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

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

Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.

Avaliação do tratamento quimioterápico paliativo com o esquema LDE- paclitaxel em pacientes portadores de metástases ósseas por neoplasia maligna / Evaluation of palliative chemotherapy treatment with the LDEpaclitaxel regimen in patients with bone metastases from malignant neoplas

Introdução: Pacientes com câncer em estádios avançados e metástases ósseas frequentemente não apresentam condições clínicas para a realização de esquemas quimioterápicos convencionais subsequentes, restringindo as opções de tratamento. Anteriormente, demonstramos que nanopartículas artificiais lipídicas (LDE), semelhantes à lipoproteína de baixa densidade (LDL) rica em colesterol, são captadas por tecidos malignos, e quando associadas aos quimioterápicos, após injeção pela via endovenosa, reduz drasticamente a toxicidade do tratamento. Os objetivos deste presente estudo foram avaliar a resposta clínica ao tratamento quimioterápico com paclitaxel (PTX) associado à LDE; avaliar as toxicidades clínicas e laboratorial, e a capacidade da associação LDE-PTX em reduzir a dor oncológica relacionada às metástases ósseas em pacientes com carcinoma de mama, próstata e pulmão, previamente tratados e não elegíveis para tratamento quimioterápico convencional subsequente. Métodos: Dezoito pacientes (8 com câncer de mama, 5 de próstata e 5 de pulmão) com metástases ósseas foram incluídos. O tratamento consistiu no esquema LDE-PTX na dose convencional do PTX (175 mg/m2 de superfície corpórea de 3/3 semanas) e os pacientes foram avaliados por resposta clínica, redução da dor óssea, uso de medicamentos opióides, e ocorrência de fraturas ósseas patológicas. Resultados: No total, 104 ciclos de quimioterapia foram realizados, e nenhum paciente apresentou toxicidade clínica, laboratorial, assim como não houve fraturas patológicas. Dos 18 pacientes incluídos, 9 tiveram sobrevida livre de progressão de doença 6 meses. Houve em todos os pacientes redução da dor óssea, permitindo substituição da medicação opióide por analgésico não opióide. Conclusão: A melhora significativa na dor óssea sem que tenha ocorrido toxicidade do tratamento, e o tempo de não progressão de doença 6 meses na metade dos pacientes sugere que esses pacientes tenham se beneficiado consistentemente do tratamento com a LDE-PTX. Portanto, a LDE-PTX pode tornar- se uma opção terapêutica interessante em pacientes com carcinomas de próstata, mama ou pulmão em estágios avançados e sem condições clínicas de se submeterem a outros esquemas quimioterápicos convencionais

Introduction: Patients with advanced cancer and bone metastases usually do not have clinical conditions to perform additional conventional chemotherapy regimens, restricting treatment options. Previously, we showed that lipid core nanoparticles (LDE), similar to cholesterol-rich low-density lipoprotein (LDL), are taken up by malignant tissues, and when associated to chemotherapy, after endovenous injection, it drastically decreases the toxicity of the treatment. The objectives of this study were to evaluate the clinical response to chemotherapy treatment with paclitaxel (PTX) associated with LDE; to evaluate the clinical and laboratorial toxicities, and the ability of the LDE-PTX to reduce cancer pain related to bone metastases in patients with breast, prostate or lung carcinoma, previously treated and not eligible for subsequent conventional chemotherapy treatment. Methods: Eighteen patients (8 with breast cancer, 5 with prostate and 5 with lung) with bone metastases were included. Treatment consisted of the LDE-PTX regimen at a conventional dose of PTX (175 mg/m2 body surface area, 3/3 weeks) and patients were evaluated for clinical response, reduction in bone pain, use of opioid medications, and the occurrence of pathological bone fractures. Results: In total, 104 chemotherapy cycles were performed, and none of the patients showed clinical or laboratorial toxicities, as well as there were no pathological fractures. Of the 18 patients evaluated, 9 had progression-fee survival 6 months. Patients had decrease in bone pain allowing replacement of opioid medication by another non-opioid analgesic. Conclusion: Significant improvement in bone pain without treatment toxicity, and time to disease progression of 6 months in half of the patients suggest that these patients have consistently benefited with LDE-PTX treatment. Therefore, LDE-PTX may become an interesting therapeutic option in patients with advanced stage of prostate, breast or lung carcinomas and without clinical conditions to undergo other conventional chemotherapy regimens

The strategy of physiological arousal of athletes in sports competition based on drug intervention / A estratégia da excitação fisiológica de atletas em competições esportivas com base em intervenção medicamentosa / Deportistas basados en intervenciones farmacéuticas, estrategia fisiológica de despertar

ABSTRACT Generally speaking, the physiological index of the human body is in a relatively stable state, which refers to the function of various organ systems with the characteristics of high-tide period, low-tide period and critical period. However, for competitive athletes, it is necessary to maintain physiological activation in both training and competition. In view of this, this study will analyze the physiological arousal degree of aspirin and acetaminophen in order to provide a reference for athletes to take analgesic drugs. In this study, the analytic hierarchy process (AHP), principal component analysis and factor analysis, were used to construct a scientific evaluation system of physiological arousal level, and the medication and non-medication status of 90 athletes were evaluated. The results showed that aspirin was better than acetaminophen in blood urea and serum creatine kinase, and the comprehensive score of some athletes was higher than 0.95. Aspirin is better in arousing athletes' physiology. The research results will provide scientific guidance for athletes to take antipyretic and analgesic drugs.

