Continuous renal replacement therapy with oXiris filter in critically ill COVID-19 patients

Introduction: COVID-19 causes a major inflammatory response, which may progress to shock and multiple organ failure. We explored whether continuous renal replacement therapy (CRRT) using adsorption membrane (oXiris) could reduce the inflammatory response in critically ill COVID-19 patients with acute renal failure (ARF) [1, 2]. Method(s): Case-control study including 24 critically ill COVID-2019 patients requiring RRT using an oXiris filter. We measured cytokines before and during treatment as well as relevant clinical endpoints. The control group was selected among COVID-19 patients included into our ongoing RECORDS trial (NCT04280497) who received RRT without adsorbing filters. Result(s): 24 severe COVID-19 patients, admitted to the intensive care unit (ICU) and treated with CRRT using the oXiris filter between March and April 2020 (20 males and 4 females);median age 67. The average time from COVID-19 symptoms to initiation of oXiris treatment was 18 +/- 7 days, and from ICU admission to initiation of oXiris treatment 9.5 +/- 7.8 days and from ARF to oXiris treatment was 3 +/- 5 days. The average length of treatment was 152.8 +/- 92.3 h. Treatment was associated with cytokine decreases for IL-1beta (p = 0.00022), MCP-1 (p = 0.03), and MIP-1 alpha (p = 0.03). The SOFA scores also showed a reduction over 48 h of therapy without reaching statistical significance. Our study found no significant effect of hemodynamic status. The average ICU stay length was 14 +/- 5 days and the mortality rate was 79% in the Oxiris group. We compared the mortality across the two matched groups, there was no evidence of any difference in mortality (Fig. 1). Conclusion(s): In our study, CRRT using the oXiris filter seemed to effectively remove IL-1 beta, MCP-1, and MIP-1 alpha in COVID-19 patients. These exploratory results should be confirmed in a randomized controlled study.

Post COVID-19 cardiac magnetic resonance findings among inpatients vs outpatients

Background: Myocardial injury and myopericarditis constitute an important complication after viral infection. The prevalence of myocardial injury among patients that survived COVID - 19 infections and its causes are still not clear. The purpose of this study is to estimate whether there is a difference in the prevalence of cardiac magnetic findings between patients treated in a hospital vs patients treated at an outpatient clinic. Method(s): We evaluated 360 cardiac magnetic resonance examinations, performed from 1st of June 2020 until the 31st of August, 2021. Out of them, 141 patients (39%) underwent cardiac magnetic resonance due to persistent symptoms after a SARS-CoV-2 infection. A conventional CMR protocol was performed to rule out myocarditis. Revised 2018 Lake Louise Criteria were used to diagnose myocarditis. All scans were performed by Phillips Medical Systems Ingenia 1.5T. T1 native values were estimated elevated when mapping values measured above 1030ms, T2 mapping values were estimated elevated when greater than 55 ms. Mid wall or subepicardial late gadolinium enhancement, pericardial effusions and extracardiac findings were evaluated. Chi-square test was used. Result(s): Out of 141 patients, 78 patients (55%) had at least one cardiac magnetic resonance finding: Either increased T1 (22%), T2 mapping (7%), T2 STIR (1.4%), left gadolinium enhancement (30%), small pericardial effusion (26%) or lung parenchymal changes (12%) after COVID-19. Twenty out of 141 patients (14%) fulfilled the criteria for myocarditis. Out of these 20 patients, 14 patients (70%) received treatment at an outpatient clinic, while 6 patients (30%) were treated from COVID-19 in a hospital (p<0.053). The most prevalent symptoms were effort intolerance and palpitations (50% and 26% respectively). There was no statistical difference in myocarditis prevalence, between hospitalized patients treated with or without corticosteroids (p=0.65), as well as between patients treated with hemodiafiltration (Oxiris filter) and patients without hemodiafiltration (p=0.95). Also, there was no statistical difference between T1 mapping among the inpatients and outpatients (p=0.58), as well as the severity of the clinical picture (p=0.72). There was no statistical difference between the in-and outpatient groups according to age (p=0.46). None of these patients had signs of fulminant myocarditis. Conclusion(s): The prevalence of myopericardial and/or lung involvement after SARS-CoV-2 infection is present in every other cardiac magnetic resonance examination performed for persistent symptoms after a survived COVID-19. Myocarditis after SARS-CoV-2 infection develops regardless of the severity of the symptoms or the treatment method. We can conclude that we have to look for the reasons for myocarditis, beyond the clinical picture and the treatment strategies.

