Polymethylmethacrylate Membrane Hemofilter Research Articles

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.

Comprehensive analysis of cytokine adsorption properties of polymethyl methacrylate (PMMA) membrane material

In acute kidney injury caused by sepsis (septic AKI), excessive production of inflammatory mediators is believed to be involved in deterioration of the disease. Renal replacement therapy using a polymethyl methacrylate (PMMA) membrane hemofilter improves the pathological condition of septic AKI by adsorbing and removing inflammatory cytokines. However, the adsorption properties of the PMMA membrane are unclear. In this study, we comprehensively analyzed the adsorption of 48 different cytokines in human plasma to PMMA and polysulfone (PS) membranes. Seventy-nine percent (38/48) of the cytokines were adsorbed more efficiently to the PMMA membrane than the PS membrane, which indicates that the PMMA membrane has high cytokine adsorption ability. The adsorption rate tended to be higher for the cytokines with lower molecular weight, and there was a significant correlation between the molecular weight of the cytokines and the adsorption rates. Electron microscopy showed that the PMMA hollow fiber membrane had a uniform internal structure from the inner to the outer layers of the membrane and had nano-pores inside the membrane that may have contributed to the adsorption of proteins with a specific molecular weight range. The clinical efficacy of a PMMA membrane hemofilter with cytokine adsorption properties against septic AKI needs further investigation including the evaluation of filtration performance of the hemofilters.

P0531CONTINUOUS HEMODIAFILTRATION WITH PMMA HEMOFILTER MODULATED COMPLEMENT ACTIVATION AND RENAL DYSFUNCTION IN A SWINE MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY

Abstract Background and Aims Sepsis-induced acute kidney injury (AKI) is a growing health care problem, refractory to conventional treatments. This disease is characterized by an overwhelmed immune response against a primary insult that become responsible for renal dysfunction and poor outcome. Therapeutic strategies based on blood purification have been developed for the treatment of this disease. The use of polymethyl methacrylate (PMMA) membrane hemofilter in continuous hemodiafiltration (CHDF) modality showed better hemodynamic stability and efficient renal support in chronic dialysis maintenance. Here we investigated the efficacy of Hemofeel PMMA membrane (TORAY, Japan) in interfering with Complement activation and renal damage in a swine model of sepsis-induced AKI. Method After 3 hours from LPS infusion, 7 hours of PMMA-CVVH treatment or 7 hours of polysulfone (PSF)-CVVH were performed. Animals were sacrificed after 24h from LPS infusion. Histologic and renal function parameters were analyzed in all pigs. Pentraxin-3 (PTX3) and C5b-9 deposits were assessed on renal biopsies. Systemic Complement activation was evaluated by Wieslab kit. Gene expression profile was obtained from isolated PBMCs by Agilent SurePrint G3 Porcine Gene Expression Microarrays. Genespring and R software were used for the analysis. Results were validated by Real-time PCR. Results Analysis of renal biopsies from septic pigs presented increased interstitial leucocyte infiltrate, extensive collagen deposition and diffuse glomerular thrombi compared to healthy pigs (p<0.05). Confocal analysis showed extensive PTX-3 and C5-b9 deposits at tubulo-interstitial level associated with significant activation of systemic complement classical and alternative pathways (p<0.05). Interestingly, PMMA-CVVH treatment significantly reduced local and systemic complement activation, leucocyte infiltrate and tubule-interstitial fibrosis (p<0.05). On the contrary, no significant improvement was observed by PSF-CVVH treatment. Then, we compared the whole-genome gene expression profiles of swine PBMC. We identified 711 differentially expressed genes comparing PBMC before LPS infusion (LPS T0) and after 24 hours from LPS infusion (LPS T24) and 913 genes comparing gene expression profiles of LPS T24 group with that of septic pigs treated with PMMA-CVVH (PMMA T24 group) (fold change >2 ; false discovery rate <0.05). The most modulated genes were Granzime B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, SERPINB-1 and TIMP-2 that were closely related to sepsis-induced immunological process. Finally, quantitative PCR confirmed the microarray data indicating that Granzime B and Complement Factor B upregulation in PBMC was significantly hampered by PMMA treatment. Conclusion Our data suggest that LPS induced AKI is characterized by activation of Classical and alternative Complement pathways resulting in significant renal tissue damage. By interfering with complement activation and inflammatory response, PMMA membrane might prevent dysfunctional activation of resident renal cells with prevention of sepsis-induced AKI.

