Implications of opioid-sparing medications in critically ill patients: A scoping review.

OBJECTIVE: The purpose of this scoping review was to evaluate literature involving opioid-sparing medications in critically ill patients with a focus on clinically meaningful outcomes. DESIGN: Scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. SETTING: Intensive care unit. PATIENTS OR PARTICIPANTS: Adult patients in an intensive care unit setting. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: PubMed and Cochrane Library were searched from October 1, 2019 to June 1, 2023. Inclusion criteria consisted of randomized controlled trials evaluating adjunctive analgesic use in adult patients in an intensive care unit setting. RESULTS: There were 343 citations and titles identified in the initial search, with 328 remaining after removal of duplicates, 294 excluded at title and abstract screening, 34 available for full text review, and six included in the scoping review. Most studies reported modest reductions in opioid use as a secondary endpoint. Improvement in clinical outcomes such as reduction in duration of mechanical ventilation or delirium were reported in two trials with dexmedetomidine. CONCLUSIONS: In recently published trials of adjunctive agents in critically ill patients, opioid-sparing effects were small. Data to support improvements in clinical outcomes remains limited.

[Appropriate use of strong opioids in medical units: Recommendations and action to be taken in daily practice]. / Bon usage des opioïdes forts dans les unités de médecine : état des lieux des recommandations et conduite à tenir en pratique quotidienne.

The use of strong opioids in medical units is recurrent, mainly for analgesic purposes. The risk of occurrence of an overdose or an opioid use disorders causes very legitimate concerns for the physician, which may limit the use of opioid treatment or the adaptation of the doses necessary to relieve the patient. We provide a summary of the literature aimed at defining the indications, the adverse effects and the risks involved, the prescribing methods in order to reassure professionals and promote the safe use of these molecules.

Dualismo, modulación alostérica y señalización diferencial en los receptores opiáceos: futuro potencial terapéutico / Dualism, allosteric modulation and biased signaling of opioid receptors: Future therapeutic potential

Los fármacos opioides permanecen como fármacos de elección en el tratamiento del dolor agudo postoperatorio y del dolor crónico oncológico. Su prescripción inadecuada, ha dado lugar, en algunos países, a una verdadera «crisis de opioides». En este contexto, puede resultar interesante el potencial terapéutico de algunos ligandos que actúan como moduladores alostéricos de la fijación de los agonistas opioides y su capacidad de modular su actividad, modificando su afinidad, potencia e incluso eficacia. (AU)

Opioids are still the drugs of choice for the treatment of acute post-surgical pain and chronic cancer pain. Overprescribing of these drugs has given rise to an “opioid crisis” in some countries. In this context, attention has been drawn to the therapeutic potential of various ligands that act as allosteric modulators of orthosteric binding sites and modulate the drug's activity, affinity, potency, and even efficacy. (AU)

Consideraciones para el uso de tramadol en dolor crónico no oncológico en atención primaria de salud (APS)

Introducción: tramadol es un analgésico opioide usado frecuentemente para el manejo del dolor crónico no oncológico (DCNO). En Chile, es parte del arsenal farmacológico de los centros de atención primaria para el tratamiento de patologías como artrosis de cadera y rodilla. Es considerado seguro y efectivo, sin embargo, existen reportes de efectos adversos serios por polimorfismos hepáticos, interacciones farmacológicas, intoxicaciones, adicción y muerte. La dosis óptima de tramadol es paciente dependiente. Por esto, es necesario contar con orientaciones específicas para prescribir tramadol de manera segura y eficaz según las características de cada paciente. Materiales y métodos: se revisaron guías actualizadas, revisiones sistemáticas y guías de sociedades internacionales sobre el uso de opioides en DCNO y el uso de tramadol en patologías de DCNO como artrosis, lumbago crónico, dolor neuropático y fibromialgia. Resultados: tramadol no está indicado en el tratamiento de cuadros de dolor primario como fibromialgia y en DCNO secundario es un fármaco de segunda línea o no está recomendado. En dolor crónico neuropático (DCN) es segunda línea de tratamiento. En osteoartritis de cadera, rodilla y mano, se reporta efecto analgésico modesto. Sopesar riesgos versus beneficios en estos pacientes. En artritis reumatoide y lumbago crónico se desaconseja su uso. Conclusiones: tramadol es un medicamento seguro y efectivo si se indica, administra, supervisa y descontinúa adecuadamente. Sin embargo, puede asociarse a interacciones farmacológicas, efectos secundarios serios, conductas de abuso y usos ilícitos, por lo que es necesario conocer y manejar adecuadamente su farmacología e indicaciones.

