探索静脉输液 (IV) 颗粒过滤的优势及解决方案
欢迎阅读本文了解更多相关信息，包括：颗粒物会为患者带来怎样的负担、颗粒物可能产生哪些有害影响，以及如何使用 IV过滤器减少颗粒数、提升临床疗效、提高医院收益。此外，您还可以阅读有关美国指南制定机构及其针对 IV过滤器使用建议的信息，了解我们将如何针对 IV 过滤器在病房中的部署为您提供支持。
颇尔 IV过滤器可截留颗粒物
“遗憾的是，颗粒物的问题在很大程度上仍未得到重视。许多临床医生可能认为他们从未见过患者受颗粒物影响，但事实上，他们很可能是还未见过哪位患者未曾受到颗粒物的影响。”
（Patrick Ball 教授 (2017)），德国柏林 PDA 会议“肠外输注溶液中的颗粒物”）。
重症监护患者通常需要接受大量静脉输液，因此如果没有 IV过滤器，每天将有多达一百万个颗粒输入患者体内。1-4 这些颗粒物进入人体后可能导致微循环障碍，而重要器官微血管血流受损则可能导致 ICU 患者器官功能障碍。5-7
实验室和临床研究表明，颇尔 IV过滤器可在临床相关条件下截留颗粒物、提升治疗成效、缩短患者在 ICU 的住院时间、提高医院收益。8-15
2020 年，美国肠外肠内营养学会 (ASPEN) 指出：“对于新生儿、危重症患者以及那些原来因创伤、手术或败血症而存在组织损伤的患者来说，输入颗粒物会产生更加明显的有害影响。需肠外营养的患者经常需要长时间或高强度的静脉输液治疗。在此类情况下，常常也可能引发因输入颗粒物导致的不良反应。”16
2021 年，美国静脉输液护理学会 (INS) 在第 8 版《输液治疗实践标准》中指出：“应考虑对溶液和药物进行过滤，以减少危重症患者体内的颗粒物，因为这些颗粒物可能导致血栓形成、微循环受损和免疫反应改变。”17
References
Perez M., Maiguy-Foinard A., Barthélémy C., Décaudin B. and Odou P. (2016). Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients. Pharm. Technol. Hosp. Pharm.; 1(2): 91-103
Langille, S.E. (2013). Particulate Matter in Injectable Drug Products. PDA J Pharm Sci and Tech; 67: 186-200
Perez M. et al. (2015). In vitro analysis of overall particulate contamination exposure during multidrug IV therapy: impact of infusion sets. Pediatr Blood Cancer; 62(6): 1042-7
Benlabed M. et al. (2019). Clinical implications of intravenous drug incompatibilities in critically ill patients. Anaesth Crit Care Pain Med;38(2): 173-180.
Lehr HA., Brunner J., Rangoonwala R. and Kirkpatrick C.J. (2002). Particulate Matter Contamination of Intravenous Antibiotics Aggravates Loss of Functional Capillary Density in Postischemic Striated Muscle. Am J Respir Crit Care Med; 165: 514-520
Kirkpatrick CJ. et al. (2013). Non-Equivalence of Antibiotic Generic Drugs and Risk for Intensive Care Patients. Pharmaceut Reg Affairs; 2(1): 1-7
Schaefer S.C., Bison P.A., Rangoonwala R., Kirkpatrick J.C. and Lehr H.A. (2008). 0.2 µm in-line filters prevent capillary obstruction by particulate contaminants of generic antibiotic preparations in postischemic muscle. Chemother J; 17: 172-8
Perez M. et al. (2018). Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol. Sci Rep; 8 (7714): 1-8
Jack T. et al. (2012). In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial. Intensive Care Med; 38: 1008-1016
Boehne M. et al. (2013). In-line filtration minimizes organ dysfunction: New aspects from a prospective, randomized, controlled trial. BMC Pediatrics; 13 (21): 1-8
Sasse M. et al. (2015). In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients. Pediatr Cardiol; 36: 1270-1278
Villa G. et al. (2018). In-Line Filtration Reduces Postoperative Venous Peripheral Phlebitis Associated With Cannulation: A Randomized Clinical Trial. Anesth Analg; 127(6): 1367-1374
Villa G. et al. (2020). In-line filtration reduced phlebitis associated with peripheral venous cannulation: Focus on cost-effectiveness and patients’ perspectives. J Vasc Access; 21(2): 154-160
Schmitt E. et al. (2019). In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients. Critical Care; 23 (373): 1-11
Unger-Hunt L. (2019). Reducing Risks and Generating Economic Benefits. Health Management; 19(4): 286-287