RESUMO Em termos gerais, o índice fisiológico do corpo humano encontra-se num estado relativamente estável, que se refere à função de vários sistemas de órgãos no corpo humano, com as características do período de altas, período de baixas e período crítico. No entanto, para atletas competitivos, é necessário manter a ativação fisiológica em treinamento e competição. Em vista disso, este estudo irá analisar o grau fisiológico de excitação de aspirina e acetaminofeno, a fim de fornecer referência para os atletas a tomar medicamentos analgésicos. Neste estudo, o Analytic Hierarchy Process (AHP), análise de componentes principal e análise de fatores foram usados para construir um sistema de avaliação científica de nível de excitação fisiológica, e o estado de medicação e de não medicação de 90 atletas foram avaliados. Os resultados mostraram que a aspirina foi melhor do que o acetaminofeno na ureia sanguínea e na creatina quinase sérica, e o escore abrangente de alguns atletas foi maior do que 0.95. A aspirina é melhor no despertar da fisiologia dos atletas. Os resultados da pesquisa fornecerão orientação científica para os atletas tomarem medicamentos antipiréticos e analgésicos.

RESUMEN En términos generales, el índice fisiológico del cuerpo humano se encuentra en un estado relativamente estable, que se refiere a la función de varios sistemas de órganos en el cuerpo humano, con las características del período de altas, período de bajas y período crítico. Mientras tanto, para atletas competitivos, es necesario mantener la activación fisiológica en entrenamiento y competición. En vista de eso, este estudio analizará el grado fisiológico de excitación de aspirina y acetaminofeno, a fin de proveer referencia para los atletas para tomar medicamentos analgésicos. En este estudio, el Analytic Hierarchy Process (AHP), análisis de componentes principal y análisis de fatores fueron usados para construir un sistema de evaluación científica de nivel de excitación fisiológica, y el estado de medicación y de no medicación de 90 atletas fueron evaluados. Los resultados mostraron que la aspirina fue mejor que el acetaminofeno en la urea sanguínea y en la creatina quinasa sérica, y el escore abarcador de algunos atletas fue mayor de 0.95. La aspirina es mejor en el despertar de la fisiología de los atletas. Los resultados de la investigación proveerán orientación científica para que los atletas tomen medicamentos antipiréticos y analgésicos.

Prescripción de analgésicos no opioides en un Servicio de Ortopedia / Prescription of non-opioid analgesics in an Orthopedics Service

Introducción: El dolor asociado a las alteraciones del sistema musculoesquelético debe ser tratado frecuentemente por los especialistas en Ortopedia. Los analgésicos no opioides se ubican dentro de los fármacos que más se prescriben en este Servicio, aunque no siempre de modo adecuado, según los principios de la prescripción racional. Objetivo: Caracterizar el uso de analgésicos no opioides en el servicio de Ortopedia del Hospital Dr. Salvador Allende. Material y Métodos: Estudio descriptivo de utilización de medicamentos del tipo prescripción-indicación y esquema terapéutico. Se revisaron las historias clínicas de 70 pacientes ingresados en el Servicio de Ortopedia del Hospital Dr. Salvador Allende, durante el período comprendido desde septiembre de 2018 hasta enero de 2019. Resultados: Predominó el sexo femenino y la media de edad de 71,3 años en los pacientes estudiados con una desviación estándar de 22.2 años. Los analgésicos más prescritos fueron dipirona, diclofenaco y paracetamol, en indicaciones aprobadas donde destacaron las fracturas, la celulitis y la seudoartrosis. En la totalidad de los casos, las dosis empleadas fueron adecuadas, no así los intervalos de administración ni la duración del tratamiento. Conclusiones: Es alentador el predominio de la prescripción de analgésicos no opioides con buena relación beneficio-riesgo. No obstante, la presencia de prescripciones irracionales en cuanto a intervalos de administración y duración del tratamiento, indica un déficit en la práctica de la terapéutica analgésica que no debe ser ignorado(AU)

Introduction: The pain associated with alterations of the musculoskeletal system should be frequently treated by the specialist in Orthopedics. Non-opioid analgesics are the most prescribed drugs in this medical service although they are not always used appropriately according to the principles of national prescription. Objective: To characterize the use of non-opioid analgesics in the orthopedics service of the Dr. Salvador Allende Hospital. Material and Methods: A descriptive study of the use of prescription-indication medications and therapeutic scheme was conducted. Medical records of 70 patients admitted to the orthopedics service of the Dr. Salvador Allende Hospital during the period between September 2018 and January 2019 were reviewed. Results: The female sex and a mean age of 71.3 years with standard deviation of 22,2 years predominated in the study. The most frequently used analgesics, which were indicated in the treatment of fractures, cellulitis and pseudarthrosis, were dipyrone, diclofenac and paracetamol. In all cases, the doses used were adequate, but not the administration intervals or the duration of treatment. Conclusions: The predominance of the prescription of non-opioid analgesics with a good benefit-risk ratio is encouraging. However, the presence of irrational prescriptions regarding administration intervals and duration of treatment indicates a deficit in analgesic therapy that should not be ignored(AU)

Eficácia e segurança de Pregabalina, Gabapentina, Memantina, Amitriptilina, treinamento físico com exercícios em solo ou aquáticos para tratamento de Fibromialgia: revisão rápida de evidências / Effectiveness and safety of Pregabalin, Gabapentin, Memantine, Amitriptyline, exercises on land or aquatic exercises for Fibromyalgia treatment: rapid evidence review

