The Efficacy of Resin Hemoperfusion Cartridge on Inflammatory Responses during Adult Cardiopulmonary Bypass.

AIM: This study aimed to evaluate the efficacy of the resin hemoperfusion device (HA380 hemoperfusion cartridge) on inflammatory responses during adult cardiopulmonary bypass (CPB). METHODS: Sixty patients undergoing surgical valve replacement were randomized into the HP group (n = 30) with an HA380 hemoperfusion cartridge in the CPB circuit or the control group (n = 30) with the conventional CPB circuit. The results of routine blood tests, blood biochemical indexes, and inflammatory factors were analyzed at V0 (pre-CPB), V1 (CPB 30 min), V2 (ICU 0 h), V3 (ICU 6 h), and V4 (ICU 24 h). RESULTS: The HP group had significantly lower levels of IL-6, IL-8, and IL-10. Significant estimation of group differences in the generalized estimating equation (GEE) models was also observed in IL-6 and IL-10. The HP group had significantly lower levels of creatinine (Cr), aminotransferase (AST), and total bilirubin (TBil) compared to the control group. The estimation of differences of Cr, AST, and TBil all reached statistical significance in GEE results. The HP group had significantly less vasopressor requirement and shorter mechanical ventilation time and ICU stay time as compared to the control group. CONCLUSION: The HA380 hemoperfusion cartridge could effectively reduce the systemic inflammatory responses and improve postoperative recovery of patients during adult CPB.

Hemoadsorption eliminates remdesivir from the circulation: Implications for the treatment of COVID-19.

Both antiviral treatment with remdesivir and hemoadsorption using a CytoSorb® adsorption device are applied in the treatment of severe COVID-19. The CytoSorb® adsorber consists of porous polymer beads that adsorb a broad range of molecules, including cytokines but also several therapeutic drugs. In this study, we evaluated whether remdesivir and its main active metabolite GS-441524 would be adsorbed by CytoSorb® . Serum containing remdesivir or GS-441524 was circulated in a custom-made system containing a CytoSorb® device. Concentrations of remdesivir and GS-441524 before and after the adsorber were analyzed by liquid chromatography-tandem mass spectrometry. Measurements of remdesivir in the outgoing tube after the adsorber indicated almost complete removal of remdesivir by the device. In the reservoir, concentration of remdesivir showed an exponential decay and was not longer detectable after 60 mins. GS-441524 showed a similar exponential decay but, unlike remdesivir, it reached an adsorption-desorption equilibrium at ~48 µg/L. Remdesivir and its main active metabolite GS-441524 are rapidly eliminated from the perfusate by the CytoSorb® adsorber device in vitro. This should be considered in patients for whom both therapies are indicated, and simultaneous application should be avoided. In general, plasma levels of therapeutic drugs should be closely monitored under concurrent CytoSorb® therapy.

Cytokine Adsorption to Polymyxin B-Immobilized Fiber: An in vitro Study.

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are episodes of acute respiratory worsening characterized by diffuse alveolar damage superimposed on usual interstitial pneumonia. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) is reported to have beneficial effects on the respiratory status and outcome in patients with AE-IPF although its mechanism of action is not fully elucidated. OBJECTIVE: To investigate whether and how the PMX-immobilized fiber (PMX-F) adsorbs cytokines because reduction of the serum levels of various cytokines has been noted in AE-IPF patients receiving PMX-DHP. METHODS: The propensity of recombinant cytokines for adsorption onto PMX-F was examined by incubating cytokines with heparin-coated or uncoated PMX-F for 2 h at 37°C. Cytokines were quantitated by multiplex bead array assay or ELISA. RESULTS: Interleukin (IL)-8, RANTES, platelet-derived growth factor-bb, and transforming growth factor-ß were substantially adsorbed onto PMX-F without heparin coating. The adsorbed cytokines could be eluted with PMX sulfate, indicating that the PMX moiety is involved in cytokine adsorption. Importantly, although IL-1ß, monocyte chemoattractant protein-1, fibroblast growth factor 2, and vascular endothelial growth factor-A were adsorbed onto PMX-F to lesser extents, the adsorption was enhanced by heparin coating of PMX-F. Furthermore, heparin-coated PMX-F acquired the capability to adsorb IL-6, IL-12, and tumor necrosis factor α. An affinity of heparin to PMX was determined (Kd = 0.061 ± 0.032 mg/mL), which accounts for the enhanced cytokine adsorption onto PMX-F upon heparin coating. CONCLUSIONS: Various cytokines involved in inflammation, fibrosis, and vascular permeability were shown to be adsorbed onto PMX-F. Removal of multiple cytokines may be associated with positive impacts of PMX-DHP in patients with AE-IPF.