Osmoprocessor for enabling highly sensitive biomarker detection via lateral flow assays

Lateral flow assays are low-cost devices suitable for point-of-care testing, particularly in low-resource settings. However, some of the lateral flow assays exhibit limited diagnostic utility because the assays can only sample <100uL specimen and the biomarker concentration is significantly lower than the assay detection limit, which compromise the sensitivity. To address the challenge, we have developed the osmoprocessor that statically and spontaneously concentrated biomarkers via osmosis. The specimen in the device interfaces with the aqueous polymer solution via a dialysis membrane. The polymer solution induces an osmotic pressure difference that extracts water from the specimen, while the membrane retains the biomarkers. The evaluation demonstrated that osmosis induced by various water-soluble polymers efficiently extracted water, ca. 15 mL/hr. The water transport kinetics can be adjusted by varying polymer molecular weights and mass concentrations. The osmoprocessor concentrated the specimens to improve the lateral flow assays' detection limits for the model analytes-human chorionic gonadotropin and SARS-CoV-2 nucleocapsid protein. The device processed a 10 mL specimen into a 100uL concentrated sample. Then, the lateral flow assays detected the corresponding biomarkers in the concentrated specimens. The test band intensities of the assays with the concentrated specimens were very similar to the reference assays with 100-fold concentrations. The mass spectrometry analysis estimated the SARSCoV- nucleocapsid protein concentration increased ca. 200-fold after the osmosis. With its simplicity and flexibility, this device demonstrates a great potential to be utilized in conjunction with the existing lateral flow assays for enabling highly sensitive detection of dilute target analytes.

Mechanical Rotatory Method of Anticoagulation-Free Hemodialysis Using a Hemodialysis Filter Rotator With the NxStage Hemodialysis Machine: A UVMMC-UVM Burlington VT Research Collaboration Effort

Background: The maintenance of blood fluidity in the extracorporeal circuit during hemodialysis (HD) often requires systemic anticoagulation. While effective, these anticoagulants cause bleeding, have other side effects, cannot be used in critically ill patients and in the peri-operative period, and add to costs. We recently described a novel mecahnical rotational approach to anticoagulation-free HD using the "Locke-Onuigbo" maneuver (Figure 1).1 Methods: Prototype Completion: In collaboration with the University of Vermont Center for Biomedical Innovation (UVM CBI), five Senior Engineering students from the UVM, under the supervision of Yves Dubief PhD, Associate Professor of Mechanical Engineering, UVM, the first author and his Home Dialysis Program at the UVM Medical Center, have successfully prototyped an AI-modulated hemodialysis filter rotator that enables anticoagulation-free HD using the NxStage HD machine (Figure 2). Result(s): The Hemodialysis Filter Rotator Prototype running test on the HD machine (Figure 2) Conclusion(s): This Hemodialysis Filter Rotator enhances the capabilities of enabling sustainable Home HD for ESRD patients and represents a most welcome option in a "post-COVID" world and expands the offering of a convenient, safe and effective Home HD option to thousands of patients who prefer this choice of treatment. Moreover, we would argue that our novel prototype will deliver the unmet need for anticoagulation-free HD in critically ill patients, in the peri-operative period, and in hospitalized patients, in general. Investors and sponsors are welcome. (Figure Presented).

Minimal recovery of drug from extracorporeal treatment in a case of phenytoin toxicity associated with coma and hypothermia

