[Ultrasound-guided caudal block with ropivacaine in infraumbilical surgeries in pediatric patients]. / Bloqueo caudal ecoguiado con ropivacaína en cirugías infraumbilicales en pacientes pediátricos.

Background: The use of local anesthetics as part of multimodal analgesia is an attractive concept in pediatric patients, since the evaluation and management of pain is a challenge in children under 7 years of age. Despite having guidelines and multiple studies on volume calculation, no safe and effective recommendation has been issued. Objective: To demonstrate that ultrasound-guided caudal block with a dose of 0.75 mL/kg of 0.2% ropivacaine has the same analgesic effect as a dose of 1.2 mL/kg. Material and methods: Randomized, prospective, longitudinal, comparative equivalence clinical trial. One hundred patients 0-7 years of age scheduled for elective or emergency infraumbilical surgery were enrolled between April 2021 and January 2022. Children were randomized 1:1 to be assigned to ultrasound-guided caudal block. Results: 100 patients divided into two groups with 0.2% ropivacaine volumes (0.75 mL vs. 1.2 mL). Both groups demonstrated the trans-anesthetic and post-anesthetic sedoanalgesia variables without significant differences for both groups on the FLACC pain scale after surgery and in recovery (p > 0.5), in the pain reassessment on the FLACC scale in the office called chronic pain (p > 0.5) in both groups. No complications were reported in the follow-up consultations and no arrhythmias were reported in both groups during surgery. Conclusions: the results of both groups did not show differences between a volume of 0.75 mL and 1.2 mL, the administration of 0.2% ropivacaine is favored with the use of ultrasound, which allows effective administration of lower doses of local anesthetic with reduced risk of complications. It is necessary to carry out studies in other types of surgery to compare the use of less volume of local anesthetic compared to the Melman formula used in this study.

Introducción: el uso de anestésicos locales como parte de la analgesia multimodal es un concepto atractivo en pacientes pediátricos, ya que la evaluación y manejo del dolor es un reto en menores de 7 años. A pesar de contar con guías y múltiples estudios del cálculo de volumen no se ha emitido una recomendación segura y eficaz. Objetivo: demostrar que el bloqueo caudal ecoguiado con dosis de 0.75 mL/kg de ropivacaína 0.2% tiene el mismo efecto analgésico que la dosis de 1.2 mL/kg. Material y métodos: ensayo clínico aleatorizado de equivalencia, prospectivo, longitudinal, comparativo. Se enrolaron 100 pacientes de 0-7 años programados para cirugía infraumbilical electiva o de urgencia entre abril del 2021 y enero del 2022. Los niños fueron aleatorizados 1:1 para asignarse a la realización del bloqueo caudal guiado por ultrasonido. Resultados: de los 100 pacientes divididos en dos grupos con volúmenes de ropivacaína 0.2% (0.75 mL frente a 1.2 mL). Ambos grupos demostraron las variables de sedoanalgesia transanestésicas y postanestésicas sin diferencias significativas para ambos grupos en la escala de FLACC de dolor después de la cirugía y en recuperación (p > 0.5), en la revaloración de dolor en la escala de FLACC en el consultorio denominado dolor crónico (p > 0.5) en ambos grupos. No se reportaron complicaciones en las consultas de seguimiento y tampoco arritmias en ambos grupos durante la cirugía. Conclusiones: los resultados en ambos grupos no mostraron diferencias entre un volumen de 0.75 mL y 1.2 mL, la administración de ropivacaina 0.2% se favorece con el empleo de ultrasonido, lo que permite administración eficaz de dosis menores de anestésico local con reducción del riesgo de complicaciones. Es necesario realizar estudios en otros tipos de cirugía para comparar el uso de menos volumen de anestésico local frente a la fórmula de Melman que ocupamos en este estudio.

Infiltração de anestésicos locais na ferida cirúrgica: efeito sobre a inflamação e cicatriz fibrosa em ratos / Infiltration of local anesthetics into the surgical wound: effect on inflammation and fibrous scar in rats

■ RESUMO Introdução: O alívio da dor após a cirurgia continua sendo um dos desafios médicos mais significativos, principalmente na cirurgia estética. A infiltração da incisão cirúrgica com anestésicos locais tem sido cada vez mais utilizada para reduzir a dor e o uso de analgésicos. No entanto, pouco se sabe sobre o efeito desta injeção na cicatrização. O objetivo é avaliar a interferência dos anestésicos locais na área de infiltrado inflamatório e cicatriz de fibrose em ratos. Métodos: Duas incisões lineares foram feitas cada uma na região dorsal de 40 ratos Wistar. A incisão esquerda foi infiltrada com doses de 1,8ml de bupivacaína, levobupivacaína, ropivacaína ou solução salina 0,9%. A incisão direita não recebeu infiltração, servindo como grupo controle. Após sete dias, amostras das incisões foram coletadas para avaliação morfométrica histológica. Resultados: Quando comparada com os grupos controle, a área de infiltrado inflamatório encontrada foi maior nos grupos bupivacaína, ropivacaína e levobupivacaína. O grupo bupivacaína apresentou um infiltrado inflamatório maior do que a levobupivacaína e a ropivacaína. A área da cicatriz fibrosa foi maior nos grupos levobupivacaína e ropivacaína. Não houve diferença entre os grupos que receberam anestésico e solução salina. Conclusão: Como não houve diferença entre os grupos de anestésico e soro fisiológico, o volume aplicado ou o trauma podem ter sido a causa das maiores áreas de infiltração e cicatriz associadas à aplicação dos anestésicos locais.

