The use of CytoSorb in a septic shock patient with ARDS due to Sars Cov-2

Background: Septic shock is a clinical condition of sepsis aggravated by circulatory, cellular and metabolic dysregulation. Diagnostic criteria include the need for vasopressors to maintain a PAM>65 and serum lactate levels>2 under adequate fluid therapy. Early identification of critically septic patients is necessary to allow early and adequate treatment with improved prognosis. In this case report we evaluate the haemodynamic impact of CytoSorb therapy in a case of septic shock in a patient with ARDS Sars cov2. Method(s): Patient with Sars Cov-2 ARDS was admitted to our department. He was intubated and had a SOFA Score 7. On day 15 the patient presented an increase in PCT CRP and WBC levels with the need for norepinephrine infusion. Empirical antibiotic therapy was started and after 24 hours also CytoSorb Therapy. Four CytoSorb cartridge columns were used. The first two were changed every 12 h and then the next two were changed every 24 h. Result(s): Two days after CytoSorb therapy there was an improvement in haemodynamic without the need of vasopressor support. There was also a reduction in inflammatory parameters and lactates. The trend of these values was shown in figure 1. Conclusion(s): In this case report we evaluated the impact of CytoSorb therapy in a case of septic shock in a patient with ARDS Sars Cov-2. The early use of hemadsorption with CytoSorb combined with re-evaluation of antibiotic therapy resulted in a marked improvement in the patient's clinical status.

CytoSorb on the Septic Shock

Background: Septic shock, defined as organ dysfunction caused by a dysregulated host response to infection, is a condition associated with high morbidity and mortality. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators that cause septic shock and multi-organ failure (MOF). New adsorbents are now available as adjuvant therapy aimed at modulating the cytokine "storm" in sepsis. They are thought to be useful if adopted early (within 8-24 hours of the diagnosis of septic shock) in patients who are unresponsive to standard therapy. Here we report our experience with CytoSorb. Method(s): From January 2021 to May 2022, 46 patients with septic shock were treated with continuous renal replacement therapy (CRRT) associated with hemoadsorption with CytoSorb. All cases presented organ failure including AKI. Surgical patients (n = 13) were treated with surgery, COVID patients (n = 15) and medical patients (n = 16) with medical therapy;all surgery cases were operated on before starting the haemadsorption and in some cases reoperation with the need to suspend the adsorption. The mean age was 69 +/- 17 years (SD). On admission the mean SAPSII score was 50 +/- 11 (SD). CRRT as hemodiafiltration (CVVHDF) was performed. All patients received at least one CytoSorb treatment and additional treatments (up to 21 filters in a Covid patient) according to our indication. The CytoSorb cartridge was installed in series to the high cut-off filter;blood flow rates were maintained between 120 and 150 mL/min while dialysis doses from 18 to 45 mL/kg/hour. CytoSorb was renewed every 24 hours. We evaluated the impact of CytoSorb on 30-day survival, haemodynamics and relevant outcomes. Result(s): The 30-day survival was 30%. During treatment with CytoSorb, patients had a hemodynamic stabilization with a significant improvement in MAP, a reduction in amines and a decrease in PCR and PCT (Figure 1). Mortality at 30 days among medical patients was almost comparable to that of COVID patients and higher than that of surgical patients (70%, 69% and 61%, respectively). It should be noted that almost half of the deceased patients arrived late in the hospital, thus leading to a late start of treatment. Conclusion(s): We confirm the efficacy and usefulness of the CytoSorb if adopted early in patients who do not respond to standard therapy. CytoSorb treatment was safe and well tolerated with no device-related adverse events during or after treatment sessions.

