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.

CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial.

BACKGROUND: Filter clotting is a major issue in continuous kidney replacement therapy (CKRT) that interrupts treatment, reduces delivered effluent dose, and increases cost of care. While a number of variables are involved in filter life, treatment modality is an understudied factor. We hypothesized that filters in pre-filter continuous venovenous hemofiltration (CVVH) would have shorter lifespans than in continuous venovenous hemodialysis (CVVHD). METHODS: This was a single center, pragmatic, unblinded, quasi-randomized cluster trial conducted in critically ill adult patients with severe acute kidney injury (AKI) at the University of Iowa Hospitals and Clinics (UIHC) between March 2020 and December 2020. Patients were quasi-randomized by time block to receive pre-filter CVVH (convection) or CVVHD (diffusion). The primary outcome was filter life, and secondary outcomes were number of filters used, number of filters reaching 72 hours, and in-hospital mortality. RESULTS: In the intention-to-treat analysis, filter life in pre-filter CVVH was 79% of that observed in CVVHD (mean ratio 0.79, 95% CI 0.65-0.97, p = 0.02). Median filter life (with interquartile range) in pre-filter CVVH was 21.8 (11.4-45.3) and was 26.6 (13.0-63.5) for CVVHD. In addition, 11.8% of filters in pre-filter CVVH were active for >72 hours, versus 21.2% in the CVVHD group. Finally, filter clotting accounted for the loss of 26.7% of filters in the CVVH group compared to 17.5% in the CVVHD group. There were no differences in overall numbers of filters used or mortality between groups. CONCLUSIONS: Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04762524. Registered 02/21/21-Retroactively registered, https://clinicaltrials.gov/ct2/show/NCT04762524?cond=The+Impact+of+CRRT+Modality+on+Filter+Life&draw=2&rank=1.

Opportunities, controversies, and challenges of extracorporeal hemoadsorption with CytoSorb during ECMO.

Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research.

Application of extracorporeal carbon dioxide removal combined with continuous blood purification therapy in ARDS with hypercapnia in patients with critical COVID-19.

INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes.

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

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

Early Cytokine Removal in Critical COVID-19 Patients with Extracorporeal Therapies (HA-380 plus High Volume Hemofiltration) May Prevent Progression of Acute Respiratory Distress Syndrome: Case Report.

We present the case of a patient who suffered from acute respiratory distress syndrome caused by pneumonia associated with COVID-19 and cytokine release syndrome. This patient received a high-volume hemofiltration plus adsorption, solving the hemodynamic deterioration, pulmonary infiltrates, and gas exchange. Our clinical case proposes that the extracorporeal therapies can have a role in the management of severe COVID-19.

Clearance of chloroquine and hydroxychloroquine by the Seraph® 100 Microbinda Affinity Blood Filter -a device approved for the treatment of COVID-19 patients.

On April 17 2020, the United States Food and Drug Administration granted Coronavirus Disease 2019 (COVID-19) emergency use authorizations for the Seraph 100 Microbind Affinity Blood Filter. The medical device is aimed to treat critically ill COVID-19 patients with confirmed or imminent respiratory failure. The aim of this life size in vitro pharmacokinetic study was to investigate the in vitro adsorption of chloroquine and hydroxychloroquine from human plasma using equipment that is also used at the bedside. After start of the hemoperfusion, Pre (Cpre ) Seraph plasma levels were obtained at 5 (C5 ), 10 (C10 ), 15 (C15 ), 30 (C30 ), 60 (C60 ), and 120 (C120 ) minutes into the procedure. At two timepoints (5 and 120 minutes) post (Cpost ) Seraph plasma levels were determined that were used to calculate the plasma clearance of the Seraph. Both drugs were determined using a validated HPLC method. Median [IQR] plasma clearance of the Seraph for chloroquine/hydroxychloroquine was 1.71 [0.51-4.38] mL/min/1.79 [0.21-3.68] mL/min respectively. The lack of elimination was also confirmed by the fact that plasma levels did not change over the 120 minutes treatment. As neither chloroquine nor hydroxychloroquine were removed by the treatment with the Seraph dose adjustments in COVID-19 patients undergoing this treatment are not necessary.

[Expert consensus on special blood purification technics in patients with corona virus disease 2019].

The outbreak of corona virus disease 2019 (COVID-19) has spread to more than 70 countries worldwide and there was a higher mortality in those who developed serious illness.Cytokine storm syndrome is an important pathophysiological basis for COVID-19 patients developing into severe or critical conditions. It was indicated in the diagnosis and treatment scheme, by the National Health Commission of the People's Republic of China, that blood purifications such as plasma exchange, plasma adsorption, hemoperfusion, hemofiltration and plasmafiltration could be considered for use in the critical patients with cytokine storm syndrome. This expert consensus, proposed by the Chinese Society of Nephrology and the Nephrology Committee of Chinese Research Hospital Association, is to guide and standardize the clinical application of blood purifications in the treatment of severe or critical patients with COVID-19.

COVID-19 infection in children and adolescents.

