Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed. METHODS: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry. RESULTS: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05). CONCLUSION: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients.

Application of Hemoperfusion in the Treatment of Acute Poisoning.

Rescue of acute poisoning is a race against time, and it is particularly important to remove toxic substances in time. Traditional methods include gastric lavage, promoting elimination, chelating agents, and other treatments. Hemoperfusion is a common blood purification technique. In the clinical practice of acute poisoning, hemoperfusion can directly remove toxic substances through its unique adsorption effect, showing its excellent efficacy. This paper reviews the experience of hemoperfusion in the treatment of various drug overdoses, pesticides, biological toxins, and industrial poisons, even drug addiction. It is hoped to provide a reference for clinicians in acute poisoning rescue.

Effect of Mechanical Vibration on Kinetics of Solute Adsorption.

INTRODUCTION: Hemadsorption with new sorbent cartridges is an emerging extracorporeal blood purification technique. Flow distribution inside the sorbent is one of the main issues concerning the device's performance and optimal sorbent utilization. In this experiment, we aimed to investigate the efficacy of vibration during adsorption by measuring the removal of vancomycin. METHODS: In this experimental study, 1,000 mL of saline with 10 g of vancomycin was circulated in a closed circuit (set flow of 250 mL/min) simulating a hemadsorption blood run using HA380 minimodule cartridge containing 75 g of wet resin. This vibration model was implemented with a damping head device installed in front of the adsorption cartridge during the experiment. The kinetics of the vancomycin were assessed by removal ratio over 120 min. RESULTS: We found no difference between the two models. Adsorption with and without vibration did not differ significantly for partial reduction ratios, overall amount of adsorbed molecule, or adsorption kinetics. CONCLUSION: The current design and structure of the minimodule cartridge demonstrated no difference in small-middle solute removal. Further improvement with the addition of mechanical vibration to the device was not observed.

Kinetics of Different Blood Biomarkers during Polymyxin-B Extracorporeal Hemoperfusion in Abdominal Sepsis.

INTRODUCTION: Comparison of the marker kinetics procalcitonin, presepsin, and endotoxin during extracorporeal hemoperfusion with polymyxin-B adsorbing cartridge (PMX-HA) has never been described in abdominal sepsis. We aimed to compare the trend of three biomarkers in septic post-surgical abdominal patients in intensive care unit (ICU) treated with PMX-HA and their prognostic value. METHODS: Ninety abdominal post-surgical patients were enrolled into different groups according to the evidence of postoperative sepsis or not. Non-septic patients admitted in the surgical ward were included in C group (control group). ICU septic shock patients with endotoxin levels <0.6 EAA receiving conventional therapy were addressed in S group and those with endotoxin levels ≥0.6 EAA receiving treatment with PMX-HA, besides conventional therapy, were included in SPB group. Presepsin, procalcitonin, endotoxin and other clinical data were recorded at 24 h (T0), 72 h (T1) and 7 days (T2) after surgery. Clinical follow-up was performed on day 30. RESULTS: SPB group showed reduced levels of the three biomarkers on T2 versus T0 (p < 0.001); presepsin, procalcitonin and endotoxin levels decreased, respectively, by 25%, 11%, and 2% on T1 versus T0, and 40%, 41%, and 26% on T2 versus T0. All patients in C group, 73% of patients in SPB group versus 37% of patients in S group survived at follow-up. Moreover, procalcitonin had the highest predictive value for mortality at 30 days, followed by presepsin. CONCLUSION: The present study showed the reliability of presepsin in monitoring PMX-HA treatment in septic shock patients. Procalcitonin showed better predicting power for the mortality riSsk.

Mid-to-late stage diquat accumulation in the central nervous system: A severe case of oral poisoning.

