Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial

Abstract Background Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. Objective We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. Methods Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5 mg.kg-1 bolus then 0.12 mg.kg-1.h-1 infusion for the first 24 hours postoperatively. Group KM: received ketamine 0.5 mg.kg-1 and Mg sulfate 50 mg.kg-1, then ketamine 0.12 mg.kg-1.h-1 and Mg sulfate 8 mg.kg-1.h-1 infusions for the first 24 hours postoperative. The primary outcome was the morphine consumption in the first 24 hours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. Results Group KM had less postoperative opioid consumption (14.12 ± 5.11 mg) than Group K (19.43 ± 6.8 mg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. Conclusion Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.

Manejo del dolor posoperatorio en pacientes beneficiarios de una artroplastia total de rodilla: comparación de tres técnicas analgésica / Postoperative pail management in patients underfgoing total knee arthroplaty: comparison of three analgesic techniques

Introducción: La artroplastia total de rodilla (ATR) es un procedimiento quirúrgico muy doloroso en cirugía ortopédica, siendo muy difícil su tratamiento. El objetivo del presente estudio fue comparar 3 estrategias de analgesia post operatoria en el manejo del dolor post ATR. Pacientes y Método: se estudiaron 60 pacientes, divididos en 3 grupos. Grupo 1: Bloqueo iliofascial (BIFC), Grupo 2: Analgesia epidural continua (AEPIC) y Grupo 3: Morfina intratecal (MIT). Se evaluó el dolor post operatorio (DPO) en reposo y movimiento con escala visual análoga en las primeras 24 hrs., consumo de morfina endovenosa (MEV), incidencia de efectos adversos: prurito, náuseas y vómitos (NVPO), retención urinaria (RU). Al término del tratamiento se evaluó la satisfacción del paciente. Resultados: El DPO fue significativamente menor entre las 6 y 24 hrs. en los pacientes del Grupo 3 versus los de los Grupos 1 y 2 (p<0,01). El consumo de MEV fue menor en los pacientes del grupo 3 (p< 0,01). La incidencia de prurito post operatorio y RU fue significativamente mayor en el grupo 3 versus los grupos 1 y 2 (p< 0, 001 y p< 0,008). La hipotensión arterial fue mayor en los grupos 2 y 3 versus el grupo 1 (p< 0,05), siendo más frecuente la hipotensión moderada en el grupo 3 versus a los grupos 1 y 2 (p< 0.01). La calidad de la analgesia fue considerada superior en los pacientes del grupo 3. Conclusión: Las 3 técnicas analgésicas son útiles para el manejo del DPO de una ATR. La MIT presenta menor índice de dolor, mejor calidad de la analgesia percibida por el paciente, pero una mayor incidencia de efectos adversos en relación con el BIFC y AEPIC.

Introduction: Total knee arthroplasty (TKA) is a very painful surgical procedure in orthopedic surgery, making its treatmentvery difficult. The objective of the present study was to compare 3 postoperative analgesia strategies in the management of post TKA pain. Patients and Method: 60 patients, divided into 3 groups, were studied. Group 1: Iliofascial blockade (BIFC), Group 2: Continuous epidural analgesia (AEPIC) and Group 3: Intrathecal morphine (MIT). Postoperative pain (POD) at rest and movement was evaluated with a visual analog scale (EVA) in the first 24 hours, intravenous morphine consumption (VEM), incidence of adverse effects: pruritus, nausea and vomiting (PONV), urinary retention (UR). At the end of treatment, patient satisfaction was evaluated. Results: The DPO was significantly lower between 6 and 24 hours in the patients of Group 3 versus those of Groups 1 and 2 (p<0.01). MEV consumption was lower in patients of group 3 (p<0.01). The incidence of postoperative pruritus and UR was significantly higher in group 3 versus groups 1 and 2 (p<0.001 and p<0.008). Arterial hypotension was greater in groups 2 and 3 versus group 1 (p<0.05), with moderate hypotension being more frequent in group 3 versus groups 1 and 2 (p<0.01). The quality of analgesia was considered superior in patients in group 3. Conclusion: The three analgesic techniques are useful for managing the DPO of a TKA. MIT presents a lower pain index, better quality of analgesia perceived by the patient, but a higher incidence of adverse effects in relation to BIFC and AEPIC.

Low-level laser acupuncture reduces postoperative pain and morphine consumption in older patients with total knee arthroplasty: A randomized placebo-controlled trial / 中西医结合学报

BACKGROUND@#Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals.@*OBJECTIVE@#To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output.@*MAIN OUTCOME MEASURES@#The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA.@*RESULTS@#Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05).@*CONCLUSION@#Low-level LA gradually reduced older patients' postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care.@*TRIAL REGISTRATION@#ClinicalTrials.gov registration number NCT03995446.

Ultrasound-Guided Continuous Thoracic Paravertebral Block Improves Patient's Quality of Recovery After Open Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial / 中国医学科学杂志(英文版)

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice / Composição química do óleo essencial de Zhumeria majdae e seus efeitos na expressão da síndrome de abstinência de morfina e tolerância ao efeito anticonvulsivante da morfina em crises induzidas por pentilenotetrazol em camundongos

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

Urgencias en cuidado paliativo oncológico / Emergencies in palliative oncological care

El paciente oncológico de cuidados paliativos puede presentar una variedad importante de condiciones clínicas que producen sufrimiento y disminución en la calidad de vida; esto se presenta como un reto para el clínico en la identificación y correcto abordaje de los pacientes. El dolor se ha considerado por años como el síntoma cardinal a tratar en el paciente oncológico, donde se deben considerar sus condicionantes fisiopatológicos, la farmacología de las intervenciones, los posibles efectos secundarios y los condicionantes familiares, sociales y personales del dolor, pero a pesar de su relevancia, no es el único síntoma, estando acompañado de un abanico de patologías, como las afectaciones gastrointestinales, pulmonares, vasculares, hematológicas y neurológicas, que favorecen la pérdida de capacidad del paciente y, en muchas ocasiones, la muerte. Se realizó una revisión actualizada en bases de datos como EMBASE, PUBMED, SCIELO, además de la revisión de guías de asociaciones internacionales con el objetivo de acercar a todos los médicos, sin distinguir su especialidad o área de trabajo, al abordaje y manejo del paciente oncológico en cuidado paliativo, favoreciendo la sensibilización con estas patologías y la importancia en el curso de vida de los pacientes.

