Polymethyl Methacrylate Hemofilters Research Articles

Exploration of Daptomycin Adsorption by Polymethylmethacrylate Hemofilter In Vitro.

Blood purification therapy with cytokine-adsorbing hemofilters has been used to treat sepsis-associated hypercytokinemia. Polymethylmethacrylate (PMMA) hemofilters are frequently used for this purpose; however, adsorption and removal of teicoplanin, a therapeutic agent, have been reported. Similar concerns have been shared regarding daptomycin because its structure resembles that of teicoplanin; nevertheless, there have been no reported effects associated with daptomycin in this context. We studied the adsorption of daptomycin onto a PMMA hemofilter in vitro and investigated its adsorption onto hollow fiber membranes by adding cut PMMA membranes to a daptomycin solution. Additionally, the daptomycin solution was circulated in a dialysis circuit connected to a PMMA hemofilter, and changes in daptomycin content were examined. The daptomycin content decreased immediately after adding the hollow fiber membranes, similar to that observed for teicoplanin. The daptomycin content was lower than that of the standard reagent in the dialysis circuit model, reaching values below the measurement limit after 20 min. These results suggested that daptomycin was adsorbed and removed by the PMMA hemofilter. Encountering this effect during clinical use is plausible; therefore, daptomycin administration via a PMMA hemofilter should be avoided during blood purification therapy.

A Retrospective Study on the Start and End of Continuous Hemodialysis Using a Polymethylmethacrylate Hemofilter for Severe Acute Pancreatitis.

Objective We previously reported the successful outcomes in severe acute pancreatitis (SAP) after continuous hemodialysis using a polymethylmethacrylate hemofilter (PMMA-CHD). The present study makes informative suggestions regarding the initiation and termination of PMMA-CHD. Methods We retrospectively studied 63 patients with SAP admitted to the intensive care unit between January 1, 2011, and December 31, 2022, including 30 who received PMMA-CHD therapy for renal dysfunction. Statistical significance was evaluated using a multiple logistic regression analysis for severity scores, prognostic factor scores in the Japanese severity criteria, the Kidney Disease: Improving Global Outcomes (KDIGO) stage, and the lung injury score (LIS). Results At the onset of blood purification therapy using PMMA-CHD, a significant increase in the KDIGO stage was shown, with a cutoff value of 2.0. The prognostic factor score and LIS at the start of blood purification therapy were significantly high, with a cutoff value of 3.0. Analyses of severity scores, the KDIGO stage, and the LIS before the start of PMMA-CHD were also increased significantly, with cutoff values of +2.0, +1.0, and +3.0, respectively. Furthermore, on analyses of improvements in values after starting PMMA-CHD, the value of KDIGO staging significantly decreased, and the cutoff value was -2.0. The prognostic factor score was also significantly decreased, with a cutoff value of -2.0. Conclusion Prognostic factor scores of the Japanese severity criteria and LIS, as well as the KDIGO stage, are valuable indicators for determining the start and end of PMMA-CHD therapy.

Removal characteristics of presepsin by operating conditions and hemofilter.

Presepsin, which is used as a biomarker for sepsis, is thought to be removed by dialysis, but the actual removal properties of dialysis are unknown. We investigated the presepsin removal properties of continuous hemodiafiltration using the high concentration of presepsin from human plasma drained by plasma exchange. Each solution in plasma exchange was connected to a continuous hemodiafiltration blood circuit and circulated at 4 conditions. The results show that presepsin was confirmed to be removed more efficiently in hemofiltration than in hemodialysis. In addition, when using a polymethylmethacrylate hemofilter for continuous hemodiafiltration, the lowest presepsin concentration is on the filtrate side, suggesting that the main removal mechanism is adsorption. Since presepsin has a molecular weight of 13,000, its removal efficiency is high by hemofiltration as per principle. In addition, since the main adsorption principle of polymethylmethacrylate hemofilter is hydrophobic bond, presepsin is considered to be adsorbed. Since presepsin is metabolized in the kidney, it is elevated in renal failure. In this paper, we confirmed that presepsin is eliminated by continuous hemodiafiltration not only in the kidney. Depending on the timing of presepsin measurement, there is a risk of missing the diagnosis of sepsis. Kidney function and continuous hemodiafiltration should be checked when measuring presepsin.