A 54-year-old woman in good health was admitted to our hospital with diquat poisoning. The patient drank an unknown dose of diquat, and acute kidney injury developed early. However, there were no obvious pulmonary abnormalities and no signs of central nervous system toxicity in the early stage. The woman underwent active treatment, which resulted in a significant decrease in blood diquat levels, but her lung condition progressively worsened and neurological symptoms developed. Fortunately, the patient survived after intensive hemoperfusion combined with continuous renal replacement therapy (CRRT), intracranial pressure reduction, and anti-infective treatment. This case report highlights the importance of being aware of the development of delayed pulmonary symptoms and neurologic complications when caring for patients poisoned with diquat, even in those with low diquat blood concentrations. Interestingly, we also detected the concentration of diquat in the cerebrospinal fluid (CSF) of patients with diquat poisoning, and found that the rate of decrease of diquat concentration in the CSF was considerably slower than that in the blood.Notably, a specific correlation was observed between the concentration of diquat in the CSF, rather than in the blood, and both the intracranial pressure (ICP) and the severity of cerebral edema in this patient.

[Two cases of pyridaben poisoning were successfully treated by blood purification].

Pyridaben is a broad-spectrum acaricide widely used in agriculture, accidental or self-administration of large doses of pyridaben can cause multiple organ failure in patients. Due to its damage to multiple organs and no specific antidote, the mortality rate is high. This paper reports two patients who took a large amount of pyridaben, developed severe metabolic acidosis, hyperlactatemia, toxic encephalopathy, and liver, kidney, heart and digestive tract damage. After timely gastric lavage, catharsis, organ support andblood purification treatment, the condition improved and discharged. It is expected to provide clinical ideas for the treatment of pyridaben poisoning.

Rationale for sequential extracorporeal therapy (SET) in sepsis.

Sepsis and septic shock remain drivers for morbidity and mortality in critical illness. The clinical picture of patients presenting with these syndromes evolves rapidly and may be characterised by: (a) microbial host invasion, (b) establishment of an infection focus, (c) opsonisation of bacterial products (e.g. lipopolysaccharide), (d) recognition of pathogens resulting in an immune response, (e) cellular and humoral effects of circulating pathogen and pathogen products, (f) immunodysregulation and endocrine effects of cytokines, (g) endothelial and organ damage, and (h) organ crosstalk and multiple organ dysfunction. Each step may be a potential target for a specific therapeutic approach. At various stages, extracorporeal therapies may target circulating molecules for removal. In sequence, we could consider: (a) pathogen removal from the circulation with affinity binders and cartridges (specific), (b) circulating endotoxin removal by haemoperfusion with polymyxin B adsorbers (specific), (c) cytokine removal by haemoperfusion with sorbent cartridges or adsorbing membranes (non-specific), (d) extracorporeal organ support with different techniques for respiratory and cardiac support (CO2 removal or extracorporeal membrane oxygenation), and renal support (haemofiltration, haemodialysis, or ultrafiltration). The sequence of events and the use of different techniques at different points for specific targets will likely require trials with endpoints other than mortality. Instead, the primary objectives should be to achieve the desired action by using extracorporeal therapy at a specific point.

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo.

BACKGROUND: The CytoSorb hemoadsorption device has been demonstrated to be capable of clearing inflammatory cytokines, but has not yet been shown to attenuate plasma cytokine concentrations. We investigated the effects of CytoSorb hemoperfusion on plasma levels of various cytokines using the repeated human experimental endotoxemia model, a highly standardized and reproducible human in vivo model of systemic inflammation and immunological tolerance induced by administration of bacterial lipopolysaccharide (LPS). METHODS: Twenty-four healthy male volunteers (age 18-35) were intravenously challenged with LPS (a bolus of 1 ng/kg followed by continuous infusion of 0.5 ng/kg/hr for three hours) twice: on day 0 to quantify the initial cytokine response and on day 7 to quantify the degree of endotoxin tolerance. Subjects either received CytoSorb hemoperfusion during the first LPS challenge (CytoSorb group), or no intervention (control group). Plasma cytokine concentrations and clearance rates were determined serially. This study was registered at ClinicalTrials.gov (NCT04643639, date of registration November 24th 2020). RESULTS: LPS administration led to a profound increase in plasma cytokine concentrations during both LPS challenge days. Compared to the control group, significantly lower plasma levels of tumor necrosis factor (TNF, - 58%, p < 0.0001), interleukin (IL)-6 ( - 71%, p = 0.003), IL-8 ( - 48%, p = 0.02) and IL-10 ( - 26%, p = 0.03) were observed in the CytoSorb group during the first LPS challenge. No differences in cytokine responses were observed during the second LPS challenge. CONCLUSIONS: CytoSorb hemoperfusion effectively attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo, whereas it does not affect long-term immune function. Therefore, CytoSorb therapy may be of benefit in conditions characterized by excessive cytokine release.

Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial.

BACKGROUND: Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA. METHODS: We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort. RESULTS: The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02). CONCLUSIONS: Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.

Clinical implications of endotoxin activity and Polymyxin-B hemoperfusion in critically ill patients with septic cardiomyopathy: A single-center, retrospective, observational study.

BACKGROUND: To explore the association between endotoxin activity (EA) and septic cardiomyopathy (SCM), the relationship between endotoxin removal by Polymyxin-B hemoperfusion (PMX-HP) and recovery from SCM (R-SCM), and the correlation between R-SCM and the 28-day mortality in septic patients admitted to the intensive care unit (ICU). METHODS: Observational study that included patients admitted to two ICUs of a tertiary university hospital between April 2011 and December 2019, who received PMX-HP for sepsis/septic shock. The SCM and R-SCM were assessed by transthoracic echocardiography. RESULTS: Among 148 patients, SCM was diagnosed in 60 (46%) of them and had no relationship with median EA (SCM group: 0.73; no-SCM group: 0.66, p = 0.48). Recovery from SCM was observed in 24 patients (49%) and was independently associated with the PMX-HP (OR 4.19, 95%CI [1.22, 14.3]; p = 0.02) and the SAPS2 II score (OR 0.94, 95%CI [0.9, 0.98]; p = 0.006). In the SCM group, the 28-day mortality was 60% and was independently predicted by R-SCM (OR 0.02, 95%CI [0.001, 0.3] p = 0.005) and SAPS II score (OR 1.11, 95%CI [1.01, 1.23] p = 0.037). CONCLUSIONS: In septic patients, EA was not associated with SCM. However, endotoxin removal by Polymyxin-B hemoperfusion was associated with recovery from cardiomyopathy, which was a predictor of lower 28-day mortality.

Bilirubin Removal by Plasmafiltration-Adsorption: Ex vivo Adsorption Kinetics Model and Single Case Report.

BACKGROUND: Extracorporeal removal of bilirubin in patients with severe liver dysfunction is a key blood purification strategy. We conducted an ex vivo study to assess the quantitative capacity to remove bilirubin from plasma of a novel adsorptive cartridge. METHODS: We studied a downscaled module of the BS330 Plasma Bilirubin Adsorption Column Cartridge (Jafron Biomedical, Zhuhai City, China) to minimize the plasma requirement in an ex vivo circulation using a solution of hyperbilirubinemic plasma. We measured the bilirubin concentration gap (ΔC) between inlet (Cpin) and outlet (Cpout) of the unit and we calculated the removal ratio (RR) as mass adsorbed at different time points. Moreover, we compared the ex vivo model with the bilirubin adsorption kinetics in a patient with acute on chronic liver failure treated with the BS330 cartridge. RESULTS: Bilirubin concentration change across the cartridge at 30 min was 16.5%, and cartridge saturation was reached at 750 min. We used a minimodule downscaled to 1:3 and containing approximately 131 g of BS330 sorbent beads: the device retained 759 mg of bilirubin with a RR of 78.1% and a RR of 42.6% at 120 min. Thus, the adsorption capacity was 5.76 mg of bilirubin per gram of sorbent. Bilirubin adsorption kinetics in our clinical case with a full-scale unit shows a coherent trend with a total bilirubin mass adsorbed after 180 min of 470 mg. DISCUSSION: Our findings provide the first assessment of bilirubin adsorption in an ex vivo model of plasma perfusion and can be used to design interventional studies in humans, providing guidance for an adequate prescription of treatment frequency and duration.

Vancomycin Adsorption during in vitro Model of Hemoperfusion with Mini-Module of HA380 Cartridge.

