Adsorption of Endotoxin and Mitigation of Sepsis.

In the fields of sepsis and systemic inflammation, endotoxin might be the most studied molecule since the term was coined by Richard Pfeiffer in 1892. Paradoxically measuring endotoxin in humans and finding an effective treatment for endotoxemia have remained challenging. While advances have been made in understanding the mechanisms of how this simple molecule can trigger an intense immune cascade, there is an ever growing need to develop better treatments. Studies measuring endotoxin levels in patients with septic shock have consistently demonstrated that there is a dose-response relationship between endotoxin levels and adverse outcomes. A rapid assay to measure endotoxin activity has been available for more than a decade, but few studies have synergized the assay with a therapeutic. Polymyxin B hemoperfusion (PMX-HP) leverages a molecule with high affinity for endotoxin with a technique to eliminate exposure. Polymyxin is bound and immobilized to fibers within a cartridge and administered as an extracorporeal therapy via veno-venous hemoperfusion. Clinical evidence of its use is plentiful yet inconsistent in studies based on an outcome for mortality at 28 days. Herein, we describe targeted patient selection using the endotoxin activity assay and clinical phenotyping followed by adsorption of endotoxin using the PMX-HP for endotoxemic sepsis.

Potential survival benefit and early recovery from organ dysfunction with polymyxin B hemoperfusion: perspectives from a real-world big data analysis and the supporting mechanisms of action.

BACKGROUND: Endotoxin (ET) removal therapy with polymyxin B-immobilized fiber column hemoperfusion (PMX-HP) has been used for the treatment of septic shock. Some observational studies reported clinical benefits, particularly in specific subgroups of patients. However, larger randomized controlled trial results have been disappointing. MAIN BODY: The four studies that revealed the survival benefit of PMX-HP were based on the Japanese Diagnosis Procedure Combination (DPC) national inpatient database (J-DPC study). Nevertheless, one J-DPC study and a randomized controlled trial (RCT) conducted in France evaluated PMX-HP in patients with abdominal septic shock and did not report a significant survival benefit. In both studies, the severity of illness was too low to find substantial significant differences in mortality. The results of the J-DPC studies further suggest that some subpopulations of patients could benefit from PMX-HP. Based on these results, this review revisited prior RCTs and other large-scale studies on PMX-HP. In addition, four J-DPC studies and one large-scale study reported a survival benefit with PMX-HP. A secondary analysis of the EUPHRATES trial, the most recent double-blinded RCT of PMX-HP conducted in North America, suggested a survival benefit in patients with high levels of endotoxemia. In the J-DPC studies and the EUPHRATES trial, ventilator-free days, vasoactive drug-free days, and renal replacement-free days were significantly improved in the PMX-HP groups. These findings suggest that PMX-HP can contribute to early recovery from organ dysfunction. The reduction of supportive care likely provides important health and economic benefits for managing patients with septic shock. Finally, the blood levels of mediators or biomarkers related to respiratory, cardiovascular, and renal dysfunction have been reported to be normalized with PMX-HP. CONCLUSIONS: These results support the biological rationale for the improvement in organ dysfunction observed in the J-DPC studies and other large-scale studies, including the EUPHRATES trial. Real-world evidence from large data sets suggests an appropriate patient population that are likely to benefit from the utility of PMX-HP for septic shock.

Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock.

Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.

Anti-endotoxin Properties of Polymyxin B-immobilized Fibers.

Polymyxin B is an antibiotic that shows strong bactericidal activity against Gram-negative bacteria, by binding to and inactivating endotoxin. Systemic administration of polymyxin B in humans is restricted because of its nephrotoxicity and neurotoxicity, and this compound was therefore considered a strong candidate ligand for the extracorporeal selective adsorption of circulating endotoxin in the blood. Toraymyxin® is a direct hemoperfusion column that uses polymyxin B attached to an insoluble carrier to bind endotoxin in the blood. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock.In this chapter, we will review the development, clinical use, and efficacy of Toraymyxin, examine the structure of the Toraymyxin column, and comment on the current position of Toraymyxin in the treatment of severe sepsis and septic shock. We will also highlight some potential new applications of Toraymyxin for pulmonary diseases.

Novel Insights into the Direct Removal of Endotoxin by Polymyxin B Hemoperfusion.

