AN69 Membrane Research Articles

Critically Ill Patients with COVID-19 Pneumonia Requiring Continuous Renal Replacement Therapy with oXiris® Membrane in a Third-Level Hospital in Northeast Mexico

Introduction: The coronavirus disease 2019 (COVID-19) pandemic represented a global public health problem with devastating consequences that have challenged conventional medical treatments. Continuous renal replacement therapy (CRRT), based on a spectrum of modalities and dialysis membranes, can modify cytokine storms, and improve the clearance of inflammatory factors. As severe COVID-19 can lead to acute kidney injury (AKI) requiring RRT, most patients require more than one extracorporeal organ support at this point. This is due to complications that lead to organ dysfunction. The aim of our study was to assess renal recovery and survival while use of the oXiris membrane, as well as a decrease in vasopressors and hemodynamic parameters. Methods: This was a retrospective, observational study. The population included adult patients (aged >18 years) with a real-time PCR COVID-19 positive test, admitted to the intensive care unit (ICU) with AKI KDIGO 3, which required CRRT, in a hospital in northern Mexico. The primary outcomes were renal recovery and survival, and the secondary outcomes were a decrease in the vasopressor requirements and changes in the hemodynamic parameters. Results: Thirteen patients were included from January 2020 to August 2021, all of whom met the inclusion criteria. oXiris, an AN69-modified membrane, was used for blood purification and cytokine storm control in all the patients. The primary outcome, renal recovery, and survival were observed in 23% of the patients. The secondary outcome was a decrease of 12% in the use of noradrenaline in the first 24 h of CRRT initiation with oXiris, in addition to a decrease in creatinine and C-reactive protein levels in all patients. Discussion: The use of the oXiris membrane in patients with severe COVID-19 improved hemodynamic parameters, with 23% of the patients achieving renal recovery. The decrease on the requirement of vasopressors in the overall patients in the first 24 h of CRRT with oXiris was achieved. The mean decrease was of 12%, accompanied by a decrease in inflammatory markers. There is literature on the benefit of CRRT with a modified AN69 membrane in Mexico; however, studies in this regard are scarce, and our research provides valuable information on our experience in this field.

The Characteristics of Dialysis Membranes: Benefits of the AN69 Membrane in Hemodialysis Patients.

Patients undergoing hemodialysis (HD) experience serious cardiovascular complications, through malnutrition, inflammation, and atherosclerosis. Amputation for peripheral arterial disease (PAD) is more prevalent in patients undergoing HD than in the general population. In addition, revascularization procedures in dialysis patients are often associated with subsequent amputation and high mortality rates. To improve the prognosis of dialysis patients, malnutrition and inflammation must be properly treated, which necessitates a better understanding of the characteristics of dialysis membranes. Herein, the characteristics of several dialysis membranes were studied, with a special reference to the AN69 membrane, noting several similarities to low-density lipoprotein (LDL)-apheresis, which is also applicable for the treatment of PAD. Both systems (LDL-apheresis and AN69) have anti-inflammatory and anti-thrombogenic effects because they use a negatively charged surface for extracorporeal adsorptive filtration from the blood/plasma, and contact phase activation. The concomitant use of both these therapeutic systems may have additive therapeutic benefits in HD patients. Here, we reviewed the characteristics of dialysis membranes and benefits of the AN69 membrane in dialysis patients.

Examination on the Usefulness of a Specific Stacked Dialyzer AN69 Membrane for Microcirculation in Hemodialysis Patients with PAD Complication

Examination on the Usefulness of a Specific Stacked Dialyzer AN69 Membrane for Microcirculation in Hemodialysis Patients with PAD Complication

AN69 Filter Membranes with High Ultrafiltration Rates during Continuous Venovenous Hemofiltration Reduce Mortality in Patients with Sepsis-Induced Multiorgan Dysfunction Syndrome.

Polyacrylonitrile (AN69) filter membranes adsorb cytokines during continuous venovenous hemofiltration (CVVH). Although high-volume hemofiltration has shown limited benefits, the dose-effect relationship in CVVH with AN69 membranes on severe sepsis remains undetermined. This multi-centered study enrolled 266 patients with sepsis-induced multiorgan dysfunction syndrome (MODS) who underwent CVVH with AN69 membranes between 2014 and 2015. We investigated the effects of ultrafiltration rates (UFR) on mortality. We categorized patients that were treated with UFR of 20–25 mL/kg/h as the standard UFR group (n = 124) and those that were treated with a UFR >25 mL/kg/h as the high UFR group (n = 142). Among the patient characteristics, the baseline estimated glomerular filtration rates (eGFR) <60 mL/min/1.73 m2, hemoglobin levels <10 g/dL, and a sequential organ failure assessment (SOFA) score ≥15 at CVVH initiation were independently associated with in-hospital mortality. In the subgroup analysis, for patients with SOFA scores that were ≥15, the 90-day survival rate was higher in the high UFR group than in the standard UFR group (HR 0.54, CI: 0.36–0.79, p = 0.005). We concluded that in patients with sepsis-induced MODS, SOFA scores ≥15 predicted a poor rate of survival. High UFR setting >25 mL/kg/h in CVVH with AN69 membranes may reduce the mortality risk in these high-risk patients.