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 cytokine hemadsorption in severe COVID-19 respiratory failure

Background: At least 20% of coronavirus disease 2019 (COVID-19) patients develop acute hypoxemic respiratory failure requiring admission to intensive care unit in 5-32% of the cases. Hyper-inflammatory activation characterized by immune cell infiltration and elevated levels of cytokines was reported as the main mechanism leading to critical illness and severe acute respiratory distress syndrome (ARDS). CytoSorb is currently used for all the conditions where elevated levels of cytokines are present. Along with the beneficial effect on systemic inflammation, CytoSorb can be easily integrated with all extracorporeal circulation systems. Case Presentation: Here, we present the laboratory and clinical outcomes of 11 patients with microbiological confirmed SARS-CoV-2 infection. These patients were treated with CytoSorb to remove the excess of cytokine. All patients were male, overweight and only 3 (27%) were over 70 years old. Median age was 62 years and median body mass index was 28. Best supportive care was provided according to hospital guidelines of that moment and included antibiotic therapy, antiretroviral therapy and protective ventilation. Result(s): Cytokines levels were evaluated before and after treatment. A significant reduction of IL-6, IL-8, IL-10 and IL-1beta was observed. A significant drop of C-reactive protein (CRP) median levels was observed starting from 48 hours after treatment start levels. The decrease in the inflammatory status was associated with a progressive improvement in the respiratory function, with a significant increase in P/F from the first day after the end of the therapy. A similar trend was observed for procalcitonin. Conclusion(s): CytoSorb therapy proved to be safe in COVID-19 patients. A clinical improvement was observed in most of the treated patients despite the severity of the disease. In this study CytoSorb was used empirically for 24- 48 hours based on previous experience in septic shock. The persistence of significant levels of IL-6 and CRP after CytoSorb treatment may suggest that a prolonged treatment can improve the efficacy in controlling COVID-19 hyperinflammatory status.

Hemoadsorption by CytoSorb in septic no-Covid and Covid patients: a case series

Background: Septic shock is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The reduction of pro-inflammatory and anti-inflammatory mediators by hemoadsorption represents a new tool in the treatment of sepsis. In the present case series, we evaluated the impact of CytoSorb on adult patients with septic shock. Method(s): Patients with septic shock, admitted to Intensive Care Unit (ICU) from March 1, 2021 to February 28, 2022 who received CytoSorb therapy within 72 hours of admission were enrolled in the study. The severity of clinical conditions at admission was assessed by the SAPS II and SOFA scores;The magnitude of the inflammatory response was estimated using the plasmatic levels of C reactive protein (CRP) and interleukin-6 (IL-6). The effect of CytoSorb therapy on the inflammatory state, was evaluated measuring the percentage reduction of IL-6 and CRP. Time elapsed from ICU admission and the start of CytoSorb therapy was also assessed. T-test was used to compare the means of the groups of Survivors and No survivors. Fisher's test was used to evaluated the difference in mortality between Covid and No covid patients. Result(s): Twelve patients were evaluated. Six patients tested positive for covid-19, while the other six did not. Table 1 shows the values of age, SAPSII, SOFA, IL-6, CRP, PCT and timing between the survivors and the no survivors. Overall, there was no significant difference between the two groups in terms of SAPSII, SOFA, age, CRP. There was a significant difference in the timing of Cytosorb start and percentage of IL-6 removal: In surviving patients the timing of intervention was shorter (3,3+/-1,8 vs 23,5+/-18,9 hours) than in non- survivors. The IL-6 removal rate was significantly higher in the survivor group (70,8+/-15,87 vs 33,2+/-12,26). Conclusion(s): In survivors the timing of CytoSorb therapy was shorter and the IL-6 removal rate was higher than in non-survivors. This suggest that the early applying of CytoSorb adsorber in combination with Continuous Renal Replacement Therapy (CRRT) techniques, could increase the survival rate of septic shock patients. Using CytoSorb was safe and well tolerated with no device-related adverse events during or after the treatment.