AIM: To demonstrate the capacity of polymyxin B-direct hemoperfusion (PMX-DHP) column Toraymyxin® 20R (PMX-20R) in removing endotoxin (LPS) from perfused blood, serum and plasma. METHODS: Endotoxin-spiked bovine serum was perfused in PMX-20R as per the recommended performance testing protocol. Samples were taken at various time points to assess the amount of endotoxin removed during a 4-h session. In another set of experiments, FITC-labelled LPS (FITC-LPS) was spiked into a pool of human whole blood, followed by perfusion with the spiked blood for 2 h in order to allow FITC-LPS to bind PMX-20R. The amount of LPS was extracted from the columns and the amount of specifically bound LPS was determined by fluorometry. RESULTS: PMX-20R columns perfused with bovine serum had an average binding rate of 88%, equivalent to approximately 12 µg of LPS. When PMX-20R was perfused with human whole blood, the columns bound an average of 20 µg of FITC-LPS. CONCLUSION: PMX-20R can bind LPS in all the biological fluids tested. The calculated binding capacity of 12-20 µg LPS suggests that in septic cases where endotoxin is present in the circulation, PMX-20R is able to adsorb clinically significant levels of endotoxin.

Extracorporeal removal of endotoxin: the polymyxin B-immobilized fiber cartridge.

Endotoxin, which consists of lipopolysaccharide (LPS), is an outer membrane component of the Gram-negative bacterial cell wall. Endotoxin in the blood stream from an infectious focus or through translocation from the gut plays an important role in the pathogenesis of severe sepsis and septic shock. It binds to monocytes and macrophages, activating them to trigger the production of a variety of mediators. These mediators injure endothelial cells and induce microcirculatory dysfunction. This leads to subsequent organ dysfunction and multiorgan failure. The neutralization or elimination of endotoxin in the blood is an enticing approach for treating severe sepsis and septic shock. Selective adsorbent therapy targeting blood endotoxin has been clinically applied for more than 15 years, mainly in Japan and more recently in Italy and other countries. Toraymyxin(TM) (PMX;Toray, Tokyo, Japan) is a selective blood endotoxin removal cartridge. PMX is composed of polymyxin B (PL-B) covalently bonded to polystyrene-derivative fibers. It is well known that PL-B binds endotoxin and has bactericidal activity. PL-B has a strong affinity to endotoxin and is able to bind the lipid A portion of endotoxin through ionic and hydrophobic interactions. Intravenous injection of PL-B has significant nephrotoxic and neurotoxic effects. However, covalently immobilized PL-B on the adsorbents of PMX do not leak out into the blood stream, thus allowing the clinical application without the known toxic effects of PL-B. Within each cartridge, an adsorbent structure made of PL-B-fixed fabrics is included. Blood flow direction is well controlled by adopting a radial flow system. PMX treatment occurs by hemoperfusion at a blood flow rate of about 80-120 ml/min. Heparinis preferably used as an anticoagulant. In Japan, PMX has been clinically used since 1994under the national health insurance system. It is estimated that over 80,000 patients have received PMX treatment in Japan. Not only has PMX been clinically used safely in Japan, but also in other countries.

Application of polymyxin B convalently immobilized fiber in patients with septic shock.

Sepsis and septic shock are major causes of morbidity and mortality in the intensive care unit. Endotoxin produced by Gram-negative bacteria contributes to the pathogenesis of sepsis and septic shock. As an adsorbent, a polymyxin B convalently immobilized fiber (PMX) was developed. This review discusses, designing of the PMX, its application in clinical practice and the clinical outcomes.

Circulating levels of advanced glycation end products (AGE) and interleukin-6 (IL-6) are independent determinants of serum asymmetric dimethylarginine (ADMA) levels in patients with septic shock.