Continuous renal replacement therapy with a polymethyl methacrylate membrane hemofilter suppresses inflammation in patients after open-heart surgery with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) induces a complex inflammatory response involving an increase in inflammatory cytokines, called postperfusion syndrome. Previous studies demonstrated that adsorption of the serum cytokines can reduce acute inflammation and improve clinical outcomes. In this study, patients were placed on continuous renal replacement therapy (CRRT) with a polymethyl methacrylate (PMMA) membrane hemofilter immediately after the start of an open-heart surgery with CPB and throughout the postoperative course to prevent postperfusion syndrome. The aim of this study was to assess whether continuous CRRT using a PMMA filter (PMMA-CRRT) could affect cytokine expression and improve perioperative outcomes. We designed a randomized controlled trial, which included 19 consecutive adult patients on maintenance dialysis and 7 consecutive adult patients who were not on maintenance dialysis (NHD group). Patients on maintenance dialysis were randomly divided into two groups: Ten patients who received CRRT with a polysulfone membrane hemofilter (PS group) and nine patients who received CRRT with a PMMA membrane (PMMA group). Blood samples were collected from the radial or brachial artery at five different time points. Comparisons between the PS, PMMA, and NHD groups revealed a significant main effect of time on changes in serum IL-6 and IL-8 concentrations (p < 0.01) and an interaction (p < 0.05) between time and group. Plasma IL-6 and IL-8 levels after surgery were significantly lower in the PMMA group than in the PS group, while other cytokines measured in this study were not significantly different. In addition, clinical outcomes were not significantly different between the groups. The continuous use of PMMA-CRRT throughout the perioperative period suppressed serum IL-6 and IL-8 concentrations, although there were no differences in clinical outcomes.

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.

Endotoxin hemadsorption in septic shock.

Endotoxin hemadsorption in septic shock.

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.

Treatment of Septic Shock with Continuous HDF Using 2 PMMA Hemofilters for Enhanced Intensity

Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock. Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups. Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028). Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.

Effectiveness of continuous venovenous hemodiafiltration using a polymethylmethacrylate membrane hemofilter judging from a multiplex suspension array system in septic shock patients

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. The effectiveness of continuous venovenous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (CVVHDF using PMMA) for critically ill patients has also been reported. This treatment was showed as cytokine adsorption therapy, but there are not so many reports in the world.

Zero Mortality of Continuous Veno-venous Hemodiafiltration with PMMA Hemofilter after Pediatric Cardiac Surgery

Continuous veno-venous hemodiafiltration (CVVH) is used as one of the modalities of continuous renal replacement therapy (CRRT) in pediatric intensive units. The aim of our study was to investigate the use of CVVH in small children with acute renal failure (ARF) after cardiac surgery. Between June 2005 and June 2008, 7 patients who required dialysis after pediatric cardiac surgery without ECMO underwent CVVH with polymethylmethacrylate membrane (PMMA) treatment. The definition of ARF was based on a 100% rise in serum creatinine (Cr) concentration, oliguria. On the other hand, PMMA-CVVH was weaned in patients with satisfactory urine output, stable biochemical markers of renal function and adequate fluid balance. All patients treated with PMMA-CVVH alone (4 boys, 3 girls) had a median age of 36 months and a median body weight of 11 kg. The averaged established time from cardiac operation to CVVH was 2.6 days. There was a significant decrease in the post-filter compared with pre-filter levels of BUN, Cr, potassium concentration. There were no significant changes in systolic blood pressure, lactate level and CRP; however, it was unnecessary for all patients to use epinephrine. Continuous veno-venous hemodiafiltration with PMMA-CVVH without ECMO achieved a surprisingly Zero mortality.

劇症型Ａ群溶血性連鎖球菌感染症に対し，ポリメチルメタクリレート膜血液濾過器を用いた持続的血液濾過透析を２系列同時施行した特発性細菌性腹膜炎の１救命例

原発性硬化性胆管炎による肝硬変患者が，Streptococcus pyogenesを起因菌とした特発性細菌性腹膜炎を発症し，劇症型A群溶血性連鎖球菌感染症（toxic shock-like syndrome, TSLS）に陥った。著明な高サイトカイン血症を呈する敗血症性ショックに対し，通常の敗血症治療に加え，2系列同時施行するポリメチルメタクリレート膜血液濾過器を用いた持続的血液濾過透析（continuous hemodiafiltration involving two consoles using a polymethylmethacrylate membrane hemofilter, double PMMA-CHDF）を行い，難治性ショックから離脱し救命し得た。TSLSの病態として，スーパー抗原活性をもつstreptococcal pyrogenic exotoxinがT細胞受容体と反応する結果惹起される著明な高サイトカイン血症が考えられている。そのため，従来の治療法では制御困難な高サイトカイン血症に対して，今回施行したdouble PMMA-CHDFが有用である可能性が示唆された。

Selection of acute blood purification therapy according to severity score and blood lactic acid value in patients with septic shock

