Tracking and considerations on the therapeutic management of neuropathic pain in adult patients with sickle cell disease / Rastreamento e considerações sobre a conduta terapêutica na dor neuropática em pacientes adultos com doença falciforme

ABSTRACT BACKGROUND AND OBJECTIVES: Sickle cell disease is considered the most common hereditary disorder in Brazil. The chronic pain resulting from some complications of sickle cell disease is still poorly understood, inadequately described, and under-researched. This study aimed to characterize chronic pain in individuals with sickle cell disease, evaluate its treatment, and discuss the importance of studying it as a distinct pathology. METHODS: A cross-sectional study based on comparative analysis between two associations of sickle cell disease patients, one in Brazil and the other in France. The Pain Detect Questionnaire was used to assess neuropathic pain, and Odds Ratio was used to evaluate the strength of the association between opioid use and the recurrence of chronic painful crises. RESULTS: In Brazil, the Pain Detect questionnaire revealed that 55% of patients had a probable neuropathic component, 23% negative, and 22% uncertain. In France, the application resulted in 51% for probable presence, 29% for negative, and 20% for uncertain. All patients reported constant pain. As for the frequent use of opioids, the results were 62% in Brazil and 32% in France. The Odds Ratio calculation results were: OR 15.14 (95% CI = 4.777- 41.4, p < 0.0001) in Brazil; and OR 7.5 (95% CI = 2.121- 25.74, p = 0.0013) in France. CONCLUSION: While it is commonly believed that pain in sickle cell disease is primarily related to somatic and visceral tissue damage after vaso-occlusive events, this study indicated emerging evidence of neuropathic processes involved. Thus, there should be a significant concern about the management of chronic pain and particularly opioid dependence in Brazil.

RESUMO JUSTIFICATIVA E OBJETIVOS: Dentre as alterações hereditárias, a doença falciforme é considerada a mais comum no Brasil. A dor crônica decorrente de suas complicações ainda é mal compreendida, inadequadamente descrita e pouco pesquisada. O presente estudo teve como finalidade caracterizar a dor crônica em indivíduos com doença falciforme, avaliar o seu tratamento e discutir a importância de seu estudo como uma doença em si. METODOS: Estudo transversal, baseado na análise comparativa entre duas associações de indivíduos acometidos pela doença falciforme, com sede no Brasil e na França. Foi aplicado o questionário Pain Detect para avaliação da dor neuropática e a Odds Ratio para avaliar a intensidade de associação entre o uso de opioides e a recorrência de crises álgicas de cunho crônico. RESULTADOS: O questionário Pain Detect apontou que no Brasil 55% de pacientes da doença calciforme apresentam componente neuropático provável, 23% negativo e 22% incerto. Na França, os resultaram foram de 51% para componente provável, 29% negativo e 20% incerto. Dos acometidos pela doença, 100% relataram dores constantes, sendo que fizeram uso frequente de opioides 62% no Brasil e 32% na França. O cálculo do Odds Ratio apontou os seguintes resultados: OR 15,14 (IC 95% = 4,777- 41,4, p < 0,0001) no Brasil; e OR 7,5 (IC 95% = 2,121- 25,74, p = 0,0013) na França. CONCLUSÃO: Embora haja uma crença de que a dor na doença falciforme seja primariamente relacionada à lesão tecidual a nível somático e visceral após os eventos vasoclusivos, o estudo apontou evidências emergentes de processos neuropáticos envolvidos. Assim, deve haver uma preocupação quanto ao manejo da dor crônica e em especial à dependência química pelos opioides no Brasil.

The brief measure of preoperative emotional stress screens preoperative maladaptive psychological features and predicts postoperative opioid use: an observational study

Abstract Background: The Brief Measure of Preoperative Emotional Stress (B-MEPS) is a suitable screening tool for Preoperative Emotional Stress (PES). However, personalized decision-making demands practical interpretation of the refined version of B-MEPS. Thus, we propose and validate cut-off points on the B-MEPS to classify PES. Also, we assessed if the cut-off points screened preoperative maladaptive psychological features and predicted postoperative opioid use. Methods: This observational study comprises samples of two other primary studies, with 1009 and 233 individuals, respectively. The latent class analysis derived emotional stress subgroups using B-MEPS items. We compared membership with the B-MEPS score through the Youden index. Concurrent criterion validity of the cut-off points was performed with the severity of preoperative depressive symptoms, pain catastrophizing, central sensitization, and sleep quality. Predictive criterion validity was performed with opioid use after surgery. Results: We chose a model with three classes labeled mild, moderate, and severe. The Youden index points −0.1663 and 0.7614 of the B-MEPS score classify individuals, in the severe class, with a sensitivity of 85.7% (80.1%-90.3%) and specificity of 93.5% (91.5-95.1%). The cut-off points of the B-MEPS score have satisfactory concurrent and predictive criterion validity. Conclusions: These findings showed that the preoperative emotional stress index on the B-MEPS offers suitable sensitivity and specificity for discriminating the severity of preoperative psychological stress. They provide a simple tool to identify patients prone to severe PES related to maladaptive psychological features, which might influence the perception of pain and analgesic opioid use in the postoperative period.