Worthington P. et al. (2020). Update on the Use of Filters for Parenteral Nutrition: An ASPEN Position Paper. Nutrition in Clinical Practice; 0(0): 1-11
输液中的颗粒污染可能由多种原因引起，包括药物的不完全重组、输液治疗期间的药物不兼容反应、肠外营养成分的聚集体、容器/安瓿上的玻璃、输液系统的塑料容器或组件（如 输液管路、导管和橡胶塞）。1-8
图2：红细胞与颇尔过滤器在临床使用中发现的颗粒大小比较（颇尔实验室图片）
References
Perez M., Maiguy-Foinard A., Barthélémy C., Décaudin B. and Odou P. (2016). Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients. Pharm. Technol. Hosp. Pharm.; 1(2): 91-103
Ball P.A. (2003). Intravenous in-line filters: filtering the evidence. Curr Opin Clin Nutr Metab Care; 6:319-325
Jack T. et al. (2010). Analysis of particulate contaminations of infusion solutions in a pediatric intensive care unit. Intensive Care Med; 36:707-711
Langille, S.E. (2013). Particulate Matter in Injectable Drug Products. PDA J Pharm Sci and Tech; 67: 186-200
Perez M. et al. (2015). In vitro analysis of overall particulate contamination exposure during multidrug IV therapy: impact of infusion sets. Pediatr Blood Cancer; 62(6): 1042-7
Benlabed M. et al. (2018). Clinical implications of intravenous drug incompatibilities in critically ill patients. Anaesth Crit Care Pain Med; 2019 Apr;38(2): 173-180
Lázaro Cebas A. et al. (2018). Precipitation limits in pediatric parenteral nutritions with organic sources of calcium and phosphate. Nutr Hosp 20; 35(5): 1009-1016
Brent B.E., Jack T. and Sasse M. (2007). In-line filtration of intravenous fluids retains ‘spearhead’-shaped particles from the vascular system after open-heart surgery. Eur Heart J; 28 (10):1192
人们通常认为，重症监护室 (ICU) 内的住院患者，在接受输液治疗时更容易遭遇颗粒输入。这是因为：
· ICU 患者常常需要接受大量药物和液体输入。
· ICU 内药物和液体主要通过静脉输注给药。
· ICU 患者通常需要借助有限数量的静脉通路使用多种药物，因此因药物不兼容导致颗粒形成的风险更高。1-3
References
Maison O. et al. (2019). Drug incompatibilities in intravenous therapy: evaluation and proposition of preventive tools in intensive care and hematology units. Eur J Clin Pharmacol;75(2): 179-187
Neininger M.P. et al. (2018). Incompatibilities in paediatric intensive care - pitfalls in drug information. Pharmazie; 73(10): 605-608
Perez M. et al. (2018). Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol. Sci Rep; 8 (7714): 1-8
无论颗粒的大小如何，一旦进入循环系统，便都可能对人体造成伤害。所输入颗粒物的具体影响取决于多种因素，如颗粒大小、形状、数量、特性和电荷等。1,2
所输入颗粒物可能导致血管阻塞3-5、因凝血系统被激活引起全身高凝效应6、微循环受损7-9、免疫调节作用和炎症反应。10-13此外，来自治疗性蛋白质的蛋白颗粒，如单克隆抗体疗法，可能导致免疫原性和超敏反应。14-16
图 3：五种可能的有害颗粒影响机制
References
Perez M., Maiguy-Foinard A., Barthélémy C., Décaudin B. and Odou P. (2016). Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients. Pharm. Technol. Hosp. Pharm.; 1(2): 91-103
Langille, S.E. (2013). Particulate Matter in Injectable Drug Products. PDA J Pharm Sci and Tech; 67: 186-200
Ilium L. et al. (1982) et al. Blood clearance and organ deposition of intravenously administered colloidal particles. The effects of particle size, nature and shape. Int J Pharm.; 12(2): 135-46
Bradley J.S., Wassel R.T., Lee L. and Nambiar S. (2009). Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics; 123(4): e609-13
Puntis J.W.L. et al. (1992). Hazards of parenteral treatment: do particles count? Archives of Disease in Childhood; 67: 1475-1477