Tecnologia: Pregabalina, drogas não-opioides disponíveis no SUS, treinamento físico no solo ou em meio aquático. Indicação: Tratamento da fibromialgia. Pergunta: Há diferenças de eficácia e segurança entre a Pregabalina e as outras drogas não opioides ou terapias disponíveis no SUS para tratamento da dor crônica relacionada à fibromialgia? Métodos: Levantamento bibliográfico foi realizado nas bases eletrônicas PUBMED e Cochrane Database, seguindo estratégias de buscas predefinidas, com busca adicional na página eletrônica da Comissão Nacional de Incorporação de Tecnologias em Saúde. Avaliou-se a qualidade metodológica das revisões sistemáticas com Assessing the Methodological Quality of Systematic Reviews versão 2 (AMSTAR-II). Resultados: Foram selecionadas e incluídas 6 revisões sistemáticas. Conclusão: A afirmação de eficácia da Gabapentina, Amitriptilina e Memantina para tratamento da fibromialgia é pouco confiável, pois as evidências são de nível 3, provenientes de ensaios clínicos de baixa qualidade metodológica. Pregabalina é eficaz para reduzir a dor em curto prazo (risco absoluto é 50%, nível 1 de evidência), mas não em longo prazo. O treinamento físico, relatado como única estratégia eficaz para tratamento da fibromialgia nas diretrizes do SUS, não tem efeito clinicamente importante sobre a dor

Technology: Pregabalin, non-opioid drugs available in Brazilian Public Health System, aquatic exercise or exercise on land. Indication: Treatment of fibromyalgia. Question: Are there differences in efficacy and safety between Pregabalin and other non-opioid drugs or therapies available in the SUS for the treatment of chronic pain related to fibromyalgia? Methods: A bibliographic survey was carried out in the electronic databases PUBMED and Cochrane Database, following pre-defined search strategies, with an additional search on the website of the National Commission for the Incorporation of Health Technologies. The methodological quality of systematic reviews was evaluated with Assessing the Methodological Quality of Systematic Reviews version 2 (AMSTAR-II). Results: Six systematic reviews were selected and included. Conclusion: There is not confidence about effectiveness of Gabapentin, Amitriptyline and Memantine for fibromyalgia treatment (level 3 of evidence, from clinical trials of low methodological quality). Pregabalin, in the short term, is effective for reducing pain (absolut risk is 50%, level 1 of evidence), but not in the long term. Physical training, reported as the only effective strategy for treating fibromyalgia in Brazilian Public Health System guidelines, has no clinically important effect on pain.

Opioid-free general anesthesia and induced recovery from anesthesia in a patient with myotonic dystrophy type-1: a case report / Anestesia geral sem opioide e recuperação induzida da anestesia em paciente com distrofia miotônica tipo-1: relato de caso

Abstract Myotonic dystrophy type-1 (Steinert disease) is an autosomal dominant, progressive multisystem disease in which myotonic crisis can be triggered by several factors including pain, emotional stress, hypothermia, shivering, and mechanical or electrical stimulation. In this report, dexmedetomidine-based general anesthesia, in combination with a thoracic epidural for laparoscopic cholecystectomy in a patient with Steinert disease, is presented. An Aintree intubation catheter with the guidance of a fiberoptic bronchoscope was used for intubation to avoid laryngoscopy. Prolonged anesthetic effects of propofol were reversed, and recovery from anesthesia was accelerated using an intravenous infusion of theophylline.

Resumo A Distrofia Miotônica (DM) tipo-1 (Doença de Steinert) é uma doença multissistêmica progressiva autossômica dominante em que a crise miotônica pode ser desencadeada por vários fatores, incluindo dor, estresse emocional, hipotermia, tremores e estímulo mecânico ou elétrico. O presente relato descreve anestesia geral realizada com dexmedetomidina em combinação com peridural torácica para colecistectomia laparoscópica em paciente com Doença de Steinert. Para evitar laringoscopia, a intubação traqueal foi realizada utilizando cateter de intubação Aintree guiado por broncofibroscopia óptica. Os efeitos anestésicos prolongados do propofol foram revertidos e a recuperação anestésica foi acelerada pelo uso de infusão intravenosa de teofilina.

Impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes: a randomized clinical trial / Impacto da analgesia pós-toracotomia com dexmedetomidina e morfina em imunócitos: estudo randomizado

Abstract Objective This study aimed to investigate the impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes. Methods A total of 118 patients with post-thoracotomy Patient-Controlled Intravenous Analgesia (PCIA) in our hospital from March 2016 to July 2018 were randomly selected and divided into the Composite (COM) Group (57 patients administered with dexmedetomidine [1.0 µg.kg-1 body weight] and morphine [0.48 mg.kg-1 body weight]) and the Morphine (MOR) group (61 patients administered with morphine [0.48 mg.kg-1]). The values of lymphocyte subsets (CD3+, CD4+, and CD8+) and Natural Killer cells in the peripheral blood of these two groups were detected by FACSCalibur flow cytometry at different time points (before anesthesia induction [T0], immediately after tracheal extubation [T1], 12 hours after surgery [T2], 24 hours after surgery [T3], 48 hours after surgery [T4], 72 hours after surgery [T5], and 7 days after surgery [T6]). The doses of morphine at T3 to T5 and the adverse reactions between the two groups were also recorded and compared. Results The CD3+ level and the CD4+/CD8+ ratio at T2 to T5 and the CD4+ level and NK cells at T3 to T5 were significantly higher in the COM Group than in the MOR Group (p< 0.05). The postoperative morphine dose and the incidence of postoperative itching, nausea, and vomiting were significantly lower in the COM Group than in the MOR Group (p< 0.05). Conclusions Dexmedetomidine combined with morphine for post-thoracotomy PCIA can improve the function of immunocytes, reduce morphine consumption, and reduce the adverse reactions during analgesia induction.

