经饮食和生活方式调节无效的原发性便秘
对于生活方式和饮食调节治疗无效的患者,泻药是药物治疗的主体,同时也是长期治疗方法。 容积性泻药和/或粪便软化是首选的一线治疗。 主诉粪便干结和排便费力的患者,可首选粪便软化剂而非容积性泻药。 便秘发作间隙偶有排稀便的患者则首选容积性泻药。
是一种天然的泻药替代品。 一项双盲随机对照研究已证实:西梅干与车前子(卵叶车前果壳)同样可以改善便秘症状。[66]Attaluri A, Donahoe R, Valestin J, et al. Randomised clinical trial: dried plums (prunes) vs. psyllium for constipation. Aliment Pharmacol Ther. 2011 Apr;33(7):822-8.http://www.ncbi.nlm.nih.gov/pubmed/21323688?tool=bestpractice.com
如果治疗至少 6 周后无临床反应(临床有效定义为患者对排便习惯和相关症状满意)并且排除协同障碍,可以考虑应用渗透性泻药,如乳果糖、聚乙二醇化合物(聚乙二醇)[67]Lee-Robichaud H, Thomas K, Morgan J, et al. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007570.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007570.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20614462?tool=bestpractice.com[68]Belsey JD, Geraint M, Dixon TA. Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation. Int J Clin Pract. 2010 Jun;64(7):944-55.http://www.ncbi.nlm.nih.gov/pubmed/20584228?tool=bestpractice.com 或含镁泻药。一项荟萃分析表明,在改善每周排便次数、粪便形状、腹痛缓解和其它物品需求等方面,聚乙二醇比乳果糖效果更好。[67]Lee-Robichaud H, Thomas K, Morgan J, et al. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007570.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007570.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20614462?tool=bestpractice.com 通常应尽可能使用单一种类的泻药。 渗透性泻药治疗至少6周后症状持续的患者应该使用刺激性泻药(口服)治疗。 刺激性泻药,如番泻叶或比沙可啶[69]Kamm MA, Mueller-Lissner S, Wald A, et al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol. 2011 Jul;9(7):577-83.http://www.ncbi.nlm.nih.gov/pubmed/21440672?tool=bestpractice.com症状缓解:有高质量的证据显示对于慢性便秘比沙可啶是一种有效且耐受性好的治疗,可以改善肠道功能、便秘相关症状和疾病相关的生活质量。[69]Kamm MA, Mueller-Lissner S, Wald A, et al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol. 2011 Jul;9(7):577-83.http://www.ncbi.nlm.nih.gov/pubmed/21440672?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 可用作使用其他种类泻药患者的补救泻药(如果患者 3 天未排便应服用)。
在此阶段也可以考虑应用鲁比前列酮和鸟苷酸环化酶 C 受体激动剂(例如,利那洛肽或普卡那肽)。[70]Johanson JF, Panas R, Holland PC, et al. Long-term efficacy of lubiprostone for the treatment of chronic constipation. Gastroenterology. 2006;130(suppl 2):M1171.[71]Johanson JF, Gargano MA, Holland PC, et al. Initial and sustained effects of lubiprostone, a chloride channel-2 (ClC2) activator for the treatment of constipation: data from a 4-week phase III study. Am J Gastroenterol. 2005;100(suppl 9):S328.[72]Barish CF, Drossman D, Johanson JF, et al. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci. 2010 Apr;55(4):1090-7.http://www.ncbi.nlm.nih.gov/pubmed/20012484?tool=bestpractice.com[73]Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut. 2011 Feb;60(2):209-18.http://www.ncbi.nlm.nih.gov/pubmed/21205879?tool=bestpractice.com[74]Currie MG, Kurtz CB, Mahajan-Miklos S, et al. Effects of a single dose administration of MD-1100 on safety, tolerability, exposure, and stool consistency in healthy subjects. Am J Gastroenterol. 2005;100:S328.[75]Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology. 2010 Dec;139(6):1877-1886.e2.http://www.ncbi.nlm.nih.gov/pubmed/20801122?tool=bestpractice.com[76]Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 11;365(6):527-36.http://www.ncbi.nlm.nih.gov/pubmed/21830967?tool=bestpractice.com[77]Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012 Nov;107(11):1714-24.http://www.nature.com/ajg/journal/v107/n11/full/ajg2012255a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/22986440?tool=bestpractice.com[78]Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012 Nov;107(11):1702-12.http://www.nature.com/ajg/journal/v107/n11/full/ajg2012254a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/22986437?tool=bestpractice.com[79]Lee N, Wald A. Linaclotide: evidence for its potential use in irritable bowel syndrome and chronic constipation. Core Evid. 2012;7:39-47.