Hearn Leslie, 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. 2016 Apr 20;4(4):CD011421. doi: 10.1002/14651858.CD011421.pub2.
Dipyrone (metamizole) is a nonsteroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in other countries because of an association with life-threatening blood disorders. This review replaces a 2010 Cochrane review that has been withdrawn.
To assess the analgesic efficacy and associated adverse events of single dose dipyrone for moderate to severe acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS to 11 August 2015; the Oxford Pain Relief Database; two clinical trial registries; and the reference lists of articles.
We included randomised, double-blind, placebo-controlled trials of single dose dipyrone for relief of established moderate to severe postoperative pain in adults. We accepted oral, rectal, intramuscular, and intravenous routes of administration.
Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used summed total pain relief or pain intensity difference (TOTPAR or SPID) over four to six hours to calculate the number of participants achieving at least 50% pain relief. From derived results, we calculated the risk ratio and number needed to treat for an additional beneficial outcome (NNT), with 95% confidence intervals (CI), for one participant to experience at least 50% pain relief over four to six hours compared to placebo. We looked at use of rescue medication and time to use of rescue medication as additional measures of efficacy. We also looked for information on adverse events and withdrawals.
We included eight studies, involving 809 participants, comparing oral dipyrone 500 mg (143 participants), oral dipyrone 1000 mg (57 participants), and intramuscular dipyrone 2000 mg (35 participants) with placebo (236 participants). In addition to placebo, all studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen; 338 participants). Seven studies used the oral route of administration, and one study used the intramuscular route. The mean age ranged from 23 to 62 years. Six studies included both men and women, and two studies included only women. All the studies were small, but were otherwise of moderate to good quality.Over 70% of participants experienced our primary outcome of at least 50% pain relief over four to six hours with oral dipyrone 500 mg compared to 30% with placebo (five studies, 288 participants; NNT 2.4 (95% CI 1.8 to 3.1)) (moderate quality evidence). There were insufficient data to assess other doses or routes of administration of dipyrone.Fewer participants needed rescue medication within four to six hours with dipyrone 500 mg than with placebo (7% with dipyrone versus 34% with placebo; four studies, 248 participants) (low quality evidence).The data on numbers of participants experiencing any adverse event was inconsistently reported and no analysis was possible. No serious adverse events or adverse event withdrawals were reported (very low quality evidence).There were too few data to compare dipyrone directly with other active treatments.
AUTHORS' CONCLUSIONS: Based on very limited information, a single dose of dipyrone 500 mg provides good pain relief to about 70% of people treated, compared to about 30% with placebo. For every five people given dipyrone 500 mg, two people would experience this level of pain relief over four to six hours who would not have done with placebo, and fewer people would need rescue medication.We were unable to compare dipyrone directly with other active treatments, or to assess the effects of different doses or routes of administration, or the number of participants experiencing adverse events, because of insufficient data and inadequate reporting.
安乃近是一种非甾体抗炎药，在一些国家用于治疗疼痛（术后疼痛、绞痛、癌症疼痛和偏头痛）；在其他国家，由于其与危及生命的血液疾病有关联而被禁用。本综述替代了已撤回的2010年Cochrane综述。
采用能与使用几乎相同方法和结局的标准化试验中评估的其他镇痛药进行比较的方法，评估单剂量安乃近治疗中度至重度急性术后疼痛的镇痛效果及相关不良事件。
我们检索了截至2015年8月11日的Cochrane对照试验中心注册库（CENTRAL）、MEDLINE、EMBASE和LILACS；牛津疼痛缓解数据库；两个临床试验注册库；以及文章的参考文献列表。
我们纳入了单剂量安乃近用于缓解成人已确诊的中度至重度术后疼痛的随机、双盲、安慰剂对照试验。我们接受口服、直肠、肌肉注射和静脉注射给药途径。
两位综述作者独立考虑纳入综述的研究，评估偏倚风险，并提取数据。我们使用四至六小时内的总疼痛缓解或疼痛强度差异（TOTPAR或SPID）来计算至少实现50%疼痛缓解的参与者数量。根据得出的结果，我们计算风险比和为获得额外有益结局所需治疗的人数（NNT），并给出95%置信区间（CI），即与安慰剂相比，一名参与者在四至六小时内至少实现50%疼痛缓解的情况。我们将使用解救药物的情况和使用解救药物的时间作为疗效的额外衡量指标。我们还查找了不良事件和退出试验的信息。
我们纳入了八项研究，涉及809名参与者，将口服500毫克安乃近（143名参与者）、口服1000毫克安乃近（57名参与者）和肌肉注射2000毫克安乃近（35名参与者）与安慰剂（236名参与者）进行比较。除安慰剂外，所有研究均使用了活性对照（布洛芬、对乙酰氨基酚、阿司匹林、氟比洛芬、酮洛芬；338名参与者）。七项研究采用口服给药途径，一项研究采用肌肉注射途径。平均年龄在23至62岁之间。六项研究纳入了男性和女性，两项研究仅纳入了女性。所有研究规模都较小，但质量中等至良好。与安慰剂组30%的参与者相比，超过70%接受口服500毫克安乃近治疗的参与者在四至六小时内实现了至少50%的疼痛缓解（五项研究，288名参与者；NNT 2.4（95%CI 1.8至3.1））（中等质量证据）。没有足够的数据来评估安乃近的其他剂量或给药途径。与安慰剂相比，接受500毫克安乃近治疗的参与者在四至六小时内需要使用解救药物的人数更少（安乃近组为7%，安慰剂组为34%；四项研究，248名参与者）（低质量证据）。关于发生任何不良事件的参与者数量的数据报告不一致，无法进行分析。没有报告严重不良事件或因不良事件退出试验的情况（极低质量证据）。数据太少，无法直接将安乃近与其他活性治疗进行比较。
基于非常有限的信息，单剂量500毫克安乃近能使约70%接受治疗的人疼痛得到良好缓解，而安慰剂组约为30%。每给五名服用500毫克安乃近的人，就有两人在四至六小时内会经历这种程度的疼痛缓解，而服用安慰剂则不会，且需要使用解救药物的人更少。由于数据不足和报告不充分，我们无法直接将安乃近与其他活性治疗进行比较，也无法评估不同剂量或给药途径的效果，以及发生不良事件的参与者数量。
