Assessing the Trends of Tramadol Utilization in the Medicare Part D Population in Rhode Island.

OBJECTIVE: To assess the trends in tramadol dispensing among Medicare Part D patients in Rhode Island. METHODS: An analysis was conducted of the Medicare Part D Provider Utilization and Payment Data Public Use File for the years 2013-2021. Chi squared tests were conducted to assess statistical significance of annual changes in proportions. RESULTS: Following tramadol becoming a controlled substance in 2014, the number of dispensed tramadol prescriptions and patients with a tramadol prescription decreased every subsequent year through 2021 (prescriptions: 42,157 to 33,026; patients: 12,654 to 9,653). The percentage of opioid prescriptions that were tramadol increased from 16.32% in 2013 to 21.19% in 2020. CONCLUSION: Tramadol utilization has been decreasing among the Medicare Part D population in Rhode Island while the percentage of opioid dispensings that were tramadol have been increasing. Future studies are needed to assess whether patients utilizing tramadol are at a higher risk for adverse outcomes.

Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis.

OBJECTIVE: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. METHODS: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. RESULTS: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. CONCLUSIONS: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

All-Cause Health Care and Work Loss Burden Associated With Nonsteroidal Anti-Inflammatory Drug and Opioid Treatment in Employed Patients With Osteoarthritis.

INTRODUCTION: This study estimated all-cause health care resource utilization (HRU) and costs and work loss outcomes associated with pain management of employed patients with osteoarthritis of the hip and/or knee. METHODS: Optum Health Care Solutions data were analyzed for employed patients prescribed nonsteroidal anti-inflammatory drugs, tramadol, or nontramadol opioids following diagnoses of osteoarthritis of the hip and/or knee. A pre-post design was used to evaluate changes in all-cause HRU and costs, and work loss days and associated costs. RESULTS: Costs rose for patients in all three cohorts (up to 198.3% for health care costs [tramadol] and up to 178.7% for work loss costs [tramadol]). Greatest increases in all-cause HRU included inpatient visits (237.9% [nonsteroidal anti-inflammatory drugs]; 600% [tramadol]). CONCLUSIONS: Study results provide evidence of increases in all-cause HRU and costs and work loss days and associated costs.

Urinalysis based assessment of compliance and drug use patterns in patients prescribed tramadol: A cross-sectional study from a tertiary care centre.

BACKGROUND: Strict adherence to pharmacological dosage regimens is a prerequisite to the success of most treatments, particularly for patients in drug abuse programs. The compliance of tramadol, an atypical non-scheduled narcotic analgesic, using objective method has not been adequately studied in an Indian setting. AIM: To evaluate the compliance and pattern of drug use among opioid-dependent subjects prescribed tramadol based on urinalysis. METHOD: Fifty male opioid-dependent patients (ICD 10), seeking treatment at a tertiary de-addiction treatment centre of North India on tramadol prescription for atleast past four weeks were included. Self-reported substance use was recorded using semi-structured proforma. Ten ml of urine was collected for the assessment of compliance of tramadol of other substance use (morphine, buprenorphine, dextropropoxyphene, pentazocine, cannabis, benzodiazepines, pheniramine). All these drugs were analyzed using the immunoassay-based Cassette test and Gas Chromatography in human urine. RESULT: Mean age of the participants was 42.8 years and the mean duration of opioid use was 15.9years. The urine specimen of all subjects tested positive for tramadol. Urinalysis revealed benzodiazepines, cannabis, and pheniramine to be the most common substances of use in this population. It was seen that agreement of self-reporting and urine test results was good for morphine (κ = 0.558) and cannabis (κ = 0.312) and was poor for buprenorphine, pentazocine, and pheniramine. CONCLUSION: The study demonstrates the continued use of several illicit or non-prescribed medications in a medication-assisted opioid treatment population. The results affirm the reliability of urinalysis as an adjunct for testing compliance in such a population.

Clinical and economic burden of prescribing tramadol and other opioids for patients with osteoarthritis in a commercially insured population in the United States.

ABSTRACT: In 2019, the American College of Rheumatology conditionally recommended tramadol and conditionally recommended against nontramadol opioids for patients with hip and knee osteoarthritis. Although tramadol is known to be less prone to opioid use disorders, little is known about the differing magnitude of negative clinical outcomes, health care resource utilization, and costs of tramadol relative to nontramadol opioids. Administrative claims records for commercially insured patients with osteoarthritis who were prescribed opioids were used to compare clinical and cost outcomes during a 3-year follow-up period by conducting a pre-post analysis and a matched case-cohort analysis. Data for 14,491 patients were analyzed: 4048 (28%) were initiated on tramadol, and 10,443 (72%) were initiated on nontramadol opioids. After matching, 4048 patients per cohort were analyzed. In each empirical analysis, tramadol patients did develop opioid use disorders; however, opioid use disorder rates were 3.5-fold higher in the nontramadol cohort (1.2% vs 4.2%). In addition, rates of other opioid-related clinical outcomes (falls, fractures, nausea, fatigue, and constipation) were also directionally lower among the tramadol cohort, although quantitatively similar (<5% difference) to the nontramadol cohort. Finally, in both analyses, the nontramadol cohort incurred higher levels of inpatient and emergency department visits and all-cause costs during the 3-year follow-up period. However, tramadol patients incur a higher incremental change (+$24,013) in costs relative to their pretreatment baseline compared with nontramadol (+$18,191). These real-world findings demonstrated lower risks with tramadol relative to other opioids, albeit risks and increased health care costs were present with tramadol, highlighting the need for further strategies to improve outcomes.

