Patients in intensive care are exposed to the risk of microparticle infusion via extracorporeal lines and the resulting complications. A possible source of microparticle release could be the extracorporeal circuit used in blood purification techniques, such as continuous renal replacement therapy (CRRT). Disposable components of CRRT circuits, such as replacement bags and circuit tubing, might release microparticles such as salt crystals produced by precipitation in replacement bags and plastic microparticles produced by spallation. In-line filtration has proven effective in retaining microparticles both in in-vitro and in-vivo studies. In our study, we performed an in-vitro model of CRRT-treatment with the aim of detecting the microparticles produced and released into the circuit by means of a qualitative and quantitative analysis, after sampling the replacement and patient lines straddling a series of in-line filters. Working pressures and flows were monitored during the experiment. This study showed that microparticles are indeed produced and released into the CRRT circuit. The inclusion of in-line filters in the replacement lines allows to reduce the burden of microparticles infused into the bloodstream during extracorporeal treatments, reducing the concentration of microparticles from 14 mg/mL pre in-line filter to 11 mg/mL post in-line filter. Particle infusion and related damage must be counted among the pathophysiological mechanisms supporting iatrogenic damage due to artificial cross-talk between organs during CRRT applied to critically ill patients. This damage can be reduced by using in-line filters in the extracorporeal circuit.

The use of in-line filters to remove fibrous material in the administration of intravenous fluids dates to the early 1830\'s. Following advancements in therapeutic interventions, high volume fluid support and parenterally administered drugs and biologic preparations, some observers are calling for a routine use of bedside filtration. Unfortunately, the assessment of filter components, their interaction and compatibility with the drug product, and the impact of use on clinical outcomes cannot be conducted by a single entity. Recommendations for use are often predicated upon fragmented and incomplete information. The current challenges in evaluating the benefit/risk profile for the use of in-line filters should not be ignored. While there are select instances showing well-defined therapeutic settings where in-line filtration of intravenous infusions would likely provide an additional safety margin and hence, net benefit, the majority of observational studies to date fail to provide sufficient scientific support for broad-based routine use. While infusion set filters are appropriate where expert opinion is well corroborated by scientific evidence, the general and routine use of filters used during parenteral administration cannot be supported by substantive studies and should not be routinely utilized. Ultimately, the determination falls to a healthcare provider with the information available at-hand.

The need for filtering intravenous infusions has long been recognized in the field of venous access, though hard scientific evidence about the actual indications for in-line filters has been scarce. In the last few years, several papers and a few clinical studies have raised again this issue, suggesting that the time has come for a proper definition of the type of filtration, of its potential benefit, and of its proper indications in clinical practice. The WoCoVA Foundation, whose goal is to increase the global awareness on the risk of intravenous access and on patients\' safety, developed the project of a consensus on intravenous filtration. A panel of experts in different aspects of intravenous infusion was chosen to express the current state of knowledge about filtration and to indicate the direction of future research in this field. The present document reports the final conclusions of the panel.

The potential harmful effects of particle-contaminated infusions for critically ill adult patients are yet unclear. So far, only significant improved outcome in critically ill children and new-borns was demonstrated when using in-line filters, but for adult patients, evidence is still missing.
This single-centre, retrospective controlled cohort study assessed the effect of in-line filtration of intravenous fluids with finer 0.2 or 1.2 μm vs 5.0 μm filters in critically ill adult patients. From a total of n = 3215 adult patients, n = 3012 patients were selected by propensity score matching (adjusting for sex, age, and surgery group) and assigned to either a fine filter cohort (with 0.2/1.2 μm filters, n = 1506, time period from February 2013 to January 2014) or a control filter cohort (with 5.0 μm filters, n = 1506, time period from April 2014 to March 2015). The cohorts were compared regarding the occurrence of severe vasoplegia, organ dysfunctions (lung, kidney, and brain), inflammation, in-hospital complications (myocardial infarction, ischemic stroke, pneumonia, and sepsis), in-hospital mortality, and length of ICU and hospital stay.
Comparing fine filter vs control filter cohort, respiratory dysfunction (Horowitz index 206 (119-290) vs 191 (104.75-280); P = 0.04), pneumonia (11.4% vs 14.4%; P = 0.02), sepsis (9.6% vs 12.2%; P = 0.03), interleukin-6 (471.5 (258.8-1062.8) ng/l vs 540.5 (284.5-1147.5) ng/l; P = 0.01), and length of ICU (1.2 (0.6-4.9) vs 1.7 (0.8-6.9) days; P <  0.01) and hospital stay (14.0 (9.2-22.2) vs 14.8 (10.0-26.8) days; P = 0.01) were reduced. Rate of severe vasoplegia (21.0% vs 19.6%; P > 0.20) and acute kidney injury (11.8% vs 13.7%; P = 0.11) was not significantly different between the cohorts.
In-line filtration with finer 0.2 and 1.2 μm filters may be associated with less organ dysfunction and less inflammation in critically ill adult patients.
The study was registered at ClinicalTrials.gov (number: NCT02281604).