Aim:As an alternative method for acute blood purification therapy, continuous venovenous hemodiafiltration (CVVHDF) has been reported as an effective clinical treatment for critically ill patients, but the optimal column for performing CVVHDF remains controversial.Patients and Methods:We used direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) to treat 88 patients with septic shock. To determine the optimal acute blood purification therapy, we subsequently divided the patients into three groups: the first group underwent CVVHDF using a polymethylmethacrylate membrane hemofilter (PMMA) after undergoing DHP-PMX (28 cases), the second group underwent CVVHDF using a polyacrylonitrile membrane hemofilter (PAN) after undergoing DHP-PMX (26 cases), and the third group did not undergo CVVHDF after undergoing DHP-PMX (34 cases).Results:The overall survival rate was 54.5%, and patient outcome was significantly related to the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the sepsis-related organ failure assessment (SOFA) score, and the blood lactic acid value before treatment (all P<0.0001). Only the PMMA-CVVHDF group showed a better outcome (survival rate of 78.6%) compared with the other groups (P = 0.0190). In addition, only the PMMA-CVVHDF group showed a significant improvement in the blood lactic acid level on day 3 (P = 0.0011).Conclusion:Our study suggests that the PMX column might be effective during the early phase of septic shock, before a high level of lactic acid is present. Furthermore, a PMMA column might be the most useful column for performing CVVHDF after DHP-PMX treatment, as suggested by the blood lactic acid value.

Pharmacokinetics and pharmacodynamics of once-daily arbekacin during continuous venovenous hemodiafiltration in critically ill patients

This study examined the pharmacokinetics of arbekacin during continuous venovenous hemodiafiltration (CVVHDF) and assessed the pharmacodynamics to consider arbekacin dosage adaptation in CVVHDF. Arbekacin was administered by 0.5-h infusion once daily, using a polymethyl methacrylate membrane hemofilter, to three critically ill patients undergoing CVVHDF; the flow rates were 0.8 l/h for the filtrate and 0.6 l/h for the dialysate. The drug concentrations in plasma and in the filtrate-dialysate were determined using a fluorescence polarization immunoassay and analyzed pharmacokinetically. The average sieving coefficient of arbekacin was 0.739 and the average drug clearance by CVVHDF was 1.03 l/h. A pharmacokinetic model with three compartments (1, central; 2, peripheral; 3, filtrate-dialysate side hemofilter) accurately reflected the concentration-time data for both plasma and filtrate-dialysate. The pharmacokinetic model assessed the pharmacodynamic profile of arbekacin once-daily regimens (0.5-h infusions) at filtrate-dialysate flow rates of 1.4 and 2.8 l/h, and demonstrated that only the 150-mg and 200-mg regimens achieved an effective target range for C(max) (9-20 microg/ml), suggesting that empirical dosages lower than the usual 150-200 mg should be avoided in patients undergoing CVVHDF. The minimum regimens needed to achieve an effective pharmacodynamic target for the free C(max)/MIC ratio (>8) were 75 mg for an MIC of 0.5 microg/ml, 200 mg for an MIC of 2 microg/ml, and 400 mg for an MIC of 4 microg/ml. These results will help us to better understand the pharmacokinetics of arbekacin during CVVHDF, while also helping in the selection of the appropriate arbekacin regimens, based on a pharmacodynamic assessment, for patients receiving this renal replacement therapy.

The role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the treatment with continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF)

Objective To examine the role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in the treatment of TLS. Design and setting Retrospective observational study in a general intensive care unit of a university hospital. Patients Four patients with hematological disorder developing TLS after the treatment of anti-tumor chemotherapy. Interventions Continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) was performed at the onset of TLS. Blood samples were collected daily after ICU admission, and clinical parameters and blood levels of cytokines were evaluated. Measurements and results All four patients underwent induction anti-tumor chemotherapy, during which they developed hyperuricemia, hyperkalemia, and acute renal failure. Two of them also developed multiple organ failure. Serum levels of tumor necrosis factor (TNF) -alpha, interleukin-6 (IL-6), and IL-10 prior to the initiation of PMMA-CHDF were 102 ± 85 pg/mL, 1097 ± 546 pg/mL, and 98 ± 83 pg/mL, respectively (mean ± SD). After three days of PMMA-CHDF treatment, corresponding blood levels were 37 ± 55 pg/mL, 326 ± 511 pg/mL, and 9 ± 8 pg/mL, respectively. Thus, all cytokine levels were significantly decreased by three days of PMMA-CHDF treatment ( p < 0.05, paired t-test). Following three days of PMMA-CHDF treatment, blood urea nitrogen (BUN) and serum creatinine (Cre.) were significantly decreased (pre/post BUN 42.3 ± 15.4/16.5 ± 8.4 mg/dL, p < 0.05, pre/post Cre. 2.7 ± 1.2/1.2 ± 0.6 mg/dL, mean ± SD, p < 0.05). Furthermore, the clinical condition of each patient was improved after the treatment of PMMA-CHDF, and all of four patients were survived. Conclusion Hypercytokinemia plays a pivotal role in the pathophysiology of TLS and PMMA-CHDF may be an effective therapeutic modality for TLS patients not only as renal replacement therapy but also as a cytokine modulator.