Tramadol para o tratamento da dor crônica / Tramadol para o tratamento da dor crônica

INTRODUÇÃO: A dor crônica está entre as condições médicas mais prevalentes em todo o mundo e pode ser considerada um importante problema de saúde pública. O tratamento adequado para a dor é uma ponderação cuidadosa entre benefícios e riscos. Para dor leve a moderada, o uso de opioides fracos é indicado como opção terapêutica após tentativa com analgésico não opioide e coadjuvante, mas que não sejam capazes de controlá-la. No entanto, estima-se que cerca de 80% da população mundial não tenha acesso, ou tenha acesso insuficiente ao tratamento. O objetivo do presente relatório é analisar as evidências científicas sobre eficácia, segurança e avaliação econômica do tramadol em pacientes com dor crônica de qualquer origem, seja musculoesquelética, dor neuropática, dor oncológica, entre outros. TECNOLOGIA: tramadol, comercializado como: Tramal®, Tramal Retard®, ANANGOR®, KELTIX®, NOVOTRAM®, TIMASEN SR®, TRAMALIV®, ATRACE®, DAISAN®, Gésico Duo®, PARATRAM®, REVANGE®, TILESTAL®, TROL PAR®, ULTRACET®, ZALDIAR®. PERGUNTA: Qual a eficácia e a segurança do tramadol em pacientes com dor crônica, quando comparado a codeína ou morfina em baixa dose (até 30mg/dia)? EVIDÊNCIAS CIENTÍFICAS: Vinte e quatro publicações foram incluídas, as quais eram ensaios clínicos randomizados (ECR) que contemplavam pessoas com dor musculoesquelética (n= 18), dor neuropática (n=4), dor oncológica (n=1) e dor nãooncológica (n=1). Não foram encontrados estudos de comparação direta entre a intervenção de interesse (tramadol) e os comparadores disponíveis no SUS (codeína ou morfina de baixas doses). Por esse motivo, quando possível, foram feitas comparações indiretas a fim de estimar o efeito relativo para as comparações de interesse (Material Suplementar 1). Dos estudos sobre dor musculoesquelética, metade foram classificados como alto risco de viés (n=9) e a outra metade, classificados como risco de viés incerto (n=9). Onze estudos contemplavam pacientes com osteoartrite - OA, um com artrite reumatoide - AR, cinco estudos de dor lombar e um estudo para dor mista (OA e lombar). As comparações incluídas foram: tramadol de liberação prolongada - ER - versus placebo (n=8); tramadol/acetaminofeno versus placebo (n=6); tramadol de liberação imediata - IR - versus placebo (n=1); morfina versus placebo (n=1); codeína versus placebo (n=1) e, por fim, codeína/acetaminofeno versus tramadol/acetaminofeno (n=1). AVALIAÇÃO ECONÔMICA: Como os resultados da meta-análise em rede demonstraram não haver diferenças estatisticamente significativas entre a eficácia e a segurança do tramadol comparado a codeína ou morfina em baixa dose, foi conduzida uma avaliação econômica do tipo análise de custo-minimização (ACM). Foi adotada a perspectiva do sistema público de saúde e os custos assumidos nessa análise foram restritos aos de aquisição dos medicamentos. Para o cálculo dos custos dos tratamentos, foram consideradas as quantidades unitárias de cada tratamento, calculadas de acordo com a dose média das posologias preconizadas nas respectivas bulas dos medicamentos de referência. Para a morfina, considerou-se a menor dosagem da bula, que corresponde a 30mg/dia (dose que pode promover analgesia equivalente a um opioide fraco). Assim, para uma mesma efetividade, foram identificados custos incrementais anuais por paciente de R$ 385,20 e R$ 104,40 do tramadol em relação a morfina e codeína, respectivamente (Material Suplementar 2). ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Foi considerado um horizonte temporal de cinco anos para estimar o impacto orçamentário da incorporação do tramadol. A população elegível foi calculada considerando os dados da demanda aferida de pacientes que utilizam os medicamentos do SUS de dor crônica, disponível na base de dados SABEIS (Sala Aberta de Situação em Saúde) com acréscimo anual da taxa de crescimento populacional do IBGE para a população brasileira. Foram propostos dois cenários: i) o cenário base: que representa o cenário atual, no qual os pacientes com dor crônica são tratados com morfina de baixa dose ou codeína; e ii) o cenário alternativo, no qual os pacientes utilizam tramadol, morfina de baixa dose ou codeína. Foi adotada uma taxa de difusão para o tramadol de 5% ao ano, iniciando com 30% e finalizando com 50% no quinto ano (2022 - 2026). Com a incorporação do tramadol no SUS para o tratamento de dor cônica, estimase um incremento de 1,6 milhão de reais no primeiro ano e em torno de 11 milhões ao final de cinco anos (Material Suplementar 3). MONITORAMENTO DO HORIZONTE TECNOLÓGICO (MHT): Os medicamentos fasinumabe, resiniferatoxin e tanezumabe foram detectados no MHT para pacientes com dor