Brazilian version of the Pasero Opioid-Induced Sedation Scale: cross-cultural adaptation study / Versión brasileña de la escala Pasero Opioid-Induced Sedation Scale: estudio de adaptación transcultural / Versão brasileira da Pasero Opioid-Induced Sedation Scale: estudo de adaptação transcultural

ABSTRACT Objective: Perform a cross-cultural adaptation of the Pasero Opioid-induced Sedation Scale to the Brazilian setting. Method: This is a methodological study using Beaton's framework, which consists in six stages: translation, synthesis of translations, re-translation, expert committee, pre-test, and sending the adapted version of the instrument to the author of the original. The study was carried out from April to December 2021. The research was conducted in a private hospitalin the city of São Paulo, in the adult hospitalization and critical care units. It was approved by the research ethics committee. Results: After translation, translation synthesis and back-translation steps, the version was evaluated by the expert committee, requiring two rounds to obtain acceptable CVI values above 0.80. In the pre-test phase, the scale was well understood, with a CVI of 0.98. Conclusion: The scale was adapted for the Brazilian context; however, further studies will be needed to analyze validity and reliability evidence.

RESUMEN Objetivo: Realizar la adaptación transcultural de la escala de Pasero Opioid-induced Sedation Scale para el contexto brasileño. Método: Estudio metodológico, utilizando el marco de referencia de Beaton, que consta de seis fases: traducción, síntesis de traducciones, traducción inversa, comité de expertos, prueba previa, y envío del instrumento adaptado ala autora del instrumento original. El estudio se realizó de abril a diciembre de 2021, y a la investigación se condujo en un hospital privado, ubicado en la ciudad de São Paulo, en las unidades de hospitalización de adultos y cuidados críticos. Recibió la aprobación del comité de ética. Resultados: Después de las etapas de traducción, síntesis de traducción y traducción inversa, la versión fue evaluada por un comité de expertos, con dos rondas para obtener valores aceptables de índice de validez de contenido superiores a 0,80. En la fase previa a la prueba, la escala mostró una buena comprensión, con una puntuación de 0,98. Conclusión: La escala fue adaptada para el contexto brasileño, sin embargo, serán necesarios más estudios para analizar las evidencias de validez y confiabilidad.

RESUMO Objetivo: Realizar adaptação transcultural da escala Pasero Opioid-Induced Sedation para o cenário brasileiro. Método: Estudo metodológico, utilizado referencial de Beaton, composto por seis fases: tradução, síntese das traduções, retradução, comitê de especialistas, pré-teste e envio dos instrumentos adaptados ao autor do instrumento original. Estudo foi realizado de abril a dezembro de 2021. A pesquisa desenvolveu-se em um hospital privado, localizado no município de São Paulo, nas unidades de internação e críticas adultos. Recebeu aprovação do comitê de ética. Resultados: Após as etapas de tradução, síntese de tradução e retrotradução a versão foi avaliada pelo comitê de especialistas, com duas rodadas para obtenção de valores aceitáveis de índice de validade de conteúdo acima de 0,80. Na fase de pré-teste a escala apresentou boa compreensão com score de 0,98. Conclusão: A escala foi adaptada para o contexto brasileiro, no entanto, novos estudos serão necessários para análises de evidências de validade e confiabilidade.

The regulatory effect of morphine postconditioning in left stellate ganglion on remodeling after myocardial infarction / 中国药理学通报

Aim To investigate the regulatory effect of morphine postconditioning in the LSG on remodeling after myocardial infarction. Methods SD rats were randomly divided into four groups: sham operation group (Sham), myocardial infarction group (MI), myocardial infarction + saline group (Control) and myocardial infarction + morphine postconditioning group (MI + Morphine) . The rat MI model was constructed by ligating the left anterior descending coronary artery, and then morphine was given to the LSG by percutaneous posterior approach. After four weeks, the changes of cardiac function in rats were detected by ultrasound. Masson staining was used to detect fibrosis changes; the expression of Collagen I and Collagen III protein was detected by Western blot. The mRNA expression of ANP and BNP was detected by RT-qPCR. The expression of JJLOR in LSG was detected by immunofluorescence. The concentration of catecholamine in plasma and myocardial tissue was detected by ELISA. Results Compared with the sham group, the cardiac function of the MI group was significantly impaired, the myocardial tissue showed significant fibrosis changes, and the concentration of catecholamine in plasma and myocardial tissue significantly increased. Compared with the control group, the MI + Morphine group reduced myocardial fibrosis collagen deposition in rats after MI, inhibited the expression of ANP and BNP in myocardial tissue, reduced the concentration of catecholamine, and improved the cardiac function of MI rats. Immunofluorescence results showed that JJLOR was expressed in LSG after MI and increased after morphine postconditioning. Conclusions This study shows that morphine postconditioning in the LSG has a protective effect on myocardial remodeling after myocardial infarction. The mechanism may be related to the activation of JJLOR in the LSG by morphine and the reduction of catecholamine release from sympathetic nerve endings.