COMPARATIVE EFFECTS OF TOCILIZUMAB AND CYTOSORB ON BLOOD CYTOKIENE LEVELS IN PATIENTS WITH SARS-CoV-2 PNEUMONIA

Background/aims: SARS-CoV-2 is responsible of respiratory failure and also causes a massive release of inflammatory mediators such as IL-6, IL-1, CRP etc. This hyperinflammatory condition, often indicated as Cytokine Release Syndrome (CRS), could led to life-threatening events. The clinical course resembles septic shock and the elevated values of inflammatory mediators are associated with a higher viral load and reduced survival. The use of techniques aiming to contrast the surge of inflammatory mediators has been advocated in the treatment of this condition. Method(s): Four patients were retrospectively admitted in Intensive Care Unit with respiratory failure caused by SARS-CoV-2 infection. Two patients were treated with Tocilizumab (TCZ) alone, the others received TCZ in association with hemoadsorption (HA) treatment. The HA procedure was performed with CytoSorb responsible of removing hydrophobic molecules with a molecular weight of up to approximately 60 kDa including cytokines and other inflammatory mediators involved in CRS. Each procedure lasts 24 hours. Blood values of IL-6, C-reactive protein (CRP) and other biochemical variables were measured in two patients who received Tocilizumab (TCZ) alone and in other two in whom it was associated with hemoadsorption (TCZ- HA). All variables were measured before, during and after the treatment. The aim of the study is to assess the variations of IL-6 in patients with SARS-CoV-2 infection treated with TCZ alone or in association with hemoadsorption (HA). Result(s): All patients full-filled the criteria of severe SARS-CoV-2 infection. In all patients the administration of TCZ was followed by an increasing in IL-6 values. Its values remained elevated in patients given TCZ but sharply decreased in the following days in those treated also with HA. The percentage variations of IL-6 from the baseline between the two groups was +344% and +89% in the two patients treated with TCZ alone and - 56% and -15% in TCZ-HA group. Both TCZ and TCZ-HA were well tolerated. Conclusion(s): The increase of the IL-6 can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ- HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators. More experience is needed to identify the best candidate for TCZ or TCZ-HA.

ECMO for the immunocompromised pediatric patient: Our experience

Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.

A systematic review of the use of CytoSorb© Hemoadsorption in patients undergoing veno-venous ECMO support for severe acute respiratory distress syndrome

Objectives: Acute respiratory distress syndrome (ARDS) often results in high mortality and morbidity. Hemoadsorption therapy, such as CytoSorb©, is being increasingly used to target the underlying hyperinflammation that occurs with ARDS. This review aims to evaluate the available data on the use of CytoSorb in combination with veno-venous extracorporeal membrane oxygenation (V-V ECMO) in severe ARDS cases, and to assess its effects on inflammatory, laboratory, and clinical parameters, as well as on patient outcomes. Method(s): A systematic literature review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement. Whenever possible, an analysis of changes in relevant biomarkers and clinical parameters was performed. Result(s): CytoSorb© therapy was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively), as well as an increase in PaO2/FiO2 levels (p = 0.028). There was also a trend towards reduced norepinephrine dosage (p = 0.067). Mortality rates in patients treated with CytoSorb©tended to be lower than in the control groups, but these studies had high heterogeneity and low power. In an exploratory analysis of 90-day mortality in COVID19 patients receiving V-V ECMO, the therapy was associated with a reduced risk of death. Conclusion(s): Overall, the reviewed data suggests that CytoSorb© therapy can effectively reduce inflammation and potentially improve survival in ARDS patients treated with V-V ECMO. Therefore, early initiation of CytoSorb ©in conjunction with ECMO may offer a promising approach to enhance lung rest and promote recovery in patients with severe ARDS. A randomised trial is warranted to confirm our findings.

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.

CytoSorb in patients with coronavirus disease 2019: A rapid evidence review and meta-analysis.