A Larger Membrane Area Increases Cytokine Removal in Polymethyl Methacrylate Hemofilters.

Blood purification is performed to control cytokines in critically ill patients. The relationship between the clearance (CL) and the membrane area during adsorption is not clear. We hypothesized that the CL increases with the hydrophobic area when hydrophobic binding contributes to cytokine adsorption. We investigated the relationship between the hemofilter membrane area and the CL of the high mobility group box 1 protein (HMGB-1) and interleukin-6 (IL-6). We performed experimental hemofiltration in vitro using polymethyl methacrylate membranes CH-1.8W (1.8 m2) and CH-1.0N (1.0 m2), as well as polysulfone membrane NV-18X (1.8 m2). After adding 100 mg of HMGB1 or 10 μg of IL-6 into the test solution, experimental hemofiltration was conducted for 360 min in a closed-loop circulation system, and the same amount of HMGB1 and IL-6 was added after 180 min. With CH-1.8W and CH-1.0N, both HMGB-1 and IL-6 showed a rapid concentration decrease of more than 70% at 180 min and 360 min after the re-addition. At 15 min, the CL of HMGB-1 was CH-1.8W: 28.4 and CH-1.0N: 19.8, and that of IL-6 was CH-1.8W: 41.1 and CH-1.0N: 25.4. CH-1.8W and CH-1.0N removed HMGB1 and IL-6 by adsorption and CH-1.8W was superior in CL, which increased with a greater membrane area.

Clinical efficacy of blood purification using a polymethylmethacrylate hemofilter for the treatment of severe acute pancreatitis.

BackgroundSevere acute pancreatitis (SAP) is a systemic inflammatory disease, and it can often complicate into acute kidney injury (AKI) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study aimed to evaluate the clinical effectiveness of blood purification using a polymethylmethacrylate (PMMA) hemofilter.MethodsWe retrospectively examined 54 patients, who were diagnosed with SAP according to the Japanese criteria from January 2011 to December 2019.ResultsOf a total of 54 SAP patients, 26 patients progressively developed AKI and required continuous hemodialysis with a PMMA membrane hemofilter (PMMA-CHD). Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were significantly higher in patients requiring PMMA-CHD than in patients not requiring hemodialysis. The lung injury scores were also significantly higher in patients requiring PMMA-CHD. Of the 26 patients, 16 patients developed ALI/ARDS and required mechanical ventilation. A total of seven patients developed severe ALI/ARDS and received additional intermittent hemodiafiltration using a PMMA hemofilter (PMMA-HDF). Although the length of intensive care unit stay was significantly longer in patients with severe ALI/ARDS, blood purification therapy was discontinued in all the patients. The survival rates at the time of discharge were 92.3% and 92.9% in patients with and without PMMA-CHD, respectively. These real mortality ratios were obviously lower than the estimated mortality ratios predicted by APACHE II scores.ConclusionsThese finding suggest that the blood purification using a PMMA hemofilter would be effective for the treatment of AKI and ALI/ARDS in SAP patients.

Population Pharmacokinetics of Vancomycin Under Continuous Renal Replacement Therapy Using a Polymethylmethacrylate Hemofilter.

