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Filtering Out the Facts: Recommendations to Optimize Performance of In-Line Filters for Parenteral Nutrition and Injectable Lipid Emulsion Infusions

Gill, Marianne MS, RN; Hirsch, Adina PharmD, BCNSP; Wilson, Nicole MSN, RN, CPHIMS

Author Information
doi: 10.1097/NAN.0000000000000464
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Injectable lipid emulsions (ILEs) are an essential component of parenteral nutrition (PN) regimens for pediatric and adult patients.1 ILEs are oil-in-water emulsions, meaning that oil droplets are dispersed in an aqueous phase. United States Pharmacopeia Chapter <729>2 specifies limits for droplet (or globule size) of manufactured ILEs to prevent intravenous (IV) infusion of large lipid globules that are associated with adverse events.2,3 ILEs are indicated as a source of essential fatty acids for patients on PN and provide a dense source of calories to help reduce the dextrose content and total volume required for PN.4 ILEs available throughout the world are composed of long-chain triglycerides (LCTs), including soybean oil (omega-6), olive oil (omega-9), fish oil (omega-3), and medium-chain triglycerides (MCTs) in different combinations and percentages. Since the introduction of PN in the early 1970s, only 100% soybean oil-based ILEs (eg, Intralipid, Baxter; Nutrilipid, B. Braun) have been available in the United States. In 2013, Clinolipid, a 2-oil lipid emulsion (80% olive oil, 20% soybean oil; Baxter) was approved in the United States but was not available until 2019. In 2016, SMOFlipid, a 4-oil lipid emulsion (soybean oil 30%, MCT 30%, olive oil 25%, and fish oil 15%; Fresenius Kabi) was approved in the United States. In 2018, Omegaven, a 10% ILE containing 100% fish oil (Fresenius Kabi) was approved in the United States for use in pediatric patients with PN-associated cholestasis.

Despite the fact that SMOFlipid is currently indicated only for adults in the United States, it has been increasingly used for neonatal and pediatric populations due to potential clinical benefits published in the medical literature.4 According to its US Food and Drug Administration–approved package insert, “The safe and effective use of SMOFlipid and Clinolipid in pediatric patients, including preterm infants, has not been established.”5(p2)

ILEs can be administered separately from PN admixtures or can be added to the PN for a total nutrient admixture. In either case, a 1.2-μm, in-line filter (refer to Figure 1) is a recommended part of the administration setup to help reduce large particulate matter (eg, enlarged lipid droplets, silicone, fibers, precipitates) and air from entering the body leading to patient injury.1,6,7 Special populations, such as the critically ill and neonatal or pediatric patients, are at a higher risk from large particulates due to their comorbidities and size, and serious adverse events including respiratory compromise and death can occur.8

Figure 1:
A 1.2-μm filter. ©Becton, Dickinson, and Co. Reprinted with permission.

Historical Overview of Clinical Guidelines

Since 1994, the use of filters for PN has been mandated by the FDA. This requirement was due to reports of interstitial pneumonitis and death associated with calcium-phosphate precipitation in an unfiltered peripheral TNA formulation. Subsequently, the FDA required the use of a 0.22-μm in-line filter for PN without ILEs and for a 1.2-μm in-line filter for TNA formulations. Of note, no recommendation was made for filtering ILE when administered separately from PN (as a 2-in-1 admixture).9

ILE filtering practices have varied historically. ILE prescribing information outside of the United States does not consistently include the recommendation to use a 1.2-μm in-line filter when administered alone. For example, the package leaflet for Lipofundin MCT/LCT 20%, an ILE currently not available in the United States, advises, “Infusion sets with in-line filters are not to be used for administration of fat emulsions.”10 Until 2013, prescribing information for ILE in the United States did not include the requirement to filter ILE when administered separately, and the recommendation to use a 1.2-μm filter was only for lipid-containing TNA formulations.