The COVID-19 pandemic has predominantly affected the adult population. The disease is less well-defined in children (≤18 years). This review summarises the current understanding of the epidemiology, clinical manifestations, and management of COVID-19 in children and adolescents. The prevalence of COVID-19 is significantly lower in children than adults, but paediatric disease is likely underdiagnosed as a result of the high numbers of asymptomatic or mild cases. Children are vulnerable to family cluster outbreaks, but are unlikely to be index cases within a household. Vertical transmission or breast milk transmission are yet to be proven. Between 10 and 90% of paediatric COVID-19 cases are asymptomatic. Symptomatic cases typically present with mild symptoms, including cough, fever and sore throat. Intensive care admission and mortality are rare. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 is a rare, but severe, newly emerging phenotype. At present, there is no specific treatment for COVID-19 in adults or children; management is usually supportive. For severe or critical disease, including paediatric multisystem inflammatory syndrome temporally associated with COVID-19, the decision to start antiviral or immunomodulatory therapy should be on a case-by-case basis; in the UK, this should be done within a clinical trial. Further research is needed into both the disease course and treatment of paediatric COVID-19.

Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19).

BACKGROUND: Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with coronavirus infection, because of its beneficial impact on elimination of inflammatory cytokines. METHODS: This controlled trial has been conducted on critically ill COVID-19 patients admitted in the state hospital affiliated to Babol University of Medical Sciences, Iran who received different antiviral and antibacterial drugs, and different modalities of respiratory treatments and did not have positive clinical improvement. No randomization and blindness was considered. All of the participants underwent three sessions of resin-directed hemoperfusion using continuous renal replacement therapy with a mode of continuous venovenous hemofiltration (CVVH). RESULTS: Five men and five women with a mean age of 57.30 ± 18.07 years have been enrolled in the study; and six of them have improved after the intervention. Peripheral capillary oxygen saturation (SpO2) changed after each session. Mean SpO2 before the three sessions of hemoperfusion was 89.60% ± 3.94% and increased to 92.13% ± 3.28% after them (p < 0.001). Serum IL-6 showed a reduction from 139.70 ± 105.62 to 72.06 ± 65.87 pg/mL (p = 0.073); and c-reactive protein decreased from 136.25 ± 84.39 to 78.25 ± 38.67 mg/L (P = 0.016). CONCLUSIONS: Extracorporeal hemoadsorption could improve the general condition in most of recruited patients with severe coronavirus disease; however, large prospective multicenter trials in carefully selected patients are needed to definitely evaluate the efficacy of hemoperfusion in COVID-19 patients. TRIAL REGISTRATION: The research protocol has been registered in the website of Iranian Registry of Clinical Trials with the reference number IRCT20150704023055N2 .

Renal replacement therapy in critically ill patients with COVID-19: A retrospective study investigating mortality, renal recovery and filter lifetime.

PURPOSE: This study aims to investigate mortality and renal recovery in patients with Acute Kidney Injury (AKI) and Renal Replacement Therapy (RRT) due to COVID-19. A secondary aim is to investigate the filter life time in Continuous VenoVenous Hemofiltration (CVVH) and the effect of different methods of anticoagulation. METHODS: All patients with COVID-19 infection admitted to the ICU between March 16th 2020 to May 10th 2020 were retrospectively studied. Patients were categorized in a AKI-group and a non-AKI-group. RESULTS: Thirty-seven patients were included. Twenty-two (60%) patients developed AKI. Mortality in the AKI-group was 41% compared to 20% in the non-AKI group, p = 0.275. Comparable mortality was seen in the RRT (39%) and the non-RRT group (44%), p = 1.000. Renal function recovered to a KDIGO-stage 1 in 64% of the patients with AKI when discharged from the ICU. Life time for the CVVH filters (n = 53) was 27 h (14-63)[2-78]. No difference was found with various methods of anticoagulation. CONCLUSION: The need for RRT in critically ill patients with COVID-19 was reversible in our cohort and RRT was not associated with an increased mortality compared to AKI without the need for RRT. Higher levels of anticoagulation were not associated with prolonged filter life.

The Combined Use of Tocilizumab and Hemoadsorption in a Patient with SARS-COV-2-19-Associated Pneumonia: A Case Report.

The SARS-COV-2-19-associated respiratory involvement is caused by the massive release of inflammatory cytokines ultimately leading to interstitial pneumonia and acute respiratory distress syndrome (ARDS). In the absence of an effective antiviral treatment, a reasonable causal approach could be constituted by the neutralization of these substances. The authors describe the clinical course of a patient with SARS-COV-2-19 interstitial pneumonia treated with the combination of an anti-interleukin 6 (IL-6) agent (tocilizumab) and hemoadsorption (HA). This combination was used to abate the surge of inflammatory mediators leading to the lung damage. Blood levels of IL-6 and C-reactive protein (CRP) were measured before the initiation of the treatment and in the following 3 days. At the end of the treatment, the values of IL-6 and CRP decreased from 1,040 to 415 pg/mL and from 229 to 59 mg/L, respectively. The gas exchanges and the chest imaging rapidly improved, and the patient was extubated 10 days later. The combination of tocilizumab and HA could be valuable in the treatment of SARS-COV-2-19-associated pneumonia and ARDS that are caused by the release of inflammatory mediators.

Cytokine Blood Filtration Responses in COVID-19.

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.