The efficacy of buprenorphine compared with dexmedetomidine in spinal anesthesia: a systematic review and meta-analysis.

BACKGROUND: This study compares dexmedetomidine and buprenorphine as potential adjuvants for spinal anesthesia. Dexmedetomidine enhances sensory block and minimizes the need for pain medication, while buprenorphine, a long-acting opioid, exhibits a favorable safety profile compared to traditional opioids. METHODS: PubMed, Cochrane and EMBASE were systematically searched in December 2023. ELIGIBILITY CRITERIA: RCTs with patients scheduled for lower abdominal, pelvic, or lower limb surgeries; undergoing spinal anesthesia with a local anesthetic and buprenorphine or dexmedetomidine. RESULTS: Eight RCTs involving 604 patients were included. Compared with dexmedetomidine, buprenorphine significantly reduced time for sensory regression to S1 (Risk Ratio [RR = -131.28]; 95% CI -187.47 to -75.08; I2 = 99%) and motor block duration (RR = -118.58; 95% CI -170.08 to -67.09; I2 = 99%). Moreover, buprenorphine increased the onset time of sensory block (RR = 0.42; 95% CI 0.03 to 0.81; I2 = 93%) and increased the incidence of postoperative nausea and vomiting (RR = 4.06; 95% CI 1.80 to 9.18; I² = 0%). No significant differences were observed in the duration of analgesia, onset time of motor block, time to achieve the highest sensory level, shivering, hypotension, or bradycardia. CONCLUSIONS: The intrathecal administration of buprenorphine, when compared to dexmedetomidine, is linked to reduction in the duration of both sensory and motor blocks following spinal anesthesia. Conversely, buprenorphine was associated with an increased risk of postoperative nausea and vomiting and a longer onset time of sensory block. Further high-quality RCTs are essential for a comprehensive understanding of buprenorphine's effects compared with dexmedetomidine in spinal anesthesia.

Preventing Pediatric Opioid Poisoning: Unusual Sources and Scenarios.

This retrospective study analyzed 230 pediatric opioid exposures from a statewide poison control center over a 5-year period. Most exposures involved pharmaceutical opioids and children below 2-years-old. Narrative details were reviewed to identify uncommon sources of opioids involved in poisoning and highlight the need for tailored prevention strategies and guidance.

Eficacia anestésica de la buprenorfina en la anestesia multimodal intratecal en histerectomías abdominales: ensayo clínico / Anesthetic efficacy of buprenorphine in intrathecal multimodal anesthesia in abdominal hysterectomies: clinical trial

Resumen: Introducción: La buprenorfina en la anestesia multimodal intratecal ofrece buena eficacia anestésica en histerectomías, pero por el mal entendimiento de su farmacocinética su efecto no está bien descrito. Objetivo: Evaluar la eficacia anestésica de la buprenorfina en la anestesia multimodal intratecal en histerectomías abdominales. Material y métodos: Ensayo clínico, controlado, aleatorizado, doble ciego, en mujeres programadas para histerectomía abdominal, distribuidas en tres grupos: grupo BBMD: buprenorfina 150 μg + bupivacaína hiperbárica 0.15% 4.5 mg + morfina 150 μg + dexmedetomidina 7.5 μg; grupo FBMD: fentanilo 50 μg + bupivacaína hiperbárica 0.15% 4.5 mg + morfina 150 μg + dexmedetomidina 7.5 μg; y grupo BM: bupivacaína hiperbárica 0.42% 12.5 mg + morfina 150 μg. Se evaluó la eficacia anestésica previo a la incisión, durante la disección de la pared abdominal, al ingreso a cavidad abdominal, en la entrada de compresas a cavidad abdominal, en la salida de compresas de cavidad abdominal y en el postquirúrgico inmediato. Resultados: Se analizaron 108 mujeres. Los tres grupos tuvieron muy buena eficacia anestésica; sin embargo, al salir compresas, antes de la dosis peridural y en el postquirúrgico inmediato, el grupo BM fue el que tuvo más molestias (p = 0.004, 0.01 y 0.01, respectivamente). Conclusión: La anestesia multimodal con BBMD demostró muy buena eficacia anestésica.