INTRODUCTION: Sepsis is a frequent complication in critically ill patients. Patients may require control of the source of infection, removal of pathogens and damaged cells, and organ support. Often, these targets can be achieved through the utilization of extracorporeal therapies including hemoperfusion for the adsorption of cytokines and other circulating mediators. On extracorporeal organ support, patients are generally treated with antibiotic therapy, and vancomycin is one of the most commonly used antibiotics. Because of the aspecific nature of adsorption, antibiotics can be removed from the circulation, leading to altered plasma levels and requiring prescription adjustment. The aim was to define the amount of vancomycin adsorbed by a sorbent cartridge (HA380, Jafron, China) during hemoperfusion and to establish possible strategies to maintain an effective plasma level in critically ill patients undergoing extracorporeal therapies. METHODS: In vitro experiments with incremental concentrations of vancomycin in the test solution (500 and 1,000 mL) were carried out in a recirculation circuit until sorbent saturation was observed. A maximum of 10 g of vancomycin were injected and mini-modules containing 25 g of dry resin were utilized. RESULTS: In different experiments with various concentration of vancomycin, a maximum amount of 244 mg/g of sorbent was adsorbed reaching saturation between 60 and 80 min from the beginning of the experiments. The kinetics of adsorption appears to be governed by a Langmuir-like isotherm with maximal removal speed in the early minutes and a plateau after 60 min. DISCUSSION/CONCLUSION: HA380 adsorbs significant amounts of vancomycin. Adjusting the achieved results with the experimental mini-module to a full-scale cartridge, a total of 25 g of antibiotic can be removed. This might have affected outcome results in clinical trials. This suggests prescribing administration to critically ill patients requiring hemoperfusion, immediately after or in the inter-session time window. In case of administration during hemoperfusion, adequate adjustment and plasma level monitoring is strongly recommended.

Hemoperfusion for Clinically Suspected Organophosphate and Carbamate Poisoning in Critically Ill Patients: A Randomized Trial.

INTRODUCTION: Organophosphate poisoning occurs frequently, and despite treatment, increased severity and intensive care unit (ICU) admissions have been observed. We hypothesized that early hemoperfusion/hemadsorption (HA) therapy would change the clinical course of the disease. METHODS: We performed a prospective, open, randomized controlled study at an academic ICU. Adult patients referred for an acute cholinergic toxidrome were screened. Patients meeting inclusion and exclusion criteria were randomized to standard of care (SoC) or HA therapy plus SoC, which included 2 6-h cycles of HA 12 h apart beginning within the first 24 h of ICU admission. The primary outcome was a comparison of ICU length of stay (LOS). RESULTS: There were no significant baseline differences between the groups. The median ICU LOS was 6.5 days (IQR 4.5-10) in the HA group compared to 8 days (IQR 3.5-17) for the control group, p = 0.58. Among patients with an excess ICU LOS ≥7 days, the median ICU LOS was significantly shorter for the HA group, 10 days (IQR 8-12) compared to 17 days (IQR 14-22) for the control group, p = 0.001, resulting in a cost saving of EUR 7308 per patient. Duration (8 days vs. 13.5 days) and cumulative dosage (316 mg vs. 887 mg) of atropine among patients with excess ICU LOS were significantly lower in the HA group compared to the SoC group, respectively. A similar reduction in the duration of mechanical ventilation (HA = 6 days vs. SoC = 15 days, p = 0.001) was found. The combination of day 28 mortality and severe complications was lower in the HA group (10%, n = 2/20) compared to the SoC group (42%, 14/33) p = 0.01. CONCLUSION: HA therapy resulted in significant cost savings driven by a reduced LOS among patients with excess ICU LOS ≥7 days. This therapy was also associated with a significant reduction in the combination of day 28 mortality and severe complications including cardiac arrest, organ dysfunction, reintubation, and tracheostomy.

Efficacy and Safety of Plasma Exchange Combined with Hemoperfusion in the Treatment of Organophosphorus Poisoning: A Meta-Analysis.

