Research progress on blood compatibility of hemoperfusion adsorbent materials.

This comprehensive review examines the latest developments in improving the blood compatibility of hemoperfusion adsorbents. By leveraging advanced coating and modification techniques, including albumin-collodion, cellulose, hydrogel, and heparin coatings, notable enhancements in blood compatibility have been achieved across diverse adsorbent types, such as carbon-based, resin-based, and polysaccharide-based materials. Despite promising laboratory results, the intricate manufacturing processes and elevated costs present significant challenges for broad clinical application. Therefore, future endeavors should focus on cost-benefit analysis, large-scale production strategies, in-depth exploration of blood-material interactions, and innovative technologies to propel the development of safer and more effective blood purification therapies.

Polymyxin B Hemoperfusion in Sepsis: A Possible Silver Lining to the Dark Clouds?

How to cite this article: Sharma J, Khatav SK. Polymyxin B Hemoperfusion in Sepsis: A Possible Silver Lining to the Dark Clouds? Indian J Crit Care Med 2024;28(10):903-905.

Case report: Manual carbon hemoperfusion for the treatment of meloxicam toxicity in a cat and suspected ibuprofen toxicity in a dog.

Extracorporeal blood purification (ECBP) has become a popular treatment option for non-steroidal anti-inflammatory drug (NSAID) toxicity in small animals. However, challenges arise when using ECBP for small dogs and cats because the priming volume required by most machine-based ECBP platforms might be excessive, leading to cardiovascular instability if a blood prime is not used. This report describes the successful use of manual carbon hemoperfusion (MCHP) to reduce plasma meloxicam levels in a cat following an inadvertent overdose and its use in a dog following suspected ibuprofen ingestion. In both animals, MCHP reduced the circuit volume needed for ECBP from 125 mL with a machine-based therapeutic plasma exchange or 104 mL with an in-series carbon hemoperfusion on an intermittent hemodialysis platform to just 40-50 mL. In the cat, MCHP reduced plasma meloxicam levels by 44%, and in both animals, the use of MCHP in these pets was well-tolerated and safe. Due to pre-existing anemia, the cat required a blood transfusion but the dog did not. MCHP is technically simple and can be performed at any hospital with access to carbon filters and blood bank resources. This technique may represent a reasonable alternative to treat NSAID toxicities in animals that are too small for conventional extracorporeal decontamination methods using either machine-based platforms without using a blood prime or in locations where these machines are unavailable.

Extracorporeal cytokine adsorption as therapeutic option for immune effector cell-associated neurotoxicity syndrome.

With the rising number of patients receiving chimeric antigen receptor T-cells, the treatment of this therapy's complications is of growing concern to intensivists and neurologists. We used extracorporeal cytokine adsorption as an add-on therapy in a patient suffering from immune effector cell-associated neurotoxicity syndrome. Interleukin-6 level, which as a readily available parameter is generally used to evaluate course of disease, was rapidly reduced using this method. The patient made a full recovery and is still in hematological remission.

Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial.

Hemoperfusion is a novel adjunct therapy that targets the dysregulated inflammatory events in severe sepsis. Previous studies have reported conflicting results on its efficacy and safety. This study was designed to assess the efficacy and safety of hemoperfusion among leptospirosis patients in septic shock and renal failure in terms of improvement in 28-day mortality, SOFA score, level of inflammatory markers, hemodynamics, and renal and pulmonary function. A total of 37 severe leptospirosis patients were enrolled and randomized into either standard medical therapy (SMT) alone, n = 20, or with hemoperfusion (HP), n = 17. Vital signs, urine output, vasopressor dose, PaO2/FiO2 (P/F) ratio, and biochemical parameters of patients from each treatment arm were compared. The hemoperfusion group showed a 36.84% (p = 0.017) risk reduction in 28-day mortality. Levels of procalcitonin, IL6, and lactate significantly decreased from baseline to day 7 in both groups. Statistically significant improvements in serum creatinine (p = 0.04) and PF ratio (p = 0.045) were observed in the hemoperfusion cohort. Intention-to-treat and per-protocol approaches showed that hemoperfusion increased the survival rate and decreased the mortality risk. This benefit for survival persisted even when patients were also receiving extracorporeal membrane oxygenation (ECMO), showing that hemoperfusion's benefits are independent of ECMO use. Hemoperfusion is a safe and effective adjunct therapy for managing severe sepsis. It promotes earlier renal and pulmonary function recovery and improves the survival of septic shock patients.