Background: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup provides a weak conditional recommendation in support of hemodialysis (HD) for select patients with severe phenytoin poisoning. Despite this recommendation, the HD clearance of phenytoin is poorly studied. We present a patient who developed phenytoin toxicity that was treated with hemodialysis and report on the efficacy of phenytoin removal during HD. Case report: An 87-year-old man with epilepsy who was maintained on a stable dose of 300mg phenytoin extended-release daily was admitted to the hospital for treatment of Coronavirus Disease 2019 and congestive heart failure. On hospital day 14, the patient had a gradual onset of depressed mental status with hypothermia (nadir 35 degrees Celsius). At this time, he had a rising total blood phenytoin concentration (peak 49.3 mcg/mL [therapeutic 10-20mcg/mL] with an albumin of 3.8 g/dL [normal 3.4-5.4 g/dL]). The patient's other medications included furosemide, aspirin, atorvastatin, digoxin, doxycycline, metoprolol tartrate, and warfarin;he was also receiving albumin and crystalloid for hypovolemia (albumin nadir on hospital day 14: 2.5 g/dL). Free phenytoin concentrations were not available. Alternate etiologies of hypothermia (endocrine, infectious) were excluded. The Poison Control Center was consulted and recommended HD because of the concern for prolonged coma, as per EXTRIP guidelines. The patient received three sessions of HD over a period of 6 days at 2.5-3 h per session using an F160 Optiflux membrane filter (Fresenius Medical Care, Waltham, MA, USA), with a blood flow rate of 350mL/min and a dialysate flow rate of 700mL/min. After the first session of HD (2.5 h) on hospital day 21, his hypothermia resolved and his phenytoin concentration fell from 39.2mcg/mL to 34.2 mcg/mL with only mild improvement in his mental status. After 6 days (hospital day 27), his phenytoin concentration decreased to 19.5 mcg/mL and his mental status normalized. Effluent from the first HD session had phenytoin concentrations below the limit of detection (0.50mcg/mL). Thus, no greater than 52mg of phenytoin was removed during a 2.5-h session of hemodialysis. Discussion(s): The reason for the sudden increase in blood phenytoin concentrations in this patient is unclear in the absence of drug-drug interactions or dosing changes to the phenytoin. Although uncommonly reported, patients with phenytoin toxicity can experience hypothermia. In this case, the patient's hypothermia resolved during HD, although it is unclear if this was related to changes in phenytoin concentration or (more likely) direct extracorporeal warming via the HD machine. If the patient's phenytoin clearance from the first session were extrapolated to subsequent sessions an estimated maximum of 166.4mg of phenytoin would be removed in 8 total hours of HD, which is far less than previously reported phenytoin clearances on the order of grams. This difference may be related to the use of high cutoff dialysis membranes in prior studies, which are not routinely used. Conclusion(s): Although HD rapidly resolved this patient's hypothermia, a minimal amount of phenytoin was recovered in the patient's dialysate. Prior studies suggesting consequential clearance and efficacy of phenytoin removal by extracorporeal treatment may not apply to routine HD methods. Further studies on the utility of extracorporeal treatment for phenytoin toxicity are needed.

ANTI-INFLAMMATORY APPROACH IN CHRONIC DIALYSIS PATIENTS WITH SARS-COV-2: ATA OR PMMA DIALYZERS?

BACKGROUND AND AIMS: High flux haemodialysis membranes may modulate the cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their impact in chronic haemodialysis (CHD) patients is not assessed [1, 2]. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers in CHD patients with SARS-CoV-2. METHOD: A prospective, observational study on CHD patients (age ≥18 years) affected by SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021 and dialysis was performed at S. Orsola University Hospital (Bologna, Italy) Dialysis Unit. Mechanical ventilation at diagnosis was exclusion criteria. Pre-and post-dialysis C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were determined at each session and corrected for haemoconcentration during the complete SARS-CoV-2 period. Patients who underwent online haemodiafiltration (OLHDF) with PMMA dialyzer (Filtryzer BG-UTM, Toray, surface area 2.1 m2, cut-off 20 kDa, KUF 43 mL/h/mmHg) were compared with those who underwent OLHDF with ATA dialyzer (SolaceaTM, Nipro, surface area 2.1 m2, cut-off 45 kDa, KUF 72 mL/h/mmHg). The primary endpoint was to assess the differences in the reduction ratio/session (RR) of CRP, PCT and IL-6. RESULTS: A total of 74 patients were enrolled, 48 were treated with ATA and 26 were with PMMA (420 versus 191 dialysis sessions). The main results are shown in Table 1. Median IL-6RR% was higher for ATA [17.08%, interquartile range (IQR) -9.0 to 40.0 versus 2.95%, IQR -34.63 to 27.32]. CRP and PCT showed higher RR with ATA in comparison to PMMA. When IL-6RR > 25% was the dependent variable in the multiple logistic regression analysis only ATA showed a significant correlation [odds ratio (OR) 1.891, 95% confidence interval (95% CI) 1.273-2.840, P = .0018) while higher CRP favoured the risk of lower IL6RR (OR 0.9101, 95% CI 0.868-0.949, P < 0.0001) (Table 2). CONCLUSION: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile than PMMA, in particular regarding IL-6 RR.