Abstract: Introduction: Buprenorphine in intrathecal multimodal anesthesia offers good anesthetic efficacy in hysterectomies, but due to the misunderstanding of its pharmacokinetics its effect is not well described. Objective: To evaluate the anesthetic efficacy of buprenorphine in intrathecal multiomodal anesthesia in abdominal hysterectomies. Material and methods: Controlled, randomized, double-blind clinical trial in women scheduled for abdominal hysterectomy, divided into three groups: BBMD group: buprenorphine 150 μg + hyperbaric bupivacaine 0.15% 4.5 mg + morphine 150 μg + dexmedetomidine 7.5 μg; FBMD group: fentanyl 50 μg + hyperbaric bupivacaine 0.15% 4.5 mg + morphine 150 μg + dexmedetomidine 7.5 μg; and BM group: hyperbaric bupivacaine 0.42% 12.5 mg + morphine 150 μg. Anesthetic efficacy was avaluated prior to the incision, during dissection of the abdominal wall, upon entry into the abdominal cavity, upon entry of compresses into the abdominal cavity, upon exit of compresses from the abdominal cavity, and in the immediate postoperative period. Results: 108 women were analyzed, the 3 groups had very good anesthetic efficacy, however, when the compresses come out of the cavity, the BM group had the most discomfort (p = 0.004). Conclusion: Multimodal anesthesia with BBMD demostrated very good anesthetic efficacy.

Transdermal Opioids and the Quality of Life of the Cancer Patient: A Systematic Literature Review.

OBJECTIVE: This systematic literature review aims to evaluate the effectiveness of transdermal opioids in managing cancer pain and their impact on the quality of life (QoL) of patients. DATA SOURCES: A systematic literature review conducted following the PRISMA protocol, focusing on randomized clinical trials found in the Lilacs, Embase, PubMed, and SciELO databases over the last 20 years. STUDY SELECTION AND DATA EXTRACTION: We included randomized clinical trials, published in English, Portuguese, or Spanish, which assessed the impact of transdermal opioids on the QoL. Data extraction was facilitated using the Rayyan app. DATA SYNTHESIS: Six articles meeting the inclusion and exclusion criteria were analyzed. These studies covered a population ranging from 24 to 422 cancer patients experiencing moderate to severe pain. The risk of bias was assessed in each study, generally being categorized as uncertain or high. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The findings indicate that the analgesic effectiveness and side effects of transdermal formulations (specifically buprenorphine and fentanyl) for managing moderate to severe cancer pain are comparable to, or in some cases superior to, those of oral opioids traditionally employed. CONCLUSIONS: Transdermal therapy was suggested to have several advantages over oral opioid therapy in enhancing cancer patients' QoL. These benefits span various dimensions, including pain management, physical functioning, mental health, vitality, overall patient improvement, anger/aversion, strength/activity, general QoL, cognitive and emotional functions, fatigue, and insomnia.

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies.

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.

Skin abscess after the use of transdermal buprenorphine. Case report / Abscesso cutâneo após o uso de buprenorfina transdérmica. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Buprenorphine is a partial agonist semi-synthetic opioid used as an option in the treatment of patients with moderate to severe pain. The only presentation of buprenorphine available in Brazil is for transdermal use. This is an important route of drug administration, especially for the treatment of chronic pain, as it has several advantages, however it is not free from complications. The objective of this study was to present a serious adverse skin reaction after the use of transdermal buprenorphine, requiring surgical intervention. CASE REPORT: Female patient, 63 years old, hypertensive and diabetic, diagnosed with rheumatoid arthritis, fibromyalgia syndrome and lumbar disc herniation, with severe chronic pain, advised to use transdermal buprenorphine 10 mg to help control algic. After 24 hours of use, the patient developed erythema and local itching, requiring removal of the adhesive, but the lesion progressively worsened with the formation of an abscess and the need for surgical drainage. CONCLUSION: Transdermal buprenorphine has a favorable safety and tolerability profile, as it reduces the risk of unwanted effects such as respiratory depression, constipation and suicidal ideation. However, its use in senior patients with comorbidities, such as the immunosuppression described in this case, requires greater vigilance, due to the possibility of developing more serious adverse reactions.