■ ABSTRACT Introduction: Pain relief after surgery remains one of the most significant medical challenges, mainly in aesthetic surgery. The infiltration of the surgical incision with local anesthetics has been increasingly used to reduce pain and other analgesic use. However, little is known about the effect of this injection on healing. The objective is to evaluate the interference of local anesthetics in the area of inflammatory infiltrate and fibrosis scar in rats. Methods: Two linear incisions each were made on the dorsal region of 40 Wistar rats. The left incision was infiltrated with doses of 1.8ml of bupivacaine, levobupivacaine, ropivacaine, or 0,9% saline solution infiltration. The right incision did not receive infiltration, serving as a control group. After seven days, samples of the incisions were collected for histological morphometric evaluation. Results: When compared with the control groups, the area of inflammatory infiltrate was found larger in the bupivacaine, ropivacaine, and levobupivacaine groups. The bupivacaine group presented a larger inflammatory infiltrate than the levobupivacaine and ropivacaine. The fibrous scar area was larger in the levobupivacaine and ropivacaine groups. There was no difference between the groups that received anesthetic and saline solution. Conclusion: As there was no difference between the anesthetics and saline solution groups, the volume applied, or the trauma may have been the cause of the larger areas of infiltrating and scar associated with local anesthetics application.

Analysis of bupivacaine and ropivacaine-related cardiac arrests in regional anesthesia: A systematic review of case reports.

Regional anesthesia as a component of multimodal analgesia protocols has become more and more a part of modern perioperative pain management. The widespread adoption of ultrasound guidance in regional anesthesia has surely played an important role in that growth and it has significantly improved patient safety, decreased the incidence of block failure, cardiac arrest, and reduced complication rates. The objective of this systematic review is to extract, analyze, and synthesize clinical information about bupivacaine and ropivacaine related cardiac arrest that we might have a clearer picture of the clinical presentation. The literature search identified 268 potentially relevant publications and 22 relevant case reports were included in the review. Patients' demographics, types of regional anesthesia, hypotension, heart rhythm disorders, seizures, cardiac arrest, fatal outcome, recommendations and limitations on prevention and treatment of bupivacaine and ropivacaine related cardiac arrest are analyzed and discussed in the systematic review. Both bupivacaine and ropivacaine-induced local anesthetic toxicity can result in cardiac arrest. Lipid emulsion, telemetry, local anesthetic toxicity resuscitation training appears to be promising in improvement of survival but more research is needed. Improvement and encouragement of reporting the local anesthetic toxicity are warranted to improve the quality of information that can be analyzed in order to make more precise conclusion.

Analgesic effect of ropivacaine after arthroscopic reconstruction of the ligament in athletes / Efeito analgésico da ropivacaína após reconstrução artroscópica do ligamento em atletas / El efecto de la ropivacaína en el dolor después de la reconstrucción artroscópica de ligamentos de un atleta

ABSTRACT After arthroscopic ligament reconstruction, athletes still need to go through a postoperative rehabilitation training period and suffer the possible pain that can go from moderate to severe. Commonly used analgesic medications, ropivacaine and fentanyl have the effect of relieving athletes' pain. To study the analgesic effect of ropivacaine on arthroscopic reconstruction of the knee ligament, the steps of reconstruction and pharmacology of ropivacaine were first introduced. Next, the analgesic effects of ropivacaine and fentanyl in 86 athletes were compared on muscle strength recovery, patient satisfaction, and pain score. The results showed that the satisfaction of patients with ropivacaine was 95.35%, and the incidence of postoperative adverse reactions was only 9.30%. These results indicate that ropivacaine has a better analgesic effect in arthroscopic reconstruction of the knee ligament in athletes, which is suitable for postoperative rehabilitation.

RESUMO Após a reconstrução artroscópica do ligamento, os atletas ainda precisam passar por um longo período de treinamento pós-operatório de reabilitação e suportar a possível dor de moderada a severa. Os medicamentos analgésicos ropivacaina e fentanilo comumente utilizados têm o efeito de aliviar a dor dos atletas. Para estudar o efeito analgésico da ropivacaína na reconstrução artroscópica do ligamento do joelho foram introduzidos, em primeiro lugar, os passos da reconstrução artroscópica do ligamento e os da farmacologia da ropivacaína. Em seguida, os efeitos analgésicos da ropivacaína e o fentanilo em 86 atletas foram comparados com a recuperação na força muscular, na satisfação do paciente e na pontuação da dor. Os resultados mostraram que a satisfação dos doentes com a ropivacaína chegava a 95.35%, e a incidência de reações adversas pós-operatórias foi apenas de 9.30%. Estes resultados indicam que a ropivacaína tem melhor efeito analgésico na reconstrução artroscópica do ligamento do joelho, o que é adequado para a reabilitação pós-operatória.

RESUMEN Después de la reconstrucción artroscópica del ligamento, los atletas aun precisan pasar por un largo período de entrenamiento posoperatorio de rehabilitación y soportar el posible dolor que puede ir de moderado a severo. Los medicamentos analgésicos, ropivacaína y fentanilo que son comúnmente utilizados, tienen el efecto de aliviar el dolor de los atletas. Para estudiar el efecto analgésico de la ropivacaína en la reconstrucción artroscópica del ligamento de la rodilla fueron introducidos, en primer lugar, los pasos de la reconstrucción y de la farmacología de la ropivacaína. Enseguida, los efectos analgésicos de la ropivacaína y el fentanilo en 86 atletas fueron comparados en la recuperación de la fuerza muscular, en la satisfacción del paciente y en la puntuación del dolor. Los resultados mostraron que la satisfacción de los pacientes con la ropivacaína llegaba a 95.35%, y la incidencia de reacciones adversas posoperatorias fue apenas de 9.30%. Estos resultados indican que la ropivacaína tiene mejor efecto analgésico en la reconstrucción artroscópica del ligamento de la rodilla de los atletas, lo que es adecuado para la rehabilitación posoperatoria.