Mioclonías positivas y negativas en paciente con enfermedad renal crónica / Positive and negative myoclonus in a patient with end stage renal disease

Introducción: Las mioclonías son contracciones musculares paroxísticas de corta duración o pérdida abrupta del tono muscular, denominadas mioclonías positivas y negativas, respectivamente. Se presenta un caso clínico de mioclonías positivas y negativas generalizadas y se pretende describir los múltiples mecanismos fisiopatológicos y etiologías que lo desencadenan. Presentación del caso: Hombre de 35 años, con diabetes mellitus tipo 1 complicada con enfermedad renal diabética en hemodiálisis, desarrolló una bacteriemia asociada a catéter por Staphylococcus aureus y presentó mioclonías positivas y negativas. Se identificaron como posibles desencadenantes la uremia, la infección y los fármacos con potencial promioclónico; el hallazgo incidental de una lesión isquémica en núcleo caudado no explicaba la semiología encontrada en el paciente. Se hizo el control y retiro de todos los factores promioclónicos enunciados, junto a manejo farmacológico con levetiracetam, y con ello se logró el control de los síntomas. Discusión: Los pacientes con enfermedad renal crónica son susceptibles a la acumulación de productos tóxicos de tipo guanidinas, que tienen potencial para producir mioclonías. Además, las infecciones, el uso de fármacos con potencial promioclónico y lesiones estructurales como las isquemias corticales son etiologías que deben considerarse en el diagnóstico diferencial. El mayor impacto en los síntomas se observa con el control del factor desencadenante, y, en caso de persistir, la terapia farmacológica proporciona buenos resultados. Conclusión: Las mioclonías son trastornos del movimiento relativamente comunes en la enfermedad renal crónica. La identificación del desencadenante es crucial para su manejo junto al uso de fármacos con actividad antimioclónica.

Introduction: Myoclonus are paroxysmal muscle contractions of short duration or abrupt loss of muscle tone, called positive and negative myoclonus respectively. A clinical case of generalized positive and negative myoclonus is presented and the aim is to describe the multiple pathophysiological mechanisms and etiologies that trigger it. Case presentation: A 35-year-old man with type 1 diabetes mellitus complicated by diabetic kidney disease on hemodialysis developed catheter-associated bacteremia due to Staphylococcus aureus and presented positive and negative myoclonus. Uremia, infection, and drugs with pro-myoclonic potential were identified as possible triggers; The incidental finding of an ischemic lesion in the caudate nucleus did not explain the semiology found in the patient. The control and removal of all the pro-myoclonic factors mentioned was carried out, along with pharmacological management with levetiracetam, thus achieving control of the symptoms. Discussion: Patients with chronic kidney disease are susceptible to the accumulation of guanidine-type toxic products, which have the potential to produce myoclonus. Furthermore, infections, the use of drugs with pro-myoclonic potential and structural lesions such as cortical ischemia are etiologies that should be considered in the differential diagnosis. The greatest impact on symptoms is observed with the control of the triggering factor and if it persists, pharmacological therapy provides good results. Conclusion: Myoclonus are relatively common movement disorders in chronic kidney disease. Identification of the trigger is crucial for its management along with the use of drugs with anti-myoclonic activity.

Postoperative analgesic efficacy of nefopam after anorectal surgery: a retrospective observational study