In 2014, the FDA mandated a prescribing information change for all ILEs marketed in the United States to include the statement “use a 1.2 micron in-line filter” when infusing ILE alone or as part of an admixture. In 2016, the Institute for Safe Medication Practices11 published a safety alert highlighting this prescribing information change and reminding clinicians that 1.2-μm filters are recommended for both TNA and ILE when infused separately.11 In recent years, consensus promoting the use of a 1.2-μm filter for ILE is growing from organizations such as American Society for Parenteral and Enteral Nutrition (ASPEN)12,13 and Infusion Nurses Society (INS)7 to reduce the potential for patient harm that may occur due to IV infusion of particulate, precipitates, and air emboli. In 2021, ASPEN published a position paper on the use of filters for PN.13 While 1.2-μm filters are not recommended as a routine infection control measure to prevent bloodstream infections,13,14 they can trap Candida albicans and therefore may be effective in mitigating the risk of this pathogen from reaching the patient. In addition, 1.2-μm filters serve the critical role of reducing exposure to particulate matter, precipitates, and large fat globules during PN therapy. Particles >2 μm pose the greatest threat of adverse events, and these particles are retained by 1.2-μm filters. The position paper recommends using a 1.2-μm filter for all PN with ILE whether administered as part of TNA or separately from the dextrose-amino acid admixture (2-in-1). When ILEs are infused via a Y-site configuration with the PN formulation (2-in-1), the recommendation is to use a 1.2-μm in-line filter that is positioned distal to the Y-site.12,13

A 2019 Georgia Society for Parenteral and Enteral Nutrition newsletter on the “Considerations for Injectable Lipid Emulsion Administration: In-Line Filters and DEHP-Free Tubing,”15 explained that, because lipid emulsions contain particles that can range from approximately 0.1 μm to 1.0 μm, they are able to pass through 1.2-μm filters without concern for shearing of the lipid particles.15 All ILEs currently approved in the United States conform to USP Chapter <729>, indicating that the mean droplet size does not exceed 500 nm (0.5 μm) and that no more than 0.05% of droplets are >5 μm.3 It is these larger lipid globules that filters can trap and prevent from reaching the patient. In addition, filters can become clogged due to precipitates and microbubbles (air), which can result in an interruption in the infusion.

The European Society for Paediatric Gastroenterology Hepatology and Nutrition recommends filtering lipid emulsion or TNA with filter pore size “around 1.2-microns to 1.5-microns” to avoid the IV infusion of precipitates and particulate matter.14(pS68) A 0.22-μm filter is recommended for a dextrose/amino acids formulation.6,7 Infusing ILEs through a 0.22-μm filter should be avoided because lipid globules can occlude the filter, and shearing of lipid particles could occur causing TNA instability.16

Hardy and Puzovic1 stated that an in-line 1.2-μm filter should be used for all TNAs, but they acknowledge it is not uncommon for filters to occlude during administration of an apparently “stable” mixture. The authors further stated that the difference between what is an acceptable admixture and what will pass through an in-line filter is still not clearly defined.1 In a Gap Analysis survey sent to ASPEN members, Christensen et al17 reported that between 9.7% and 19.4% of users do not use filters for ILE IV infusions (9.7% for pediatric patients, 15.1% for adult patients, 19.4% for infant patients). These clinicians reported having occlusion issues during the IV infusion of ILEs with a 1.2-μm filter, with no cause identified in 54% to 80% of the cases.17


Filter Change Intervals

There is a general consensus within most clinical practice guidelines for how often the 1.2-μm filter should be changed when infusing TNA, PN, and separate ILE infusions. In a 2014 publication titled “ASPEN Parenteral Nutrition Safety Consensus Recommendations,” Ayers et al6 specified replacing the administration set and filter with each new PN container every 24 hours for TNA and 2-in-1 infusions. Changing the administration set and filter every 12 hours when ILE is infused separately is also recommended.7 If a prolonged infusion of ILE is required, the ILE dose should be divided into 2 portions, with a new container and administration set used every 12 hours.6 The recommendations did not provide specific guidelines for filtering ILE when administered separately and stated that this was a topic for further research.6 The recently published ASPEN position paper on the use of filters13 and the ASPEN ILE Safety Paper for PN12 support the recommendation for changing filters every 24 hours for PN and total nutrient admixture and every 12 hours for ILE when infused separately.

The 2021 Infusion Therapy Standards of Practice practice recommendations for administration of PN are consistent with the 2014 and 2020 ASPEN updates.7,18 INS further recommends changing the administration set for PN formulations at least every 24 hours, as well as changing the administration set with each new PN container, as the characteristics of ILE (iso-osmotic, near neutral-alkaline pH, and containing glycerol) are conducive to the growth of microorganisms. The recommendations also state the hang time for ILE administered separately not to exceed 12 hours and that filters be changed every 12 hours. To avoid clogging the filter during administration setup, priming is recommended immediately before use.7,18 The Royal College of Physicians of Ireland Clinical Practice Guidelines for Neonatal and Paediatric Units state that amino acid/glucose infusion sets can be left in situ for up to 48 hours, with lipid administration sets changed every 24 hours.19

