Gaps in our knowledge and future research on the endocannabinoid system and the painful phenomenon / As lacunas do nosso conhecimento e as pesquisas futuras sobre o sistema endocanabinoide e o fenômeno doloroso

ABSTRACT BACKGROUND AND OBJECTIVES: This article aimed to discuss and point out the main gaps and bottlenecks in national and international clinical research regarding medicinal cannabinoid compounds and their respective relevance to pain management practices. Other objectives were to establish standards and regulations for testing the quality, efficacy, and safety of cultivation and manufacturing of cannabis products (similar to biopharmaceutical standards) before prescribing or marketing, and to investigate approaches in order to establish robust guidelines for cannabinoid-influenced driving. CONTENTS: A search with the terms "cannabinoids" and "pain" in the domain www.clinicaltrials.gov, international data platform for registration of clinical research trials, found only two Brazilian studies, on fibromyalgia and chronic headache. The search for the term "cannabinoid" in Plataforma Brasil returned only nine mentions of studies related to pain, most of them being case reports or observational studies, without active intervention or control group. CONCLUSION: There are still few clinical, randomized, controlled trials evaluating effective doses, routes and interval of administration, pharmacological interaction with opioids or among the various cannabinoids, interaction with adjunct analgesics, potential injury in the context of long-term use, and individual factors that predispose to indiscriminate cannabinoid use.

RESUMO JUSTIFICATIVA E OBJETIVOS: O presente artigo teve como objetivo debater e apontar as principais lacunas e gargalos na pesquisa clínica nacional e internacional relativas aos compostos canabinoides de uso medicinal e suas respectivas relevâncias nas práticas relacionadas ao controle da dor. Outros objetivos foram estabelecer padrões e regulamentos para testar a qualidade, eficácia e segurança de cultivo e fabricação de produtos de cannabis (semelhantes aos padrões biofarmacêuticos) antes de prescrever ou comercializar, e investigar abordagens a fim de estabelecer orientações robustas para dirigir sob influência de canabinoides. CONTEÚDO: Uma pesquisa com os termos "canabinoides" e "pain" no domínio do www.clinicaltrials.gov, plataforma internacional de dados de registro de ensaios de pesquisa clínica, cita apenas dois estudos brasileiros, sobre fibromialgia e cefaleia crônica. A busca do termo "canabinoide" na Plataforma Brasil retornou apenas nove menções de estudos relacionados ao tema dor, sendo a maioria relatos de casos ou estudos observacionais, sem intervenção ativa, ou sem grupo controle. CONCLUSÃO: Ainda há poucos estudos clínicos, randomizados e controlados avaliando doses eficazes, vias e intervalo de administração, interação farmacológica com opioides ou entre os diversos canabinoides, interação com analgésicos adjuvantes, lesões potenciais no contexto do uso a longo prazo e fatores individuais que predisponham ao uso indiscriminado dos canabinoides.

Simulação in situ e suas diferentes aplicações na área da saúde: uma revisão integrativa / In situ simulation and its different applications in healthcare: an integrative review

Resumo Introdução: A simulação in situ (SIS) consiste em técnica de capacitação que ocorre no local real de trabalho como um método relevante para promover a fidelidade ambiental no cenário simulado. Objetivo: Este estudo teve como objetivo verificar o uso da SIS no mundo para compreender sua aplicabilidade na área de saúde. Método: Trata-se de uma revisão integrativa que adotou a seguinte questão norteadora: "Como tem sido utilizada a simulação in situ por profissionais da área da saúde?". Foram realizadas buscas nas bases PubMed, SciELO, LILACS e Web of Science, com as diferentes combinações dos descritores "simulação in situ", "saúde" e "medicina" (em português, inglês e espanhol) e os operadores booleanos AND e OR, com utilização de filtro temporal de 2012 a 2021. Encontraram-se 358 artigos, nos quais se aplicaram os critérios de inclusão e exclusão, seguindo as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Após revisão independente realizada por pares, com o uso do Rayyan, restaram 190 para esta revisão. Resultado: Os resultados mostraram que os Estados Unidos detêm a maioria absoluta das produções (97/51%), seguidos do Canadá, porém com grande diferença numérica (18/9,5%). A maior parte dos trabalhos está escrita em inglês (184/96,8%), é quase experimental (97/51%) e tem equipes multiprofissionais como público-alvo (155/81,6%). Os artigos têm 11.315 participantes e 2.268 intervenções de simulação. Os principais cenários de SIS foram os setores de urgência e emergência (114/60%), seguidos de UTI (17/9%), sala de parto (16/8,42%) e centro cirúrgico (13/6,84%). Os temas mais estudados foram RCP (27/14,21%), Covid-19 (21/11%), complicações do parto (13/6,8%) e trauma (11/5,8%). As vantagens apontadas incluem: atualização profissional e aquisição de habilidades e competências em ambiente próximo do real e de baixo custo por não depender de dispendiosos centros de simulação. Conclusão: Em todo o mundo, a SIS tem sido utilizada por profissionais da saúde como estratégia de educação na área de saúde, com bons resultados para aprendizagem e capacitações de diferentes momentos da formação profissional e com melhora da assistência. Ainda há muito o que expandir em relação ao uso da SIS, sobretudo no Brasil, na publicação de estudos sobre essa abordagem.