Selective Polymyxin Hemoperfusion in Complex Therapy of Sepsis in Children after Cardiac Surgery.

BACKGROUND: To date, sepsis remains one of the main challenges of intensive care in pediatrics. Newborns with low birth weight and infants with chronic diseases and congenital disorders are particularly at risk. The incidence of infectious complications in pediatric cardiac surgery is known to be approximately 15-30%. The main etiological factor of sepsis is endotoxin. AIM: To evaluate the efficiency and safety of polymyxin (PMX) B-immobilized column-direct hemoperfusion in complex intensive therapy of sepsis in children after cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective cohort study. METHODS: This study enrolled 15 children, aged 9-96 months, with congenital heart diseases and with body weights of 6.2-22.5 kg. The criteria for admission were body weight >6 kg and clinical and laboratory signs of sepsis (microbiological analysis, procalcitonin [PCT] >2 ng/mL, and endotoxin activity assay [ЕАА] >0.6). Intensive care included inotropic and vasopressor support, mechanical ventilation, broad-spectrum antibiotic therapy, and PMX hemoperfusion procedures. Extracorporeal therapy was initiated within 24 h following the sepsis diagnosis. Every patient underwent 2 hemoperfusion sessions with the use of a PMX B-immobilized column; the session duration was 180 min. RESULTS: We noted improvements in hemodynamic parameters, oxygenation index, and laboratory signs of sepsis, with decreases in the endotoxin concentration according to the EAA, PCT, and presepsin levels. The 28-day survival of the patients in this severely affected group was 80%. Main Conclusion: The inclusion of extracorporeal methods of blood purification, aimed at the selective elimination of circulating endotoxin, in the treatment of sepsis increases the survival rates of children after open heart surgery. Second Conclusion: The obtained results of sepsis therapy with PMX hemoperfusion in children after cardiac surgery enable us to suggest the sufficient safety and efficiency of the procedures in this category of severely affected patients.

Hemoadsorption to Reduce Plasma-Free Hemoglobin During Cardiac Surgery: Results of REFRESH I Pilot Study.

Generation of plasma-free hemoglobin (pfHb) and activated complement during complex cardiac surgery contributes to end-organ dysfunction. This prospective, multicenter REFRESH I (REduction in FREe Hemoglobin) randomized controlled trial evaluated the safety and feasibility of CytoSorb hemoadsorption therapy to reduce these factors during prolonged cardiopulmonary bypass (CPB). Eligible patients underwent elective, nonemergent complex cardiac surgery with expected CPB duration ≥3 hours. Exclusions included single procedures including primary coronary artery bypass graft, single valves, transplant, and left ventricular assist device extraction. TREATMENT used 2 parallel 300 mL CytoSorb hemoadsorption cartridges in a side circuit during CPB. CONTROL was standard of care. Of 52 enrolled patients, 46 underwent surgery (Safety group, n = 23 vs Control, n = 23), and 38 were evaluated for pfHb reduction (EFFICACY group, n = 18 vs CONTROL, n = 20). Type and number of serious adverse events (44 vs 43 CONTROL) were similar, as was 30-day mortality. Transient reduction in platelets during CPB was observed in both groups, especially TREATMENT, but returned to pretreatment levels after CPB without bleeding. Peak pfHb was positively correlated with CPB length (P = 0.01) but the high variability of pfHb, due to the broad surgical procedure mix, prevented detection of changes in pfHb in the overall EFFICACY population. However, the valve replacement surgery subgroup (8 vs 10 CONTROL) had the highest peak pfHb levels, and TREATMENT demonstrated significant pfHb reductions vs CONTROL (P ≤ 0.05) in CPB ≥3 hours. In the EFFICACY group, C3a and C5a were significantly reduced by treatment throughout surgery. Intraoperative hemoadsorption with CytoSorb was safe and feasible in this randomized, controlled pilot study during complex cardiac surgery. Treatment with CytoSorb resulted in significant reductions in pfHb during valve replacement surgery and reductions in C3a and C5a in the overall EFFICACY group. Future studies will target complex cardiac surgery patients with prolonged CPB to assess hemoadsorption effect on end-organ dysfunction and outcomes.

