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)

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)

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.

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.

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.

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.

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.

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.

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

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

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

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.

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

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. 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: This study reveals the wide variability in current clinical practice and shows which are the most used analgesic parenteral admixtures in our country.

Mastectomía libre de opioides bajo anestesia-analgesia epidural torácica en un paciente con estenosis traqueal crítica: caso clínico / Opioid-free mastectomy under thoracic epidural anesthesia-analgesia in a patient with critical tracheal stenosis: A case report

Mastectomy is traditionally performed under general anaesthesia and invasive ventilation, and is often complemented with regional techniques. In this setting, tracheal stenosis can pose a challenge to airway management. The aim of this report is to describe the successful management of a 68-year-old woman with severe subglottic tracheal stenosis undergoing mastectomy due to breast cancer. Surgery was performed without airway instrumentation under an opioid-free regimen consisting of thoracic epidural, propofol and dexmedetomidine perfusion, and non-opioid analgesics. Spontaneous ventilation and adequate perioperative analgesia were achieved. Opioid-free anaesthesia without airway instrumentation, consisting of thoracic epidural anaesthesia and sedation, is a good alternative in patients undergoing mastectomy in whom airway manipulation is best avoided.(AU)

La mastectomía se realiza tradicionalmente bajo anestesia general y ventilación invasiva, complementándose a menudo con técnicas regionales. En este contexto, la estenosis traqueal puede suponer un reto para el manejo de la vía aérea. El objetivo de este informe es describir el manejo exitoso de una mujer de 68 años de edad con estenosis traqueal subglótica severa, sometida a mastectomía debido a cáncer de mama. La cirugía se realizó sin instrumentación de la vía aérea bajo un régimen libre de opioides consistente en epidural torácica, propofol y perfusión de dexmedetomidina, y analgésicos no opioides, lográndose ventilación espontánea y analgesia perioperatoria adecuada. La anestesia libre de opioides sin instrumentación de la vía aérea, consistente en anestesia epidural torácica y sedación, es una buena alternativa en pacientes sometidos a mastectomía, en los que es mejor evitar la manipulación de la vía aérea.(AU)

[Opioid overdose prevention and naloxone diffusion (POP program): Results of an overview conducted among addiction specialized centres]. / Prévention des surdoses opioïdes et diffusion de naloxone (programme POP) : résultats d'un état des lieux réalisé auprès des structures d'addictologie.

INTRODUCTION: In France, opioids are responsible for the majority of overdose deaths in France. The antidote naloxone is available in France in take home formulations since 2016. Addiction specialized centres are in front-line for naloxone diffusion. The objective was to provide an overview of professional practices, difficulties and needs regarding overdose prevention and naloxone diffusion in these centres of the Provence-Alpes-Côte d'Azur (PACA) region. METHODS: The POP programme "Prevention and harm reduction of opioid overdoses in PACA region" aims to improve the care of patients at risk of overdose and facilitate naloxone diffusion. The 75 addiction specialized centres of the PACA region were invited to respond to a semi-structured interview or a telephone questionnaire. Data collected included 2020 centres' activity and professionals' perceptions of overdose risk in their active file, their practices, difficulties and needs. RESULTS: Overall, 33 centres answered. Among them, 22 were dispensing naloxone with a mean of 20 kits dispensed in 2020 (min-max: 1-100). Two strategies were pointed out: systematically offering of naloxone to all opioids users or targeting people considered at risk. Several difficulties limiting naloxone diffusion were expressed: a lack of knowledge from opioids users, refusal from people not feeling concerned or refusing the injectable formulation, a lack of training of some professionals to be comfortable with the tool or reglementary or time constraints. CONCLUSION: Naloxone diffusion is incrementally getting into common practices. However barriers are persisting. On the basis of expressed difficulties and needs, information and training materials were co-designed and diffused.

Estudio transversal retrospectivo de la evolución del consumo de opioides farmacológicos y de heroína en un grupo poblacional del área de Barcelona / Retrospective cross-sectional study of the evolution of the use of pharmacological opioids and heroin in a population group in the Barcelona area

Antecedentes: La dependencia de opioides está causando una epidemia en Estados Unidos, pero, a diferencia de la de los años setenta, parece más relacionada con los opioides de prescripción que con la heroína.ObjetivosEl objetivo de este estudio es evaluar si esta nueva epidemia ha llegado ya a nuestro medio y ver si hay cambios en el consumo y en las características de los consumidores.Pacientes y métodosEstudio transversal retrospectivo. Se incluyeron 1.140 pacientes entre el periodo 2012 y 2019, 633 de los cuales fueron primeras visitas a Centros de Atención y Seguimiento a las drogadicciones (CAS), 502 corresponden a visitas en urgencias por problemas relacionados con sobredosis o abstinencia de heroína o de opioides con receta, y los 5 restantes son recién nacidos de madres adictas a la heroína. Se analizaron los datos demográficos y las características de las sustancias de abuso, comparándose entre períodos parciales.ResultadosSe produjo una disminución global de las primeras visitas de pacientes a los CAS que referían adicción a la heroína (p=0,001), mientras que los adictos a los opioides de farmacia se han mantenido estables. Ha habido un aumento irregular del total de urgencias, consultas por sobredosis y por abstinencia, tanto de heroína como de opioides con receta (p=0,062, p=0,166 y p=0,005, respectivamente). Las urgencias relacionadas con opioides han sido menos frecuentes que las relacionadas con heroína. Los pacientes europeos no españoles han aumentado respecto los españoles.ConclusiónNo se ha producido un aumento preocupante del abuso de heroína ni de opioides con receta en nuestro medio. (AU)