INTRODUCTION: The aim of the study was to systematically evaluate the efficacy and safety of plasma exchange combined with hemoperfusion in the treatment of organophosphorus poisoning. METHODS: PubMed, Embase, the Cochrane Library, China National Knowledge Internet, Wanfang database, and Weipu database were searched for articles about this subject. Literature screening and selection were conducted in strict accordance with the inclusion and exclusion criteria. RESULTS: 14 randomized controlled trials with 1,034 participants were included in this meta-analysis study, including 518 cases in plasma exchange combined with hemoperfusion group (the combination treatment group) and 516 cases in hemoperfusion group (the control group). Compared with the control group, the combination treatment group was associated with a higher effective rate (relative risk [RR] = 1.20, 95% confidence interval [CI] [1.11, 1.30], p < 0.00001) and lower fatality rate (RR = 0.28, 95% CI [0.15, 0.52], p< 0.0001); reduced TNF-α (standardized mean difference [SMD] = -1.95, 95% CI [-2.42, -1.48], p < 0.00001), IL-6 (SMD = -1.94, 95% CI [-3.08, -0.80], p = 0.0009), and C-reactive protein (CRP) (SMD = -1.94, 95% CI [-2.86, -1.03], p < 0.0001); shorten coma time (SMD = -1.99, 95% CI [-2.75, -1.24], p < 0.00001), recovery time of cholinesterase activity (SMD = -1.71, 95% CI [-1.90, -1.53], p < 0.00001), and hospital stay (SMD = -1.29, 95% CI [-1.59, -0.98], p < 0.00001). The incidence of complications in the combination treatment group such as liver and kidney damage (RR = 0.30, 95% CI [0.18, 0.50], p < 0.00001), pulmonary infection (RR = 0.29, 95% CI [0.18, 0.47], p < 0.00001), and intermediate syndrome (RR = 0.32, 95% CI [0.21, 0.49], p < 0.00001) was lower than that in the control group. CONCLUSIONS: The current evidence suggests that the combination of plasma exchange with hemoperfusion therapy can reduce the mortality of patients with organophosphorus poisoning, shorten the recovery time of cholinesterase activity and the time of coma, reduce the average length of hospital stay, and reduce the levels of IL-6, TNF-α, and CRP, but high-quality randomized double-blind controlled trials are still required to confirm the current findings in the future.

Prolonged Intermittent Renal Replacement Therapy Combined with Hemoperfusion Can Improve Early Recovery of Moderate and Severe Acute Pancreatitis, Especially in Patients with Acute Kidney Injury.

INTRODUCTION: The aim of this study was to investigate the efficacy of prolonged intermittent renal replacement therapy (PIRRT) plus hemoperfusion (HP) in treating moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS: A total of 105 MSAP and SAP patients were enrolled. Sixty of them received routine internal medical therapy (control group), and 45 received PIRRT and HP in addition to routine internal medical therapy (PIRRT + HP group). The vital signs, laboratory results, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared between the two groups before treatment and on the 3rd and 7th days of treatment. RESULTS: No deaths or treatment-related serious adverse reactions occurred in both groups. After 3 and 7 days of treatment, the APACHE II score decreased more significantly in the PIRRT + HP group than in the control group (3 days: 5.47 [±3.30] vs. 7.53 [±3.89], p = 0.005. 7 days: 4.82 [±3.49] vs. 6.87 [±3.54], p = 0.004). After 3 days of treatment, the inflammatory combination parameters systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in the PIRRT + HP group decreased more significantly than those in the control group (SII: 1,239.00 [737.80-1,769.00] vs. 2,013.00 [1,260.00-3,167.00], p = 0.001. NLR: 8.78 [±4.52] vs. 11.88 [±7.30], p = 0.009). After 7 days of treatment, SII, NLR, and hypersensitive C-reactive protein decreased significantly compared with baseline, but no statistical differences between the two groups were observed. AST in both groups remained stable with treatment. There was no significant difference in baseline creatinine between the two groups of AKI patients, but after 3 and 7 days of treatment, the proportion of acute kidney injury (AKI) patients in the PIRRT + HP group whose creatinine decreased by 50% from baseline or fell to the normal range was significantly higher than that in the control group (p < 0.05). CONCLUSION: PIRRT + HP therapy could not only improve the general conditions, as measured by APACHE II score, but also reduce the inflammatory cascade of patients with acute pancreatitis. For MSAP and SAP patients complicated with AKI, this therapy may accelerate the recovery of renal function.

