对乙酰氨基酚、布洛芬及吲哚美辛治疗早产儿动脉导管未闭的快速卫生技术评估

    Rapid Health Technology Assessment of Acetaminophen, Ibuprofen, Indometacin in the Treatment of Patent Ductus Arteriosus in Preterm Infants

    • 摘要:
      目的  采用快速卫生技术评估(Health Technology Assessment,HTA)方法,评价对乙酰氨基酚(acetaminophen,APAP)、布洛芬(ibuprofen,IB)及吲哚美辛(indometacin,ID)治疗早产儿动脉导管未闭(patent ductus arteriosus,PDA)的有效性、安全性和经济性,为临床治疗提供循证依据。
      方法 计算机检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方、中国生物医学文献数据库、维普等中外数据库和相关卫生技术评估网站。收集APAP、IB、ID治疗早产儿PDA的系统评价/meta分析、HTA报告及药物经济学研究,检索时限为建库至2024年10月31日。2位研究者独立筛选文献、提取资料、对文献进行质量评价,对纳入的研究结果进行描述性分析。
      结果 共纳入23篇系统评价/meta分析,2篇药物经济学研究。有效性结果显示,APAP、IB、ID在第一疗程PDA关闭率、第二疗程PDA关闭率、总PDA关闭率、PDA手术闭合率及重新开放率等方面差异无统计学意义。进一步细分到给药途径及剂量的比较,对于PDA关闭率,口服IB和APAP较相应的静脉制剂有优势,其中口服高剂量IB最有优势,其次为口服标准剂量APAP、口服标准剂量IB。安全性结果显示,与APAP相比,IB增加了肾功能不全、少尿、消化道出血/穿孔、高胆红素血症的发生率,ID增加了少尿、新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)的发生率;与IB相比,ID增加了少尿、消化道出血/穿孔、NEC的发生率。经济性结果显示,国外研究表明APAP在成功关闭PDA中具有较好的成本-效果比。
      结论 综合分析有效性和安全性,对于有症状的PDA,口服IB、口服APAP较有优势;APAP的总体安全性较好,IB次之,然而目前关于早产儿早期接触APAP后的长期影响仍不明确;在国外APAP具有较好的经济学优势,但还需开展国内药物经济学研究。

       

      Abstract:
      OBJECTIVE To rapidly evaluate the effectiveness, safety and economy of acetaminophen(APAP), ibuprofen(IB), indometacin(ID) in the treatment of patent ductus arteriosus(PDA) in preterm infants, to provide evidence-based reference for clinical treatment.
      METHODS Chinese and foreign databases such as PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, CBM, VIP and related health technology assessment websites were searched by computer. HTA reports, systematic evaluation/meta-analysis and pharmacoeconomic studies on APAP, IB, ID in the treatment of PDA were collected during the inception to October 31, 2024. Two researchers independently screened literature, extracted data, evaluated the quality of the literature, and conducted a descriptive analysis of the included research results.
      RESULTS A total of 23 systematic evaluation/meta-analysis and 2 pharmacoeconomic studies were included. Effectiveness analysis showed that, there was no significant difference between APAP, IB and ID in the first and second course of treatment PDA closure rate, total PDA closure rate, PDA surgical closure rate and reopening rate. Further subdivided into the comparison of administration routes and doses, for PDA closure rate, Oral IB and APAP had advantages over the corresponding intravenous preparations. Among them, oral high-dose IB was more advantageous, followed by oral standard dose of APAP, oral standard dose of IB. Safety analysis showed that, compared with APAP, IB increased the incidence of renal dysfunction, oliguria, gastrointestinal bleeding/perforation and hyperbilirubinemia; ID increased the incidence of oliguria and neonatal necrotizing enterocolitis(NEC). Compared with IB, ID increased the incidence of oliguria, gastrointestinal bleeding/perforation, NEC. Economic analysis showed that, foreign studies indicated that APAP had a higher cost-effectiveness ratio in closed PDA successfully.
      CONCLUSION Comprehen-sive analysis of effectiveness and safety, oral IB, oral APAP are recommended for symptomatic PDA. The overall safety of APAP is relatively good, followed by IB. However, the long-term effects of early exposure to APAP in premature infants remain unclear at present. APAP has better economic advantages in foreign countries, but domestic pharmacoeconomics studies are urgently needed.

       

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