The palliative care cancer patient can present a significant variety of clinical conditions that produce suffering and a decrease in the quality of life. This is a challenge for the clinician in the identification and correct approach of patients. Pain has been considered for years as the cardinal symptom to be treated in cancer patients, where its pathophysiological factors, the pharmacology of the interventions, possible side effects and the family, social and personal conditions of pain must be considered, but despite its relevance is not the onset of symptoms and is accompanied by a range of pathologies such as gastrointestinal, pulmonary, vascular, hematological and neurological affectations that favor the loss of capacity of the patient and in many cases death. An updated review was carried out in databases such as EMBASE, PUBMED, SCIELO in addition to the revision of guides from international associations with the aim of bringing all doctors without distinguishing their specialty or area of work to the approach and management of cancer patients in palliative care favoring awareness of these pathologies and their importance in the life course of patients.

Segurança do paciente oncológico em uso de morfina: protocolo de escopo / Safety of cancer patients using morphine: scoping review protocol / Seguridad de los pacientes con cáncer que utilizan morfina: protocolo de alcance

OBJETIVO: Mapear as práticas de segurança do paciente realizadas em pacientes oncológicos paliativos em uso de morfina para o controle da dor. MÉTODO: Revisão de escopo para responder à pergunta: Quais as evidências sobre as práticas de segurança do paciente realizadas em pacientes oncológicos paliativos que fazem uso de morfina para o controle da dor? A busca será realizada nas bases de dados MEDLINE, LILACS, Scopus, Embase, Web of Science, Cochrane e CINAHL e literatura cinzenta. Após a busca, todos as citações serão agrupadas no software Rayyan e as duplicatas removidas. Os títulos e resumos serão selecionados por dois revisores independentes. O texto completo das citações selecionadas será avaliado em detalhes em relação aos critérios de inclusão por dois revisores independentes. Os dados extraídos serão apresentados em um diagrama ou forma tabular de maneira que se alinhe com o objetivo desta revisão de escopo, e um resumo narrativo será fornecido

OBJECTIVE: To map the patient safety practices performed in palliative cancer patients using morphine for pain control. METHOD: A scoping review to answer the following question: What is the evidence on the patient safety practices performed in palliative cancer patients using morphine for pain control? The search will be carried out in the MEDLINE, LILACS, Scopus, Embase, Web of Science, Cochrane and CINAHL databases, as well as in the gray literature. After the search, all citations will be grouped in the Rayyan software and the duplicates will be removed. Titles and abstracts will be selected by two independent reviewers. The full text of the selected citations will be evaluated in detail in relation to the inclusion criteria by two independent reviewers. The extracted data will be presented in diagram or table formats so that it aligns with the objective of this scoping review, and a narrative abstract will be provided.

OBJETIVO: Mapear las prácticas de seguridad del paciente realizadas en pacientes con cáncer paliativo que utilizan morfina para el control del dolor. MÉTODO: Revisión de alcance para responder a la pregunta: ¿Cuál es la evidencia sobre las prácticas de seguridad del paciente que se implementan en pacientes con cáncer paliativo que utilizan morfina para el control del dolor? La búsqueda se realizará en las bases de datos MEDLINE, LILACS, Scopus, Embase, Web of Science, Cochrane y CINAHL y literatura gris. Después de la búsqueda, todas las citas se agruparán en el software Rayyan y se eliminarán los duplicados. Los títulos y resúmenes serán seleccionados por dos revisores independientes. El texto completo de las citas seleccionadas será evaluado en detalle según los criterios de inclusión por dos revisores independientes. Los datos extraídos se presentarán en un diagrama o en forma de tabla para que se alineen con el objetivo de esta revisión de alcance, y se proporcionará un resumen narrativo.

Representações sociais de pessoas com câncer em cuidados paliativos sobre a morfina / Social representations of people with cancer in palliative care on morphine

INTRODUÇÃO: A dor se apresenta como sintoma frequente nas pessoas com câncer, e os opioides são os fármacos de escolha para o seu alívio. Dentre eles tem-se a morfina, que é um dos mais utilizados. OBJETIVOS: Descrever as representações sociais de pessoas com câncer em cuidados paliativos sobre a morfina; Analisar tais representações e suas implicações para a adesão ou não a esse opioide no tratamento/alívio da dor do câncer; Propor estratégias de cuidados afinadas às representações das pessoas com câncer que requerem o uso de morfina. MÉTODO: Pesquisa com abordagem qualitativa, do tipo descritiva e exploratória, realizada em uma instituição pública hospitalar. Os participantes foram pessoas com câncer atendidas no Ambulatório. Critérios de inclusão: maiores de 18 anos, com índice ≥ 50% na Escala de Karnofsky (KPS) e prescrição analgésica de morfina. Critérios de exclusão: presença de dor de moderada a intensa no momento da coleta de dados; e aqueles com comprometimento verbal, cognitivo e/ou psiquiátrico. Os dados foram coletados por questionário e entrevista semiestruturada. Os dados do questionário foram analisados por estatística descritiva simples e percentual, e aos conteúdos verbais aplicou-se a análise de conteúdo do tipo lexical, com o uso do software Alceste. Projeto aprovado pelos Comitês de Ética em Pesquisa da instituição proponente e cooperante, com pareceres no 3.296.128 e no 3.453.968, respectivamente. Todos os participantes assinaram o Termo de Consentimento Livre e Esclarecido. RESULTADOS: A média de idade foi de 54,7 anos; sexo feminino (69,7%); predomínio da religião evangélica (60,6%); 81,8% afirmaram seguir corretamente a prescrição da morfina; na Escala de Karnofsky, 45,5% apresentaram índice de 60%, evidenciando a necessidade de assistência ocasional, mas com capacidade de trabalhar; a intensidade da dor pela escala visual analógica variou entre leve (grau 1) e moderada (grau 4), ambas com 21,2% de respostas. O processamento dos dados no Alceste gerou dois blocos, o primeiro com a Classe 1, que expressa a representação medicamentosa do tratamento com a morfina e os fatores associados a esse tratamento; o segundo foi composto pelas Classes 2 e 3 e expressam as relações sociais envolvidas no contexto do tratamento, o vínculo da pessoa que usa morfina com o mundo que a cerca, bem como a relação estabelecida com esse medicamento, o conhecimento sobre a morfina e as atitudes adotadas diante desse uso. Houve ambiguidade nas representações da morfina, colocando-a entre a dor e o temor, pois a indicam como um importante recurso para alívio/tratamento da dor do câncer, mas sinalizam que também pode trazer repercussões negativas associadas aos seus efeitos. CONSIDERAÇÕES FINAIS: Apesar de haver aderência dos pacientes à morfina, a opiofobia ainda precisa ser combatida por meio de estratégias que façam circular informações que possam reconstruir representações sobre a morfina e seu uso terapêutico. A educação terapêutica por meio da atuação de equipe multidisciplinar se destaca como uma boa estratégia de difusão de informações seguras sobre o uso de opioides.