RESUMO JUSTIFICATIVA E OBJETIVOS: A buprenorfina é um opioide agonista parcial semissintético utilizado como opção no tratamento de pacientes com dor de moderada a intensa. A única apresentação disponível da buprenorfina no Brasil é para uso por via transdérmica. Esta é uma via importante de administração de fármacos, principalmente para o tratamento de dor crônica, já que apresenta diversas vantagens, no entanto não é isenta de complicações. O objetivo deste estudo foi apresentar uma reação cutânea adversa grave após o uso de buprenorfina transdérmica, com necessidade de intervenção cirúrgica. RELATO DO CASO: Paciente do sexo feminino, 63 anos, hipertensa e diabética, com diagnósticos de artrite reumatoide, síndrome fibromiálgica e hérnia de disco lombar, portadora de dor crônica intensa, com orientação de utilizar buprenorfina transdérmica 10 mg para auxiliar o controle álgico. Após 24 h de uso, a paciente evoluiu com eritema e prurido local, sendo indicada a remoção do adesivo, porém a lesão piorou progressivamente com formação de abscesso e necessidade de drenagem cirúrgica. CONCLUSÃO: A buprenorfina transdérmica apresenta um perfil favorável de segurança e tolerabilidade, pois reduz o risco de efeitos indesejados, como depressão respiratória, constipação e ideação suicida. No entanto, seu uso em pacientes idosos portadores de comorbidades, como a imunossupressão descrita no caso, exige maior vigilância, devido à possibilidade de desenvolvimento de reações adversas mais graves.

Stability Study of a Compounded Sublingual Buprenorphine Solution for Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: Sublingual (SL) buprenorphine is a cornerstone of care in the treatment of adult opioid use disorder. Recent studies have demonstrated its advantages in the management of neonatal opioid withdrawal syndrome (NOWS). Commercially available SL tablets and transdermal patches are not amenable to neonatal use, and published compounding formulas of SL solutions contained undesirable excipients, including ethanol, sugars, and preservatives. The objective of this research is to explore the stability of a novel SL buprenorphine formulation free of alcohol, sugars, and preservatives. METHODS: A 0.075 mg/mL buprenorphine solution was prepared by diluting the commercial injectable solution with normal saline and packaged into polyethylene terephthalate amber prescription bottles and polypropylene amber oral syringes and stored in refrigeration. Quality assessments were conducted by visual, pH, and high-performance liquid chromatography (HPLC) analysis immediately after preparation, and at 7 and 14 days of storage. RESULTS: There were neither visual nor pH changes detected through 14 days. HPLC analysis indicated that all samples retained >99% initial buprenorphine concentration. Drug concentration increased slightly in the oral syringe after day 7, probably due to moisture loss. No degradation peaks were observed in chromatograms. CONCLUSIONS: This novel buprenorphine is free of alcohol, sugar, and preservatives, and it may offer a significant safety advantage for NOWS patients. Additional clinical studies are recommended to verify the bioavailability and efficacy of this formulation.

Stakeholder-Driven Intervention Development for Dialysis Trials Using a Design Sprint Methodology.

Rationale & Objective: Stigma contributes to ineffective treatment for pain among individuals with kidney failure on dialysis, particularly with buprenorphine pain treatment. To address stigma, we adapted a Design Sprint, an industry-developed structured exercise where an interdisciplinary group works over 5 days to clarify the problem, identify and choose a solution, and build and test a prototype. Study Design: Adapted Design Sprint which clarified the problem to be solved, proposed solutions, and created a blueprint for the selected solution. Settings & Participants: Five individuals with pain and kidney disease receiving dialysis, 5 physicians (nephrology, palliative care, and addiction medicine) and 4 large dialysis organization leaders recruited for specific expertise or experience. Conducted through online platform (Zoom) and virtual white board (Miro board). Analytical Approach: Descriptions of the Design Sprint adaptations and processes. Results: To facilitate patient comfort, a patient-only phase included four 90-minute sessions over 2-weeks, during which patient participants used a mapping process to define the critical problem and sketch out solutions. In a physician-only phase, consisting of two 120-minute sessions, participants accomplished the same tasks. During a combined phase of two 120-minute sessions, patients, physicians, and large dialysis organization representatives vetted and developed solutions from earlier phases, leading to an intervention blueprint. Videoconferencing technology allowed for geographically diverse representation and facilitated participation from patients experiencing medical illness. The electronic whiteboard permitted interactive written contributions and voting on priorities instead of only verbal discussion, which may privilege physician participants. A skilled qualitative researcher facilitated the sessions. Limitations: Challenges included the time commitment of the sessions, absences owing to illness or emergencies, and technical difficulties. Conclusions: An adapted Design Sprint is a novel method of efficiently and rapidly incorporating multiple stakeholders to develop solutions for clinical challenges in kidney disease. Plain Language Summary: Stigma contributes to ineffective treatment for pain among individuals with kidney failure on dialysis, particularly when using buprenorphine, an opioid pain medicine with a lower risk of sedation used to treat addiction. To develop a stigma intervention, we adapted a Design Sprint, an industry-developed structured exercise where an interdisciplinary group works over 5 days to clarify the problem, identify and choose a solution, and build and test a prototype. We conducted 3 sprints with (1) patients alone, (2) physicians alone, and (3) combined patients, physicians, and dialysis organization representatives. This paper describes the adaptations and products of sprints as a method for gathering diverse stakeholder voices to create an intervention blueprint efficiently and rapidly.

