Extracorporeal Blood Purification Therapies Research Articles

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study

BackgroundSeptic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy.MethodsThe EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes.ConclusionsThe EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Prevalence of extracorporeal blood purification techniques in critically ill patients before and during the COVID-19 pandemic in Egypt.

Extracorporeal blood-purification techniques are frequently needed in the pediatric intensive care unit (PICU), yet data on their clinical application are lacking. This study aims to review the indications, rate of application, clinical characteristics, complications, and outcomes of patients undergoing extracorporeal blood purification (i.e., by continuous renal replacement therapy [CRRT] or therapeutic plasma exchange [TPE]) in our PICU, including before the coronavirus disease 2019 (COVID-19) pandemic in 2019 and during the pandemic from 2020 to 2022. This study included children admitted for extracorporeal blood-purification therapy in the PICU. The indications for TPE were analyzed and compared to the American Society for Apheresis categories. In 82 children, 380 TPE sessions and 37 CRRT sessions were carried out children, with 65 patients (79%) receiving TPE, 17 (20.7%) receiving CRRT, and four (4.8%) receiving both therapies. The most common indications for TPE were neurological diseases (39/82, 47.5%), followed by hematological diseases (18/82, 21.9%). CRRT was mainly performed for patients suffering from acute kidney injury. Patients with neurological diseases received the greatest number of TPE sessions (295, 77.6%). Also, the year 2022 contained the greatest number of patients receiving extracorporeal blood-purification therapy (either CRRT or TPE). The use of extracorporeal blood-purification techniques increased from 2019 through 2022 due to mainly autoimmune dysregulation among affected patients. TPE can be safely used in an experienced PICU. No serious adverse events were observed in the patients that received TPE, and overall survival over the 4 years was 86.5%.

The clinical efficacy and suitable implementation of two extracorporeal blood purification therapies: AN69-oXiris versus PMX-HP.

In septic shock patients, pathogens and excessive endotoxins continuously overstimulate the host's immune system with a cytokine storm that can lead to multi-organ failure and even mortality. Various types of extracorporeal blood purification treatments have recently been introduced to remove excessive endotoxins and cytokines. Herein, we compared the clinical efficacy of two blood purification methods, PMX-HP and AN69-oXiris, and discussed their detailed indications according to disease severity. From December 2016 to April 2023, patients who underwent emergent surgery due to septic shock secondary to peritonitis and subsequently received blood purification treatment with AN69-oXiris or PMX-HP were enrolled. Propensity score (PS)-matching was conducted to adjust for baseline characteristics between the two groups, and the changes in clinical parameters and outcomes were compared. Clinical outcomes were assessed in subgroups of patients who underwent PMX-HP treatment divided according to SOFA scores into low (0-7), intermediate (8-13), and high (> 13) disease severity groups. Forty patients received blood purification therapy with either PMX-HP or AN69-oXiris during the study period. After 1:2 PS matching, six patients in the AN69-oXiris group and 12 patients in the PMX-HP group were finally analyzed. Vasoactive-inotropic scores (VISs) decreased in both groups after 48 h of treatment compared to the baseline values, but the change in VISs was more pronounced in the PMX-HP group {-57.6 [interquartile range (IQR) = -166.4 - (-10)] vs. -22.9 [IQR = -64-0], respectively, p = 0.041}. Decreases in cardiovascular SOFA scores were significantly pronounced in the PMX-HP group [-1.5 (IQR = -4 - 0) vs. 0 (IQR = -1 - 1), respectively, p = 0.035]. The 7-day mortality rate was significantly lower than the predicted mortality rate in a subgroup analysis of patients treated with PMX-HP in both the low disease severity group and the intermediate disease severity group. PMX-HP and AN69-oXiris could be therapeutic options for refractory septic shock patients with intra-abdominal origins, especially after the surgical elimination of the infectious sources. A tailored modality choice that takes into account patient characteristics, such as disease severity and cost burden, could optimize the efficacy of this strategy.

Clinical effects of occupational clonidine poisoning and efficacy of extracorporeal blood purification therapies

Clinical effects of occupational clonidine poisoning and efficacy of extracorporeal blood purification therapies

Sorbent functionalization with vancomycin enhances bacteria killing in extracorporeal hemoadsorption.