Introduction: Tramadol is an opioid pain medicine commonly used for chronic non-cancer pain (CNCP) management. In Chile, it is part of the pharmacological arsenal available in primary care centers for treating specific CNCP pathologies, such as hip and knee arthrosis. Tramadol is considered a safe and effective drug. Nevertheless, there are reports of serious adverse effects of tramadol, such as poisoning, addiction, and death, probably caused by liver polymorphisms and drug interaction. The optimal dose of tramadol is patient-specific. Specific knowledge is needed to prescribe tramadol in a safe and effective way according to the patient's medical backward. Methods: We review updated guidelines, systematic reviews, and guidelines from international societies about the use of opioids and tramadol in CNCP pathologies such as osteoarthritis, chronic low back pain, neuropathic pain, and fibromyalgia. Results: Tramadol has no role in primary pain treatment, such as fibromyalgia, but is a second-line drug for chronic neuropathic pain (CNP) and some secondary pain syndromes. Tramadol has a modest analgesic effect in osteoarthritis patients. Clinicians should always weigh the risks and benefits before prescribing tramadol. Tramadol use is discouraged in rheumatoid arthritis and chronic lumbago. Conclusions: Tramadol is a safe and effective drug if correctly indicated, administered, supervised, and discontinued. However, it may be associated with pharmacological interactions, serious side effects, abuse behaviors, and illicit uses, and it is necessary that clinicians know and manage its pharmacology and indications appropriately.

La adición de midazolam intratecal al anestésico local mejora los bloqueos sensorial y motor y reduce la puntuación del dolor sin incrementar los efectos secundarios en la cirugía de miembros inferiores. Metaanálisis y revisión sistemática / Adding intrathecal midazolam to local anesthetics improves sensory and motor block and reduces pain score without increasing side effects in lower limb surgeries: A meta-analysis and systematic review

Este metaanálisis investiga el impacto de midazolam intratecal en la anestesia espinal, el control del dolor postoperatorio y los efectos secundarios relacionados con la anestesia en la cirugía de miembros inferiores. Realizamos una búsqueda en Medline, Science Direct, Google Scholar y Cochrane Library de los estudios que reportaron el inicio y la duración de los bloqueos sensorial y motor, el tiempo transcurrido hasta la primera solicitud de analgesia, el consumo de opioides durante 24h, el control del dolor postoperatorio y los efectos secundarios tras la administración de midazolam intratecal en pacientes sometidos a cirugía de miembros inferiores. Se identificaron 10 estudios, que se incluyeron en el metaanálisis. La revisión fue realizada siguiendo las directrices PRISMA, registrándose en la base de datos PROSPERO (ID-CRD42022346361) en agosto de 2022. Nuestros resultados muestran que los pacientes que reciben 1mg de midazolam intratecal reflejaron un tiempo de inicio de bloqueo significativamente más alto (p=0,001 [IC: −0,98, −0,31]), mayor duración de los bloqueos sensorial y motor (p<0,00001 [IC: 18,08, 39,12]; p=0,002 [IC: 0,45, 2]), y mayor tiempo transcurrido hasta la primera solicitud de analgesia de rescate (p=0,0003 [IC: 1,22, 4,14]). Las puntuaciones de dolor a las 4 y 12h postoperatorias fueron significativamente inferiores en los pacientes que recibieron midazolam intratecal (p=0,00001 [: −1,20, −0,47] y p=0,05 [IC: −0,52, −0,01] respectivamente). En conclusión, la adición de midazolam intratecal al anestésico local en la cirugía de miembros inferiores acorta el tiempo de inicio de los bloqueos sensorial y motor, incrementa la duración del bloqueo y prolonga el tiempo transcurrido hasta la primera solicitud de analgesia. Las puntuaciones del dolor a las 4 y 12horas postoperatorias fueron menores, no observándose efectos secundarios adicionales.(AU)

