Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis.

We aimed to investigate the clinical efficacy of blood purification technology based on cytokine adsorption in the treatment of sepsis. Sixty patients with sepsis were randomly divided into control (n = 30) and experimental (n = 30) groups. Both groups were given routine treatment and continuous venovenous hemofiltration, and on this basis, the experimental group received acrylonitrile/sodium methacrylate (AN69ST) blood purification. The levels of C-reactive protein, procalcitonin, white blood cell count, albumin, platelets, total bilirubin, creatinine, lactic acid, and APACE II score, as well as secretion of inflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF-α) were compared. The hospitalization time, mechanical ventilation (MV) time, drug use time, and mortality were analyzed. After treatment, the secretion levels of IL-6 and TNF-α were decreased, and other indicators were significantly improved compared with those before treatment (P < 0.05), especially in the experimental group (P < 0.05). The hospitalization time, MV time, and drug use time in the experimental group were significantly lower than those of the control group (P < 0.05), and the mortality was lower than that in the control group (P < 0.05). In conclusion, blood purification technology based on cytokine adsorption can significantly improve various indicators of sepsis patients, reduce hospitalization time, reduce mortality, and improve the prognosis.

Comparison of the Clinical Effectiveness of AN69-oXiris versus AN69-ST Filter in Septic Patients: A Single-Centre Study.

INTRODUCTION: The clinical effectiveness of AN69-oXiris remains unclear. This study aimed to compare the effects of AN69-oXiris and AN69-ST filters on cytokine levels and clinical improvement in septic patients. METHODS: This prospective observational study recruited septic patients who underwent blood purification in the First Affiliated Hospital of Soochow University between December 2019 and May 2020. Patients were assigned to an AN69-oXiris (oXiris) or AN69-ST (ST) group based on their preferred filter. Patients' clinical data, cytokine levels, and prognostic indicators were analysed at baseline (T0), 24 h after treatment (T1), and at the end of the treatment (T2). RESULTS: Forty-four patients participated in this study (22 patients in each group). Participants in both groups showed improvements in mean arterial pressure (MAP) values, oxygenation indices, and urinary output, and decreased vasoactive-inotropic scores (VISs), heart rates, lactic acid levels, and serum creatinine levels after blood purification. Reductions in cytokine levels were observed at T1 in both groups. Improvement the haemodynamic status was higher in the oXiris group than in the ST group at T2 (MAP: 79.0 [76.0, 85.0] vs. 77.0 [72.75, 79.25] mm Hg, p = 0.04; VISs: 9.10 [0.00, 16.69] vs. 19.05 [10.60, 26.33], p = 0.03, respectively). Patients in the oXiris group also had lower cytokine levels than those in the ST group at T1 (tumour necrosis factor-α: 24.55 [16.9, 30.15] vs. 30.15 [23.38, 34.13] pg/mL, p = 0.04; interleukin (IL)-6: 66.63 [46.21, 102.20] vs. 125.48 [79.73, 167.97] pg/mL, p = 0.01; IL-8: 53.59 [35.10, 66.01] vs. 63.60 [45.58, 83.37] pg/mL, p = 0.04; IL-10: 13.50 [10.35, 18.68] vs. 17.15 [13.80, 21.95] pg/mL, p = 0.04, respectively). There were no significant differences between the 2 groups regarding hospital mortality, intensive care unit length of stay (LOS), and hospital LOS. CONCLUSION: Blood purification using the AN69-oXiris or AN69-ST filter proved useful for septic patients, which was associated with reduced cytokine levels and improved clinical condition. Patients treated with AN69-oXiris had a more remarkable improvement in haemodynamic status and lower cytokine levels than those treated with AN69-ST filter, but there were no differences in clinical outcomes. Further investigations are needed to prove this finding.

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.

Vancomycin pharmacokinetics in critically ill patients receiving continuous haemodiafiltration with a polyethyleneimine-coated polyacrylonitrile membrane.

