Effect of Continuous Renal Replacement Therapy with the oXiris Hemofilter on Critically Ill Patients: A Narrative Review.

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions.

Case Report: Successful Treatment of a Child With COVID-19 Reinfection-Induced Fulminant Myocarditis by Cytokine-Adsorbing oXiris® Hemofilter Continuous Veno-Venous Hemofiltration and Extracorporeal Membrane Oxygenation.

Background: Indirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities. Case Presentation: We reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of oXiris ® hemofilter continuous venovenous hemofiltration (CVVH) and VA-ECMO. The patient made a full recovery without any sequelae. Conclusion: We conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced fulminant myocarditis. Our report highlights the need for further well-designed investigations to confirm this extrapolation.

Blood filters in children with COVID-19 and acute kidney injury: A review.

COVID-19 has challenged the global healthcare system through rapid proliferation and lack of existing treatment resulting in over 180 million cases and 3.8 million deaths since December 2019. Although pediatric patients only comprise 1%-2% of diagnosed cases, their incidence of acute kidney injury ranges from 8.2% to 18.2% compared to 49% in adults. Severe infection, initiated by dysregulated host response, can lead to multiorgan failure. In this review, we focus on the use of various blood filters approved for use in pediatric kidney replacement therapy to mitigate adverse effects of severe illness. Therapeutic effects of these blood filters range from cytokine removal (CytoSorb, HA330, HCO/MCO), endotoxin removal (Toraymyxin, CPFA), both cytokine and endotoxin removal (oXiris), and nonspecific removal of proteins (PMMA) that have already been established and can be used to mitigate the various effects of the cytokine storm syndrome in COVID-19.

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

Continuous Hemodiafiltration with the oXiris Filter Ameliorates Cytokine Storm and Induces Rapid Clinical Improvement in COVID-19 - A Case Report.

Delayed interferon secretion and cytokine dysregulation are responsible for the life-threatening acute respiratory distress syndrome (ARDS), multiorgan dysfunction and shock in COVID 19, which closely resembles secondary hemophagocytic lymphohistiocytosis (sHLH). IL-6, a marker of hypercytokinemia in patients with COVID-19 is positively correlated with disease severity, development and progression of ARDS, and mortality. Therapy to either reduce IL-6 or inhibit its action with either non-specific inhibitors of inflammation like dexamthasone or Toclizumab a specific inhibitor of IL-6 has produced decrease in mortality. We describe a novel method of treatment in a patient with multiorgan involvement in COVID 19, using the oXiris hemofilter which delivers renal replacement therapy while also reducing cytokines like IL-6.

Blood purification could tackle COVID-19?

Coronavirus disease 2019 (COVID-19) threatened human lives worldwide since first reported. The current challenge for global intensivists is to establish an effective treatment for severe COVID-19. Blood purification has been applied to the treatment of various critical illnesses. Theoretically, its technique also has an enormous possibility of treating severe COVID-19 in managing inflammatory cytokines and coagulopathy. Recent clinical studies have revealed the positive clinical effect of therapeutic plasma exchange. Other studies have also indicated the considerable potential of other blood purification techniques, such as Cytosorb, AN69 surface-treated membrane, and polymyxin b hemoperfusion. Further research is needed to elucidate the actual effects of these applications.

Hemoperfusion and blood purification strategies in patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19. METHODS: We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients. RESULTS: We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment. CONCLUSION: Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.

Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation. With this work, we evaluated the longitudinal changes of systemic inflammatory markers in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) haemofilter. METHODS: We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing haemofilter (CAH) according to local practice; we visualize longitudinal results of biochemical, inflammatory, blood gas, and vital sign parameters focussing on systemic levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. RESULTS: All patients were treated with ≥1 cycle extracorporeal continuous venovenous haemofiltration (CVVH) with CAH; of these, 30 severe patients received CVVH-CAH within 4-12 h of admission after recognizing a hyper-inflammatory state. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and were placed on EBP during hospitalization. The treatment was associated with a reduction of ferritin, CRP, fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3%. CONCLUSION: EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.

The absorbing filter Oxiris in severe coronavirus disease 2019 patients: A case series.

Hypercytokines cause acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients, which is the main reason for intensive care unit treatment and the leading cause of death in COVID-19 patients. Cytokine storm is a critical factor in the development of ARDS. This study evaluated the efficacy and safety of Oxiris filter in the treatment of COVID-19 patients. Five patients with COVID-19 who received continuous renal replacement therapy (CRRT) in Henan provincial people's hospital between January 23, 2019 and March 28, 2020, were enrolled in this study. Heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO2 /FiO2 ), renal function, C-reactive protein (CRP), cytokines, procalcitonin (PCT), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure score (SOFA), and prognosis were compared after CRRT. Five COVID-19 patients, three males and two females, aged 70.2 ± 19.6 years, were enrolled. After treatment, HR (101.4 ± 14.08 vs. 83.8 ± 6.22 bpm/min), CRP (183 ± 25.21 vs. 93.78 ± 70.81 mg/L), IL-6 (3234.49 (713.51, 16038.36) vs. 181.29 (82.24, 521.39) pg/mL), IL-8 (154.86 (63.97, 1476.1) vs. 67.19 (27.84, 85.57) pg/mL), and IL-10 (17.43 (9.14, 41.22) vs. 4.97 (2.39, 8.70) pg/mL), APACHE II (29 ± 4.92 vs. 18.4 ± 2.07), and SOFA (17.2 ± 1.92 vs. 11.2 ± 3.4) significantly decreased (P < .05), while MAP (75.8 ± 4.92 vs. 85.8 ± 6.18 mm Hg), and PaO2 /FiO2 (101.2 ± 7.49 vs. 132.6 ± 26.15 mm Hg) significantly increased (P < .05). Among the five patients, negative conversion of nucleic acid test was found in three cases, while two cases died. No adverse events occurred during the treatment. Our study observed a reduced level of overexpressed cytokines, stabilization of hemodynamic status, and staged improvement of organ function during the treatment with Oxiris filter.

First Reported Use of Highly Adsorptive Hemofilter in Critically Ill COVID-19 Patients in the USA.

Critically ill patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop respiratory failure and septic shock. Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis and aims at controlling the dysregulated autoimmune system. We describe our experience in treating COVID-19 patients with the oXiris® hemofilter which adsorbs both cytokines and endotoxins, provides renal replacement therapy and has anti-thrombogenic properties. It was approved by the US Food and Drug Administration (FDA) under emergency use authorization for COVID-19 patients in April 2020. In our study, the use of the oXiris® filter decreased levels of inflammatory markers including interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and improved clinical outcomes in two out of three patients.

Is there a role for blood purification therapies targeting cytokine storm syndrome in critically severe COVID-19 patients?

The coronavirus disease-19 (COVID-19) has spread over many countries and regions since the end of 2019, becoming the most severe public health event at present. Most of the critical cases developed multiple organ dysfunction, including acute kidney injury (AKI). Cytokine storm syndrome (CSS) may complicate the process of severe COVID-19 patients. This manuscript reviews the different aspects of blood purification in critically ill patients with AKI and increased inflammatory factors, and examines its potential role in severe COVID-19 treatment. Continuous renal replacement therapy (CRRT) has been practiced in many sepsis patients with AKI. Still, the timing and dosing need further robust evidence. In addition to the traditional CRRT, the high-throughput membrane with adsorption function and cytokine adsorption column are two representatives of recently emerging novel membrane technologies. Their potential in removing inflammatory factors and other toxins prospects for the treatment of severe COVID-19.