The Key Role of Intravenous (IV) In-Line Filters for Parenteral Nutrition (PN)

Please introduce yourselves and tell us something about your role within ASPEN.

PW: My name is Pat Worthington; I have worked most of my career as a Nutrition Support Clinical Nurse Specialist in a large academic medical center in Philadelphia. I have also been active in a variety of ASPEN activities, including the Parenteral Nutrition Safety Committee, which first identified the need for the filtration position paper. I currently serve as a member of the ASPEN Board of Directors.

PG: I’m Dr. Peggi Guenter, I am a nutrition support nurse and spent 20 years practicing nutrition support in acute care medical centers in the Philadelphia area. Following that, I came to ASPEN and have for 20 years served as the Senior Director for Clinical Practice, Quality and Advocacy before I retired from that position about three months ago. I continue to serve at ASPEN as a Consultant for Special Projects.

Do we know how many patients receive PN in the US each year? And is the administration of PN increasing or decreasing?

PG: The latest public data we have is from 2016 which shows 225,000 hospitalized patients who received PN in the US per the AHRQ HCUP National Inpatient Sample database. We also have unpublished data from 2018 that shows a continued downwards trend in the use of parenteral nutrition. However, 2018 was in the middle of a prolonged and severe amino acid solution shortage. We cannot be sure exactly why these numbers are trending down over time, except perhaps clinicians are using indications guidelines and are more carefully evaluating the use of this high-alert medication.

Have you noticed any changes in how PN is administered over the past 20 years? If so, how has the use of IV in-line filters factored into those changes?

PG: In the US, more and more commercial multi-chamber bags – 2-in-1 and 3-in-1 – are being used. Having more of these admixtures might help standardize practice a bit more and get nurses into the routine of placing the 1.2-micron IV in-line filter closest to the patient.

Could you estimate what percent of patients in the US receive PN through an IV in-line filter?

PG: According to a 2017 survey by Mike Christensen², between 80-90% of PN is filtered, depending on the type of PN. Another way to look at it is that 15 to 20% of respondents did not filter either the 3-1 PN or the ILE [Intravenous Lipid Emulsion]. So, we still have a lot of room to move forward.

Outside the US, some countries and societies have different recommendations for neonates, pediatrics, and adults regarding the use of IV in-line filters. In your view, is there any difference in the importance of filtration between these patient groups?

PG: This matter can affect any population, but neonates are most vulnerable to particulate matter in their lungs. Therefore, I believe it would be most important for this group to have filters on all parts of their parenteral nutrition. Some research suggests that the critically ill and those with pre-existing tissue damage from trauma, surgery or sepsis may also experience more pronounced adverse effects from particle infusion. Overall, I think everyone needs IV in-line filters, but we do need more research to confirm this.

Why would a clinician choose not to use an IV in-line filter and how would you address those potential concerns?

PG: According to the Christensen² paper, clinicians do not use IV in-line filters due to lack of evidence and lack of understanding. This includes the beliefs that IV in-line filters are only used in neonates, that they get clogged with lipids, are very costly (purchasing committee denied purchase), and that IV in-line filters are only useful for filtering particulate matter and not microbes. Another initial concern reported to the ASPEN national office were problems with filtering ILE as a separate infusion. Our paper addressed many of these concerns.

Who in the hospital makes the decision to implement the use of IV in-line filters?

PG: The Nutrition Support Service or Committee, Nursing, Pharmacy, or Supply/Purchasing departments.

How will parenteral nutrition change over the next 20 years? And what role will IV filters have in administration? 

PG: I think there will be more conversion to multichambered bags. Regarding IV in-line filters: Up unto this point we have been asking clinicians to use two in-line filters, even though when I was practicing, we decided to use just one without adverse events. IV in-line filters were also recommended to be used on both sides of the infusion, a 0.22-micron in-line filter for the 2-in-1 solution and a 1.2-micron in-line filter for the ILE, and then, when 3-in-1 solutions were introduced which required just one in-line filter, the 1.2-micron. This sometimes led to confusion for the nurses, trying to understand which in-line filter to use when. We want to get the message out to just use one IV in-line filter as we move towards more standardized solutions.

Why did ASPEN initially want to publish a position paper? Did you think clinicians were unaware of the recommendations from lipid manufacturers regarding the use of filters?

PW: We learned that there was a lot of confusion in practice, stemming from the recommendation to filter ILE with two IV in-line filters. We wanted to review the literature on filtering and find out the reasons for two IV in-line filters, then make a practice change recommendation and get the word out to clinicians about filtering appropriately.

What were your expectations when beginning to write the 2020 position paper? How did those expectations change during the writing process?

PW: We learned from the Christensen² paper that there was far more confusion and considerable variation regarding how in-line filters were used. Our literature search revealed more controversy surrounding filter use than I expected, especially outside of the U.S. Many articles held the view that the primary purpose of in-line filters is to protect against infectious complications, while the danger presented by particulate matter was not widely appreciated and basically overlooked.

How was the writing process organized? How did you arrive at the recommendations made in the 2020 position paper?

PW: ASPEN first convened a working group of clinicians to participate in the project, which included two nurses and four pharmacists who were all members of the PN Safety Committee. We reviewed the literature to develop a picture of current IV in-line filter use and the challenges that clinicians faced. As the work progressed, some recommendations became obvious, such as the critical importance of filtering PNat all times. We then held group conference calls with the entire author panel to develop the consensus recommendations that appeared in the paper. There was unanimous agreement among the group regarding the final recommendations.

What were the most important recommendations made in the 2020 position paper?