crônica. CONSIDERAÇÕES FINAIS: As evidências clínicas sumarizadas mostram que, no geral, os opioides fracos e morfina em baixa dose foram superiores ao placebo na população de dor crônica (independentemente da doença de base), porém quando comparados entre si (por meio de NMA) não apresentam diferença significativa com relação aos desfechos de eficácia e segurança. Estudos envolvendo pacientes com dor musculoesquelética crônica foram a maior amostra deste relatório. Para os desfechos dor, incapacidade e eventos adversos, tramadol monoterapia ou associado foi superior ao placebo, porém tramadol não apresentou diferença significativa em relação à codeína ou morfina em baixas doses. Para qualidade de vida, tramadol monoterapia ou associado foi superior ao placebo no componente físico, porém não houve diferença entre os grupos para o componente mental. Em geral, os estudos apresentaram alto risco de viés e a qualidade da evidência foi avaliada como baixa ou muito baixa para a maioria dos desfechos. Já nos estudos incluídos de dor neuropática, a eficácia da redução da dor em pacientes que receberam tramadol de liberação controlada foi superior ao placebo e ao tramadol/acetaminofeno. Não houve diferença entre tramadol/acetaminofeno versus placebo na redução da dor. Além disso, pacientes que receberam tramadol/acetaminofeno tiveram maior risco de ter eventos adversos de qualquer tipo, náusea, tontura, constipação e sonolência. Nesta classificação de dor, metade dos estudos teve alto risco de viés e a outra metade risco incerto, a qualidade da evidência foi avaliada como baixa ou muito baixa para a maioria dos desfechos. Em pacientes com dor oncológica, não foram incluídos estudos que avaliaram eficácia, porém houve maior incidência de eventos adversos naqueles tratados com tramadol comparado a codeína/acetaminofeno. O risco de viés do estudo foi classificado como incerto e a qualidade da evidência foi muito baixa. Por fim, em pacientes com dor não oncológica, não foi observada diferença entre tramadol vs. placebo para redução da intensidade da dor, enquanto para segurança o grupo tramadol obteve maior proporção de eventos adversos que aqueles que receberam placebo. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O relatório foi apreciado na 97ª Reunião Ordinária da Conitec, ocorrida no dia 06 de maio de 2021. O plenário recomendou o encaminhamento do relatório para consulta pública com parecer inicial desfavorável à incorporação de tramadol em razão de não ser superior em eficácia tampouco em segurança aos comparadores disponíveis no SUS considerados (codeína e morfina em baixa dose). Ademais, houve estimativa de aumento do impacto orçamentário com a possível incorporação. Por esses motivos, a comissão recomendou, preliminarmente, a sua não incorporação. CONSULTA PÚBLICA: A consulta pública nº 48 ficou vigente no período entre 27/05/2021 e 15/06/2021. Foram recebidas 95 contribuições, sendo 27 pelo formulário para contribuições técnico-científicas e 68 pelo formulário para contribuições experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Nas contribuições técnico-científicas poucas referências foram enviadas para avaliação e nenhum critério específico foi questionado, seja sobre evidência clínica, avaliação econômica ou impacto orçamentário. Dentre os comentários gerais das contribuições técnico científicas foi questionada a solicitação de uso do tramadol para pacientes com dor por infecção pela Chikungunya; o uso do tramadol para oncologia paliativa; e para fibromialgia. Nas contribuições sobre experiência de pacientes, profissionais, familiares ou pessoas interessadas no tema, eles opinam principalmente sobre a melhora e controle da dor, o aumento da qualidade de vida e a baixa dependência dos usuários quando comparado a outros opioides. Sobre os efeitos negativos do tramadol, profissionais que tiveram experiência com a tecnologia relataram, principalmente, náuseas e vômitos; sonolência; constipação intestinal; depressão respiratória; e que muitos pacientes intolerantes ao tramadol. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da Conitec presentes na 100ª reunião ordinária, no dia 04 de agosto de 2021, deliberaram por unanimidade pela não incorporação do tramadol para o tratamento da dor crônica. O Plenário considerou que não houve evidências adicionais suficientes para alterar a recomendação inicial, além de ressaltarem os medicamentos já disponíveis no SUS para o tratamento da dor crônica. Foi assinado o Registro de Deliberação nº 646/2021. DECISÃO: Não incorporar o tramadol para o tratamento da dor crônica, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 59, publicada no Diário Oficial da União nº 171, seção 1, página 76, em 9 de setembro de 2021.