The level of bacteremia in patients with sepsis and septic shock is a predictor of complications and mortality, regardless of the type of bacteria. Devices for bacteria, endotoxin and cytokines removal by adsorption have been recently developed. Thus, extracorporeal blood purification therapies have been proposed as adjunctive therapy in sepsis in combination with drugs. Some potentially useful drugs, however, are precluded due to their organ or metabolic toxicity. The present study represents a preliminary report on the invitro effect of a sorbent device (minimodule with HA380 beads, Jafron medical, Zhuhai, China) in which the particles have been functionalized with vancomycin on the surface. The impact of the surface-modified beads on circulating bacteria (Staphylococcus aureus) has been tested in a simulated invitro circulation. In vitro experiments were carried out with 800 mL of blood enriched with S. aureus species. Blood was circulated in the vancomycin-functionalized and non-functionalized mini-module cartridges in hemoadsorption setup (300 mL each) and the bactericidal effect was assessed. Also, 200 mL of blood was used as a control. A significant increase in the time to positivity of blood cultures was observed after 60 min and also after 120 min of therapy with the mini-module functionalized with vancomycin as opposed to the non-functionalized cartridge. These results suggest a possible way of treating sepsis by using drug- or antibiotic-functionalized cartridges without worrying about pharmacological toxicity. The prolongation of the time to bacterial culture positivity to S. aureus after a passage through a column packed with beads functionalized with vancomycin represents a proof of concept.

Adjunctive Hemoadsorption Therapy with CytoSorb in Patients with Septic/Vasoplegic Shock: A Best Practice Consensus Statement

A dysregulated host response is a common feature in critically ill patients due to both infectious and non-infectious origins that can lead to life-threatening organ dysfunction, which is still the primary cause of death in intensive care units worldwide. In its course, pathologic, unregulated levels of inflammatory mediators are often released into the circulation, a phenomenon also referred to as a “cytokine storm”. To date, there are no approved therapies to modulate the excessive immune response and limit hyperinflammation with the goal of preventing related organ failure and death. In this context, extracorporeal blood purification therapies aiming at the alteration of the host inflammatory response through broad-spectrum, non-selective removal of inflammatory mediators have come into focus. A novel hemoadsorption device (CytoSorb®, CytoSorbents Inc., Princeton, NJ, USA) has shown promising results in patients with hyperinflammation from various origins. Although a significant body of literature exists, there is ongoing research to address many important remaining questions, including the optimal selection of patient groups who might benefit the most, optimal timing for therapy initiation, optimal schedule for adsorber exchanges and therapy duration, as well as an investigation into the potential removal of concomitant antibiotics and other medications. In this review, we discuss the existing evidence and provide a consensus-based best practice guidance for CytoSorb® hemoadsorption therapy in patients with vasoplegic shock.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field.Graphical abstract

Impact of Extra-Corporeal Membrane Oxygenation and Blood Purification Therapy on Early Mobilization in the Intensive Care Unit: Retrospective Cohort Study

Objective: To investigate the effect on early mobilization in patients undergoing extra-corporeal membrane oxygenation (ECMO) and acute blood purification therapy in the intensive care unit (ICU).Methods: We conducted this multicenter retrospective cohort study by collecting data from six ICUs in Japan. Consecutive patients who were admitted to the ICU, aged ≥18 years, and received mechanical ventilation for >48 hours were eligible. The analyzed were divided into two groups: ECMO/blood purification or control group. Clinical outcomes; time to first mobilization, number of total ICU rehabilitations, mean and highest ICU mobility scale (IMS); and daily barrier changes were also investigated.Results: A total of 204 patients were included in the analysis, 43 in the ECMO/blood purification group and 161 in the control group. In comparison of clinical outcome, the ECMO/blood purification group had a significantly longer time to first mobilization: ECMO/blood purification group 6 vs. control group 4 (p=0.003), higher number of total ICU rehabilitations: 6 vs. 5 (p=0.042), lower mean: 0 vs. 1 (p=0.043) and highest IMS: 2 vs. 3 (p=0.039) during ICU stay. Circulatory factor were most frequently described as barriers to early mobilization on days 1 (51%), 2 (47%), and 3 (26%). On days 4 to 7, the most frequently described barrier was consciousness factors (21%, 16%, 19%, and 21%, respectively)Conclusion: The results of this study comparing the ECMO/blood purification group and the untreated group in the ICU showed that the ECMO/blood purification group had significantly longer days to mobilization and significantly lower mean and highest IMS.