Multimodal postoperative analgesia with transdermal buprenorphine is a safe option in arthroscopic rotator cuff repair.

BACKGROUND: Arthroscopic rotator cuff repairs are associated with moderate-to-severe pain. Opioids are not the first line for postsurgical pain control due to their potential misuse and side effects. Transdermal buprenorphine represents an alternative for multimodal postoperative pain control. METHODS: This was a single-centre, prospective longitudinal exploratory study of patients undergoing arthroscopic rotator cuff repairs managed with multimodal analgesia with transdermal buprenorphine. Patients were followed-up by telephone at eight time points, assessing pain levels, rescue analgesics requirement and side effects. FINDINGS: Twenty-five patients with an average age of 63.4 ± 8.2 were included. Fourteen patients were ⩾65 years. Pain levels were similar among age groups at all time points, with no pain or mild pain (visual analogue scale 1-4) in most patients. The most frequent side effects were dizziness and somnolence. CONCLUSION: Transdermal buprenorphine provided a sustained analgesic effect after an arthroscopic rotator cuff repair during the acute postsurgical period. It showed a similar safety profile among younger and older patients.

Prescription of transdermal patches in Colombia: A real-world evidence study.

BACKGROUND: Transdermal drug delivery has contributed positively to medical practice. However, prescriptions that do not meet minimum quality criteria and medication errors are common. OBJECTIVE: The objective was to determine how transdermal patches are being prescribed to a group of patients in Colombia, the compliance with established requirements of such prescriptions and the comparisons between correct and incorrect prescriptions. METHODS: This was a cross-sectional study of prescriptions for transdermal patches using data from a population-based drug dispensing database between December 1 and 31, 2019. Medical prescriptions were randomly reviewed, establishing whether the drugs were appropriately prescribed by the manufacturer's indications or national regulations. Descriptive and bivariate analysis was performed. RESULTS: A total of 415 prescriptions were reviewed; the prescription was provided to 412 patients with a median age of 76.9 years, and 63.3% were women. Rivastigmine was the most prescribed transdermal patch (57.8%). 66.3% of all prescriptions did not meet the minimum appropriate prescribing standards, especially those for rivastigmine (97.1%). The 7.0% of all prescriptions had posology errors, especially prescriptions for buprenorphine (43.8%). Older patients (84.4% vs 52.5%), from the Pacific region (34.4% vs 23.7%), with manual formulations (22.1% vs 0.8%), dementia (49.0% vs 6.8%), and in management with lipid-lowering drugs (41.8% vs 30.5%), presented incorrect transdermal patch formulations more frequently (p < 0.05). CONCLUSION: The high proportion of inappropriately prescribed transdermal patches should draw the attention of those responsible for health care to improve the training of physicians and create prescription quality verification systems.

Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series.

PURPOSE: Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its impact on the adherence to and outcomes of OUD treatments. The objective of this case series was to describe patient and provider experiences, perceptions, and preferences when said patients were abruptly switched from Suboxone to one of the generic versions manufactured by Sandoz or Alvogen. PATIENTS AND METHODS: A retrospective chart review of 24 Suboxone-maintained OUD patients from a single clinic who were forced to switch to a generic was performed to collect withdrawal and craving symptoms that occurred after the switch, as well as toxicology results and changes in dose (documented by the provider). RESULTS: The medical records of 9 (37.5%) of the 24 patients showed that they were suffering from withdrawal symptoms and/or cravings, had had their doses adjusted, and/or had had a positive urine toxicology screen. All 9 subjects communicated a preference for the brand formulation over that of either of the generic versions; few expressed a preference for one generic formulation over the other. None of patients were able to switch back to the brand formulation, nor were any of them able to choose the generic that worked best for them. Insomnia, muscle pain, and gooseflesh skin were the most common withdrawal symptoms reported by the patients using the generics. Better outcomes were observed in patients who received a buprenorphine dose increase (2 mg) to suppress the withdrawal symptoms experienced while using the generics. CONCLUSION: Our study serves as a reference to prescribers regarding approaches (eg, a small dose adjustment) that may potentially encourage OUD treatment adherence and even improve outcomes in patients who appear to be decompensating after the brand-to-generic switch.

