Explore the Benefits & Solutions of IV Particle Filtration
Read more with in the following chapters about the particle burden for patients, the potential harmful effects of particles, and how IV in-line filters can be used as a strategy to reduce the numbers of particles, improve the clinical outcome for patients and increase revenues for hospitals. Read about US guideline makers and their recommendation regarding the use of IV in-line filters and how we can support theimplementation of IV filters on your ward.
Our IV In-Line Filters Can Retain Particles
“Unfortunately, the problem of particles remains largely invisible, although many clinicians may believe they have never seen a patient affected by particles, the truth is they probably have not seen a patient who is not in some way affected by particles.”
(Prof. Patrick Ball (2017), PDA Conference “Particles In Parenteral Injection Solutions” at Berlin, Germany).
Intensive care patients usually receive a multitude of IV infusions that, without IV in-line filters, can infuse up to one million particles per day.1-4 Infused particles may lead to a disturbance in the microcirculation and a compromised microvascular flow in vital organs may result in organ dysfunction of ICU patients.5-7
Laboratory and clinical studies have been shown that our IV in-line filters can retain particles in a clinical set up, improve patient outcomes, reduce the length of stay in ICU and could have a positive financial impact on the hospital’s revenues.8-15
In 2020 the American Society for Parenteral and Enteral Nutrition states that “The detrimental effects of particulate infusion appear to be more pronounced in neonates, the critically ill, and those with preexisting tissue damage from trauma, surgery, or sepsis. The need for prolonged or intensive intravenous therapy, as is frequently the case for patients receiving Parenteral Nutrition, also increases the risk for adverse events related to particle infusion.”16
In 2021 the Infusion Nursing Society states in the 8th Edition of the Infusion Therapy Standards of Practice: “Consider filtration of solutions and medications to reduce particulate matter in critical ill patients that can cause thrombogenesis, impaired microcirculation, and alter immune response.”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
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Particle contamination of IV solutions can arise from many sources, including incomplete reconstitution of drugs, drug incompatibility reactions during IV therapy, conglomerates of parenteral nutrition components, glass from containers / ampoules, plastic containers or components of the infusion systems, such as IV tubing, catheters and rubber stoppers.1-8
Figure 2: Size comparison of a red blood cell with particles that have been found on Pall filters in clinical use (internal Pall images)
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
Patients hospitalized in intensive care units (ICUs) are considered a high-risk group for exposure to particles associated with infusion therapy.
ICU patients receive high volumes of drugs and fluids.
Drugs and fluids are predominantly administered intravenously in ICUs.
ICU patients commonly require the use of multiple drugs through a limited number of venous accesses and therefore have a higher risk of drug incompatibilities leading to particle formation.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
No matter what size particles are, they have the potential to hurt the human body once they are in the circulatory system. The effect of infused particles depends on several factors, such as particle size, shape, number, characteristics and electrical charge.1,2
Infused particles may lead to blockages of blood vessels3-5, systemic hypercoagulability effects due to the activation of the coagulation system6, impairment of the microcirculation7-9, immune-modulation effects and inflammatory reactions.10-13 Furthermore, proteinaceous particles from therapeutic proteins, such as monoclonal antibody therapies may lead to immunogenicity and hypersensitivity reactions.14-16
Figure 3: Five possible mechanisms of harmful particle effects
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
How many particles are infused into patients? The numbers vary, depending on the set-up of the ICU infusion regime, the drugs tested, the frequency of drug incompatibilities and the sizes of particles counted. Research projects over the last years counted the number of particles potentially infused into patients. Particles up to 100 microns are classified as subvisible.1 Particles detected from infusion regimes, single drugs, parenteral nutrition solutions and drug containers fall mainly into the subvisible range. The rule of thumb is that the smaller the particle size, the higher the number.