Adsorción extracorpórea de citoquinas en el tratamiento del shock séptico refractario: casos clínicos / Extracorporeal cytokine hemadsorption for the treatment of refractory septic shock: report of two cases

If Septic shock (SS) evolves to refractory SS, mortality could reach 90%, despite giving an optimal treatment. Nowadays, extracorporeal devices which adsorb inflammatory cytokines are available, reducing the systemic inflammatory response syndrome. These devices can be used with continuous renal replacement therapy or conventional hemodialysis. We report two diabetic females aged 50 and 58 years, who underwent a total colectomy and amputation of diabetic foot and who developed a SS with high requirements of vasoactive drugs (norepinephrine and adrenaline) to maintain a mean arterial pressure about 60 mmHg. Both were subjected to hemodialysis, connected to a cytokine hemadsorption device. The most important finding was the progressive reduction of vasopressor doses, effect that was observed nine hours after the beginning of the hemadsorption and lasted until its removal at 26 hours. Both patients survived.

Low-flow veno-venous extracorporeal CO2 removal: first clinical experience in lung transplant recipients.

BACKGROUND: Low-flow extracorporeal CO2 removal devices are easy to setup and manage and may provide valuable ventilation support. METHODS: We employed a new device (ProLUNG) recently introduced into the clinical arsenal that exploits a simple hemoperfusion technique sustained by blood flows lower than 500 ml/min to remove CO2 from the venous blood. It was used as an adjunctive support to mechanical ventilation during and after four lung transplantations in our center. RESULTS: Two patients with cystic fibrosis, one with pulmonary fibrosis, and one with emphysema were included. They underwent lung transplantation and presented hypercapnia and respiratory acidosis before, during, or after the surgical procedure. After 1 h of treatment with the ProLUNG circuit, all patients showed reduced CO2 levels and increased pH; these variables remained stable until the end of treatment. CONCLUSIONS: Our data suggest that this new device is effective in removing CO2 and stabilizing the pH.

[Clinical experience of double plasma molecular absorption with a combination of two hemoperfusion machines in treatment of liver failure].

OBJECTIVE: To evaluate the effect of the double plasma molecular adsorption system (DPMAS) with a combination of two hemoperfusion machines in treatment of liver failure. METHODS: A retrospective analysis was conducted. The clinical data from 42 patients with liver failure admitted to Tianjin Second People's Hospital from September 2012 to September 2013 were enrolled. Patients received 166 courses of blood purification treatment, including 97 courses of plasmapheresis (PE) and 69 courses of DPMAS. The DPMAS treatment was performed with a combination of two hemoperfusion machines, with one a blood pump and the other a plasma pump, for 2-3 hours. Liver function, tumor necrosis factor-α (TNF-α), electrolytes and blood routine were determined before and after treatment. Adverse reactions were observed and the nursing experiences were summarized. RESULTS: The survival rate of 42 liver failure patients was 64.29%, and the total bilirubin (TBil), NH3, total bile acid (TBA) and TNF-α were decreased and the albumin (ALB) was increased after PE and DPMAS. Further analysis of the rate of changes after treatment (after treatment/before treatment×100%) showed that when compared with that in DPMAS, the TBil and TBA were decreased significantly in PE [TBil: (62.21 ± 5.51)% vs. (64.39 ± 4.61)%, t=2.683, P=0.008; TBA: (77.10 ± 4.44)% vs. (85.91 ± 6.95)%, t=9.952, P=0.000], and the level of ALB was elevated significantly in PE when compared with that in DPMAS [(113.12 ± 2.90)% vs. (101.87 ± 2.91)%, t=24.602, P=0.000]. NH3 and TNF-α were decreased in both groups withe no statistical significance [NH3: (79.59 ± 5.72)% vs. (80.56 ± 7.56)%, t=0.934, P=0.351; TNF-α: (61.66 ± 4.67)% vs. (62.73 ± 3.67)%, t=1.638, P=0.108]. The blood electrolytes and routine blood test showed that there was no significant change before and after treatments in DPMAS group (K⁺: 3.92 ± 0.83 mmol/L vs. 3.91 ± 0.82 mmol/L, t=0.501, P=0.618; Na⁺: 136.89 ± 5.69 mmol/L vs. 136.74 ± 5.83 mmol/L, t=1.077, P=0.285; Cl⁻: 96.58 ± 3.33 mmol/L vs. 96.55 ± 3.27 mmol/L, t=0.245, P=0.807; white cell count: 5.22 ± 0.93 × 109/L vs. 5.43 ± 1.11 × 109/L, t=1.125, P=0.265; hemoglobin: 110.97 ± 19.20 g/L vs. 112.69 ± 19.67 g/L, t=0.643, P=0.522; platelet count: 105.28 ± 26.82 × 109/L vs. 101.96 ± 3.08 × 109/L, t=0.727, P=0.470). Sixty-four out of the 69 courses of DPMAS treatment were successfully completed, and 5 times were ended because of line coagulation. There was no uncomfortable symptom complained by 53 patients during the treatment. Hypotension occurred for 3 times, and discomfort and nausea during treatment were complained for 9 times. Low fever occurred 4 times after treatment. Those uncomfortable symptoms were relieved spontaneously or by symptomatic treatment. Psychological nursing care should be given to the patients before and after DPMAS to relieve anxiety. Circulating tubes should be well rinsed to prevent line coagulation. General condition of the patient should be closely monitored in order to adjust therapeutic measures. CONCLUSIONS: DPMAS could be effectively performed with a combination of two hemoperfusion machines without inadvertent side reactions, and it is safe in operation with smaller amount of plasma.