Renal Replacement Techniques in Septic Shock.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.

In vivo Elimination of Clonidine by Continuous Venovenous Hemofiltration in Critically Ill Patients

Background: Clonidine is an α₂-agonist that is commonly used for sedation in the intensive care unit. When patients are on continuous venovenous hemofiltration (CVVH) in the presence of kidney dysfunction, the sieving coefficient of clonidine is required to estimate how much drug is removed by CVVH. In the present study, we measured the sieving coefficient of clonidine in critically ill, ventilated patients receiving CVVH. Methods: A total of 20 samples of plasma and ultrafiltrate of 3 patients on CVVH, using a standard 1.5 m² polyacrylonitrile AN69 membrane, during continuous clonidine infusion were collected. After correction for the effect of predilution, we calculated the sieving coefficient for clonidine. Results: The mean sieving coefficient of clonidine was 0.52 (SD 0.097). Conclusion: Using a polyacrylonitrile AN69 membrane in a CVVH machine, the in vivo sieving coefficient of clonidine was 0.52.

Septik Şok Ilişkili Akut Böbrek Hasari Olan Hastalarda Oxiris Ve An69 Filtreleriyle Kontinyu Hemodiyafiltrasyon Uygulamasinin Etkinliğinin Değerlendirilmesi

Septik Şok Ilişkili Akut Böbrek Hasari Olan Hastalarda Oxiris Ve An69 Filtreleriyle Kontinyu Hemodiyafiltrasyon Uygulamasinin Etkinliğinin Değerlendirilmesi

Management Strategies during a VA ECMO Run in a Neonate with E. Coli Septic Shock Masquerading as Hypoxic Ischemic Encephalopathy

Advances in neonatal care for hypoxic respiratory failure, with high-frequency ventilation and inhaled nitric oxide, have led to a decreased need for extracorporeal membrane oxygenation (ECMO). However, neonates resistant to such therapies are more complex and at higher risk of mortality. One such population includes those with hypoxic ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH). We present a challenging case of a full-term neonate with inotrope-resistant Escherichia coli septic shock, profound coagulopathy, hypoxic respiratory failure, and HIE requiring CH and venoarterial (VA) ECMO. We illustrate that family-centered decision-making, ECMO, primary team, and subspecialist support is critical to success. In addition, we share the strategic medical interventions concomitantly used with VA ECMO to aid in the survival of this high-risk infant such as continuous veno-venous hemofiltration with AN69 membrane for cytokine and fluid removal, prostaglandin use to relieve right ventricular strain in malignant pulmonary hypertension, and cautious use of bronchoscopy to assist in lung recruitment.

The effect of continuous veno venous hemofiltration on neutrophil gelatinase-associated lipocalin plasma levels in critically ill patients with acute kidney injury

Objective: To evaluate the effect of continuous veno venous hemofiltration (CVVH) on neutrophil gelatinase associated lipocalin (NGAL) in critically ill patients with acute kidney injury (AKI). Methods: Critically ill patients with AKI who needed CVVH and admitted to Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled prospectively from January 2015 to June 2015. AN69 membrane filters were used for CVVH. Prefilter, postfilter,and plasma NGAL measurements were taken at 10 mins, 4 hours and 8 hours (T 10 min, T 4 h, T 8 h) after CVVH. The influence of membrane filter and volume management on NGAL level was analyzed. Results: Forty patients were recruited.The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 22.9±7.0. The sequential organ failure score (SOFA) was 12.1±2.9, and ICU mortality was 27.5%. During CVVH, there were no significant differences in NGAL levels between prefilter [T 10 min:39.3 (24.8, 62.4) μg/min; T 4 h: (45.1±23.2)μg/min; and T 8 h: (45.5±22.4)μg/min] and postfilter [T 10 min: 33.5 (25.1, 60.7) μg/min; T 4 h: (44.2±24.3)μg/min, and T 8 h: (45.9±22.4)μg/min] (P> 0.05 for all). Compared with the survival group[310.0(162.0, 588.0) μg/L], plasma NGAL level in T 10 min [684.0(270.0, 944.0) μg/L] was significantly higher in death group (P= 0.033). After fluid balance correction, T 4 h [603.4(484.8, 620.2) μg/L] and T 8 h [590.2 (475.9, 749.4) μg/L] plasma NGAL levels in death group were significantly higher than those in the survival group [T4 h: 419.5 (227.5, 552.4) μg/L;T 8 h: 400.7(196.1, 517.4) μg/L] with statistical significance (P<0.01 for both). Conclusions: During CVVH, AN69 membrane filter does not have significant effect on plasma NGAL level in critically ill patients with AKI. After volume balance correction, plasma NGAL level could be used as an effective indicator in these patients.