Protein immunogenicity is intensively researched by academics, biopharmaceutical companies, and authorities as it can compromise the safety and efficacy of a biopharmaceutical drug. So far, the exact protein aggregate properties inducing immune responses are not known. Possible protein-related factors could be size, chemical modifications, or higher order structures. It is impossible to achieve an absolute absence of protein aggregates even for very stable formulations. The application of \"bedside filtration,\" meaning filtration during the preparation or administration of the drug product immediately before injection, has the potential to increase the safety of every drug container and could prevent the undesired injection of particulate matter into the patient. In this study, the high efficiency of filtration for reducing the amount of protein particles was demonstrated with more than 19 stressed and nonstressed biopharmaceutical products which covered a broad concentration and molecular weight range. Furthermore, critical aspects regarding the usage of filters such as particle shedding from filters, protein loss as a result of protein adsorption, or the hold-up volume of the filters were assessed. Although differences between the filters were observed, no negative impact by the investigated filters could be found. A broader application of bedside filtration is therefore proposed.

Forest catchments can produce high quality source water with a low turbidity. However, the combination of low turbidity, low organic carbon, and low temperature water conditions presents operating challenges in conventional water treatment processes. In this study, in-line filtration was tested using pilot-scale filter columns, and was found to be an appropriate option to treat a typical low turbidity water originating from the Rocky Mountains near Calgary, Alberta, Canada. When alum and cationic polymer were dosed simultaneously, in-line filtration produced high quality effluent with a turbidity and a particle count value of less than 0.1 NTU and 50 counts/mL, respectively. However, the alum and polymer doses and their ratios played important roles in the filtration efficiency. In general, short filter ripening times (i.e. <15 min) required an alum dose of at least 3 mg/L and an alum to polymer dose ratio of less than 180:1. A longer filter stable period was associated with lower alum and polymer doses, as long as their doses were at least 2 and 0.024 mg/L, respectively, and their dose ratio was maintained in the range of 30:1 to 130:1. The optimal alum and polymer doses were observed to be 3 and 0.072 mg/L, respectively. Filter performance was enhanced when higher alum and polymer doses were used for ripening, and lower doses were applied during the stable filtration period. In addition, in-line filtration resulted in the reduction of microspheres by 3.6 logs under the tested water conditions. Hence, a similar removal efficiency is anticipated for Cryptosporidium.

Protein drug products play an important role in the treatment of severe diseases. However, due to the instability of these complex molecules, protein aggregates can form which can compromise drug safety and efficacy including immunogenic reactions. In-line filtration during the administration of these drugs can serve as a final safeguarding step to protect patients from risks associated with proteinaceous particles. A unique analysis of more than 300 marketed protein drug products revealed that already around 16% of all these products are filtered during preparation or administration. Further, the research revealed that no standardized filtration practice exists. Broad variances regarding filter membrane or pore size are found and sometimes no specifications are mentioned at all. The benefits as well as possible negative impacts of filtration like filter shedding, extractables or drug adsorption are critically assessed. Several proposals to improve the current filtration practice and to expand the number of in-line filtered protein drug products are made. The suggestions include the demand for the specific usage of one filter membrane type, the establishment of a filtration routine for unfiltered protein drugs and a statistical analysis between filtered and non-filtered products with similar formulations to identify possible differences in the immunogenicity rate.

Recent evidence has shown improved outcomes in pediatric intensive care units with the intensive use of intravenous in-line filtration. This has caused resurgence in interest in filter use but has raised questions in relation to emulsion-based formulations such as propofol. Our objective was to test two propofol products, Diprivan(®) and Fresofol(®), with the Pall Lipipor(®) TNA and Lipipor NLF intravenous in-line filters and to assay the content before and after filtration under typical infusion conditions. The propofol emulsions were delivered from a 50 mL syringe through an extension set and into either a Lipipor TNA (50 mL/h(-1)) or Lipipor NLF (20 mL/h(-1)) filter. Samples were taken at regular intervals and assayed using a high-performance liquid chromatography method before and after filtration. No evidence was found of a significant concentration change during passage of either product through either model of filter. Propofol from two products was found to pass through two different types of Pall 1.2 μm intravenous in-line filters. There was no significant change in concentration before and after filtration under typical conditions of administration. In conclusion, administration of these products through these models of in-line filter would be safe and effective.

BACKGROUND: The aim of this study was to provide data on concurrent red blood cell (RBC) and platelet (PLT) apheresis with RBC in-line leukoreduction and automated addition of saline-adenine-glucose-mannitol (SAGM) using the new version (V6.0) of Trima Accel®.
METHODS: In this two-center paired study, each subject completed a test and a control procedure with an interval of 9 weeks between procedures. In the test arm, single RBC and PLT units were collected on the Trima Accel V6.0 (in-line leukofiltration and automated addition of SAGM). In the control arm, they were collected on Trima Accel V5.1/V5.2 (post-collection leukoreduction, manual SAGM addition). RBC percent hemolysis, potassium concentration and adenosine triphosphate over storage, hemoglobin (Hb) yield, and residual white blood cells (WBC) were determined.
RESULTS: 34 subjects successfully completed both test and control procedures. Post-storage hemolysis was similar in both groups, and all values were less than 0.8% for both arms. Residual WBC counts in all RBC units were less than 1 × 10(6)/unit. In-line processed RBC units (V6.0) have a significantly higher volume and more Hb/unit due to filtration recovery improvements. All procedures were well tolerated by the subjects.
CONCLUSIONS: In-line filtration and automated addition of storage solution on Trima Accel V6.0 allows collection of ready-to-use RBC units that meet EU requirements.