Rare skin color changes in an acute pancreatitis patient undergoing maintenance hemodialysis.

BACKGROUND: Skin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently. CASE PRESENTATION: A 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient's dialysis effluent initially appeared red. Upon examination of the patient's peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient's method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged. CONCLUSIONS: In the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Add-on hemoperfusion in SARS-CoV-2-infected pregnant patients: a case series.

BACKGROUND: Pregnant women are more likely to have a higher severity of illness after being infected with coronavirus disease 2019 compared with the general population, particularly in the hyperinflammatory phase. However, immunomodulatory drugs are contraindicated and have been associated with an increased risk of fetal abnormalities. Therefore, we are reporting our experience with the use of HA330 hemoperfusion in combination with standard therapy in severe to critical coronavirus disease 2019 cases among pregnant patients. CASE PRESENTATION: From January 2020 to December 2021, four pregnant Thai women were treated with hemoperfusion using a cytokine adsorptive technique. The patients' ages ranged from 21 to 36 years old, and their gestational ages at the time of admission ranged from 18 to 38 weeks. Two patients required intubation. Extracorporeal blood purification with an adsorptive cartridge (HA330®, Jafron, China) was applied as an adjunctive strategy to standard therapy approximately one week after the onset of symptoms, and most patients received three sessions of hemoperfusion. The baseline C-reactive protein level was greater than 80 mg/dL. The results showed that hemoperfusion could decrease the C-reactive protein level by approximately 80% and improve oxygenation. The newborns were delivered by Cesarean section without complications. Neither mortality nor serious adverse events related to hemoperfusion occurred. CONCLUSION: This report may help ensure the use of the hemoperfusion strategy in pregnant patients during a cytokine storm. However, a larger cohort is needed to confirm its safety and efficacy.

A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses.

With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine.

Factors associated with refusing hemoperfusion in patients with acute paraquat poisoning.

Background: Paraquat poisoning remains a critical public health issue with no established effective treatment. Hemoperfusion (HP) has been recognized for its potential to remove toxins and is widely employed in several developing countries for managing acute paraquat poisoning cases. However, the reluctance of some patients to undergo this recommended treatment has been observed but not thoroughly investigated. This study aimed to explore the factors associated with the refusal of HP in patients suffering from paraquat intoxication. Materials and Methods: In this retrospective study, data of 358 patients with acute paraquat poisoning were analyzed in Xi'an, China. The outcome of our study was mortality, and the influential factors were age, gender, marital status, educational level, symptoms at presentation, and laboratory findings. A logistic regression model was utilized to explore the independent risk factors. Results: In a total of 358 paraquat-poisoned patients, the significant differences were found between patients who underwent HP and those who did not, particularly regarding mean age (48.02 years vs. 42.32 years; P = 0.01), mental disorders (15.6% vs. 6.1%; P = 0.01), poisoning severity score (2.36 vs. 2.57; P = 0.03), organ failure (10.9% vs. 23.5%; P = 0.02), and mechanical ventilation (18.8% vs. 33.3%; P = 0.02). Patients who refused HP exhibited a higher mortality (20.3% vs. 10.9%; P = 0.03) compared to those who received HP. Age (odds ratio (OR), 1.76; 95% confidence interval (CI): 1.01-3.82; P = 0.01) and history of mental disorders (OR, 2.81; 95% CI: 1.19-6.61; P = 0.02) were identified as significant independent predictors for the refusal of HP. Conclusion: The results of this study showed that elderly individuals and those with a history of mental disorders were independently associated with refusing HP in patients with acute paraquat poisoning.

Management of Paraquat Poisoning-The Way Forward.