WHAT IS KNOWN AND OBJECTIVE: We investigated the elimination efficiency and pharmacokinetics (PK) parameters of vancomycin (VCM) in patients undergoing continuous haemodiafiltration (CHDF) using a polyethyleneimine-coated polyacrylonitrile membrane (AN69ST) for dosage adjustment. METHODS: We conducted a retrospective study of CHDF patients treated with VCM from December 2017 to August 2019. We calculated PK parameters of VCM and determined the 24-hour dose required to maintain the target trough concentration of VCM (VCM_trough ). RESULTS AND DISCUSSION: The average (95% CI) volume of distribution and total clearance of VCM were 75.5 L (63.7-87.3 L) and 1.84 L/h (1.38-2.30 L/h), respectively, and the elimination rate constant and half-life were 0.026/h (0.017-0.034/h) and 31.2 h (22.8-39.5 h), respectively. The average AN69ST clearance of VCM (CL_CHDF ) was 0.69 L/h (0.52-0.86 L/h). The estimated average doses required to maintain VCM_trough of 10, 15 and 20 µg/mL were 623.1 mg (379.8-866.4 mg), 934.6 mg (569.7-1299.5 mg) and 1246.2 mg (759.6-1732.8 mg), respectively. WHAT IS NEW AND CONCLUSION: The PK of VCM and CL_CHDF of AN69ST were clarified. These results suggest that it is possible to adjust the dose of VCM in using AN69ST, which efficiently removes cytokines, and contributes to improvement of serious infections.

A case of complete atrioventricular block in secondary hemophagocytic syndrome/hemophagocytic lymphohistiocytosis recovered by plasma exchange and cytokine absorbing therapy with AN69ST continuous hemodiafiltration.

We report a case of incipient systemic lupus erythematosus (SLE) that rapidly progressed to complete atrioventricular block (cAVB). A 20-year-old man was admitted with facial erythema, painless oral aphtha, polyarthritis, and myalgia of each extremity. On admission, he developed first-degree atrioventricular block, pericarditis, pleuritis, renal failure, hemophagocytic lymphohistiocytosis, neurophychiatric SLE (left cerebellar infarction), and Staphylococcus aureus bacteremia. He was subsequently diagnosed with SLE based on several positive findings on immunological tests (including positive for antinuclear antibody). Despite immediate glucocorticoid pulse therapy and plasma exchange (PE) along with antibiotic, he developed cAVB that required temporary pacing on day 2. Because it was thought that hypercytokinemia exacerbated pericarditis, which progressed to myocarditis and cAVB, we decided to PE and cytokine-adsorbing therapy with AN69ST-continuous hemodiafiltration (CHDF). Other than renal failure, his organ dysfunctions improved with the multidisciplinary therapy. CAVB improved and temporary pacing was no longer required on day 11. Even a first-degree atrioventricular block can rapidly progress to cAVB; therefore, strict attention to electrocardiogram is necessary in severe SLE cases. When presenting with organ dysfunctions caused by hypercytokinemia such as severe SLE cases or SLE with severe infection cases, use of the combination of PE and AN69ST-CHDF might be beneficial.

Involvement of ionic interactions in cytokine adsorption of polyethyleneimine-coated polyacrylonitrile and polymethyl methacrylate membranes in vitro.

Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30 min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10 min and 30 min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10 min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6 mL/min, 23 ± 7 mL/min, and 78 ± 3 mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76 mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design.

Comparison of the circulatory effects of continuous renal replacement therapy using AN69ST and polysulfone membranes in septic shock patients: A retrospective observational study.

The acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane is expected to improve hemodynamics in patients with sepsis through cytokine adsorption. However, the clinical literature on AN69ST membranes is very limited. We aimed to compare the circulatory effects of continuous renal replacement therapy (CRRT) between patients using the AN69ST membrane and polysulfone (PS) membrane (a nonadsorbing membrane). This retrospective observational study enrolled 38 patients with septic shock, as defined by Sepsis-3 criteria, who required CRRT from April 2013 to March 2018. Those who died within 24 hours after CRRT initiation and received polymyxin B-immobilized fiber column direct hemoperfusion, extracorporeal membrane oxygenation, and CRRT using other membranes were excluded. The primary outcome was the vasopressor dependency index during the 12 hours after CRRT initiation, which was calculated as (inotropic score)/(mean arterial pressure). Of 38 patients analyzed, 16 underwent CRRT with an AN69ST membrane and 22 with a PS membrane. The median patient age was 68 years, and the median Acute Physiology and Chronic Health Evaluation (APACHE) II score at intensive care unit admission was 29.5. The vasopressor dependency index decreased significantly during the 12 hours after CRRT initiation in both groups (AN69ST: from 0.50 ± 0.43 to 0.33 ± 0.27 [P < .05], PS: from 0.34 ± 0.30 to 0.21 ± 0.22 [P < .05]). The time course of the vasopressor dependency index during the 12 hours did not differ between the two groups (P = .11). The vasopressor dependency index decreased significantly after CRRT initiation in both groups. The time course of the vasopressor dependency index did not differ between the groups.