Abstract Introduction: The in situ simulation (ISS) consists of a training technique that takes place in the real workplace as a relevant method to promote environmental fidelity in the simulated scenario. Objective: To verify the use of the ISS in the world, to understand its applicability in healthcare. Method: This is an integrative review, which used the following guiding question: How has in situ simulation been used by health professionals? Searches were carried out in the PubMed, SciELO, LILACS and Web of Science databases, with different combinations of the following descriptors: in situ simulation, health and medicine (in Portuguese, English and Spanish) and the Boolean operators AND and OR using a temporal filter from 2012 to 2021. A total of 358 articles were found and the inclusion and exclusion criteria were applied, following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and also with an independent peer review, using Rayyan, leaving 190 articles for this review. Results: The results showed that the United States has the absolute majority of productions (97/51%), followed by Canada, but with a large numerical difference (18/9.5%). Most of the works are written in English (184/96.8%), are quasi-experimental studies (97/51%), and have multidisciplinary teams as the target audience (155/81.6%). The articles have 11,315 participants and 2,268 simulation interventions. The main ISS scenarios were the urgent and emergency sectors (114/60%), followed by the ICU (17/9%), delivery room (16/8.42%) and surgical center (13/6.84%). The most frequently studied topics were CPR (27/14.21%), COVID-19 (21/11%), childbirth complications (13/6.8%) and trauma (11/5.8%). Discussion: The pointed-out advantages include the opportunity for professional updating with the acquisition of knowledge, skills and competencies, in an environment close to the real thing and at low cost, as it does not depend on expensive simulation centers. Conclusion: In situ simulation has been used by health professionals worldwide, as a health education strategy, with good results for learning and training at different moments of professional training, with improved care and low cost. There is still much to expand in relation to the use of ISS, especially in Brazil, in the publication of studies and experience reports on this approach.

Polypropylene oxygenators: risk of SARS-CoV-2 contamination in the operation theatre?

It is established that coronaviruses are transmitted most through aerosols produced when an infected individual coughs or sneezes.1 Although there is no clear evidence of person-to-person airborne transmission, it is possible that part of this component could be due to microscopic respiratory droplets at short to medium distances (up to several meters, or room scale) and deposits from respiratory droplets on surfaces.2,3 However, recent studies revealed that infected patients can potentially be a source of the virus not only through respiratory but also fecal­oral or body fluid routes, raising also the theoretical possibility of bloodborne transmission.4 Based on these arguments, the possibility has also been raised of some equipment that could be a new source of transmission, like the membranes used for extracorporeal oxygenation, which act the same as lungs and also have a direct contact with the blood. Most centers worldwide report a reduction in the cardiac procedures due to the pandemic, however emergency surgeries with conventional cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) procedures have been performed every day. Despite guidelines and modifications for operating theatre preparation for the management of suspected or confirmed SARS-CoV-2 patients submitted to cardiac surgery, many aspects still need to be clarified.5 Potential risk of transmission with these membranes exists, so much that Dres et al.6 reported a study evaluating the risks of SARS-CoV-2 dissemination through membranes used for extra corporeal organ support in critically ill patients, within 48 h after ECMO and continuous renal replacement therapy (CRRT) initiation. They investigated whether SARS-CoV-2 RNA was detected in the dialysis effluent fluid or in the condensate collected from the ECMO membrane gas outlet, when the virus was present in the lower respiratory tract and the plasma. Results showed that in 25 patients on veno-venous ECMO, SARSCoV-2 RNA was not detected in the membrane oxygenator gas outlet condensate in any of 25 patients of whom 13 were plasma RNA positive. Also, they were not able to measure any SARS-CoV-2 RNA in the dialysate of those patients who additionally were treated by CRRT.