INTRODUCTION: Pain is a frequent symptom in people with cancer, and opioids are the drug of choice for its relief, including morphine, which is one of the most used. OBJECTIVES: To describe the social representations of people with cancer in palliative care about morphine; To analyze such representations and their implications for adherence or not to this opioid in the cancer pain treatment/relief; To propose care strategies related to the representations of people with cancer that require the use of morphine. METHOD: Descriptive and exploratory research with a qualitative approach, carried out in a public hospital. The participants were people with cancer treated at the clinic. Inclusion criteria: over 18 years old, with an index ≥ 50% on the Karnofsky Scale (KPS) and morphine as an analgesic medication prescribed. Exclusion criteria: presence of moderate to severe pain at the time of data collection; and those with verbal, cognitive and/or psychiatric impairment. Data was collected by questionnaire and semi-structured interview. The questionnaire data were analyzed using simple and percentage descriptive statistics, and the verbal content was analyzed using lexical content with the Alceste software. Project approved by the Research Ethics Committees of the proposing and cooperating institution, with opinions No. 3,296,128 and 3,453,968, respectively. All participants signed the Free and Informed Consent Form. RESULTS: The average age was 54.7 years; female gender (69.7%); prevalence of the evangelical religion (60.6%); 81.8% said they correctly followed the prescription of morphine; on the Karnofsky Scale, 45.5% had an index of 60% showing the need for occasional assistance, but with the ability to work; pain intensity by visual analog scale ranged from mild (grade 1) to moderate (grade 4), both with 21.2% responses. The data processing at Alceste generated two blocks, the first with class 1, which expresses the drug representation of the treatment with morphine and the factors associated with that treatment; the second was composed of Classes 2 and 3 and expresses the social relationships involved in the context of the treatment, the bond of the person who uses morphine with the world around her, as well as the relationship established with this medicine, the knowledge about the morphine and the attitudes towards the use of the medicine. There was ambiguity in the representations of morphine, placing it between pain and fear, as they indicate it as an important resource to relieve/treat cancer pain, but it can also bring negative repercussions associated with its effects. FINAL CONSIDERATIONS: Despite patient adherence to morphine, opiophobia still needs to be fought through strategies that spread information that can reconstruct representations about morphine and its therapeutic use. Therapeutic education through the work of a multidisciplinary team stands out as a good strategy to disseminate safe information about the use of opioids.

INTRODUCCIÓN: El dolor es un síntoma frecuente en las personas con cáncer y los opioides son los fármacos de elección para su alivio; entre ellos está la morfina, que es uno de los más utilizados. OBJETIVOS: Describir las representaciones sociales de las personas con cáncer en cuidados paliativos sobre la morfina; analizar tales representaciones y sus implicaciones para la adherencia o no a este opioide en el tratamiento / alivio del dolor producido por el cáncer; Proponer estrategias de cuidados en sintonía con las representaciones de las personas con cáncer que requieren el uso de morfina. MÉTODO: Investigación con enfoque cualitativo, descriptivo y exploratorio, realizada en un hospital público. Los participantes fueron personas con cáncer tratadas en modalidad ambulatorial. Criterios de inclusión: mayores de 18 años, con índice ≥ 50% en la Escala de Karnofsky (KPS) y prescripción analgésica de morfina. Criterios de exclusión: presencia de dolor de moderado a intenso en el momento de la recogida de datos; y aquellos con comprometimiento verbal, cognitivo y/o psiquiátrico. Datos recogidos mediante cuestionario y entrevista semiestructurada. Los datos del cuestionario se analizaron mediante estadística descriptiva simple y porcentual y el contenido verbal fue sometido a análisis de contenido de tipo lexical, utilizándose el software Alceste. Proyecto aprobado por los Comités de Ética en Investigación de la institución proponente y cooperante, con dictámenes núm. 3.296.128 y 3.453.968, respectivamente. Todos los participantes firmaron una declaración de Consentimiento Libre e Informado. RESULTADOS: La edad promedio fue de 54,7 años; sexo femenino (69,7%); predominio de la religión evangélica (60,6%). El 81,8% afirmó que seguía correctamente la prescripción de morfina. En la Escala de Karnofsky, el 45,5% presentó un índice del 60%, lo que indica la necesidad de asistencia ocasional, pero con capacidad para trabajar. La intensidad del dolor, según la escala visual analógica (EVA), varió de leve (grado 1) a moderado (grado 4), ambos con 21,2% de respuestas. El procesamiento de datos en el software Alceste generó dos bloques: el primero con la Clase 1, que expresa la representación farmacológica del tratamiento con morfina y los factores asociados a ese tratamiento; el segundo estaba compuesto por las Clases 2 y 3 y expresa las relaciones sociales involucradas en el contexto del tratamiento, el vínculo de la persona que usa morfina con el mundo que la rodea, así como la relación que establece con ese medicamento, el conocimiento sobre la morfina y las actitudes adoptadas con respecto a su uso. Hubo ambigüedad en las representaciones de la morfina, pues se la situó entre el dolor y el miedo: los participantes la señalaron como un recurso importante para el alivio/tratamiento del dolor oncológico, pero también mencionaron la posibilidad de repercusiones negativas asociadas a sus efectos. CONSIDERACIONES FINALES: A pesar de la adherencia de los pacientes a la morfina, la opiofobia aún debe combatirse mediante estrategias que hagan circular información que permita la reconstrucción de las representaciones sobre la morfina y su uso terapéutico. La educación terapéutica mediante la actuación de un equipo multidisciplinario descolla como una buena estrategia para difundir información segura sobre el uso de opioides.