[An in vitro blood compatibility assessment on the adsorptive resin in hemoperfusion filter cartridges].

OBJECTIVE: To investigate necessity of the further processing for adsorptive resin material. METHODS: According to GB/ T 16886.4, coagulation tests, haematology tests, in vitro spontaneous platelet-adhesion test and complement activation tests were conducted respectively to assess the in vitro blood compatibility of adsorptive resin material. RESULTS: In comparison with polypropylene, he adsorptive resin material appears to be a very slight activator to the endogenous blood coagulation system, it can inhibited the exogenous blood coagulation system very significantly (P < 0.01), it can adhere to fibrinogen, red blood cells, reticulocytes very significantly (P < 0.01), and platelet significantly (P < 0.05). The adsorptive resin material is also revealed to be a very significant activator (P < 0.01) to the complement system. CONCLUSIONS: The in vitro blood compatibility assessment witnesses that it is very necessary for the adsorptive resin material to go through the certain special processing(such as the surface modification and the microencapsulation technology, etc) before its application to human being.

Combination of maintenance hemodialysis with hemoperfusion: a safe and effective model of artificial kidney.

OBJECTIVE: To investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve the quality of life of MHD patients and reduce their mortality rate. METHODS: This study was a prospective, randomized, controlled clinical trial. 100 MHD patients were selected and then randomly divided into two groups after four weeks of run-in period. Group 1 received HD alone 2 times a week and the combined treatment of HD with HP (HD+HP) once a week, whereas Group 2 was given HD alone 3 times a week. This study was followed up for a mean of 2 years. The primary outcome was the death of patients. Secondary end points included normal clinical data, leptin, high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), ß(2) microglobulin (ß(2)-MG), immunoreactive parathyroid hormone (iPTH), tumor necrosis factor-α (TNF-α) and the index of dimensions of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 Chinese Edition ). RESULTS: At the end of the two-year observation, the serum concentration of leptin, hsCRP, iPTH, IL-6, ß(2)-MG and TNF-α, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiothoracic ratio, left ventricular mass index (LVMI), the EPO doses and the types of antihypertensive drugs used were lower with Group 1 than with Group 2 (p<0.05); Group 1 had higher hemoglobin (Hb), ejection fraction (EF), and body mass index (BMI) (p<0.05). No statistical difference between the two groups was observed in terms of serum albumin, serum iron (SI), total iron binding capacity (TIBC), cardiac output (CO), Kt/V, early/atrial mitral inflow velocities (E/A) (p>0.05). Besides, the SF-36 indicated that the total score of overall dimentions of Group 1 was higher than Group 2 (p<0.05) and the quality of life of Group 1 was evidently better than Group 2. The Kaplan-Meier Survival Curves for the 2-year observation period showed that patients in Group 1 had obvious survival advantage while Log-rank test results showed p<0.05. No serious adverse incidents occurred during the HD+HP treatment. CONCLUSIONS: HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body. These findings suggest a potential role for HD+HP in the treatment to improve the quality of life and survival rate of MHD patients.