[Ropivacaine withdrawal syndrome: a case report]. / Síndrome de abstinência de ropivacaína: relato de caso.

INTRODUCTION AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic that causes prolonged anesthesia and is beneficial for a wide variety of surgeries. Systemic toxicity has been reported after usage of high dose ropivacaine or inadvertent intravascular administration. We report a case of ropivacaine withdrawal, which to our knowledge has not been previously described in the literature. CASE REPORT: The patient presented to our department with uncontrolled belt-like upper-abdominal pain, self-rated as a 9/10 on the numeric rating scale. We decided to use continuous epidural analgesia with ropivacaine through a multi-port epidural catheter. Pain was well controlled for one month without significant adverse effects. However, ropivacaine unexpectedly ran out and two hours later the patient developed agitation, generalized tremor, tachycardia, and tachypnea. These symptoms resolved 30 minutes after reinitiating epidural ropivacaine. DISCUSSION: Our hypothesis of ropivacaine withdrawal was related to the timing of symptoms in relation to drug administration over two episodes. The possible mechanism of the observed withdrawal syndrome is upregulation of voltage-gated sodium channels after prolonged inhibition, resulting in increase in sodium influx and genetic variation.

Ropivacaine withdrawal syndrome: a case report / Síndrome de abstinência de ropivacaína: relato de caso

Abstract Introduction and objectives: Ropivacaine is a long-acting local anesthetic that causes prolonged anesthesia and is beneficial for a wide variety of surgeries. Systemic toxicity has been reported after usage of high dose ropivacaine or inadvertent intravascular administration. We report a case of ropivacaine withdrawal, which to our knowledge has not been previously described in the literature. Case report: The patient presented to our department with uncontrolled belt-like upper-abdominal pain, self-rated as a 9/10 on the numeric rating scale. We decided to use continuous epidural analgesia with ropivacaine through a multi-port epidural catheter. Pain was well controlled for one month without significant adverse effects. However, ropivacaine unexpectedly ran out and two hours later the patient developed agitation, generalized tremor, tachycardia, and tachypnea. These symptoms resolved 30 minutes after reinitiating epidural ropivacaine. Discussion: Our hypothesis of ropivacaine withdrawal was related to the timing of symptoms in relation to drug administration over two episodes. The possible mechanism of the observed withdrawal syndrome is upregulation of voltage-gated sodium channels after prolonged inhibition, resulting in increase in sodium influx and genetic variation.

Resumo Justificativa e objetivos: A ropivacaína é um anestésico local de ação prolongada indicado em uma ampla variedade de cirurgias. Toxicidade sistêmica tem sido relatada após o uso de dose alta de ropivacaína ou administração intravascular inadvertida. Relatamos um caso de crise de abstinência de ropivacaína que, até onde sabemos, não foi descrita anteriormente na literatura. Relato do caso: O paciente procurou nosso departamento com dor não controlada abdominal do tipo em cinta, avaliada pelo paciente como sendo 9/10 no escala de avaliação numérica. Decidimos usar analgesia peridural contínua com ropivacaína através de cateter peridural multiperfurado. A dor foi bem controlada por um mês sem efeitos adversos significativos. No entanto, a ropivacaína inesperadamente se esgotou e, duas horas depois, o paciente desenvolveu agitação, tremor generalizado, taquicardia e taquipneia. Esses sintomas regrediram completamente 30 minutos após o reinício da ropivacaína por via peridural. Discussão: Nossa hipótese de abstinência de ropivacaína foi relacionada à cronologia dos sintomas em relação à administração da droga ao longo de dois episódios. O possível mecanismo da síndrome de abstinência observada é a regulação positiva dos canais de sódio dependentes de voltagem após inibição prolongada, resultando em aumento do influxo de sódio e variação genética.

Intranasal self-administration of local anesthetic (ropivacaine) for sphenopalatine ganglion block, for treatment of second trigeminal branch neuralgia secondary to maxillary sinus curettage: A case report. / Autoadministración intranasal de anestésico local (ropivacaína) para bloqueo del ganglio esfenopalatino, para tratamiento de neuralgia de la segunda rama del trigémino secundaria a curetaje del seno maxilar: informe de un caso.

Trigeminal neuralgia (TN) is a severe and often underestimated facial pain that affects quality of life. Pharmacological treatment is insufficient for pain control in 30% of cases and, although intervention techniques may be effective, there is a possibility of relapse and associated complications. The second division of the trigeminal nerve (V2) runs through the sphenopalatine ganglion (SPG), which is anatomically accessible to blocking due to its superficial location in the nasal cavity. We report a clinical case of a patient with uncontrolled V2 TN that was put on ambulatory self-administered SPG block with nasal swabs soaked in 0.75% ropivacaine. In the follow-up visits, we confirmed that this adjuvant treatment provided a significant pain relief over 24hours with a decrease in the number of exacerbations.

Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed neonatal rodent model / Efeito de doses equipotentes de bupivacaína e ropivacaína em modelo de roedor neonatal alimentado com dieta rica em gordura

Abstract Objectives: The increase in the prevalence of obesity presents a significant health and economic problem. Obesity has been reported to be a major contributor to variety of chronic diseases. Childhood obesity has been rising over the past decades leading to various complications in health. Millions of infants and children undergo surgery every year on various health grounds. The present investigation was undertaken to evaluate the effect of spinal anesthesia of equipotent doses of ropivacaine and bupivacaine on over-weight neonatal rats. Methods: The Sprague-Dawley rat pups were overfed on high fat diet to induce obesity. Behavioral assessments for sensory and motor blockade was made by evaluating thermal and mechanical withdrawal latencies at various time intervals following intrathecal injections of bupivacaine (5.0 mg·kg-1) and ropivacaine (7.5 mg·kg-1) in P14 rats. Spinal tissue was analyzed for apoptosis by determination of activated caspase-3 using monoclonal anti-activated caspase-3 and Fluoro-Jade C staining. Long-term spinal function in P30 rat pups was evaluated. Results: Exposure to intrathecal anesthesia in P14 increased thermal and mechanical latencies and was observed to increase apoptosis as presented by increase in activated caspase-3 and Fluro-Jade C positive cells. Significant alterations in spinal function were observed in high fat diet-fed pups as against non-obese control pups that were on standard diet. Bupivacaine produced more pronounced apoptotic effects on P14 pups; ropivacaine however produced long lasting effects as evidenced in motor function tests at P30. Conclusion: Ropivacaine and bupivacaine induced spinal toxicity that was more pronounced in over-fed rat pups as against normal controls.

Resumo Objetivos: O aumento da prevalência da obesidade é um problema sério de saúde e econômico. A obesidade tem sido relatada como um dos principais contribuintes para uma variedade de doenças crônicas. A obesidade infantil tem aumentado nas últimas décadas e levado a complicações de saúde. Milhões de bebês e crianças são submetidos a cirurgia todos os anos por diversos motivos de saúde. O presente estudo foi feito para avaliar o efeito da raquianestesia com doses equipotentes de ropivacaína e bupivacaína em ratos recém-nascidos com sobrepeso. Métodos: As crias de ratos Sprague-Dawley foram alimentadas em excesso com dieta rica em gordura para induzir obesidade. Avaliações comportamentais para bloqueio sensorial e motor foram feitas por meio da avaliação das latências de retirada térmicas e mecânicas em vários intervalos de tempo após injeções por via intratecal de bupivacaína (5,0 mg·kg-1) e ropivacaína (7,5 mg·kg-1) em ratos P14. Tecido medular foi analisado para apoptose por determinação da caspase-3 ativada, com o uso de anticorpo monoclonal anti-caspase 3 ativada e ecoloração com Fluoro-Jade C. A função da coluna vertebral em longo prazo em filhotes de ratos P30 foi avaliada. Resultados: A exposição à anestesia intratecal em P14 aumentou as latências térmicas e mecânicas e observamos aumento da apoptose, como apresentado pelo aumento da caspase-3 ativada e células positivas para Fluro-Jade C. Alterações significativas da função da coluna vertebral foram observadas em filhotes alimentados com dieta rica em gordura versus filhotes controles não obesos em dieta padrão. Bupivacaína produziu efeitos apoptóticos mais pronunciados sobre os filhotes P14; ropivacaína, entretanto, produziu efeitos duradouros, como evidenciado nos testes de função motora em P30. Conclusão: Ropivacaína e bupivacaína induziram toxicidade medular mais pronunciada nos filhotes de ratos sobrealimentados do que nos controles normais.

Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed neonatal rodent model.

OBJECTIVES: The increase in the prevalence of obesity presents a significant health and economic problem. Obesity has been reported to be a major contributor to variety of chronic diseases. Childhood obesity has been rising over the past decades leading to various complications in health. Millions of infants and children undergo surgery every year on various health grounds. The present investigation was undertaken to evaluate the effect of spinal anesthesia of equipotent doses of ropivacaine and bupivacaine on over-weight neonatal rats. METHODS: The Sprague-Dawley rat pups were overfed on high fat diet to induce obesity. Behavioral assessments for sensory and motor blockade was made by evaluating thermal and mechanical withdrawal latencies at various time intervals following intrathecal injections of bupivacaine (5.0mg·kg-1) and ropivacaine (7.5mg·kg-1) in P14 rats. Spinal tissue was analyzed for apoptosis by determination of activated caspase-3 using monoclonal anti-activated caspase-3 and Fluoro-Jade C staining. Long-term spinal function in P30 rat pups was evaluated. RESULTS: Exposure to intrathecal anesthesia in P14 increased thermal and mechanical latencies and was observed to increase apoptosis as presented by increase in activated caspase-3 and Fluro-Jade C positive cells. Significant alterations in spinal function were observed in high fat diet-fed pups as against non-obese control pups that were on standard diet. Bupivacaine produced more pronounced apoptotic effects on P14 pups; ropivacaine however produced long lasting effects as evidenced in motor function tests at P30. CONCLUSION: Ropivacaine and bupivacaine induced spinal toxicity that was more pronounced in over-fed rat pups as against normal controls.

[Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed neonatal rodent model]. / Efeito de doses equipotentes de bupivacaína e ropivacaína em modelo de roedor neonatal alimentado com dieta rica em gordura.