Resumo Objetivo Estudar o impacto em linfócitos causado pelo uso da dexmedetomidina associada à morfina para analgesia pós-toracotomia. Método Um total de 118 pacientes utilizando Analgesia Intravenosa Controlada pelo Paciente (AICP) pós-toracotomia em nosso hospital, de março de 2016 a julho de 2018, foram selecionados aleatoriamente e divididos em dois grupos: o Grupo Combinado [COM, 57 pacientes que receberam dexmedetomidina (1,0 µg.kg-1 de peso corpóreo) associada à morfina (0,48 mg.kg-1 de peso corpóreo)] e o Grupo Morfina [MOR, 61 pacientes, que receberam somente morfina (0,48 mg.kg-)]. Os valores dos subconjuntos de linfócitos (CD3+, CD4+ e CD8+) e das células NK no sangue periférico desses dois grupos foram medidos por citometria de fluxo FACSCalibur em diferentes momentos do estudo [antes da indução anestésica (T0), imediatamente após extubação traqueal (T1), 12 horas após a cirurgia (T2), 24 horas após a cirurgia (T3), 48 horas após a cirurgia (T4), 72 horas após a cirurgia (T5) e 7 dias após a cirurgia (T6)]. As doses de morfina do momento T3 ao T5 e as reações adversas entre os dois grupos também foram registradas e comparadas. Resultados O nível de CD3+ e a razão CD4+/CD8+ de T2 a T5, e o nível de CD4+ e as células NK de T3 a T5 do Grupo COM foram significantemente maiores (p< 0,05) quando comparados ao Grupo MOR. A dose de morfina no pós-operatório e a incidência de prurido, náusea e vômito no pós-operatório foram significantemente menores no grupo MOR (p< 0,05). Conclusões Dexmedetomidina combinada com morfina para AICP no período pós-toracotomia pode melhorar a função dos linfócitos, reduzir o consumo de morfina e diminuir reações adversas durante a analgesia.

Dexmedetomidine combined with protective lung ventilation strategy provides lung protection in patients undergoing radical resection of esophageal cancer with one-lung ventilation / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of dexmedetomidine combined with pulmonary protective ventilation against lung injury in patients undergoing surgeries for esophageal cancer with one-lung ventilation (OLV).@*METHODS@#Forty patients with undergoing surgery for esophageal cancer with OLV were randomly divided into pulmonary protective ventilation strategy group (F group) and dexmedetomidine combined with protective ventilation strategy group (DF group; =20). In F group, lung protective ventilation strategy during anesthesia was adopte, and in DF group, the patients received intravenous infusion of dexmedetomidine hydrochloride (0.3 μg · kg ·h) during the surgery starting at 10 min before anesthesia induction in addition to protective ventilation strategy. Brachial artery blood was sampled before ventilation (T), at 30 and 90 min after the start of OLV (T and T, respectively) and at the end of the surgery (T) for analysis of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), arterial oxygenation pressure (PaO), oxygenation index (OI) and lung compliance (CL).@*RESULTS@#At the time points of T, T and T, SOD level was significantly higher and IL-6 level was significantly lower in the DF group than in F group ( < 0.05). The patients in DF group showed significantly higher PaO, OI and CL index than those in F group at all the 3 time points.@*CONCLUSIONS@#Dexmedetomidine combined with pulmonary protective ventilation strategy can reduce perioperative lung injury in patients undergoing surgery for esophageal cancer with OLV by suppressing inflammation and oxidative stress to improve lung function and reduce adverse effects of the surgery.

Falla hepática aguda / Acute liver failure

La falla hepática aguda es la pérdida súbita de la función hepática en un corto plazo en un paciente sin enfermedad hepática previa, que se acompaña de coagulopatía y encefalopatía. Es una entidad rara con una incidencia muy baja que afecta especialmente a personas jóvenes. La principal causa en países desarrollados es la toxicidad por acetaminofén, mientras que en los países subdesarrollados son las hepatitis virales. El curso natural de la enfermedad es la progresión rápida a muerte por falla orgánica multisistémica, sepsis o edema cerebral. Después del diagnóstico, los pacientes deben remitirse tempranamente a la unidad de cuidado intensivo y a centros que ofrezcan trasplante hepático. La supervivencia sin trasplante hepático hasta hace pocos años era menor al 15%; sin embargo, en la actualidad puede ser hasta del 50%, dependiendo de la causa, y está relacionada con tratamientos específicos, la disponibilidad de trasplante hepático y una atención óptima en las unidades de cuidados intensivos. El trasplante hepático se constituye en el tratamiento de elección para los pacientes con falla hepática aguda y criterios de mal pronóstico del King's College.

Acute liver failure is the severe short-term liver function impairment in a patient without previous liver disease, which is accompanied by coagulopathy and encephalopathy. It is a rare condition with a very low incidence that affects young people. The leading cause in developed countries is acetaminophen toxicity, while in developing countries is mainly caused by viral hepatitis. The natural course is characterized by a rapid progression to death due to multisystemic organ failure, sepsis, or cerebral edema. After diagnosis, patients must be transferred to the intensive care unit and liver transplantation centers. Survival without liver transplantation until a few years ago was less than 15%; however, currently it can be up to 50% depending on the cause, and it is related to specific treatments, availability of liver transplantation and optimal care in the intensive care units. Liver transplantation is the treatment of choice for patients with acute liver failure and King's College criteria for poor prognosis.

Resultados tras implantación de un protocolo de sedoanalgesia para procedimientos en ámbito hospitalario / Results after implementation of a sedoanalgesia protocol for procedures in hospital environment