This meta-analysis was done to investigate the role of intrathecal midazolam in lower limb surgeries regarding prolongation of spinal block, postoperative pain control and associated side effects. The included studies reported onset and duration of sensory and motor block, time to first request analgesia, 24hours opioid consumption, postoperative pain control, and associated side effects following use of intrathecal midazolam for lower limb surgeries. This review was performed following the PRISMA guidelines and using the online databases, Medline, Science Direct, Google scholar and Cochrane library. We registered this review with the PROSPERO database (ID-CRD42022346361) in August 2022. A total of 10 randomised controlled trials were included in this meta-analysis. Our results showed patients receiving 1mg intrathecal midazolam showed significantly faster onset of sensory block (P=.001 [CI: −0.98, −0.31]). Duration of sensory and motor block were also significantly prolonged in intrathecal midazolam group (P<.00001 [CI: 18.08, 39.12], P=.002 [CI: 0.45, 2]). Intrathecal midazolam also increased the time to first request analgesia (P=.0003 [CI: 1.22, 4.14]). Pain scores at 4 and 12hours postoperatively were significantly lower in patients receiving intrathecal midazolam (P=.00001[CI: −1.20, −0.47] and P=0.05 [CI: −0.52, −0.01] respectively). In conclusion, the addition of intrathecal midazolam to local anesthetics in lower limb surgeries results in early onset of sensory and motor block. It also increases the duration of sensory and motor block. The time to first request analgesia is increased. VAS pain scores at 4 and 12hours postoperatively were also lower without any increased side effects.(AU)

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA.

OBJECTIVES: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX. METHODS: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2-24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions. RESULTS: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment. CONCLUSION: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.

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.

Anestesia libre de opioides en pacientes con tumor cerebralsupratentorial

Introducción: La anestesia para craneotomías es desafiante debido a las características del paciente neuroquirúrgico. Objetivo: Describir el comportamiento perioperatorio de los pacientes operados de tumor cerebral supratentorial con anestesia libre de opioides. Métodos: Se realizó un estudio descriptivo, longitudinal y retrospectivo en 75 pacientes intervenidos de tumor cerebral supratentorial con técnica de anestesia libre de opioides entre enero de 2018 a diciembre de 2019, en el Hospital Docente Clínico Quirúrgico General Calixto García. Se analizaron variables hemodinámicas (frecuencia cardíaca, tensión arterial sistólica, diastólica y media) y respiratorias (frecuencia respiratoria, saturación de oxígeno y dióxido de carbono espirado), antecedentes personales y complicaciones posoperatorias. Resultados: La edad promedio fue 54,2 ± 16,8 con predominio de mujeres, pacientes ASA II e hipertensos. El comportamiento de todos los parámetros evaluados estuvo en el rango de la normalidad. El 96 % de los pacientes no presentó complicaciones. Se presentaron cuatro complicaciones en tres pacientes y ninguna de ellas tuvo repercusión clínica importante. Conclusiones: La técnica libre de opioides proporcionó estabilidad en los parámetros hemodinámicos y respiratorios, con escasas complicaciones posoperatorias.