Clinical Practice Challenges With Filtering ILE

The consensus for in-line filter use as it relates to PN and ILE infusions is evident in the literature. What is not well-described are methods to maximize the life of an in-line filter. For valid reasons discussed previously, filter blockage can occur from retention of particulate matter, which is one of the primary reasons 1.2-μm filters are used. As the filter is “doing its job” of trapping particulate matter before it is infused to the patient, the pressure upstream of the filter may increase over time due to the filter retaining particulate matter and, in the case of ILE, considerable amounts of enlarged lipid droplets. Filter blockage may result in a patient-side occlusion alarm, as higher pressures exist upstream of the filter versus downstream. In these cases, the clinician must respond to the audible/visual infusion pump alarm and investigate the root cause of the occlusion.20

The ASPEN PN Safety Consensus Recommendation states than an occluded filter should never be removed in response to occlusion alarms, thus allowing the unfiltered formulation to infuse.6,13 Rather, nurses must be well-versed in the appropriate actions and troubleshooting steps in response to high-pressure alarms or an occluded filter.6 The ASPEN Consensus recommendation emphasizes that “a filter that becomes occluded during PN administration should raise suspicions that the incorrect filter size was used or that a precipitate or particulate is present in the formulation. Before resuming PN, a pharmacist should review the PN formulation to determine if incompatibility issues are the cause of the problem and to identify actions to prevent further occurrences.”6(p34) Recommendations similar to ASPEN on occluded filter causes is noted throughout the literature.15,17,20

Spiers et al21 tested 3 different Pall Medical 1.2-μm filters with lipid-containing admixtures and undiluted lipids in a technical report titled, “Pall Lipipor IV Filters for PN: A Characterisation of Pumped Infusion Pressures.” Their testing demonstrated that upstream pressures increased during the testing period; pressures below the filter stayed substantially lower. Additionally, the testing identified that SMOFlipid infusions consistently resulted in higher pressures above the filter than Intralipid, with a greater increase over time. Spiers et al21 theorized that pressures would increase over the service life of the filter and are dependent upon formulation of the lipid particulate size, filter type, and flow rate (See Table 1, adapted from Spiers et al21). At the time of this publication, there are no available test data below 6.3 mL/h, which present a potential impact to slower infusion rates for the neonatal and pediatric population.

TABLE 1 - Maximum Upstream Pressure Recorded Over a 24-hour Period for Each Filter, Lipid, and Flow Rate21
Rate (Filter Type)
Lipid Brand Name
6.3 mL/h
12 mL/h
25 mL/h
160 mm Hg 483 mm Hg 523 mm Hg
99 mm Hg 238 mm Hg 350 mm Hg
Abbreviations: NLF2E = NLF Filter (Europe) for Paediatric Parenteral Nutrition Lipipor; TNA1E = TNA Filter (Europe) for Parenteral Nutrition Lipipor.
Data from Spiers S, Rothery R, O'Sullivan S. Pall Lipipor intravenous (IV) filters for parenteral nutrition; a characterisation of pumped infusion pressures. Pall Life Sciences Technical Report. Scientific & Laboratory Services; September 2016.

Techniques to Troubleshoot Patient-Side Occlusion Alarms When Filtering PN/ILE

Patient-side occlusion alarms can occur for reasons unrelated to the filter becoming clogged. These issues should be thoroughly investigated first, before a clogged filter issue is assumed.

Some common causes for a patient-side occlusion alarm, irrespective of filter use, are:

  • A closed clamp or stopcock below the infusion pumping mechanism
  • A positional/kinked IV line or catheter
  • An occluded needleless connector
  • Occlusion of IV line
  • Occlusion pressure limit is set too low

There are proactive measures and known best practices clinicians can take to reduce the occurrence of patient-side occlusion alarms during ILE or PN infusions that result from a clogged filter. These measures include:

  • Understanding how air-eliminating filters work22
  • Selecting the right filter appropriate for the type of PN formulation23
  • Being cognizant of correct filter placement in relationship to the patient23
  • Correctly priming the filter per manufacturer instructions7
  • Setting the most appropriate occlusion pressure limit on the infusion pump (ie, start at a lower pressure limit and incrementally increasing as needed)
  • Before resuming PN after an occlusion alarm, it is important that a pharmacist review the PN formulation to determine whether incompatibility issues are the cause of the problem and to identify actions to prevent further occurrences6
  • If stored in refrigerator prior to use, remove in time to allow return to room temperature
  • Examine the solution for signs of instability before hanging the bag and periodically throughout administration