Background: After its approval by the European Union in 2011, CytoSorb therapy has been applied to control cytokine storm and lower the increased levels of cytokines and other inflammatory mediators in blood. However, the efficiency of this CytoSorb treatment in patients with coronavirus disease (COVID-19) still remains unclear. To elucidate the Cytosorb efficiency, we conducted a systematic review and single-arm proportion meta-analysis to combine all evidence available in the published literature to date, so that this comprehensive knowledge can guide clinical decision-making and future research. Methods: The literature published within the period 1 December 2019 to 31 December 2021 and stored in the Cochrane Library, Embase, PubMed, and International Clinical Trials Registry Platform (ICTRP) was searched for all relevant studies including the cases where COVID-19 patients were treated with CytoSorb. We performed random-effects meta-analyses by R software (3.6.1) and used the Joanna Briggs Institute checklist to assess the risk of bias. Both categorical and continuous variables were presented with 95% confidence intervals (CIs) as pooled proportions for categorical variables and pooled means for continuous outcomes. Results: We included 14 studies with 241 COVID-19 patients treated with CytoSorb hemadsorption. Our findings reveal that for COVID-19 patients receiving CytoSorb treatment, the combined in-hospital mortality was 42.1% (95% CI 29.5-54.6%, I2 = 74%). The pooled incidence of adjunctive extracorporeal membrane oxygenation (ECMO) support was 73.2%. Both the C-reactive protein (CRP) and interleukin-6 (IL-6) levels decreased after CytoSorb treatment. The pooled mean of the CRP level decreased from 147.55 (95% CI 91.14-203.96) to 92.36 mg/L (95% CI 46.74-137.98), while that of IL-6 decreased from 339.49 (95% CI 164.35-514.63) to 168.83 pg/mL (95% CI 82.22-255.45). Conclusions: The majority of the COVID-19 patients treated with CytoSorb received ECMO support. In-hospital mortality was 42.1% for the COVID-19 patients who had CytoSorb treatment. Both CRP and IL-6 levels decreased after Cytosorb treatment.

Effects of cytokine hemadsorption as salvage therapy on common laboratory parameters in patients with life-threatening COVID-19.

BACKGROUND: The COVID-19 pandemic has led to emergency approval of treatment modalities unusual for viruses, such as therapeutic cytokine Hemadsorption(HA). This study aims to investigate the experience of salvage HA therapy and the effect of HA on routine laboratory tests. METHODS: Life-threatening COVID-19 patients followed up between April 2020 and October 2022 who underwent HA salvage therapy were retrospectively enrolled. Data derived from the medical records were evaluated to meet the assumptions of statistical tests, and those that met the relevant statistical rules were selected for further analysis. Tests of Wilcoxon, Paired-T, and repeated measures-ANOVA were used to analyse the laboratory tests performed before and after HA among the surviving and nonsurviving patients. P < 0.05 was selected for the statistical significance of the alpha. RESULTS: A total of 55 patients were enrolled in the study. Fibrinogen (p = 0.007), lactate dehydrogenase (LDH) (p = 0.021), C-reactive protein (CRP) (p < 0.0001), and platelet (PLT) (p = 0.046) levels showed a significant decrease with the HA effect. WBC (p = 0.209), lymphocyte (p = 0.135), procalcitonin (PCT) (p = 0.424), ferritin (p = 0.298), and D-dimer (p = 0.391) levels were not affected by HA. Ferritin level was significantly affected by survival status (p = 0.010). All patients tolerated HA well, and 16.4 % (n = 9) of the patients with life-threatening COVID-19 survived. CONCLUSION: HA is well tolerated even when used as a last option. However, HA may not affect WBC, lymphocyte, and D-dimer levels. In contrast, the effect of HA could limit the benefits of LDH, CRP, and fibrinogen in various clinical assessments. This study suggests that HA treatment could be beneficial even if selected as a salvage therapy.

Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial.