Introduction: Anesthesia for craniotomies is challenging due to the characteristics of the neurosurgical patient. Objective: To describe the perioperative behavior of patients operated on for supratentorial brain tumor with opioid-free anesthesia. Methods: A descriptive, longitudinal and retrospective study was conducted in 75 patients operated on for supratentorial brain tumor with the opioid-free anesthesia technique between January 2018 and December 2019 at Hospital Universitario General Calixto García. Hemodynamic (heart rate, as well as systolic, diastolic and mean blood pressure) and respiratory (respiratory rate, oxygen saturation and exhaled carbon dioxide) variables were analyzed, together with individual history and postoperative complications. Results: The average age was 54.2 ± 16.8, with a predominance of women, as well as of ASA II and hypertensive patients. The behavior of all the evaluated parameters was within the normal range. 96 % percent of the patients had no complications. Four complications occurred in three patients and none of them had important clinical repercussions. Conclusions: The opioid-free technique provided stability in hemodynamic and respiratory parameters, with few postoperative complications.

Anestesia libre de opioides en cirugía bariátrica laparoscópica

Introducción: La anestesia libre de opioides surge de las alternativas farmacológicas que permiten otra opción anestésica en el arsenal del anestesiólogo. Objetivo: Evaluar la efectividad y seguridad de una técnica anestésica libre de opioides en el paciente intervenido con cirugía bariátrica laparoscópica. Métodos: Se realizó un estudio observacional analítico, prospectivo y longitudinal en 23 pacientes operados con anestesia general multimodal libre de opioides. Pacientes mayores de 18 años con un índice de masa corporal mayor o igual a 35 kg/m2, con estado físico ASA II y III. Se evaluó la analgesia posoperatoria e intraoperatoria como una necesidad de la analgesia de rescate en el tiempo de recuperación y los efectos adversos. Resultados: Se demostró que la edad promedio fue 38,19 ± 8,73 con un predominio en el sexo femenino, los pacientes fueron clasificados como ASA II y obesos grados III. Hubo una estabilidad hemodinámica intraoperatoria. El 82,6 % de los pacientes no presentaron dolor posoperatorio en las primeras 24 h. No se presentaron pacientes con dolor severo. Requirieron analgesia de rescate cinco pacientes (21,7 %) en posoperatorio, y las complicaciones fueron escasas sin repercusión clínica. El tiempo promedio para la extubación fue de 6,7 ± 0,8 min y la recuperación total de 29,6 ± 0,8 min. Conclusiones: La técnica multimodal libre de opioides resultó segura y efectiva, con un adecuado estado de analgesia perioperatoria y escasas complicaciones en los pacientes intervenido con cirugía bariátrica laparoscópica.

Introduction: Opioid-free anesthesia arises from pharmacological alternatives that allow another anesthetic option in the anesthesiologist's arsenal. Objective: To evaluate the effectiveness and safety of an opioid-free anesthetic technique in patients undergoing laparoscopic bariatric surgery. Methods: An analytical, prospective and longitudinal observational study was carried out in 23 patients operated on with opioid-free multimodal general anesthesia. The patients studied were over 18 years of age, with a body mass index greater than or equal to 35 kg/m2, ASA physical status II and III. Postoperative and intraoperative analgesia were evaluated as a need for rescue analgesia in recovery time and adverse effects. Results: It was shown that the average age was 38.19 ± 8.73 with a predominance in the female sex, the patients were classified as ASA II and grade III obese. There was intraoperative hemodynamic stability. 82.6% of patients did not experience postoperative pain in the first 24 hours. There were no patients with severe pain. Five patients (21.7%) required rescue analgesia postoperatively, and complications were rare without clinical repercussions. The average time for extubation was 6.7 ± 0.8 min and total recovery was 29.6 ± 0.8 min. Conclusions: The opioid-free multimodal technique was safe and effective, with adequate state of perioperative analgesia and few complications in patients undergoing laparoscopic bariatric surgery.

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.

Adding intrathecal midazolam to local anesthetics improves sensory and motor block and reduces pain score without increasing side effects in lower limb surgeries: A meta-analysis and systematic review.

