Cooper Tess E, Fisher Emma, Gray Andrew L, Krane Elliot, Sethna Navil, van Tilburg Miranda Al, Zernikow Boris, Wiffen Philip J
Cochrane Pain, Palliative and Supportive Care Group, Pain Research Unit, Churchill Hospital, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.
Cochrane Database Syst Rev. 2017 Jul 26;7(7):CD012538. doi: 10.1002/14651858.CD012538.pub2.
Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Opioids are used worldwide for the treatment of pain. They bind to opioid receptors in the central nervous system (mu, kappa, delta, and sigma) and can be agonists, antagonists, mixed agonist-antagonists, or partial agonists. Opioids are generally available in healthcare settings across most high-income countries, but access may be restricted in low- and middle-income countries. For example, opioids currently available in the UK include: buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. Opioids are used in varying doses (generally based on body weight for paediatric patients) by means of parenteral, transmucosal, transdermal, or oral administration (immediate release or modified release). To achieve adequate pain relief in children using opioids, with an acceptable grade of adverse effects, the recommended method is a lower dose gradually titrated to effect in the child.
To assess the analgesic efficacy and adverse events of opioids used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing opioids with placebo or an active comparator.
Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.
No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome.
AUTHORS' CONCLUSIONS: There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of opioids to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that some opioids, such as morphine and codeine, can be effective in certain chronic pain conditions.This means that no conclusions could be made about efficacy or harm in the use of opioids to treat chronic non-cancer pain in children and adolescents.
疼痛是全球儿童和青少年的常见特征，对许多年轻人来说，这种疼痛是慢性的。世界卫生组织关于儿童持续性疼痛药物治疗的指南承认，儿童疼痛是世界上大多数地区的一个重大公共卫生问题，具有高度重要性。过去，疼痛在很大程度上被忽视，常常得不到治疗，但随着时间的推移，人们对儿童疼痛的看法发生了变化，现在疼痛缓解被视为重要的事情。我们设计了一组七项关于慢性非癌性疼痛和癌性疼痛的综述（将抗抑郁药、抗癫痫药、非甾体抗炎药、阿片类药物和对乙酰氨基酚作为优先领域），以便回顾在儿童和青少年中使用药物干预治疗儿童疼痛的证据。
作为当今世界儿童和青少年发病的主要原因，慢性病（及其相关疼痛）是一个主要的健康问题。慢性疼痛（持续三个月或更长时间）可在儿科人群中以多种病理生理分类出现：伤害性疼痛、神经性疼痛、特发性疼痛、内脏性疼痛、神经损伤疼痛、慢性肌肉骨骼疼痛、慢性腹痛以及其他不明原因。
阿片类药物在全球范围内用于治疗疼痛。它们与中枢神经系统中的阿片受体（μ、κ、δ和σ）结合，可以是激动剂、拮抗剂、混合激动 - 拮抗剂或部分激动剂。在大多数高收入国家的医疗机构中，阿片类药物通常都有，但在低收入和中等收入国家，获取可能受到限制。例如，英国目前可用的阿片类药物包括：丁丙诺啡、可待因、芬太尼、氢吗啡酮、美沙酮、吗啡、羟考酮和曲马多。阿片类药物通过胃肠外、经粘膜、经皮或口服给药（即释或缓释），以不同剂量（通常根据儿科患者体重）使用。为了在使用阿片类药物的儿童中实现充分的疼痛缓解并伴有可接受程度的不良反应，推荐的方法是逐渐滴定较低剂量以达到对儿童的治疗效果。
评估用于治疗出生至17岁儿童和青少年慢性非癌性疼痛的阿片类药物的镇痛效果和不良事件，适用于任何环境。
我们通过Cochrane图书馆检索了Cochrane对照试验中央登记册（CENTRAL），通过Ovid检索了MEDLINE，通过Ovid检索了Embase，检索时间从创刊至2016年9月6日。我们还检索了检索到的研究和综述的参考文献列表，并检索了在线临床试验注册库。
随机对照试验，无论是否设盲，任何剂量和任何给药途径，治疗儿童和青少年慢性非癌性疼痛，将阿片类药物与安慰剂或活性对照进行比较。
两位综述作者独立评估研究的纳入资格。我们计划使用二分法数据计算风险比和治疗所需人数，采用标准方法。我们评估了GRADE（推荐分级评估、制定和评价）并计划创建一个“结果总结”表。
没有研究符合纳入本综述的条件。我们将证据质量评为极低。由于未报告任何结果的数据，我们将证据质量下调了三个级别。
随机对照试验没有证据支持或反驳使用阿片类药物治疗儿童和青少年慢性非癌性疼痛。我们无法评论使用阿片类药物治疗儿童和青少年慢性非癌性疼痛的疗效或危害。我们从成人随机对照试验中知道，一些阿片类药物，如吗啡和可待因，在某些慢性疼痛情况下可能有效。这意味着无法就使用阿片类药物治疗儿童和青少年慢性非癌性疼痛的疗效或危害得出结论。