Background: Opioid dependence is causing an epidemic in the US, but unlike the 1970s it seems more related to prescription opioids than heroin.ObjectivesThe objective of this study is to assess whether this new epidemic has already reached our environment and to see if there are changes in consumption and in the characteristics of consumers.Patients and methodsRetrospective cross-sectional study. 1,140 patients were included between 2012 and 2019, 633 of whom were first visits to Drug Addiction Care and (CAS) Monitoring Centers, 502 corresponding to emergency room visits for problems related to overdose or withdrawal of heroin or opioids with prescription, and the remaining 5 are newborns of mothers addicted to heroin. Demographic data and characteristics of the substances of abuse were analyzed, comparing between partial periods.ResultsThere was a global decrease in the first visits of patients to the CAS who reported heroin addiction (P=.001), while those addicted to pharmacy opioids have remained stable. There has been an irregular increase in total emergency visits, overdose consultations, and withdrawal consultations, both for heroin and prescription opioids (P=.062, P=.166 and P=.005, respectively). Opioid-related emergencies have been less frequent than for heroin. Non-Spanish European patients have increased compared to Spanish patients.ConclusionThere has been no worrying increase in heroin or prescription opioid abuse in our setting. (AU)

Política pública en cuidados paliativos y sus implicaciones sobre servicios, opioides y educación en Colombia / Public policy on palliative care and its implications for services, opioids, and education in Colombia

Introducción: El desarrollo de cuidados paliativos exige la intervención de múltiples dimensiones de salud pública, incluyendo la disponibilidad de servicios de salud, medicamentos esenciales y programas educativos. En Colombia se han realizado diversos cambios en las políticas públicas para promover la atención de personas con necesidades paliativas. Objetivo: Evaluar empíricamente las políticas públicas, existentes en cuidados paliativos y sus implicaciones sobre disponibilidad de servicios, opioides y programas educativos en los años 2010 ­ 2019 en Colombia. Materiales y métodos: Se diseñó un estudio mixto exploratorio secuencial en tres fases: identificación de indicadores empíricos de políticas nacionales, diagnostico situacional de cuidados paliativos y evaluación cualitativa de los resultados de la implementación de políticas en siete nodos territoriales de Colombia. Resultados: Se revisaron siete normas obteniendo 12 indicadores empíricos para la evaluación, seis de ellos no contaban con fuentes de información. El diagnostico nacional evidencia un aumento gradual de servicios y consumo de opioides en los años hito del desarrollo de políticas. 44 profesionales de cuidados paliativos perciben un efecto positivo de las políticas públicas en el consumo de opioides y bajos resultados para el dominio de servicios y educación Conclusiones: Existe una relación positiva entre políticas públicas y consumo de opioides, una relación cuantitativa positiva para servicios de cuidados paliativos y una relación cuanticualitativa negativa para programas educativos, lo que denota un bajo estatus operativo de las políticas construidas para mejorar el dolor y sufrimiento asociado a la enfermedad crónica avanzada.

Introduction: Palliative care development requires the intervention of multiple dimensions of public health, including the availability of health services, essential medicines, and educational programs. In Colombia, several changes have been made in public policy to promote the care of people with palliative needs. Objective: To empirically evaluate existing public policies on palliative care and their implications for the availability of services, opioids, and educational programs during the years 2010 to 2019 in Colombia. Materials and methods: A mixed sequential exploratory study was designed in three phases: identification of empirical indicators of national policies, palliative care situational diagnosis, and qualitative assessment of the results of policy implementation in seven regional nodes in Colombia. Results: Seven standards were reviewed, yielding 12 empirical indicators for assessment, six of which had no sources of information. The national diagnosis shows a gradual increase in services and opioid use during the landmark years of policy development. Forty-four palliative care professionals perceive a positive effect of public policy on opioid use and low outcomes for service and education domains. Conclusions: There is a positive relationship between public policy and opioid use, a positive quantitative relationship with palliative care services, and a negative quantitative-qualitative relationship with educational programs. This indicates a low operational status of policies designed to alleviate the pain and suffering associated with advanced chronic diseases.

Introdução: O desenvolvimento dos cuidados paliativos requer a intervenção de múltiplas dimensões da saúde pública, incluindo a disponibilidade de serviços de saúde, medicamentos essenciais e programas educativos. Na Colômbia, várias mudanças foram feitas nas políticas públicas para promover o cuidado de pessoas com necessidades paliativas. Objetivo: Avaliar empiricamente as políticas públicas existentes em cuidados paliativos e suas implicações na disponibilidade de serviços, opioides e programas educacionais nos anos 2010 - 2019 na Colômbia. Materiais e métodos: Desenhou-se um estudo misto exploratório sequencial em três fases: identificação de indicadores empíricos de políticas nacionais, diagnóstico situacional de cuidados paliativos e avaliação qualitativa dos resultados da implementação de políticas em sete nodos territoriais da Colômbia. Resultados: Sete normas foram revisadas, obtendo-se 12 indicadores empíricos para avaliação, seis delas não possuíam fontes de informação. O diagnóstico nacional mostra um aumento gradual nos serviços e consumo de opioides nos anos marcantes do desenvolvimento de políticas. 44 profissionais de cuidados paliativos percebem efeito positivo das políticas públicas sobre o consumo de opioides e resultados baixos para o domínio serviços e educação Conclusões: Existe relação positiva entre políticas públicas e consumo de opioides, relação quantitativa positiva para serviços de cuidados paliativos e negativa relação quantitativo-qualitativa para programas educativos, o que denota um baixo status operacional das políticas destinadas a melhorar a dor e o sofrimento associados à doença crônica avançada.