This meta-analysis was done to investigate the role of intrathecal midazolam in lower limb surgeries regarding prolongation of spinal block, postoperative pain control and associated side effects. The included studies reported onset and duration of sensory and motor block, time to first request analgesia, 24h opioid consumption, postoperative pain control, and associated side effects following use of intrathecal midazolam for lower limb surgeries. This review was performed following the PRISMA guidelines and using the online databases, Medline, Science Direct, Google scholar and Cochrane library. We registered this review with the PROSPERO database (ID-CRD42022346361) in August 2022. A total of 10 randomised controlled trials were included in this meta-analysis. Our results showed patients receiving 1mg intrathecal midazolam showed significantly faster onset of sensory block [P=.001 (CI: -0.98, -0.31)]. Duration of sensory and motor block were also significantly prolonged in intrathecal midazolam group [P<.00001 (CI: 18.08, 39.12), P=.002 (CI: 0.45, 2). Intrathecal midazolam also increased the time to first request analgesia [P=.0003, (CI: 1.22, 4.14)]. Pain scores at 4 and 12h postoperatively were significantly lower in patients receiving intrathecal midazolam [P=.00001 (CI: -1.20, -0.47) and P=.05 (CI: -0.52, -0.01) respectively]. In conclusion, the addition of intrathecal midazolam to local anesthetics in lower limb surgeries results in early onset of sensory and motor block. It also increases the duration of sensory and motor block. The time to first request analgesia is increased. VAS pain scores at 4 and 12h postoperatively were also lower without any increased side effects.

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.

Directive clinique no 443b : Opioïdes aux différentes étapes de la vie des femmes : Grossesse et allaitement.

OBJECTIF: Présenter aux professionnels de la santé les données probantes concernant l'utilisation des opioïdes et la santé des femmes. Les domaines d'intérêt sont la grossesse et les soins post-partum. POPULATION CIBLE: Toutes les femmes qui utilisent des opioïdes. RéSULTATS: Un dialogue ouvert et éclairé sur l'utilisation des opioïdes améliorera les soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation d'opioïdes par une approche tenant compte des traumatismes antérieurs donne au professionnel de la santé et à la patiente l'occasion de bâtir une alliance solide, collaborative et thérapeutique. Cette alliance permet aux femmes de faire des choix éclairés. Elle favorise le diagnostic et le traitement possible du trouble lié à l'utilisation d'opioïdes. L'utilisation ne doit pas être stigmatisée, puisque la stigmatisation affaiblit le partenariat (le partenariat entre patiente et professionnel de la santé). Les professionnels de la santé ceus-ci doivent comprendre l'effet potentiel des opioïdes sur la santé les femmes enceintes et les aider à prendre des décisions éclairées sur leur santé. DONNéES PROBANTES: Une recherche a été conçue puis effectuée dans les bases de données PubMed et Cochrane Library pour la période d'août 2018 à mars 2023 des termes MeSH et mots clés suivants (et variantes) : opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome et breastfeeding. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Tous les professionnels de la santé qui prodiguent des soins aux femmes et aux nouveaux-nés. RéSUMé POUR TWITTER: La consommation d'opioïdes pendant la grossesse coïncide souvent avec des problèmes de santé mentale et est associée à des conséquences néfastes pour la mère, le fœtus et le nouveau-né ; le traitement des troubles liés à la consommation d'opioïdes par agonistes peut être sûr pendant la grossesse lorsque les risques sont plus nombreux que les avantages. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Dualism, allosteric modulation, and biased signaling of opioid receptors: Future therapeutic potential.

Opioids are still the drugs of choice for the treatment of acute post-surgical pain and chronic cancer pain. Overprescribing of these drugs has given rise to an "opioid crisis" in some countries. In this context, attention has been drawn to the therapeutic potential of various ligands that act as allosteric modulators of orthosteric binding sites and modulate the drug's activity, affinity, potency, and even efficacy.

Patient opinion and acceptance of emergency department buprenorphine/naloxone to-go home initiation packs.