How to cite this article: Ahmed A, Prasad A, Bhattacharjee A. Management of Paraquat Poisoning-The Way Forward. Indian J Crit Care Med 2024;28(8):722-723.

A Study of Paraquat Poisoning Presentation, Severity, Management and Outcome in a Tertiary Care Hospital: Is There a Silver Lining in the Dark Clouds?

Introduction: Accidental or intentional ingestion of paraquat leads to many local and systemic effects and the mortality rate is very high. There is limited data from North India and our objectives were to study the spectrum of presentation, treatment given, and its relation with outcome in a tertiary care setting. Materials and methods: This retrospective observational study was conducted after ethical approval and data regarding demography, clinical features, duration of presentation, organ involvement, renal replacement therapy (RRT), management, and outcome was collected. Statistical analysis was done by calculating mean and standard deviation (SD). Chi-square (χ2) test was applied to categorical variables and the Fisher exact test was used when the expected frequency was less than 5. Results: The study population consisted of 91 male (84%) and 18 female patients. Out of 109 patients, 13 survived (12%) and 88% had a fatal outcome. Nearly 92% of patients belonged to rural background, and 68% were of younger (<30 years) age group. Age, gender, occupation, and amount taken did not have any significant relation with mortality. Patients having metabolic acidosis (58.7%), altered renal (75.2%), and hepatic function (62.3%) at presentation had a statistically significant relation with mortality. Duration of presentation was significantly lesser in patients who survived (17.26 ± 17.23, median 14 hours vs 80.18 ± 90.07, median 48 hours) compared to patients who did not survive. Renal replacement therapy (n = 57) had no relation with mortality whereas 36% of the patients who received hemoperfusion (HP) survived (p = 0.03). Conclusion: Treatment should be started early as the duration of the presentation has a significant association with the outcome. Currently there is no antidote available. Supportive treatment includes oxygenation, immunosuppression, antioxidants, RRT, and HP wherever the resources are available. How to cite this article: Goyal P, Gautam PL, Sharma S, Paul G, Taneja V, Mona A. A Study of Paraquat Poisoning Presentation, Severity, Management and Outcome in a Tertiary Care Hospital: Is There a Silver Lining in the Dark Clouds? Indian J Crit Care Med 2024;28(8):741-747.

[Extracorporeal procedures in sepsis]. / Extrakorporale Verfahren bei der Sepsis.

Sepsis and septic shock are frequent and severe clinical pictures in intensive care medicine that result from a dysregulated immune response to an infection and cause a high mortality rate. This article provides an overview of the various extracorporeal procedures used to treat sepsis. Various procedures are used to treat sepsis and septic shock. These include high-volume hemofiltration (HVHF), very high-volume hemofiltration (VHVHF), high cut-off filter (HCO), polymyxin B hemoperfusion and cytokine adsorption filters. The HVHF and VHVHF remove inflammatory mediators but show no significant benefit in terms of stabilization and survival in sepsis patients. The HCO filters effectively eliminate cytokines but so far there is no evidence of a survival benefit. Polymyxin B hemoperfusion shows promising results in initial studies in certain patient groups, while evidence for cytokine adsorption filters is limited. Combined plasma filtration and adsorption (CPFA) and therapeutic plasma exchange (TPE) have so far shown promising results in small studies. Although CPFA shows no survival benefit, TPE may have protective effects on the vascular glycocalyx. Extracorporeal procedures carry risks such as thrombosis and loss of proteins and clotting factors. The therapeutic benefit of these procedures in the treatment of sepsis remains unclear and further prospective randomized multicenter studies are needed to evaluate their efficacy and safety. There are currently no guideline recommendations for the routine use of these procedures in sepsis.

Use of extracorporeal hemoperfusion therapy in an adult horse with Clostridioides difficile colitis and severe systemic inflammatory response syndrome.

An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.

Treatment of an accident of imidacloprid poisoning.