OBJECTIVES: The increase in the prevalence of obesity presents a significant health and economic problem. Obesity has been reported to be a major contributor to variety of chronic diseases. Childhood obesity has been rising over the past decades leading to various complications in health. Millions of infants and children undergo surgery every year on various health grounds. The present investigation was undertaken to evaluate the effect of spinal anesthesia of equipotent doses of ropivacaine and bupivacaine on over-weight neonatal rats. METHODS: The Sprague-Dawley rat pups were overfed on high fat diet to induce obesity. Behavioral assessments for sensory and motor blockade was made by evaluating thermal and mechanical withdrawal latencies at various time intervals following intrathecal injections of bupivacaine (5.0mg·kg-1) and ropivacaine (7.5mg·kg-1) in P14 rats. Spinal tissue was analyzed for apoptosis by determination of activated caspase-3 using monoclonal anti-activated caspase-3 and Fluoro-Jade C staining. Long-term spinal function in P30 rat pups was evaluated. RESULTS: Exposure to intrathecal anesthesia in P14 increased thermal and mechanical latencies and was observed to increase apoptosis as presented by increase in activated caspase-3 and Fluro-Jade C positive cells. Significant alterations in spinal function were observed in high fat diet-fed pups as against non-obese control pups that were on standard diet. Bupivacaine produced more pronounced apoptotic effects on P14 pups; ropivacaine however produced long lasting effects as evidenced in motor function tests at P30. CONCLUSION: Ropivacaine and bupivacaine induced spinal toxicity that was more pronounced in over-fed rat pups as against normal controls.

Infrared image monitoring of local anesthetic poisoning in rats / Monitorização por imagem infravermelha da intoxicação por anestésico local em ratos

Abstract Background and objectives: To evaluate the thermographic predictive value of local anesthetic poisoning in rats that indicates the early recognition of thermal signs of intoxication and enable the immediate start of advanced life support. Methods: Wistar rats underwent intraperitoneal injection of saline and ropivacaine; they were allocated into pairs, and experiments performed at baseline and experimental times. For thermography, central and peripheral compartment were analyzed, checking the maximum and average differences of temperatures between groups. Thermographic and clinical observations were performed for each experiment, and the times in which the signs of intoxication occurred were recorded. In the thermal analysis, the thermograms corresponding to the times of interest were sought and relevant data sheets extracted for statistical analysis. Results: Basal and experimental: the display of the thermal images at times was possible. It was possible to calculate the heat transfer rate in all cases. At baseline it was possible to see the physiology of microcirculation, characterized by thermal distribution in the craniocaudal direction. It was possible to visualize the pathophysiological changes or thermal dysautonomias caused by intoxication before clinical signs occur, characterized by areas of hyper-radiation, translating autonomic nervous system pathophysiological disorders. In animals poisoned by ropivacaine, there was no statistically significant difference in heat transfer rate at the experimental time. Conclusions: The maximum temperature, medium temperature, and heat transfer rate were different from the statistical point of view between groups at the experimental time, thus confirming the systemic thermographic predictive value.

Resumo Justificativa e objetivos: Estudar o valor preditivo termográfico na intoxicação por anestésico local em ratos que efetue o reconhecimento precoce dos sinais térmicos de intoxicação e possibilite o início imediato do suporte avançado de vida. Método: Ratos Wistar foram submetidos à injeção intraperitoneal de soro fisiológico e ropivacaína, alocados aos pares, e foram feitos experimentos em tempos basal e experimental. Para o estudo termodinâmico foram analisados o compartimento central e o periférico, verificaram-se as diferenças das temperaturas máximas e médias entre os grupos. Foram feitas observações clínicas e termográficas para cada experimento e anotados os tempos em que os sinais de intoxicação ocorriam. Foram buscados na análise termográfica os termogramas correspondentes aos tempos de interesse e extraídas as planilhas de dados correspondentes, para análise estatística. Resultados: Foi possível a visibilização das imagens térmicas nos momentos basal e experimental. Foi possível calcular a taxa de transferência de calor em todos os casos. No momento basal foi possível observar a fisiologia da microcirculação, caracterizada por distribuição térmica no sentido craniocaudal. Foi possível visibilizar as alterações fisiopatológicas ou disautonomias térmicas causadas pela intoxicação antes que os sinais clínicos ocorressem, caracterizadas por áreas de hiperradiação e traduziram perturbações fisiopatológicas do Sistema Nervoso Autônomo. Nos animais intoxicados por ropivacaína houve diferença estatisticamente significativa na taxa de transferência de calor no momento experimental. Conclusões: Constatou-se que a temperatura máxima, a temperatura média e a taxa de transferência de calor foram diferentes do ponto de vista estatístico entre os grupos no momento experimental, o que corrobora o valor preditivo termográfico sistêmico.

Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines / Efeitos citotóxicos de anestesia local com lidocaína/ropivacaína em linhagens celulares de melanoma humano

Abstract Background: Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Methods: Melanoma cell lines, A375 and Hs294T, were exposed to 1 h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Results: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p < 0.001), concentration- (p < 0.001), and agent dependant. In both A375 and Hs294T cell lines, minimum cell viability rates were found after 72 h of exposure to these agents. Lidocaine 2% caused a reduction of vital cells to 10% ± 2% and 14% ± 2% in A375 and Hs294T, respectively after 72 h of exposure. Ropivacaine 0.75% after 72 h reduced viable cells to 15% ± 3% and 25% ± 3% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to the combination was 10% ± 2% and 18% ± 2% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to melphalan was 8% ± 1% and 12% ± 2%, in A375 and Hs294T, respectively. Conclusion: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