Although continuous hemodiafiltration (CHDF) is often performed in critically ill patients during sepsis treatment, the pharmacokinetics of vancomycin (VCM) during CHDF with a polymethylmethacrylate hemofilter (PMMA-CHDF) have not been revealed. In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CLhemofilter). This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed, and CLhemofilter was assessed. Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions for CHDF were 107.5 ± 18.3 mL/min for blood flow rate and 26.3 ± 6.3 mL/kg/h for effluent flow rate. The mean parameter estimates were distribution volume of the central compartment (V1), 59.1 L; clearance of the central compartment (CL1), 1.35 L/h; distribution volume of the peripheral compartment (V2), 56.1 L; and clearance of the peripheral compartment (CL2), 3.65 L/h. BW and SOFA score were significantly associated with V1 (P < 0.05) and CL1 (P < 0.05), respectively, and were thus selected as covariates in the final model. The estimated dosage of VCM to achieve a target area under the concentration-time curve/minimum inhibitory concentration ≥400 was 27.1 mg/kg for loading and 9.7 mg/kg every 24 hours for maintenance; these dosages were affected by BW and SOFA score. Mean CLhemofilter obtained from 8 patients was 1.35 L/h, which was similar to CL1. The authors clarified the pharmacokinetics and CLhemofilter of VCM in PMMA-CHDF patients. The PK of VCM in patients undergoing CHDF appeared to vary not only with the CHDF setting and BW but also with SOFA score.

Involvement of ionic interactions in cytokine adsorption of polyethyleneimine-coated polyacrylonitrile and polymethyl methacrylate membranes in vitro.

Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10min and 30min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6mL/min, 23 ± 7mL/min, and 78 ± 3mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design.

The 28‐day survival rates of two cytokine‐adsorbing hemofilters for continuous renal replacement therapy: a single‐center retrospective comparative study

AimContinuous renal replacement therapy (CRRT) with a cytokine‐adsorbing hemofilter (CAH) is effective in the treatment of sepsis. Two filter types, namely polymethyl methacrylate (PMMA) and surface‐treated AN69 (AN69ST) hemofilters, have been successfully used for CRRT, but no direct comparisons have been published to date. This study compared the efficacy, as measured by 28‐day survival rates, of PMMA and AN69ST hemofilters in patients receiving CAH‐CRRT.MethodsThis retrospective observational study reviewed the medical records of 142 patients who received CAH‐CRRT between November 2013 and February 2015.ResultsThe 28‐day survival rates were higher in the AN69ST group than in the PMMA group for patients with or without sepsis (all patients, 79.4% versus 54.1%; patients with sepsis, 77.3% versus 50.0%; patients without sepsis, 83.3% versus 57.5%; P < 0.05). No significant differences were observed regarding 28‐day survival rates of patients with or without sepsis (AN69ST, 77.3% versus 83.3%; P = 0.51; PMMA, 50.0% versus 57.5%; P = 0.61) using the same hemofilter.ConclusionThe AN69ST hemofilter could be more effective than PMMA hemofilters for improving the survival outcomes of patients with or without sepsis.

Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study.

Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters. We isolated adsorbates from the hemofilters after use and performed comprehensive proteome analysis. A total of 429 proteins were identified in these adsorbates. Adsorbates from the hemofilters of patients with sepsis had significantly increased frequency of proteins associated with "immune system process" and "biological adhesion" functions compared to those of non-sepsis patients (P<0.05). Of 429 proteins, 197 were identified only in sepsis adsorbates. Of these, 3 proteins including carbonic anhydrase 1 (CA1) and leucine-rich alpha-2-glycoprotein (LRG1) were identified in all samples from sepsis patients and have not been previously reported in sepsis patients. Validation analysis of patient serum revealed that patients with sepsis had increased serum levels of CA1 and LRG1 compared to patients without sepsis (P<0.05). To conclude, there were significant differences in the characteristics of the adsorbates from sepsis and non-sepsis patients. CA1 and LRG1 appear to be novel substances associated with sepsis.

