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Authors
Abstract(s)
Introdução: o Síndrome Doloroso Regional Complexo (SDRC) é um quadro doloroso crónico que afecta predominantemente as extremidades e cursa com alterações sensitivas, autonómicas, motoras e tróficas. Os subtipos I e II reflectem, respectivamente, a ausência ou presença de lesão nervosa periférica associada. O conhecimento da patofisiologia é incompleto, mas podem estar envolvidos fenómenos de sensibilização, disfunção vasomotora, inflamação neurogénica e neuroplasticidade patológica. O diagnóstico é clínico e o tratamento é multidisciplinar, sendo que não existe até agora nenhum tratamento farmacológico específico ou tido como primeira linha.
Objectivo: avaliar a eficácia dos bifosfonatos orais e/ou intravenosos na redução da dor e outros sintomas em adultos com SDRC tipo I.
Métodos: nesta revisão sistemática da literatura incluímos ensaios aleatorizados controlados que comparassem o efeito da administração oral e/ou intravenosa de bifosfonatos com a administração de placebo. Fizemos pesquisas na PubMed/MEDLINE, EMBASE, Scopus, Scielo, Índex RMP, DARE e ClinicalTrials.gov para encontrar estudos publicados entre 1970 e Fevereiro de 2017 sobre a utilização de bifosfonatos no tratamento do SDRC tipo I. Todos os títulos e abstracts foram avaliados de forma independente por dois revisores e a extração de dados dos artigos elegíveis também foi feita de forma independente com recurso a um formulário de extração de dados. O risco de viés das publicações foi avaliado com a “Cochrane collaboration’s tool for assessing risk of bias”. A dor foi o outcome primário a avaliar. No final da análise dos estudos e da avaliação dos outcomes considerados, procedeu-se à síntese narrativa dos resultados encontrados.
Resultados: identificámos cinco estudos aleatorizados, duplamente cegos e controlados com placebo que cumpriam os nossos critérios de inclusão. Estes estudos reuniram um total de 201 doentes e estudaram a utilização de Alendronato, Pamidronato, Clodronato ou Neridronato no tratamento de adultos com SDRC tipo I. Todos eles encontraram reduções estatisticamente significativas nos níveis de dor registados através da Escala Visual Analógica (EVA) dos doentes tratados com um bifosfonato. A diferença entre o grupo tratado com bifosfonatos e o grupo placebo também foi estatisticamente significativa em todos eles. A utilização de bifosfonatos teve um impacto positivo na redução da impotência funcional e na recuperação da densidade mineral óssea. Não ficou provado o efeito benéfico na redução do edema.
Discussão: as intervenções foram consideradas eficazes na redução da dor quando, em comparação com os valores obtidos inicialmente, se registaram reduções relativas >50% ou reduções absolutas >3cm na EVA, após o período de dupla-ocultação. A análise isolada de cada um dos RCT’s aponta para um efeito positivo dos bifosfonatos sobre a dor, apesar de nem todos terem sido considerados eficazes. Em relação aos restantes outcomes avaliados, os bifosfonatos contribuíram para uma melhoria estatisticamente significativa na maior parte deles.
Conclusões: os bifosfonatos têm um efeito positivo de redução da dor e também na impotência funcional e densidade mineral óssea. Encontrámos evidência de eficácia na redução da dor com a administração intravenosa (IV) de Clodronato, Alendronato e Neridronato.
