Because of its efficacy, ease of dosing, and safety, the direct oral anticoagulant rivaroxaban is increasingly applied in a number of indications, for example, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation [1] and treatment of deep vein thrombosis and pulmonary embolism [2]. Median therapeutic peak plasma concentrations range from 46 to 270 µg/L, depending on the respective indication [3]. However, there are concerns regarding the accumulation of the drug in patients with impaired renal clearance or in case of overdosing, potentially leading to an increased risk of bleeding [4]. With its high degree of protein binding of 92–95% [3], rivaroxaban is regarded as non-dialyzable, as also suggested by results from a clinical study conducted by Dias et al. [5]. Since protein binding is regarded as not a limiting factor in hemoperfusion [6], the removal of rivaroxaban, as for example by commonly available coated charcoal cartridges, has been deemed possible, but experimental evidence is still lacking [7]. While Andexanet alfa may offer a promising approach to reverse the FXa inhibitor-mediated anticoagulation of rivaroxaban, it has not yet been approved [8]. In case of rivaroxaban-related major bleeding events or emergency interventions with a high bleeding risk, therefore, a fast and effective countermeasure is urgently needed.

Introduction: The use of hemoadsorption devices is increasingly gaining impact as an adjunct therapy for various critical conditions in ICU patients, including systemic hyperinflammation, cytokine release syndrome, sepsis, and more. A key concern in this therapy is its impact on the plasma levels of concurrently administered drugs, which could potentially be reduced to subtherapeutic levels, affecting patient care. The present study investigates the adsorption behavior of various drugs in an in vitro hemoadsorption model using human whole blood, aiming to provide insights for optimizing drug dosing during hemoadsorption therapy. Methods: The study assessed the removal rates and clearances of several drugs, namely, apixaban, argatroban, carbamazepine, oxcarbazepine, lamotrigine, phenytoin, valproate, levosimendan, methylene blue, and metformin, by circulating the blood through CytoSorb adsorbers in an in vitro setup. Results: Significant removal (75 to 100% of the initial concentration) and high initial plasma clearances (approximately 10–25 mL/min) were observed for most of the tested drugs within the first 30–60 min of recirculation. Lower removal rates and clearances were noted for valproate (approximately 40% and 5 mL/min) and metformin (approximately 15% and 1 mL/min). Conclusion: The findings indicate considerable differences in the adsorption of the tested drugs and should be confirmed by additional in vivo studies with careful monitoring of drug levels throughout the course of therapy. Understanding the in vivo dynamics is crucial for adjusting dosages appropriately during hemoadsorption use to ensure therapeutic efficacy and patient safety.

Introduction: Continuous renal replacement therapies (CRRTs) are essential in the treatment of critically ill patients with acute kidney injury and are also discussed as a supporting sepsis therapy. CRRT can affect antibiotics plasma concentrations. Objective: The effect of continuous venovenous hemofiltration (CVVH) with an asymmetric triacetate (ATA) membrane hemofilter on concentrations of antibiotics with low (meropenem), medium (vancomycin), and high (daptomycin) protein binding (PB) was investigated. Methods: 1 L human whole blood supplemented with antibiotics was recirculated and filtrated for 6 h in vitro. Clearances and sieving coefficients (SC) were determined from antibiotics concentrations measured at filter inlet, outlet, and filtrate side. Reservoir concentration data were fitted using a first-order kinetic model. Results: Meropenem and vancomycin concentrations decreased to 5–10% of the initial plasma level, while only 50% of daptomycin were removed. Clearances and SCs were (10.8 [10.8–17.4] mL/min, SC = 0.72 [0.72–1.16]) for meropenem, (13.4 [12.3–13.7] mL/min, 0.89 [0.82–0.92]) for vancomycin, and (2.1 [1.8–2.1] mL/min, 0.14 [0.12–0.14]) for daptomycin. Removal by adsorption was negligible. Conclusions: The clearances and SCs presented are comparable with findings of other authors. Meropenem and vancomycin, which exhibit low and medium PB, respectively, were strongly removed, while considerably less daptomycin was removed because of its high PB. Our results suggest that in clinical use of the tested antibiotics during CRRT with the ATA hemofilter, the same factors have to be considered for determining the dosing strategy as with filters with other commonly applied membrane materials.

Immunoadsorption (IA) has proven to be clinically effective in the treatment of steroid-refractory multiple sclerosis (MS) relapses, but its mechanism of action remains unclear. We used miniaturized adsorber devices with a tryptophan-immobilized polyvinyl alcohol (PVA) gel sorbent to mimic the IA treatment of patients with MS in vitro. The plasma was screened before and after adsorption with regard to disease-specific mediators, and the effect of the IA treatment on the migration of neutrophils and the integrity of the endothelial cell barrier was tested in cell-based models. The in vitro IA treatment with miniaturized adsorbers resulted in reduced plasma levels of cytokines and chemokines. We also found a reduced migration of neutrophils towards patient plasma treated with the adsorbers. Furthermore, the IA-treated plasma had a positive effect on the endothelial cell barrier’s integrity in the cell culture model. Our findings suggest that IA results in a reduced infiltration of cells into the central nervous system by reducing leukocyte transmigration and preventing blood–brain barrier breakdown. This novel approach of performing in vitro blood purification therapies on actual patient samples with miniaturized adsorbers and testing their effects in cell-based assays that investigate specific hypotheses of the pathophysiology provides a promising platform for elucidating the mechanisms of action of those therapies in various diseases.

Hemoadsorption with polystyrene-divinylbenzene (PS-DVB)-based adsorbents is explored as an adjunctive extracorporeal therapy in selected critically ill patients with dysregulated systemic inflammation. However, such therapy must not interfere with standard treatments, including antimicrobial therapy and hemodynamic stabilization with vasoactive drugs. As catecholamines are rarely quantified analytically in clinical practice, there are currently no studies reporting actual plasma levels during hemoadsorption. This in vitro study evaluated whether hemoadsorption with PS-DVB-based adsorbents alters plasma concentrations of epinephrine, norepinephrine, and dobutamine. Miniaturized PS-DVB adsorbers were used in 300-minute experiments; serial plasma samples were quantified, and apparent plasma clearance was derived from concentration-time data. Epinephrine and norepinephrine concentrations remained essentially unchanged over 300 min, with very low apparent plasma clearance (< 5 mL/min), indicating no meaningful removal under the tested conditions. By contrast, dobutamine demonstrated consistent, measurable clearance (approximately 5–15 mL/min), indicating non-negligible adsorption. Under these in vitro conditions, PS-DVB hemoadsorption did not materially remove epinephrine or norepinephrine but produced measurable removal of dobutamine. These findings are compatible with observational reports of reduced overall vasopressor requirements during hemoadsorption, while highlighting the potential for dobutamine underexposure. Future clinical studies should directly measure therapeutic plasma levels – particularly for dobutamine – during PS-DVB hemoadsorption and assess whether dosing adjustments are required to maintain intended inotropic effects without compromising safety.