Comparison of outcomes and costs of extracorporeal blood purification therapies in critically ill COVID-19 patients.

Plasmapheresis and hemoperfusion are used against cytokine release syndrome in COVID-19. This study aims to compare their outcomes, costs, and side-effects. Survival, costs and side-effects were compared in intensive care unit (ICU) patients receiving plasmapheresis (n= 49), hemoperfusion (n= 20), or none (n= 107), followed until death or discharge. Plasmapheresis survival time was higher than hemoperfusion or controls (HR=0.764, p= 0.397 and HR=0.483, p= 0.002, respectively), although the latter diminished after controlling for age and disease severity (p= 0.979). There was no significant difference in ICU costs for plasmapheresis and hemoperfusion (p= 0.738) while both costed more than controls (both p< 0.001). Hypocalcemia and thrombocytopenia incidence did not differ between two groups (p= 0.124 and p=0.389, respectively) while being higher than controls in plasmapheresis (both p< 0.001) and hemoperfusion (p< 0.001 and p= 0.056, respectively). Plasmapheresis and hemoperfusion do not differ significantly in patient survival, ICU costs and side-effects with a higher incidence of hypocalcemia and thrombocytopenia compared witcontrols.

Successful Extracorporeal Blood Purification Therapy using Double Haemoadsorption Device in Severe Endotoxin Septic Shock: A Case Report.

In patients admitted to the Intensive Care Unit (ICU), sepsis can lead to acute kidney injury (AKI), which may require the initiation of continuous renal replacement therapy (CRRT) in 15-20% of cases. There is no consensus about the best extracorporeal treatment to choose in septic patients with AKI. We describe the case of a 70-year-old woman admitted to the ICU with a severe endotoxin septic shock due to Neisseria meningitidis serogroup C. Despite prompt medical intervention, including fluid resuscitation, high dose vasopressor, inotrope support, and broad-spectrum antimicrobial treatment, in a few hours patient's haemodynamic worsened and she developed multi-organ failure, including severe AKI, requiring CRRT. So, continuous veno-venous haemodiafiltration was started, using an oXiris® haemodiafilter set, in series with an adsorber device (CytoSorb®). After 48 hours of this combined extracorporeal treatment, haemodynamic parameters improved, allowing a significant reduction of the vasoactive therapy, with a concomitant decrease in endotoxin and inflammatory markers serum levels. In the following days patient's conditions still improved and renal function recovered. Timely extracorporeal blood purification therapy, using a double haemoadsorption device, may be effective in the management of severe septic shock.

Comparative Effectiveness of Combined IgM-Enriched Immunoglobulin and Extracorporeal Blood Purification Plus Standard Care Versus Standard Care for Sepsis and Septic Shock after Cardiac Surgery

