A world without IV in-line filters

1969: The year that rocked the world

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"In 1969, a whole range of famous events changed the world for good, leaving its mark in history as one of the most culturally defining years to date: the first-ever Concorde test flight, a mere 350,000 music fans descending on Woodstock and, of course, the first man on the moon." (1)

Astronaut Neil Armstrong’s epic walk on the moon proved to be "one small step for man," but also a remarkable success for us. Why? Because our bacterial retentive filters were used in the Lunar Module carrying Neil Armstrong and fellow astronaut Edwin Aldrin from the mother ship the surface of the moon. Our filters played a key role in protecting the astronauts, as the filters screened the gases vented from the Lunar Module as part of the process to equalize cabin pressure with the near-vacuum conditions on the moon. (2)

Nowadays within the medical industry, our IV in-line filters screen infusion fluids in modern infusion management. 1969 was pivotal for that development as well: In this year, Douglas W. Wilmore and Stanley J. Dudrick from the University of Pennsylvania and the Veterans Administration Hospital in Philadelphia published an article describing the use of an in-line filter to ensure solution sterility during prolonged intravenous (IV) therapy. (3)

50 years later, IV in-line filters are used in many hospitals protecting severely ill patients around the world.

2022: Imagine a world without IV in-line filters

Every year, more than 5 million patients are admitted to intensive care units (ICUs) across the United States, with costs of roughly $82 billion, or 0.66% of the gross domestic product. (4) These numbers stress the importance of constant critical care efficiency improvement in the US and most likely also in all other countries around the globe.

IV in-line filter technology developed over the course of 50 years went from protecting patients from bacteria into small bedside manufactured devices, which today can protect ICU patients from not only intraluminal bacteria, but also from endotoxin, air, and particles that may enter the blood stream. Over the last five decades, numerous studies have shown a wide range of benefits of IV in-line filters. Without these benefits, ICU patients and medical staff could be in a very different situation. So, what could the world look like without 0.2 µm and 1.2 µm IV in-line filters and no other technology substituting bedside filtration?

Join us on a journey of discovery: 12 points worth thinking about.

1. Duration of stay on ICU

Two clinical studies including 807 pediatric and 3,215 adult ICU patients evaluated the impact of filtration with 0.2 µm and 1.2 µm IV filters on the length of stay (LOS) in the ICU. (5,6) Both studies showed a significant reduction of LOS. The average LOS for the pediatric ICU patient was decreased from 3.89 days to 2.98 days, (5) and for the adult ICU patient from 1.7 to 1.2 days. (6)

2. Differences in severe complications on ICU

Clinical studies on pediatric ICU (PICU) patients have suggested that 0.2 µm and 1.2 µm IV in-line filters play a role in preserving respiratory, renal, and hematological function. Furthermore, the use of filters can significantly reduce the overall complication rate during the PICU stay, including circulatory failure, acute respiratory distress syndrome, acute renal failure, acute liver failure, thrombosis, sepsis, and systemic inflammatory response syndrome. (5,7,8) In adult ICU patients, a study has shown equally that 0.2 µm and 1.2 µm IV in-line filters can be associated with less organ dysfunction and reduced inflammation. (6)

3. Effects on budget for hospitals and ICU allocation flexibility

An analysis evaluating the economic value of IV in-line filters on a German PICU revealed that an investment of 50K € in 0.2 µm and 1.2 µm IV in-line filters led to a return of investment for the hospital of 1.6 million €, due to a shorter LOS and a consequent increase of ICU patients treated per year. (9)

Other economic aspects should be considered as well, as Dr. Michael Sasse, leading senior physician of the PICU at Hannover Medical School (MHH), stated during the EAHM congress in Cascais, Portugal in September 2018: “Less severe complications result in fewer drugs such as antibiotics, reduction of organ replacement, medical staff workload and 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.” (9)

4. Incidence of phlebitis

Over the years, many studies have evaluated the effect of in-line filters on the incidence of phlebitis. The most recent one has included 268 surgical patients and has shown that 0.2 µm and 1.2 µm IV in-line filters have a significant protective effect regarding postoperative phlebitis, as well as prolonging the cannula lifespan during peripheral venous cannulation. (10) The incidence of phlebitis within 48 hours postoperatively was 2.2% for the IV in-line filter versus 26.9% for the no-filter group.

5. Comfort and satisfaction for patients

IV in-line filters could reduce the incidence of postoperative peripheral phlebitis and its severity. Eventually, IV in-line filters may contribute to increasing patient satisfaction and reducing the discomfort associated with short peripheral venous cannulation. A quantitative and qualitative survey performed among patients enrolled in the trial illustrated that the use of 0.2 µm and 1.2 µm IV in-line filters modified the satisfaction perceived for the vascular access management. Patients who previously underwent short peripheral venous cannulation clearly flagged up in-line filtration as an innovation they would like to have during future hospitalizations. (11)

6. Nursing time

A trial on a neonatal ICU (NICU) demonstrated that IV in-line filters significantly reduce the time nurses must spend changing the IV administration systems: 10 ± 5 minutes in the filter group versus14 ± 7 minutes in the non-filter group. In addition, IV in-line filters guarantee a more continuous administration of IV medication and parenteral nutrition. (12)

