TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.

Successful treatment of a severe 5-hydroxytrytophan intoxication using carbon hemoperfusion, hemodiafiltration, and mechanical ventilation in a dog.

OBJECTIVE: To describe the successful use of carbon hemoperfusion and hemodiafiltration in combination with mechanical ventilation (MV) to treat a severe intoxication of 5-hydroxytryptophan (5-HTP) in a dog. CASE SUMMARY: A dog ingested a minimum of 550 mg/kg of extended-release 5-HTP, resulting in serotonin syndrome that progressed to a comatose state and severe hypoventilation requiring MV. Extracorporeal carbon hemoperfusion coupled with hemodiafiltration was performed to remove 5-HTP from this patient. A carbon hemoperfusion cartridge was placed in series upstream in the extracorporeal circuit from the hemodialyzer. A total of 46.5 L of blood (4.89 L/kg) was processed during a 4.85-hour treatment. Serial plasma samples were obtained at 0, 60, 90, and 150 minutes during the session and 14 hours after the session. These samples were later analyzed for 5-HTP and serotonin concentrations. The extraction ratio of 5-HTP was 93.6%-98.9% through the carbon filter. The dog was weaned from MV within 8 hours after extracorporeal therapy and, after a full recovery, was successfully discharged. NEW OR UNIQUE INFORMATION PROVIDED: Despite an extensive review of the available literature, this appears to be the first reported case of using a carbon hemoperfusion, hemodiafiltration, and MV to treat severe serotonin syndrome secondary to 5-HTP intoxication in a dog. The combination of carbon hemoperfusion and hemodiafiltration can significantly reduce plasma 5-HTP concentrations after acute intoxication and may serve to decrease morbidity and mortality in patients with severe intoxication.

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.

The potential role of extracorporeal cytokine removal with CytoSorb® as an adjuvant therapy in Acute Respiratory Distress Syndrome.

Management of acute respiratory distress syndrome (ARDS) represents one of the greatest challenges in intensive care and despite all efforts mortality remains high. One common phenotype of ARDS is that of a secondary injury to a dysregulated inflammatory host response resulting in increased capillary congestion, interstitial lung edema, atelectasis, pulmonary embolism, muscle wasting, recurring infectious episodes, and multiple organ failure. In cases of hyperinflammation, immunomodulation by extracorporeal cytokine removal such as the CytoSorb hemoadsorption cartridge could conceptually enhance lung recovery during the early course of the disease. The aim of this narrative review is to summarize the currently available data in this field and to provide an overview of pathophysiology and rationale for the use of CytoSorb hemoadsorption in patients with hyperinflammatory ARDS.

Nanobody-functionalized conduit with built-in static mixer for specific elimination of cytokines in hemoperfusion.

Removing excessively produced cytokines is of paramount significance in blood purification therapy for hypercytokinemia-associated diseases. In this study, we devised a conduit that is modified with nanobodies (Nb) and incorporates static mixers (Nb-SMC) to eliminate surplus cytokines from the bloodstream. The low-pressure-drop (LPD) static mixer, with each unit featuring two 90°-crossed blades, was strategically arranged in a tessellated pattern on the inner wall of the conduit to induce turbulent mixing effects during the flow of blood. This arrangement enhances mass transfer and molecular diffusion, thereby assisting in the identification and elimination of cytokines. By utilizing computational fluid dynamics (CFD) studies, the Nb-SMC was rationally designed and prepared, ensuring an optimal interval between two mixer units (H/G = 2.5). The resulting Nb-SMC exhibited a remarkable selective clearance of IL-17A, reaching up to 85 %. Additionally, the process of Nb immobilization could be adjusted to achieve the simultaneous removal of multiple cytokines from the bloodstream. Notably, our Nb-SMC displayed good blood compatibility without potential adverse effects on the composition of human blood. As the sole documented static mixer-integrated conduit capable of selectively eliminating cytokines at their physiological concentrations, it holds promise in the clinical potential for hypercytokinemia in high-risk patients. STATEMENT OF SIGNIFICANCE: High-efficient cytokines removal in critical care still remains a challenge. The conduit technique we proposed here is a brand-new strategy for cytokines removal in blood purification therapy. On the one hand, nanobody endows the conduit with specific recognition of cytokine, on the other hand, the build-in static mixer enhances the diffusion of antigenic cytokine to the ligand. The combination of these two has jointly achieved the efficient and specific removal of cytokine. This innovative material is the only reported artificial biomaterial capable of selectively eliminating multiple cytokines under conditions close to clinical practice. It has the potential to improve outcomes for patients with hypercytokinemia and reduce the risk of adverse events associated with current treatment modalities.