Background: The combination of surgery, bacterial spread-out, and artificial cardiopulmonary bypass surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyper-inflammatory condition frequently associated with compromised hemodynamics and organ dysfunction. A promising approach could be extracorporeal blood purification therapies in combination with IgM enriched immunoglobulin. This approach might perform a balanced control of both hyper and hypo-inflammatory phases as an immune-modulating intervention. Methods: We performed a retrospective observational study of patients with proven infection after cardiac surgery between January 2020 and December 2021. Patients were divided into two groups: (1) the first group (Control Group) followed a standard care approach as recommended by the Surviving Sepsis Campaign Guidelines; The second group (Active Group) underwent extracorporeal blood purification therapy (EBPT) in combination with intravenous administration of IgM enriched immunoglobulin 5 mL/kg die for at least three consecutive days, in conjunction with the standard approach (SSC Guidelines). In addition, ventriculo-arterial (V/A) coupling, Interleukin 6 (IL-6), Endotoxin Activity Assay (EAA), Procalcitonin, White Blood Cells (WBC) counts, Sequential Organ Failure Assessment (SOFA) Score and Inotropic Score were assessed in both two groups at different time points. Results: Fifty-four patients were recruited; 25 were in the Control Group, while 29 participants were in the Active Group. SOFA score significantly improved from baseline [12 (9–16)] until at T3 [8 (3–13)] in the active group; it was associated with a median EAA reduction from 1.03 (0.39–1.20) at T0 to 0.41 (0.2–0.9) at T3 in the active group compared with control group 0.70 (0.50–1.00) at T0 to 0.70 (0.50–1.00) at T3 (p &lt; 0.001). V/A coupling tended to be lower in patients of the active arm ranging from 1.9 (1.2–2.7) at T0 to 0.8 (0.8–2.2) at T3 than in those of the control arm ranging from 2.1 (1.4–2.2) at T0 to 1.75 (1.45–2.1) at T3 (p = 0.099). The hemodynamic improvement over time was associated with evident but no significant decrease in inotropic score in the active group compared with the control group. Changes in EAA value from T0 to T4 were directly and significantly related (r = 0.39, p = 0.006) to those of V/A coupling. Conclusions: EBPT, in combination with IgM enriched immunoglobulin, was associated with a mitigated postoperative response of key cytokines with a significant decrease in IL-6, Procalcitonin, and EAA and was associated with improvement of clinical and metabolic parameters.

Continuous Renal Replacement Therapy in Critically Ill Children.

Continuous renal replacement therapy is an extracorporeal blood purification therapy that aims to support kidney and other organ functions over an extended period. The high-quality continuous renal replacement therapy requires understanding basic mechanisms of clearance, factors influencing these processes, and the appropriate selection of treatment candidates. This article reviews the different aspects of continuous renal replacement therapy in critically ill pediatric patients.

The Supporting Role of Combined and Sequential Extracorporeal Blood Purification Therapies in COVID-19 Patients in Intensive Care Unit.

Critical clinical forms of COVID-19 infection often include Acute Kidney Injury (AKI), requiring kidney replacement therapy (KRT) in up to 20% of patients, further worsening the outcome of the disease. No specific medical therapies are available for the treatment of COVID-19, while supportive care remains the standard treatment with the control of systemic inflammation playing a pivotal role, avoiding the disease progression and improving organ function. Extracorporeal blood purification (EBP) has been proposed for cytokines removal in sepsis and could be beneficial in COVID-19, preventing the cytokines release syndrome (CRS) and providing Extra-corporeal organ support (ECOS) in critical patients. Different EBP procedures for COVID-19 patients have been proposed including hemoperfusion (HP) on sorbent, continuous kidney replacement therapy (CRRT) with adsorbing capacity, or the use of high cut-off (HCO) membranes. Depending on the local experience, the multidisciplinary capabilities, the hardware, and the available devices, EBP can be combined sequentially or in parallel. The purpose of this paper is to illustrate how to perform EBPs, providing practical support to extracorporeal therapies in COVID-19 patients with AKI.

MO353: Extracorporeal Blood Purification of Complications After Aortic Valve Replacement. Surgical Aortic Valve Replacement Compared With Transcatheter Aortic Valve Replacement

Abstract BACKGROUND AND AIMS Complications after cardiac surgery have serious negative consequences, prolonging the average ICU stay days and costs. Prevention and treatment of complications after aortic valve replacement is a serious problem. According to numerous authors, the incidence of complications after aortic valve replacement varies from 10 to &amp;gt;60% of cases. Development of complications is associated with a higher hospital mortality rate, the risk of infection and a more complex course of the disease. Advances in cardiac surgery have led to a reduction in the overall mortality associated with open-heart surgery; however, it can still exceed 40% among those patients who develop a postoperative complication and can reach 50% in patients requiring extracorporeal blood purification therapy. Impaired renal function or active infectious process has significant prognostic consequences, which are the cause of up to 40% of deaths. The aim of this work is to structure or compare complications in immediate postoperative period after aortic valve replacement by the surgical and transcatheter method. METHOD Retrospective analysis of 267 medical records. All patients in study were after aortic valve replacement, hospitalized in JSC NSCC Nur-Sultan, Kazakhstan, from 1 January 2020 to 31 October 2021. A total of 127 patients SAVR, 137 patients TAVR. Of those, 3 patients were excluded from the study due to chronic haemodialysis. Inclusion criteria: informed consent to participate in research. Age is&amp;gt;18 years old. Prosthetics of the aortic valve by the SAVR or TAVR methods. Treatment of postoperative complications by the extracorporeal blood purification methods. Exclusion criteria: refusal to participate in research. Age is &amp;lt;18 years old. Chronic dialysis. Active bleeding. The patients were divided into two groups: group 1—patients after aortic valve replacement by the TAVR method and group 2—patients after open surgery aortic valve—SAVR. Indications for extracorporeal blood purification methods: acute kidney injury (AKI), acute liver injury, the systemic inflammatory response syndrome (SIRS) and cytokine storm. RESULTS Period from 2020 to 2021. TAVR group—137 patients, male―65 (47.45%), female—72 (52.55%), the average age of patients was 69.2±11.16 years. In the SAVR group, there were 127 patients, of which male 43 (33.9%) and female 84 (66.1%), the average age was 47.04 ± 13.67 years. CONCLUSION Complications and mortality rate are more common after open surgery SAVR than after TAVR. Extracorporeal blood purification methods are required after an open valve replacement. Extracorporeal blood purification methods are an effective way to treat complications such as AKI and SIRS after aortic valve replacement.