In vitro evaluation of filter life and protein adsorption of polymethylmethacrylate hemofilter with large membrane surface area

<i>In vitro</i> evaluation of filter life and protein adsorption of polymethylmethacrylate hemofilter with large membrane surface area

Comparison of the efficacy between continuoushemodiafiltration with polymethylmethacrylate (PMMA) membrane hemofilter CH-1.8W® and with pmma membrane dialyzer BK-2.1P® in the treatment of critically ill patients

We have reported the efficacy of continuous hemodiafiltration (CHDF) with a cytokine-adsorbing hemofilter in the treatment of hypercytokinemia, such as severe sepsis, septic shock, using a polymethylmethacrylate (PMMA) membrane dialyzer (BK-2.1P®; Toray Medical Co Ltd, Tokyo, Japan) [1], [2]. In 2013, a new PMMA hemofilter (CH-1.8W®; Toray Medical Co Ltd, Tokyo, Japan) was released in Japan. It is covered by Japanese medical insurance for continuous renal replacement therapy.

Clinical Comparative investigation on cytokine absorption removal and circuit interval pressure of polymethylmethacrylate hemofilters with different membrane surface area

Clinical Comparative investigation on cytokine absorption removal and circuit interval pressure of polymethylmethacrylate hemofilters with different membrane surface area

Efficacy of Series Double Continuous Hemodiafiltration Using Two Polymethyl Methacrylate Membrane Hemofilters for Patients With Hypercytokinemia

Continuous hemodiafiltration using a hemofilter made from a membrane with cytokine adsorption properties is thought to be effective to remove cytokines in septic patients. In order to enhance cytokine removal capacity by increasing adsorption area, we devised a double polymethyl methacrylate continuous hemodiafiltration method, which involves serial connection of two polymethyl methacrylate membrane hemofilters, and we report clinical efficacy with this method. Of 74 patients who underwent continuous hemodiafiltration and had interleukin-6 blood levels measured during their ICU stay between March 2010 and June 2012, 13 patients with hypercytokinemia (interleukin-6 blood level >900 pg/mL) underwent series double continuous hemodiafiltration to be treated for hypercytokinemia. Cytokine reduction rate and clinical efficacy were compared between those 13 patients and those with a similar pathological condition who underwent continuous hemodiafiltration using the single polymethyl methacrylate membrane hemofilter. Interleukin-6 blood levels 6 h after continuous hemodiafiltration initiation increased in the single continuous hemodiafiltration group from 17040 ± 33660 pg/mL to 26290 ± 66250 pg/mL; however, interleukin-6 blood level significantly decreased in the series double continuous hemodiafiltration group from 20220 ± 29120 pg/mL to 6790 ± 10820 pg/mL. Interleukin-6 reduction rate during the period between initiation and 6 h after initiation of continuous hemodiafiltration was significantly higher in the series double continuous hemodiafiltration group(63.5 ± 38.9%) compared to that of the single continuous hemodiafiltration group (-342 ± 1306%)(P = 0.039). Series double continuous hemodiafiltration using two polymethyl methacrylate hemofilters with cytokine adsorbing capacity is effective to remove cytokine in hypercytokinemic septic patients.

