各类基础输液产品包装的综合评价:文献系统综述

Comprehensive evaluation on different types of basic intravenous infusion product packaging:a systematic review

目的对现有各类基础输液产品的包装进行综合评估,阐明其在药物稳定性、安全性、便捷性、经济性等重要指标上的差异,为临床合理选择输液包装和医疗保险支付决策提供科学依据。方法利用系统综述方法总结不同基础输液产品包装的文献评估证据。结果共纳入161篇文献,其证据表明:在适宜的储存条件下,绝大多数药物都能在玻璃、聚烯烃共挤膜、聚丙烯材质的输液包装中稳定存在,被检测的包装材质安全性都符合《中华人民共和国药典2015年版四部》的要求。相对于其他材质的容器,玻璃瓶有更为广泛的稳定性。不同包装形式的基础输液产品在临床使用的安全性、输液后残液量、便捷性、经济性方面有明显差异。全密闭式较半开放式输液容器可降低中央导管相关血流感染的发生率,临床安全性较优,且性价比更高;双阀软袋输液后的残液量普遍低于塑瓶,因而可以节省药物费用,目前缺乏直立式聚丙烯输液袋及内封式聚丙烯输液袋残液量的研究;将使用玻璃瓶储备的药液转换为软袋时,可节约因备药、储存和破损而造成的成本;直立式输液袋(直立式聚丙烯输液袋、内封式聚丙烯输液袋)的临床使用便捷性优于非PVC软袋,玻璃瓶的使用便捷性最差。不同生产工艺的基础输液产品在控制小粒径不溶性微粒和漏液率方面表现不同。与非PVC软袋、塑料瓶、玻璃瓶和直立式聚丙烯输液袋相比,内封式聚丙烯输液袋在控制空白输液中不溶性微粒(直径≥5μm和≥10μm)方面表现出一定的优势。在与临床常用药配伍后,内封式聚丙烯输液袋的优势则主要表现在控制2~5μm的小粒径不溶性微粒方面,但目前证据仅支持内封式聚丙烯输液袋优于某厂家的双阀软袋。与漏液率相关的文献均只涉及非PVC软袋类的基础输液产品,其漏液问题可能与具体生产工艺相关,而且不同厂家的漏液比例悬殊。结论各种基础输液产品的包装因材料、形式、生产工艺方面的不同,表现为部分评估指标的确有明显差异,但仍需要更多数据的支持。建议开展更多的覆盖多厂家、多批次随机抽样的实证研究来比较各种不同包装形式或不同生产工艺的基础输液产品在与临床常用药配伍后在不溶性微粒、临床安全性、残液量和使用便捷性方面的表现。

Objective To develop a comprehensive evaluation on basic intravenous infusion containers,a clearer understanding of different types of basic infusion product packaging on key assessment indicators such as stability,safety,convenience,and economy would help make informed decision in clinical practice and coverage policy-making.Methods A systematic review was conducted to summarize literature evidences about basic infusion containers.Results A total of 161 articles were included.The literature evidences demonstrated:Regarding compatibility between medicine and container material,most medicines were compatible with the materials glass,non-polyvinyl chloride,polyolefin and polypropylene under appropriate storage conditions and all tested materials were in accordance with the national standards;in general,glass bottles were more compatible with medicines than other types of materials.Infusion containers of various structural forms showed differences in clinical safety,residual fluid volume,efficiency in preparation and cost-effectiveness.Closed infusion containers would reduce the incidence of central line-associated bloodstream infection and were regarded more costeffective than semi-open infusion containers.The residual volumes of double-port soft bags were significantly lower than glass/plastic bottles,resulting in a cost saving in medicine expenditure,but there is a lack of research on residual fluid volume of upright polypropylene and blow-fill-seal bags;switching from glass bottles to soft bags could reduce costs via gaining efficiency in infusion preparation,storage and avoid fluid leakage;upright bags(including upright polypropylene and blowfill-seal bags)required shorter time in preparation for infusion than non-polyvinyl chloride bags,and glass bottles were the most inconvenient type of containers for clinical use.The blow-fill-seal infusion bags were better at controlling the number of insoluble particles(sizes≥5μm and≥10μm in diameters)in blank infusion fluid than non-polyvinyl chloride bags,plastic/glass bottles and upright polypropylene bags.After admixture preparation,the major advantage of the blow-fill-seal bags was found in controlling insoluble particles of a smaller size(2-5μm),as compared with non-polyvinyl chloride double ports bags from a particular manufacturer.Only non-polyvinyl chloride soft bags were reported with a leakage problem and the leakage rate varied across manufacturers,suggesting that it may be related to the differences in both type and quality due to different manufacturers.Conclusion Basic intravenous infusion containers with different materials,structural forms,manufacturing techniques had varying performance on several key assessment indicators.In view of the limited evidence,it is suggested to develop comparative studies of different types of containers and manufacturing techniques with a more representative sample including different types of basic infusion containers across multiple batches from all the major manufacturers.