Intraoperative direct hemoperfusion with a polymyxin-B immobilized fiber column for treatment of infective endocarditis.

PURPOSE: Endotoxin adsorption treatment (direct hemoperfusion using a polymyxin-B immobilized fiber column, or PMX-DHP) is now considered a useful option for treating severe sepsis. However, the efficacy of PMX-DHP for infective endocarditis (IE), in which the causative microorganisms are usually gram-positive cocci, remains unclear. In the present study, we investigated the impact of intraoperative PMX-DHP on clinical parameters during the treatment of IE. METHODS: From November 2006 to December 2009, a total of 11 patients with active IE underwent emergent surgery using intraoperative PMX-DHP. The perioperative courses of these patients were compared with those of seven patients who underwent emergent surgery for active IE with the conventional method from January 2003 to October 2006. RESULTS: PMX-DHP was associated with a significant decrease in the postoperative catecholamine dose and duration. Intubation time and intensive care unit length of stay for the PMX-DHP group was significantly shorter than that for the conventional therapy group. There was also a significant difference in the number of failed organs postoperatively between the two groups. CONCLUSION: Intraoperative PMX-DHP demonstrated several positive effects, such as a drastic decrease in the doses of inotropic agents and shortening of the duration of mechanical ventilation, in patients who underwent emergent surgery for active IE. Intraoperative PMX-DHP can be a useful option for the treatment of critically ill patients with IE.

The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management.

Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α(1) fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α(1) fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure.

Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial.

CONTEXT: Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with polymyxin B hemoperfusion could potentially improve patient clinical outcomes. OBJECTIVE: To determine whether polymyxin B hemoperfusion added to conventional medical therapy improves clinical outcomes (mean arterial pressure [MAP], vasopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) conducted at 10 Italian tertiary care intensive care units between December 2004 and December 2007. Sixty-four patients were enrolled with severe sepsis or septic shock who underwent emergency surgery for intra-abdominal infection. INTERVENTION: Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34). MAIN OUTCOME MEASURES: Primary outcome was change in MAP and vasopressor requirement, and secondary outcomes were PaO(2)/FIO(2) (fraction of inspired oxygen) ratio, change in organ dysfunction measured using Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality. RESULTS: MAP increased (76 to 84 mm Hg; P = .001) and vasopressor requirement decreased (inotropic score, 29.9 to 6.8; P < .001) at 72 hours in the polymyxin B group but not in the conventional therapy group (MAP, 74 to 77 mm Hg; P = .37; inotropic score, 28.6 to 22.4; P = .14). The PaO(2)/FIO(2) ratio increased slightly (235 to 264; P = .049) in the polymyxin B group but not in the conventional therapy group (217 to 228; P = .79). SOFA scores improved in the polymyxin B group but not in the conventional therapy group (change in SOFA, -3.4 vs -0.1; P < .001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20-0.94; adjusted HR, 0.36; 95% CI, 0.16-0.80). CONCLUSION: In this preliminary study, polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal gram-negative infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00629382.

Effects of polymyxin B-immobilized fiber using a rat cecal ligation and perforation model.

We evaluated the efficacy of polymyxin B-immobilized fiber (PMX-F) on organ dysfunction using a rat cecal ligation and perforation (CLP) model. Fifteen-week-old Sprague-Dawley rats (n = 21) were divided into three groups. For a PMX group, n = 7, peritonitis was induced by CLP. After 24 hours from CLP, endotoxin adsorption was performed for 1 hour with a PMX-F column. A sham group, n = 7, external circulation was performed with nonimmobilized fiber column. A control group, n = 7, were sacrificed 25 hours after CLP (no hemoperfusion performed). The changes in interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha and plasminogen activator inhibitor (PAI)-1 were measured. The lungs, liver, and kidneys were stained with hematoxylin and eosin and anti-PAI-1 antibodies. Terminal uridine-triphosphate nick-end labeling assay was performed to evaluate apoptosis. The PMX group showed a tendency to decrease in blood levels of IL-6 and PAI-1 compared with the sham group. Anti-PAI-1 antibody staining was seen in the lungs of the control and sham groups. The PMX group showed significantly decreased apoptotic cells in renal tubule cells compared with sham and control groups. We conclude that PMX-F may have inhibited PAI-1 expression in the lungs and decreased apoptosis of renal tubule cells.