Objective: To examine the effectiveness of nefopam on postoperative pain control after anorectal surgeries. Methods: We retrospectively reviewed the electronic medical records of patients who underwent anorectal surgeries from January 2019 to March 2022 at two medical centers. The data were divided into nefopam and conventional groups. The primary outcome was the number of patients who requested additional opioids in the 24-h postoperative period. The secondary outcomes were numeric rating pain scores (NRPS) within a 24-h postoperative period and analgesic drugs-related side effects. Results: Eighty-seven patients in the conventional group and 60 in the nefopam group were recruited. The nefopam group reported less additional opioid consumption than the conventional group in all dimensions of analysis, including overall, adjusted to anesthetic techniques and types of surgery. However, these did not reach statistical significance (P = 0.093). Only patients in the nefopam group who underwent hemorrhoidectomy under TIVA or spinal anesthesia significantly required fewer additional opioids (P = 0.016, 60% mean difference). Similarly, the 24-h postoperative morphine consumption was lower in the nefopam group (mean difference = -3.4, 95%CI: 0.72,6.08). Furthermore, significantly lower NRPS were reported in the nefopam group during the 12-18 h postoperative period (P = 0.009). On the other hand, analgesic drugs related side effects were similar in both groups. Conclusions: The administration of nefopam after major anorectal surgery is beneficially evident in reducing postoperative opioid requirements. (AU)

Effects of cannabinoids on pain control, quality of life and opioid-sparing in cancer patients: systematic review / Utilização de canabinoides no controle da dor, na qualidade de vida e no efeito poupador de opioides em pacientes com câncer: revisão sistemática

ABSTRACT BACKGROUND AND OBJECTIVES: Cannabinoids, such as delta-9-tetrahydrocannabinol and cannabidiol, have several therapeutic properties that may be useful in medicine. The objective of this study was to analyze the impact of cannabinoid use on pain control, quality of life and opioid-sparing in patients with advanced cancer. CONTENTS: A systematic review of the evidence for the use of cannabinoids in patients with advanced cancer was conducted on 1) Pain control; 2) Quality of life; and 3) Opioid-sparing effect. PubMed, Web of Science and Cochrane databases were searched for articles, written in English, published between January 1, 2011, and December 31, 2022, with the filters "randomized controlled trials" and "clinical trials". Using oral formulations of cannabinoids was accepted as "intervention" and placebo as "control". Risk of bias analysis was performed with Cochrane's RoB 2 and ROBINS-I tools. This review followed the 2020 PRISMA- statement. Ten studies were included, with 1169 participants, most with moderate risk of bias. The studies were from Australia (n=4), Canada (n=1), Israel (n=1), Mexico (n=1), The United Kingdom (n=1); two were multinationals. Eight were randomized, placebo-controlled trials; two were non-randomized studies. The most used formulation was nabiximols oral spray. Cannabinoids provide a clinical improvement in pain control. Evidence of improved quality of life with cannabinoids is inconclusive. Cannabinoids do not affect the daily dose of opioids in refractory cancer pain. Cannabinoid use cannot be said to have an opioid-sparing effect. CONCLUSION: It is necessary to expand research on the prescription of cannabinoids in individuals with cancer and other progressive diseases, with several comorbidities and multiple medications, in different health contexts.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os canabinoides, como o delta-9-tetrahidrocanabinol e o canabidiol, possuem propriedades terapêuticas que podem ser úteis em pacientes oncológicos. O objetivo deste estudo foi avaliar o impacto do uso de canabinoides no controle da dor, na melhoria da qualidade de vida, e no efeito poupador de opioides em pacientes com câncer avançado. CONTEÚDO: Realizou-se uma revisão sistemática sobre a evidência da utilização de canabinoides em pacientes com câncer avançado, relativamente a: 1) Controle da dor; 2) Qualidade de vida; e 3) Efeito poupador de opioides. Foram buscados artigos na Pubmed, Web of Science e Cochrane, em inglês, publicados entre 2011 e 2022, com os filtros "randomized controlled trials" e "clinical trials". Aceitaram-se como "intervenção" qualquer uso de formulações orais de canabinoides e como "controle" o uso de placebo. Fez-se análise de viés com as ferramentas da Cochrane RoB 2 e ROBINS-I. Seguiu-se a Declaração PRISMA 2020. Foram incluídos 10 estudos, com 1169 participantes, a maioria com risco moderado de viés. Os estudos provinham de Austrália (n=4), Canadá (n=1), Israel (n=1), México (n=1), Reino Unido (n=1); dois eram multinacionais. Oito eram ensaios randomizados controlados com placebo; dois eram não randomizados. A formulação mais usada foi spray bucal de nabiximóis. Os canabinoides proporcionam uma melhoria clínica do controle da dor. A evidência da melhoria da qualidade de vida com canabinoides é inconclusiva. Os canabinoides não afetam a dose diária de opioides na dor oncológica refratária. Não se pode afirmar que o uso de canabinoides tem um efeito poupador de opioides. CONCLUSÃO: É necessário incrementar a investigação sobre a prescrição de canabinoides em indivíduos com câncer e outras doenças progressivas, com comorbilidades e polimedicação, em diferentes contextos de saúde.