Novel hemoperfusion adsorbents based on collagen for efficient bilirubin removal - A thought from yellow skin of patients with hyperbilirubinemia.

Hemoperfusion is a well-developed method for removing bilirubin from patients with hyperbilirubinemia. The performance of adsorbents is crucial during the process. However, most adsorbents used for bilirubin removal are not suitable for clinical applications, because they either have poor adsorption performance or limited biocompatibility. Patients with hyperbilirubinemia usually have distinctive yellow skin, indicating that collagen, a primary component of the skin, may be an effective material for absorbing bilirubin from the blood. Based on this idea, we designed and synthesized collagen (Col) and collagen-polyethyleneimine (Col-PEI) microspheres and employed them as hemoperfusion adsorbents for bilirubin removal. The microspheres have an efficient adsorption rate, higher bilirubin adsorption capacity, and competitive adsorption of bilirubin in the bilirubin/bovine serum albumin (BSA) solution. The maximum adsorption capacities of Col and Col-PEI microspheres for bilirubin are 150.2 mg/g and 258.4 mg/g, respectively, which are higher than those of most traditional polymer microspheres. Additionally, the microspheres exhibit excellent blood compatibility originating from collagen. Our study provides a new collagen-based strategy for the hemoperfusion treatment of hyperbilirubinemia.

A novel recyclable hemoperfusion adsorbent based on TiO2 nanotube arrays for the selective removal of ß2-microglobulin.

Prolonged and excessive accumulation of ß2-microglobulin (ß2m) in the blood can lead to various kidney-related and other diseases. Currently, the most effective method of removing ß2m from the blood is hemoperfusion. Although some traditional hemoperfusion adsorbents such as cellulose and polystyrene microspheres have been used for the removal of ß2m, their selectivity still needs improvement. Immunosorbents have been developed to address this issue, but high cost and limited application are concerns. TiO2 nanotube arrays (TNTAs) have shown great potential in adsorption-related biomedical applications. In this study, we designed and developed a novel TNTA-based hemoperfusion adsorbent for the removal of ß2m, which has demonstrated good biocompatibility, selectivity, and reusability. We investigated the ß2m adsorption capacities of TNTAs with different pore sizes. The results indicate that TNTAs with a pore size matching the size of ß2m exhibit higher adsorption capacity while also having lower adsorption capacity for albumin, showing the importance of pore size on the selectivity of adsorbents. Additionally, green regeneration of TNTAs is achieved via the photocatalytic activity originating from TiO2. Even after five cycles, the adsorption capacity of TNTAs remained above 70%. Our work demonstrates that inorganic materials with ordered pores are capable to be candidates for hemoperfusion, possessing advantages over traditional organic materials such as high stability, security, and low cost.

Hemoperfusion with CytoSorb®: Current Knowledge on Patient Selection, Timing, and Dosing.

Direct hemoperfusion with the CytoSorb® adsorbent has experienced widespread use in several critical care settings including sepsis and multiorgan failure. The reported conditions of clinical usage and resulting outcomes vary considerably. The aim of the study was to provide an overview on current treatment recommendations based on the available clinical evidence. We performed a literature analysis using PubMed/MEDLINE and ClinicalTrials.gov to identify clinical data describing parameters of clinical usage of CytoSorb® in patients with septic shock (inclusion and exclusion criteria, starting, and dosing of treatment) and their impact on outcome. The literature search terms yielded 146 entries in September 2022, including clinical case reports, case series, and controlled and uncontrolled clinical trials. Five recommendations were identified linking usage parameters with improved outcome. These were (a) early start of treatment within 12-24 h after onset of septic shock, (b) individualized patient selection (preferably with higher severity scores, procalcitonin >3 ng/mL, serum interleukin 6 >500 pg/mL), (c) exclusion of patients with lactate ≥6 mmol/L or platelets <100 GPT/L, (d) intense treatment (>6 L of blood/kg body weight), and (e) early change of the adsorbent (e.g., every 12 h). Moreover, there is a rationale suggesting therapeutic drug monitoring when possible, avoidance of drug application at the beginning of treatment, and/or usage of increased dosages of antibiotics. However, for the later recommendations, no links to clinical outcome were reported yet. All recommendations are based on the best available knowledge. They need confirmation in future clinical investigations. Currently available clinical data on the use of CytoSorb® in septic patients suggest that early and intense treatment in carefully chosen patients increases the chance of survival. The analysis can inform current clinical practice and future clinical trials.