Resumo Justificativa: Os anestésicos locais (ALs) são geralmente considerados como seguros, mas citotoxicidade foi relatada em vários anestésicos locais usados em seres humanos, a qual não é bem investigada. No presente estudo, a citotoxicidade de lidocaína e ropivacaína e da combinação de lidocaína e ropivacaína foi avaliada em linhagens celulares de melanoma humano. Melfalano, um agente alquilante de mostarda nitrogenada, foi usado como um agente de controle para a comparação da atividade citotóxica. Métodos: Linhagens celulares de melanoma, A375 e Hs294T foram expostas por uma hora a concentrações diferentes dos agentes mencionados acima. A viabilidade celular após a exposição foi determinada por citometria de fluxo. Resultados: Os ALs investigados mostraram citotoxicidade prejudicial nas linhagens celulares de melanoma estudadas dependente do tempo (p < 0,001), da concentração (p < 0,001) e do agente. Em ambas as linhagens de células A375 e Hs294T, níveis mínimos de viabilidade celular foram encontrados após 72 horas de exposição a esses agentes. Lidocaína a 2% provocou uma redução das células vitais para 10% ± 2% e 14% ± 2% em A375 e Hs294T, respectivamente, após 72 horas de exposição. Ropivacaína a 0,75% após 72 horas reduziu as células viáveis para 15% ± 3% e 25% ± 3%, em A375 e Hs294T, respectivamente. A viabilidade celular mínima após exposição de 72 horas para a combinação foi de 10% ± 2% e 18% ± 2% em A375 e Hs294T, respectivamente. A viabilidade celular mínima após exposição de 72 horas ao melfalano foi de 8% ± 1% e 12 ± 2, em A375 e Hs294T, respectivamente. Conclusão: Os ALs têm atividade citotóxica em linhagens de celulares de melanoma humano de modo dependente do tempo, da concentração e do agente. A apoptose nas linhagens celulares foi mediada por meio da atividade das caspases-3 e caspases-8.

Infrared image monitoring of local anesthetic poisoning in rats.

BACKGROUND AND OBJECTIVES: To evaluate the thermographic predictive value of local anesthetic poisoning in rats that indicates the early recognition of thermal signs of intoxication and enable the immediate start of advanced life support. METHODS: Wistar rats underwent intraperitoneal injection of saline and ropivacaine; they were allocated into pairs, and experiments performed at baseline and experimental times. For thermography, central and peripheral compartment were analyzed, checking the maximum and average differences of temperatures between groups. Thermographic and clinical observations were performed for each experiment, and the times in which the signs of intoxication occurred were recorded. In the thermal analysis, the thermograms corresponding to the times of interest were sought and relevant data sheets extracted for statistical analysis. RESULTS: Basal and experimental: the display of the thermal images at times was possible. It was possible to calculate the heat transfer rate in all cases. At baseline it was possible to see the physiology of microcirculation, characterized by thermal distribution in the craniocaudal direction. It was possible to visualize the pathophysiological changes or thermal dysautonomias caused by intoxication before clinical signs occur, characterized by areas of hyper-radiation, translating autonomic nervous system pathophysiological disorders. In animals poisoned by ropivacaine, there was no statistically significant difference in heat transfer rate at the experimental time. CONCLUSIONS: The maximum temperature, medium temperature, and heat transfer rate were different from the statistical point of view between groups at the experimental time, thus confirming the systemic thermographic predictive value.

Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines.

BACKGROUND: Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. METHODS: Melanoma cell lines, A375 and Hs294T, were exposed to 1h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. RESULTS: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p<0.001), concentration- (p<0.001), and agent dependant. In both A375 and Hs294T cell lines, minimum cell viability rates were found after 72h of exposure to these agents. Lidocaine 2% caused a reduction of vital cells to 10%±2% and 14%±2% in A375 and Hs294T, respectively after 72h of exposure. Ropivacaine 0.75% after 72h reduced viable cells to 15%±3% and 25%±3% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to the combination was 10%±2% and 18%±2% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to melphalan was 8%±1% and 12%±2%, in A375 and Hs294T, respectively. CONCLUSION: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

[Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines]. / Efeitos citotóxicos de anestesia local com lidocaína/ropivacaína em linhagens celulares de melanoma humano.

BACKGROUND: Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. METHODS: Melanoma cell lines, A375 and Hs294T, were exposed to 1h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. RESULTS: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p<0.001), concentration- (p<0.001), and agent dependant. In both A375 and Hs294T cell lines, minimum cell viability rates were found after 72h of exposure to these agents. Lidocaine 2% caused a reduction of vital cells to 10%±2% and 14%±2% in A375 and Hs294T, respectively after 72h of exposure. Ropivacaine 0.75% after 72h reduced viable cells to 15%±3% and 25%±3% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to the combination was 10%±2% and 18%±2% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to melphalan was 8%±1% and 12%±2%, in A375 and Hs294T, respectively. CONCLUSION: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

Avaliação da analgesia pós-operatória com instilação de ropivacaína intraperitoneal em colecistectomia videolaparoscópica / Evaluation of postoperative analgesia with intraperitoneal ropivacaine instillation in videolaparoscopic cholecystectomy

RESUMO JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar a analgesia pós-operatória com instilação de solução de ropivacaína dentro da cavidade peritoneal em colecistectomia videolaparoscópica. MÉTODOS: Trata-se de um ensaio clinico randomizado com 60 pacientes. No grupo intervenção (RP, n =30) foi realizada instilação de solução de ropivacaína a 0,5% nas regiões subdiafragmáticas direita e esquerda e no leito da vesícula biliar em iguais volumes de 10 mL. No grupo controle (SF, n =30) foi realizada instilação de solução fisiológica a 0,9%. Os pacientes de ambos os grupos receberam analgesia multimodal. No período pós-operatório foram avaliados os escores de dor abdominal e referida no ombro ao despertar e após 1, 2, 4, 6, 12 e 24 horas, além da necessidade de analgesia de resgate, consumo de opioide e eventos adversos. Foi considerado estatisticamente significativo o valor de p<0,05. RESULTADOS: Não houve diferença estatística entre os grupos em relação a dados demográficos e tempo anestésico-cirúrgico. O grupo intervenção apresentou escores de dor menores e estatisticamente significativos comparado ao grupo controle ao despertar (p=0,001), com 1 hora (p=0,019) e 2 horas (p=0,04) de pós-operatório, bem como menor consumo de opioide ao despertar (p=0,022) e no total nas primeiras 24 horas (p=0,001). O tempo para necessidade da primeira analgesia de resgate foi maior no grupo intervenção (p=0,001). CONCLUSÃO: A instilação de ropivacaína dentro da cavidade peritoneal reduziu os escores de dor nas primeiras duas horas e o consumo de opioide no pós-operatório.