Continuous hemodiafiltration in the treatment of reactive hemophagocytic syndrome refractory to medical therapy

Reactive (or secondary) hemophagocytic syndrome (RHS) is a potentially lethal condition and characterized by hypercytokinemia. Immune modulating drugs sometimes fail to achieve satisfactory control. Therefore we investigate the efficacy of continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA-CHDF) for cytokine removal in patients with RHS. Eight consecutive patients who admitted to our ICU with RHS complicating organ failures and refractory to medical therapy were initiated intensive care including PMMA-CHDF. Although remission was achieved in six patients, remaining two patients died of exacerbation of underlying diseases. Changes in blood levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) as indices of cytokine network activation, and serum ferritin level as an index of severity of RHS were investigated during PMMA-CHDF. PMMA-CHDF performed for 3 days significantly reduced blood TNF-α level (183 ± 159 pg/ml to 84 ± 98 pg/ml, p < 0.05) and also blood IL-6 level (1113 ± 903 pg/ml to 402 ± 411 pg/ml, p < 0.01). Furthermore, serum ferritin level was significantly decreased 3 days after initiation of PMMA-CHDF (52390 ± 65168 ng/ml to 4136 ± 2932 ng/ml, p < 0.05) although it tended to increase before initiation of PMMA-CHDF. No PMMA-CHDF-related adverse events were observed in any of the patients. PMMA-CHDF was effective to remove cytokine and improved disease severity. Thus, PMMA-CHDF may be an adjunctive treatment in RHS refractory to medical therapy.

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.

Effectiveness of Continuous Hemodiafiltration Using a Polymethylmethacrylate Membrane Hemofilter After Polymyxin B-Immobilized Fiber Column Therapy of Septic Shock

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. Direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) was first developed in Japan in 1994 and has since been used for the treatment of septic shock. On the other hand, the effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA- CHDF) for critically ill patients has also been reported. We treated 27 septic shock patients by DHP-PMX. The patients, except for the nine in whom CHDF was not performed after DHP-PMX, were divided into two groups: namely, a group in which PMMA-CHDF therapy was added after DHP-PMX (11 cases), and a group in which continuous hemodiafiltration using a polyacrylonitrile membrane hemofilter (PAN-CHDF) therapy was added after DHP-PMX (7 cases). The outcomes in the two groups were compared. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score and the average sepsis-related organ failure assessment (SOFA) score were not significantly different between the two groups. The PMMA-CHDF group showed significantly better outcomes, with significant improvements of the serum PAI-1, protein C, IL-6 and N-arachidonoylethanolamine (AEA) levels. We conclude that PMMA-CHDF may be more effective than PAN-CHDF in the management of septic shock.

Effectiveness of continuous venovenous hemodiafiltration using a polymethylmethacrylate membrane hemofilter in septic shock patients

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. The effectiveness of continuous venovenous hemodiafiltration (CVVHDF) using a polymethylmethacrylate membrane hemofilter (PMMA) for critically ill patients has also been reported.

Management of Intra‐abdominal Hypertension in Patients With Severe Acute Pancreatitis With Continuous Hemodiafiltration Using a Polymethyl Methacrylate Membrane Hemofilter

To evaluate, with a prospective observational study, whether continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA-CHDF) is effective for prevention and treatment of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on patients with severe acute pancreatitis (SAP). The study was carried out in the general intensive care unit (ICU) of a university hospital. Seventeen consecutive patients with SAP were treated in the intensive care unit and underwent PMMA-CHDF whether or not they had renal failure. Blood level of interleukin (IL)-6, as an indicator of cytokine network activation, and intra-abdominal pressure (IAP) were measured daily to investigate their time-course of changes and the correlation between the two. The blood level of IL-6 was high at 1350+/-1540 pg/mL on admission to the ICU. However, it significantly decreased to 679+/-594 pg/mL 24 h after initiation of PMMA-CHDF (P<0.05), and thereafter decreased rapidly. Mean intra-abdominal pressure (IAP) on admission was high, at 14.6+/-5.3 mm Hg, with an IAP of 20 mm Hg or over in 2 of 17 patients, showing that they had already developed IAH. The IAP was significantly lower (P<0.05) 24 h after initiation of PMMA-CHDF, and subsequently decreased. There was a significant positive correlation between blood level of IL-6 and IAP, suggesting that PMMA-CHDF improved vascular permeability through elimination of cytokines, and that it thereby decreased interstitial edema to lower IAP. Sixteen of the 17 patients were discharged from the hospital in remission from SAP without development of complications. Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter appears to be effective for prevention and treatment of IAH in patients with SAP through the removal of causative cytokines of hyperpermeability.