INTRODUCTION: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. METHODS: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18-24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). RESULTS: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948-3,679) and 3,747 (1,301-5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. CONCLUSION: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

Update on the treatment of multisystem inflammatory syndrome in children associated with COVID-19.

In late 2019, SARS-CoV-2 was detected in China and spread worldwide. In rare cases, children who were infected with COVID-19 may develop multisystem inflammatory syndrome (MIS-C), which could have higher mortality than COVID-19 itself. Therefore, diagnosis and management are critical for treatment. Specifically, most of the initial treatment options of MIS-C choose intravenous immunoglobulin (IVIG) and steroids as the first-line treatment for patients. Moreover, antagonists of some cytokines are used as potential future therapeutics. Of note, therapeutic plasmapheresis can be used as a treatment for refractory severe MIS-C. We believe that each patient, especially those with comorbid conditions, should have individualized treatment based on both multidisciplinary consensus approach and expert opinion.

Treating Complications of Extracorporeal Life Support in a Patient with COVID-19 (Case Report)

We present a case of mechanical hemolysis as a complication of extracorporeal membrane oxygenation (ECMO) occurring in a COVID-19 patient as a result of pump head thrombosis. After emergency extracor-poreal circuit replacement, hemoadsorption was initiated to address the negative hemolysis effects and plasma free hemoglobin rise in the setting of rapid clinical deterioration and impaired renal function. During therapy hemolysis severity reduced, the lactate dehydrogenase (LDH) levels decreased, while the P/F ratio increased two-fold. The patient was discharged from hospital on day 54 without the need for ei-ther oxygen therapy or dialysis. In the discussion section we addressed frequent issues of choosing therapy for ECMO complications. Conclusion. The timely, properly chosen, and clinically relevant use of hemoadsorption combined with advanced high-technology therapeutic procedures can have a positive impact on the patient's outcome. Copyright © 2022, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Clinical Profile and Outcomes of Coronavirus Disease 19 (COVID-19) Patients who Underwent Hemoperfusion (HP) in a Tertiary COVID-19 Referral Hospital: A Descriptive Study

Introduction. As of February 4, 2021, a total of 530,118 COVID-19 cases were recorded in the Philippines with a fatality rate of 2.1%. Significant morbidity from COVID-19 is caused by hyperinflammation. Hemoperfusion (HP), which adsorbs inflammatory cytokines, has been performed in the Philippine General Hospital (PGH) as an adjunct to management given to COVID-19 patients. Objectives. This study aimed to describe the clinical and laboratory profile, ventilatory support, therapeutic regimens, and outcomes of COVID-19 patients who underwent hemoperfusion in PGH. Methods. The COVID-19 patient electronic database (April to September 2020) of the Division of Nephrology was reviewed and we included patients with COVID-19 who underwent hemoperfusion. Demographic, clinical, and laboratory data as well as therapeutics and outcomes were described. Results. Sixty-six patients with COVID-19 underwent hemoperfusion. The majority were male (59.1%) with an average age of 61.3 years (SD 15). Hypertension was the most common comorbidity (62.1%). Acute kidney injury (AKI) requiring dialysis comprised 28.8% while 33.3% had diagnosed chronic kidney disease (CKD). The majority were critical COVID-19 cases who had acute respiratory distress syndrome (ARDS) (56.1%). The mean baseline inflammatory marker levels (Il-6, CRP, LDH, ferritin) were elevated. Post-HP inflammatory markers decreased except for IL-6 among patients who died. Most patients were mechanically ventilated (54.5%). Steroids were the most common medications administered (71.2%). Mortality occurred in 62.1% of the patients. The average length of hospital stay was 20.8 days (SD 19.5), duration from admission to first HP 5.9 days (SD 5.8), and 15.3 days (SD 17.4) from first HP to death or discharge. Conclusion. Our study showed the characteristics of patients with COVID-19 who underwent HP. Majority were hypertensive men in their early 60s with critical COVID-19 disease. The mean inflammatory markers were elevated with a decrease in most markers post-hemoperfusion (except for IL-6 among those who died). Despite this, mortality was still high and the average length of hospital stay was long. © 2022 University of the Philippines Manila. All rights reserved.

