesia.This paper reviewed the research status of long-acting drug delivery systems for local anesthetics, and discussed the advantages and existing problems.

Período de latência, progressão e duração do bloqueio da anestesia epidural com lidocaína, bupivacaína ou sua associação em cães / Period of latency, progression and duration of blockade of epidural anesthesia with lidocaine, bupivacaine or its association in dogs

O objetivo deste estudo foi avaliar latência, duração do efeito, progressão cranial da lidocaína e da bupivacaína isoladas, ou em associação, pela via epidural, em cães, além de mensurar a pressão média do canal epidural antes e após a realização dela. Utilizaram-se 18 cães, alocados em três grupos, os quais receberam, por via epidural: lidocaína 2% (GL) 0,25mL/kg; bupivacaína 0,5% (GB) no mesmo volume, ou a associação de ambas (GLB) na proporção de 1:1. Avaliaram-se as frequências cardíaca e respiratória e a pressão arterial sistólica (PAS) previamente aos tratamentos (M0) e até 60 minutos após a anestesia epidural. Ainda, avaliou-se a pressão no canal epidural antes e após a administração dos tratamentos, o período de latência, a progressão e a duração do bloqueio pelo pinçamento interdigital e do panículo paravertebral. Houve redução de 12% da PAS no GL em todos os momentos e de 16% aos 30 minutos no GLB quando comparados ao basal. A pressão média no espaço epidural antes e após a anestesia epidural foi de -1,5 (±3,9) e 41 (±16) mmHg; 55% apresentaram pressão negativa no espaço epidural. O período de latência não diferiu entre os grupos (GL: 3,5±1,6; GB: 4,5±4,5; e GLB: 2,4±1 minutos) e a duração do bloqueio foi maior no GB em relação ao GL (GL: 125±24; GB: 176±24; e GLB: 153±35 minutos). A progressão máxima dos anestésicos foi até L1-T13 no GL, L4-L3 no GB e L3-L2 no GLB. Conclui-se que a associação de lidocaína com bupivacaína não apresenta vantagens em relação ao uso dos fármacos isolados pela via epidural, tendo a lidocaína progredido mais cranialmente em relação à bupivacaína ou à associação. A lidocaína promoveu redução da PAS, mesmo quando associada à bupivacaína, permanecendo dentro dos valores de referência. Apenas 55% dos cães apresentaram pressão média negativa no espaço epidural antes da administração dos fármacos, dessa forma o teste da gota pendente pode não ser eficiente para localização do espaço epidural em todos os animais.(AU)

The objective of this study was to evaluate the latency, duration of the effect, and cranial progression of lidocaine and bupivacaine alone or in combination, by epidural route in dogs, and measuring the average pressure of the epidural channel before and after the completion thereof. Eighteen dogs were allocated in three groups, which received epidural: lidocaine 2% (GL) 0.25ml / kg; bupivacaine 0.5% (GB) in the same volume, or the association of both (GLB) in a 1: 1 ratio. Heart and respiratory rates and systolic blood pressure (SBP) were evaluated before treatment (M0) and up to 60 minutes after epidural anesthesia. In addition, the pressure in the epidural canal was evaluated before and after the administration of the treatments, latency period, progression and duration of the block by interdigital and paravertebral pannicus clamping. There was a 12% decrease in SBP in the GL at all times and 16% at 30 minutes in GLB when compared to the baseline. The mean pressure in the epidural space before and after epidural anesthesia was -1.5 (±3.9) and 41 (±16) mmHg), 55% presented negative pressure in the epidural space. The latency period did not differ between groups (GL: 3.5±1.6; GB: 4.5±4.5; and GLB: 2.4±1 minutes) and the duration of blockade was higher in GB (GL: 125±24, GB: 176±24, and GLB: 153±35 minutes). The maximum progression of anesthetics was up to L1-T13 in GL, L4-L3 in GB and L3-L2 in GLB. It is concluded that the association of lidocaine with bupivacaine does not present advantages in relation to the use of the drugs isolated by the epidural route, with lidocaine progressing more cranially in relation to bupivacaine or the association. Lidocaine promoted the reduction of SBP, even when associated with bupivacaine, remaining within the reference values. Only 55% of the dogs presented negative mean pressure in the epidural space before administration of the drugs, so the drop test may not be efficient for locating the epidural space in all animals.(AU)

Use of a local anesthetic and opioid combination in spinal anesthesia in short urologic surgeries

Background: To investigate how low-dose levobupivacaine affects both surgical comfort and hemodynamics in patients undergoing short urologic procedures using spinal anesthesia.Methods: Our study was conducted prospectively and double-blind. The study group comprised 40 patients aged 18-65 years from the ASA I-III risk group who had undergone short urological interventions, randomly split into two groups. Informed consent and ethics committee approval were received. Using a media approach and placed in the lateral decubitus position, the patients were given spinal anesthesia using 22 G catheter. Group L was given 1.5ml of levobupivacaine (7.5mg) at 0.5% concentration +0.5ml of saline. Group LF was given 1.2ml levobupivacaine (6mg) at 0.5% concentration +25μg fentanyl (0.5ml) +0.3ml saline. Patient data including peripheral oxygen saturation; systolic, diastolic, mean arterial pressure; time to first postoperative need for analgesics, and spinal block characteristics were recorded at 3, 5, 10, 15, 30, 60, 120 and 360minutes after spinal anesthesia.Results: No significant differences were observed in the demographic and hemodynamic data between groups. Motor blocks were seen to wear off more in Group LF than in Group L at 120minutes. Group LF required first postoperative analgesics later than Group L; this difference was not significant.Conclusions: Sufficient anesthesia was achieved in both groups via spinal block using local anesthetic or local anesthetic plus opioid for relatively short urological procedures. The latter group recovered faster.

Effectiveness of anterior middle superior alveolar injection using a computer-controlled local anesthetic delivery system for maxillary periodontal flap surgery

BACKGROUND: Profound anesthesia with adequate duration is required in periodontal flap surgery, which involves the manipulation of both hard and soft tissues. The anterior middle superior alveolar (AMSA) injection may be an alternative to multiple injections required for this purpose in the maxilla. The present study aimed to assess the effectiveness of AMSA injection using computer-controlled local anesthetic delivery (CCLAD) system to anesthetize buccal hard tissue (BHT), buccal soft tissue (BST), palatal hard tissue (PHT), and palatal soft tissue (PST) around the maxillary teeth. METHODS: Thirty-five patients who were indicated for open flap debridement in a whole maxillary quadrant were given AMSA injection using the CCLAD. The effectiveness of anesthesia was evaluated using subjective and objective parameters around each tooth. Supraperiosteal infiltrations were administered to complete the surgery wherever the AMSA injection was ineffective. RESULTS: The AMSA injection was more effective on the palatal tissues than on the buccal tissues, as 94.14% of PST and 87.89% of PHT sites were anesthetized compared to 49.22% and 43.75% of BHT and BST sites, respectively. There was no significant difference in the frequency of anesthesia around the anterior and posterior teeth. The PHT was significantly more anesthetized (P = 0.003) in males than in females. CONCLUSIONS: The AMSA injection using CCLAD is highly effective on palatal tissues and could be used as a first-line anesthesia for periodontal flap surgery. However, its effect on buccal tissues is less predictable, with supraperiosteal infiltration often required to supplement the AMSA injection.