The Role of Blood Purification by HA330 as Adjunctive Treatment in Children with Septic Shock.

INTRODUCTION: Despite advances in supportive care for critically ill patients, sepsis remains an important cause of death worldwide in the PICU. One of the hallmarks of sepsis is hyperinflammation due to the excessive release of inflammatory mediators. Recently, new therapeutic approaches, such as immune modulation and blood purification, have been tried to improve outcomes in patients with septic shock. METHODS: This study is a prospective observational study composed of children with septic shock and the PELOD-2 score ≥10 or the PRISM-3 score ≥15. All received 2-4 h of HA330 treatment on 2 consecutive days, used as adjunctive therapy. The effectiveness of HA330 hemoperfusion was evaluated by improving the PELOD-2 and PRISM-3 scores, the vasoactive inotropic score (VIS), and inflammatory markers from baseline to 72 h after the use of HA330 hemoperfusion. RESULTS: Twelve patients hospitalized in the PICU and diagnosed with septic shock between July 2021 and May 2022 were included in this study and received hemoperfusion with HA330. The average PELOD-2 and PRISM-3 scores decreased significantly from 9.5 (IQR: 6.5-13.0) at baseline to 2.0 (IQR: 0-6.5) at 72 h (p = 0.002) and from 16.5 (IQR: 15.0-20.5) at baseline to 5.5 (IQR: 2.0-9.5) at 72 h (p = 0.002), respectively. The VIS decreased significantly from baseline to 72 h (p = 0.003). IL-6, procalcitonin, and lactate levels also decreased significantly from baseline to 72 h (p = 0.005, 0.03, and 0.03, respectively). Two of 12 patients expired due to their underlying condition (2/12, 16.7%). Device-related adverse events did not occur in this study. CONCLUSIONS: Our observational case series suggests a possible role for HA330 hemoperfusion as an adjunctive treatment of refractory septic shock in children with high severity scores in the context of rapid improvement in organ dysfunction, without serious adverse effects.

Hemoperfusion with Seraph 100 Microbind Affinity Blood Filter Unlikely to Require Increased Antibiotic Dosing: A Simulations Study Using a Pharmacokinetic/Pharmacodynamic Approach.

INTRODUCTION: The Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) is a hemoperfusion device that can remove pathogens from central circulation. However, the effect of Seraph 100 on achieving pharmacodynamic (PD) targets is not well described. We sought to determine the impact of Seraph 100 on ability to achieve PD targets for commonly used antibiotics. METHODS: Estimates of Seraph 100 antibiotic clearance were obtained via literature. For vancomycin and gentamicin, published pharmacokinetic models were used to explore the effect of Seraph 100 on ability to achieve probability of target attainment (PTA). For meropenem and imipenem, the reported effect of continuous kidney replacement therapy (CKRT) on achieving PTA was used to extrapolate decisions for Seraph 100. RESULTS: Seraph 100 antibiotic clearance is likely less than 0.5 L/h for most antibiotics. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on vancomycin PTA in virtual patients with creatinine clearance (CrCl) = 14 mL/min and CrCl >14 mL/min, respectively. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on gentamicin PTA in virtual patients with CrCl = 120 mL/min and CrCl <60 mL/min, respectively. CKRT intensity resulting in antibiotic clearance up to 2 L/h generally does not require dose increases for meropenem or imipenem. As Seraph 100 is prescribed intermittently and likely contributes far less to antibiotic clearance, dose increases would also not be required. CONCLUSION: Seraph 100 clearance of vancomycin, gentamicin, meropenem, and imipenem is likely clinically insignificant. There is insufficient evidence to recommend increased doses. For aminoglycosides, we recommend extended interval dosing and initiating Seraph 100 at least 30 min to 1 h after completion of infusion to avoid the possibility of interference with maximum concentrations.

Efficacy of Hemoperfusion in Severe and Critical Cases of COVID-19.