A Follow up Study Among Patients on Opioid Substitution Therapy (OST) in Terms of Relapse Rate, Factors Affecting Relapse Rate and HCV Incidence

Background: Many countries are facing a serious problem with opioid dependence. Opioid Substitution Therapy (OST) is prescribed to dependent opioid users to diminish the use and effects of illicitly acquired opioids. The high relapse rate has been affecting the effectiveness of anti-drug work all over the world.Material & Methods:In this study, 200 patients were taken by simple random sampling technique. 100 patient on Buprenorphine substitution therapy and 100 on Methadone maintenance treatment were studied. Patients diagnosed as cases of Opioid dependence as per ICD-10 were selected within the first 3 months and followed up to 1 year at 3, 6 and 9 months. The study was conducted after approval from the institutional ethics and thesis committee. A 14-item questionnaire based on a four-point scale describing the number of times certain events had occurred in the previous week for relapse was used to find factors affecting relapse.Results:The relapse rate among patients in the BPN group at 3, 6 and 9 months relapse was 29.33%, 20.34% and 19.51% while in the Methadone group, it was 24.05%, 15.87% and 12% respectively. The overall HCV Incidence was 75% among patients on Opioid Substitution Therapy. Conclusion:The findings of the study highlight the role of multiple determinants in opioid dependence and relapse. The obtained results showed that HCV infection was an alarming problem among IV opiate drug users in Punjab.

Urinary retention after lipoabdominoplasty: case report / Retenção urinária após lipoabdominoplastia: relato de caso

Introduction: Postoperative urinary retention may predispose to permanent bladder damage. Risk factors include type of anesthesia, type of surgery, and use of anticholinergics, analgesics, and opioids. Once the lesion is established, complementary urodynamic tests are essential for etiological diagnosis and treatment. The objective of this study is to report a case of a patient with urinary retention in the postoperative period of lipoabdominoplasty. Case Report: 27-year-old female patient, without comorbidities or use of continuous medication. She underwent lipoabdominoplasty and evolved postoperatively with urinary retention and bladder distention, diagnosed as detrusor contractility and sensitivity deficit in the urodynamic study. She was maintained in outpatient follow-up with the surgical team and Urology, with a progressive reduction in urinary catheter use and complete removal in eight months of follow-up. Discussion: The objective of aesthetic plastic surgery is to improve the physical appearance of the body. It is subject to complications like other surgical procedures, and pain seems to be the most frequent. Urinary retention may be secondary to the use of opioids, and its diagnosis in the postoperative period of lipoabdominoplasty still has some obstacles. Plication of the rectus muscle diastasis, liposuction, and the use of a compressive abdominal belt make it difficult to identify a possible bladder distention. An episode of bladder overdistention can result in significant morbidity. Conclusion: The present report demonstrated the good evolution of a patient who developed urinary retention in the postoperative period of lipoabdominoplasty. The main diagnostic hypothesis was that it was secondary to the use of opioids.

Introdução: A retenção urinária pós-operatória pode predispor a danos permanentes à bexiga. Os fatores de risco incluem tipo de anestesia, tipo de cirurgia e uso anticolinérgicos, analgésicos e opioides. Uma vez que a lesão está estabelecida, os exames complementares urodinâmicos são fundamentais para diagnóstico etiológico e tratamento. O objetivo deste trabalho é relatar caso de paciente com quadro de retenção urinária no pós-operatório de lipoabdominoplastia. Relato de Caso: Paciente de 27 anos, sexo feminino, sem comorbidades ou uso de medicamentos contínuos. Foi submetida a lipoabdominoplastia, e evoluiu no pós-operatório com quadro de retenção urinária e bexigoma, diagnosticada como acontratilidade detrusora e déficit de sensibilidade no estudo urodinâmico. Manteve acompanhamento ambulatorial com a equipe cirúrgica e a Urologia, com redução progressiva do uso do cateter vesical e retirada completa em oito meses de seguimento. Discussão: O objetivo da cirurgia plástica estética é melhorar o aspecto físico do corpo. Como os demais procedimentos cirúrgicos, está sujeita a complicações e a dor parece ser a mais frequente. A retenção urinária pode ser secundária ao uso de opioides e seu diagnóstico no pós-operatório da lipoabdominoplastia ainda possui alguns obstáculos. A plicatura da diástase do músculo reto, a lipoaspiração e o uso de cinta abdominal compressiva dificultam a identificação do possível bexigoma. Um episódio de hiperdistensão da bexiga pode resultar em morbidade significativa. Conclusão: O presente relato demonstrou boa evolução de paciente que desenvolveu retenção urinária no pós-operatório de lipoabdominoplastia. A principal hipótese diagnóstica foi de ser secundária ao uso de opioide.

