我国示范乡镇卫生院基本药物循证评价与遴选之三:普通感冒

Evidence-Based Evaluation and Selection of Essential Medicine for Township Health Centre in China: 3.Common Cold

目的循证评价与遴选我国乡镇卫生院治疗感冒患儿发热、成人胃肠型感冒的基本药物。方法针对示范乡院反映的感冒药物配备问题,应用本系列研究之二制定的基本药物循证评价与遴选标准、方法和流程,循证评价并推荐相关药物。采用RevMan 5.1和GRADEpro等软件统计分析数据和评价证据质量。结果①共纳入12个治疗指南,其中11个是循证或结合专家意见制定,推荐药物包括解热镇痛、解充血、抗组胺、止咳、祛痰、治疗胃肠道症状。②4个RCT(极低质量证据)表明布洛芬混悬液对感冒患儿的解热效果与对乙酰氨基酚悬浮液相似,其6小时解热有效率合并结果为RR=1.48,95%CI(0.66,3.30),P=0.34;不良反应主要是消化道不良反应和出汗较多[RR=1.23,95%CI(0.72,2.11),P=0.45];药费1.93元/d;口服且不需督导用药,适用性好。③与布洛芬混悬液相比,3个RCT(低质量证据)表明用药30分钟、1小时后,对乙酰氨基酚(扑热息痛)栓剂降低体温效果较优[MD=–0.16°C,95%CI(–0.21,–0.11),P<0.01)与MD=–0.19°C,95%CI(–0.28,0.10),P<0.01];不良反应主要是肛门刺激不适症状、皮疹、出汗较多;药物不良反应[RR=1.84,95%CI(0.62,5.44),P=0.27];发热患儿药费0.90元/d;经肛门用药,适用性好。④与吗丁啉相比,5个CCT(低级证据质量)显示藿香正气软胶囊治疗胃肠道症状效果更好,有效率合并结果为RR=3.09,95%CI(2.01,4.75),P<0.05;1个RCT(中级证据质量)表明,该药治疗感冒所致胃肠道症状总有效率98.06%;无药物不良反应事件发生;药费0.67元/d;口服,适用性好。⑤治疗对乙酰氨基酚中毒,国外1项回顾性研究表明,15例(23%)在8小时内给予乙酰半胱氨酸注射液治疗的患者无死亡或进展为肝衰竭、肾衰竭。8小时后接受乙酰半胱氨酸注射液治疗的患者住院时间>3天,而8小时内接受该药治疗患者仅1天;15 min组肝毒性发生率为0%～9%(95%CI);25例60 min组为0%～12%(95%CI);可导致潮红、皮疹及瘙痒。注射用药需专业人员监督、指导使用,适用性差;药费儿童40元/d,成人160元/d。结论①儿童普通感冒发热对症治疗疼痛不适强推荐布洛芬混悬液、扑热息痛栓剂;强推荐藿香正气软胶囊治疗成人感冒胃肠症状。弱推荐乙酰半胱氨酸注射液治疗对乙酰氨基酚中毒。②建议尽量报道大样本对照研究,完善结局指标,以便生产高质量本土化证据。

Objective To evaluate and select essential medicine for children with fever and adult gastrointestinal flu caused by common cold 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） 12 guidelines were included,11 of which were evidence-based or based on expert consensus.We offered a recommendation for medicines used in the treatment including analgesics and antipyretics,decongestants,antihistamines,cough-relieving drug,phlegm-removing drug and drug for gastrointestinal symptoms.（2） A result of four RCTs（very low quality） indicated that in the treatment of children with cold,ibuprofen suspension had an antipyretic effect similar to paracetamol solution（for oral use） with a pooled result of 6-hour efficiency in relieving fever（RR 1.48,95%CI 0.66 to 3.30,P=0.34）.The major adverse effects of ibuprofen suspension included gastrointestinal reaction and profuse sweats（RR=1.23,95%CI 0.72 to 2.11,P=0.45）.With good applicability,ibuprofen suspension（for oral use with no need to be supervised） cost 1.93 yuan daily.（3） A result of three RCTs（low quality） indicated that after given for 30 minutes and one hour,paracetamol solution（suppository） was fairly superior to ibuprofen suspension in lowering the high temperature caused by fever（given for 30 min： MD= –0.16°C,95%CI –0.21 to –0.11,P〈0.01;given for one hour： MD= –0.19°C,95%CI –0.28 to 0.10,P〈0.01）.As to adverse reaction,paracetamol solution（suppository） mainly included anal irritation,skin rashes and profuse sweats,which had a comparative result of incidence with ibuprofen suspension（RR=1.84,95%CI 0.62 to 5.44,P=0.27）.For children with fever,paracetamol solution（suppository） cost 0.90 yuan daily.With good applicability,paracetamol solution（suppository） was administered via the anus.（4） A result of five RCTs（low quality） indicated that Huo Xiang Zheng Qi Jiao Nang（name of a Chinese patent drug） was more effective than motilium in alleviating gastrointestinal symptoms（RR=3.09,95%CI 2.01 to 4.75,P〈0.05）.A result of one RCT（moderate quality） indicated that Huo Xiang Zheng Qi Jiao Nang（for oral use） had a total efficiency of 98.06% for gastrointestinal flu caused by cold.With good applicability,it caused no adverse reaction and cost 0.67 yuan daily.（5） A result of a foreign retrospective study indicated that 15 cases（accounting for 23%） who were injected acetylcysteine within eight hours had neither death nor aggravation such as liver failure or kidney failure.Patients injected acetylcysteine after eight hours spent more than three days in hospital,while those injected acetylcysteine with eight hours spent only one day.The incidence of hepatotoxicity was 0% to 9%（95%CI） in 15 min group,and 0% to 12% in 60 min group（25 cases）.The major adverse effects of acetylcysteine included tidal flushing,skin rashes and itching.The injection of acetylcysteine should be applied under the guidance and supervision of professionals.With poor applicability,it cost 40 yuan daily for children and 160 yuan daily for adults.Conclusion （1） We offer a strong recommendation for ibuprofen suspension（2 g/100 mL） or acetaminophen（0.1 g/suppository） as symptomatic treatment used in children with fever,pain and discomfort caused by common cold,and for Huo Xiang Zheng Qi Jiao Nang（0.3 g/ capsule） used in adults with gastrointestinal flu.We also offer a weak recommendation for acetylcysteine（injection,300 mg/mL,10 mL/ampoule） used in patients with paracetamol poisoning.（2） In order to produce high-quality local evidence,we proposed that large-scale,well-designed,high-quality clinical and pharmacoeconomic studies on ibuprofen suspension and acetaminophen suppository in the treatment of children with fever,pain and discomfort caused by common cold should be further carried out.Besides,we proposed that large-scale,well-designed,high-quality clinical and pharmacoeconomic studies on Chinese patent drugs of Huo Xiang Zheng Qi used in chidren and Huo Xiang Zheng Qi Jiao Nang used in adults should further carried out.Moreover,we suggest that epidemiological investigation as well as clinical and pharmacoeconomic studies of acetylcysteine injection for paracetamol poisoning should be carried out and the instructions of acetylcysteine injection should be added in the guidelines of essential medicine in China.Finally,further studies on evidence of oxymetazoline,dextromethorphan and other Chinese patent drugs with the effect of relieving cough and treating cold should be carried out.