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.

Eficacia analgésica de la combinación morfina/dexketoprofeno versus morfina/paracetamol en pacientes sometidos a cirugía de miembros inferiores / Analgesic efficiency of the combination morphine/dexketoprofen versus morphine/paracetamol in patients admitted for lower limb surgery

En cirugía traumatológica y ortopédica se han propuesto la combinación de distintos analgésicos y/o técnicas analgésicas para el tratamiento del dolor postoperatorio. Por esta razón, se realizó un ensayo clínico controlado, no ciego, con una muestra de 40 pacientes cuyo objetivo fue determinar la eficacia analgésica de la combinación Morfina/Dexketoprofeno versus Morfina/Paracetamol en pacientes sometidos a cirugía de miembros inferiores en el Servicio de Traumatología y Ortopedia del Hospital Central Universitario Dr. Antonio María Pineda. Los pacientes fueron distribuidos aleatoriamente en dos grupos: grupo M/D a quienes se les administró 100 mcg de morfina y 50 mg de dexketoprofeno y grupo M/P quienes recibieron 100 mcg de morfina y 1 gr de paracetamol. Ambos grupos reportaron ausencia de dolor en las primeras 6 horas, a las 18 horas 80% del grupo M/D y 100% del grupo M/P mostraron ausencia del dolor mientras que a las 24 horas ambos grupos reportaron dolor leve. Sólo 35% de los pacientes del grupo M/D recibió analgesia de rescate. Los efectos adversos fueron observados en 15% del grupo M/D y 5% del grupo M/P. Las combinaciones Morfina/Dexketoprofeno y Morfina/Paracetamol son seguras y eficaces para disminuir el dolor postoperatorio de los pacientes sometidos a cirugía de miembros inferiores, no obstante este último no requiere analgesia de rescate y los efectos adversos son menores(AU)

In trauma and orthopedic surgery, combination of different analgesics and/or analgesic techniques has been used for treatment of pain after surgery. For this reason, a clinical controlled study with 40 patients was performed to test the analgesic efficiency of the combination Morphine/Dexketoprofen versus Morphine/Paracetamol in patients admitted for lower limb surgery at the Service of Orthopedic Surgery and Orthopedics of the Hospital Central Universitario Dr. Antonio María Pineda. Patients were distributed in two groups: Group M/D which received 100 mcg of morphine and 100 mg of Dexketoprofen and Group M/P which received 100 mcg of morphine and 1 gr of paracetamol. Both groups did not show pain in the first 6 hours, 18 hours post surgery 80% of group M/D and 100% of the group M/P showed absence of pain while 24 hours after both groups reported slight pain. Only 35% of patients of group M/D received rescue analgesia; 15 % of group M/D and 5 % of group M/P showed minor adverse effects. The combination Morphine/Dexketoprofen and Morphine/Paracetamol are effective and safe in diminishing post operatory pain in patients submitted for lower limb surgery; nevertheless, the latter does not need rescue analgesia and has minor adverse effects(AU)

Comparison of postoperative analgesia with methadone versus morphine in cardiac surgery / Comparação da analgesia pós-operatória com uso de metadona versus morfina em cirurgia cardíaca

Abstract Background and objectives: Pain is an aggravating factor of postoperative morbidity and mortality. The aim of this study was to compare the effects of methadone versus morphine using the numerical rating scale of pain and postoperative on-demand analgesia in patients undergoing myocardial revascularization. Method: A randomized, double-blind, parallel clinical trial was performed with patients undergoing coronary artery bypass grafting. The subjects were randomly divided into two groups: morphine group and methadone group. At the end of cardiac surgery, 0.1 mg.kg−1 adjusted body weight of methadone or morphine was administered intravenously. Patients were referred to the ICU, where the following was assessed: extubation time, time to first analgesic request, number of analgesic and antiemetic drug doses within 36 h, numerical pain scale at 12, 24, and 36 h postoperatively, and occurrence of adverse effects. Results: Each group comprised 50 patients. Methadone showed 22% higher efficacy than morphine as it yielded a number-needed-to-treat score of 6 and number-needed-to-harm score of 16. The methadone group showed a mean score of 1.9 ± 2.2 according to the numerical pain scale at 24 h after surgery, whereas as the morphine group showed a mean score of 2.9 ± 2.6 (p = 0.029). The methadone group required less morphine (29%) than the morphine group (43%) (p = 0.002). However, the time to first analgesic request in the postoperative period was 145.9 ± 178.5 min in the methadone group, and 269.4 ± 252.9 in the morphine group (p = 0.005). Conclusions: Methadone was effective for analgesia in patients undergoing coronary artery bypass grafting without extracorporeal circulation.