Relationship between optical coherence tomography findings and clinical variables in patients with opiate use disorder / Relação entre os achados da tomografia de coerência óptica e as variáveis clínicas em pacientes com transtorno por uso de opiáceos

ABSTRACT Purpose: This study aimed to examine optical coherence tomography findings in patients with opiate use disorder by comparing them with healthy controls. Methods: The study included 30 opiate use disorder patients and 30 controls. The participants' detailed biomicroscopic examinations, visual acuity, intraocular pressure, and both eye examinations were evaluated. A total of 120 eyes were evaluated using optical coherence tomography, measuring the central macular thickness, mean macular thickness, mean macular volume and retinal nerve fiber layer thickness. Moreover, all participants filled in the demographic data form and Barratt Impulsiveness Scale. Results: Upon examination of the optical coherence tomography findings, central macular thickness, mean macular thickness, and mean macular volume were thinner in both eyes in patients with opiate use disorder (p<0.01 in all measurements in both eyes). Similarly, the total values of the superior quadrant and retinal nerve fiber layer thickness were statistically significant in both eyes compared to that in the control group (p=0.007, p=0.002; p=0.049, p=0.007, in the right and left eyes, respectively). Only the left eye was positively correlated with retinal nerve fiber layer superior quadrant measurement and hospitalization (r=0.380, p=0.039). Conclusion: Our results revealed that the patients' central macular thickness, mean macular thickness, and mean macular volume values were thinner. Increase in the retinal nerve fiber layer thickness superior quadrant thickness and total value was also observed. Further studies with larger sampling groups that evaluate neuroimaging findings should be conducted.

RESUMO Objetivo: O objetivo foi investigar foi, os achados da tomografia de coerência óptica em pacientes com transtorno do uso de opiáceos, comparando-os com controles saudáveis. Métodos: O estudo incluiu 30 pacientes com transtorno do uso de opiáceos e 30 controles. Os exames biomicroscópicos detalhados de todos os participantes, acuidade visual, pressão intraocular e ambos os exames oculares foram avaliados com tomografia de coerência óptica. Um total de 120 olhos foram avaliados usando tomografia de coerência óptica, e a espessura macular central, espessura macular média, volume macular médio e a espessura da camada de fibra nervosa da retina dos participantes foram medidos. Além disso, todos os participantes preencheram o Formulário de Dados Demográficos e a Escala de Impulsividade Barratt (BIS-11). Resultados: Quando os achados de tomografia de coerência óptica foram examinados, espessura macular central, espessura macular média e volume macular médio eram mais finos de acordo com controles saudáveis em ambos os olhos em pacientes com transtorno do uso de opiáceos (p<0,01 em todas as medições em ambos os olhos). Da mesma forma, os valores totais do quadrante superior e espessura da camada de fibra nervosa da retina estavam mais em níveis estatisticamente significativos em ambos os olhos em comparação com o grupo controle (p=0,007, p=0,002; p=0,049, p=0,007, no olho direito e esquerdo, respectivamente). Estar internado em hospital e apenas a medida do quadrante superior da espessura da camada de fibra nervosa da retina do olho esquerdo associou-se positivamente (r=0,380, p=0,039). Conclusão: Em nossos resultados, descobrimos que os valores de espessura macular central, espessura macular média e volume macular médio dos pacientes eram mais finos. Verificamos também espessamento no quadrante superior e valor total da espessura da camada de fibra nervosa da retina. Nosso estudo deve ser apoiado por novos estudos com grupos de amostragem maiores, nos quais os achados de neuroimagem são avaliados.

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

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

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

Association of opioid use disorder with outcomes of hospitalizations for acute myocardial infarction in the United States

Abstract Objective While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. Methods All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. Results Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. Conclusions Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization.

Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown

Background: Temporary shelters were established for street-based people during the national level 5 coronavirus disease 2019 (COVID-19) lockdown. However, street-based substance users' need to access substances was not addressed, resulting in large numbers of people experiencing withdrawal. The Community Oriented Substance Use Programme (COSUP) in Tshwane provided methadone to manage opioid withdrawal. Methods: A cross-sectional, descriptive study was conducted using the daily methadone dosing records from shelters in Tshwane between March 2020 and September 2020. Results: The final analysis included 495 participants, of which 64 (12.9%) were initiated on 20 mg ­ 30 mg of methadone, 397 (80.2%) on 40 mg ­ 50 mg, and 34 (6.9%) on 60 mg ­ 70 mg. A total of 194 (39.2%) participants continued their initiation dose for 1­2 months, after which 126 (64.9%) had their doses increased, and 68 (35.1%) had their doses decreased. Approximately 12 (2.4%) participants were weaned off methadone after 1­3 months and 46 (9.3%) after 4­6 months. In all, 100 (20.2%) participants left the shelter prematurely and did not continue with methadone. A total of 126 (25.5%) participants continued to stay in the shelters and received methadone for 6 months, with 125 (25.3%) participants leaving the shelter with continued follow-up at a COSUP site. Conclusion: This study demonstrates variability in methadone dosing regimens among shelter residents. As the lockdown measures eased, many chose to leave the shelters, while others remained to receive methadone and other services. The COSUP appears to be effective during periods of increased vulnerability, since a large number of participants were successfully followed up. Contribution: Opioid dependence is a persistent, lifelong disease. It is multifaceted with complex environmental and individual determinants. This study highlighted the use of opioid substitution therapy during a period of increased vulnerability.