There is a growing body of evidence that nitric oxide (NO) excess plays a central role in the pathogenesis of hypotension and organ failure in patients with septic shock. In addition, recently, asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been shown to contribute to the regulation of vascular tone via modulation of NO generation in vivo. However, the kinetics and regulation of serum levels of ADMA in patients with septic shock are largely unknown. Since high mobility group box 1 (HMGB1)-receptor for advanced end products (RAGE) axis is supposed to be involved in the lethality in septic shock, we examined the correlations among serum levels of ADMA, endotoxin, interleukin-6 (IL-6), soluble form of RAGE (sRAGE) and RAGE ligands such as HMGB1 and advanced glycation end products (AGE) in septic shock patients. Fifteen septic shock patients (10 males and 15 females, mean age: 70.1+/-8.5 years) and fifteen age- and sex-matched healthy volunteers were included in this study. The criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were used for diagnosis of septic shock. All the subjects underwent a complete history and physical examination, determination of blood chemistries, including serum levels of ADMA, endotoxin, IL-6, HMGB1, AGE and sRAGE. Linear and multiple stepwise regression analysis were performed for the determinants of serum levels of ADMA. Serum levels of ADMA were significantly higher than those in healthy volunteers (0.98+/-0.21nmol/mL vs. 0.30+/-0.05nmol/mL, p<0.0001). In univariate analysis, creatinine (p<0.005), endotoxin (p<0.001), IL-6 (p<0.001), HMGB1 (p<0.001), AGE (p<0.001) and sRAGE (p<0.001) were significantly associated with serum ADMA levels. After performing multivariate stepwise regression analyses, IL-6 (p=0.001), AGE (p=0.002) and creatinine (p=0.013) still remained significant independently. The present study is the first demonstration that ADMA levels were significantly elevated in patients with septic shock and that serum IL-6, AGE and creatinine levels were independent determinants of ADMA in these patients. Given the harmful effects of NO excess in septic shock, ADMA levels may be increased as a counter-system against inflammation and oxidative stress in this life-threatening disorder.

Polymyxin B-immobilized fiber hemoperfusion with the PMX-05R column in elderly patients suffering from septic shock.

BACKGROUND: Direct hemoperfusion with the polymyxin B-immobilized fiber (PMX-20R) column has a positive effect on outcome in patients with sepsis or septic shock. The PMX-05R column has a low priming volume and has been used in pediatric patients with septic shock. The aim of the present study was to determine whether PMX-F treatment with the PMX-05R column is effective in elderly patients with septic shock. PATIENTS AND METHODS: We performed direct hemoperfusion twice with the PMX-05R column in 8 septic shock patients who were over 80 years of age. Five of the 8 patients survived. The 3 patients who died were undergoing hemodialysis for chronic renal failure, and methicillin-resistant Staphylococcus aureus was detected in all 3. RESULTS: PMX-F treatment significantly increased systolic and diastolic blood pressures (P = 0.0004 for both) and significantly reduced heart rate (P < 0.0001), the blood endotoxin level (P = 0.0011), blood IL-6 level (P = 0.039), C-reactive protein level (P < 0.0001), and white blood cell count (P < 0.0001). CONCLUSIONS: Direct hemoperfusion with the PMX-05R column is effective in ameliorating clinical and laboratory abnormalities in elderly septic shock patients.

Changes in plasma interleukin-18 by direct hemoperfusion with polymyxin B-immobilized fiber in patients with septic shock.

BACKGROUND/AIMS: Polymyxin B-immobilized fiber (PMX-F) treatment is reported to be safe and effective in patients with severe sepsis and septic shock. The aim of the present study was to determine whether plasma levels of interleukin (IL)-18, which is linked with sepsis, are associated with plasma endotoxin levels and sepsis-related scores and whether PMX-F treatment affects these variables in patients with septic shock. PATIENTS AND METHODS: Twenty-six patients with septic shock (15 men and 11 women; mean age 56.5 years) and 20 age-matched healthy subjects (12 men and 8 women; mean age 54.0 years) were included in this study. Septic shock patients were divided into 2 groups: a PMX-F treatment group (9 men and 5 women; mean age 57.5 years) and a conventional treatment group (7 men and 5 women; mean age 55.3 years). Standard supportive care was continued without change during PMX-F treatment. Plasma endotoxin, plasma IL-18, and clinical variables were measured before, immediately after the first and second PMX-F treatment, and the following day. RESULTS: The plasma IL-18 levels were significantly higher in septic shock patients (1,320+/- 360 pg/ml) than in healthy volunteers (140+/- 60 pg/ml; p< 0.001). The IL-18 level was significantly correlated with the plasma endotoxin level (p < 0.001), the Acute Physiology and Chronic Health Evaluation II score (p<0.01), the Sepsis Severity Score (p<0.01), the number of failed organs (p<0.01), and the Goris score (p<0.01). PMX-F treatment reduced the plasma endotoxin and IL-18 levels significantly after the first treatment (p<0.05), after the second treatment (p<0.01), and on the following day (p<0.001). However, these variables did not change significantly during conventional treatment. CONCLUSIONS: IL-18 may be associated with the severity of septic shock, and PMX-F treatment is effective in reducing the IL-18 level in patients with septic shock.