INTRODUCTION: Uncontrolled overproduction of inflammatory mediators is predominantly observed in patients with severe COVID-19. The excessive immune response gives rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients. METHOD: We conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and continuous renal replacement therapies were initiated in the hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, oxygen saturation (SPO2) at the admission, and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron© (HA330) and CytoSorb® 300. RESULT: A total of 128 COVID-19-confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission day in the control and hemoperfusion groups was 80% and 75%, respectively (p value = 0.113). The mortality rate was significantly lower in the hemoperfusion group compared to the matched group (67.3% vs. 89%; p value = 0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; p < 0.001). The median final SPO2 was statistically higher in the hemoperfusion group than in the matched group, and the median PaCO2 was lower. CONCLUSION: Among critically ill COVID-19 patients, based on our study, the use of hemoperfusion may reduce the mortality rate and improve SPO2 and PaCO2.

Efficacy of Hemoperfusion Cartridge Procedure on Patients Undergoing Cardiac Valve Replacement Surgery with Cardiopulmonary Bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) induces inflammatory homeostasis dysregulation, closely related to many postoperative adverse effects. Minimizing the systemic inflammatory response to CPB is imperative to improving cardiac surgery safety. This study aimed to retrospectively evaluate the efficacy of the hemoperfusion cartridge, a device recently designed for extracorporeal blood purification to remove cytokines from the blood for patients undergoing cardiac valve replacement surgery using CPB. METHODS: The hemoperfusion (HP) group consisted of 138 patients, who underwent a hemoperfusion cartridge procedure during CPB. The control group included 149 patients, who received standard CPB management. The evaluated indices included inflammatory cytokines, blood biochemical indices, and postoperative outcome indices. RESULTS: Patients in the HP group had relatively lower interleukin (IL)-6 levels (days one and two post-CPB) and IL-8 (day one post-CPB) compared with the control group. Some relatively decreased biochemical blood indices also were observed in the HP group, including a significantly lower lactic acid level (days one, two, and three post-CPB), platelet counts (days one, two, and three post-CPB), and aspartate aminotransferase (days one and three post-CPB). Regarding the postoperative outcomes, no severe complications occurred in the patients; however, the HP group required less ventilation time than the control group. CONCLUSIONS: The hemoperfusion cartridge seems promising in limiting the inflammatory reactions during CPB, with noteworthy potential for application in cardiac surgery.

Adjunctive hemoperfusion with Resin Hemoadsorption (HA) 330 cartridges improves outcomes in patients sustaining multiple Blunt Trauma: a prospective, quasi-experimental study.

BACKGROUND: Multi-organ dysfunction syndrome and multi-organ failure are the leading causes of late death in patients sustaining severe blunt trauma. So far, there is no established protocol to mitigate these sequelae. This study assessed the effect of hemoperfusion using resin-hemoadsorption 330 (HA330) cartridges on mortality and complications such as acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS) among such patients. METHODS: This quasi-experimental study recruited patients ≥ 15 years of age with blunt trauma, injury severity score (ISS) ≥ 15, or initial clinical presentation consistent with SIRS. They were divided into two groups: the Control group received only conventional acute care, while the case group received adjunctive hemoperfusion. P-values less than 0.05 were statistically significant. RESULTS: Twenty-five patients were included (Control and Case groups: 13 and 12 patients). The presenting vital signs, demographic and injury-related features (except for thoracic injury severity) were similar (p > 0.05). The Case group experienced significantly more severe thoracic injuries than the Control group (Thoracic AIS, median [IQR]: 3 [2-4] vs. 2 [0-2], p = 0.01). Eleven and twelve patients in the Case group had ARDS and SIRS before the hemoperfusion, respectively, and these complications were decreased considerably after hemoperfusion. Meanwhile, the frequency of ARDS and SIRS did not decrease in the Control group. Hemoperfusion significantly reduced the mortality rate in the Case group compared to the Control group (three vs. nine patients, p = 0.027). CONCLUSIONS: Adjunctive Hemoperfusion using an HA330 cartridge decreases morbidity and improves outcomes in patients suffering from severe blunt trauma.