Effect of opioid-sparing analgesia on incidence of sepsis in severely burned patients: a retrospective cohort study / 中华麻醉学杂志

Objective:To evaluate the effects of opioid-sparing analgesia on the incidence of sepsis in severely burned patients in the retrospective cohort study.Methods:The clinical data from patients with severe burns admitted to three teaching hospitals in Guangdong from 2011 to 2020 were retrospectively extracted and analyzed. The patients were divided into 2 groups based on the analgesic regimen within 30 days after injury: continuous opioids analgesia group (continuous opioid infusion at a relative constant rate for more than 72 h) and opioid-sparing analgesia group (patient-controlled intravenous analgesia/intermittent administration/opioid-free analgesia). Patient′s age, severity of burn, inhalation injury and basal pain score at rest were matched by the propensity score at a 1∶1 ratio. The primary outcome measure was the occurrence of sepsis within 90 days of admission. Secondary outcome measures included 30-day and 90-day all-cause mortality, clinical diagnosis of multiple organ dysfunction syndrome, and prevalence of burn wound infection. The amount of opioid used was also recorded.Results:A total of 328 severely burned patients were finally enrolled, with 145 patients in continuous opioid analgesia group and 183 patients in opioid-sparing analgesia group, and 110 pairs of patients (220 cases) were finally matched by the propensity score.Compared with continuous opioid analgesia group, the total consumption of opioid, daily consumption per analgesia, and consumption per burn area were significantly decreased, and the incidence of sepsis and wound infection was decreased( P<0.05), and no significant change was found in the incidence of multiple organ dysfunction syndrome, 30-day and 90-day all-cause mortality in opioid-sparing analgesia group( P>0.05). Conclusions:Compared with the continuous opioid analgesia regimen, opioid-sparing analgesia can reduce the risk of sepsis in severely burned patients.

Application of multimodal low opioid combined with saphenous nerve block analgesia in elderly patients undergoing knee arthroplasty / 中华老年医学杂志

Objective:To investigate the clinical application of multimodal low-opioid combined with saphenous nerve block analgesia in elderly patients undergoing knee arthroplasty.Methods:This study is a randomized controlled study.A total of 60 elderly patients who underwent elective knee arthroplasty in the Department of Orthopedics, the First Hospital of Shanxi Medical University from January 2021 to December 2021 were selected and divided into 2 groups by numerical randomization: mode low opioid analgesia regimen group(observation group)and traditional analgesia regimen group(control group), 30 cases in each group.Observation group: (1)Preemptive analgesia: Oral celecoxib 200 mg, qd.from 3 days before surgery, the mini-mental state examination(MMSE)score was used to evaluate the cognitive function; (2)Intraoperative analgesia: After the prosthesis was installed, choose to inject analgesics around the knee joint(ropivacaine 200 mg, morphine 5 mg, epinephrine 0.25 mg, dexamethasone 5 mg/100 ml normal saline, also known as "cocktail" solution); (3)Postoperative analgesia: After the operation, continuous saphenous nerve block(0.2% ropivacaine, 2 ml/h)was performed under ultrasound guidance, and the dose of nerve block was adjusted according to the degree of rehabilitation training.Control group: no special treatment before and during the operation, traditional postoperative patient-controlled intravenous analgesia(PCIA)was used after the operation, the formula WAs as follows: sufentanil(2 μg/kg)+ flurbiprofen axetil(200-300 mg)+ Tropisetron(5-10 mg). The numerical rating scale(NRS)scores were observed and recorded 1 day before surgery, 6, 12, 24, and 48 hours after surgery; the time of the first active straight leg raising after surgery, the time of landing; the range of motion(ROM)of the knee joint 3, 7, and 14 days after surgery; the American Hospital for Special Surgery Knee Score(HSS)at 14 days, 1, 3, and 6 months after surgery; serum substance P(SP)and interleukin-6(IL-6)concentrations 1 day before surgery and 48 hours after surgery, and adverse events were recorded.Results:Compared with the control group, the patients in the observation group had lower NRS scores at 6, 12, 24, and 48 hours after the operation( t=27.705, 27.532, 21.739, 25.780, all P<0.05); the first active straight leg raising time and the time of landing earlier after the operation, and the knee joint at 3, 7, and 14 days after the operation, the range of motion(ROM)was better( t=35.496, 43.716, 3.766, 5.216, 6.009, all P<0.05). And the American hospital for special surgery knee score(HSS)was higher at 14 days, 1 month, and 3 months after surgery( t=19.247, 32.337, 22.651, all P<0.05), but there was no significant difference at 6 months after surgery.Simultaneously, the serum SP and IL-6 concentrations in the observation group 48 h after the operation were (431.0±11.3)ng/L and(11.9±2.7)ng/L, respectively.Compared with the control group(442.5±15.6)ng/L, (14.4±2.9)ng/L( t=5.362, 4.144, both P<0.05). Compared with the control group, which were lower than those in the incidence of postoperative nausea and vomiting was lower, the length of hospital stay was shorter in the observation group( χ2=4.630, t=3.311, P=0.031, 0.002), and the other indicators had no statistical differences(all P>0.05). Conclusions:Multimodal low-opioid combined with saphenous nerve block analgesia can significantly reduce perioperative pain in elderly patients undergoing knee arthroplasty, improve early postoperative mobility, and speed up postoperative functional recovery.