PW: The change in the recommendation from using two in-line filters to one in-line filter closest to the patient.

Is there a reason why 0.2-micron filters are not mentioned in the 2020 position paper?

PW: Primarily our interest was to eliminate them. Using two different sized filters led to confusion and increased the potential for errors among nurses and lay caregivers who administer parenteral nutrition at home. The working group felt that using a single 1.2-micron in-line filter would streamline parenteral nutrition administration procedures and improve compliance with IV in-line filter use.

In the paper you mention: “Particles greater than 2 microns, which are retained by 1.2-micron filters, appear to pose the most serious risk for adverse consequences. ” Do particles smaller than 2 microns pose less of a risk to patients? How should clinicians consider the risk posed by smaller particles in practice?

PW: Studies of particles found in parenteral nutrition formulations have shown that the size can vary from 1.3 microns to greater than 10 microns. We found very little evidence that particles smaller than 2 microns cause problems. The primary risk stems from particles > 5microns. The risk posed by these particles is related to the diameter of the pulmonary capillaries, which generally range between 5-8 microns: Particles larger than the capillary will become trapped in the lungs, leading to pulmonary complications.  Particles smaller than the capillary diameter pass through the lungs and will be deposited into organs such as the liver or spleen, to be eliminated through the action of the reticuloendothelial system. While particles 5 microns or larger pose the greatest risk for pulmonary complications, we also found evidence that suggest that higher levels of organ dysfunction occurred in critically ill adults when 5-micron in-line filters were compared to in-line filters with finer pore sizes.³  However, at the present time, there is insufficient evidence regarding the impact of particles smaller than 2 microns to make recommendations to clinicians.

The position paper mostly focuses on the risk of particles in IV administration. Did you consider other risks such as air, bacteria, microorganisms, or endotoxins?

PW: In the paper, we do note that IV in-line filters serve all those purposes, that they “block microbes, air, and enlarged lipid droplets from reaching the circulation.” However, we focus on the ability of in-line filters to capture particles because this carries the most prominent, and often overlooked, risk to patients by clinicians. Clinicians feel that this is an unusual event occurring due to compounding errors or calcium or phosphate in inappropriate amounts, so there is insufficient appreciation that particulate matter is always present. By emphasizing the risk posed by particulate matter, we also wanted to clarify that in-line filters serve a limited role in reducing infectious complications of parenteral nutrition– because in most cases, contamination occurs after the fluid has passed through the in-line filter. The US Centers for Disease Control advise against using IV in-line filters for infection control purposes, which has led some clinicians to incorrectly believe that in-line filters are not needed if infection rates are low—we aimed to correct that misconception.

It’s very common for filters to block or clog during administration, but that simply means that they’re doing their job! Do you address filter blocking in the paper? How would you address any concerns related to blocking?

PW: Yes, we do. Because we were concerned that clinicians may be tempted to simply remove a clogged in-line filter, we emphasize that parenteral nutrition admixture should never be allowed to infuse without an in-line filter. We outline a series of troubleshooting steps to follow if an in-line filter does clog. These steps include ruling out occlusions that are not caused by the in-line filter, verifying that the correct size in-line filter has been used, and consulting a pharmacist to review the prescription.

Which studies were most important to arrive at the conclusions made in the position paper?

PW: First, we owe a great debt to the clinicians who first identified and reported adverse events related to the administration of unfiltered parenteral nutrition, particularly Dr. Puntis⁴ in his 1992 paper on the subject. In addition, the review on particulate matter by Dr. Stephen Langille⁵ provided an excellent foundation for our paper. And finally, the numerous studies done by a group of researchers from the University of Lille, led by Maxime Perez et al.^6,7,8,9, gave insight into the problem of particles present in IV fluids and highlighted the important role of in-line filters in IV therapy.

What feedback have you received since publishing the 2020 position paper? How was it received by clinicians and other stakeholders? 

PG: So far, we have received a few general procedural questions from clinicians, which led us to develop the factsheet, trying to get our message across in the community. The Intravenous Nurses Society writes standards for intravenous care, and they continue to have two in-line filter standards in these recommendations. We have reached out to them and together with Pat they have written a practice change brief that should be published in their journal shortly. We have also sent out the factsheet to various nurses organization as well as to the national home infusion association: 25,000 people are on home parenteral nutrition in the US, and this applies to them as well.

In terms of clinical evidence and studies, what is missing that could have strengthened your recommendations regarding the usefulness of in-line filters?

PW:

1. More information is needed regarding impact of filtration on clinical outcomes especially regarding different patient populations.
2. What is the impact of the accumulation of particles in organs over time?
3. What level, if any, level of particle infusion could be considered acceptable?
4. What impact does particle infusion have on the immune system? 
5. Any clinical outcome studies comparing 1.2 to 0.22-micron in-line filter, to determine if there is any additional benefit to using 0.22-micron in-line filters, would also be helpful.

Moving forward, how do you plan to educate clinicians and other stakeholders? Do you plan to work together with other societies (national or international) in order to educate “the market?”

PG: We’ve developed a fact sheet and distributed it to the ASPEN database as well as to multiple nursing organizations. We are also planning to write a similar brief for Infusion, the NHIA (National Home Infusion Association) journal, for their September-October issue. We are also, with support from PALL, working on two short videos on the background of this practice change and how to implement it. We will present this at our next national conference in Seattle in 2022. We need to get our message out to pharmacists and to nurses especially in critical care and medical surgical areas, as it is the nurses who actually deliver nutrition to the patient.

Peggi, Pat, thank you for your time!