ABSTRACT BACKGROUND AND OBJECTIVES: This study aimed at evaluating postoperative analgesia with ropivacaine instillation inside the peritoneal cavity in videolaparoscopic cholecystectomy. METHODS: This is a randomized clinical trial with 60 patients. The intervention group (RP, n = 30) received 0.5% ropivacaine instillation in right and left subdiaphragmatic regions and in gallbladder bed in equal volumes of 10 mL. The control group (SS, n = 30) received 0.9% saline solution instillation. Patients of both groups received multimodal analgesia. Scores of abdominal pain and referred pain in shoulder were evaluated at emergence and after 1, 2, 4, 12 and 24 hours, in addition to the need for rescue analgesia, opioid consumption and adverse events, considering statistically significant p<0.05. RESULTS: There has been no statistical difference between groups with regard to demographic data and anesthetic-surgical time. The intervention group had lower and statistically significant pain scores as compared to control group at emergence (p=0.001), 1 (p=0.019) and 2 (p=0.04) postoperative hours, in addition to lower opioid consumption at emergence (p=0.022) and in total in the first 24 hours (p=0.001). Time for first request for rescue analgesia was longer in the intervention group (p=0.001). CONCLUSION: Ropivacaine instillation inside the peritoneal cavity has decreased pain scores in the first 2 hours and postoperative opioid consumption.

Anestesia geral inalatória ou total intravenosa associada à anestesia subaracnoidea, em ovinos / General inhalation anesthesia or total intravenous associated with subarachnoid anesthesia in sheep

Avaliou-se a eficácia e a segurança anestésica em ovinos mantidos sob anestesia geral inalatória com isofluorano ou anestesia total intravenosa com propofol, ambas associadas à anestesia subaracnoidea. Quatorze ovinos foram pré-medicados com 0,3mg.kg-1 de morfina IM, e cinco minutos após, receberam 20mcg.kg-1 de detomidina IV. Posteriormente, foram alocados aleatoriamente em dois grupos: GISO (n=7), os quais foram induzidos à anestesia geral com 0,5mg.kg-1 de diazepam e 5mg.kg-1 de cetamina IV, e mantidos em anestesia geral inalatória com isoflurano diluído em oxigênio a 100%; e GPRO (n=7), induzidos com 4mg.kg-1 de propofol IV seguido inicialmente de infusão contínua na taxa de 0,3mg.kg-1.min-1. Para realização da osteotomia bilateral, todos os animais receberam 0,5mg.kg-1 de ropivacaína 0,75% associado a 0,1mg.kg-1 de morfina pela via subaracnoidea. Houve redução de 40% nos valores médios de frequência cardíaca após sedação em ambos os grupos, permanecendo em média 23% reduzida até o final da avaliação. A pressão arterial média aumentou 16%, após a indução anestésica no GISO, mas se reduziu até o final do procedimento, assim como no GPRO. A EtISO média foi de 0,57V% e a taxa média de infusão do propofol foi de 0,24mg.kg-1.min-1. Os tempos totais de cirurgia, anestesia e extubação foram de 66±9,8, 92±13,8 e 7,0±1,5 minutos no GISO e 56±2,4, 82,9±4,6 e 5,4±1,5 minutos no GPRO, não havendo diferença significativa entre grupos. A manutenção anestésica com isoflurano ou propofol promoveu plano anestésico similar com mínimos efeitos cardiovasculares ou hemogasométricos, que são bem tolerados em ovinos hígidos.

The purpose of this study was to evaluate the efficacy and safety of sheep submitted to inhalation anesthesia with isoflurane or total intravenous anesthesia with propofol, both associated with subarachnoid anesthesia. Fourteen animals were pre-medicated with 0.3mg.kg-1 morphine IM, and 5 minutes later received 20mcg.kg-1 detomidine IV. Then they were allocated into two groups: GISO (n=7), which were induced with 0.5mg.kg-1 of diazepam and 5mg.kg-1 of ketamine IV, and anesthesia maintenance was performed by isoflurane diluted in 100% oxygen; or GPRO (n=7), where animals were induced with 4mg.kg-1 propofol IV and subsequent maintenance anesthesia with its own infusion of 0.3mg.kg.min-1. To perform the bilateral tibial osteotomy, all animals received 0.5mg.kg-1 0.75% ropivacaine combined with 0.1mg.kg-1 morphine by the intrathecal route. There was a 40% reduction in mean heart rate after the sedative protocol in both groups, resulting in a 23% average reduction until the end of the review. Mean arterial pressure showed transient elevation of around 16%, after induction of anesthesia in GISO, but reducing it to the end of the procedure, as well as in GPRO. The average EtISO was 0.57 V% and average infusion rate of propofol was 0.24mg.kg-1.min-1. The total time of surgery, anesthesia and extubation was 66± 9.8, 92±7.0 and 13.8±1.5 minutes in GISO and 56±2.4, 82.9±4.6 and 5.4±1.5 minutes in GPRO. The maintenance of anesthesia with propofol or isoflurane produced similar anesthesia with minimal cardiovascular and blood gas effects, which are well tolerated in healthy sheep.

[Infrared image monitoring of local anesthetic poisoning in rats]. / Monitorização por imagem infravermelha da intoxicação por anestésico local em ratos.