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Introduction: It is widely accepted that excess inflammatory cytokines play a pivotal role in severe sepsis and septic shock. Various blood purification techniques have proven to be effective at removing these cytokines. At SCCM 2012, we reported on the use of a polymethyl methacrylate (PMMA) membrane hemofilter for removal of high concentrations of IL-6 and HMGB1 in human waste plasma. The initial concentration of IL-6 in the plasma was 470,000 pg/ml, which was extremely high. At 6 hrs after the initiation, the IL-6 concentration had dramatically decreased to 11,000 and 6,600 pg/ml in continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemofiltration (CVVH). These results indicated that a PMMA membrane hemofilter has very high adsorption properties. Therefore, we decided to study the differences between PMMA and polyarylonitrile (AN69ST) membranes; both membrane are considered which have high adsorption capacity. Hypothesis: To verify whether there is a difference in effect between PMMA and AN69ST membrane hemofilters. Methods: This study was conducted using human plasma (2,000 ml). Informed consent was obtained from the family. The plasma was divided into 2 parts, one for the PMMA (1,000 ml), the other for AN69ST (1,000 ml). This study was conducted using the following operating conditions: plasma flow rate (QP), 80 ml/min; replacement flow rate (QR), 400 ml/hr; filtration rate (QF), 400 ml/hr; body fluid removal rate, 0 ml/hr. The plasma samples from the inlet side of the hemofilter and the sample of filtrated solution was collected at the start and after 0.5, 1, 3, 6, 12, 18, 24, 30, 36, 48 hours. Parameters including original concentration, clearance of plasma (CLp), sieving coefficient (SC), trans-membrane pressure (TMP) of IL-6 and HMGB1 were assessed. Results: At 0, 0.5, 1, 6 h, in PMMA and AN69ST, the IL-6 was 2,600/2,600, 1,600/1,900, 1,200/1,500, 320/600 pg/ml, respectively. At 0, 0.5, 1, 6 h, in PMMA and AN69ST, the HMGB1 was 530/530, 280/68, 180/18, 14/7 ng/ml, respectively. Conclusions: IL-6 concentration was quickly reduced by use of the PMMA hemofilter, whereas HMGB1 concentration went down with use of the AN69ST hemofilter. These two membranes therefore have different adsorption characteristics, suggesting the possibility of membrane selection specific to the disease.

Etanercept Clearance during an in vitro Model of Continuous Venovenous Hemofiltration

Background/Aims: Etanercept is a tumor necrosis factor-α antagonist used in inflammation-mediated conditions. Continuous venovenous hemofiltration (CVVH) has also been used in patients with inflammatory conditions. This study evaluated etanercept clearance using an in vitro CVVH model. Methods: Etanercept clearance was assessed in vitro in bovine blood at 1–3 mg/l final serum concentration, and urea control at 750 mg/l. CVVH was performed using polyacrylonitrile, polysulfone, and polymethylmethacrylate filters at 3 l/h ultrafiltrate and 200 ml/min blood flow rates. Transmembrane clearance was estimated using sieving coefficient calculations, and adsorptive removal rate was approximated using a mass balance calculation. Results: Urea sieving coefficient remained constant (1.04 ± 0.01). Ultrafiltrate etanercept concentrations were undetectable (sieving coefficient < 0.02) and transmembrane and adsorptive clearances were negligible. Conclusion: Etanercept is not cleared appreciably by transmembrane or adsorptive mechanisms in CVVH using polyacrylonitrile, polysulfone, or polymethylmethacrylate hemofilters.

Continuous Hemodiafiltration with PMMA Hemofilter in the Treatment of Patients with Septic Shock

Septic shock is the most severe form of sepsis. It is widely accepted that cytokines play pivotal roles in the pathophysiology of septic shock. We reported previously that continuous hemodiafiltration (CHDF) using a polymethylmethacrylate (PMMA) membrane hemofilter removed various cytokines from blood continuously and efficiently, mainly by adsorption to membrane matrix of the hemofilter. Furthermore, in April 2000, we introduced to clinical practice a rapid assay system that determines blood levels of IL (interleukin)-6 in approximately 30 min. This enabled us to routinely measure blood IL-6 as an index of cytokine cascade activation in critically ill patients for real-time clinical monitoring of hypercytokinemia. The aim of the present cohort study was to evaluate the clinical efficacy of PMMA-CHDF in septic shock, a typical condition associated with hypercytokinemia. Forty-three patients with septic shock were assessed by monitoring of blood IL-6 level with a rapid assay system and immediate initiation of critical care including PMMA-CHDF for cytokine removal. Following initiation of PMMA-CHDF, early improvement of hemodynamics was noted, as well as an increase in urine output. PMMA-CHDF treatment improved both hypercytokinemia (assessed by measurement of blood IL-6 level) and dysoxia (assessed by measurement of blood lactate level). The present findings suggest that cytokine-oriented critical care using PMMA-CHDF might be an effective strategy for the treatment of septic shock.