The use of an in-line, 1.2-μm filter is recommended for all PN formulations that contain lipids (TNA) and for separate lipid emulsion infusions. Professional organizations and regulatory bodies in large part recommend a 24-hour filter change interval for TNA solution and a 12-hour filter change interval for lipid emulsions infused alone. However, end user postmarket surveillance data and published literature cite reports of patient-side occlusion alarms and clogged filters when a 1.2-μm filter is used. These issues can lead to an interruption of the patient's PN or ILE infusion, which can be prolonged if efforts to resume the infusion are unsuccessful. Clinical proficiency in air-eliminating filter technologies, their appropriate use, and adherence to manufacturer's recommendations in the IV administration setup support filter functionality. Support by the pharmacy team is needed to thoroughly investigate possible causes of a clogged filter, particularly when infusing at lower infusion rates over longer periods of time. Further testing is needed to provide clinicians data on the effect of infusing lipid formulations at lower infusion rates. In situations where off-label use may increase the likelihood of occlusion, considerations should be made to increasing the frequency of changing the filter. Finally, it is incumbent upon pharmaceutical and medical technology companies to ensure that end users have the appropriate resources and equipment available for use as new medications become available in the market.20


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2. The United States Pharmocopeial Convention. <729> Globule size distribution in lipid injectable emulsions. In: United States Pharmacopeia/National Formulary. Vol. 2. 32nd ed. The United States Pharmocopeial Convention; 2008:283–285.
3. Driscoll DF, Ling PR, Bistrian BR. Pharmacopeial compliance of fish oil-containing parenteral lipid emulsion mixtures: globule size distribution (GSD) and fatty acid analyses. Int J Pharm. 2009;379(1):125–130.
4. Anez-Bustillos L, Dao DT, Baker MA, Fell GL, Puder M, Gura KM. Intravenous fat emulsion formulations for the adult and pediatric patient: understanding the differences. Nutr Clin Pract. 2016;31(5):596–609.
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7. Gorski LA, Hadaway L, Hagle ME, et al. Infusion therapy standards of practice, 8th edition. J Infus Nurs. 2021;44(suppl 1):s1–s224.
8. Perez M, Decaudin B, Abou Chahla W, et al. Effectiveness of in-line filters to completely remove particulate contamination during a pediatric multidrug infusion protocol. Sci Rep. 2018;8(1):7714.
9. Lumpkin MM. Safety alert: hazards of precipitation associated with parenteral nutrition. Am J Hosp Pharm. 1994;51(11):1427–1428.
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14. Koletzko B, Goulet O, Hunt J, et al. Guidelines on paediatric parenteral nutrition of the European Society of paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr. 2005;41(suppl 2):S1–87.
15. Hirsch A. Considerations for injectable lipid emulsion administration: in-line filters and DEHP-free tubing. GASPEN Newsletter. 2019;5:6–9.
16. Driscoll DF, Bacon MN, Bistrian BR. Effects of in-line filtration on lipid particle size distribution in total nutrient admixtures. JPEN J Parenter Enteral Nutr. 1996;20(4):296–301.
17. Christensen ML, Ayers P, Boullata JI, et al. Lipid injectable emulsion survey with gap analysis. Nutr Clin Pract. 2017;32(5):694–702.
18. 2021 Infusion Therapy Standards of Practice Updates. J Infus Nurs. 2021;44(4):189–190. doi:10.1097/NAN.0000000000000436
19. National Clinical Programme for Paediatrics and Neonatology Parenteral Nutrition Expert Group. Guideline on the use of parenteral nutrition in neonatal and paediatric units, version 2.0. Ireland Health Services, National Clinical Programmes. July 2020. Accessed on Oct 14, 2021.
20. Institute for Safe Medication Practices. Two unsafe practices: administration of a product with a precipitate and reuse of a saline flush syringe. ISMP Newsletter. 2017;22(7).
21. Spiers S, Rothery R, O'Sullivan S. Pall Lipipor intravenous (IV) filters for parenteral nutrition; a characterisation of pumped infuson pressures. Pall Life Sciences Technical Report. Scientific & Laboratory Services; September 2016.
22. IV in-line fliters FAQs. Product Information. Becton, Dickinson, and Company (formerly CareFusion). Updated 2010. Accessed October 14, 2021.
23. Guenter P, Worthington P, Ayers P, et al. Standardized competencies for parenteral nutrition administration: the ASPEN model. Nutr Clin Pract. 2018;33(2):295–304.

filter; ILE; infusion; injectable lipid emulsion; intravenous; nutrition

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