Continuous Renal Replacement Therapy With Adsorbing Filter oXiris in Acute Kidney Injury With Septic Shock: A Retrospective Observational Study

Background and ObjectiveSepsis/septic shock-associated acute kidney injury (S-AKI) is associated with prolonged kidney recovery and extremely high mortality. Extracorporeal blood purification therapy for the removal of endotoxin and cytokines might benefit patients with S-AKI. The purpose of this study was to compare the efficacy of adsorbing filter oXiris in the treatment of S-AKI.Design, Setting, Participants, and MeasurementsThis was a retrospective observational study conducted from September 2017 to June 2020 in ICU. All patients received CRRT for ≥24 h. The primary outcomes were mortality. The secondary outcomes included cardiovascular SOFA score and vasoactive-inotropic score (VIS), the SOFA, the reduction of inflammatory mediators.ResultsA total of 136 septic shock patients with AKI were included. The interventional group (oXiris group; n = 70) received CRRT with endotoxic and cytokine adsorption function hemofilter (oXiris), while the control group (ST150 group; n = 66) was treated with the ST150 hemofilter. The early mortality in 7 and 14 days was significantly lower in oXiris group compared with ST150 group (7 days: 47.1 vs. 74.2%, P = 0.007; 14 days: 58.5 vs. 80.3%, P = 0.005), but the difference was not significant in 90-day mortality (71.4 vs. 81.8%, P = 0.160). Additionally, the reduction of the SOFA score in the oXiris group at 24, 48, and 72 h CRRT was significantly faster than that in the controlled group. Meanwhile, the reduction of VIS score in the oXiris group compared with the ST150 group at 24 and 48 h after the initiation of CRRT was statistically significant (P < 0.05). Furthermore, the decreases in procalcitonin were greater in the oXiris group than those in the ST150 group at 24, 48, and 72h after initiation of CRRT. Multivariate Cox regression model demonstrated that oXiris (vs. ST150) played a favorably important role in the prognosis of septic shock patients with a hazard ratio (HR) of 0.500 (95% CI: 0.280–0.892; P = 019).ConclusionAlthough no difference was found in 90-day mortality, oXiris might reduce the short-term (<14-day) mortality compared with ST150 groups in septic shock with AKI. Further investigation in randomized controlled trials or high-quality prospective studies is warranted to validate the present findings.

Management of Acute Kidney Injury and Extracorporeal Blood Purification Therapies During the COVID-19 Pandemic: The Italian SIN-SIAARTI Joint Survey (and Recommendations for Clinical Practice).

