Hemoperfusion with CytoSorb as Adjuvant Therapy in Critically Ill Patients with SARS-CoV2 Pneumonia

Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.

Blood purification treatment and cytokine removal using Cytosorb device in critically ill patients with COVID-19 infection

Introduction: Acute kidney injury (AKI) is a complication of SARS-CoV-2 disease, associated with worse clinical outcomes. Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBPT) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions. Method(s): We retrospectively analyzed 20 patients admitted in ICU for ARDS and who developed moderate-to-severe AKI requiring RRT. Cytokine hemadsorption with Cytosorb was performed in association with CRRT. The main indication for this treatment was the worsening of hemodynamic and respiratory conditions and suspicion of cytokine storm. The protocol consisted in the use of 3-4 cartridges in total;among these, the first 2 were changed after 12 hours of treatment to maximize cytokine removal, while the others after 24 hours. We examined comorbidities, clinical and laboratory characteristics and the impact of treatment in terms of mortality rate and changes in data before and after treatment. Result(s): Nineteen patients (95%) had an AKI at any time during their ICU stay. Of these, 5 patients (25%) had AKI stage II and 14 patients (70%) had AKI stage III. All patients included in this subgroup were mechanical ventilated and required vasopressor's use. Mean prescribed CRRT dose was 31.2 +/- 11.7 ml/kg/h. The median time to strating RRT after ICU admission was 7 days (IQR 3.5-15 days) and the median duration was 7 days (IQR 2.5-12.5 days). Mean SOFA score at the time of RRT start was extremely high (14.5 +/- 2.8). Mortality rate was important (18 patients, 90%) in our cohort. Comparing clinical and laboratory data before and after treatment, a significant improvement of inflammatory markers was reported, with the reduction of C-reactive protein (CRP, 143 [62.1- 328.5] vs 83.5 [66.7-153.5] mg/L);however, no significant changes in IL-6, WBC and PCT values were observed. A slight increase of PaO2/FiO2 were described, although not statistically significant (PaO2/FiO2 ratio 144 [82.7-174.2] vs 183 [132-355.5] mmHg). Conclusion(s): Our experience supports the need of an adequate timing for the use of Cytosorb in critically ill patients with Covid-19. Although a discrete efficacy in improving inflammatory cascade, the late use of EBPT, when organ dysfunction was already ongoing, didn't impact survival.

Extracorporeal blood purification benefits in post-caesarean patient with severe acute respiratory distress syndrome due to miliary tuberculosis: a case report.

BACKGROUND: Miliary tuberculosis is a life-threatening disease caused by the hematogenous spread of Mycobacterium tuberculosis. It is uncommon in pregnancy. Mortality rates for patients with miliary tuberculosis who require mechanical ventilation are high (60-70%). CASE PRESENTATION: We reported a rare and challenging case, a 35-year-old Asian woman with 34 weeks of pregnancy, and miliary tuberculosis with acute respiratory distress syndrome and septic shock. The patient presented with severe acute respiratory distress syndrome, necessitating mechanical ventilation, vasopressor, and pregnancy termination with caesarean section. The patient underwent blood purification with continuous veno-venous hemofiltration using an oXiris filter for 24 hours. After continuous veno-venous hemofiltration, the patient's condition was greatly improved, and the patient was successfully extubated and was able to breathe spontaneously without vasopressor on the third day. High levels of interleukin-6, interleukin-10, procalcitonin, C-reactive protein, interferon-γ, and tumor necrosis factor-α were found postoperatively. CONCLUSION: The bacterial infection of tuberculosis, acute respiratory distress syndrome, and the stress response from the caesarean section contributed to the high levels of cytokines, which correlated with the patient's severe inflammatory condition. The cytokine levels were greatly reduced after the blood purification procedure and this might be associated with the patient's clinical improvement. Extracorporeal blood purification could help to disrupt the vicious cycle of inflammation.

Therapeutic apheresis in sepsis.