Antipanic-like effect of esketamine and buprenorphine in rats exposed to acute hypoxia.

The antidepressant effect of ketamine has been widely acknowledged and the use of one of its enantiomers, S-ketamine (esketamine), has recently been approved for the clinical management of treatment-resistant depression. As with ketamine, the non-selective opioid receptor-interacting drug buprenorphine is reported to have antidepressant and anxiolytic properties in humans and rodents. Given the fact that antidepressant drugs are also first line treatment for panic disorder, it is surprising that the potential panicolytic effect of these compounds has been scarcely (ketamine), or not yet (buprenorphine) investigated. We here evaluated the effects of ketamine (the racemic mixture), esketamine, and buprenorphine in male Wistar rats submitted to a panicogenic challenge: acute exposure to hypoxia (7% O2). We observed that esketamine (20 mg/kg), but not ketamine, decreased the number of escape attempts made during hypoxia, and this effect could be observed even 7 days after the drug administration. A panicolytic-like effect was also observed with MK801, which like esketamine, antagonizes NMDA glutamate receptors. Buprenorphine (0.3 mg/kg) also impaired hypoxia-induced escape, an effect blocked by the non-selective opioid receptor antagonist naloxone, indicating an interaction with classical ligand sites, such as µ and kappa receptors, but not with nociception/orphanin FQ receptors. Altogether, the results suggest that esketamine and buprenorphine cause rapid-onset panicolytic-like effects, and may be alternatives for treating panic disorder, particularly in patients who are refractory to standard pharmacological treatment.

Analgesia postoperatoria para craneotomías en pediatría: experiencia en un Hospital de Tercer Nivel / Postoperative analgesia for craniotomies in pediatrics: experience in a Third Level Hospital

Resumen: Introducción: Existe la creencia de que los pacientes no experimentan dolor intenso después de cirugía intracraneal. La estimulación simpática secundaria a dolor puede ocasionar hipertensión intracraneal y sangrado postoperatorio. Es controvertido el uso de opioides para analgesia postcraneotomías por temor a sus efectos colaterales que pueden enmascarar signos de alteración neurológica. En pediatría hay estudios limitados. Objetivo: Describir el nivel de control del dolor postcraneotomías al usar buprenorfina ketorolaco y ondansetrón en pacientes pediátricos. Métodos: Estudio de cohorte descriptivo. Incluimos niños de 0-17 años programados para cirugía intracraneal electiva. Para el control del dolor se administró buprenorfina, ketorolaco y ondansetrón en infusión por 30 horas. Se investigó dolor al iniciar la infusión a las cuatro, ocho, 12, 24 y 30 horas; variables hemodinámicas y grado de sedación. Resultados: 109 pacientes fueron incluidos. Se observó adecuado control del dolor en 71.56%, 28.4% tuvo control insuficiente con una diferencia estadísticamente significativa (p < 0.001). Hubo sedación moderada en 5.6% iniciando la infusión y a las 24 horas (4.5%) sin repercusión hemodinámica. Se detectó náusea en 8.2% y vómito en 6.64%; no se presentó sedación profunda, ni depresión respiratoria. Conclusiones: Estos hallazgos sugieren que es una opción efectiva para tratar el dolor postcraneotomías en pediatría.

Abstract: Introduction: There is still a belief that patients do not experience intense pain after intracranial surgery. Sympathetic stimulation associated with pain can lead to elevated intracranial pressure and postoperative haemorrhage. There is controversy about the use of opioids for postoperative analgesia in craniotomies, owing to fear of its side effects, which can mask signs of neurological alteration. There are limited studies in the pediatric patient for post-craniotomy analgesia. Objective: To describe the postcraneotomies pain control level, using buprenorphine in partnership with ketorolac and ondansetron in pediatric patients. Methods: Descriptive cohort study. For postoperative pain control, patients were given continuous infusion buprenorphine, ketorolac and ondansetron for 30 hours. The main variables to investigate were pain at beginning of infusion, at four, eight, 12, 24 and 30 hours, hemodynamic variables and depth of sedation. Results: 109 patients were included. Adequate control of pain was observed in 71.56% of patients, whereas in 28.4% insufficient control was found, with a statistically significant difference (p < 0.001). There was moderate sedation in 5.6% of the patients at the start of infusion and at 24 hours (4.5%), without significant impact on hemodynamic variables. Nausea was found in 8.2% and vomiting in 6.64%. No deep sedation, or respiratory depression was presented. Conclusions: These findings suggest that is an effective option to treat postcraneotomy pain in pediatric patients.

