寇　温　杨天宁　武新安



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聚乙二醇4000治疗8岁以下儿童便秘安全性和疗效的系统评价

寇温1杨天宁2武新安1

目的评价聚乙二醇(PEG)4000治疗<8岁儿童便秘的安全性和有效性。方法 计算机检索PubMed、EMBASE、Cochrane 图书馆、中国知网和维普数据库，检索起止时间为1981年1月1日至2016年4月1日，获得PEG4000治疗<8岁儿童便秘的RCT文献，评估纳入文献的偏倚风险。评估PEG4000治疗期间的安全性和疗效指标。采用 RevMan 5.0软件行Meta分析。结果4篇RCT文献进入系统评价，共纳入344例<8岁便秘患儿，观察时间为2～12周，PEG4000与乳果糖、氧化镁和PEG-电解质对照的文献分别为2、1和1篇。4篇文献均描述了随机序列的产生、分配隐藏和受试者的脱落或失访，3篇文献采用双盲法。因对照组和结局指标不同行描述性分析，①4篇文献PEG4000治疗期间均未观察到严重不良事件，1篇文献显示PEG4000组治疗12周至少1项血生化指标异常的比例与治疗前基线数据差异无统计学意义(35/39vs31/39)，1篇文献显示腹泻发生率低于氧化镁对照组(2/46vs12/43)，1篇文献显示恶心发生率低于PEG-电解质对照组(1/49vs9/42)。②1篇文献显示用药后4周每天大便次数PEG4000组与乳果糖对照组差值为0.36次(95%CI:0.16～0.56次)，1篇文献显示用药后12周每周大便次数PEG4000组和乳果糖对照组相近(8.5vs11.5次)。治疗4周后好转率率PEG4000组优于氧化镁对照组(42/46vs28/43，P=0.003)；治疗4周后每周大便次数PEG4000组优于PEG-电解质对照组，(9.2 ± 3.2)vs(7.8 ±2.4) 次，P=0.025。结论现有临床证据表明，PEG4000治疗<8岁儿童便秘的安全性和疗效较好。

聚乙二醇4000；便秘；儿童；系统评价；安全性；疗效

AbstractObjectiveTo assess the efficacy and safety of polyethylene glycol 4000 (PEG4000) in constipated children younger than 8 years.MethodsThe randomized controlled trials of PEG4000 compared with other active comparator in children younger than 8 years with primary chronic constipation were conducted by an electronic search of Cochrane library, PubMed, EMBASE, ISI Web of Science, VIP, and CNKI, with the retrieval time from January 1981 to April 2016. ResultsFour qualifying studies involving 344 children were identified. Two were comparisons of PEG4000 with lactulose, one with milk of magnesia and one with PEG-electrolyte(PEG-EL). Study duration ranged from 2 weeks to 12 weeks. Four studies described the generation of random sequence, the allocation concealment and reported the subjects lost to follow-up, 3/4 articles used double-blind method. ①There was no severe adverse reaction observed in four studies. The rate of at least one blood biochemical indexes outside normal of PEG4000 was similar between after and before treatment(35/39vs31/39). The incidence of diarrhea was lower in PEG4000 group (2/46vs12/43) than in milk of magnesia group; the incidence of nausea was lower in PEG4000 group compared to PEG-EL group (1/49vs9/42). ②The stool frenqency was similar in PEG4000 and lactulose groups(8.5vs11.5 per week), after four weeks follow up, PEG4000 group had great increase in stool frenqency than PEG-EL group[(9.2 ± 3.2)vs(7.8 ±2.4) times，P=0.025] and PEG4000 group had significantly higher improvement compared with the patients in the milk of magnesia group (42/46vs28/43，P=0.003).ConclusionLimited scientific evidence demonstrated that for children younger than 8 years , PEG4000 use was more effective and tolerated than other active comparators.

国外资料报道儿童便秘的发生率为0.3%～8.0%，约3%的门诊患儿和25%儿科胃肠病的咨询与排便有关[1]。仅有少数儿童为器质性便秘[2]。便秘的治疗首先强调生活方式的改变，主要包括增加膳食纤维和液体的摄入[3]。但单纯饮食习惯的改变仅对25%的2岁以下便秘儿童有效[4]。聚乙二醇(PEG)4000为渗透性缓泻剂, 口服后在胃肠道内不吸收，通过氢键结合水分子增加肠腔内的渗透浓度，促进排便[5]。国外大量临床研究已经证实PEG4000能安全有效地治疗成人便秘, 并已逐渐成为儿童便秘的首选药物[6～10]。PEG4000说明书适用年龄为≥8岁，但有研究探索性在<8岁儿童观察PEG4000的安全性和有效性。2009年有系统评价对PEG4000和其他缓泻剂在<18岁便秘患儿中应用的安全性和有效性进行比较[11]，但未对<8岁儿童行分层分析。本文检索文献，系统评价PEG4000用于<8岁便秘儿童的安全性和有效性，为临床用药提供依据。

1　方法

1.1文献纳入标准①RCT；②中文和英文语种；③文献中描述了便秘的诊断标准；④观察对象<8岁且便秘症状持续>3个月；⑤试验组予PEG4000,对照组予安慰剂或其他缓泻剂。

1.2文献排除标准①研究对象伴代谢性或内分泌疾病； ②重复发表的文献。

1.3结局指标

1.3.1安全性指标治疗期间的严重不良事件(死亡、致残和需住院治疗)和一般不良事件(除严重不良事件外的其他不良事件)，实验室检查(血、尿常规，肝、肾功能等)。

1.3.2疗效指标主要疗效指标：每周或每天排便次数。次要疗效指标：腹痛次数、腹痛持续时间、便秘好转率(每周大便≥3次，排便时无疼痛)。

1.4文献检索策略以PEG4000, Polyethylene, Glycol Macrogol, Constipated, dyschezia, dry stool, astriction为检索词检索Cochrane图书馆、PubMed、EMBASE、ISI Web of Science数据库。以PEG4000，福松，便秘为检索词检索中国知网和维普数据库。……