Efficacy of a Recombinant Humanized Anti-IL-6 Receptor Monoclonal Antibody Compared to Hemoperfusion in Severe COVID-19 Pneumonia: Ambispective Cohort Study

Background: Coronavirus disease 2019 (COVID-19) is a newly emerging disease caused by the SARS-CoV-2 virus resulting in a global crisis. Activation of the cytokine cascades plays a crucial role in the pathophysiology of severe pneumonia caused by COVID-19. Several treatments targeting pro-inflammatory cytokines have been introduced, however, their efficacy remains controversial. We aimed to demonstrate the comparative efficacy between hemoperfusion and tocilizumab in the reduction of mortality from severe COVID-19 pneumonia. Method(s): A multicentered, ambispective study was conducted on adult patients who were diagnosed with COVID-19 pneumonia between January 1st, 2020, and December 31th, 2021. Clinical parameters including the specific therapy with hemoperfusion (Hemoadsorption cartridge, HA330 JACFRON) or tocilizumab were collected for analysis. Univariable and multivariable regression analyses were performed to determine the association between the specific therapy and the 28-day mortality. Result(s): A total of 92 patients with COVID-19 pneumonia were eligible for analyses (25 patients received hemoperfusion and 67 patients received tocilizumab). The 28-day mortality in the hemoperfusion and tocilizumab groups were 64.0% and 25.4% respectively (p=0.001). However, receiving Tocilizumab was not associated with mortality rate, compared to hemoperfusion in the multivariable analysis [OR 0.56 (95%CI 0.13 -2.39);p=0.428]. Receiving invasive mechanical ventilator (%), duration of hospitalization, and successful withdrawal of invasive mechanical ventilation was not different between the two groups. Inflammatory marker (CRP) was significantly reduced with hemoperfusion and tocilizumab -46.2 (-88.37, -24.9) (p=0.013) and -45.1 (-54.6, -26.15) (p=<0.001). Conclusion(s): The 28-day mortality of COVID-19 pneumonia patients receiving hemoperfusion and tocilizumab were comparable.

Early initiation of hemoadsorption reduces the need for organ support in critically ill COVID-19 patients on ECMO: A post-hoc analysis from the CytoSorb Therapy in COVID-19 (CTC) Registry

Objectives: Preliminary results of the CTC Registry on the first 52 patients showed survival of 69% at 90 days [1]. The current exploratory analysis aimed to examine whether the time of initiation of hemoadsorption (i.e.: early vs late) had any effect organ support requirements and survival. Method(s): We included all 100 patients recruited in the CTC Registry in 5 U.S. intensive care units (ICU). The median time from ICU admission to the start of hemoadsorption was 86.7 h. We created two post hoc groups: <=86.7 h (group-early, GE) and >86.7 h (group-late, GL) and compared outcomes with special focus on the need of mechanical ventilation (MV), vasopressor, renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). Result(s): There was no difference between groups in baseline characteristics. 90-day survival was 78% in GE and 62% in GL (p=0.08). Patients in the GL vs GE spent longer time on ECMO (p=0.021), mechanical ventilation (p=0.02) and needed significantly longer ICU-stay (p=0.002), (Fig. 1). There was also a trend for longer vasopressor support (8 [4-21] vs 4 [1-17] days, p=0.13). There was no significant difference between the groups regarding the need of CRRT. Conclusion(s): The current analysis shows that early initiation of hemoadsorption with ECMO in critically ill COVID-19 patients is associated with shorter duration of organ support measures and shorter ICU stays.