Treatment of septic patients with an arginine-based endotoxin adsorber column improves hemodynamics and reduces oxidative stress: results of a feasibility study.

BACKGROUND: Mortality of severe sepsis and septic shock is unacceptably high. Adsorptive removal of endotoxin may interrupt the inflammatory cascade triggered by lipopolysaccharide. METHODS: Prospective feasibility study with plasma separation and adsorption (PSA) treatment using a novel arginine-coated adsorber column was performed in a tertiary care gastroenterological intensive care unit. RESULTS: 10 patients with severe sepsis/septic shock (median APACHE II score: 27, hospital mortality 40%) were treated with PSA on 5 consecutive days. There were no serious adverse events. No patient died during the treatment period. During treatment sessions, mean arterial pressure and cardiac power index increased while vasopressors could be reduced. Advanced oxidation protein products and in vitro pro- apoptotic activity of plasma decreased. We could not demonstrate any changes in endotoxin levels. CONCLUSIONS: PSA resulted in a reduction of indicators of oxidative stress and pro-apoptotic activity of the plasma and an improvement in hemodynamic parameters, suggesting increased myocardial contractility and reduced septic vasodilation.

Endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge improves cardiopulmonary function after cardiopulmonary bypass.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass (CPB) is performed widely, given the progress in cardioprotective methods. However, endotoxemia caused by CPB leads to systemic inflammatory response syndrome and deterioration of organ function. We evaluated the effectiveness of endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge (PMX) in CPB. MATERIALS AND METHODS: Pigs weighing about 25 kg were divided into control (n = 5) and PMX (n = 5) groups. Normothermic CPB was performed in the control group, while endotoxin was removed with PMX under normothermic CPB in the PMX group. Endotoxin removal was performed from the start to end of CPB. The end-systolic pressure-volume ratio (E(max)), left ventricular pressure (LVP), maximum and minimum rates of increase in LVP (+/-LVdp/dt), and cardiac output (CO) were measured 2 h after CPB, and the recovery rates of the parameters were compared between the two groups. A histopathological study was also conducted. RESULTS: The recovery rates of E(max), CO, and LVP were significantly better (P < 0.05) in the PMX group than in the control group. The PaO(2) 2 h after CPB was significantly higher (P < 0.05) in the PMX group than in the control group. The interleukin (IL)-8 level 2 h after CPB was significantly lower (P < 0.05) in the PMX group. Histopathologically, the heart and pulmonary tissues were better preserved in the PMX group. CONCLUSION: The PMX treatment reduced the inflammatory reaction caused by CPB, and cardiac and pulmonary functions after normothermic CPB were well preserved.

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.

Biocompatibility of a novel avidin-agarose adsorbent for extracorporeal removal of redundant radiopharmaceutical from the blood.

The use of monoclonal antibodies (MAbs) in cytotoxic conjugates (radionuclides, toxins, or drugs) for targeting tumor cells is restricted due to toxicity in vital organs. Through improved tumor targeting, it is possible to administer larger amounts of such labeled MAbs, thus improving the ability to eradicate tumor cells without increased normal organ toxicity. Extracorporeal affinity adsorption treatment (ECAT) has therefore been developed using an avidin-agarose (AA) adsorbent with high binding affinity for the biotinylated radiolabeled MAb, rituximab. During ECAT, excess radioimmunoconjugates, not bound to the tumor cells, can be removed improving tumor targeting. The present study was performed to estimate the biocompatibility of the AA adsorber. Seven patients with B-cell lymphoma not responding to conventional treatment were studied. During the ECAT procedure, blood (B) components, plasma (P) complement fragments C3a, C5a, and P-bradykinin were analyzed, and other laboratory tests were carried out. Slight decreases in B-hemoglobin (8.3%), B-thrombocytes (11.4%), and P-albumin (14.3%) were observed, and could be explained by the dilution of the blood with normal saline and acid citrate dextrose. The AA adsorbent had no effect on the blood cells, immunological status or P-bradykinin level. The AA adsorber demonstrated good hemocompatibility and biocompatibility, without any side effects in the patients.