Eficácia da associação do tramadol aos antieméticos antagonistas do receptor da serotonina no tratamento da dor aguda pós-operatória: revisão sistemática e metanálise
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2017-02-22
Autores
Lima, Vinicius Sepúlveda [UNESP]
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Universidade Estadual Paulista (Unesp)
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Introdução: A dor é um dos sintomas mais prevalentes relatados pelos pacientes e representa um significativo problema de saúde em todo o mundo, porque afeta a qualidade de vida. Tramadol é uma escolha racional para o manejo da dor no cenário pós-operatório. Entretanto, há um aumento do risco de náuseas e vômitos com o tramadol quando doses maiores são rapidamente injetadas. Por essa razão, um antiemético é frequentemente prescrito em associação com o tramadol. Entre esses fármacos, os antieméticos antagonistas do receptor da serotonina (AARS) ex: ondansetrona, dolasetron, granisetron, etc são opções de tratamentos bem estabelecidos, que podem ter valor especial na redução da êmese associada ao tramadol. Ambas as drogas atuam via serotonina (5-HT). Os AARS são antagonistas do receptor da 5-HT, enquanto o tramadol é um inibidor da recaptação e aumenta a liberação deste neurotransmissor. A coadministração desses fármacos pode influenciar as suas cinéticas. Objetivo: Avaliar a relação risco/benefício do uso do tramadol em conjunto aos antieméticos antagonistas da serotonina para tratamento de dor e náuseas e vômitos pós-operatórios (NVPO), em adultos, por meio de revisão sistemática da literatura. Tipo de estudo: revisão sistemática e metanálise de ensaios clínicos randomizados. Estratégias de busca: Foram pesquisadas as bases de dados Medline, CENTRAL, Embase e Lilacs. A última busca foi em 30 de dezembro de 2015. Critério para a seleção dos estudos: Foram incluídos ensaios clínicos que avaliaram qualquer interação dos AARS na eficácia analgésica do tramadol e os efeitos deste último na eficácia antiemética dos AARS no manejo da dor aguda pós-operatória, em adultos. Análise e coletas de dados: Dois revisores selecionaram independentemente os estudos relevantes, avaliaram a qualidade metodológica e extraíram os dados. Calculamos o risco relativo (RR) e o número necessário para o tratamento (NNT). Também coletamos informações sobre efeitos adversos. Resultados: Treze estudos foram incluídos com um total de 899 participantes. Fomos capazes de incluir os dados de 510 participantes de sete estudos na metanálise. Os resultados obtidos dos ECR sugerem um aumento significativo no consumo de tramadol com ondansetrona quando comparado a solução salina em todos os períodos estudados, especialmente na décima segunda hora (Diferença de médias (DM) 182,46, 95% Intervalo de Confiança (IC) 137,85 a 227,07; p < 0,00001). Além disso, há um possível aumento na necessidade de resgate antiemético nos pacientes que receberam a solução salina quando comparado a ondansetrona (Risco relativo (RR) 0,61, 95% IC 0,37 a 1,01; p = 0,05). Na comparação dos AARS com outros antieméticos, houve maior consumo de tramadol na associação com AARS nos momentos 4, 12 e 24 h (DM (4h) 29,12, 95% IC 21,83 a 36,42; p < 0,00001). Houve melhor desempenho na prevenção de NVPO dos AARS quando comparados com outros antieméticos, especialmente a metoclopramida (RR (8h) 0,13, 95% IC 0,02 a 0,7; p = 0,02). Conclusões: Existe evidência de qualidade moderada a baixa de pequenos estudos que mostram uma possível interação entre dos AARS no efeito analgésico do tramadol no manejo da dor aguda em adultos. Embora o efeito antiemético profilático da ondansetrona pareça permanecer o mesmo com o uso concomitante com o tramadol, este último parece perder a sua eficácia analgésica no manejo pós-operatório da dor, em adultos. Esta revisão ressalta a necessidade de estudos bem conduzidos sobre o tema, utilizando uma estratificação dos pacientes de acordo ao número de fatores de risco para náuseas e vômitos pós-operatórios que cada paciente possui. Seria de extrema importância se os períodos de avaliação fossem padronizados, nos tempos: 0, 4, 8, 12 e 24 horas após a cirurgia.