Resumo Justificativa e objetivos: A dor é fator agravante da morbidade e mortalidade pós-operatória. O objetivo foi comparar o efeito da metadona versus morfina quanto à dor e demanda de analgesia pós-operatória em pacientes submetidos à revascularização do miocárdio. Método: Ensaio clínico randomizado, duplo-cego, em paralelo. Pacientes submetidos à cirurgia de revascularização do miocárdio foram randomizados por blocos em dois grupos: Grupo Morfina (Gmo) e Grupo Metadona (Gme). No fim da cirurgia cardíaca, 0,1 mg.Kg−1 peso corrigido de metadona ou morfina foi administrado por via venosa. Os pacientes foram levados à UTI, onde foram avaliados o tempo até a extubação e a necessidade do primeiro analgésico, o número de doses necessárias de analgésicos e antieméticos em 36 horas, a escala numérica de dor em 12, 24 e 36 horas após a cirurgia e a ocorrência de efeitos adversos. Resultados: Foram incluídos 50 pacientes em cada grupo. A metadona apresentou eficácia 22% maior do que a morfina com Number Needed to Treat(NNT) de 6 e Number Needed to Harm(NNH) de 16. Gme apresentou média de dor pela escala numérica em 24 horas após o procedimento de 1,9 ± 2,2 em comparação com o Gmo, cuja média foi de 2,9 ± 2,6 (p= 0,029). O Gme necessitou de menos morfina de resgate 29% do que o grupo Gmo 43% (p= 0,002). Entretanto, o tempo até a necessidade de analgésico no pós-operatório foi de 145,9 ± 178,5 minutos no Grupo Gme e de 269,4 ± 252,9 no Gmo (p= 0,005). Conclusões: A metadona mostrou-se eficiente para a analgesia em cirurgias cardíacas de revascularização do miocárdio sem circulação extracorpórea.

Efectividad de la anestesia espinal con morfina y bupivacaína en la cirugía de próstata / Effectiveness of spinal anesthesia with morphine and bupivacaine in prostate surgery

Introducción: El dolor posoperatorio constituye la principal causa de dolor agudo en el mundo. Brindar analgesia adecuada en el posquirúrgico garantiza la disminución del tiempo de estancia hospitalaria y tiene un impacto positivo en el resultado final de los pacientes. Objetivo: Evaluar la calidad de la analgesia posoperatoria con bupivacaína más morfina intratecal en la cirugía electiva de próstata, así como la incidencia de efectos adversos. Métodos: Se realizó una investigación cuasiexperimental, entre enero de 2014 y julio de 2017. La muestra quedó conformada de manera no probabilística por los pacientes que dieron su consentimiento informado y reunieron criterios para entrar en el estudio. Quedaron distribuidos de manera aleatoria en dos grupos denominados bupivacaína (B) y morfina-bupivacaína (MB). Para recolectar la información se emplearon las historias clínicas anestésicas y un formulario elaborado al efecto. Los datos se mostraron en tablas y gráficos, los resultados se expresaron numéricamente y en porcientos, se determinaron algunas medidas descriptivas de interés que mostraron el comportamiento de las variables que lo requirieron. Resultados: El resultado más relevante fue el efecto analgésico muy significativo en el grupo MB en las primeras 24 h del posoperatorio. La reacción adversa más frecuente fue el prurito y solo se presentó en el grupo que recibió morfina. Conclusiones: La anestesia espinal con morfina y bupivacaína es efectiva y segura, proporcionando mejor analgesia en el posoperatorio inmediato cuando se compara con bupivacaína sola(AU)

Introduction: Postoperative pain is the main cause of acute pain worldwide. Providing adequate analgesia postoperatively guarantees hospital stay reduction and positively affects patient outcome. Objective: To evaluate the quality of postoperative analgesia with bupivacaine plus intrathecal morphine in elective prostate surgery, as well as the incidence of adverse effects. Methods: A quasiexperimental research was carried out between January 2014 and July 2017. The sample was chosen in a non-probabilistic way and made up by the patients who gave their informed consent and met the inclusion criteria to enter the study. They were randomly distributed into two groups identified as bupivacaine (B) and morphine-bupivacaine (MB). To collect the information, the anesthetic medical records were used, together with a form prepared for such purpose. The data were shown in charts and graphs, the results were expressed numerically and in percentages, some descriptive measures of interest were determined that showed the behavior of the variables that required it. Results: The most relevant outcome was the very significant analgesic effect in the MB group in the first 24 hours after surgery. The most common adverse reaction was pruritus and only occurred in the group that received morphine. Conclusions: Spinal anesthesia with morphine and bupivacaine is effective and safe because it provides better analgesia in the immediate postoperative period in comparison to bupivacaine alone(AU)

Evaluation of nicotine patch in pain control of patients undergoing laparoscopic cholecystectomy / Avaliação do adesivo de nicotina no controle da dor em pacientes submetidos à colecistectomia videolaparoscópica

ABSTRACT Objective: to analyze the effects of nicotine patch on pain control, occurrence of nausea and its hemodynamic repercussions in laparoscopic cholecystectomy procedures. Methods: we conducted an analytical, prospective, randomized, triple-blinded, clinical study between January and July 2017. The sample consisted of 17 patients who underwent laparoscopic cholecystectomy for the treatment of cholelithiasis. Nine patients used nicotine patch, and eight, placebo patch. The studied variables were pain, nausea, patient satisfaction, blood pressure, heart rate, oximetry and morphine rescue. Results: taking into account the pain and nausea parameters, there was no statistically significant difference between the groups (p>0.05). Also, the evaluation of rescue medication, both opioids and prokinetics, did not show any significant statistical difference between the groups. Among the hemodynamic parameters, there was only one statistically significant difference in the analysis of oxygen saturation and systolic blood pressure (SBP) six hours after surgery: the mean oxygen saturation was higher in the Test group (97.89 x 95.88) and the mean SBP was higher in the Control group (123.89 x 110.0). Conclusion: although pain levels were lower for nicotine within 24 hours, the action of nicotine and the need for rescue opioids in pain control were not statistically significant between the groups and at the time intervals studied. There was no clinical repercussion in the hemodynamic parameters.