Background and AimThe novel coronavirus disease 2019 remains challenging. A large number of hospitalized patients are at a high risk of developing AKI. For this reason, we conducted a nationwide survey to assess the incidence and management of AKI in critically ill patients affected by the SARS-CoV-2 infection.MethodsThis is a multicenter, observational, nationwide online survey, involving the Italian Society of Nephrology and the critical care units in Italy, developed in partnership between the scientific societies such as SIN and SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected for a period of 1 week during the COVID-19 pandemic.ResultsA total of 141 responses were collected in the SIN–SIAARTI survey: 54.6% from intensivists and 44.6% from nephrologists. About 19,000 cases of COVID-19 infection have been recorded in hospitalized patients; among these cases, 7.3% had a confirmed acute kidney injury (AKI), of which 82.2% were managed in ICUs. Only 43% of clinicians routinely used the international KDIGO criteria. Renal replacement therapy (RRT) was performed in 628 patients with continuous techniques used most frequently, and oliguria was the most common indication (74.05%). Early initiation was preferred, and RRT was contraindicated in the case of therapeutic withdrawal or in the presence of severe comorbidities or hemodynamic instability. Regional anticoagulation with citrate was the most common choice. About 41.04% of the interviewed physicians never used extracorporeal blood purification therapies (EBPTs) for inflammatory cytokine or endotoxin removal. Moreover, 4.33% of interviewed clinicians used these techniques only in the presence of AKI, whereas 24.63% adopted them even in the absence of AKI. Nephrologists made more use of EBPT, especially in the presence of AKI. HVHF was never used in 58.54% of respondents, but HCO membranes and adsorbents were used in more than 50% of cases.ConclusionThis joint SIN–SIAARTI survey at the Italian Society of Nephrology and the critical care units in Italy showed that, during the COVID-19 pandemic, there was an underestimation of AKI based on the “non-use” of common diagnostic criteria, especially by intensivists. Similarly, the use of specific types of RRT and, in particular, blood purification therapies for immune modulation and organ support strongly differed between centers, suggesting the need for the development of standardized clinical guidelines.

CytoSorb Therapy in COVID-19 (CTC) Patients Requiring Extracorporeal Membrane Oxygenation: A Multicenter, Retrospective Registry.

Introduction: CytoSorb extracorporeal blood purification therapy received FDA Emergency Use Authorization (EUA) to suppress hyperinflammation in critically ill COVID-19 patients. The multicenter CTC Registry was established to systematically collect patient-level data, outcomes, and utilization patterns of CytoSorb under the EUA.Methods: Patient-level data was entered retrospectively at participating centers. The primary outcome of the registry was ICU mortality. Patient disposition of death, continuing ICU care, or ICU discharge was analyzed up to Day 90 after start of CytoSorb therapy. Demographics, comorbidities, COVID-19 medications, inflammatory biomarkers, and details on CytoSorb use were compared between survivors and non-survivors in the veno-venous extracorporeal membrane oxygenation (ECMO) cohort.Results: Between April 2020 and April 2021, 52 patients received veno-venous ECMO plus CytoSorb therapy at 5 U.S. centers. ICU mortality was 17.3% (9/52) on day 30, 26.9% (14/52) on day 90, and 30.8% (16/52) at final follow-up of 153 days. Survivors had a trend toward lower baseline D-Dimer levels (2.3 ± 2.5 vs. 19.8 ± 32.2 μg/mL, p = 0.056) compared to non-survivors. A logistic regression analysis suggested a borderline association between baseline D-Dimer levels and mortality with a 32% increase in the risk of death per 1 μg/mL increase (p = 0.055). CytoSorb was well-tolerated without any device-related adverse events reported.Conclusions: CytoSorb therapy for critically ill COVID-19 patients on ECMO was associated with high survival rates suggesting potential therapeutic benefit. Elevated baseline D-Dimer levels may suggest increased risk of mortality. Prospective controlled studies are warranted to substantiate these results.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT0439192, identifier: NCT04391920.

