Candy Bridget, Jones Louise, Goodman Margaret Lynn, Drake Robyn, Tookman Adrian
Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, Royal Free & University College Medical School, Hampstead Campus, Rowland Hill Street, London, UK, NW3 2PF.
Cochrane Database Syst Rev. 2011 Jan 19(1):CD003448. doi: 10.1002/14651858.CD003448.pub3.
Constipation is common in palliative care; it can generate considerable suffering due to the unpleasant physical symptoms. In the first Cochrane Review on effectiveness of laxatives for the management of constipation in palliative care patients, published in 2006, no conclusions could be drawn because of the limited number of evaluations. This article describes the first update of this review.
To determine the effectiveness of laxatives or methylnaltrexone for the management of constipation in palliative care patients.
We searched databases including MEDLINE and CENTRAL (The Cochrane Library) in 2005 and in the update to August 2010.
Randomised controlled trials (RCTs) evaluating laxatives for constipation in palliative care patients. In the update we also included RCTs on subcutaneous methylnaltrexone; an opioid-receptor antagonist that is now licensed for the treatment of opioid-induced constipation in palliative care when response to usual laxative therapy is insufficient.
Two authors assessed trial quality and extracted data. The appropriateness of combining data from the studies depended upon clinical and outcome measure homogeneity.
We included seven studies involving 616 participants; all under-reported methodological features. In four studies the laxatives lactulose, senna, co-danthramer, misrakasneham, and magnesium hydroxide with liquid paraffin were evaluated. In three methylnaltrexone.In studies comparing the different laxatives evidence was inconclusive. Evidence on subcutaneous methylnaltrexone was clearer; in combined analysis (287 participants) methylnaltrexone, in comparison with a placebo, significantly induced laxation at 4 hours (odds ratio 6.95; 95% confidence interval 3.83 to 12.61). In combined analyses there was no difference in the proportion experiencing side effects, although participants on methylnaltrexone suffered more flatulence and dizziness. No evidence of opioid withdrawal was found. In one study severe adverse events, commonly abdominal pain, were reported that were possibly related to methylnaltrexone. A serious adverse event considered to be related to the methylnaltrexone also occurred; this involved a participant having severe diarrhoea, subsequent dehydration and cardiovascular collapse.
AUTHORS' CONCLUSIONS: The 2010 update found evidence on laxatives for management of constipation remains limited due to insufficient RCTs. However, the conclusions of this update have changed since the original review publication in that it now includes evidence on methylnaltrexone. Here it found that subcutaneous methylnaltrexone is effective in inducing laxation in palliative care patients with opioid-induced constipation and where conventional laxatives have failed. However, the safety of this product is not fully evaluated. Large, rigorous, independent trials are needed.
便秘在姑息治疗中很常见；由于令人不适的身体症状，它会给患者带来相当大的痛苦。在2006年发表的关于泻药治疗姑息治疗患者便秘有效性的第一篇Cochrane系统评价中，由于评估数量有限，未能得出结论。本文介绍了该评价的首次更新。
确定泻药或甲基纳曲酮治疗姑息治疗患者便秘的有效性。
我们在2005年以及截至2010年8月的更新中检索了包括MEDLINE和CENTRAL（Cochrane图书馆）在内的数据库。
评估泻药治疗姑息治疗患者便秘的随机对照试验（RCT）。在更新中，我们还纳入了关于皮下注射甲基纳曲酮的RCT；这是一种阿片受体拮抗剂，当对常规泻药治疗反应不足时，现已被批准用于治疗姑息治疗中阿片类药物引起的便秘。
两名作者评估试验质量并提取数据。合并研究数据是否合适取决于临床和结局测量的同质性。
我们纳入了7项研究，共616名参与者；所有研究均未充分报告方法学特征。在4项研究中，评估了乳果糖、番泻叶、复方丹蒽醌、密斯拉卡什内姆以及氢氧化镁与液状石蜡等泻药。在3项研究中评估了甲基纳曲酮。在比较不同泻药的研究中，证据尚无定论。关于皮下注射甲基纳曲酮的证据更明确；在合并分析（287名参与者）中，与安慰剂相比，甲基纳曲酮在4小时时显著促进排便（优势比6.95；95%置信区间3.83至12.61）。在合并分析中，出现副作用的比例没有差异，尽管使用甲基纳曲酮的参与者腹胀和头晕更多。未发现阿片类药物戒断的证据。在一项研究中，报告了可能与甲基纳曲酮有关的严重不良事件，通常为腹痛。还发生了一起被认为与甲基纳曲酮有关的严重不良事件；一名参与者出现严重腹泻，随后脱水和心血管衰竭。
2010年的更新发现，由于RCT不足，关于泻药治疗便秘的证据仍然有限。然而，自最初的评价发表以来，本次更新的结论有所变化，因为现在纳入了关于甲基纳曲酮的证据。此处发现皮下注射甲基纳曲酮对治疗阿片类药物引起便秘且常规泻药治疗无效的姑息治疗患者有效。然而，该产品的安全性尚未得到充分评估。需要进行大规模、严谨、独立的试验。