Effect over time of endotoxin adsorption therapy in sepsis.

Despite the use of potent antibiotics and intensive supportive care, the mortality among patients with sepsis and Gram-negative bacteremia remains high. In recent years, endotoxin adsorption therapy (PMX-DHP, polymyxin-direct hemoperfusion) has been widely used in Japan to remove endotoxin, a causative agent of sepsis. In septic patients whose clinical condition may change at any moment, the decision of when to perform blood purification in addition to conventional intensive care is a critical factor in the therapeutic strategy and prognosis. In the present study, we investigated the effect over time of PMX-DHP in sepsis. The subjects were 16 patients with systemic inflammatory response syndrome (SIRS) who required surgical treatment including a surgical operation and drainage. The following six parameters were compared between the first and second PMX-DHP: mean blood pressure and time-restricted urine at four time points - at baseline and at 6, 24 and 72 h after PMX-DHP; and white blood cell count, platelet count, base excess and Septic Severity Score (SSS) at 24 and 72 h after PMX-DHP. Mean blood pressure improved over time up to 24 h after both the first and second PMX-DHP. Time-restricted urine volume improved only at 6 h after the first PMX-DHP. White blood cell count improved over time up to 24 h after both the first and second PMX-DHP. The SSS improved at all time points studied except for 3 days after the second PMX-DHP. We conclude that PMX-DHP is expected to have important implications in terms of (i) correction of clinical conditions (by severity assessment); (ii) improvement of hemodynamics; (iii) possible anti-inflammatory effect; and (iv) possible improvement of oxygen metabolism in tissues.

Effect of polymyxin B-immobilized fiber on blood metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in acute respiratory distress syndrome patients.

BACKGROUND/AIMS: Metalloproteinase (MMP)-9 plays a role in the pathogenesis of acute respiratory distress syndrome (ARDS). Polymyxin B-immobilized fiber (PMX-F) treatment improves circulatory disturbance and oxygenation in ARDS patients. We aimed to assess whether PMX-F treatment alters the blood MMP-9 and tissue inhibitor of MMP (TIMP)-1 levels in ARDS patients. METHODS: Twelve ARDS patients who received PMX-F treatment and 20 healthy control volunteers were included in this study. PMX-F was carried out twice at a rate of 100 ml/min for 2 h with a time interval of 24 h. Blood MMP-9 and TIMP-1 levels were measured before and after PMX-F treatment. We monitored blood pressure and the PaO2/FiO2 (PF) ratio before and after PMX-F treatment. RESULTS: The mortality of ARDS patients after PMX-F treatment was 16.7%. Chest X-ray abnormalities were ameliorated in surviving patients after PMX-F treatment. Systolic and diastolic blood pressure increased significantly after PMX-F treatment (p < 0.01). The PF ratio also increased significantly after PMX-F treatment (p < 0.01). Blood MMP-9 and TIMP-1 levels in ARDS patients (126.4 +/- 36.4 and 326.5 +/- 52.5 ng/ml) were significantly higher than in controls (34.5 +/- 12.5 and 160.5 +/- 24.5 ng/ml; p < 0.01). PMX-F treatment reduced these levels significantly (the first treatment: MMP-9 85.4 +/- 28.6 ng/ml, p < 0.05, TIMP-1 265.8 +/- 36.6 ng/ml, p < 0.05; the second treatment: MMP-9 56.5 +/- 18.8 ng/ml, p < 0.01, TIMP-1 220.6 +/- 30.5 ng/ml, p < 0.01). CONCLUSION: These data suggest that MMP-9 and TIMP-1 may play a role in the pathogenesis of ARDS and that PMX-F treatment ameliorated increased MMP-9 and TIMP-1 levels in ARDS patients.

Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin).

Toray Industries Inc. has developed an endotoxin removal cartridge (Toraymyxin) composed of a polymyxin B immobilized, fibrous adsorbent. Toraymyxin has been listed as a blood purification medical device for endotoxin removal to be reimbursed by the Japanese national health insurance since 1994. Toraymyxin can be applied to patients with endotoxemia or suspected gram-negative infection, which fulfilll the conditions of Systemic Inflammatory Response Syndrome (SIRS) and have septic shock demanding vasopressor infusion. Since 1994, over 30,000 patients have received this treatment. The safety of this device has been confirmed and improvement of hemodynamic dysfunction has been shown to be a major benefit. Infection resulting from an acute abdominal condition requiring surgery has been shown to be one of the good indications for Toraymyxin. Further studies are now ongoing to establish Toraymyxin treatment as one of the options to treat sepsis and septic shock patients and to clarify the mechanisms involved in this therapy.

Endotoxin adsorption by polymyxin B immobilized fiber column in patients with systemic inflammatory response syndrome: the Japanese experience.

The polymyxin B immobilized fiber column (PMX) has been used to treat septic shock patients since 1994 under the Japanese health insurance system. In 1997, the results of the first multicenter clinical study enrolling 42 patients were published, showing a significant reduction in the plasma endotoxin level of the survivors, whilst there was no change with the non-survivors, following treatment with PMX. Body temperature, blood pressure and hemodynamic abnormalities were significantly improved after PMX treatment. The second multicenter study enrolling 88 patients demonstrated that in the survivors, the plasma level of mediators such as TNF-alpha, IL-6, IL-10 and plasminogen activator inhibitor-1 (PAI-1) was significantly decreased following treatment with PMX. Recent studies investigating the mechanisms of PMX treatment have indicated that various mediators other than endotoxin might be adsorbed by PMX. Possible mediators include endogenous cannabinoids, such as macrophage-derived anandamide, and platelet-derived 2-arachidonyl glyceride (2-AG) and tetrahydrobiopterin (BH4), an essential cofactor for inducible NO synthase. The interaction between PMX and activated monocytes may suggest an alternative mechanism for the improvement in patient condition following PMX treatment. Further studies are needed to clarify the mechanisms of PMX treatment and to strengthen the scientific basis of this treatment.

Hemoperfusion with polymyxin B-immobilized fiber in septic patients with methicillin-resistant Staphylococcus aureus-associated glomerulonephritis.

BACKGROUND/AIMS: We investigated whether urinary podocytes are present in septic patients with methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis and whether polymyxin B-immobilized fiber (PMX-F) treatment affects proteinuria and urinary podocyte excretion in these patients. METHODS: Twenty septic patients with MRSA-associated glomerulonephritis (mean age: 63.7 years) and 80 septic patients whose MRSA infection was not followed by glomerulonephritis (mean age: 60.5 years) were included in this study. All septic patients were treated with fosfomycin sodium, beta-lactams, arbekacin sulfate, and teicoplanin, or a combination of these. Twenty septic patients with MRSA-associated glomerulonephritis were randomly assigned to one of two treatments: PMX-F treatment (group A, n = 10) and conventional treatment (group B, n = 10). PMX-F treatment was repeated twice. RESULTS: Urinary podocytes and urinary protein excretion were not detected in MRSA septic patients without glomerulonephritis. However, urinary podocytes (1.7 +/- 0.6 cells/ml) and proteinuria (2.6 +/- 0.6 g/d) were detected in the 20 septic patients with MRSA-associated glomerulonephritis. Plasma endotoxin levels were decreased from 13.6 +/- 4.6 pg/ml to 6.6 +/- 2.2 pg/ml (p < 0.05) in group A. Levels in group B, however, showed little difference after treatment. Urinary podocytes were reduced in group A (from 1.8 +/- 0.6 cells/ml to 0.4 +/- 0.2 cells/ml, p < 0.01) as was urinary protein excretion (from 3.0 +/- 0.5 g/d to 0.8 +/- 0.4 g/d, p < 0.01) but urinary podocytes and protein excretion levels showed little difference after treatment in group B. CONCLUSION: PMX-F treatment may be effective in reducing urinary protein and urinary podocyte excretion in septic patients with MRSA-associated glomerulonephritis.

Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion in septic patients with trauma.

We investigated whether microalbuminuria/urinary creatinine ratio (MACR) is increased in septic patients with trauma and whether polymyxin B immobilized fiber (PMX-F) treatment decreases MACR. Twelve trauma patients without sepsis, 18 trauma patients with sepsis, and 10 healthy controls were included in this study. The 18 trauma patients with sepsis were randomly assigned to one of two groups, PMX-F treatment or conventional treatment. Urinary microalbumin and creatinine were measured before and after treatment. Plasma endotoxin levels were determined by endospecy test. Hemoperfusion with PMX-F was carried out twice, for 2 hours, at a flow rate of 100 ml/min. MACR increased in the 30 trauma patients (5.2+/-2.2 mg/mmol) in comparison to that in the healthy controls (1.0+/-0.6 mg/mmol, p < 0.01). In the 18 trauma patients with sepsis, MACR after sepsis (16.6+/-4.8 mg/mmol) was significantly greater than that before sepsis (5.5+/-2.3 mg/mmol, p < 0.01). There was a significant correlation between plasma endotoxin levels and MACR in septic trauma patients (p < 0.001). MACR was reduced from 17.0+/-5.0 mg/mmol to 4.2+/-1.5 mg/mmol (p < 0.01) with PMX-F, and plasma endotoxin levels were also reduced from 34.5+/-18.5 pg/ml to 10.8+/-6.6 pg/ml (p < 0.01). Neither MACR nor plasma endotoxin levels were affected by conventional treatment, however. In summary, trauma patients with sepsis appear to show increased MACR, and PMX-F therapy may be effective for attenuating the increase in MACR.

Removal of endotoxin in blood by polymyxin B immobilized polystyrene-derivative fiber.

Polymyxin B, a cationic cyclic decapeptide antibiotic, is well known to bind endotoxin and to neutralize its toxicity. Based on this principle, polymyxin B was immobilized on the chloroacetamidomethylated polystyrene fiber that is reinforced by polypropylene. The adsorbing capacity of the obtained fibers (polymyxin B immobilized fiber [PMX-F]) was evaluated on endotoxin and other serum components in serum and on heparin in phosphate-buffered saline. Fluorescein isothiocyanate-labeled or tetramethylrhodamine isothiocyanate-labeled lipopolysaccharide (LPS) was used as endotoxin. The measurement of the fluorescence intensity showed that PMX-F adsorbed these LPSs depending on their concentration and on amount. The adsorption of endotoxin was confirmed by desorption of LPS from PMX-F as well. PMX-F adsorbed serum amyloid protein A besides LPS, but neither C-reactive protein nor low-density lipoprotein. The adsorbing property of heparin was low.

Effects of hemoperfusion on serum cardiac troponin T concentrations using polymyxin B-immobilized fibers in septic patients undergoing hemodialysis.

We investigated whether serum cardiac troponin T levels are altered in septic patients undergoing hemodialysis and whether polyinyxin B-immobilized fiber (PMX-F) treatment affects these levels. Fourteen heinodialysis patients with sepsis, 14 hemodialysis patients without sepsis, and 12 age matched healthy controls were included in this study. Cardiac troponin T levels in hemodialysis patients with sepsis (0.56+/-0.28 microg/L) were higher than levels in hemodialysis patients without sepsis (0.16+/-0.06 microg/L, p < 0.01) and healthy control subjects (0.03+/-0.01 microg/L, p < 0.001). The 14 hemodialysis patients with sepsis were randomly assigned to one of two treatment approaches: PMX-F treatment (n = 7) or conventional treatment (n = 7). Plasma endotoxin levels were significantly reduced from 46.6+/-17.8 pg/mI to 8.2+/-2.4 pg/ml, p < 0.01, in patients treated with PMX-F, and serum cardiac troponin T levels were also reduced from 0.62+/-0.30 microg/L to 0.26 = 0.12 microg/L, p < 0.05. Cardiac troponin T levels were unchanged in patients under conventional treatment. These data suggest that cardiac troponin T is indeed elevated in septic patients undergoing hemodialysis and niay reflect subclinical myocardial cell damage. PMX-F is effective in reducing myocardial damage, in part, due to reducing plasma endotoxin levels.