CLINICAL CHARACTERISTICS, MANAGEMENT AND OUTCOMES OF CRITICALLY ILL COVID-19 PATIENTS UNDERGOING CRRT: COMPARISON BETWEEN THE FIRST TWO PANDEMIC WAVES

BACKGROUND AND AIMS: Acute kidney injury (AKI) is a common complication of coronavirus disease-19 (COVID-19), which, particularly in critically ill patients requiring continuous renal replacement therapy (CRRT), is associated with an elevated mortality risk [1, 2]. However, knowledge about COVID-19 pathogenesis and management is evolving, and clinical practice is changing rapidly. Here, we evaluated if this process had an impact on the management and outcome of AKI patients. METHODS: We performed a retrospective observational study on critically ill adult COVID-19 patients who received CRRT in the intensive care unit (ICU) during the first two pandemic waves before the availability of COVID-19 vaccines: the first one from March to August 2020 (first) and the second one (second) from September to December 2020. RESULTS: Overall, we considered 63 patients, aged 65 (60-69) years, 76.2% males. The main comorbidities were diabetes (DM), cardiovascular disease (CVD) and chronic kidney disease (CKD). Among them, 28 (44%) were in the first group and 35 (66%) in the second group. There were no significant differences in general characteristics, such as in comorbidities, except for a higher prevalence of CVD in the first group (Fig. 1). Lab examinations at ICU admission, including serum creatinine level (sCr), were not different between the two groups. While all patients required respiratory support, non-invasive ventilation was more prevalent in the second wave. Notably, during this period, decapneization combined with CRRT was introduced. Regarding drugs, we found that in the second group, hydroxychloroquine was abandoned, tocilizumab use was reduced and heparin administration significantly increased. The AKI time course was similar between the patients of the two waves (Fig. 2). There were no significant differences in CRRT techniques. However, in the second, the use of additional CRRT-devices, in particular adsorption-based filters, significantly increased. In most cases, citrate anticoagulation was used in both groups. Looking at the outcomes, we found no significant difference between the two waves. Indeed, 17 (60.2%) and 22 (62.8%) patients died in the ICU in the first and second groups, respectively. The length of ICU hospitalization, days on CRRT, invasive ventilation and DM were significantly related to overall mortality;time of ICU hospitalization was the only remaining significant at multivariate Cox regression. Overall, 21 (33%) patients survived hospitalization. At the 6 months after the discharge, 3 of them died, 3 were on HD and 15 were dialysis-free, even if 6 of them presented CKD. CONCLUSION: Our data confirm the high complexity and mortality of COVID-19 patients undergoing CRRT. Comparing the first two pandemic waves, we found that the patients also presented similar characteristics in terms of renal function and AKI time course. Regarding treatments, we observed some significant modifications in the management of ventilation, drug administration and dialysis membranes, mainly because of the results of ongoing clinical trials. However, these changes did not impact patients' outcomes. These data support the view that only game-change strategies, such as vaccination or infection-specific drugs, may impact the presentation and outcome of COVID-19 patients undergoing CRRT. Finally, patients surviving this condition deserve special attention in the follow-up. (Table Presented).

Abstracts from the 39th Annual Meeting of the Vicenza Course on AKI and CRRT

The proceedings contain 33 papers. The topics discussed include: acute kidney injury in children and adolescents hospitalized for diabetic ketoacidosis;urinary biomarkers as predictors of AKI in COVID-19 hospitalized patients with pneumonia;critically ill patients with COVID-19 pneumonia requiring renal replacement therapy with Oxiris membrane in a third level hospital in north-east Mexico;legionellosis followed by acute respiratory distress syndrome successfully treated with antibiotics and polymyxin B hemoperfusion therapy;the role of serum miRNA in leptospirosis-associated acute kidney injury;and polymixin B hemoperfusion in patients with COVID-19 infection and endotoxin shock: a case report.

Fluctuations in Interleukin-6 Levels during Hemodialysis Sessions with Medium Cutoff Membranes: An Analysis on COVID-19 Case Series.