A pilot study into the use of Continuous Venous Hyperfiltration to manage patients in a critical state with dysregulated inflammation. / Estudio piloto sobre el uso de la Hiperfiltración Venosa Continua para el manejo de pacientes en estado crítico con inflamación desregulada.

INTRODUCTION: Haemofiltration paradigms used to manage critically ill patients with a dysregulated inflammatory response (DIR) assess kidney function to monitor its onset, adaptation, and completion. A Continuous Venous Hyperfiltration (CONVEHY) protocol is presented, in which a non-specific adsorption membrane (AN69-ST-Heparin Grafted) is used with citrate as an anticoagulant and substitution fluid. CONVEHY uses tools readily available to achieve kidney related and non-related objectives, and it is guided by the monitoring of pathophysiological responses. OBJECTIVES: To compare the response to an AN69-ST-HG membrane when heparin (He, n=5: Standard protocol) or citrate (Ci, n=6: CONVEHY protocol) was used to evaluate whether a larger study into the benefits of this protocol would be feasible. MATERIALS AND METHODS: In a retrospective pilot study, the benefits of the CONVEHY protocol to manage patients with a DIR in a surgical critical care unit (CCUs) were assessed by evaluating the SOFA (Sequential Organ Failure Assessment) (He 11 ± 2.35; Ci 11 ± 3.63: p=0.54) and APACHE II (He 28.60 ± 9.40; Ci 24 ± 8.46: p=0.93) scores. RESULTS: Nights in hospital (He 35.2 ± 16.3 nights; Ci 9 ± 2.53: p=0.004), hospital admission after discharge from the CCUs (He 40.25 ± 21.82; Ci 13.2 ± 4.09: p=0.063), patients hospitalised >20 days (He 80%; Ci 0%: p=0.048), days requiring mechanical ventilation (He 16 ± 5.66; Ci 4 ± 1.72: p=0.004), and the predicted (55.39 ± 26.13%) versus real mortality in both groups (9.1%: p=0.004). CONCLUSIONS: The CONVEHY protocol improves the clinical responses of patients with DIR, highlighting the potential value of performing larger and confirmatory studies.

The Effect of Continuous Renal Replacement Therapy with the AN69ST Membrane on Inflammatory Markers and the Level of Consciousness of Hemodialysis Patients with Stroke: Comparison with Hemodialysis with Low Blood Flow Rate.

INTRODUCTION: Hemodialysis (HD) with low blood flow rate, continuous renal replacement therapy (CRRT), and peritoneal dialysis are recommended for patients with stroke complications to prevent intracranial hypertension because of the low diffusion capacity of the brain barrier. However, detailed guidelines are not currently available; thus, there is an urgent need to establish such guidelines. MATERIAL AND METHODS: We developed a novel protocol for performing CRRT with the AN69ST membrane, which has excellent adsorption capacity for various cytokines. The objective of this study was to compare the effect of the novel protocol with that of the current standard protocol, i.e. hemodialysis with low blood flow rate. To compare the effect of hemodialysis with low blood flow (HD group, n=27) and CRRT with AN69ST membrane (CRRT group, n=8), we measured the following consciousness and blood inflammatory parameters in patients with stroke complications at baseline and after 1 week of treatment: Glasgow Coma Scale (GCS) score, C-reactive protein (CRP) levels, and white blood cell (WBC) and platelet count. RESULTS: After 1 week, the total GCS score did not improve in the HD group, but improved significantly in the CRRT group (HD group: 13.1±3.0 to 13.3±3.1, p=0.5508, CRRT group: 8.9±3.9 to 11.5±3.9, p=0.0313). Improvement in the CRRT group was significantly higher than in the HD group (p=0.0039). CRP levels did not change significantly in either the HD (3.8±5.5 to 5.3±4.3 n.s.) or CRRT groups (7.7±10.0 to 3.7±3.2 n.s.); however, they tended to increase in the HD group and decrease in the CRRT group. No significant changes were observed in WBC and platelet counts after 1 week of treatment in either group. CONCLUSION: CRRT with the AN69ST membrane might have a beneficial effect on the consciousness level and inflammation of patients with stroke.