INTRODUCCIÓN: Se analiza la efectividad y seguridad de un protocolo específico de sedoanalgesia para procedimien tos, y evalúa la satisfacción del personal sanitario con cada procedimiento. PACIENTES Y MÉTODO: Estudio prospectivo de un protocolo de sedoanalgesia para procedimientos en ámbito hospitalario en menores de 18 años, con una estrategia individualizada según la situación basal del paciente, el tipo de procedimiento y la experiencia del pediatra responsable de la sedación. Se registraron las variables: diagnóstico que motiva el procedimiento, tipo de procedimiento, datos antropométri cos, alergias, medicación, estado ASA y enfermedad de base, tiempo de ayuno, auscultación pul monar, temperatura, saturación de oxígeno, frecuencia respiratoria, frecuencia cardiaca, tensión arterial, lugar de sedación, tipo de fármaco, dosis, tipo de vía, escala de sedación Ramsay, duración de la sedación, tipo y tratamiento de efectos adversos, presencia de familiares durante todo el pro cedimiento y satisfacción del paciente. RESULTADOS: Se realizaron 279 sedaciones. Los fármacos más usados fueron óxido nitroso (62,7%) y midazolam (16,5%); las vías de administración más utili zadas fueron la inhalada (62,4%) y la intravenosa (15,8%). La satisfacción fue alta para el pediatra (92,5%), el enfermero (94,3%), los familiares (96,8%) y los pacientes (93,6%), con una buena correlación entre ellos, y fue significativamente menor al usar midazolam y las vías nasal y bucal. La tasa de efectos adversos fue del 3,2%, y ninguno fue grave. CONCLUSIONES: La implementación de un protocolo específico de sedoanalgesia para procedimientos en el ámbito hospitalario consigue una alta efectividad y seguridad, además de un alto nivel de satisfacción, tanto en familiares como en personal sanitario.

INTRODUCTION: We analyze the effectiveness and safety of a specific analgosedation protocol for procedures, and eva luate the satisfaction of the health personnel with each procedure. PATIENTS AND METHOD: Prospective study of an analgosedation protocol for hospital procedures in children under 18 years of age, with an individualized strategy based on the patient's baseline situation, the type of procedure and the experience of the pediatrician responsible for the sedation. The following variables were recorded: diagnosis motivating the procedure, type of procedure, anthropometric data, allergies, medication, ASA status and baseline disease, fasting time, lung auscultation, temperature, oxygen saturation, res piratory rate, heart rate, blood pressure, sedation location, type of drug, dose, route of administra tion, Ramsay sedation scale, duration of sedation, type and treatment of adverse effects, presence of family members throughout the procedure, and patient satisfaction. RESULTS: 279 sedations were performed. The most commonly used drugs were nitrous oxide (62.7%) and midazolam (16.5%); the most commonly used routes of administration were the inhaled one (62.4%) and the intravenous one (15.8%). The satisfaction was high for the pediatrician (92.5%), the nurse (94.3%), the family (96.8%), and patients (93.6%), with a good correlation between them, and it was significantly lower when using midazolam and the nasal and oral routes. The adverse effects rate was 3.2%, and none was severe. CONCLUSIONS: The implementation of a specific analgosedation protocol for procedures in the hospital environment achieves high levels of effectiveness and safety, as well as a high level of satisfaction, both in family members and in health personnel.

Eficácia hepatoprotetora do extrato metanólico de Indigofera suffruticosa (Mill) em lesão hepática induzido por paracetamol em camundongos / Hepatoprotective efficacy of methanolic extract of indigofera suffruticosa (mill) on paracetamol-induced liver damage in mice

ABSTRACT BACKGROUND: Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE: This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS: MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS: MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION: This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.

RESUMO CONTEXTO: Indigofera suffruticosa Mill (Fabaceae) é abundante no nordeste do Brasil e popularmente utilizada no tratamento de processos infecciosos e inflamatórios. Várias propriedades biológicas, como anti-inflamatório, anticâncer, antitumoral, hepatoprotetor e baixa toxicidade, são relatadas para esta planta. OBJETIVO: Este estudo investigou a atividade hepatoprotetora e o efeito antioxidante do extrato metanólico de folhas de I. suffruticosa (MEIS) em camundongos albinos suíços submetidos a modelos experimentais de lesão hepática induzida por paracetamol. MÉTODOS: O MEIS na dose de 50 mg/kg (via oral) foi padronizado de acordo com a LD50 e sua propriedade hepatoprotetora em camundongos albinos Swiss avaliados durante um período de sete dias. No oitavo dia, a lesão hepática foi induzida por paracetamol em todos grupos pre-tratados. Foram medidos os níveis sericos enzimaticos, alanina aminotransferase, aspartato aminotransferase e bilirrubina, análise histomorfométrica do tecido hepático e atividade antioxidante. RESULTADOS: O MEIS restaurou os níveis séricos de enzimas e os resultados foram próximos aos do controle positivo (silimarina) quando comparados ao controle negativo. As análises histopatológicas e histomorfométricas confirmaram a atividade hepatoprotetora do MEIS, mostrando reorganização das unidades estruturais das células, núcleos e capilares sinusoidais dos hepatócitos, reduzindo os danos no tecido hepático e aumentando a taxa de regeneração de órgãos. O MEIS apresentou alto potencial antioxidante nas concentrações de 1000 e 500 µg/mL. CONCLUSÃO: Este estudo sugere que I. suffruticosa tem atividade hepatoprotetora e alto potencial antioxidante.

Do we still need central blocks while we have erector spinae plane block? Case of 2. 5 month old infant / Ainda precisamos de bloqueios centrais enquanto temos o bloqueio do eretor da espinha? Caso de criança de 2, 5 meses de idade

Abstract Erector spinae plane block is gaining popularity both for its ease of application and as its comparable effect on postoperative analgesia with central regional techniques like paravertebral block or epidural anesthesia. Its use for many indications has been reported in the literature for pediatric patients. We would like to share our experiences in a 2.5-month infant scheduled for thoracotomy for a giant congenital cyst. Single shot erector spinae plane block was done at T4 level before the start of the surgery for both surgical and postoperative analgesia. No complication was seen during both surgery and follow up period. Erector spinae plane block with the combination of paracetamol was adequate for pain relief.