Tramadol para o tratamento da dor crônica / Tramadol for the treatment of chronic pain

O QUE É DOR CRÔNICA?: A dor crônica é definida como a dor que persiste por um período igual ou superior a três meses. É uma das condições de saúde mais prevalentes em todo o mundo, podendo ser considerada um importante problema de saúde pública. Um estudo brasileiro estima que a prevalência de dor crônica em diferentes cidades pode estar entre 28% e 76%. Essa variação pode ser influenciada por fatores como idade e gênero, mas pessoas em idades avançadas e mulheres são mais propensas a desenvolvê-la. A dor crônica possui grande impacto na qualidade de vida e pode apresentar consequências físicas, psicológicas e sociais, sendo a principal causa de anos vividos com incapacidade, no mundo. A dor crônica tem diferentes origens e pode ser dividida em quatro grandes grupos: oncológica, musculoesquelética, neuropática e não específica. A dor crônica oncológica está relacionada ao câncer e pode ser decorrente não apenas dos tumores e suas metástases (formações de novos tumores em outras regiões do corpo), mas também do tratamento ou dos métodos de diagnóstico. Estima-se que esse subtipo de dor afete cerca de metade dos pacientes oncológicos em qualquer estágio e até 70% daqueles em estágio avançado. COMO OS PACIENTES COM DOR CRÔNICA SÃO TRATADOS NO SUS?: O Protocolo Clínico e Diretrizes Terapêuticas da Dor Crônica, publicado em 2012, indica o tratamento farmacológico para os diferentes tipos de dores, classificadas de acordo com uma escala em degraus numéricos que correspondem a uma determinada combinação de medicamentos. No caso de dor associada à inflamação ativa (nociceptiva) ou mista (que combina origens nociceptivas e neuropáticas), no degrau 1 podem ser utilizados analgésicos, anti-inflamatórios e fármacos para o tratamento de condições que podem estar associadas (antidepressivos e relaxantes musculares). Caso os sintomas não se atenuem após uma semana, com a utilização da dose máxima recomendada desses medicamentos, ocorre a passagem para o degrau seguinte, quando podem ser utilizados opioides fracos (no degrau 2) e fortes (no degrau 3). O tratamento da dor neuropática, por sua vez, envolve o uso de antidepressivos tricíclicos, de forma isolada ou em combinação com antiepilépticos, ficando os opioides reservados apenas para pacientes que não respondem aos medicamentos mencionados. Os opioides fracos disponíveis no SUS são a codeína e a morfina em baixas doses (30 mg/dia). O PCDT também menciona que pacientes com qualquer tipo de dor podem e devem lançar mão de tratamentos não medicamentosos como, por exemplo, a prática de atividade física regular, terapia cognitiva-comportamental, terapia com calor local e fisioterapia, conforme a capacidade de cada um e sob orientação de profissional habilitado. MEDICAMENTO ANALISADO: Tramadol: O cloridrato de tramadol é um analgésico (medicamento que combate a dor) opioide indicado para o alívio da dor de intensidade moderada a grave. É comercializado de forma isolada ou em associação com paracetamol, fármaco com propriedades analgésica e antipirética (que combate a febre). Os opioides são substâncias que atuam em uma área do cérebro chamada sistema nervoso central e possuem potentes propriedades analgésicas. Os opioides fracos atualmente disponíveis no SUS para o tratamento da dor crônica são a codeína e a morfina em baixas doses. Motivada pela atualização do PCDT da Dor Crônica, a Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde, do Ministério da Saúde (SCTIE/ MS), demandou a incorporação do tramadol para o tratamento de pacientes com dor crônica no Sistema Único de Saúde (SUS). Para determinar se o uso do tramadol é eficaz, efetivo e seguro, e se sua incorporação é viável para o SUS, recorreu-se a análises científicas e econômicas. As evidências clínicas mostram que, no geral, os opioides fracos orais foram superiores ao placebo (substância sem efeito). Porém, quando comparados entre si, não apresentaram diferença significativa com relação aos desfechos de eficácia e segurança. PERSPECTIVA DO PACIENTE: As chamadas públicas para participar da Perspectiva do Paciente sobre os temas de dor crônica foram abertas em dois períodos distintos: de 13/01/2021 a 17/01/2021 e de 19/01/2021 a 02/02/2021. As quatro chamadas públicas abertas tiveram um total de 32 inscrições. A indicação dos representantes titular e suplente foi feita a partir de consenso entre o grupo de inscritos. A participante relatou que é paciente de dor crônica há mais de 20 anos, com diagnóstico de fibromialgia e tenossinovite crônica. Mencionou que o tratamento da dor crônica deve ser multimodal e feito de acordo com o quadro e o histórico de cada paciente No seu caso, também é feito um tratamento psicoterápico e psiquiátrico e acompanhamento com reumatologista e endocrinologista. Disse que possui um neuroestimulador magnético medular implantado na região lombar para controle da dor, mas ainda assim necessita fazer uso de opioides fracos e fortes. O manejo é feito por um médico especialista, de acordo com a intensidade da dor. Dentre os medicamentos que estavam em avaliação, contou que apenas o diclofenaco não apresentou qualquer efeito no seu caso e que não pode mais fazer uso de anti-inflamatórios por ter adquirido uma gastrite medicamentosa. RECOMENDAÇÃO INICIAL DA CONITEC: A Conitec recomendou inicialmente a não incorporação no SUS do cloridrato de tramadol para o tratamento da dor crônica. A Comissão considerou que o medicamento (monodroga ou associado), além de não apresentar superioridade em eficácia ou segurança em relação aos opioides fracos já disponíveis no SUS (codeína e morfina em baixa dose), ainda provocaria aumento do impacto orçamentário. Esse tema foi discutido durante a 97ª Reunião Ordinária da Comissão, realizada nos dias 05 e 06 de maio de 2021. O assunto esteve disponível na consulta pública nº 48, durante 20 dias, no período de 27/05/2021 a 15/06/2021, para receber contribuições da sociedade (opiniões, sugestões e críticas) sobre o tema. RESULTADO DA CONSULTA PÚBLICA: Foram recebidas 95 contribuições, sendo 27 de natureza técnico-científica e 68 de experiência ou opinião. As contribuições técnico-científicas trouxeram poucas referências para avaliação e não houve questionamento de nenhum critério específico, seja sobre evidência clínica, avaliação econômica ou impacto orçamentário. As contribuições sobre experiência e opinião mencionaram a melhora e controle da dor, o aumento da qualidade de vida e a baixa dependência dos usuários quando comparado a outros opioides. Profissionais que tiveram experiência com a tecnologia relataram aspectos como náuseas e vômitos; sonolência; constipação intestinal; depressão respiratória; e a intolerância de muitos pacientes ao tramadol. Tais resultados não alteraram o entendimento do Plenário e a recomendação inicial da Conitec foi mantida. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da Conitec presentes na 100ª Reunião Ordinária, no dia 04 de agosto de 2021, recomendaram por unanimidade a não incorporação do tramadol para o tratamento da dor crônica no SUS. O Plenário ressaltou a disponibilidade de outros medicamentos para tratamento da dor crônica e considerou que as contribuições enviadas por meio da consulta pública não trouxeram argumentos que justificassem a alteração da recomendação inicial. DECISÃO FINAL: Com base na recomendação da Conitec, o secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde, no uso de suas atribuições legais, decidiu pela não incorporação, no âmbito do Sistema Único de Saúde (SUS), do tramadol para o tratamento da dor crônica.