Sepsis is a leading cause of morbidity and mortality worldwide. Dysregulated immune response to infection is a hallmark of sepsis, leading to life-threatening organ dysfunction or even death. Advancing knowledge of the complex pathophysiological mechanisms has been a strong impetus for the development of therapeutic strategies aimed at rebalancing the immune response by modulating the excess of both pro- and anti-inflammatory mediators. There is a wealth of preclinical data suggesting clinical benefits of various extracorporeal techniques in an attempt to modulate the exaggerated host inflammatory response. However, the evidence base is often weak. Owing to both an advancing comprehension of the pathophysiology and the increased quality of clinical trials, progress has been made in establishing extracorporeal therapies as part of the general therapeutic canon in sepsis. We aim for a comprehensive overview of the technical aspects and clinical applications in the context of the latest evidence concerning these techniques.

Predictors of Clinical Efficacy of Cytokine Hemoadsorption in COVID-19 (Clinical Trial).

Aim of the study. To evaluate the value of predictors of hemoadsorption clinical efficacy in patients with COVID-19. Materials and methods. This study analyzed the results of treatment of 62 patients with severe COVID-19 in the intensive care unit using selective hemoadsorption of cytokines. All patients with severe COVID-19 were admitted to the intensive care unit within 14 days from the disease onset were subdivided into two groups. Group 1 patients (n=32) received on a top of standard treatment the hemoperfusion (HP) procedure for 4 hours, for 2-3 days in a row, using a cytokine sorption column composed of mesoporous styrene-divinilbenzen copolymer matrix. Group 2 patients were not subjected to extracorporeal blood purification. All patients received IL-6 inhibitors at a baseline in accordance to the temporary guidelines. We evaluated factors of unfavorable outcomes by analyzing changes in biochemical markers of systemic inflammatory response and mortality rates in patients of both groups. Results. Initiation of HP later than 10 days from NCI onset (P < 0.001), length of stay in the ICU, extent of lung damage (P = 0.036) and the SOFA (Sequential Organ Failure Assessment) score (P = 0.009) were the most powerful predictors of unfavorable outcome. Levels of systemic inflammatory response markers (in-terleukin-6, CRP, D-dimer) in both groups did not significantly affect the survival rates and length of hospital stay (P > 0.05). HP group demonstrated better survival (P < 0.05). Mean hospital stay was 31 and 27 days, ICU stay - 11 and 8 days for Groups 1 and 2, respectively (P < 0.05). Conclusion. Treatment of severe COVID-19 patients with HP using novel domestic hemosorbent composed of styrene-divinilbenzen copolymer matrix resulted in decrease in CRP levels on the first day after application and, with early onset, contributed to a significant increase in survival and decreased hospital and ICU stay. Additional studies are warranted to clarify the optimal timing of the initiation of HP in severe COVID-19 patients.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Predictors of Clinical Efficacy of Cytokine Hemoadsorption in COVID-19 (Clinical Trial).

Aim of the study. To evaluate the value of predictors of hemoadsorption clinical efficacy in patients with COVID-19. Materials and methods. This study analyzed the results of treatment of 62 patients with severe COVID-19 in the intensive care unit using selective hemoadsorption of cytokines. All patients with severe COVID-19 were admitted to the intensive care unit within 14 days from the disease onset were subdivided into two groups. Group 1 patients (n=32) received on a top of standard treatment the hemoperfusion (HP) procedure for 4 hours, for 2-3 days in a row, using a cytokine sorption column composed of mesoporous styrene-divinilbenzen copolymer matrix. Group 2 patients were not subjected to extracorporeal blood purification. All patients received IL-6 inhibitors at a baseline in accordance to the temporary guidelines. We evaluated factors of unfavorable outcomes by analyzing changes in biochemical markers of systemic inflammatory response and mortality rates in patients of both groups. Results. Initiation of HP later than 10 days from NCI onset (P < 0.001), length of stay in the ICU, extent of lung damage (P = 0.036) and the SOFA (Sequential Organ Failure Assessment) score (P = 0.009) were the most powerful predictors of unfavorable outcome. Levels of systemic inflammatory response markers (in-terleukin-6, CRP, D-dimer) in both groups did not significantly affect the survival rates and length of hospital stay (P > 0.05). HP group demonstrated better survival (P < 0.05). Mean hospital stay was 31 and 27 days, ICU stay - 11 and 8 days for Groups 1 and 2, respectively (P < 0.05). Conclusion. Treatment of severe COVID-19 patients with HP using novel domestic hemosorbent composed of styrene-divinilbenzen copolymer matrix resulted in decrease in CRP levels on the first day after application and, with early onset, contributed to a significant increase in survival and decreased hospital and ICU stay. Additional studies are warranted to clarify the optimal timing of the initiation of HP in severe COVID-19 patients.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Expert consensus on the application of artificial liver blood purification system in the treatment of severe and critical COVID-19.