Hemoperfusion and Immunomodulation.

Recent development in sorbent technology has spurred new interest in the potential of hemoperfusion (HP) in clinical conditions such as cytokine release syndromes and sepsis. Although the role of nonselective HP in such conditions requires solid evidence and more studies, the rationale for clinical application is clearly emerging. Greater biocompatibility and safety of the new sorbents may allow easy and safe application of HP in those conditions where the innate and the adaptive immune response of the individual appears to be dysregulated. Recent results in small studies seem to confirm the plausibility for this therapeutic approach. The concept suggested by the peak concentration hypothesis justifies new studies and the application of HP in selected patients to remove the peaks of circulating mediators responsible for conditions of hyperinflammation or immunodepression.

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.

Chemical-Physical Mechanisms of Adsorption for Blood Purification.

The removal of soluble toxins from blood is necessary in patients with severe kidney failure. The majority of blood purification techniques are based on the use of semipermeable membranes, such as for dialysis treatment. But, whenever there is the need to remove small soluble molecules from blood, the use of such purification techniques may exhibit limited efficiency. This leads to a search for better-performing treatments. Hemoperfusion, given the recent strong advances in the sorption media biocompatibility with plasma (or blood), is considered a promising blood purification technique. This introductive chapter aims at briefly presenting the phenomenology of the adsorption process, also providing some basic elements related to how to use equilibrium load data to define an adsorption isotherm, which can be used to size a hemoperfusion cartridge.

Hemoperfusion techniques using Jafron HA330 cartridge combined with BBraun Dialog+ dialysis machine in patient with coronavirus disease 2019 pneumonia and septic shock: a case report.

BACKGROUND: The use of hemoperfusion for cytokine removal and inflammatory mediators is increasingly intense, especially in coronavirus disease 2019 patients who are already known to the general public for having cytokine storms. However, we have known about these cytokine storms for a long time in the critical care world. One of the modalities to remove cytokines is to use filtration and adsorption techniques with continuous renal replacement therapy. The use of continuous renal replacement therapy is usually constrained by its very high cost compared with standard care, especially in Indonesia, where health costs are covered by national health insurance. In this case, we use hemodialysis and hemoperfusion, using a dialysis machine, which is more cost-effective and easy to use. CASE PRESENTATION: We used the Jafron HA330 cartridge, modified for the BBraun Dialog+ dialysis machine. This case report presents an 84-year-old Asian man with septic shock due to pneumonia, congestive heart failure, and acute chronic kidney disease accompanied by fluid overload. After undergoing hemodialysis and hemoperfusion separately, there was a gradual and significant clinical improvement. Clinical indicators, including the vasopressor inotropic score and infection markers, should all be considered when deciding whether to begin hemodialysis and hemoperfusion. CONCLUSION: In general, using hemoperfusion to treat septic shock patients can reduce the length of stay in the intensive care unit, and morbidity and mortality.

HEMOPERFUSION USING THE LPS-SELECTIVE MESOPOROUS POLYMERIC ADSORBENT IN SEPTIC SHOCK: A MULTICENTER RANDOMIZED CLINICAL TRIAL.