MO675HEMOADSORPTION WITH CYTOSORB® CARTRIDGE IN PEDIATRIC INTENSIVE CARE UNIT – A SERIES OF FOUR CASES

Abstract Background and Aims Hemoadsorption with Cytosorb® cartridge is one of extracorporeal blood purification therapies increasingly used in adult intensive care units in conditions with elevated inflammatory mediators. Many positive experiences of hemodynamic improvement of patients treated with hemoadsorption have resulted in attempts of its application also in critically ill pediatric patients. Here we present a case series of four children treated with hemoadsorption in pediatric intensive care unit (PICU) of University Medical Centre Ljubljana from September 2018 to January 2019. Method All patients were mechanically ventilated and required vasopressor and inotropic support. Hemoadsorption was used as a rescue therapy after all standard treatments for their underlying condition had been insufficient. CytoSorb® cartridge was coupled with continuous veno-venous hemodialysis (CVVHD, Prismaflex system, Gambro) in pre-filter (ST60 set, Gambro) position. In children &amp;lt;10 kg body weight (2 infants), the extracorporeal circuit was prefilled with a 1:1 mixture of packed red blood cells and saline, with heparin added. Automated regional citrate anticoagulation was used, blood flow was 30-100 ml/min and dialysate flow 500 ml/h. Results The youngest child was 10 days old 1.9 kg premature female with acute liver failure due to gestational alloimmune liver disease. CVVHD was started for hyperammonemia and concomitant CytoSorb® for severe hyperbilirubinemia (335 umol/l). Procedure was discontinued after 6 hours due to uncontrollable sepsis and hemodynamic collapse. We managed to normalize ammonia values and reduce bilirubin concentration (116 umol/l). Further treatment was withdrawn as a result of irreversible multiorgan failure. One month old 2.5 kg female patient was treated in PICU due to necrotizing enterocolitis and refractory septic shock with multiorgan failure. Oliguric acute kidney injury (AKI) required CVVHD and later on Cytosorb ® was added as an attempt to limit severe hyperinflammatory condition. During 19 hours of treatment the need for vasopressor support was increasing and metabolic acidosis was deepening. The patient required a short resuscitation a couple of hours into the procedure due to bradycardia which resulted in catheter and CVVHD circuit thrombosis. Dialysis was discontinued as urgent surgery was necessary. The patient later died of uncontrolled septic shock. Three years old 17 kg male was admitted with meningococcal septic shock, requiring initiation of veno-arterial ECMO. Cytosorb® with CVVHD was started and attached to the ECMO circuit. A significant decline of interleukine-6 (IL-6) was achieved without any procedure-related side effect and treatment was discontinued after 68 hours as patient's clinical status notably improved. The patient survived. Five years old 20 kg female patient, actively treated for acute lymphoblastic leukemia, was admitted with E. coli sepsis. Septic shock was unresponsive to conventional treatment therefore she was started on Cytosorb® with CVVHD as oliguric AKI also developed. Two consecutive procedures were preformed, the first for 31 and the second for 37 hours. Level of IL-6 decreased (from &amp;gt; 5000 ng/L to 1000 ng/L) and lactate level normalized. We achieved reduction in vasopressors and oxygen need during both procedures and patient's overall status greatly improved. Conclusion Although significantly increasing the volume of extracorporeal circuit, the use of Cytosorb® cartridge within CVVHD circuit is technically feasible even in critically ill children with low body weight, if principles of pediatric renal replacement therapy are considered. More efficacy and safety data on Cytosorb® utilization are necessary before inclusion in routine clinical practice. Treatment outcome is highly dependent on primary disease and severity of patient condition.

MO799IS COMBINATION OF MAINTENANCE HEMODIALYSIS WITH HEMOPERFUSION AN EFFECTIVE METHOD IN MANAGEMENT OF RENAL OSTEODYSTROPHY AND INFLAMMATION IN HEMODIALYSIS PATIENTS?

Abstract Background and Aims Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications. Method A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs. Results At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p&amp;lt;0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p&amp;lt;0.05), P04 (p&amp;lt;0.001), CRP (p&amp;lt;0.011), SBP and DBP (p&amp;lt;0.05). Conclusion HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.

Continuous renal replacement therapy principles.

Continuous renal replacement therapy (CRRT) is an extracorporeal blood purification therapy that aims to support kidney function over an extended period of time. One of the main objectives of CRRT is the removal of excess fluid and solutes retained as a consequence of acute kidney injury. Because prescription of CRRT requires goals to be set with regard to the rate and extent of solute and fluid removal, a comprehensive understanding of the mechanism by which solute and fluid removal occurs during CRRT is essential. Basic mechanisms of fluid transport and solute removal (ultrafiltration, diffusion, convection, and adsorption) and the factors influencing these processes in CRRT are described. From the combination of the different transport mechanisms, a number of CRRT modalities are identified and described. Finally, these principles are applied to provide a brief overview of the concept of effluent-based CRRT dose.