The prevention and treatment of COVID-19 nationwide has entered a tackling phase. Effective treatment of severe and critically ill patients is the key to reducing the fatality of the disease. The artificial liver blood purification system can remove inflammatory factors, alleviate the damage of the inflammatory response to the body, and has important value for the treatment of severe COVID-19. Led by academician Li Lanjuan, based on the experience of treating patients across the country, integrating the opinions of experts from all over the country, the center summarized and formulated the consensus including the basic principles, treatment indications, relative contraindications, mode selection, monitoring indicators, and efficacy evaluation of artificial liver, which provides reference for treatment of severe COVID-19 patients.Copyright © 2020 by the Chinese Medical Association.

Cytokine Storm and Immunomodulation in COVID-19: A Review

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has taken over the world, and more than 38 lakh deaths had been reported till now due to this infectious disease. It has been declared a global pandemic by the world health organization. SARS-CoV-2 causes coronavirus disease of 2019 (COVID-19), and the major problem called "Cytokine storm" is reported, which may lead to death among the COVID-19 patients. This study aimed to review the Cytokine storm and its mechanism along with few immunomodulatory therapies for SARSCoV-2 infection suppression effectively. Method(s): The recently published works of literature were selected and reviewed based on the subject of this study. The databases, including Pubmed, ScienceDirect, Scopus, and Google Scholar, were searched extensively. Result(s): The review of the literature showed that an uncontrolled immune response causes excess inflammation. Evidence from recent trials has demonstrated that cytokine storms can be an important factor in the COVID-19 severity, leading to multiple organ failure and death. Conclusion(s): This study reviewed immunomodulatory therapies and strategies for SARS-CoV-2 infected patients to suppress the immune response. Ultimately, the cytokine storm can prove to be a boon and reduce the significant death tolls to SARS-CoV-2 infection.Copyright © 2022 Bentham Science Publishers.

Ultraefficiently Calming Cytokine Storm Using Ti3C2T x MXene.

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3C2T x MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.

Hemoperfusion that was popular during the COVID-19 pandemic: A case series

The medical world has been seeking solutions in solving the Coronavirus disease 2019 (COVID-19) outbreak since 2019. Amongst several alter-natives, hemoperfusion therapy has been reported to be beneficial for alleviating symptoms and reducing mortality in severely ill COVID-19 patients. Hemoperfusion is a process of filtering blood to eliminate toxins and inflammatory factors from the body. This case series aims to high-light the unexpected adverse clinical and labora-tory outcomes in the majority of COVID-19 patients treated with hemoperfusion in our hospi-tal. We included fifteen patients admitted to the Intensive Care Unit (ICU) with moderate-to-se-vere COVID-19 between August and December 2020 and were all given two to four sessions of hemoperfusion using the MG150 cartridge. All ten men and five women showed no improve-ment in their neutrophil-lymphocyte ratio (NLR), ferritin, D-dimer, and C-reactive protein (CRP) values after the hemoperfusion regiments, both survivors and non-survivors. In addition, eleven out of twelve patients with respiratory failure who were then intubated resulted in death. Based on our findings and previous evi-dence, we recommended only performing hemoperfusion for investigational instead of therapeutic purposes due to its poorly under-stood pathophysiology in COVID-19. We also recommended further research regarding the us-age of hemoperfusion in COVID-19 patients, es-pecially in the matter of determining the best time to start the therapy.Copyright © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.

Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

Effect of extracorporeal hemoadsorption in critically ill patients with COVID-19: A narrative review.

COVID-19 has been affecting the world unprecedentedly and will remain widely prevalent due to its elusive pathophysiological mechanism and the continuous emergence of new variants. Critically ill patients with COVID-19 are commonly associated with cytokine storm, multiple organ dysfunction, and high mortality. To date, growing evidence has shown that extracorporeal hemoadsorption can exert its adjuvant effect to standard of care by regulating immune homeostasis, reducing viremia, and decreasing endotoxin activity in critically ill COVID-19 cases. However, the selection of various hemofilters, timing of initiation and termination of hemoadsorption therapy, anticoagulation management of extracorporeal circuits, identification of target subgroups, and ultimate survival benefit remain controversial. The purpose of this narrative review is to comprehensively summarize the rationale for the use of hemoadsorption in critically ill patients with COVID-19 and to gather the latest clinical evidence in this field.

Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients: a systematic review and meta-analysis.

BACKGROUND: Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT). METHODS: The Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies. RESULTS: Four randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = -10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution. CONCLUSION: Given the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.

Apheresis and COVID-19 in intensive care unit (ICU).

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, and on March 2020 the World Health Organization (WHO) declared it as pandemic, causing a public health crisis. Symptoms of COVID-19 are variable, ranging from mild symptoms like fever, cough, and fatigue to severe illness. Elderly patients and those with comorbidities like cardiovascular disease, diabetes, chronic respiratory disease, or cancer are more likely to develop severe forms of the disease. Asymptomatic infections have been well documented. Accumulating evidence suggests that the severity of COVID-19 is due to high levels of circulating inflammatory mediators including cytokines and chemokines leading to cytokine storm syndrome (CSS). Patients are admitted in ICU with severe respiratory failure, but can also develop acute renal failure and multi organ failure. Advances in science and technology have permitted the development of more sophisticated therapies such as extracorporeal organ support (ECOS) therapies that includes renal replacement therapies (RRTs), venoarterial (VA) or veno-venous (VV) extracorporeal membrane Oxygenation (ECMO), extracorporeal CO2 removal (ECCO2R), liver support systems, hemoperfusion, and various blood purification devices, for the treatment of ARDS and septic shock.

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

[Display omitted] • Porous hollow carbon spheres (HCSs) with adjustable size and pore width distribution were synthesized. • The clearance rate of HCSs to interleukin 6 (IL-6) in PBS buffer solution was up to 99.8%. • HCSs had a high adsorption rate and removal efficiency for PTH, β 2 -MG, IL-6 and TNF-α in the serum of uremic patients. • The selective adsorption of middle-macromolecular toxins or cytokines was achieved by regulating the pore structure of HCSs. Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8 %, even in the serum of uremic patients, HCSs could remove 94.75 % and 98.33 % of parathyroid hormone (PTH) and β 2 -microglobulin (β 2 -MG) efficiently within 5–10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment. [ FROM AUTHOR]

The efficacy of hemoadsorption for severe Multisystem Inflammatory Syndrome in children (MIS-C): a case series

Background: In the COVID-19 pandemic, children with COVID-19 infection have mild symptoms. However, some children may develop a hyperinflammatory response called multisystem inflammatory syndrome in children (MIS-C) after the COVID-19 infection. The main pathophysiology of this syndrome is mainly dysregulated inflammatory response lead to multi-organ dysfunction especially cardiovascular system. Despite early treatment with IVIG and corticosteroid, some children with MIS-C are still refractory disease and progressive symptoms. Additional from biologic agent, we try to find the treatment options as adjunctive treatment for rapid removing the inflammatory mediators. Blood purification by hemoadsorption may be a good choice for improve this clinical symptoms. Method(s): Five critically ill children with severe MIS-C who received initiated treatment with IVIG and corticosteroid, all children were received an extracorporeal blood purification by using HA330 disposable hemoperfusion cartridge (HA330;Jafron, Zhuhai City, China) combined with a continuous renal replacement therapy (CRRT) machine. Hemoadsorption (HA) will be performed for a maximum of 4 hours, and the second session will be started approximately 12-24 hours after the end of the first session. We observed the reduction of the PELOD-2 and PRISM-3 score compared between baseline and 72 hours after HA treatment. The reduction of VIS and inflammatory markers such as IL-6, procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP), lactate levels at 72 hours will be recorded. Result(s): This small case series, a total of 5 children who diagnosed with MIS-C were compared the severity score before and after HA treatment. The average PELOD-2 score decreased significantly from 9.0 (IQR;7.0-10.0) at baseline to 2.0 (IQR;0-7.0) at 72 hours (p = 0.04). The median PRISM-3 score also decreased significantly from 15.0 (IQR;15.0-18.0) at baseline to 2.0 (IQR;0-8.0) at 72 hours (p = 0.04). The median VIS decreased from 20.0 (IQR;20.0-52.0) at baseline to 7.0 (IQR;3.0-7.0) at 72 hours but no statistically significant in reduction. Similar to VIS, there were no statistically difference in other inflammatory markers such as IL-6, PCT, hs- CRP and lactate levels at 72 hours. Conclusion(s): MIS-C is rare and may have a serious complications especially cardiovascular dysfunction. Early initiated treatment with IVIG and corticosteroid may have a favorable outcome. In the severe MIS-C and refractory disease, using HA330 may be a good option and safe for adjunctive treatment with IVIG and corticosteroid for rapid improvement in organ dysfunction and mortality score in context of rapid reduction of the inflammatory cytokines.