ABSTRACT: Extracorporeal hemoperfusion (EHP) may improve the course and outcomes of patients with septic shock by targeting cytokines or bacterial endotoxins (lipopolysaccharide [LPS]). Here, we present the results of a multicenter randomized controlled trial ( clinicaltrials.gov/ct2/show/NCT04827407 ) to assess the efficiency and safety of Efferon LPS hemoperfusion cartridges engineered for multimodal targeting LPS, host-derived cytokine, and damage-associated molecule pattern molecules. Patients with intra-abdominal sepsis (IAS) and septic shock (Sepsis-3) were subjected to EHP procedures (n = 38). Control patients with IAS and septic shock (n = 20) were treated using conventional protocols without EHP. The primary end point was resolution of septic shock. Secondary end points included MAP, vasopressor drug dose, partial pressure of arterial oxygen/fraction of inspired oxygen ratio, Sequential Organ Failure Assessment score, length of stay in the intensive care unit, and satisfaction with device use by a 5-point Likert scale. Clinical laboratory tests for a blood cells count, lactate and creatinine concentration, nephelometry test for C-reactive protein, immunochemiluminescent test for procalcitonin, and immunoenzyme analysis for IL-6 concentration were used to monitor the EHP effect versus the control group. Data were analyzed followed the intention-to-treat approach. Wilcoxon STATA 16.0 (StataCorp, College Station, TX) and Excel 2019 with XLStat 2019 add-in (Addinsoft, Paris, France) were used for statistical analysis of the results. The Fine and Gray method of competing risks was used to analyze the primary end point and other data representing the time to event. EHP resulted in a significant and rapid increase in MAP and partial pressure arterial oxygen/fraction of inspired oxygen ratio, progressive decline in norepinephrine doses, and multiorgan deficiency, as evaluated by Sequential Organ Failure Assessment scores. Importantly, EHP led to significantly rapid cumulative mechanical ventilation weaning compared with the control group (subdistribution hazard ratio, 2.5; P = 0.037). Early 3-day mortality was significantly reduced in the Efferon LPS versus control group; however, no significant improvements in survival in 14 and 28 days were revealed. Laboratory tests showed rapidly decreased levels of LPS, procalcitonin, C-reactive protein, IL-6, creatinine, leukocytes, and neutrophils only in the Efferon LPS group. Results demonstrate that EHP with Efferon LPS is a safe procedure to abrogate septic shock and normalize clinical and pathogenically relevant biomarkers in patients with IAS.

Extracorporeal therapy in the treatment of sepsis: In vitro assessment of the effect of an absorbent cartridge on the circulating bacterial concentration and its interaction with the antibiotic therapy.

Sepsis is one of the major causes of death worldwide. In its physiopathological process, a broad spectrum of pro and antiinflammatory mediators plays a strategic role, leading to a sepsis induced state of immunoparalysis. The rationale behind the employment of extracorporeal purification techniques as a complement to therapy for sepsis is based on their ability to remove the mediators involved. Until now, attention was focused on the immunomodulation allowed by purification therapies. However, the focus of studies on the application possibilities that these techniques offer as a supplement to antimicrobial therapy and resuscitation of critically ill patients must be extended. In this study, the possible removal by adsorption that the Jafron® HA330 cartridge operates against bacteria (S. aureus) was evaluated in vitro. Subsequently, it was evaluated whether the adsorptive capabilities toward bacteria were maintained by using a cartridge functionalized with Vancomycin and whether the latter maintains its bactericidal activity. This study showed that HA330 reduces the circulating bacterial load, even in the presence of pre-adsorbed Vancomycin. Vancomycin, once adsorbed by the cartridge, does not guarantee its bactericidal activity during the 2-h of hemoperfusion treatment.

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.

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.

Outcome and Complications of Hemoperfusion in Patients with COVID-19 in Intensive Care Unit: A Cross-Sectional Study.