Boehne M. et al. (2013). In-line filtration minimizes organ dysfunction: New aspects from a prospective, randomized, controlled trial. BMC Pediatrics, 13 (21): 1-8
Kirkpatrick CJ. et al. (2013). Non-Equivalence of Antibiotic Generic Drugs and Risk for Intensive Care Patients. Pharmaceut Reg Affairs; 2(1): 1-7
Schaefer SC. et al. (2008). 0.2 µm in-line filters prevent capillary obstruction by particulate contaminants of generic antibiotic preparations in postischemic muscle. Chemother J; 17: 172-8
Lehr HA., Brunner J., Rangoonwala R. and Kirkpatrick C.J. (2002). Particulate Matter Contamination of Intravenous Antibiotics Aggravates Loss of Functional Capillary Density in Postischemic Striated Muscle. Am J Respir Crit Care Med; 165: 514-520
Jack T. et al. (2012). In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial. Intensive Care Med, 38, 1008-1016
Jack T. et al. (2010). Analysis of particulate contaminations of infusion solutions in a pediatric intensive care unit. Intensive Care Med; 36:707-711
Schmitt E. et al. (2019). In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients. Critical Care; 23 (373): 1-11
Chisholm C.F., Behnke W., Pokhilchuk Y., Frazer-Abel A.A. and Randolph T.W. (2020). Subvisible Particles in IVIg Formulations Activate Complement in Human Serum. J Pharm Sci.; 109(1): 558-565
Berger M. (2013). Adverse effects of IgG therapy. Journal of Allergy and Clinical Immunology: In Practice; 1(6): 558-566.
Kessler M., Goldsmith D. and Schellekens H. (2006). Immunogenicity of biopharmaceuticals. Nephrol Dial Transplant; 21 [Suppl 5]: v9–v12
Rosenberg A.S. (2006). Effects of protein aggregates: An immunologic perspective. The AAPS Journal; 8: E501–E507
有多少颗粒被输入到患者体内？实际数字可能会有所不同，具体取决于 ICU 输液系统的设置、被测试的药物、药物不兼容的频率以及所计数颗粒的大小。过去几年，曾有研究项目统计了可能被输入患者体内的颗粒的数量。粒径在 100 微米及以下的颗粒被归类为亚可见颗粒（在显微镜下才能看见的颗粒）。1 从输液系统、单一药物、肠外营养液和药物容器中检测到的颗粒大都属于亚可见颗粒。经验法则表明，颗粒的粒径越小，数量就越多。
表：旨在评估可能被输入患者体内的颗粒数量的研究概述
References
- Melchore JA. (2011). Sound practices for consistent human visual inspection. AAPS Pharm Sci Tech;12 (1): 215-221
- Perez M. et al. (2018). Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol. Sci Rep; 8 (7714): 1-8
- Benlabed M. et al. (2018). Analysis of particulate exposure during continuous drug infusion in critically ill adult patients: a preliminary proof-of concept in vitro study. Intensive Care Medicine Experimental; 6 (38): 1-9
- Perez M. et al. (2017). Dynamic Image Analysis To Evaluate Subvisible Particles During Continuous Drug Infusion In a Neonatal Intensive Care Unit. Scientific Reports; 7 (9404): 1-8
- Joo G.E., Sohng K.Y. and Park M.Y. (2016). The effect of different methods of intravenous injection on glass particle contamination from ampules. SpringerPlus; 5 (15): 1-8
- Perez M. et al. (2015). In vitro analysis of overall particulate contamination exposure during multidrug IV therapy: impact of infusion sets. Pediatr Blood Cancer; 62(6):1042-7
- Ernst C, Keller M. and Eckstein J. (2012). Micro-Infusion Filters and Particulate Matter in Injections. Pharm. Ind; 74 (12): 2009-2020 (German Language)
- Oie S. and Kamiya A. (2005). Particulate and microbial contamination in in-use admixed parenteral nutrition solutions. Biol Pharm Bull; 28 (12): 2268-2270.