Evaluación del efecto analgésico transoperatorio del tramadol comparado con la lidocaína en caninos oncológico / Assessment of the adverse effect of tramadol compared to lidocaine in the oncologic intraoperative in canines

Introducción: El estudio y tratamiento del dolor ha sido una de las preocupaciones más importantes en los últimos 30 años en el ámbito médico mundial. Desde hace varias décadas a nivel internacional se realizan estudios sobre el efecto del tramadol y la lidocaína como analgésicos intraoperatorio, con el fin de obtener una adecuada analgesia durante el procedimiento quirúrgico y el periodo posoperatorio inmediato. Objetivo: Comparar el efecto analgésico del tramadol y la lidocaína durante el período transoperatorio en caninos programados para intervención quirúrgica. Método: Se realizó un estudio prospectivo, comparativo, con animales programados para tratamiento quirúrgico por presentar tumores periféricos. Se incluyeron 10 animales divididos en 2 grupos. El grupo control (G-C) que recibió lidocaína sin preservo (lidocaína SP) en infusión continua durante el procedimiento quirúrgico y el grupo 1 (G-1) que se le administró tramadol endovenoso previo al acto quirúrgico. Se evaluaron variables hemodinámicas y de oxigenación como indicadores indirectos de dolor transoperatorio. Resultados: La muestra fue homogénea para la edad y el sexo. El comportamiento de las variables hemodinámicas resultó más estable durante la infusión de lidocaína. La saturación periférica de oxígeno fue similar con ambos medicamentos, así como la temperatura. Conclusiones: La infusión intravenosa de lidocaína SP durante el periodo transoperatorio en caninos oncológico demostró una mejor efectividad analgésica en comparación con el tramadol aplicado preoperatoriamente, según los parámetros evaluados(AU)

Introduction: Study and treatment of pain has been one of the most important concerns in the last thirty years in the worldwide medical field. For several decades, international studies have been carried out on the effect of tramadol and lidocaine as intraoperative analgesics, in order to achieve adequate analgesia during surgical procedures and the immediate postoperative period. Objective: To compare the analgesic effect of tramadol and lidocaine during the intraoperative period in canines scheduled for surgical intervention. Method: A prospective, comparative study was carried out with animals scheduled for surgical treatment due to peripheral tumors. Ten animals were included, divided into two groups: the control group, which received lidocaine without preservation in continuous infusion during the surgical procedure, and group 1, which was administered intravenous tramadol prior to the surgical act. Hemodynamic and oxygenation variables were assessed as indirect indicators of intraoperative pain. Results: The sample was homogeneous for age and sex. The behavior of the hemodynamic variables was more stable during the lidocaine infusion. Peripheral oxygen saturation was similar in both drugs, as well as temperature. Conclusions: Intravenous infusion of lidocaine without preservation during the intraoperative period in oncological canines showed better analgesic effectiveness compared to tramadol applied preoperatively, according to the parameters assessed(AU)

Single-Port vs Conventional Three-Port Video-Assisted Thoracoscopic Pulmonary Wedge Resection: Comparison of Postoperative Pain and Surgical Costs.