Exploración de la eficacia analgésica de dos parches transdérmicos analgésicos de opioides, buprenorfina y fentanilo, según sus variaciones de dosis en el control del dolor en pacientes paliativos oncológicos / Exploration of the analgesic efficacy of two-transdermal analgesic patches of opioids, buprenorphine and fentanyl, according to their dose variations in pain control in palliative cancer patients

Objetivo: El presente trabajo de investigación tuvo como objetivo explorar la eficacia analgésica mediante la comparación de la respuesta analgésica de los parches transdérmicos (PTD) de buprenorfina y fentanilo en dolor oncológico y patrón de uso. Material y Método: Se obtuvieron los datos y variables desde los registros clínicos de pacientes ingresados a la Unidad de Cuidados Paliativos (UCP) del Instituto Nacional del Cáncer (INC) que estaban bajo tratamiento en mayo del 2017. Se incluyó en este estudio a 78 pacientes con PTD, que representan el 13% de los pacientes en control mensual. De estos, 66 estaban bajo tratamiento con buprenorfina y 8 bajo tratamiento con fentanilo. Resultados: Los resultados mostraron que el PTD de buprenorfina se utiliza más frecuentemente que el de fentanilo. El principal motivo de rotación fue dolor no controlado, seguido por imposibilidad de contar con la administración por vía oral. En pacientes con mayores intensidades de dolor somático o visceral se indicó fentanilo y en aquellos con componente neuropático se prefirió el uso de buprenorfina. PTD de fentanilo fue indicado en dosis mayores que buprenorfina, incluso al comparar sus dosis equianalgésicas, siendo la variación de dosis alta para ambos parches: aumentó en promedio 257%. Se logró una mejor respuesta analgésica con buprenorfina, con una variación de intensidad de escala numérica verbal (ENV) de 2,94 y 1,88 puntos de promedio para buprenorfina y fentanilo, respectivamente. Adicionalmente, se presentó mayor reacción local dérmica con fentanilo. Conclusiones: Se evidenció diferencias en patrón de uso y, a diferencia de lo esperado, se obtuvo una mejor eficacia analgésica con buprenorfina. Datos que deben ser corroborados en estudios con mayor número de pacientes bajo tratamiento con fentanilo.

Objective: This study aims to explore analgesic efficacy comparisons of buprenorphine and fentanyl transdermal patches (TDP) in cancer pain and it's usage pattern. Material and Method: Data and variables were collected from patient's clinical reports who were admitted in the National Cancer Institute's (NCI) Palliative Care Unit (PCU) and were under treatment with TDP in May 2017. 78 TDP patients were studied and represented 13% of the monthly control patients in the PCU. Of these, 66 were under buprenorphine treatment and 8 under fentanyl treatment. Results: The results showed that buprenorphine TDP is more frequently used than fentanyl TDP, and the main reason for exchange between them was uncontrolled pain, followed by oral administration impossibility. Fentanyl TDP was indicated in patients with higher somatic or visceral pain intensities and Buprenorphine TDP was preferred in patients with neuropathic pain. Fentanyl TDP was indicated in higher doses than buprenorphine, even when comparing its equianalgesic doses, the dose variation was high for both patches throughout the treatment: it increased on average by 257%. A better analgesic response was achieved with buprenorphine, with a variation of intensity of the Verbal Numerical Scale (VNS) of 2.94 and 1.88 average points, for buprenorphine and fentanyl respectively. Additionally, there was a higher local dermal reaction with fentanyl TDP. Conclusions: Differences in usage patterns were evidenced and, unlike what was expected, better analgesic efficacy was obtained with buprenorphine TDP. This data should be corroborated in receiving fentanyl treatment.

Brand-to-Generic Substitution of Buprenorphine/Naloxone Sublingual Film in Puerto Rico: A Case Study.