Objective: Accidental oral imidacloprid poisoning occurred in a family in Shandong, China, in May 2023. This study aimed to analyze the clinical characteristics of this imidacloprid poisoning event and investigated the detection of toxicants. Methods: Clinical data of four patients with oral imidacloprid poisoning were collected and retrospectively analyzed. The relevant literature was then reviewed. Results: Four patients from the same family received different oral doses of imidacloprid. The main clinical manifestations were digestive and neurological symptoms, including nausea, vomiting, and varying degrees of consciousness. Laboratory tests showed an increased white blood cell count, neutrophil proportion, and mild elevation of transaminase and urea nitrogen levels in some patients. Following comprehensive treatment, which included hemoperfusion, gastric lavage, total gastrointestinal decontamination, and drug symptomatic treatment, the patient's symptoms were quickly relieved, and the concentration of imidacloprid in the blood rapidly decreased. Conclusion: Toxicant detection is an important criterion for the differential diagnosis of poisoning and is helpful for disease assessment, treatment plan formulation, and in determining patient prognosis.

Assessing the efficacy of hemoperfusion for dermatomyositis-associated acute exacerbation of interstitial pneumonia: a multicenter retrospective study.

OBJECTIVES: Hemoperfusion (HP) is used to treat various diseases, including sepsis and acute respiratory distress syndrome. However, few studies have explored the efficiency of HP in dermatomyositis-associated acute exacerbation of interstitial lung disease. METHODS: We conducted a retrospective study. Two hundred and sixteen patients with dermatomyositis-associated acute exacerbation of interstitial lung disease were included. Patients were divided into the HP group (treatment group) and the control group. Changes in oxygenation, hemodynamic parameters, lung ultrasound scores, and inflammatory cytokine levels were evaluated before and after HP in the treatment group. The length of intensive care unit (ICU) stays, duration of ventilator therapy, mortality rate, and incidence of complications were compared between the treatment and control groups. RESULTS: Hemodynamic and oxygenation variables in the treatment group significantly improved after treatment. However, the levels of the inflammatory factors significantly decreased after treatment. The length of ICU stay and the duration of ventilator therapy were significantly shorter in the treatment group than in the control group. The mortality rate of the treatment group was significantly lower than that of the control group. CONCLUSION: This study demonstrated that HP could improve treatment efficacy in patients with dermatomyositis-associated acute exacerbation of interstitial lung disease.

Extracorporeal membrane oxygenation combined with hemoperfusion to assist in the rescue of aconitine poisoning: A case report.

Extracorporeal membrane oxygenation (ECMO) has been widely used as a clinical bridge for cardiopulmonary failure. We recently used combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and haemoperfusion to successfully treat a patient with acute aconitine poisoning. The patient was admitted to the Emergency Intensive Care Unit (EICU) in a state of coma and shock. Her received comprehensive treatment, including haemoperfusion and anti-shock therapy. 40 minutes after admission, the patient experienced sudden respiratory and cardiac arrest. After conventional defibrillation and cardiopulmonary resuscitation proved ineffective, veno-arterial ECMO was immediately initiated. One hour after initiation of VA-ECMO, the patient's heart rhythm stabilised to sinus rhythm. After 33 h of supportive care, the patient was awake, haemodynamically stable and the VA-ECMO was successfully removed. The patient made full recovery 7 days after admission.

A Case of High-Dose Intravenous MgSO4 and Hemoperfusion for Aconite Poisoning with Chronic Kidney Disease.