BACKGROUND AND OBJECTIVES: To evaluate the thermographic predictive value of local anesthetic poisoning in rats that indicates the early recognition of thermal signs of intoxication and enable the immediate start of advanced life support. METHODS: Wistar rats underwent intraperitoneal injection of saline and ropivacaine; they were allocated into pairs, and experiments performed at baseline and experimental times. For thermography, central and peripheral compartment were analyzed, checking the maximum and average differences of temperatures between groups. Thermographic and clinical observations were performed for each experiment, and the times in which the signs of intoxication occurred were recorded. In the thermal analysis, the thermograms corresponding to the times of interest were sought and relevant data sheets extracted for statistical analysis. RESULTS: Basal and experimental: the display of the thermal images at times was possible. It was possible to calculate the heat transfer rate in all cases. At baseline it was possible to see the physiology of microcirculation, characterized by thermal distribution in the craniocaudal direction. It was possible to visualize the pathophysiological changes or thermal dysautonomias caused by intoxication before clinical signs occur, characterized by areas of hyper-radiation, translating Autonomic Nervous System pathophysiological disorders. In animals poisoned by ropivacaine, there was no statistically significant difference in heat transfer rate at the experimental time. CONCLUSIONS: The maximum temperature, medium temperature, and heat transfer rate were different from the statistical point of view between groups at the experimental time, thus confirming the systemic thermographic predictive value.

Digital block with or without the addition of epinephrine in the anesthetic solution / Bloqueios em dedos de mãos com epinefrina incluída ou não nas soluções anestésicas

BACKGROUND AND OBJECTIVES: Review of various techniques for digital blocks with local anesthetic, with or without epinephrine. CONTENTS: Description of various procedures and comparison of results reported in the literature, mainly on latency and quality of anesthesia, details on vasoconstrictor effect of epinephrine, intraoperative bleeding, necessity of tourniquet use, duration of anesthesia and postoperative analgesia, blood flow and digital SpO2 behavior, local and systemic complications, and also approaches and drugs to be used in certain situations of ischemia. CONCLUSIONS: The advantages of adding epinephrine to the anesthetic solution are minor when compared to the risks of the procedure, and it seems dangerous to use a vasoconstrictor in the fingers, unless the safety of the technique and the possibility of discarding the tourniquet are definitely proven.

JUSTIFICATIVA E OBJETIVOS: Revisão das diversas técnicas para bloqueios em dedos de mãos, com anestésico local associado ou não à epinefrina. CONTEÚDO: São descritos os procedimentos usados e comparados os resultados obtidos na literatura, principalmente em relação a: latência e qualidade da anestesia, detalhes sobre o efeito vasoconstritor da epinefrina, sangramento intraoperatório, necessidade ou não do uso de torniquete, duração da anestesia e da analgesia pós-operatórias, comportamento do fluxo arterial e da SpO2 digitais, complicações locais e sistêmicas e, ainda, condutas e medicamentos a serem usados em determinadas situações de isquemia. CONCLUSÕES: As vantagens da inclusão de epinefrina na solução anestésica são de pouca importância quando comparadas aos riscos do procedimento e parece perigoso usar o vasoconstritor em dedos de mão, a não ser que fiquem definitivamente comprovadas a inocuidade da técnica e a possibilidade do descarte do torniquete.

Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes / Efeitos comparativos de vitamina C sobre os efeitos dos anestésicos locais ropivacaína, bupivacaína e lidocaína em condrócitos humanos

BACKGROUND: Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. OBJECTIVES: The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. METHODS: The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500 µM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. RESULTS: On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine < bupivacaine < lidocaine. Vitamin C effectively improved the reduced chondrocyte viability and decreased the raised apoptosis levels following exposure to anesthesia. At higher doses, vitamin C was found efficient in reducing the generation of reactive oxygen species and as well down-regulate the expressions of caspases 3 and 9. CONCLUSIONS: Vitamin C was observed to effectively protect chondrocytes against the toxic insult of local anesthetics ropivacaine, bupivacaine and lidocaine.

JUSTIFICATIVA: Injeções de anestésicos locais por via intra-articular são comumente usadas para melhorar a analgesia no período pós-operatório de cirurgia ortopédica como artroscopia. No entanto, relatos recentes de complicações graves devido ao uso de anestésico local por via intra-articular causou preocupações. OBJETIVOS: O objetivo do estudo foi avaliar o uso de vitamina C para reduzir os efeitos adversos dos anestésicos mais comumente usados (ropivocaína, bupivacaína e lidocaína) sobre condrócitos humanos. MÉTODOS: A viabilidade dos condrócitos após a exposição à bupivacaína a 0,5% ou ropivacaína a 0,75% ou lidocaína a 1,0% e/ou vitamina C em doses de 125, 250 e 500 µM foi determinada pelo ensaio Vivo/Morto e coloração com anexina V. Os níveis de expressão das caspases 3 e 9 foram avaliados com o uso de anticorpos pela técnica Western blotting. Citometria de fluxo foi feita para analisar a geração de espécies reativas ao oxigênio. RESULTADOS: Na exposição aos anestésicos locais, condrotoxicidade foi encontrada na seguinte ordem: ropivacaína < bupivacaína < lidocaína. A vitamina C efetivamente melhorou a redução da viabilidade dos condrócitos e diminuiu os níveis elevados de apoptose após a exposição à anestesia. Em doses mais altas, a vitamina C foi eficiente para reduzir a geração de espécies reativas ao oxigênio e assim regular negativamente a expressão das caspases 3 e 9. CONCLUSÕES: Observamos que a vitamina C foi eficaz na proteção dos condrócitos contra a agressão tóxica dos anestésicos locais ropivacaína, bupivacaína e lidocaína.