7. Exposure to intraluminal particles

Several research projects over the last few years have calculated the number of particles potentially infused into patients, as well as the amount retained by IV in-line filters. (13-20) According to these data, IV in-line filters retain particles with an efficacy of between 99.9% and 98.2%, depending on counted particle sizes. (13,17) Infused particles have been associated with several adverse events, including blockages of blood vessels, systemic hypercoagulability effects due to the activation of the coagulation system, impairment of the microcirculation, immune-modulation effects, and inflammatory reactions. (21-29)

8. Vascular air embolism

Estimates of the frequency of vascular air embolism (VAE) associated with central venous catheters (CVCs) vary widely and range from 1 in 47 to 1 in 3.000 catheterization events. (30) The reported frequency of VAE associated with use of a central catheter ranges from 0.1% to 2%. (31-34) Even the most conservative estimates (5 million CVCs per year in US, air embolus 0.1% of CVCs, and 23% mortality) point to 1150 deaths per year from this complication in the US alone. (35) Hydrophobic vent membranes on our IV in-line filters allow the effective elimination of air in infusions. (36)

9. What about microorganisms and endotoxins?

Microorganisms and associated endotoxins may inadvertently enter the patient’s blood stream from an external source, such as contaminated equipment or fluids (exogenous endotoxins). There have been many reports of Gram-negative bacterial contamination of IV infusion fluids leading to septicemia, while other studies have shown the risk of endotoxin release from an accumulation of Gram-negative bacteria within an infusion system. (37-42) This is where IV in-line filters come into play — retaining microorganisms and endotoxin in the case of in-line filters with positively charged membranes. (43,44)

10. Information about physicochemical incompatibilities

Many high pressure alarms where an IV in-line filter is in place are due to the filters doing their job: protecting the patient from harmful events. Physicochemical incompatibilities in drug solutions may have serious consequences, such as the obstruction of a catheter, therapeutic failure, or the occurrence of embolism or fatalities and are still a threat to patients. (45-48) It is not possible to test every combination of drugs and therefore high pressure alarms where filters are in place can prevent unintended particulates from entering the patient and act as a warning about the combination.

11. What about drugs requiring filters?

Particles in protein-based drug products, such as monoclonal antibodies, can pose a potential immunogenic risk to patients. (50-57) Protein particles may be formed not only during the manufacturing and filling process, but also afterwards, during shipping, storage, and handling. (57) A recent article published in Hospital Pharmacy showed that 93 IV drugs approved by the FDA between December 2011and April 2019 require filtration with a syringe or an IV in-line filter. (58) IV filters form an essential part of these products being available for use.

12. What about guidelines?

Considering the benefits of IV in-line filters seen in laboratory and clinical trials, several national and international associations that establish guidelines, such as the Infusion Nurses Society (INS) and the American Society for Parenteral and Enteral Nutrition (ASPEN.), have started to recommend the use of IV in-line filters over the last few years. (59-63)

Table 1. Summary of IV in-line filter guidelines from select groups and organizations

Society	Country	Year	Selected IV in-line filter statement
Infusion Nurses Society (59)	USA	2021	"Consider filtration of solutions and medications to reduce particulate matter in critically ill patients that can cause thrombogenesis, impaired microcirculation, and alter immune response."
American Society for Parenteral and Enteral Nutrition (60)	USA	2021	"ASPEN recommends that healthcare organizations that do not filter PN admixtures or 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."
The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) (61)	Europe	2018	"PN solutions may be administered through a terminal filter: lipid emulsions (or all-in-one mixes) can be passed through a membrane pore size of 1.2 µm - 1.5 µm; aqueous solutions can be passed through a 0.22 µm filter."
European Society for Clinical Nutrition and Metabolism (ESPEN) (61)
European Society for Paediatric Research (ESPR) (61)
Chinese Society for Parenteral and Enteral Nutrition (CSPEN) (61)
Recommendation for parenteral nutrition in neonatology: French National Authority for Health (Haute Autorité de Santé) (62)	France	2018	"Use antibacterial (0.22 µm) and particulate (1.2 µm) in-line filters. Antibacterial filters cannot be used with lipids." (translated from French)
Commission for Hospital Hygiene and Infection Prevention (KRINKO) (63)	Germany	2017	"The Commission recommends: For those treated in intensive care particle retentive filters should be used in the infusion system (air separation, less systemic inflammatory response reaction)." (translated from German)

Patients deserve “rocket science" filter protection 

Over the last 50 years, IV in-line filter technology has made huge developmental strides, becoming so much more than “just” the potential solution for ensuring sterility during prolonged IV therapy described by Douglas W. Wilmore & Stanley J. Dudrick in 1969. Today, IV in-line filters protect patients from particles, air, microorganisms, and endotoxin; they come in different pore sizes and with different filter media (such as polyethersulfone or nylon) and can be charged or uncharged; they are engineered to work with a variety of infusion protocols and drugs classes, such as protein-based drugs, clear fluid medication or lipids. We believe that as much as Neil Armstrong needed a protective filter to set foot on the moon, patients deserve “rocket science” IV in-line filter protection.

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Author bio

Dr. Volker Luibl, MBA

Dr. Luibl is a Demand Generation Marketing Manager with knowledge in medical devices and clinical science.