- Puntis J.W., Wilkins K.M., Ball P.A., Rushton D.I. and Booth I.W. (1992). Hazards of parenteral treatment: do particles count? Arch Dis Child;67 (12):1475-1477
两项模拟真实医院场景的研究证明，IV过滤器能够截留颗粒物。1
Perez 等人 证明，在儿科重症监护室患者常用的多药物输液管中引入过滤器，可显著减少颗粒物的总量。在经多药物输液管给药 24 小时后，研究人员评估了总颗粒数。本部分的表格示出了 99.9% 至 98.2% 的颗粒截留率，具体数值取决于所计数颗粒的大小。此研究使用了颇尔的 AEF1NTE 过滤器。1
表：对儿科多药物输液系统所输注药液进行过滤前后的颗粒数量
References
Perez M. et al. (2018). Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol. Sci Rep; 8 (7714): 1-8
自 2008 年以来，颗粒物对 ICU 患者的影响，或者说 IV过滤器截留颗粒物对 ICU 患者产生的影响，一直是研究人员和临床医生关注的焦点。在这方面，颇尔 IV 过滤器一直是并将继续是一股强劲的推动力。已有多项研究证明，使用 IV过滤器能够为患者带来临床益处。1-8
早在 2008 年，Schaefer 等人便利用动物模型证明，输入颗粒物会对关键组织灌注构成重大威胁，并证明 IV过滤器可防止缺血后功能性毛细血管密度进一步降低。动物研究的结果表明：“对于原来（因创伤、重大手术、败血症而存在）重要器官微血管受损的患者，过滤器很可能能产生巨大的积极影响。”1
过去 10 年来，多项人体临床研究表明，IV过滤器确实能够对 ICU 患者产生积极影响，因为其可以保护器官功能、降低全身炎症反应综合征 (SIRS) 的发病率、降低外科患者术后静脉炎的发生率。2-8
图 5：IV过滤器能够带来的临床益处
表：证明 IV过滤器临床益处的研究概述 (2012-2013)
表：证明 IV过滤器临床益处的研究概述 (2019)
表：证明 IV过滤器临床益处的研究概述 (2008)
表：证明 IV过滤器临床益处的研究概述 (2015-2016)
表：证明 IV过滤器临床益处的研究概述 (2020)
References
Schaefer SC. et al. (2008). 0.2 µm in-line filters prevent capillary obstruction by particulate contaminants of generic antibiotic preparations in postischemic muscle. Chemother J; 17: 172-8
Jack T. et al. (2012). In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial. Intensive Care Med; 38: 1008-1016
Boehne M. et al. (2013). In-line filtration minimizes organ dysfunction: New aspects from a prospective, randomized, controlled trial. BMC Pediatrics; 13 (21): 1-8
Sasse M. et al. (2015). In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients. Pediatr Cardiol; 36: 1270-1278
Villa G. et al. (2018). In-Line Filtration Reduces Postoperative Venous Peripheral Phlebitis Associated With Cannulation: A Randomized Clinical Trial. Anesth Analg; 127(6): 1367-1374
Schmitt E. et al. (2019). In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients. Critical Care; 23 (373): 1-11
Virlouvet A.L. et al. (2020). In-line filtration in very preterm neonates: a randomized controlled trial. Scientific Reports; 10 (5003): 1-8
