Wiffen Philip J, Derry Sheena, Moore R Andrew
Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.
Cochrane Database Syst Rev. 2014 May 29;2014(5):CD011056. doi: 10.1002/14651858.CD011056.pub2.
There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be "phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient".The impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient.
To determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain.
We assessed adverse event data reported in studies included in current Cochrane reviews of opioids for cancer pain: specifically morphine, fentanyl, oxycodone, and codeine.
We included randomised studies using multiple doses of four opioid drugs (morphine, fentanyl, oxycodone, and codeine) in cancer pain. These were taken from four existing or ongoing Cochrane reviews. Participants were adults aged 18 and over. We included only full journal publication articles.
Two review authors independently extracted adverse event data, and examined issues of study quality. The primary outcomes sought were numbers of participants experiencing adverse events of reduced consciousness, appetite, and thirst. Secondary outcomes were possible surrogate measures of the primary outcomes: delirium, dizziness, hallucinations, mood change and somnolence relating to patient consciousness, and nausea, vomiting, constipation, diarrhoea, dyspepsia, dysphagia, anorexia, asthenia, dehydration, or dry mouth relating to appetite or thirst.Comparative measures of harm were known to be unlikely, and we therefore calculated the proportion of participants experiencing each of the adverse events of interest with each opioid, and for all four opioid drugs combined.
We included 77 studies with 5619 randomised participants. There was potential bias in most studies, with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young, with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found, including failing to report adverse events in all participants who received medication, all adverse events experienced, how adverse events were collected, and not defining adverse event terminology or whether a reporting system was used.Direct measures of patient consciousness, patient appetite, or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change, hallucinations and dehydration occurred at incidence rates of 5% and below.
AUTHORS' CONCLUSIONS: We found no direct evidence that opioids affected patient consciousness, appetite or thirst when used to treat cancer pain. However, somnolence, dry mouth, and anorexia were common adverse events in people with cancer pain treated with morphine, fentanyl, oxycodone, or codeine.We are aware that there is an important literature concerning the problems that exist with adverse event measurement, reporting, and attribution. Together with the known complications concerning concomitant medication, data collection and reporting, and nomenclature, this means that these adverse events cannot always be attributed unequivocally to the use of opioids, and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance, and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.
目前人们越来越关注为临终患者提供高质量护理，无论其疾病或病因如何，且涵盖所有环境。在过去十年中，使用护理路径来帮助临终患者治疗在全球范围内变得普遍。英国利物浦护理路径的使用受到了批评。在英格兰，利物浦护理路径是由一位卫生部长委托进行的独立审查的主题。纽伯格审查承认，利物浦护理路径基于合理的伦理原则，在正确实施时为患者及其家属提供优质护理的基础。它还发现，利物浦护理路径往往没有得到正确实施，反而成为优质护理的障碍；它提出了40多项建议，包括教育和培训、研发、获得专科姑息治疗服务，以及确保对所有临终患者给予护理和关怀的必要性。2013年7月，卫生部发表声明称，利物浦护理路径的使用应“在未来6至十二个月内逐步淘汰，取而代之的是针对每位患者的个性化临终护理方法”。由于阿片类药物对临终患者的意识、食欲和口渴有潜在影响，其影响尤其令人担忧。有人担心患者意识受损可能导致过早死亡，阿片类药物对食欲和口渴的影响可能导致不必要的痛苦。这项由英国国家卫生研究院委托进行的快速审查，采用了标准的考克兰方法，以研究吗啡、芬太尼、羟考酮和可待因在癌症疼痛研究中的不良反应，以此作为对临终患者可能产生影响的近似估计。
确定在吗啡、芬太尼、羟考酮或可待因治疗癌症疼痛的随机对照试验中，阿片类药物治疗对患者意识、食欲和口渴的影响。
我们评估了考克兰当前关于阿片类药物治疗癌症疼痛的综述中所纳入研究报告的不良事件数据：具体为吗啡、芬太尼、羟考酮和可待因。
我们纳入了使用四种阿片类药物（吗啡、芬太尼、羟考酮和可待因）多剂量治疗癌症疼痛的随机研究。这些研究取自四项现有或正在进行的考克兰综述。参与者为18岁及以上的成年人。我们仅纳入完整的期刊发表文章。
两位综述作者独立提取不良事件数据，并检查研究质量问题。主要寻求的结果是经历意识降低、食欲降低和口渴等不良事件参与者的数量。次要结果是主要结果的可能替代指标：与患者意识相关的谵妄、头晕、幻觉、情绪变化和嗜睡，以及与食欲或口渴相关的恶心、呕吐、便秘、腹泻、消化不良、吞咽困难、厌食、乏力、脱水或口干。已知不太可能进行伤害的比较测量，因此我们计算了每种阿片类药物以及所有四种阿片类药物组合下，经历每种感兴趣不良事件的参与者比例。
我们纳入了77项研究，共5619名随机参与者。大多数研究存在潜在偏倚，样本量小是最常见的情况；在60项研究中，各个治疗组的参与者少于50人。参与者相对年轻，研究中的平均年龄通常在50至70岁之间。发现不良事件报告存在多个主要问题，包括未报告所有接受药物治疗参与者的不良事件、所有经历的不良事件、不良事件的收集方式，以及未定义不良事件术语或是否使用报告系统。未发现对患者意识、患者食欲或口渴进行的直接测量。用于治疗癌症疼痛的阿片类药物不良事件发生率为：便秘25%，嗜睡23%，恶心21%，口干17%，呕吐、厌食和头晕13%。乏力、腹泻、失眠、情绪变化、幻觉和脱水的发生率在5%及以下。
我们未发现直接证据表明用于治疗癌症疼痛的阿片类药物会影响患者意识、食欲或口渴，但嗜睡、口干和厌食是使用吗啡、芬太尼、羟考酮或可待因治疗癌症疼痛患者中的常见不良事件。我们意识到，关于不良事件测量、报告和归因存在的问题有重要文献记载。连同已知的关于合并用药、数据收集和报告以及术语的并发症，这意味着这些不良事件不能总是明确归因于阿片类药物的使用，因此它们仅提供了癌症疼痛中阿片类药物不良事件的大致情况。研究议程包括为具有不同严重程度或重要性的不良事件制定定义，以及开发用于记录此类事件的适当测量工具，以辅助临床实践和临床研究。