PURPOSE: Single-port video-assisted thoracoscopic (VATS) pulmonary wedge resection was reported in 2004. We started using single-port VATS (SPVATS) pulmonary wedge resection in 2017 and compared results between conventional three-port VATS (VATS group) and SPVATS (SPVATS group). METHODS: We identified 145 consecutive patients with VATS group and SPVATS group. Perioperative characteristics including pain and the number of stapler cartridges used were examined as the surgical outcomes, retrospectively. RESULTS: In all, 66 cases of SPVATS group and 79 cases of VATS group pulmonary wedge resection were compared. The rate of epidural anesthesia (p <0.0001) was significantly higher and operative time (p <0.0001) was significantly longer with VATS group than with SPVATS group. The number of stapler cartridges used, duration of drain insertion, and rate of postoperative complications did not differ significantly between groups. Average numerical rating scale (NRS) score on postoperative day 1 and postoperative day 7 (p <0.0001 each), maximum NRS score on postoperative day 7 (p = 0.0082) and amount of 25 mg tramadol (p = 0.0062) were significantly lower in SPVAS group than in VATS group. CONCLUSION: Our results suggest that SPVATS pulmonary wedge resection offers better pain control and cost-effectiveness than three-port VATS pulmonary wedge resection. These findings should contribute to the body of evidence for SPVATS.

Increasing tramadol utilisation under strict regulatory control of opioid prescribing - A cross-sectional study in Taiwan from 2002 through 2016.

BACKGROUND/PURPOSE: Prescribing of opioids to patients with non-cancer pain is strictly regulated in Taiwan, but tramadol is not included in the regulation on chronic opioid prescribing. This study aims to identify the utilization trend of prescribing tramadol and other opioid analgesics and investigate the influence of government regulation on opioid prescribing in Taiwan. METHODS: This cross-sectional study used the Taiwan National Health Insurance claims database and the cancer registry from 2001 through 2016. The annual number of adult opioid users, opioid utilization (Defined Daily Doses [DDDs]/1000 registrants) and the number of supply days were enumerated for each calendar year and stratified by cancer or non-cancer patients. Descriptive statistics were used to report the trends in utilization for each calendar year. RESULTS: The regulation strictly limited persistent use of opioids for patients with non-cancer pain, of which only a small proportion of fentanyl (20%) and morphine (<2%) users were prescribed with an annual number of supply days greater than 28 days. The annual utilization of morphine (6.4-53.5 vs. 1.1 to 9.6 DDD/1000 registrants) and fentanyl (8.3-37.0 vs. 0.16 to 1.8 DDD/1000 registrants) to patients with cancer was consistently higher than patients without cancer. In contrast to morphine and fentanyl, the utilization of tramadol prescribed to patients without cancer increased 92.2-fold (3.7-341.2 DDD/1000 registrants) from 2002 to 2016. CONCLUSION: The regulation in Taiwan limited the prescribing of selective opioids for patients with non-cancer pain and the substitution of tramadol for other opioids may have safety implications.

Continued Prescribing of Periprocedural Codeine and Tramadol to Children after a Black Box Warning.

BACKGROUND: Codeine and tramadol are commonly used analgesics in surgery. In 2013, the Food and Drug Administration (FDA) issued a contraindication to the use of codeine in tonsillectomy and adenoidectomy patients aged below 18 y. This warning was expanded in April 2017 to include tramadol and all children aged below 12 y. We sought to describe the prescribing of codeine and tramadol to contraindicated populations in Wisconsin before and after the release of the expanded FDA warning. MATERIALS AND METHODS: Using a statewide Wisconsin claims database, we identified common pediatric ambulatory surgical procedures across the specialties of otolaryngology, urology, general surgery, orthopedics, and ophthalmology. For these procedures, we examined the rates of perioperative codeine and tramadol prescription fills and change in prescribing after the FDA contraindication. RESULTS: Surgeons in all of the specialties studied continued to prescribe codeine to pediatric patients after the contraindication, but tramadol was rarely prescribed. Procedures with relatively high rates of codeine fills were strabismus repair (65% of opioid fills), circumcision >1 yo (22%), and laparoscopic appendectomy (15%). Codeine fills significantly declined after the contraindication to 6% for circumcision >1 yo and 5% for orchiopexy and inguinal hernia repair. Otolaryngology, which was subject to the 2013 codeine contraindication, has low rates of codeine fills (under 2.5%) for the whole period studied. Codeine prescribing for strabismus repair showed no significant decline. CONCLUSIONS: Codeine, and to a lesser extent tramadol, continue to be prescribed to contraindicated populations of children. This represents a target for future de-implementation interventions.

Use of the French healthcare insurance database to estimate the prevalence of exposure to potential drug-drug interactions.