Tramadol wound infiltration is not different from intravenous tramadol in children: a randomized controlled trial.

STUDY OBJECTIVE: The purpose of this trial was to assess if tramadol wound infiltration is superior to intravenous (IV) tramadol after minor surgical procedures in children because tramadol seems to have local anesthetic-like effect. DESIGN: Randomized double-blind controlled trial. SETTING: Postanesthesia care unit. PATIENTS: Forty children, American Society of Anesthesiologists physical status I or II, scheduled to elective inguinal hernia repair. INTERVENTIONS: Children were randomly distributed in 1 of 2 groups: IV tramadol (group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the surgery, group 1 received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline into the surgical wound; group 2 received 2 mg/kg tramadol (3 mL) into the surgical wound and 3-mL saline by IV route. MEASUREMENTS: In the postanesthesia care unit, patients were evaluated for pain intensity, nausea and vomiting, time to first rescue medication, and total rescue morphine and dipyrone consumption. MAIN RESULTS: Pain scores measured during the postanesthesia recovery time were similar between groups. Time to first rescue medication was shorter, but not statistically significant in the IV group. The total dose of rescue morphine and dipyrone was also similar between groups. CONCLUSIONS: We concluded that tramadol was effective in reducing postoperative pain in children, and there was no difference in pain intensity, nausea and vomiting, or somnolence regarding IV route or wound infiltration.

Experimental models for the study of neuropathic pain / Modelos experimentais para o estudo da dor neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Ideal models should reproduce just sensory deficits, such as alodynia, hyperalgesia and spontaneous pain for short periods. There are different types of animal models to evaluate different neuropathic pain etiologies and manifestations. Some models study neuropathic pain peripheral mechanisms and other study its central mechanisms. This review focuses on animal models most commonly used for neuropathic pain research. CONTENTS: Animal models based on peripheral nerves ligation which are more commonly used are described. From all models described in this review, spared nerve injury is that producing more reproducible behavioral abnormalities for a longer period, while chronic sciatic nerve compression produces behavioral signs of less predictable painful neuropathies. Spinal hemisection and cytokines-induced spinal injury are the models of choice for the study of central pain mechanisms. Other specific models are used for the study of the specific etiology of pain. CONCLUSION: Since neuropathic pain is multifactorial, different neuropathic pain animal models were developed throughout the years, which have been critical for the study of neuropathic pain, since much of current knowledge comes from studies with rats and mice. Current animal models need to be further refined and more efforts should be made to determine which animal models may be more predictive, with less biases and more complex and objective analysis parameters.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os modelos ideais deveriam reproduzir apenas déficits sensitivos, como alodínea, hiperalgesia e dor espontânea por curtos períodos de tempo. Existem diversos tipos de modelos animais, que avaliam as diversas etiologias e manifestações da dor neuropática. Alguns modelos estudam os mecanismos periféricos e outros estudam mecanismos centrais da dor neuropática. Esta revisão enfoca os modelos animais mais comumente utilizados para pesquisa em dor neuropática. CONTEÚDO: São descritos modelos animais baseados em ligadura de nervos periféricos que são mais comumente empregados. De todos os modelos descritos nesta revisão, a lesão poupadora de nervo é aquela que produz anormalidades comportamentais mais reprodutíveis, por um período mais longo, ao passo que a constrição crônica do ciático produz sinais comportamentais de neuropatia dolorosas menos previsíveis. Hemisecção espinhal e lesão espinhal induzida por citocinas são os modelos de escolha para estudar mecanismos de dor central. Outros modelos específicos são utilizados para estudo da etiologia específica da condição dolorosa. CONCLUSÃO: Como a dor neuropática é multifatorial, diferentes modelos animais de dor neuropática foram desenvolvidos ao longo dos anos que têm sido fundamentais para o estudo da dor neuropática, uma vez que muito do conhecimento atual provém de estudos em ratos e camundongos. São necessários maiores refinamentos nos modelos animais atualmente empregados e mais esforços para determinar quais modelos animais podem ser mais preditivos, com menos vieses e com parâmetros de análises mais complexos e objetivos.