BACKGROUND & OBJECTIVE: The use of the hemoperfusion method is recommended for treating cytokine storms and reducing complications in patients with COVID-19. The side effects of this treatment are not known; therefore, this study was performed to determine the final outcome and complications of hemoperfusion in patients with COVID-19 hospitalized in ICU. METHODS: In this retrospective cross-sectional study, all patients with severe COVID-19 without any comorbidities or organ failure underwent hemoperfusion treatment in ICU at Kosar Hospital in Semnan, Iran, from March to November 2021 were included. The clinical data and short-term complications up to 10 days after hemoperfusion and the final outcome were extracted from medical files. RESULTS: The mean age of 40 patients with severe COVID-19 undergoing hemoperfusion was 57.5±15.9 years. Most (24, 60%) patients were male. The time interval from hospitalization to hemoperfusion and the time interval between hemoperfusion and final outcome was 4.85 days and 8.30 days, respectively. Arrhythmia, bleeding, thrombocytopenia, and coagulation disorders were the most common short-term complications of hemoperfusion in patients with COVID-19, respectively. Most complications occurred on the second and third days after hemoperfusion. Mortality occurred in 20 (50 %) patients with severe COVID-19 undergoing hemoperfusion in ICU. CONCLUSION: It seems that the short-term complications and deaths due to hemoperfusion are relatively high in patients with COVID-19 admitted to the ICU. Further studies are recommended.

Efficacy of hemoperfusion with Seraph-100 in series with single pass albumin dialysis in acute hepatitis B infection: A case report.

Acute and acute-on-chronic liver failure is a cause of death in patients suffering from viral hepatitis, and many cases need liver transplantation. Infection from hepatitis B virus may range from asymptomatic to severe acute and fulminant hepatitis. In this setting, treatment is mainly supportive as there is no consensus on antiviral therapy based on non-nucleoside reverse transcriptase inhibitors. Single-pass albumin dialysis is a liver-support technique for patients suffering from liver failure, that has shown effectiveness in the removal of both water-soluble and albumin-bound toxins, which accumulate due to impairment of the liver's cleansing function. We report here the case of a 62-year-old male who presented with a severe acute hepatitis B infection, liver failure, and marked hyperbilirubinemia. Treatment with single-pass albumin dialysis combined with a hemoperfusion device was successful in improving clinical, physiological, and laboratory parameters.

[Effects and significance of continuous hemoperfusion on patients with diquat poisoning].

OBJECTIVE: To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance. METHODS: A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. RESULTS: Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (µg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (µmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ 2 = 7.288, P = 0.007]. CONCLUSIONS: Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

The effect of HA330 hemoperfusion adsorbent method on inflammatory markers and end-organ damage levels in sepsis: a retrospective single center study.

OBJECTIVE: In this study, we aimed at evaluating the impact of HA330 hemoperfusion adsorbent application on inflammatory markers and end-organ damage markers in patients with sepsis/septic shock. PATIENTS AND METHODS: Patients who were diagnosed with sepsis/septic shock and treated with HA330 hemoperfusion adsorbent in addition to the standard treatment were included in this retrospective study conducted at Inonu University Turgut Ozal Medical Center between January 1, 2019 and January 1, 2021. RESULTS: A total of 150 patients were included in the study. The mean±SD age of the patients was 51.9±17.7 years. 102 patients (68%) were in septic shock. Mean±SD APACHE II scores were 15.3±4.8. The need for mechanical ventilation was noted in 64 patients (42.7%). WBC, neutrophil count, hemoglobin, platelet count, BUN, creatinine, AST, ALT, CRP and procalcitonin levels were measured before and after the procedure. Overall, 104 patients (69.3%) died median (min-max) 2.5 (1-114) days after the cytokine adsorption, while 46 patients (30.7%) recovered from sepsis and were discharged. The increase in BUN levels and decrease in platelet count after the procedure were statistically significant (p≤0.001, 0.041, respectively) in the overall study population. The laboratory findings in 46 survivors indicated significantly decreased AST and ALT levels after cytokine adsorption compared to baseline pre-treatment levels. WBC, neutrophil count, CRP, procalcitonin, BUN and creatinine values were also decreased after cytokine adsorption in survivors, whereas the change was not statistically significant. There was also a non-significant tendency for an increase in platelet count and hemoglobin levels after cytokine adsorption compared to pre-treatment values in these patients. CONCLUSIONS: Although no effect of HA330 hemoperfusion application on inflammatory markers and end-organ damage markers was demonstrated in our study, we used the HA330 hemoperfusion adsorbent method as a last resort in terminal patients with a mortality rate of approximately 90% and for whom antibiotic treatment did not benefit. Therefore, multicenter, prospective studies are needed to clarify the effect of early HA330 hemoperfusion use in the treatment of sepsis.