Cytosorb Dialysis: An Adjunct for Survival in the Covid-19 Patient in Cytokine Storm? A Case Series

BACKGROUND: The COVID-19 pandemic has led to the biggest global health crisis of our lifetime. There is accumulating evidence that a substantial number of critically ill COVID-19 patients exhibit a dysregulated host response manifesting as cytokine storm or cytokine release syndrome which in turn contributes to the high observed rates of mortality. Just as in other hyperinflammatory conditions extracorporeal cytokine removal may have potential beneficial effects in this subgroup of COVID-19 patients. The CytoSorb blood purification device is the most extensively investigated cytokine removal platform with considerable evidence suggesting that early intervention can provide rapid hemodynamic stabilization and improvement in vital organ functions AIM OF THE STUDY: Here we describe 4 cases of severely ill adult patients with coronavirus disease 2019 admitted to intensive care unit who were treated with CytoSorb therapy. METHOD(S): All 4 patients were admitted in the ICU with CT severity score of >15/25. During their clinical course, all patients were prescribed tocilizumab (an interleukin-6 receptor blocker) antivirals hydroxychloroquine azithromycin and other antibiotics and general antipyretic drugs. All patients received low-molecular-weight heparin thromboprophylaxis adjusted to baseline weight and renal function Patient A and C required invasive mechanical ventilation whereas Patients B D were on NIV The mean age of the patients was 67.7 years (range = 29-79) Patients received a median of 2 attempts of hemoperfusion. The median CytoSorb perfusion time was 20hrs. RESULT(S): The level of IL-6 significantly decreased after treatments. It reduced by 95% for Patient A, 70% for Patient B, 99% for Patient D Mean Arterial Pressure improved by 15 mmHg average for Patients A, B, D PaO2/FiO2 Ratio improved by 143 average for Patients A, B, D HsCRP levels fell by average of 39 mg/l for patients A, B, D Patient A expired 2 days after the cytosorb dialysis (Refractory Shock) Patient C expired following Dialysis Albumin mildly decreased after CytoSorb. No significant changes were found in red blood cell counts, white cell counts, and platelets. ICU and in-hospital mortality was 50%. CONCLUSION(S): In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and MAP were also observed.

Hämoperfusion und Plasmapherese auf der Intensivstation

In addition to kidney replacement procedures, several other extracorporeal procedures are employed in the intensive care unit. Hemoperfusion with activated charcoal was the predominant treatment used for removal of toxins from the 1970s until the millennium. Nowadays, this treatment does no longer play a clinically meaningful role as even strongly protein-bound toxins can be removed by effective dialysis procedures in case poisoning. The concept of a cytokine adsorber was introduced 10 years ago, which is directed towards withstanding the cytokine storm. Despite negative data from prospective randomized controlled studies, its use is steadily increasing in Germany. A totally different treatment concept is the biomimetic pathogen adsorber, which removes bacteria, viruses and fungi from the bloodstream by binding to immobilized heparin. Whether this rapid reduction of the pathogen load translates into an improvement of clinically relevant endpoints is unclear, as prospective randomized controlled studies are lacking. For the early hours of septic shock a very old procedure, plasmapheresis, has recently regained interest. The results of two large randomized controlled studies in this setting from Europe and Canada will become available in 2025/2026. The rationale to use plasma exchange in early sepsis is that this procedure not only removes cytokines but also replenishes reduced levels of protective factors, such as angiopoietin-1, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) and protein C, if fresh plasma is used as exchange fluid. All afore mentioned procedures do not only have a different mode of action but are also used at seperate time points of bloodstream infections and/or sepsis.

What did we learn about coronavirus disease-19-associated acute kidney injury during the pandemic?

Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.