OBJECTIVES: Many emergency department (ED) patients with opioid use disorder are candidates for home buprenorphine/naloxone initiation with to-go packs. We studied patient opinions and acceptance of buprenorphine/naloxone to-go packs, and factors associated with their acceptance. METHODS: We identified patients at two urban EDs in British Columbia who met opioid use disorder criteria, were not presently on opioid agonist therapy and not in active withdrawal. We offered patients buprenorphine/naloxone to-go as standard of care and then administered a survey to record buprenorphine/naloxone to-go acceptance, the primary outcome. Survey domains included current substance use, prior experience with opioid agonist therapy, and buprenorphine/naloxone related opinions. Patient factors were examined for association with buprenorphine/naloxone to-go acceptance. RESULTS: Of the 89 patients enrolled, median age was 33 years, 27% were female, 67.4% had previously taken buprenorphine/naloxone, and 19.1% had never taken opioid agonist therapy. Overall, 78.7% believed that EDs should dispense buprenorphine/naloxone to-go packs. Thirty-eight (42.7%) patients accepted buprenorphine/naloxone to-go. Buprenorphine/naloxone to-go acceptance was associated with lack of prior opioid agonist therapy, less than 10 years of opioid use and no injection drug use. Reasons to accept included initiating treatment while in withdrawal; reasons to reject included prior unsatisfactory buprenorphine/naloxone experience and interest in other treatments. CONCLUSION: Although less than half of our study population accepted buprenorphine/naloxone to-go when offered, most thought this intervention was beneficial. In isolation, ED buprenorphine/naloxone to-go will not meet the needs of all patients with opioid use disorder. Clinicians and policy makers should consider buprenorphine/naloxone to-go as a low-barrier option for opioid use disorder treatment from the ED when integrated with robust addiction care services.

RéSUMé: OBJECTIFS: De nombreux patients des services d'urgence (SU) atteints d'un trouble lié à la consommation d'opioïdes sont des candidats à l'initiation à la buprénorphine/naloxone à domicile avec des trousses à emporter. Nous avons étudié les opinions des patients et l'acceptation des paquets de buprénorphine/naloxone à emporter, ainsi que les facteurs associés à leur acceptation. MéTHODES: Nous avons identifié des patients à deux urgences urbaines de la Colombie-Britannique qui répondaient aux critères relatifs aux troubles liés à l'utilisation d'opioïdes, qui ne suivaient pas actuellement un traitement aux agonistes des opioïdes et qui n'étaient pas en sevrage actif. Nous avons offert aux patients la buprénorphine/naloxone à emporter comme norme de soins, puis nous avons administré une enquête pour enregistrer l'acceptation de la buprénorphine/naloxone à emporter, le critère de jugement principal. Les domaines d'enquête comprenaient la consommation actuelle de substances, l'expérience antérieure avec le traitement aux agonistes opioïdes et les opinions liées à la buprénorphine/naloxone. Les facteurs du patient ont été examinés pour déterminer l'association avec l'acceptation de la buprénorphine/naloxone à emporter. RéSULTATS: Sur 89 patients inscrits, l'âge médian était de 33 ans, 27,0% étaient des femmes, 67,4% avaient déjà pris de la buprénorphine/naloxone et 19,1% n'avaient jamais pris de traitement aux agonistes opioïdes. Dans l'ensemble, 78,7% des répondants étaient d'avis que les SU devraient distribuer des paquets de buprénorphine/naloxone à emporter. Trente-huit (42,7%) patients ont accepté la buprénorphine/naloxone à emporter. L'acceptation de la buprénorphine/naloxone à emporter était associée à l'absence de traitement antérieur par agonistes opioïdes, à moins de 10 ans d'utilisation d'opioïdes et à l'absence de consommation de drogues injectables. Les raisons d'accepter comprenaient le fait de commencer un traitement pendant le sevrage; les raisons de rejeter comprenaient une expérience antérieure insatisfaisante de buprénorphine/naloxone et un intérêt pour d'autres traitements. CONCLUSION: Bien que moins de la moitié de notre population à l'étude ait accepté la buprénorphine/naloxone à emporter lorsqu'elle lui était offerte, la plupart ont pensé que cette intervention était bénéfique. Isolément, la buprénorphine/naloxone à emporter à l'urgence ne répondra pas aux besoins de tous les patients atteints de troubles liés à l'utilisation d'opioïdes. Les cliniciens et les décideurs devraient considérer la buprénorphine/naloxone à emporter comme une option à faible barrière pour le traitement des troubles liés à la consommation d'opioïdes par l'urgence lorsqu'elle est intégrée à de solides services de soins de la toxicomanie.