RESUMO Objetivo: analisar os efeitos do adesivo de nicotina sobre o controle da dor, ocorrência de náuseas e suas repercussões hemodinâmicas em cirurgias de colecistectomia videolaparoscópica. Métodos: estudo analítico, do tipo ensaio clínico, prospectivo, randomizado e triplo-cego realizado entre janeiro e julho de 2017. A amostra foi composta de 17 pacientes em pós-operatório de colecistectomia videolaparoscópica para tratamento de colelitíase. Nove pacientes fizeram uso do adesivo com nicotina e oito de adesivo placebo. As variáveis estudadas foram: dor, náusea, satisfação do paciente, pressão arterial, frequência cardíaca, oximetria e resgate de morfina. Resultados: levando em consideração os parâmetros dor e náuseas, não houve diferença estatisticamente significativa entre os grupos (p>0,05). Ainda, a avaliação da medicação de resgate, tanto opioide como procinéticos, também não evidenciou diferença estatística relevante entre os grupos. Dentre os parâmetros hemodinâmicos, só houve diferença estatística nas análises da saturação de oxigênio e da pressão arterial sistólica (PAS) seis horas após a cirurgia: a média da saturação de oxigênio foi maior no grupo Teste (97,89 x 95,88) e a média da PAS foi maior no grupo Controle (123,89 x 110,0). Conclusão: apesar dos níveis de dor terem sido menores para nicotina no intervalo de 24 horas, a ação da nicotina e a necessidade de opioide de resgate no controle da dor não foram estatisticamente significantes entre os grupos e intervalos de tempo estudados. Não houve repercussão clínica nos parâmetros hemodinâmicos.

Distribución de morfina y opioides / CURRENT STATUS AND DISTRIBUTION OF MORPHINE AND OPIOIDS

La liberación del uso terapéutico de los opioides se ha hecho cada vez mas frecuente como una propuesta para mejorar la distribución de éstos en las instituciones de salud pública y privadas con el fin de garantizar su alcance a población que cursa con dolor. A pesar de esto, aún no se logra una distribución homogénea de estos recursos en la población requirente. El objetivo de este trabajo es dar a conocer el panorama actual de los opioides en México y algunos países sudamericanos.

The release of therapeutic opioid use is mentioned with increasing frequency as a proposal to improve their tion in Public and Private Health Care Institutions, in order to scope opioids to population who needs them. Although this, homogeneous distribution of opioids is not achieved. The aim of this paper is to present the current panorama of opioids in Mexico and Latin American countries

Cólico biliar inducido por morfina / Morphine induced biliary pain: case report

Morphine produces contraction of Oddi’s sphincter, which can be severe and of longer duration in some pathological conditions. This exaggerated response can manifest as a colicky biliary pain, frequently accompanied by a dramatic increase in hepatic enzymes. We report a 32 years old female who consulted in the emergency room for severe low abdominal pain of gynecologic origin, which was completely controlled by morphine. However, she presented a sudden epigastric colicky pain irradiating in the back, which persisted for several hours in spite of the repeated administration of analgesics. Transaminases elevated from previously normal value to over 1,000 U/L, and returned to the normal level without further treatment after several days. Magnetic resonance cholangiography showed normal fine bile duct, without stones. This transient increase in hepatic enzymes was considered as a consequence of high biliary pressure secondary to morphine-induced spastic contraction of Oddi’s sphincter and a consecutive hepatocellular necrosis.

Eficacia analgésica y seguridad de dosis única de morfina intratecal / Analgesic effectiveness and safety of single-dose intrathecal morphine

Introducción: el dolor posoperatorio del hemiabdomen superior es intenso y su control es imprescindible para evitar complicaciones. Objetivos: evaluar la eficacia analgésica y seguridad de dosis única de morfina intratecal en el posoperatorio de la cirugía de hemiabdomen superior de gran envergadura. Método: ensayo clínico aleatorizado a simple ciegas en 40 pacientes, tras intervenciones de hemiabdomen superior. Se emplearon dosis única de morfina intratecal (MIT) de 1 o 2 µg/kg de peso del paciente de acuerdo al grupo de tratamiento. Análisis estadístico con las pruebas Chi cuadrado (x2), exacta de Fisher, análisis de varianza univariado, la prueba de W de Mauchly y la prueba F univariada; nivel de significación de 0,05. Resultados: la administración de opioides durante el acto quirúrgico fue similar en ambos grupos (3,1 ± 2,2 mL vs. 4,1 ± 2,7 mL). En el grupo de dosis de 2 µg/kg de peso de MIT a las 12 y 24 h los pacientes no refirieron dolor; existieron diferencias entre los tratamientos en cuanto al alivio del dolor (p< 0,001) y también entre los momentos en que se midió el mismo (p= 0,001). Se utilizó analgesia de rescate en 25 por ciento de los pacientes. Solo se presentó como complicación la depresión respiratoria. Conclusiones: la dosis única de 2 µg/kg de morfina intratecal es un método eficaz para la analgesia posoperatoria en la cirugía de hemiabdomen superior, la incidencia de complicaciones fue baja y se demostró que ambas dosis son seguras(AU)

Introduction: The superior hemiabdomen postoperative pain is severe and essential to be managed in order to avoid complications. Objectives: To assess the analgesic effectiveness and safety of single-dose intrathecal morphine in the postoperative period of the upper hemiabdomen major surgery. Method: Single-blind randomized clinical trial in 40 patients, after upper hemiabdomen interventions. We used single doses of intrathecal morphine (ITM) of 1 or 2 mg/kg per patient weight according to the treatment group. The statistical analysis used the Chi-square test, Fisher's exact test, univariate analysis of variance, Mauchly's test and Univariate F-test; the significance level was 0.05. Results: Opioids administration during surgery was similar in both groups (3.1 ± 2.2 mL vs. 4.1 ± 2.7 mL). In the 2 mg/kg of ITM dose group, the patients reported no pain after 12 and 14 hours; there were differences between treatments regarding pain relief (p< 0.001) and also between the time when it was measured (p= 0.001). Rescue analgesia was used in 25 percent of the patients. Respiratory depression was the only onset complication. Conclusions: ITM at a single dose of 2 µg/kg is an effective method for postoperative analgesia in upper hemiabdomen surgery, the incidence of complications was low and both doses proved safe(AU)

Uso de opiáceos en niños con cáncer avanzado en cuidados paliativos / Use of opioids in palliative care of children with advanced cancer