Introduction: Pain is one of the most prevalent symptoms reported by patients and it represents a significant public health problem world-wide, because it affects quality of life. Tramadol is a reasonable choice for pain management in the postoperative setting. However, there is an increased risk of nausea and vomiting with the use of tramadol when larger doses are quickly injected. For this reason, an anti-emetic drug is often prescribed in association with tramadol. Among these drugs, the serotonin receptor antagonists antiemetics (SRAA (e.g. ondansetrona, dolasetron, granisetron)) are well-established treatment options that may be of particular value in reducing tramadol-associated emesis. Therefore, we aim to identify any interaction of serotonin receptor antagonist anti-emetic drugs on the analgesic effect of tramadol. Objectives: to evaluate the risk/benefit from the coadministration of tramadol and any serotonin receptor antagonist antiemetic for the pain and/or nausea and vomiting (PONV) management in the postoperative setting. Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Latin American and Caribbean Health Science Information Database (LILACS) from inception to February 2015. We searched ClinicalTrials.gov for ongoing clinical trials. We applied no language restrictions. The date of the most recent search was 30 December 2015. Selection Criteria: We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) concerning any interaction of serotonin receptor antagonist anti-emetic drugs with the analgesic effect of tramadol for acute pain management in adults. Data collection and analysis: We used the standard methodological procedures expected by The Cochrane Collaboration. Two review authors independently considered trials for inclusion in the review, assessed the risk of bias, and extracted data. We calculated the risk ratio (RR) and number needed to treat to benefit (NNTB). We also collected information on adverse effects. Results: Thirteen studies were included with a total of 899 participants. We were able to include data from 510 participants from seven studies into the meta-analysis. Results provided by the RCTs suggest a significantly increase in the tramadol consumption with ondansetron compared to saline in all periods, mainly in 12 hours (Mean difference (MD) 182.46, 95% Confidential Interval (CI) 137.85, 227.07; p < 0.00001). Moreover, there is a possible increase in the need for antiemetic rescue for the patients receiving placebo compared to ondansetron (Risk ratio (RR) 0.61, 95% CI 0.37, 1.01; p = 0.05). In the comparison between AARS and other antiemetics, there was an increase in tramadol consumption, when it was used with AARS in the moments 4, 12 e 24 h (MD (4h) 29,12, 95% CI 21,83 to 36,42; p < 0,00001). There was better PONV prophylaxis when SRAA were used, especially when compared to metoclopramide (RR (8h) 0,13, 95% CI 0,02 to 0,7; p = 0,02). Conclusion: There is limited moderate to low quality evidence from small studies to show that there may be an interaction of serotonin receptor antagonist anti-emetic drugs with the analgesic effect of tramadol for acute pain management in adults. Although the effect of ondansetrona on postoperative anti-emetic prophylaxis remains the same with the concomitant use of tramadol, the latter seems to lose its analgesic efficacy in acute pain management in adults. This review underlines the need to conduct well-designed trials in this field with a subset of participants related to the PONV risk factors. It would also be extremely helpful if the period of assessment of the outcome measures were standardized, such as 0, 4, 8, 12 and 24 h after surgery.
Introduction: Pain is one of the most prevalent symptoms reported by patients and it represents a significant public health problem world-wide, because it affects quality of life. Tramadol is a reasonable choice for pain management in the postoperative setting. However, there is an increased risk of nausea and vomiting with the use of tramadol when larger doses are quickly injected. For this reason, an anti-emetic drug is often prescribed in association with tramadol. Among these drugs, the serotonin receptor antagonists antiemetics (SRAA (e.g. ondansetrona, dolasetron, granisetron)) are well-established treatment options that may be of particular value in reducing tramadol-associated emesis. Therefore, we aim to identify any interaction of serotonin receptor antagonist anti-emetic drugs on the analgesic effect of tramadol. Objectives: to evaluate the risk/benefit from the coadministration of tramadol and any serotonin receptor antagonist antiemetic for the pain and/or nausea and vomiting (PONV) management in the postoperative setting. Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Latin American and Caribbean Health Science Information Database (LILACS) from inception to February 2015. We searched ClinicalTrials.gov for ongoing clinical trials. We applied no language restrictions. The date of the most recent search was 30 December 2015. Selection Criteria: We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) concerning any interaction of serotonin receptor antagonist anti-emetic drugs with the analgesic effect of tramadol for acute pain management in adults. Data collection and analysis: We used the standard methodological procedures expected by The Cochrane Collaboration. Two review authors independently considered trials for inclusion in the review, assessed the risk of bias, and extracted data. We calculated the risk ratio (RR) and number needed to treat to benefit (NNTB). We also collected information on adverse effects. Results: Thirteen studies were included with a total of 899 participants. We were able to include data from 510 participants from seven studies into the meta-analysis. Results provided by the RCTs suggest a significantly increase in the tramadol consumption with ondansetron compared to saline in all periods, mainly in 12 hours (Mean difference (MD) 182.46, 95% Confidential Interval (CI) 137.85, 227.07; p < 0.00001). Moreover, there is a possible increase in the need for antiemetic rescue for the patients receiving placebo compared to ondansetron (Risk ratio (RR) 0.61, 95% CI 0.37, 1.01; p = 0.05). In the comparison between AARS and other antiemetics, there was an increase in tramadol consumption, when it was used with AARS in the moments 4, 12 e 24 h (MD (4h) 29,12, 95% CI 21,83 to 36,42; p < 0,00001). There was better PONV prophylaxis when SRAA were used, especially when compared to metoclopramide (RR (8h) 0,13, 95% CI 0,02 to 0,7; p = 0,02). Conclusion: There is limited moderate to low quality evidence from small studies to show that there may be an interaction of serotonin receptor antagonist anti-emetic drugs with the analgesic effect of tramadol for acute pain management in adults. Although the effect of ondansetrona on postoperative anti-emetic prophylaxis remains the same with the concomitant use of tramadol, the latter seems to lose its analgesic efficacy in acute pain management in adults. This review underlines the need to conduct well-designed trials in this field with a subset of participants related to the PONV risk factors. It would also be extremely helpful if the period of assessment of the outcome measures were standardized, such as 0, 4, 8, 12 and 24 h after surgery.
Descrição
Palavras-chave
Antieméticos antagonistas da serotonina, Dor aguda pós-operatória, Náuseas e vômitos pós-operatórios, Ondansetrona, Tramadol