Mapa de utilización de mezclas analgésicas por vía parenteral en España. Proyecto MEDPAIN / Map of use of parenteral analgesic admixtures in Spain. MEDPAIN project

Objetivo: este estudio corresponde a la primera etapa del proyecto MEDPAIN «Actualización de mezclas analgésicas por vía parenteral: estudios de utilización, compatibilidad y estabilidad», y tiene por objetivo la elaboración de un mapa a nivel nacional del empleo de mezclas analgésicas en los hospitales y los centros sociosanitarios. Material y método estudio transversal, basado en una encuesta dirigida a farmacéuticos hospitalarios, durante el período diciembre 2020 - abril 2021. Se diseñó un cuestionario multirrespuesta en la plataforma RedCap® para su difusión a través de la lista de distribución de la Sociedad Española de Farmacia Hospitalaria. Se definió mezcla analgésica como la combinación de 2 o más principios activos, de los cuales al menos uno es analgésico. Una misma combinación de fármacos a distintas concentraciones, o administrada por diferentes vías, se consideró una misma mezcla a efectos de este estudio. Se registraron variables relacionadas con el centro participante y otras relacionadas con las mezclas analgésicas: composición farmacológica de la mezcla, vía de administración, frecuencia de uso, indicación, tipo de paciente (adulto/pediátrico), ámbito en el que se utiliza (hospitalario/domicilio) y lugar de preparación. Resultados se recibieron un total de 67 encuestas válidas (55,4%) procedentes de 13 comunidades autónomas. Los 67 centros sanitarios comunicaron un total de 462 mezclas analgésicas. La mediana de mezclas informadas por centro participante fue de 6 (RIC p25-p75 = 4,0-9,0). La mayoría de las mezclas notificadas se utilizan en adultos (93,9%) y en el ámbito hospitalario (91,8%); mayoritariamente se trata de mezclas protocolizadas y de uso frecuente. El 21,4% se preparan en el servicio de farmacia. En las mezclas descritas aparecen 26 fármacos distintos; predominan los analgésicos opioides, presentes en el 87,4% de las mezclas. El fármaco coadyuvante más frecuente es el midazolam. ... (AU)

Objetive: This study is the first part of the MEDPAIN project “Update of analgesic parenteral admixtures: studies of use, compatibility and stability”, and its goal is to develop a national map about the use of analgesic parenteral admixtures in healthcare settings. Methods Observational study, based on a survey aimed at Spanish hospital pharmacists, during the period December 2020–April 2021. The questionnaire was designed in the RedCap® platform and disseminated through the Spanish Society of Hospital Pharmacy distribution list. An analgesic parenteral admixture (AM) was defined as the combination of two or more drugs, with at least one of them being an analgesic. The same combination of active ingredients, at different concentration and/or administered by different routes, was considered as a unique AM in this study. Some registered endpoints were related to the characteristics of the healthcare settings participating in the study, and others were related to the AM, such as drugs, doses and concentration range, route of administration, frequency of use, indication and type of patient (adult/pediatric) and where they are prepared. Results A total of 67 valid surveys from healthcare settings of 13 Spanish Autonomous Communities were received. They reported 462 AM. Every healthcare center informed an average of 6 AM (ICR p25-p75 =4.0-9.0). Most of the reported mixtures were used in adults (93.9%) at hospital settings (91.8%), and they were mostly protocolized and frequently used. The 21.4% of them were compounded at the Pharmacy service. The AM included 26 different drugs, with opioid analgesics being present at the 87.4% of them. Midazolam was the most usual adjuvant drug. ... (AU)

[Translated article] Map of use of parenteral analgesic admixtures in Spain. MEDPAIN project.