INTRODUCCIÓN A pesar del avance en el tratamiento del cáncer en pediatría, en Chile el 15% de niños fallece por progresión de la enfermedad, siendo el dolor el síntoma más importante en esta etapa. Las pautas de la OMS demuestran que los opiáceos son fundamentales para controlar el dolor, sin embargo aún existe resistencia a su utilización. OBJETIVO Describir la experiencia en el uso de opiáceos para el manejo del dolor en pacientes pediátricos con cáncer avanzado en cuidados paliativos (CP). PACIENTES Y MÉTODO Estudio retrospectivo de datos registrados en fichas clínicas de pacientes oncológicos ingresados en el Programa de CP, Hospital de Niños Dr. Roberto del Río entre los años 2002 y 2013. Se analizaron datos demográficos, diagnóstico oncológico, intensidad del dolor al ingreso y egreso según escalas validadas. Se registró el uso de antiinflamatorios no esteroideos, opiáceos débiles, opiáceos fuertes, fármacos coadyuvantes, efectos secundarios por uso de morfina y necesidad de sedación paliativa. RESULTADOS Se analizaron 99 fichas médicas, 64,6% de hombres, mediana de 8 años, distribución similar en grupos de enfermedades oncológicas. Al ingreso un 43,4% manifestó de dolor intenso a severo y al egreso solo 4 pacientes, pero con EVA máxima de 7 solo en un caso. De 66 pacientes que utilizaron opiáceos fuertes el 89% requirió menos de 0,5 mg/kg/h de morfina. El estreñimiento fue el efecto secundario más frecuente. Un 77% recibió algún fármaco coadyuvante para el manejo del dolor: 40 utilizaron corticoides, 11 benzodiacepinas y en 25 casos combinación de estos fármacos, incluyendo el uso de gabapentina en 7 casos. CONCLUSIONES Dos tercios de los pacientes requirieron opiáceos fuertes, logrando un adecuado control del dolor, sin observar complicaciones severas. El uso de opiáceos en este grupo de pacientes, siguiendo un protocolo, es efectivo y seguro.

INTRODUCTION Despite advances in the treatment of cancer in paediatric patients, 15% of children die from the illness progression in Chile, and pain is the most significant symptom in advanced stages. Although the World Health Organization guidelines demonstrate that opioids are fundamental in pain management, there is still resistance to their use. The main objective of this article was to describe the experience in the use of opioids for pain management in paediatric patients with advanced cancer in palliative care (PC). PATIENTS AND METHOD Retrospective study of patients admitted into the PC Program at the Hospital Roberto del Río between 2002 and 2013. Analysis was carried out on demographic data; oncological diagnosis; pain intensity on admission and discharge, according to validated scales; use of non-steroidal anti-inflammatory drugs; weak opioids; strong opioids; adjuvants drugs; the presence of secondary effects resulting from the use of morphine, and the need for palliative sedation. RESULTS Of the 99 medical records analysed, the median age was 8 years, 64.6% were male, and there was a similar distribution in three oncological diagnosis groups. Upon admission, 43.4% presented intense to severe pain, and upon discharge there were four patients, but with a maximum VAS score of 7 in only one case. Of the 66 patients taking strong opioids, 89% required less than 0.5 mg/kg/hr. Constipation was the most frequently observed secondary effect. CONCLUSIONS Two thirds of the patients studied required strong opioids, with which adequate pain management was achieved, with no serious complications observed. The use of opioids in this group of patients, following a protocol, is considered effective and safe.

Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis / Efeitos da morfina na expressão de citocinas e de mediadores inflamatórios em coelhos com uveítes experimental induzida por endotoxina

ABSTRACT Purpose: To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1beta), prostaglandin E2 (PGE2), and myeloperoxidase (MPO) in rabbits with endotoxin-induced experimental uveitis. Methods: Twenty four New Zealand white rabbits were divided into four groups (n=6 each): control (CG), morphine (MG), naloxone (NG), and morphine-naloxone (MNG) groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 µg of lipopolysaccharide (LPS) endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge) and laser flaremetry were performed before (baseline), and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-α, IL-1 beta, PGE2, and MPO. Results: No significant differences in clinical parameters and flare values were observed between the study groups. TNF-α and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P<0.05). Significant differences in PGE2 levels were observed between the MG and NMG groups (P<0.05). A trend toward increased MPO activity was observed in response to uveitis induction; however, this trend did not reach statistical significance (P>0.05). Conclusions: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS.

RESUMO Objetivo: Estudaram-se os efeitos da instilação de morfina 1% sobre parâmetros clínicos, turbidez do humor aquoso e expressão de fator de necrose tumoral alfa (TNF-alfa), de interleucina-1 beta (IL-1beta), de prostaglandina E2 (PGE2) e de mieloperoxidase (MPO), em olhos de coelhos com uveíte induzida por endotoxina. Material e Métodos: Vinte e quatro coelhos da raça Nova Zelândia Branco foram distribuídos em quatro grupos (n=6, em cada): grupo controle (GC), morfina (GM), naloxona (GN) e morfina-naloxona (GMN). Sob anestesia dissociativa, injetou-se 0,1 mL de solução contendo 0,2 µg de lipossacarídeo (LPS) endotóxico da parede celular de Salmonella typhimurium na câmara vítrea. Realizou-se avaliação clínica (hiperemia conjuntival, quemose, blefaroespasmo e secreção ocular) e a flaremetria a “laser” antes (basal) e após 10 e 20 horas da indução da uveíte. No final, os coelhos foram submetidos à eutanásia e os olhos com uveíte foram enucleados para a quantificação dos níveis de TNF-alfa, IL-1 beta, PGE2 e MPO. Diferenças foram consideradas significativas quando p<0,05. Resultados: Os grupos da pesquisa não diferiram quanto aos parâmetros clínicos e os valores de “flare”. Observou-se elevação significativa nos níveis de TNF-alfa e de IL-1 beta, comparativamente ao basal, nos grupos GC, GM, GN e GMN (p<0,05). Valores de PGE2 variaram entre os grupos GM e GNM (p<0,05). A atividade de MPO aumentou após a indução da uveíte, porém, sem significância estatística (p>0,05). Conclusões: A morfina não atuou sobre parâmetros clínicos, “flare” e expressão dos mediadores inflamatórios estudados, quando instilada em olhos de coelhos com uveíte induzida por injeção intravítrea de LPS.