Resumo O bloqueio do plano do músculo eretor da espinha tem ganhado popularidade, tanto pela facilidade de aplicação quanto pelo efeito comparável em analgesia pós-operatória com técnicas regionais centrais, como o bloqueio paravertebral ou a anestesia peridural. Seu uso tem sido relatado na literatura para muitas indicações em pacientes pediátricos. Gostaríamos de compartilhar nossas experiências no caso de um bebê de 2,5 meses de idade programado para toracotomia para excisão de um cisto congênito gigante. O bloqueio do plano do eretor da espinha dorsal com injeção única foi realizado no nível de T4 antes do início da cirurgia para analgesia cirúrgica e pós-operatória. Nenhuma complicação foi observada durante a cirurgia e o período de acompanhamento. O bloqueio do plano do eretor da espinha com a combinação de paracetamol foi adequado para o alívio da dor.

Efectividad Analgésica de Paracetamol Post-Cirugía Mucogingival: Ensayo Clínico Aleatorizado Paralelo / Analgesic Effectiveness of Paracetamol Post-Mucogingival Surgery: Parallel Randomized Clinical Trial

RESUMEN: El objetivo de este trabajo fue determinar la efectividad analgésica de paracetamol post-cirugía mucogingival. El estudio, prospectivo, longitudinal, comparativo y experimental, se desarrolló en la Clínica Odontológica de la Universidad Privada Antenor Orrego (Trujillo, Perú) con los pacientes de la asignatura Periodoncia II. Se incluyeron 39 pacientes, quienes fueron distribuidos de manera aleatoria en 2 grupos de 19 y 20 cada uno, según los criterios establecidos. La medicación se inició 20 minutos después de concluida la cirugía, y se mantuvo por 24 horas. Para determinar la efectividad analgésica se usó la escala visual analógica (0-100 mm) y se recogió la información que fue procesada, utilizando la prueba de U Mann-Whitney con un nivel de significancia del 5 %. No existe diferencia en cuanto a la efectividad analgésica post-cirugías mucogingivales entre paracetamol y el control a las 2 horas (p=0.415), 8 horas (p=0.279) y 24 horas (p=0.736). Paracetamol es efectivo como analgésico post-cirugía mucogingival.

ABSTRACT: The objective of this study was to determine the analgesic effectiveness of paracetamol after mucogingival surgery. This prospective, longitudinal, comparative and experimental study was developed in the Stomatology Clinic of the Universidad Privada Antenor Orrego (Trujillo, Perú) with the patients of the Periodontics II subject. We included 39 patients, who were randomly distributed into 2 groups of 19 and 20 each, according to the established criteria. The medication was started 20 minutes after the surgery was completed, and was maintained for 24 hours. To determine the analgesic effectiveness, the analogue visual scale (0-100 mm) was used and the information that was processed was collected, using the U Mann-Whitney test with a level of significance of 5 %. There is no difference in terms of analgesic effectiveness post-mucogingival surgery between paracetamol and control at 2 hours (p = 0.415), 8 hours (p = 0.279) and 24 hours (p = 0.736). Paracetamol is effective as a mucogingival post-surgery analgesic.

Addition of dexmedetomidine to bupivacaine in ultrasonography-guided paravertebral blockade potentiates postoperative pain relief among patients undergoing thoracotomy / Adição de dexmedetomidina à bupivacaína em bloqueio paravertebral guiado por ultrassom potencializa o alívio da dor pós-operatória em pacientes submetidos à toracotomia

Abstract Background and objective: Thoracic paravertebral blockade is an alternative regional technique for comforting post-thoracotomy pain, thereby decreasing opioid consumption, postoperative nausea and vomiting, dizziness, respiratory depression and health care costs. The objective of this study was to investigate the effects of bupivacaine and bupivacaine plus dexmedetomidine on postoperative pain score and analgesic consumption in thoracotomy patients who had undergone ultrasonography-guided paravertebral blockade. Material and method: 93 ASA I-II patients aged 18-65 years were included in the study and scheduled for thoracic surgery. Prior to anesthesia induction, the paravertebral blockade procedure was performed by an anesthetist with ultrasonography. Cases were randomly stratified into three groups. The paravertebral blockade procedure was performed with 20 mL 0.5% bupivacaine injection in Group B (n = 31) and 20 mL 0.5% bupivacaine + 1 mL dexmedetomidine (100 µg) injection in Group BD. Group C received postoperative i.v. morphine via patient-controlled analgesia without paravertebral blockade. Post-operative pain scores were recorded in the recovery room and post-operatively using a VAS. Hemodynamic parameters, adverse effects and morphine consumption were also recorded. Results: No significant difference was determined between Group B and Group C regarding intra-operative adverse effects such as bradicardia and hypotension, while these adverse effects were significantly higher in Group BD (p = 0.04). VAS scores with rest and upon movement were significantly lower in Group BD compared to Group C (p < 0.001). Total morphine consumption was significantly lower in both Group B and Group BD in comparison with Group C (p < 0.001). In Group BD, HR and MAP were lower, but this was not clinically significant (p < 0.05). Conclusion: The addition of dexmedetomidine to bupivacaine lowers postoperative pain scores and morphine consumption in thoracotomy patients who receive ultrasonography guided paravertebral blockade.