Effect of intraoperative intravenous lidocaine on pain and plasma interleukin-6 in patients undergoing hysterectomy / Efeito da lidocaína venosa intraoperatória sobre dor e interleucina-6 plasmática em pacientes submetidas a histerectomia / Efecto de la lidocaína venosa intraoperatoria sobre el dolor e interleucina-6 plasmática en pacientes sometidas a histerectomía

BACKGROUND AND OBJECTIVES: Interleukin-6 is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma interleukin-6 after hysterectomy. METHOD: A prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2 mg kg-1 h-1) or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24 h), first analgesic request, and dose of morphine in 24 h were evaluated. Interleukin-6 was measured before starting surgery (T0), 5 h after the start (T5), and 24 h after the end of surgery (T24). RESULTS: There was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0 ± 104.4 min) than in G1 (26.7 ± 23.3 min). There was no difference in supplemental dose of morphine between G1 (23.5 ± 12.6 mg) and G2 (18.7 ± 11.3 mg). There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5 ± 364.1 ng mL-1 in T5 and 30.1 ± 14.2 ng mL-1 in T24. CONCLUSION: Intravenous lidocaine (2 mg kg-1 h-1) did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy. .

JUSTIFICATIVA E OBJETIVOS: A interleucina-6 (IL-6) é preditora de intensidade no trauma. O objetivo deste estudo foi avaliar o efeito da lidocaína por via venosa sobre a intensidade da dor e IL-6 após histerectomia. MÉTODO: O estudo foi prospectivo, randomizado, comparativo e duplo-encoberto em 40 pacientes, entre 18 e 60 anos. Foi administrada lidocaína (2 mg.kg-1.h-1) no G1 ou solução salina a 0,9% no G2 durante a operação. A anestesia foi com O2/isoflurano. Foi avaliada a intensidade da dor (T0: despertar e seis, 12, 18 e 24 horas), a primeira solicitação de analgésico, a dose de morfina nas 24 horas. A IL-6 foi medida antes do início da operação (T0), após cinco horas do início (T5) e 24 horas após o término (T24). RESULTADOS: Não houve diferença na intensidade da dor entre os grupos. Ocorreu diminuição da intensidade da dor entre T0 e os outros momentos avaliados no G1. O tempo para primeira complementação foi maior no G2 (76,0 ± 104,4 min) do que no G1 (26,7 ± 23,3 min). Não houve diferença na dose de morfina complementar entre G1 (23,5 ± 12,6 mg) e G2 (18,7 ± 11,3 mg). Houve aumento das concentrações de IL-6 em ambos os grupos de T0 para T5 e T24. Não houve diferença na dosagem de IL-6 entre os grupos. A concentração de lidocaína foi 856,5 ± 364,1 ng.mL-1 em T5 e 30,1 ± 14,2 ng.mL-1 em T24. CONCLUSÃO: A lidocaína (2 mg.kg-1.h-1) por via venosa não promoveu redução da intensidade da dor e dos níveis plasmáticos de IL-6 em pacientes submetidas a histerectomia abdominal. .