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396047/http://www.ncbi.nlm.nih.gov/pubmed/22807692?tool=bestpractice.com[80]Quigley EM, Tack J, Chey WD, et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther. 2013 Jan;37(1):49-61.http://onlinelibrary.wiley.com/doi/10.1111/apt.12123/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23116208?tool=bestpractice.com[81]DeMicco M, Barrow L, Hickey B, et al. Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation. Therap Adv Gastroenterol. 2017 Nov;10(11):837-51.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673020/http://www.ncbi.nlm.nih.gov/pubmed/29147135?tool=bestpractice.com症状缓解:有高质量的证据显示利那洛肽治疗慢性便秘可显著减少肠道和腹部症状且显著改善自主排便、粪便性状、排便费力、腹部不适、胀气、全面评估和生活治疗。[73]Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut. 2011 Feb;60(2):209-18.http://www.ncbi.nlm.nih.gov/pubmed/21205879?tool=bestpractice.com[76]Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 11;365(6):527-36.http://www.ncbi.nlm.nih.gov/pubmed/21830967?tool=bestpractice.com[77]Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012 Nov;107(11):1714-24.http://www.nature.com/ajg/journal/v107/n11/full/ajg2012255a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/22986440?tool=bestpractice.com[78]Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012 Nov;107(11):1702-12.http://www.nature.com/ajg/journal/v107/n11/full/ajg2012254a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/22986437?tool=bestpractice.com[79]Lee N, Wald A. Linaclotide: evidence for its potential use in irritable bowel syndrome and chronic constipation. Core Evid. 2012;7:39-47.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396047/http://www.ncbi.nlm.nih.gov/pubmed/22807692?tool=bestpractice.com[80]Quigley EM, Tack J, Chey WD, et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther. 2013 Jan;37(1):49-61.http://onlinelibrary.wiley.com/doi/10.1111/apt.12123/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23116208?tool=bestpractice.com 然而,需要进一步的研究评价利那洛肽治疗慢性便秘的长期风险和受益。[76]Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 11;365(6):527-36.http://www.ncbi.nlm.nih.gov/pubmed/21830967?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 这些药物通常用作单一疗法,而不是与其他泻药联合使用。不建议孕妇患者使用此类药物,因为欠缺与妊娠期间使用有关的安全性数据。普卢卡必利是该阶段治疗的另一治疗选择,该药是一种 5-羟色胺 4 受体激动剂并具有促运动作用。使用该药后,24% 的慢性便秘患者达到每周至少 3 次的完全自主排便。[82]Tack J, van Outryve M, Beyens G, et al. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009 Mar;58(3):357-65.http://www.ncbi.nlm.nih.gov/pubmed/18987031?tool=bestpractice.com[83]Camilleri M, Kerstens R, Rykx A, et al. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008 May 29;358(22):2344-54.http://www.nejm.org/doi/full/10.1056/NEJMoa0800670#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/18509121?tool=bestpractice.com[84]Camilleri M, Deiteren A. Prucalopride for constipation. Expert Opin Pharmacother. 2010 Feb;11(3):451-61.http://www.ncbi.nlm.nih.gov/pubmed/20102308?tool=bestpractice.com[85]Müller-Lissner S, Rykx A, Kerstens R, et al. A double-blind, placebo-controlled study of prucalopride in elderly patients with chronic constipation. Neurogastroenterol Motil. 2010 Sep;22(9):991-8.http://www.ncbi.nlm.nih.gov/pubmed/20529205?tool=bestpractice.com[86]Quigley EM, Vandeplassche L, Kerstens R, et al. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation - a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2009 Feb 1;29(3):315-28.http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2008.03884.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19035970?tool=bestpractice.com[87]Yiannakou Y, Piessevaux H, Bouchoucha M, et al. A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation. Am J Gastroenterol. 2015 May;110(5):741-8.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424376/http://www.ncbi.nlm.nih.gov/pubmed/25869393?tool=bestpractice.com 在3项III期临床试验的4000例患者中超过10%的患者出现头痛、恶心、腹痛和腹泻等表现。无心脏不良反应的临床报道。