Resumo Justificativa e objetivo: O bloqueio paravertebral torácico é uma técnica regional opcional para o alívio da dor pós-toracotomia, deste modo diminui o consumo de opioides, náuseas e vômitos no pós-operatório, tontura, depressão respiratória e custos com saúde. O objetivo deste estudo foi investigar os efeitos de bupivacaína isolada e bupivacaína + dexmedetomidina no escore de dor pós-operatória e no consumo de analgésicos em pacientes submetidos à toracotomia sob bloqueio paravertebral guiado por ultrassom. Material e método: Noventa e três pacientes, ASA I-II, com idades entre 18 e 65 anos, foram incluídos no estudo e programados para cirurgia torácica. Antes da indução anestésica, o procedimento de bloqueio paravertebral foi realizado por um anestesista com o uso de ultrassom. Os casos foram estratificados aleatoriamente em três grupos. O procedimento de bloqueio paravertebral foi realizado com injeção de 20 mL de bupivacaína a 0,5% no Grupo B (n = 31) e de 20 mL de bupivacaína a 0,5% + 1 mL de dexmedetomidina (100 µg) no Grupo BD. O Grupo C recebeu morfina intravenosa via analgesia controlada pelo paciente sem bloqueio paravertebral. Os escores de dor pós-operatória foram registrados na sala de recuperação e no pós-operatório usando a escala VAS. Parâmetros hemodinâmicos, efeitos adversos e consumo de morfina também foram registrados. Resultados: Não houve diferença significativa entre os grupos B e C em relação a efeitos adversos intraoperatórios, como bradicardia e hipotensão, enquanto esses efeitos adversos foram significativamente maiores no Grupo BD (p = 0,04). Os escores VAS em repouso e movimento foram significativamente menores no Grupo BD em relação ao Grupo C (p < 0,001). O consumo total de morfina foi significativamente menor nos grupos B e BD em comparação com o Grupo C (p < 0,001). No Grupo BD, a frequência cardíaca e a pressão arterial média foram menores, mas esse resultado não foi clinicamente significativo (p < 0,05). Conclusão: A adição de dexmedetomidina à bupivacaína reduz os escores de dor pós-operatória e o consumo de morfina em pacientes submetidos à toracotomia sob bloqueio paravertebral guiado por ultrassom.

Effect of intravenous acetaminophen versus fentanyl on postoperative pain after transurethral lithotripsy / Efeito do acetaminofeno versus fentanil intravenosos na dor pós litotripsia transuretral

Abstract Background: Postoperative pain is the most common postoperative complication. This study was conducted to assess the effect of acetaminophen versus fentanyl on postoperative pain relief in patients who underwent urologic surgeries. Methods: This clinical trial was conducted on patients aged 18-65 years. Patients were randomly assigned to receive either 2000 mg acetaminophen (propacetamol) or 2 mcg.kg-1 fentanyl intravenously, 15 min before the end of surgery. The postoperative pain was evaluated every 6 h for 24 h using the Visual Analog Scale. Total morphine dose taken in 24 h and hemodynamic status were evaluated. Results: Eighty patients were enrolled into the trial. The mean score of pain in 6, 12, 18, and 24 h after surgery was lower in the acetaminophen group than in the fentanyl group but the difference was not statistically significant except in 12 and 18 h after surgery (p < 0.05). The amount of administered morphine was higher in the fentanyl group than in the acetaminophen group, but the difference was not statistically significant. The hemodynamic status including systolic and diastolic blood pressure and heart rates were nearly the same in the two groups but the SpO2 mean was significantly higher in the acetaminophen group than the fentanyl group. Conclusions: This trial indicated that intravenous acetaminophen is as effective as intravenous fentanyl in pain relief after urologic surgeries (transurethral lithotripsy).

Resumo Justificativa: A dor pós-operatória é a complicação mais comum no período pós-operatório. Este estudo foi realizado para avaliar o efeito de acetaminofeno versus fentanil no alívio da dor pós-operatória em pacientes submetidos a cirurgias urológicas. Métodos: Este ensaio clínico foi realizado com pacientes cujas idades variou entre 18 e 65 anos. Os pacientes foram randomicamente designados para receber 2.000 mg de acetaminofeno (propacetamol) ou 2 mcg.kg-1 de fentanil por via intravenosa 15 min antes do final da cirurgia. A dor pós-operatória foi avaliada a cada 6 horas por 24 horas, utilizando a escala visual analógica. A dose total de morfina administrada em 24 horas e o estado hemodinâmico foram avaliados. Resultados: Oitenta pacientes foram incluídos no estudo. O escore médio de dor em 6, 12, 18 e 24 horas após a cirurgia foi menor no grupo acetaminofeno que no grupo fentanil, mas a diferença não foi estatisticamente significativa, exceto em 12 e 18 horas após a cirurgia (p < 0,05). A quantidade de morfina administrada foi maior no grupo fentanil que no grupo acetaminofeno, mas a diferença não foi estatisticamente significativa. O estado hemodinâmico, incluindo pressão arterial sistólica e diastólica e frequência cardíaca, foi quase o mesmo nos dois grupos, mas a média de SpO2 foi significativamente maior no grupo acetaminofeno que no grupo fentanil. Conclusões: Este estudo indicou que acetaminofeno intravenoso é tão eficaz quanto fentanil intravenoso no alívio da dor após cirurgias urológicas (litotripsia transuretral).

Dose-response Relationship of Dexmedetomidine Combined with Sufentail for Postoperative Intravenous Analgesia in Video-assisted Thoracoscopic Surgery / 中国医学科学院学报