Table: Overview of studies evaluating the number of particles potentially infused to a patient
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
Two studies mimicking real hospital scenarios have proven that IV in-line filters can retain particles.1
Perez et al. demonstrated that the introduction of in-line filters in multidrug infusion lines typical for pediatric intensive care unit patients led to a significant reduction in overall particulate matter. The total number of particles was assessed after a 24-hour multidrug administration. The data in the table below shows a particle retention between 99.9% and 98.2% depending on counted particle sizes. This study was conducted with a Pall AEF1NTE filter.1
Table: Number of particles before and after filtration in a pediatric multidrug infusion regime
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
The impact of particles, or the impact of IV in-line filters retaining particles, on ICU patients has been in the spotlight of researchers and clinicians since 2008. Our IV filters have been and continue to be a driving force in this regard. Several studies have demonstrated the clinical benefits of using IV in-line filters.1-8
Already in 2008 Schaefer et al. demonstrated in an animal model that infusion of particles poses a major threat to critical tissue perfusion and that IV in-line filters prevent further a reduction of the postischemic functional capillary density. The results of the animal studies suggest that “in-line filters have potentially enormous relevance for patients with prior microvascular compromise of vital organs (i. e. post trauma, major surgery, sepsis).”1
Over the last 10 years several human clinical studies suggest that IV in-line filters have a positive impact on ICU patients by preserving organ functions and reducing the incidence of the systemic inflammatory response syndrome (SIRS) and reducing postoperative phlebitis rates in surgical patients.2-8
Figure 5: Clinical Benefits of IV In-Line Filters
Table: Overview of studies demonstrating the clinical benefits of IV in-line filters (2012-2013)
Table: Overview of studies demonstrating the clinical benefits of IV in-line filters (2019)
Table: Overview of studies demonstrating the clinical benefits of IV in-line filters (2008)
Table: Overview of studies demonstrating the clinical benefits of IV in-line filters (2015-2016)
Table: Overview of studies demonstrating the clinical benefits of IV in-line filters (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 in-line filters reduce the length of stay in ICUs and hospitals
Two clinical studies evaluated length of stay (LOS) in the ICU and the total length of hospital stay.1,2
The table below shows a summary of the data from a study by Jack et al. which included 807 pediatric patients. Pediatric ICU patients with IV in-line filters were able to leave the ICU significantly earlier than patients without IV in-line filters.1
The table below shows a summary of the data from a study by Schmitt et al. which included 3215 adult patients. Adult ICU patients with IV in-line filters were able to leave the ICU and the hospital significantly earlier than patients without IV in-line filters.2
Table: Impact of IV in-line filters on the LOS in the PICU and total stay in the hospital
Table: Impact of IV in-line filters on the LOS in the adult ICU and total stay in the hospital
Return of investment of IV in-line filters
An analysis evaluating the economic value of in-line filters in a German PICU revealed that an investment of 50K € in in-line filters led to a return of investment for the hospital of 1.6 million €.3
Dr Michael Sasse, leading senior physician of the PICU at Hannover Medical School (MHH), added additional economic aspects at the EAHM (European Association of Hospital Managers) congress in Portugal 2018:
“Less severe complications result in fewer drugs such as antibiotics, reduction of organ replacement, medical staff workload and also a decrease in costs for diagnostic procedures. Being able to release patients sooner also increases the flexibility of ICU allocation and the capacity for surgeries.”3
Moreover, the Van Lingen’s study evaluated the costs in treating sick newborn infants during a standard 8-day stay. Besides a significant decrease in major clinical complications, substantial cost savings were also observed.4
Figure 6: An economic analysis of IV in-line filter in a German PICU at the Hannover Medical School, Germany
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
In light of laboratory and clinical trial results demonstrating the benefits of IV in-line filters on intensive care patients, the Infusion Nurses Society (INS) and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) are recommending in-line filtration.1,2,3
Regarding the use of IV filters ASPEN stated in a position paper in 2020 that “healthcare organizations that do not filter parenteral nutrition (PN) admixtures or Intravenous Lipid Emulsions (ILE) reevaluate these decisions and consider the small price of filters in comparison to increased morbidity and mortality that may result from not filtering ILE or PN.”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
Our highly skilled technical experts in our “Scientific Laboratory Services” (SLS) are here to support you and offer advice on optimal intravenous filtration and infusion solutions or to perform drug compatibility studies.
Our Clinical Specialists support customers who wish to implement Pall intravenous, breathing and gas filtration devices. They implement and evaluate our products in hospitals at the patient’s bedside and advise on any problems that might arise.
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