A 56-year-old patient with a 1-year history of stable maintenance treatment with Suboxone for opioid use disorder (OUD) was switched to a generic formulation in May of 2019. The patient reported experiencing-over the course of the following 3 months-withdrawal symptoms when switched to the Alvogen-produced generic formulation in May of 2019 and then to the Sandoz-produced version in July of that same year, she also was positive for fentanyl during that time. As a result, the buprenorphine dose was increased, and the patient was stable at this new dose using the generic versions. Blood levels pre- and post-change (not reported in previous case reports) showed maximum buprenorphine concentration being reached more quickly when the brand-name drug was used. Additionally, the area under the curve (AUC) values indicate that the generic formulation had higher exposures than the brand-name drug. Based on the clinical impact of the brand-to generic switch in this patient, further research in this area is warranted. In the meantime, clinicians should carefully monitor their patients so that, if warranted, dose adjustments can be made quickly and safely to minimize negatively impacting the OUD therapy outcomes of patients.

Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico.

BACKGROUND: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. METHODS: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. RESULTS: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0-8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0-8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h-1), distribution (k12= 2.34 h-1, k14 = 1.29 h-1), metabolism (k24 = 1.28 × 10-1 h-1, k23 = 6.43 × 10-2 h-1, k35 = 1.23 × 10-1 h-1, k45 = 8.73 × 10-1 h-1), and elimination (k30 = 3.81 × 10-3 h-1, k50 = 1.27 × 10-1 h-1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. CONCLUSIONS: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico.

Use of Sublingual Nitrates for Management of Limb Ischemia Secondary to Inadvertent Intra-Arterial Buprenorphine/Naloxone (Suboxone®) Film Injection.

Multiple case reports have signaled a rise in buprenorphine abuse in the US, particularly among inmates. We present the case of limb ischemia secondary to accidental intra-arterial buprenorphine/naloxone film injection successfully treated with sublingual nitroglycerin. A 39-year-old man with history of intravenous drug use presented sudden severe left hand pain since three days prior to evaluation. Pain was preceded by self-injection of dissolved buprenorphine/naloxone sublingual film onto the affected arm. An arteriogram suggested severe vasoconstriction in the absence of frank thrombosis. Patient was initially treated with continuous heparin infusion and nifedipine. Forty-eight hours later, due to poor response, sublingual nitroglycerin was added to therapy. Digits regained color, sensation, and pain resolved within 15 minutes of administration of sublingual nitroglycerin. The presence of acute limb ischemia caused by prolonged vasospasm is a very rare complication. A normal angiogram should raise suspicion regarding vasospasm as the mechanism of ischemia, and prompt nitroglycerin therapy.

[Transdermal buprenorphine for acute postoperative pain: a systematic review]. / Uso da buprenorfina transdérmica na dor aguda pós­operatória: revisão sistemática.

BACKGROUND AND OBJECTIVES: Postoperative pain is still a major concern in several surgical procedures. Multimodal analgesia is best for postoperative pain management; however, opioid therapy is still the main treatment for pain after surgical procedures. Transdermal buprenorphine is a partial µ agonist opioid widely used for chronic pain syndromes, with limited evidence for acute postoperative pain. A systematic review of studies examining transdermal buprenorphine for acute pain management after surgery was conducted. CONTENTS: Data from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials that evaluated total postoperative pain, postoperative analgesic consumption, drug-related side effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients) were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours before surgery, maintaining use from 1 to 8 days after the procedure. Most studies showed lower or similar postoperative pain scores, postoperative analgesic consumption and patient satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, flurbiprofen and parecoxib. The incidence of side effects varied between studies, with most showing no increase in drug-related side effects with buprenorphine use, except one study, which compared buprenorphine to oral tramadol, and one to transdermal fentanyl. However, most results were derived from evidence with an overall high or unclear risk of bias. CONCLUSIONS: Although more studies are necessary, initial results show that transdermal buprenorphine seems to be an effective and safe opioid choice for management of acute postoperative pain.