PURPOSE: Drug-drug interactions (DDIs) require monitoring in an aging population with increasing polypharmacy exposure. We aimed to estimate the prevalence of exposure to potential DDIs using the French healthcare insurance system database, for six DDIs with various clinical relevance: angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs (ARBs-ACEIs + NSAIDs), antiplatelet agents and NSAIDs (AAP + NSAIDs), serotonergic drugs and tramadol (SD + T), statins and macrolides (S + M), oral anticoagulant and NSAIDs (OAC + NSAIDs), and colchicine and macrolides (C + M). METHODS: We used exhaustive healthcare data from a 1/97th random sample of the population covered by the French health insurance system (EGB) between 2006 and 2016. Exposure to a DDI was defined as overlapping exposure to two interacting drugs. The prevalence of exposure was estimated by year. RESULTS: Prevalence of exposure in 2016 was estimated at 3.7% for ARBs-ACEIs + NSAIDs, 1.5% for AAP + NSAIDs, 0.76% for SD + T, 0.36% for S + M, 0.24% for AOC + NSAIDs, and 0.02% for C + M. In 26% to 58% of episodes of exposure, the two interacting drugs were prescribed by the same physician and dispensed by the same pharmacy the same day. Between 2006 and 2016, the yearly prevalence was increasing for SD + T and for DDIs involving NSAIDs, and it was decreasing for those involving macrolides. CONCLUSION: Exposures to potential DDIs in France are not uncommon with a high proportion resulting from a co-prescription by the same physician. Monitoring the prevalence of exposure to DDIs is needed to implement prevention measures. Administrative data enable this surveillance in large and representative cohorts.

Drug utilization review of tramadol hydrochloride in a regional hospital in South Africa; findings and implications.

BACKGROUND: Drug utilization reviews (DURs) can be used to promote rational prescribing and ensure compliance with standard treatment guidelines. In recent years, the use of tramadol hydrochloride (HCl) for pain has increased significantly across countries. We sought to determine prescribing patterns and the use of tramadol in a regional hospital in South Africa to provide future guidance in view of increasing concerns with the prescribing of tramadol. METHOD: A prospective, quantitative and descriptive study was conducted over two months. Outpatient and inpatient prescriptions and ward requisitions where tramadol HCl was prescribed or ordered were identified, which included outpatients collecting antiretroviral treatment. Prescriptions were reviewed and evaluated to determine the level of compliance to the Standard Treatment Guidelines and Essential Medicines List (STGs/EML) for South Africa as a measure of rational prescribing. Quantities issued to the inpatient wards and expenditure incurred by the pharmacy departments were assessed to determine overall usage and total costs. RESULTS: In total, 415 tramadol HCl prescriptions were collected over a 2-month period. Compliance was 70.1% to the STGs/EML. The outpatient pharmacy department had the highest compliance at 76.4% while the antiretroviral pharmacy compliance was 29.1%. Most prescriptions dispensed at the outpatient pharmacy were from the Surgical Outpatient Department (140; 33.7%) and the Orthopedic Outpatient Department (108; 26.0%). The outpatient pharmacy had the highest tramadol HCl consumption and expenditure at $4,874.13 (R72,054.28), while the inpatient pharmacy's expenditure was $2,526.63 (R37,351.20), and the antiretroviral pharmacy $590.13 (R8,722.75). The hospital's tramadol HCl expenditure increased when compared to previous financial years, from $10,576.04 (R156,326.00) in 2014-2015 to $39,584.00 (R585,088.80) in 2016-2017. CONCLUSION: This study highlights the need for the implementation of monitoring and evaluation tools to enhance rational prescribing and use of tramadol HCl. These are being implemented and will be evaluated in future projects.

Medical Use of Long-term Extended-release Opioid Analgesics in Commercially Insured Adults in the United States.

OBJECTIVES: We examined the proportion of patients initiating extended-release (ER) opioids who become long-term users and describe how pain-related diagnoses before initiation of opioid therapy vary between drugs and over time. METHODS: Using MarketScan (2006-2015), a US national commercial insurance database, we examined pain-related diagnoses in the 182-day baseline period before initiation of ER opioid therapy to characterize indications for opioid initiation. We report the proportion who became long-term users, the median length of opioid therapy, and the proportion with cancer and other noncancer chronic pain, by active ingredient. RESULTS: Among 1,077,566 adults initiating ER opioids, 31% became long-term users, with a median length of use of 209 days. The most common ER opioids prescribed were oxycodone (26%) and fentanyl (23%), and the most common noncancer pain diagnoses were back pain (65%) and arthritis (48%). Among all long-term users, 16% had a diagnosis of cancer. We found notable variation by drug. Eighteen percent of patients initiating drugs approved by the Food and Drug Administration >10 years ago had evidence of cancer during baseline compared with only 8% of patients who received newer drugs. CONCLUSIONS: In a national sample of adults with private insurance, back pain was the most common diagnosis preceding initiation of opioid therapy. Opioids that have been approved within the last 10 years were more frequently associated with musculoskeletal pains and less frequently associated with cancer. Amid increasing concerns regarding long-term opioid therapy, our findings provide context regarding the conditions for which long-term opioid therapy is prescribed.

Oral Opioid Use during Vaginal Delivery Hospitalizations.