Relationship of lung oxygenation to timing of hemoadsorption therapy initiation in COVID-19 patients requiring extracorporeal mechanical oxygenation (ECMO): an observational analysis from the CytoSorb therapy in COVID-19 (CTC) Registry

Introduction: The multicenter CTC Registry study collected patientlevel data in COVID-19 patients receiving CytoSorb therapy under FDA Emergency Use Authorization. An earlier report on the first 52 CTC patients on ECMO treated with CytoSorb showed 69% overall survival [1]. The current analysis focuses on changes in pulmonary function relative to the time of CytoSorb therapy. Methods: A total of 56 patients from 5 U.S. centers were included. Data on demographics, mechanical ventilation (MV), ECMO, and arterial blood gases during CytoSorb therapy were analyzed. Linear regression was used to evaluate the relationship between the timing of initiation of CytoSorb therapy to lung oxygenation according to changes in PaO2/FiO2 ratio. Results: In the current analysis, 71% (40/56) overall survival was observed. For these survivors, time to CytoSorb start after ICU admission, MV start, and ECMO start was 138 ± 171.3 h, 83 ± 111.0 h, and 55 ± 156.5 h, respectively, with mean duration of CytoSorb therapy of 83 ± 29.1 h. At the first 24 h following CytoSorb therapy, oxygenation was improved evidenced by decreased MV FiO2 and ECMO FdO2 requirements and an increased PaO2/FiO2 ratio (90.2 ± 58.13 mmHg to 166.3 ± 98.67 mmHg, p < 0.001, N = 21). Linear regression analysis suggested that earlier initiation of CytoSorb therapy following ICU admission may be correlated to greater improvements in PaO2/FiO2 ratio (r = -0.37, p = 0.103), however, this trend did not achieve statistical significance. Conclusions: High survival rates have been observed with adjunct CytoSorb therapy in critically ill COVID-19 patients on ECMO. The current analysis suggests that early initiation of hemoadsorption following ICU admission may contribute to earlier improvements in native lung oxygenation.

Kinetics of Bilirubin and Ammonia Elimination during Hemadsorption Therapy in Secondary Sclerosing Cholangitis Following ECMO Therapy and Severe COVID-19.

In critically ill patients, liver dysfunction often results in coagulopathy and encephalopathy and is associated with high mortality. Extracorporeal clearance of hepatotoxic metabolites, including bilirubin and ammonia, aims to attenuate further hepatocyte damage and liver injury, resulting in decreased mortality. The efficacy of hemadsorption combined with conventional hemodialysis to eliminate bilirubin and ammonia to support the liver's excretory function in acute liver injury has been described previously. However, the optimal use of liver support systems in chronic liver dysfunction due to secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has not been defined yet. We herein describe the kinetics of successful bilirubin and ammonia elimination by hemadsorption in a patient with SSC-CIP after extracorporeal membrane oxygenation (ECMO) therapy for severe acute respiratory distress syndrome (ARDS) in a patient with coronavirus disease 2019 (COVID-19). During the course of the disease, the patient developed laboratory signs of liver injury during ECMO therapy before clinically detectable jaundice or elevated bilirubin levels. A diagnosis of SSC-CIP was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) based on intraductal filling defects in the intrahepatic bile ducts due to biliary casts. The patient showed stable elevations of bilirubin and ammonia levels thereafter, but presented with progressive nausea, vomiting, weakness, and exhaustion. Based on these laboratory findings, hemadsorption was combined with hemodialysis treatment and successfully eliminated bilirubin and ammonia. Moreover, direct comparison revealed that ammonia is more efficiently eliminated by hemadsorption than bilirubin levels. Clinical symptoms of nausea, vomiting, weakness, and exhaustion improved. In summary, bilirubin and ammonia were successfully eliminated by hemadsorption combined with hemodialysis treatment in SSC-CIP following ECMO therapy and severe COVID-19. This observation is particularly relevant since it has been reported that a considerable subset of critically ill patients with COVID-19 suffer from liver dysfunction associated with high mortality.