Acupuncture and pharmacopuncture are as effective as morphine or carprofen for postoperative analgesia in bitches undergoing ovariohysterectomy

ABSTRACT PURPOSE : To investigate the analgesic effect of acupuncture (AP) or micro-dose pharmacopuncture (PA), using carprofen or morphine, in bitches undergoing ovariohysterectomy (OHE). METHODS: Thirty five dogs were randomly assigned to five groups after sedation with acepromazine IM: AP, 0.5 mg.kg-1 of morphine subcutaneously (SC), 4 mg.kg-1 of carprofen SC, and PA with 0.05 mg.kg-1 of morphine or 0.4 mg.kg-1 of carprofen. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed after OHE by a blind observer for 24h, by dynamic visual analogue scale (DIVAS), Glasgow (CMPS-SF), Melbourne (UMPS) and Colorado University pain scale (CSU). Animals reaching 33% of the UMPS score received rescue analgesia with morphine IM. Non parametric data were analysed by Kruskal-Wallis or Friedman tests where applicable, followed by Dunn´s test. Parametric data were analysed by two way ANOVA, followed by Tukey test. RESULTS: There were no differences among groups in number of rescue analgesia. Except for the DIVAS score where animals treated with morphine had the lowest score compared with AP and carprofen, at 1h after surgery, there were no other differences among groups. CONCLUSION: Acupuncture or pharmacopuncture were equally effective as morphine or carprofen to control postoperative pain in bitches undergoing ovariohysterectomy.

Morphine as first medication for treatment of cancer pain / Morfina como primeiro medicamento para tratamento da dor de câncer / Morfina como primer medicamento para el tratamiento del dolor de cáncer

BACKGROUND AND OBJECTIVES: the medications used according to the recommendation of the World Health Organization do not promote pain relief in a number of patients with cancer pain. The aim of this study was to evaluate the use of morphine as first medication for the treatment of moderate cancer pain in patients with advanced and/or metastatic disease, as an option to the recommendations of the World Health Organization analgesic ladder. METHOD: sixty patients without opioid therapy, with >18 years of age, were randomized into two groups. G1 patients received medication according to the analgesic ladder and started treatment with non-opioids in the first, weak opioids in the second, and strong opioids in the third step; G2 patients received morphine as first analgesic medication. The efficacy and tolerability of initial use of morphine were evaluated every two weeks for three months. RESULTS: the groups were similar with respect to demographic data. There was no significant difference between the groups regarding pain intensity, quality of life, physical capacity, satisfaction with treatment, need for complementation and dose of morphine. In G1 there was a higher incidence of nausea (p = 0.0088), drowsiness (p = 0.0005), constipation (p = 0.0071) and dizziness (p = 0.0376) in the second visit and drowsiness (p = 0.05) in the third. CONCLUSIONS: the use of morphine as first medication for pain treatment did not promote better analgesic effect than the ladder recommended by World Health Organization, with higher incidence of adverse effects. .

JUSTIFICATIVA E OBJETIVOS: Os medicamentos usados segundo a recomendação da Organização Mundial de Saúde (OMS) não promovem alívio da dor de uma parcela dos pacientes com dor oncológica. O objetivo deste estudo foi avaliar o uso de morfina como primeiro medicamento para o tratamento da dor oncológica moderada, em pacientes com doença avançada e/ou metástases, como opção às recomendações da escada analgésica preconizada pela OMS. MÉTODO: Sessenta pacientes sem terapia com opioide, com idade maior ou igual a 18 anos, foram distribuídos aleatoriamente em dois grupos. Os pacientes do G1 receberam medicamentos segundo a escada analgésica e iniciaram o tratamento com não opioide no primeiro degrau, opioide fraco no segundo e opioide potente no terceiro; os do G2 receberam morfina como primeiro medicamento analgésico. Foram avaliadas a eficácia e a tolerabilidade do uso inicial de morfina, a cada duas semanas durante três meses. RESULTADOS: Os grupos foram semelhantes quanto aos dados demográficos. Não houve diferença significante entre os grupos quanto à intensidade da dor, qualidade de vida, capacidade física, satisfação com o tratamento, necessidade de complementação e dose de morfina usada. No G1 houve maior incidência de náusea (p = 0,0088), sonolência (p = 0,0005), constipação (p = 0,0071) e tontura (p = 0,0376) na segunda consulta e para sonolência (p = 0,05) na terceira. CONCLUSÕES: O uso de morfina como primeiro medicamento para tratamento da dor não promoveu melhor efeito analgésico do que a escada preconizada pela OMS e houve maior incidência de efeitos adversos. .

JUSTIFICACIÓN Y OBJETIVOS: los medicamentos usados según la recomendación de la Organización Mundial de la Salud (OMS) no generan alivio del dolor de un grupo de pacientes con dolor oncológico. El objetivo de este estudio fue evaluar el uso de la morfina como primer medicamento para el tratamiento del dolor oncológico moderado en pacientes con enfermedad avanzada y/o metástasis, como opción a las recomendaciones de la escala analgésica preconizada por la OMS. MÉTODO: sesenta pacientes sin terapia con opiáceos, con una edad mayor o igual a los 18 años, fueron distribuidos aleatoriamente en 2 grupos. Los pacientes del G1 recibieron medicamentos según la escala analgésica iniciando el tratamiento con no opiáceo en la primera etapa, opiáceo débil en la segunda y opiáceo potente en la tercera; los del G2 recibieron morfina como primer medicamento analgésico. Fueron evaluadas la eficacia y la tolerabilidad del uso inicial de la morfina cada 2 semanas durante 3 meses. RESULTADOS: los grupos fueron similares en cuanto a los datos demográficos. No hubo diferencia significativa entre los grupos en lo que respecta a la intensidad del dolor, calidad de vida, capacidad física, satisfacción con el tratamiento, necesidad de complementación y dosis de morfina usada. En el G1 hubo una mayor incidencia de náuseas (p = 0,0088), somnolencia (p = 0,0005), estreñimiento (p = 0,0071) y mareos (p = 0,0376) en la segunda consulta, y de somnolencia (p = 0,05) en la tercera. CONCLUSIONES: el uso de la morfina como primer medicamento para el tratamiento del dolor no generó un efecto analgésico mejor que la escala preconizada por la OMS, habiendo una mayor incidencia de efectos adversos. .