我国示范乡镇卫生院基本药物循证评价与遴选之八:急性胃肠炎

Evidence-Based Evaluation and Selection of Essential Medicine for Township Health Centre in China: 8.Acute Gastroenteritis

目的基于疾病负担,循证评价与遴选我国示范乡镇卫生院合理治疗成人、儿童急性胃肠炎的基本药物。方法按本系列研究之二制定的方法、标准和流程,参考国内外循证或权威指南的推荐意见,结合国内相关临床研究证据,循证评价并推荐相关药物。主要采用RevMan 5.1、GRADEpro 3.6等软件处理数据、评价证据质量。结果①共纳入5个指南,其中2个为循证制定。②指南涉及急性胃肠炎止泻药4类8种,止吐药3种。③根据WHO EML(2011)、NEML(2009)、CNF(2010版)和其它指南推荐药物的各类及其证据数量与质量,弱推荐昂丹司琼、胃复安、蒙脱石、消旋卡多曲、洛哌丁胺;不推荐抗生素、地塞米松、高岭土、活性炭、绿坡缕石、水杨酸铋。④国内研究证据:14个CCT(n=1 635,低质量)显示蒙脱石(思密达)治疗儿童急性腹泻的显效率和总有效率优于常规补液、诺氟沙星、庆大霉素、痢特灵;2个CCT报道了3例恶心、呕吐,1个CCT报告了1例腹痛、腹胀和1例全身不适,余均未报告不良反应。10个CCT(n=1 017,低质量)显示消旋卡多曲治疗急性腹泻的显效率和总有效率优于常规治疗[OR=2.55,95%CI(1.64,3.94),P<0.01;OR=4.32,95%CI(2.96,6.30),P<0.01]。2个CCT(n=344,低质量)显示消旋卡多曲治疗急性腹泻的总有效率优于蒙脱石[OR=8.02,95%CI(3.48,18.47),P<0.01]。2个CCT(n=1 056,低质量)显示消旋卡多曲治疗成人急性腹泻的总有效率优于常规治疗[OR=5.19,95%CI(3.54,7.63),P<0.01]。2个CCT(n=182,低质量)报告2例儿童恶心,1个CCT(n=947,低质量)报告15例成人便秘、4例厌食、9例头痛和1例腹痛。结论弱推荐蒙脱石口服散剂(成人:3 g/次,tid,倒入温水摇匀吞服。<1岁幼儿:3 g/d,分2次服用。>1岁幼儿:3 g/次,qd或bid。儿童可采用保留灌肠疗法)。弱推荐消旋卡多曲胶囊(成人:1粒/次,tid,连续用药≤7天。因无临床试验证据,孕妇、哺乳期妇女及儿童不使用本品)。建议今后的临床研究和实践应规范、统一诊断及标准,提高临床研究设计和实施质量,并全面开展药物适用性和经济性的原始研究,生产高质量本土化证据。

Objective To evaluate and select essential medicine for acute gastroenteritis using evidence-based approaches based on the burden of disease for township health centers located in eastern,central and western regions of China.Methods By means of the approaches,criteria,and workflow set up in the second article of this series,we referred to the recommendations of evidence-based or authority guidelines from inside and outside China,collected relevant evidence from domestic clinical studies,and recommended essential medicine based on evidence-based evaluation.Data were analyzed by Review Manager（RevMan） 5.1 and GRADE profiler 3.6 to evaluate quality of evidence.Results （1） Five guidelines were included,two of which were evidence-based.（2） Recommended medicines included eight antidiarrheals（of four classes） and three antemetics.（3） According to WHOEML（2011）,NEML（2009）,CNF（2010）,other guidelines and the quantity and quality of evidence,we offered a weak recommendation for ondansetron,metoclopramide,smectite,racecadotril and loperamide applied in the treatment of acute gastroenteritis.We made a recommendation against antibiotics,dexamethasone,kaolin-pectin,activated charcoal,attapulgite and bismuth subsalicylate.（4） Evidence from domestic studies： a result of 14 CCTs（n=1 635,low quality） indicated that in the significant efficiency and total efficiency,smectite（smecta） was superior to routine liquid infusion,norfloxacin,gentamicin or furaxone.Among these 14 CCTs,two CCTs reported smectite（smecta） caused nausea and vomiting（three cases）;one CCT reported pain and distention in the abdomen（one case） and general discomfort（one case）;and the rest reported no adverse reaction.A result of 10 CCTs（n=1 017,low quality） indicated that for acute diarrhea,racecadotril was superior to routine treatment in the significant efficiency（OR=2.55,95%CI 1.64 to 3.94,P〈0.01） and total efficiency（OR=4.32,95%CI 2.96 to 6.30,P〈0.01）.A result of two CCTs（n=344,low quality） indicated that racecadotril was superior to smectite in the total efficiency in treating acute diarrhea.A result of two CCTs（n=1 056,low quality） indicated that racecadotril was superior to routine treatment in the total efficiency in treating acute adult diarrhea（OR=5.19,95%CI 3.54 to 7.63,P〈0.01）.A result of two CCTs（n=182,low quality） reported children presented with nausea（two cases）.A result of one CCT（n=947,low quality） reported adults presented with constipation（fifteen cases）,anorexia（four cases）,headache（nine cases） and abdominal pain（one case）.Conclusion For acute gastroentitis,we offer a weak recommendation for smectite（powder,for oral use） used in adults（once 3 g,tid.,mixed with warm water before intake）,child under one year of age（3 g daily,bid.）,and child above one year of age（once 3 g,qd.or bid.）.Retention enema could be appiled to children with acute gastroenteritis.We also offer a weak recommendation for racecadotril（capsule） used in adults（one capsule,tid.,taken continuously less than seven days）.Due to the lack of evidence from clinical trials,we make a recommendation against racecadotril applied to women with pregnancy and lactation or children.In order to produce high-quality local evidence,we propose that（1） Further clinical studies should be standardized in diagnosis and criteria.（2） The design and implementation quality of clinical studies should be improved.（3） Original studies on pharmacoeconomic studies and drug applicability are needed.