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

A Case of Withdrawal Syndrome after Opioid Discontinuation Following Pain Relief of Bone Metastases

Introduction: In patients receiving opioids, relief of cancer pain by palliative radiation therapy or other means can lead to opioid discontinuation and subsequent withdrawal symptoms, such as agitation, insomnia, and diarrhea, due to opioid-related physical dependence. Appropriate steps should be taken to prevent these symptoms. Case: A 72-year-old man underwent surgery for esophageal cancer. He developed low back pain and right lower limb pain, and was diagnosed with sacral and right iliac bone metastases. His pain was resistant to oxycodone (OXC), so he was simultaneously treated with methadone (MDN) and palliative radiotherapy. His pain gradually decreased, and MDN was tapered and switched to OXC, which was in turn discontinued at 20 mg/day at the patient's strong request. After OXC discontinuation, akathisia, anxiety, and diarrhea appeared as withdrawal symptoms. These were treated with immediate-release OXC, transdermal fentanyl, and suvorexant. Discussion: When discontinuing opioids, dose reduction below 10% per week is recommended, de-escalation to the lowest possible dose should be followed by cessation. In case of withdrawal symptoms, immediate-release opioids may be used, and opioid tapering should be attempted in parallel with symptom control.

Refractory Diarrhea Associated with Carcinoid Syndrome Improved after Opioid Switching from Fentanyl to Morphine

Background: In the case of refractory diarrhea that cannot be treated with loperamide only, drugs such as octreotide and serotonin receptor antagonists are generally recommended. We have reported a case of refractory diarrhea associated with carcinoid syndrome in which symptoms improved only with opioid switching, without octreotide. Case: We experienced a case of a 28-year-old female with cervical cancer. She was diagnosed with recurrence after cervical cancer surgery and presented with pain and diarrhea. Her diarrhea did not improve sufficiently after taking loperamide. She was admitted to the palliative care hospital for symptom control due to persistent diarrhea and right lower extremity pain associated with bone metastasis. We diagnosed the cause of her diarrhea as carcinoid syndrome by some laboratory examination. For pain management, we switched opioids from transdermal fentanyl to continuous subcutaneous infusion of morphine. It resulted in pain relief and improvement in the frequency of diarrhea, and she was able to be discharged home. Conclusion: In cases of refractory diarrhea and in patients who need opioids, there is one option to use morphine. If it is effective, it may simply resolve both pain and diarrhea and reduce the use of multiple medications.

Research progress on analgesic effect and adverse drug reactions of opioid receptor agonist-antagonists / 中国药房

Opioid receptor agonist-antagonists are a class of drugs which have both agonistic and antagonistic effects on opioid receptors. These drugs already on the market mainly include pentazocine， butorphanol， nalbuphine， buprenorphine， dezocine and so on. Compared with pure opioid receptor agonists such as morphine and fentanyl， these drugs have strong analgesic effects， less addictive， and less side effects such as cough， itching and respiratory depression. Due to the different tendentious effects of opioid receptor agonists-antagonists among different endogenous opioid receptors （μ， κ， δ， etc.）， different receptors of subtypes can exhibit different or even opposite effects in terms of affecting emotions and drug dependence. Therefore， the rational use of these drugs can effectively reduce the occurrence of adverse reactions and drug abuse caused by opioid drugs. With the deepening of research on various endogenous opioid receptor subtypes and related drugs in the academic community， opioid receptor agonists- antagonists have broad application space and prospects in improving adverse reactions to opioid drugs and enhancing patient drug compliance.