OBJECTIVE: This study aimed to determine the receipt of short-acting opioid medications during vaginal delivery hospitalizations. STUDY DESIGN: The Perspective database was analyzed to evaluate patterns of short-acting oral opioid use during vaginal delivery hospitalizations from January 2006 to March 2015. Unadjusted and adjusted models evaluating the role of demographic and hospital factors were created evaluating use of opioids. Hospital-level rates of opioid use were evaluated. Opioid receipt among women with opioid abuse or dependence was evaluated based on overall hospital rates of opioid use. RESULTS: Of 3,785,396 vaginal delivery hospitalizations from 2006 to 2015, 1,720,899 (45.5%) women received an oral opioid for pain relief. Opioid use varied significantly among the 458 hospitals included in the analysis, with one-third of hospitals providing opioids to <38% of patients, one-third to 38 to <59% of patients, and one-third to ≥59% of patients. When hospitals were stratified by overall opioid administration rates, women with opioid abuse or dependence were less likely to be given opioids in hospitals with low overall opioid rates. DISCUSSION: The use of opioid pain medications during vaginal delivery hospitalizations varied significantly among hospitals, suggesting that standardization of pain management practices could reduce opioid use.

A safe bet? Inter-laboratory variability in behaviour-based severity assessment.

Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment tools that provide species-relevant measurements of the animals' physical and affective state. In a three-centre study inter-laboratory robustness of body weight monitoring, mouse grimace scale (MGS) and burrowing test were evaluated. The parameters were assessed in naïve and tramadol treated female C57BL/6J mice. During tramadol treatment a body weight loss followed by an increase, when treatment was terminated, was observed in all laboratories. Tramadol treatment did not affect the MGS or burrowing performance. Results were qualitatively comparable between the laboratories, but quantitatively significantly different (inter-laboratory analysis). Burrowing behaviour seems to be highly sensitive to inter-laboratory differences in testing protocol. All locations obtained comparable information regarding the qualitative effect of tramadol treatment in C57BL/6J mice, however, datasets differed as a result of differences in test and housing conditions. In conclusion, our study confirms that results of behavioural testing can be affected by many factors and may differ between laboratories. Nevertheless, the evaluated parameters appeared relatively robust even when conditions were not harmonized extensively and present useful tools for severity assessment. However, analgesia-related side effects on parameters have to be considered carefully.

Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events.

OBJECTIVE: Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipts and outcomes among propoxyphene users before and aftermarket withdrawal. STUDY DESIGN: Using OptumLabs data, we studied 3 populations: commercial, Medicare Advantage (MA) aged (age 65+ y) and MA disabled (age below 65 y) enrollees. The exposed enrollees received propoxyphene in the 3 months before market withdrawal (n=13,622); historical controls (unexposed) received propoxyphene 1 year earlier (n=9971). Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures. PRINCIPAL FINDINGS: Aged MA enrollees illustrate the experience of all 3 populations examined. Following the market withdrawal, propoxyphene users in the exposed cohort experienced an abrupt decline of 69% in average daily MME, compared with a 14% decline in the unexposed. Opioids were discontinued by 34% of the exposed cohort and 18% of the unexposed. Tramadol and hydrocodone were the most common opioids substituted for propoxyphene. The proportion of each group receiving ≥4 g of prescription acetaminophen per day decreased from 12% to 2% in the exposed group but increased from 6% to 8% among the unexposed. Adverse events were rare and not significantly different in exposed versus unexposed groups. CONCLUSIONS: After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.

A national study on the use of opioid analgesics in dentistry.

The aim of this study was to assess the frequency of opioid analgesics prescribed by Brazilian dentists, potential regional differences and their association with socioeconomic and health-related factors. Data for all opioid prescriptions by dentists was obtained from the 2012 database of the National Controlled Substances Management System, regulated by the Brazilian Health Surveillance Agency. The number of defined daily doses (DDD) and DDDs per 1,000 inhabitants per day for each Brazilian state were calculated as the primary outcomes. DDDs were compared by regions and Brazilian states. Spearman's rho correlation coefficient was used to determine the influence of the states' characteristics, such as the Human Development Index; poverty; education; number of dentists per 100,000 inhabitants; visit to the dentist; dental care plan; good or very good oral health; number of pharmaceutical establishments per 100,000/inhabitants; and ability to get all prescribed medications. Data analysis was performed using IBM SPSS Statistics 25.0. A total of 141,161 prescriptions for opioids analgesics by 36,929 dentists were recorded, corresponding to 658,855 doses of opioids dispensed in 2012. The most commonly dispensed opioids were codeine associated with paracetamol (83.2%; n = 117,493). The national DDDs per 1,000 inhabitants per day was 0.0093 (range: 0.0002-0.0216). DDD per 1,000 inhabitants per day was positively associated to visits to dentists (rs = 0.630; P < 0.001) and inversely associated to poverty (rs = -0.624; p = 0.001). There are significant differences in opioid prescriptions in dentistry among the Brazilian states. These differences may be associated with non-clinical factors.

Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits.

OBJECTIVES: Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic. DESIGN: Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days. SETTING: Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012. PARTICIPANTS: We identified 96 753 patients with seizure and 888 540 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure. RESULTS: In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79). CONCLUSIONS: Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study.