OBJECTIVE: This study is the first part of the MEDPAIN project "Update of analgesic parenteral admixtures: studies of use, compatibility and stability", and its goal is to develop a national map about the use of analgesic parenteral admixtures in healthcare settings. METHODS: Observational study, based on a survey aimed at Spanish hospital pharmacists, during the period December 2020 - April 2021. The questionnaire was designed in the RedCap® platform and disseminated through the Spanish Society of Hospital Pharmacy distribution list. An analgesic parenteral admixture (AM) was defined as the combination of two or more drugs, with at least one of them being an analgesic. The same combination of active ingredients, at different concentration and/or administered by different routes, was considered as a unique AM in this study. Some registered endpoints were related to the characteristics of the healthcare settings participating in the study, and others were related to the AM, such as drugs, doses and concentration range, route of administration, frequency of use, indication and type of patient (adult/pediatric) and where they are prepared. RESULTS: A total of 67 valid surveys from healthcare settings of 13 Spanish Autonomous Communities were received. They reported 462 AM. Every healthcare center informed an average of 6 AM (ICR p25-p75 = 4.0-9.0). Most of the reported mixtures were used in adults (93.9%) at hospital settings (91.8%), and they were mostly protocolized and frequently used. The 21.4% of them were compounded at the Pharmacy service. The AM included 26 different drugs, with opioid analgesics being present at the 87.4% of them. Midazolam was the most usual adjuvant drug. According to the definition of AM in this study, there were finally 137 different combinations mainly with two drugs (40.6%), but also with three (37.7%), four (15.2%) and five ingredients (6.5%). CONCLUSION: In conclusion, this study reveals the wide variability in current clinical practice and shows which are the most used analgesic parenteral admixtures in our country.

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.

Amapola, lindísima amapola: de los opiáceos y los opioides, utilidad y riesgos / Poppy, beautiful poppy: opiates and opioids, utility and risks

Resumen El opio y sus derivados, y recientemente los opioides, han acompañado a la humanidad desde las civilizaciones más antiguas hasta la actualidad. Sus efectos analgésicos, hipnóticos y placenteros no pasaron desapercibidos para los antiguos, los consideraron de utilidad médica y beneficiosa para el estado de ánimo. Hoy en día no existe otro tipo de medicamentos que puedan tratar el dolor más intenso tan eficientemente como estos potentes analgésicos. Sin embargo, el uso médico y recreativo de los opiáceos y los opioides conlleva riesgos para la salud, como la tolerancia, la hiperalgesia y la adicción. Actualmente, además de ser indiscutiblemente el tratamiento médico más poderoso para mitigar el sufrimiento ocasionado por el dolor, se ha convertido también en un problema de salud pública debido a la alta cantidad de personas con trastorno por uso de opioides y por las muertes ocasionadas por sobredosis. En esta revisión se hará mención de las bondades de los opiáceos y opioides, y también de los efectos no deseados que estos producen.

Abstract Opium and its derivatives, and recently the opioids have accompanied the humankind since the ancient civilizations to the present day. Its analgesic, hypnotic and pleasant effects did not go unnoticed by ancient people, which considered most of these effects of medical utility and noticed that they had remarkable mood benefits. Currently, there are no other kind of drugs that can palliate intense pain as efficiently as these powerful analgesics. However, the medical and recreational use of opiates and opioids may carry health risks such as tolerance, hyperalgesia, and addiction. Nowadays, in addition to being indisputably the most powerful medical treatment to alleviate the suffering caused by pain, it has also become a public health problem due to the high number of people with opioid use disorder that have facilitated deaths caused by opioids overdose. In this review we will discuss the medical benefits of opiates and opioids, as much as the unwanted effects they produce.