A Role of Circuit Clotting and Strategies to Prevent It during Blood Purification Therapy with oXiris Membrane: An Observational Multicenter Study.

INTRODUCTION: Membrane fouling is a significant complication potentially reducing clinical effects of extracorporeal blood purification (EBP) in critically ill septic patients with acute kidney injury. Although fascinating, the effect of heparin coating in preventing membrane fouling is currently unknown. This multicenter prospective study aims to preliminary describe the incidence, associated factors, and clinical consequences of premature circuit clotting in a cohort of adult critically ill septic patients treated with EBP using a high biocompatible heparin-coated hemodiafilter characterized by advanced adsorption properties. METHODS: This study was a retrospective analysis of prospectively entered data in the oXirisNet Registry; overall, 97 septic patients undergoing EBP with oXiris between May 2019 and March 2020 were enrolled in this study. Patients were divided into two groups according to the occurrence of filter clotting (premature vs. nonpremature). Logistic regression analysis was used to identify factors associated with premature circuit clotting. RESULTS: Premature clotting occurred in 18 (18.6%) patients. Results of the multivariate logistic regression analysis demonstrated that hematocrit (p = 0.02, odds ratio [OR] 1.15 [1.05; 1.30]), serum procalcitonin (PCT) (p = 0.03, OR 1.1 [1.05; 1.2]), and anticoagulation strategy (p = 0.05 at Wald's test) were independent predictors of circuit clotting. Systemic anticoagulation (p = 0.02, OR 0.03 [0.01; 0.52]) and regional citrate anticoagulation (p = 0.10, OR 0.23 [0.04; 1.50]) were both protective factors if compared to no-anticoagulation strategy. Patients with nonpremature circuit clotting showed more rapid recovery from hemodynamic instability, pulmonary hypo-oxygenation, and electrolyte disorders and greater improvement of inflammatory markers and SOFA scores. CONCLUSION: Although in this study the incidence of premature circuit clotting was relatively low (18.6%) compared to previously reported values (54%), membrane clotting in adult critically ill septic patients could cause clinically relevant interferences with treatment performances. Prevention of clotting should be based on avoiding higher patients' hematocrit, high serum PCT, and no-anticoagulation strategy which resulted as independent predictors of circuit clotting.

Methods for dose quantification in continuous renal replacement therapy: Toward a more precise approach.

Periodic dose assessment is quintessential for dynamic dose adjustment and quality control of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI). The flows-based methods to estimate dose are easy and reproducible methods to quantify (estimate) CRRT dose at the bedside. In particular, quantification of effluent flow and, mainly, the current dose (adjusted for dialysate, replacement, blood flows, and net ultrafiltration) is routinely used in clinical practice. Unfortunately, these methods are critically influenced by several external unpredictable factors; the estimated dose often overestimates the real biological delivered dose quantified through the measurement of urea clearance (the current effective delivered dose). Although the current effective delivered dose is undoubtedly more precise than the flows-based dose estimation in quantifying CRRT efficacy, some limitations are reported for the urea-based measurement of dose. This article aims to describe the standard of practice for dose quantification in critically ill patients with AKI undergoing CRRT in the intensive care unit. Pitfalls of current methods will be underlined, along with solutions potentially applicable to obtain more precise results in terms of (a) adequate marker solutes that should be used in accordance with the clinical scenario, (b) correct sampling procedures depending on the chosen indicator of transmembrane removal, (c) formulas for calculations, and (d) quality controls and benchmark indicators.

Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study.

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.

Use of Fluoride as a Marker Solute to Quantify the Current Effective Delivered Dose in Continuous Renal Replacement Therapy: An "in vitro" Study.

BACKGROUND: The current effective delivered dose is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the current effective delivered dose using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. METHODS: We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. RESULTS: In CVVH, the median SC values were 1.06 (1.02-1.07) and 1.02 (1.01-1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01-31.31) mL/kg/h and 30.30 (29-31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96-1.02) and 1 (0.95-1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52-31.32) mL/kg/h and 31.16 (30-31.75) mL/kg/h (discrepancy of -2.97%), respectively. CONCLUSION: Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the current effective delivered dose during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.

A New Series of Sorbent Devices for Multiple Clinical Purposes: Current Evidence and Future Directions.

Adsorption is an extracorporeal technique utilized for blood purification. It complements convection and diffusion (the main modalities of solute removal). It involves the passage of blood (or plasma) through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridges, with improved characteristics have been developed. Furthermore, the therapeutic applications of adsorption have expanded. These now involve the treatment of inflammatory conditions, chronic uremic symptoms, and autoimmune disease, in addition to intoxication, which was once considered the classical indication for adsorption therapy. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. There has been sufficient body of evidence to support their effectiveness and safety. In this review, we aim to highlight their main clinical applications.

Biocompatibility and Cytotoxic Evaluation of New Sorbent Cartridges for Blood Hemoperfusion.

BACKGROUND/AIMS: The use of adsorption cartridges for hemoperfusion (HP) is rapidly evolving. For these devices, the potential induced cytotoxicity is an important issue. The aim of this study was to investigate potential in vitro cytotoxic effects of different sorbent cartridges, HA130, HA230, HA330, HA380 (Jafron, China), on U937 monocytes. METHODS: Monocytes were exposed to the sorbent material in static and dynamic manners. In static test, cell medium samples were collected after 24 h of incubation in the cartridges. In dynamic test, HP modality has been carried out and samples at 30, 60, 90, and 120 min were collected. RESULTS: Compared to control samples, there was no evidence of increased necrosis or apoptosis in monocytes exposed to the cartridges both in the static and dynamic tests. CONCLUSION: Our in vitro testing suggests that HA cartridges carry an optimal level of biocompatibility and their use in HP is not associated with adverse reactions or signs of cytotoxicity.