灌肠剂、栓剂以及手法助便通常不推荐用于治疗慢性便秘。
怀疑协同障碍
怀疑协同障碍性型便秘的患者可能已经接受了与慢性原发性便秘患者相同的治疗方法治疗:患者教育、生活方式改善、高纤维饮食、容积性泻药、增加液体摄入和锻炼。 也可能已经粪便软化剂和/或渗透性泻药或聚乙二醇治疗过。 当上述治疗无效时,可考虑协同障碍性便秘的可能性。 相关症状包括肛门堵塞感、排便费力以及手法助便。 确诊需要进行生理检查。 生物反馈治疗协同障碍有效。[88]Chiarioni G, Whitehead WE, Pezza V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology. 2006 Mar;130(3):657-64.http://www.ncbi.nlm.nih.gov/pubmed/16530506?tool=bestpractice.com[89]Rao SS, Seaton K, Miller M, et al. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation. Clin Gastroenterol Hepatol. 2007 Mar;5(3):331-8.http://www.ncbi.nlm.nih.gov/pubmed/17368232?tool=bestpractice.com[90]Rao SS, Kinkade K, Miller MJ, et al. Randomized controlled trial of long term outcome of biofeedback therapy (BT) for dyssynergic defecation. Am J Gastroenterol. 2005;100:386.[91]Heymen S, Wexner SD, Vickers D, et al. Prospective, randomized trial comparing for biofeedback techniques for patients with constipation. Dis Colon Rectum. 1999 Nov;42(11):1388-93.http://www.ncbi.nlm.nih.gov/pubmed/10566525?tool=bestpractice.com 用于改进腹部和肛门直肠肌肉协调性的生物反馈技术包括:
膈肌训练模拟排便
通过测压指导盆底训练
模拟排便训练。
三项随机对照临床试验 (RCT) 分别将生物反馈治疗与假反馈、药物治疗或安慰剂治疗进行了比较。[88]Chiarioni G, Whitehead WE, Pezza V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology. 2006 Mar;130(3):657-64.http://www.ncbi.nlm.nih.gov/pubmed/16530506?tool=bestpractice.com[89]Rao SS, Seaton K, Miller M, et al. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation. Clin Gastroenterol Hepatol. 2007 Mar;5(3):331-8.http://www.ncbi.nlm.nih.gov/pubmed/17368232?tool=bestpractice.com[91]Heymen S, Wexner SD, Vickers D, et al. Prospective, randomized trial comparing for biofeedback techniques for patients with constipation. Dis Colon Rectum. 1999 Nov;42(11):1388-93.http://www.ncbi.nlm.nih.gov/pubmed/10566525?tool=bestpractice.com 一项随机对照试验发现生物反馈治疗优于假反馈治疗和通过饮食、运动及泻药的标准医疗方法。[89]Rao SS, Seaton K, Miller M, et al. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation. Clin Gastroenterol Hepatol. 2007 Mar;5(3):331-8.http://www.ncbi.nlm.nih.gov/pubmed/17368232?tool=bestpractice.com 另一项随机对照试验发现生物反馈治疗比地西泮(5mg)或安慰剂更有效。[91]Heymen S, Wexner SD, Vickers D, et al. Prospective, randomized trial comparing for biofeedback techniques for patients with constipation. Dis Colon Rectum. 1999 Nov;42(11):1388-93.http://www.ncbi.nlm.nih.gov/pubmed/10566525?tool=bestpractice.com 第三项随机对照试验发现5个阶段的生物反馈治疗比连续服用聚乙二醇(14 g/d)治疗协同障碍性便秘更有效并且疗效可以持续至少2年。[88]Chiarioni G, Whitehead WE, Pezza V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology. 2006 Mar;130(3):657-64.http://www.ncbi.nlm.nih.gov/pubmed/16530506?tool=bestpractice.com 60% 的排便协同失调患者存在直肠感觉受损,[92]Rao SS, Enck P, Loening-Baucke V. Biofeedback therapy for defecation disorders. Dig Dis. 1997;15(suppl 1):78-92.http://www.ncbi.nlm.nih.gov/pubmed/9177947?tool=bestpractice.com 所以调节直肠感觉能够提供额外的治疗益处。[90]Rao SS, Kinkade K, Miller MJ, et al. Randomized controlled trial of long term outcome of biofeedback therapy (BT) for dyssynergic defecation. Am J Gastroenterol. 2005;100:386.[92]Rao SS, Enck P, Loening-Baucke V. Biofeedback therapy for defecation disorders. Dig Dis. 1997;15(suppl 1):78-92.http://www.ncbi.nlm.nih.gov/pubmed/9177947?tool=bestpractice.com 两项随机对照试验报告:生物反馈治疗可持续缓解症状并改善结直肠功能(1年),由此,其长效性得以证实。[88]Chiarioni G, Whitehead WE, Pezza V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology. 2006 Mar;130(3):657-64.http://www.ncbi.nlm.nih.gov/pubmed/16530506?tool=bestpractice.com[90]Rao SS, Kinkade K, Miller MJ, et al. Randomized controlled trial of long term outcome of biofeedback therapy (BT) for dyssynergic defecation. Am J Gastroenterol. 2005;100:386.