INTRODUCTION: Interleukin-6 (IL-6) is one of the most important mediators of inflammation. It is also the culprit for a severe disease course in COVID-19. While COVID-19 has higher mortality in hemodialysis (HD) patients, medium cutoff (MCO) membranes were previously suggested as promising tools for better patient outcomes by purging inflammatory mediators. The aim of this study was to analyze changes in IL-6 levels of HD patients who were dialyzed via MCO membranes during their COVID-19 treatments. METHODS: This is an observational study on a group of HD patients who were admitted with COVID-19 diagnosis in a university hospital and intermittently dialyzed using MCO membranes during their hospital stay. IL-6 levels of the patients were measured before and after consecutive dialysis sessions by a commercial kit. Measurements were interpreted together with the clinical data. RESULTS: Nine patients with a total of 54 measurements were evaluated. IL-6 levels were significantly higher in patients who died (median and interquartile ranges [IQRs] of IL-6 levels for patients who died and survived were 112.0 pg/mL [48.3-399.4] and 5.3 pg/mL [2.2-27.4], respectively; p < 0.001). In the comparison of changes in IL-6 levels with dialysis sessions, patients who survived had lower post-dialysis levels (median: 4.5 pg/mL; IQR: 2.2-7.6). However, IL-6 levels had a tendency to increase with dialysis sessions in patients who could not survive COVID-19 (median: 237.0 pg/mL; IQR: 53.8-418.2). CONCLUSION: This study describes over time variations in IL-6 levels of COVID-19 patients undergoing HD with MCO membranes. The trend for the changes of IL-6 levels during dialysis sessions was not uniform for all patients. Surviving patients had decreasing levels of IL-6 with consecutive dialysis sessions, while nonsurvivors had an increasing trend.

SINGLE-CENTER EXPERIENCE WITH THE USE OF THE SERAPH-100 MICROBIND AFFINITY BLOOD FILTER IN-PARALLEL WITH EXTRACORPOREAL MEMBRANE OXYGENATION CIRCUIT IN SEPTIC PATIENTS

TYPE: Late Breaking Case Report TOPIC: Critical Care INTRODUCTION: Patients who require extracorporeal membrane oxygenation (ECMO) have a high mortality if they develop septic shock. With the emergence of novel and resistant pathogens, new therapies are needed to treat septic patients. The Seraph–100 Microbind Affinity Blood Filter was granted Emergency Use Authorization by the FDA to treat severe COVID-19. The Seraph-100 filter contains microbeads that can bind bacteria, fungi, viruses and cytokines. Recommended configurations for the Seraph–100 utilize hemodialysis or continuous renal replacement therapy (CRRT) machines in a stand-alone fashion or in-combination with a hemodialysis filter. In this series, we explore a new configuration for the Seraph-100 for patients requiring ECMO. CASE PRESENTATION: Five septic patients underwent treatment with the Seraph-100 in-parallel with ECMO. This configuration allowed for pressures generated by the ECMO circuit to drive blood flow through the Seraph-100. All five patients were on multiple high dose vasopressors prior to therapy with the Seraph-100. Within 12-24 hours of treatment, vasopressor support significantly decreased and repeat blood cultures showed clearance of pathogens. DISCUSSION: All our patients treated with Seraph–100 in-parallel with ECMO had significant reduction in vasopressor support. Benefits of this configuration include limiting need for additional vascular access and need for dialysis circuits, along with the associated risks of renal replacement therapy. CONCLUSIONS: The Seraph-100 represents an innovative solution for the treatment of septic patients. This case series demonstrated the effectiveness and safety of a new configuration for the Seraph-100 in patients requiring ECMO. Further studies are needed to elucidate the optimal use of the Seraph-100 blood filter. DISCLOSURE: Nothing to declare. KEYWORD: Seraph-100 Blood Filter

The first case of COVID-19 pneumonia in a hemodialysis patient in Japan.

On 31 December 2019, cases of pneumonia whose cause was later identified as SARS-CoV-2 were detected in Wuhan City, Hubei Province of China, and now COVID-19 has spread worldwide. On March 1, 2020, a 69-year-old Japanese man who had been on hemodialysis for 3 years was diagnosed as having COVID-19 pneumonia and hospitalized at our Medical Center. Pulmonary CT revealed bilateral multiple consolidation with bilateral pleural effusion. Aggressive weight reduction was needed to improve the patient's respiratory condition. Hemodialysis therapy was performed in isolation with hydroxychloroquine administration, but the formation of a dialysis membrane clot forced the withdrawal of dialysis therapy. Changing the dialysis membrane material and anticoagulant enabled the resumption of dialysis therapy, allowing the body weight to correct downward. On the 5th hospitalization day, the patient's fever dropped and he showed improved oxygenation and chest X-ray. He was eventually discharged. The hydroxychloroquine and appropriate fluid management may have contributed to the patient's recovery. Clinicians should pay close attention to avoid dialysis-related problems when treating a patient with COVID-19.