Aconite contains four highly toxic diester-diterpene alkaloids, including aconitine, mesaconitine, hypaconitine, and jesaconitine, in all plant parts. Aconite has been used as for suicide, murder, and as an arrow poison since ancient Greek and Roman times. Ventricular tachyarrhythmias are the most common cause of death in aconite poisoning, and antiarrhythmic drugs and cardioversion are ineffective. A 61-year-old woman ingested the crushed raw roots of a single aconite plant. An ambulance brought her to the Tottori University Hospital 30 min after ingestion. She had a history of chronic stage 5 kidney disease but was not on dialysis. Her heart rate (HR) was 120 bpm upon arrival. The patient developed sustained supraventricular tachycardia (SVT) at an HR of 165 bpm with frequent premature ventricular contractions (PVCs) 15 min after arrival. She then developed sustained monomorphic ventricular tachycardia (VT) at an HR of 200 bpm 20 min after arrival, which progressed to pulseless polymorphic VT. Cardioversion was unsuccessful. External cardiac massage restored spontaneous circulation; however, her underlying rhythm remained sustained SVT with frequent PVCs. These arrhythmias repeatedly led to circulatory arrest. She was administered six intravenous boluses of 2 g of MgSO4 in the emergency department, which prevented her from going into sustained pulseless VT. Hemoperfusion (HP) with activated charcoal was performed 1.5 h after arrival. The aconitine, mesaconitine, and hypaconitine plasma concentrations were high at 8.9, 23.5, and 5.5 ng/mL, respectively, before the start of HP but decreased to 1.7, 4.0, and 2.7 ng/mL, respectively, after 7 h of HP. She returned to sinus rhythm on the second day of hospitalization; however, the patient required maintenance hemodialysis. We concluded that high-dose IV MgSO4 is an effective treatment for fatal tachyarrhythmias due to aconite poisoning, and that in cases of renal failure, HP may be required to remove aconite toxins from the body.

[Application of Modified Polyether Sulfone Microspheres in Hyperbilirubinemia]. / æ”¹æ€§èšé†šç œå¾®çƒåœ¨é«˜èƒ†çº¢ç´ è¡€ç—‡ä¸­çš„åº”ç”¨ç ”ç©¶.

Objective: To design and prepare a high efficiency bilirubin adsorbent with good mechanical properties and biocompatibility. Methods: In this study, quaternary ammonium pyridine was designed and synthesized, and then modified polyether sulfone microspheres, or PES/p(4-VP-co-N-VP)@6 microspheres, were prepared by phase conversion and electrostatic spraying. The morphology of the polymer components and the microspheres were studied by means of nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy. The basic properties of the microspheres and their bilirubin adsorption efficiency were tested, and the adsorption mechanism was further explored. Blood cell counts and the clotting time of the microspheres were also measured. Results: The diameter of the modified polyether sulfone microspheres prepared in the study was approximately 700-800 µm. Compared with the original PES microspheres, the surface and internal structure of PES/p(4-VP-co-N-VP)@6 microspheres did not change significantly, and they also had a loose porous structure, with some micropores scattered around in addition to irregular large pores. Compared with the control group, the bilirubin removal effect of the modified microspheres was (94.91±0.73)% after static adsorption in bilirubin PBS buffer solution for 180 min, with the difference being statistically significant (P<0.0001). According to the findings for the clotting time, the activated partial thromboplastin time (APTT) of the blank plasma group, the control PES group, and the modified PES microsphere group were (27.57±1.25) s, (28.47±0.45) s, and (30.4±0.872) s, respectively, and the difference between the experimental group and the other two groups was statistically significant (P<0.01, P<0.05). There was no significant change in red blood cell and white blood cell counts. Conclusion: The microspheres prepared in the study have high efficiency in bilirubin adsorption, excellent mechanical properties and thermal stability, and good blood biocompatibility, and are expected to be used in the clinical treatment of patients with liver failure.

High adsorption capacity of hemoperfusion on imipenem in critically ill patients with septic shock: a case report.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion. CASE PRESENTATION: The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem. CONCLUSIONS: This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion.

[Extracorporeal treatment in poisoning]. / Extrakorporale Verfahren bei Vergiftungen.

In rare cases, intoxicated patients may require an extracorporeal procedure for enhanced toxin elimination. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup provides consensus- and evidence-based recommendations regarding the use of extracorporeal procedures in the management of critically ill, poisoned patients, with ongoing updates. Extracorporeal clearance is highest for low molecular weight substances with low volume of distribution, low plasma protein binding, and high water-solubility. To maximize the effect of extracorporeal clearance, blood and dialysate flow rates should be as high as possible, and the membrane with the largest surface area should be utilized. Intermittent hemodialysis is the most commonly employed extracorporeal procedure due to its highest effectiveness, while hemodynamically compromised patients can benefit from a continuous procedure.