IV过滤器有助于缩短患者在 ICU 和医院接受治疗的时间
有两项临床研究对患者在 ICU 的住院时间 (LOS) 以及在医院接受治疗的总时间进行了评估。1,2
本部分的表格示出了 Jack 等人的研究数据摘要，该研究涉及到了 807 名儿童患者。显然，与不使用 IV过滤器的儿科 ICU 患者相比，使用 IV过滤器的儿科 ICU 患者能够更早离开 ICU。1
同时，本部分的表格还示出了 Schmitt 等人的研究数据摘要，该研究涉及到了 3215 名成年患者。显然，与不使用 IV过滤器的成年 ICU 患者相比，使用 IV过滤器的成年 ICU 患者能够更早离开 ICU 和医院。2
表：IV过滤器对儿童患者在 ICU 的住院时间以及在医院接受治疗的总时间的影响
表：IV过滤器对成年患者在 ICU 的住院时间以及在医院接受治疗的总时间的影响
IV过滤器的投资回报
一项评估德国某儿科重症监护室 (PICU) 所用过滤器经济价值的分析显示，对过滤器投资 5 万欧元，可为医院带来 160 万欧元的投资回报。3
汉诺威医学院 (MHH) PICU 首席高级医师 Michael Sasse，在 2018 年葡萄牙欧洲医院管理者协会 (EAHM) 大会上，补充了 IV过滤器能够带来的其他经济影响：
“不太严重的并发症将仅需少量抗生素等药物，器官置换、医务人员的工作量将减少，诊断程序的成本也将降低。患者将能够更快出院，因此 ICU 分配的灵活性将得到提升、手术也将能力增强。”3
此外，Van Lingen 的研究还评估了在 8 天的标准住院时间内治疗患病新生儿的成本。最后，除了主要临床并发症显著减少外，研究人员实际上还发现了大幅的成本节省。4
图 6：德国汉诺威医学院儿科重症监护室对 IV过滤器进行经济分析
References
Jack T. et al. (2012). In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial. Intensive Care Med; 38: 1008-1016
Schmitt E. et al. (2019). In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients. Critical Care; 23 (373): 1-11
Unger-Hunt L. (2019). Reducing Risks and Generating Economic Benefits. Health Management; 19(4): 286-287
Van Lingen R.A., Baerts W., Marquering A.C. and Ruijs G.J. (2004). The use of in-line intravenous filters in sick newborn infants. Acta Paediatr; 93: 658-662
鉴于实验室和临床试验结果均表明，IV过滤器能够为重症监护患者带来益处，因此美国静脉输液护理学会 (INS) 和美国肠外肠内营养学会 (ASPEN) 均推荐采用输液过滤。1,2,3
有关 IV 过滤器的使用，ASPEN 在 2020 年的一份立场文件中指出：“那些不过滤肠外营养 (PN) 混合物或静脉输注用脂质乳剂 (ILE) 的医疗保健机构应重新评估这些决定，与因未过滤 ILE 或 PN 导致的发病率和死亡率上升相比，使用过滤器的成本要低得多。”2
References
Gorski L.A. et al. (2021). Infusion Therapy Standards of Practice, 8th Edition. J Infus Nurs; 01(44): S1-S224
Worthington P. et al. (2020). Update on the Use of Filters for Parenteral Nutrition: An ASPEN Position Paper. Nutrition in Clinical Practice; 0(0): 1-11
Ayers P. et al. (2014) A.S.P.E.N. Parenteral Nutrition Safety Consensus Recommendations. Journal of Parenteral and Enteral Nutrition; 38 (3): 296-333
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