Objective To investigate the 50% effective dose(ED)and 95% effective dose(ED)of dexmedetomidine(DEX)combined with 0.032 μg/(kg·h)sufentanil as well as its analgesic effect for patient-controlled intravenous analgesia(PCIA)after video-assisted thoracoscopic surgery(VATS).Methods Totally 25 patients undergoing elective VATS were enrolled. DEX and 0.032 μg/(kg·h)sufentanil were used for postoperative PCIA. The loading dose of DEX was 0.048 μg/(kg·h),and the dose difference between two adjacent patients was 0.008 μg/(kg·h). The DEX dose of a current patient was determined by whether the previous patient was satisfied with postoperative analgesic effect. If the previous patient was satisfied with postoperative analgesic effect,the DEX dose of the current patient was decreased by 0.008 μg/(kg·h);and if the previous analgestic effect was not satisfactory,DEX dose of the current patient was increased by 0.008 μg/(kg·h). The study endpoint was dexmedetomidine dose was<0.008 μg/(kg· h) within 7 upper and lower cycles in 7 consecutive cases. Finally,the probability unit regression was used to estimate the ED and ED of DEX and their 95% .Results When DEX combined with 0.032 μg/(kg·h) sufentanil was used for postoperative PCIA in young patients undergoing VATS,the ED and EDof DEX were 0.0346 μg/(kg· h)[95%:0.0283-0.0408 μg/(kg·h)] and 0.0459 μg/(kg·h)[95%:0.0400-0.0880 μg/(kg·h)],respectively. No adverse reaction such as vomiting,respiratory depression,or bradycardia occurred. The average Visual Analogue Scale(VAS)scores at rest(=-5.128,=0.000)and cough(Z=-6.642,=0.000)and the Ramsay sedation score(Z=-2.335,=0.020)within 6 hours after surgery were higher than those after 6 hour.Conclusion DEX combined with 0.032 μg/(kg·h) sufentanil are effective for postoperative PCIA in patients undergoing VATS when the ED and ED are 0.0346 μg/(kg·h)and 0.0459 μg/(kg·h),respectively.

Compromiso neuropático y autonómico en Enfermedad de Fabry: presentación de casos clínicos / Neuropathy and Fabry's disease: report of five cases

Fabry's disease is an X-linked multisistemic lisosomal storage disorder caused by deficiency or absence in α-Galatosidase A. Symptoms develop early in childhood with small fiber neuropathy, autonomic disorders and skin lesions (angiokeratomas). More severe in males, patients develop over years heart disease (hypertrophic cardiomyopathy, bradycardia), proteinuria, renal failure, transient ischemic attacks and stroke, associated with decreased life expectancy. We report five patients with Fabry's disease aged between 21 to 56 years and with family history. Neuropathic symptoms are described and neurophysiological testing findings of nerve conduction studies, quantitative sensory testing, autonomic testing and sympathetic skin response are presented.

The effect of dexmedetomidine on the acute pain after cardiothoracic surgeries: a systematic review

Abstract Introduction: Acute post-operative pain remains a troublesome complication of cardiothoracic surgeries. Several randomized controlled trials have examined the efficacy of dexmedetomidine as a single or as an adjuvant agent before, during and after surgery. However, no evidence-based conclusion has been reached regarding the advantages of dexmedetomidine over the other analgesics. Objective: To review the effect of dexmedetomidine on acute post-thoracotomy/sternotomy pain. Methods: Medline, SCOPUS, Web of Science, and Cochrane databases were used to search for randomized controlled trials that investigated the analgesia effect of dexmedetomidine on post-thoracotomy/sternotomy pain in adults' patients. The outcomes were postoperative pain intensity or incidence, postoperative analgesia duration, and the number of postoperative analgesic requirements. Results: From 1789 citations, 12 trials including 804 subjects met the inclusion criteria. Most studies showed that pain score was significantly lower in the dexmedetomidine group up to 24 hours after surgery. Two studies reported the significant lower postoperative analgesia requirements and one study reported the significant lower incidence of acute pain after surgery in dexmedetomidine group. Ten studies found that the total consumption of narcotics was significantly lower in the dexmedetomidine group. The most reported complications of dexmedetomidine were nausea/vomiting, bradycardia and hypotension. Conclusion: Dexmedetomidine can be used as a safe and efficient analgesic agent for reducing the postoperative pain and analgesic requirements up to 24 hours after cardiothoracic surgeries. However, further well-designed trials are needed to find the optimal dosage, route, time, and duration of dexmedetomidine administration.

Amitriptyline and intraoral devices for migraine prevention: a randomized comparative trial / Amitriptilina e dispositivos intraorais para a prevenção da migrânea: estudo randomizado e comparativo

ABSTRACT Objectives: Nonpharmacological treatments, such as the Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), are approved for migraine prophylaxis. We aimed at evaluating the effectiveness of the NTI-tss and to compare its efficacy with amitriptyline and with a sham intraoral device in the preventive treatment of migraine. Methods: Consecutive patients with migraine were randomized to receive 25 mg of amitriptyline/day (n = 34), NTI-tss (n = 33) and a non-occlusal splint (n = 30). The headache frequency was evaluated at six and 12 weeks. Results: The amitriptyline group showed, respectively, 60% and 64% reduction in attack frequency at six and 12 weeks (P = 0.000). In the NTI-tss and non-occlusal splint groups, reduction was 39% and 30%, respectively, at six weeks and 48% for both groups at 12 weeks. Conclusions: Amitriptyline proved superior to the NTI-tss and the non-occlusal splint. Despite its approval by the United States Food and Drug Administration, the NTI-tss was not superior to a sham device.

RESUMO Objetivo: Tratamentos não farmacológicos como o Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), são aprovados para a prevenção da migrânea. Avaliamos a eficácia do NTI-tss no tratamento preventivo da migrânea e comparamos sua eficácia com a de um medicamento tradicional (amitriptilina) e com um dispositivo intraoral que não interfere com a oclusão (placa palatina). Métodos: Pacientes consecutivos com migrânea foram randomizados e receberam 25mg de amitriptilina/dia (n = 34), NTI-tss (n = 33) ou placa palatina não oclusal (n = 30). A frequência da cefaleia foi comparada após seis e 12 semanas. Resultados: No grupo da amitriptilina houve redução de 60% em seis semanas e de 64% em 12 semanas (P = 0.000). Nos grupos do NTI-tss e da placa não oclusal a redução foi respectivamente de 39% e 30% após seis semanas, e de 48% para ambos em 12 semanas. Conclusões: Amitriptilina foi superior ao NTI-tss e à placa palatina no tratamento da migrânea sem aura. O NTI-tss obteve resultados similares aos da placa não oclusal.