Transdermal buprenorphine for acute postoperative pain: a systematic review / Uso da buprenorfina transdérmica na dor aguda pós-operatória: revisão sistemática

Background and objectives: Postoperative pain is still a major concern in several surgical procedures. Multimodal analgesia is best for postoperative pain management; however, opioid therapy is still the main treatment for pain after surgical procedures. Transdermal buprenorphine is a partial µ-agonist opioid widely used for chronic pain syndromes, with limited evidence for acute postoperative pain. A systematic review of studies examining transdermal buprenorphine for acute pain management after surgery was conducted. Contents: Data from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials that evaluated total postoperative pain, postoperative analgesic consumption, drug-related side effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients) were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours before surgery, maintaining use from 1 to 28 days after the procedure. Most studies showed lower or similar postoperative pain scores, postoperative analgesic consumption and patient satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, flurbiprofen and parecoxib. The incidence of side effects varied between studies, with most showing no increase in drug-related side effects with buprenorphine use, except one study, which compared buprenorphine to oral tramadol, and one to transdermal fentanyl. However, most results were derived from evidence with an overall high or unclear risk of bias. Conclusions: Although more studies are necessary, initial results show that transdermal buprenorphine seems to be an effective and safe opioid choice for management of acute postoperative pain

Justificativa e objetivos: A dor pós-operatória ainda é uma queixa importante em vários procedimentos cirúrgicos. A analgesia multimodal é a melhor conduta para a dor pós-operatória, embora a terapia com opioides ainda seja o principal tratamento para a dor após procedimentos cirúrgicos. A buprenorfina transdérmica é um opioide agonista µ amplamente prescrito nas síndromes de dor crônica, mas com limitada evidência do seu uso para dor aguda no pós-operatório. Realizamos revisão sistemática de estudos que examinaram o papel da buprenorfina transdérmica no tratamento da dor aguda pós-operatória. Conteúdo: Revisamos os dados de PubMed, Embase, Registro Central de Ensaios Controlados Cochrane (CENTRAL), CINAHL via EBSCOhost e LILACS, incluindo estudos clínicos randomizados que avaliaram a dor pós-operatória total, consumo de analgésicos pós-operatórios, efeitos colaterais relacionados a medicamentos e satisfação do paciente com esquema de analgesia. Dados de nove estudos (615 pacientes) foram incluídos nesta revisão. A maioria dos estudos iniciou o uso transdérmico de buprenorfina 6 a 48 horas antes da cirurgia, mantendo o uso de 1 a 28 dias após o procedimento. A maioria dos estudos encontrou valores semelhantes ou menores para o escore de dor pós-operatória, consumo pós-operatório de analgésicos e satisfação do paciente quando a buprenorfina foi comparada ao placebo, tramadol, celecoxibe, flurbiprofeno e parecoxibe. A incidência de efeitos colaterais oscilou nos estudos, e a maioria não mostrou aumento de efeito colateral relacionado ao uso de buprenorfina, exceto em dois estudos, um que comparou buprenorfina ao tramadol oral e outro ao fentanil transdérmico. No entanto, a maioria dos resultados foi obtida a partir de evidências com um risco geral alto ou risco de viés impreciso. Conclusões: Embora sejam necessários mais estudos, os resultados iniciais mostram que a buprenorfina transdérmica parece ser uma forma de administração segura e efetiva de opioide no tratamento da dor aguda pós-operatória

Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome.

OBJECTIVE: To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome (NAS) admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: From the Pediatrix Clinical Data Warehouse database, we identified all infants born at ≥36 weeks of gestation between 2011 and 2015 who were diagnosed with NAS (International Classification of Diseases, Ninth Revision code 779.5) and treated with methadone or morphine in the first 7 days of life. We used multivariable Cox proportional hazards regression analysis to quantify the association between initial treatment and LOS after adjusting for maternal age, maternal race/ethnicity, maternal drug use, maternal smoking, gestational age, small for gestational age status, inborn status, and discharge year. RESULTS: We identified a total of 7667 eligible infants, including 1187 treated with methadone (15%) and 6480 treated with morphine (85%). Birth weight, gestational age, and sex were similar in the 2 groups. Methadone treatment was associated with a 22% shorter median LOS (18 days [IQR, 11-30 days] vs 23 days [IQR, 16-33]; P < .001) and a 19% shorter median NICU stay (17 days [IQR, 10-29 days] vs 21 days [IQR, 14-36 days]; P < .001). After adjustment, methadone was associated with a shorter LOS (hazard ratio for discharge, 1.24; 95% CI, 1.11-1.37; P < .001) CONCLUSION: Among infants born at ≥36 weeks of gestation with NAS, initial methadone treatment was associated with a shorter LOS compared with morphine treatment. Future prospective comparative effectiveness trials to treat infants with NAS are needed to verify this observation.