Introduction: Complex regional pain syndrome (CRPS) is a chronic pain condition that presents with sensory, autonomic, motor and trophic disturbances, predominantly of the extremities. Types I and II respectively reflect the absence or the presence of associated peripheral nerve lesion. There is incomplete understanding of the pathophysiology but sensitization, vasomotor dysfunction, neurogenic inflammation and maladaptive neuroplasticity might be involved. Diagnosis is based solely on clinical signs and symptoms and treatment requires an interdisciplinary approach given that there is no clear definition of the pharmacological treatment of choice for CRPS. Objective: Evaluate the effectiveness of IV or oral bisphosphonates in reducing pain, functional impotence and other symptoms in adult patients with CRPS type I. Methods: In our review, we included RCT’s comparing the use of oral and/or IV bisphosphonates with placebo. We searched PubMed/MEDLINE, EMBASE, Scopus, Scielo, Índex RMP, DARE and ClinicalTrials.gov in order to find studies published between 1970 and February 2017 concerning bisphosphonates as a therapy for CPRS type I. Two reviewers independently scanned all titles and abstracts for eligible studies and extracted data from these last using a data extraction form. Risk of bias was accessed using the “Cochrane collaboration’s tool for assessing risk of bias”. Our primary outcome was pain. After having summarized the data we performed a narrative synthesis of the results. Results: we identified five randomized, double-blind, placebo controlled studies that fulfilled our inclusion criteria. These studies assembled a total of 201 patients and evaluated the use of Alendronate, Pamidronate, Clodronate or Neridronate in the treatment of adult patients with CRPS type I. There was a significant reduction in the level of pain evaluated by the Visual Analog Scale of patients treated with bisphosphonates in all five studies. The difference between bisphosphonates and placebo was significant as well. Bisphosphonates achieved positive results in reducing functional impotence and improving bone mineral content. There is no evidence of bisphosphonates ability to reduce edema. Discussion: a relative pain reduction of 50% or more and an absolute pain reduction of at least 3cm on the Visual Analog Scale were used as the cut-off point to consider an intervention effective. The independent analysis of each included RCT showed a positive effect of bisphosphonates on pain reduction, even though not all of them were considered effective. There was a statistically significant benefit of bisphosphonates in most of other considered outcomes. Conclusion: bisphosphonates have a positive effect in reducing pain and in functional impotence and bone mineral content. We found evidence of the effectiveness of intravenous Clodronate, Alendronate and Neridronate in reducing pain.
Introduction: Complex regional pain syndrome (CRPS) is a chronic pain condition that presents with sensory, autonomic, motor and trophic disturbances, predominantly of the extremities. Types I and II respectively reflect the absence or the presence of associated peripheral nerve lesion. There is incomplete understanding of the pathophysiology but sensitization, vasomotor dysfunction, neurogenic inflammation and maladaptive neuroplasticity might be involved. Diagnosis is based solely on clinical signs and symptoms and treatment requires an interdisciplinary approach given that there is no clear definition of the pharmacological treatment of choice for CRPS. Objective: Evaluate the effectiveness of IV or oral bisphosphonates in reducing pain, functional impotence and other symptoms in adult patients with CRPS type I. Methods: In our review, we included RCT’s comparing the use of oral and/or IV bisphosphonates with placebo. We searched PubMed/MEDLINE, EMBASE, Scopus, Scielo, Índex RMP, DARE and ClinicalTrials.gov in order to find studies published between 1970 and February 2017 concerning bisphosphonates as a therapy for CPRS type I. Two reviewers independently scanned all titles and abstracts for eligible studies and extracted data from these last using a data extraction form. Risk of bias was accessed using the “Cochrane collaboration’s tool for assessing risk of bias”. Our primary outcome was pain. After having summarized the data we performed a narrative synthesis of the results. Results: we identified five randomized, double-blind, placebo controlled studies that fulfilled our inclusion criteria. These studies assembled a total of 201 patients and evaluated the use of Alendronate, Pamidronate, Clodronate or Neridronate in the treatment of adult patients with CRPS type I. There was a significant reduction in the level of pain evaluated by the Visual Analog Scale of patients treated with bisphosphonates in all five studies. The difference between bisphosphonates and placebo was significant as well. Bisphosphonates achieved positive results in reducing functional impotence and improving bone mineral content. There is no evidence of bisphosphonates ability to reduce edema. Discussion: a relative pain reduction of 50% or more and an absolute pain reduction of at least 3cm on the Visual Analog Scale were used as the cut-off point to consider an intervention effective. The independent analysis of each included RCT showed a positive effect of bisphosphonates on pain reduction, even though not all of them were considered effective. There was a statistically significant benefit of bisphosphonates in most of other considered outcomes. Conclusion: bisphosphonates have a positive effect in reducing pain and in functional impotence and bone mineral content. We found evidence of the effectiveness of intravenous Clodronate, Alendronate and Neridronate in reducing pain.
Description
Keywords
Adultos Bifosfonatos Dor Síndrome Doloroso Regional Complexo