JUSTIFICACIÓN Y OBJETIVOS: La interleucina-6 (IL-6) es predictora de intensidad en el trauma. El objetivo de este estudio fue evaluar el efecto de la lidocaína por vía venosa sobre la intensidad del dolor e IL-6 después de la histerectomía. MÉTODO: El estudio fue prospectivo, aleatorizado, comparativo y doble ciego en 40 pacientes, entre 18 y 60 años. Fue administrada lidocaína (2 mg/kg-1.h-1) en el G1 o solución salina al 0,9% en el G2 durante la operación. La anestesia fue con O2/isoflurano. Se calculó la intensidad del dolor (T0: despertar y 6, 12, 18 y 24 h), la primera solicitud de analgésico, y la dosis de morfina en las primeras 24 h. La IL-6 se midió antes del inicio de la operación (T0), después de 5 h del inicio (T5) y 24 h después de finalizada (T24). RESULTADOS: No hubo diferencia en la intensidad del dolor entre los grupos. Hubo disminución de la intensidad del dolor entre T0 y los otros momentos evaluados en el G1. El tiempo para la primera complementación fue mayor en el G2 (76 ± 104,4 min) que en el G1 (26,7 ± 23,3 min). No hubo diferencia en las dosis de morfina complementaria entre G1 (23,5 ± 12,6 mg) y G2 (18,7 ± 11,3 mg). Hubo aumento en las concentraciones de IL-6 en los 2 grupos de T0 para T5 y T24. No hubo diferencia en la dosificación de IL-6 entre los grupos. La concentración de lidocaína fue 856,5 ± 364,1 ng/ml-1 en T5 y 30,1 ± 14,2 ng/ml-1 en T24. CONCLUSIÓN: La lidocaína (2 mg/kg-1 /h-1) por vía venosa no generó reducción de la intensidad del dolor y de los niveles plasmáticos de IL-6 en pacientes sometidas a histerectomía abdominal. .

[Effect of intraoperative intravenous lidocaine on pain and plasma interleukin-6 in patients undergoing hysterectomy]. / Efeito da lidocaína venosa intraoperatória sobre dor e interleucina-6 plasmática em pacientes submetidas a histerectomia.

BACKGROUND AND OBJECTIVES: Interleukin-6 (IL-6) is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma IL-6 after hysterectomy. METHOD: A prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2mg.kg(-1).h(-1)) or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24hours), first analgesic request, and dose of morphine in 24hours were evaluated. IL-6 was measured before starting surgery (T0), five hours after the start (T5), and 24hours after the end of surgery (T24). RESULTS: There was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0±104.4min) than in G1 (26.7±23.3min). There was no difference in supplemental dose of morphine between G1 (23.5±12.6mg) and G2 (18.7±11.3mg). There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5±364.1 ng.mL(-1) in T5 and 30.1±14.2 ng.mL(-1) in T24. CONCLUSION: Intravenous lidocaine (2mg.kg(-1).h(-1)) did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy.

Randomized evidence for reduction of perioperative mortality.

OBJECTIVE: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. DESIGN AND SETTING: A web-based international consensus conference. PARTICIPANTS: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. INTERVENTIONS: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. MEASUREMENTS AND MAIN RESULTS: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. CONCLUSIONS: Future research and health care funding should be directed toward studying and evaluating these interventions.

O papel do anestesiologista no atendimento do trauma / Anesthesiologist's role in trauma management

O papel do anestesiologista, dentro da equipe de atendimento multiprofissional no trauma, tem aumentado progressivamente nos últimos anos. Esta revisäo aborda o papel do especialista tanto em relaçäo ao atendimento pré quanto intra-hospitalar até a fase de reabilitaçäo do trauma. Métodos de controle da via aérea, reposiçäo volêmica, monitorizaçäo e uso de drogas anestésicas no traumatizado säo discutidos. A analgesia pós-operatória é apresentada como método de reduçäo da morbimortalidade pós-operatória com diminuiçäo dos custos de internaçäo hospitalar

Analgesia, sedaçäo e bloqueio neuromuscular em UTI / Analgesia, sedation and neuromuscular blockade in the ICU

A dor é um sintoma freqüentemente associado ao paciente crítico. O tratamento adequado desta condiçäo está relacionado näo apenas aos processo de humanizaçäo na UTI como também a modificar o prognóstico e reduzir os custos hospitalares. Säo apresentados métodos de avaliaçäo da intensidade da dor e técnicas de tratamento, desenvolvidos pela equipe atuante na UTI. Exposiçäo a um ambiente com grande sobrecarga de estímulos sensitivos, dolorosos, ruído, aspiraçäo traqueal e a privaçäo de sono pode requerer o uso de drogas para controlar a ansiedade e a inquietude. Além disso, algumas situaçöes clínicas, tais como a ventilaçäo mecânica, podem näo dispensar a sedaçäo para lograrem sucesso. A importância e as indicaçöes clínicas do uso de relaxantes musculares säo revistas.