Micafungin Plasma Levels Are Not Affected by Continuous Renal Replacement Therapy: Experience in Critically Ill Patients.

Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (±21.7 ml/min; n = 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (±0.002 ml/min; n = 75 individual time points). Total body clearance was measured to be 14.0 ml/min (±7.0 ml/min; n = 12). The population area under the curve from 0 to 24 h (AUC0-24) was calculated as 158.5 mg · h/liter (±79.5 mg · h/liter; n = 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.).

Polyethyleneimine-treated polyacrylonitrile membrane hemofilter for critically ill patients receiving anticoagulant-free prolonged intermittent renal replacement therapy: a single-center, prospective, self-controlled pilot study

BackgroundCritically ill patients requiring renal replacement therapy (RRT) are at risk of disease-related bleeding. Systemic heparinization should be avoided. AN69ST, a polyethyleneimine-treated polyacrylonitrile (AN69) membrane hemofilter, can be primed with heparin, improving its local anticoagulative activity. Prolonged intermittent RRT (PI-RRT) is of shorter duration and cheaper, considered as an alternative to continuous RRT. This study was performed to compare the success rate of anticoagulant-free PI-RRT using AN69ST versus AN69 membrane hemofilter. We also evaluated risk factors for filter clotting.MethodsThis crossover, double-blind, randomized study included patients requiring PI-RRT but at high bleeding risk treated with AN69ST and AN69 hemo filters. The success rate of RRT, filter lifespan and severity of filter clotting were compared between the hemo filters. Factors associated with the filter clotting risk were analyzed with a Cox proportional hazards model.ResultsThis study included 60 patients (mean age, 68.1 ± 15.8 years). Thirty-three (55.0%) patients were in the intensive care unit, 34 (56.8%) had disease-related thrombocytopenia, and 14 (23.3%) had local hemorrhagic diseases. The success rate of PI-RRT with the AN69ST and AN69 hemofilter was 51.7% and 50.9%, respectively (P > 0.05). The mean PI-RRT duration was 543.1 ± 119.0 min in the completed sessions and 387.3 ± 140.8 min in the prematurely terminated sessions, without significant difference between AN69ST and AN69 hemofilters. Cox regression analysis showed that age (odds ratio [OR], 1.023 per year), platelet count (OR, 1.07 per 10 × 109/L), hemoglobin concentration (OR, 1.035 per 1 g/L), and activated partial thromboplastin time (aPTT; OR, 0.973 per second) were associated with a hemofilter clotting risk. The AN69ST hemofilter lifespan was significantly prolonged averaging an extra 251.7 min in patients with an aPTT of <35.3 s, hemoglobin concentration of >83 g/L and platelet count of <70 × 109/L.ConclusionsAnticoagulant-free PI-RRT by a heparin-primed AN69ST hemofilter reached a 51.7% success rate. The risk of premature clotting of the extracorporeal circuit remains unsatisfactory. For select patients at high risk of bleeding, the heparin-primed AN69ST hemofilter may be more appropriate for anticoagulation-free PI-RRT.Trial registrationhttps://www.clinicaltrials.gov; study number: NCT02355873. Release Date 01/21/2015

The effect of AN69 ST membrane on filter lifetime in continuous renal replacement therapy without anticoagulation in patients with high risk of bleeding

To evaluate whether AN69 ST membrane would prolong filter lifetime in continuous renal replacement therapy (CRRT) without anticoagulation in patients with high risk of bleeding. A single-center, prospective, randomized, double-blind control trial with crossover design was conducted. From March 1st to December 31st in 2013, patients who were admitted to Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University meeting CRRT treatment indications, but could not receive systemic anticoagulation because of high risk of bleeding were studied. The selected patients were randomly divided into two groups according to a random number table, and four filters consisting of two AN69 ST100 membrane filters (A) and two traditional AN69 M100 membrane filters (B) were used for them. Group I with the filter order of A-B-A-B, and group II with the order of B-A-B-A. The clinical data of patients was recorded in detail, and conventional AN69 ST and AN69 membrane filter lifetime, their influence on coagulability, and the incidence of bleeding complications were compared. Seventeen patients were enrolled, with 10 in groupI, and 7 in group II. The basic medical characteristics including gender, age, acute physiology and chronic health evaluation II ( APAECH II) score, sequential organ failure score (SOFA), Acute Renal Injury Network (AKIN) stage, activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), platelet count (PLT), and use of mechanical ventilation were not significantly different between two groups. But the use of vasoactive drug was more frequent in group IIcompared with that of group I[ 100.0% (7/7) vs. 30.0% (3/10), χ² = 8.330, P = 0.010]. AN69 ST filter lifetime (n = 34) was (15.92±2.10) hours, there was no statistically significant difference compared with that of AN69 membrane (t = 0.088, P = 0.942), filter lifetime of which (n = 34) was (16.12±1.38) hours. It was also found by Kaplan-Meier survival analysis that there was no significant difference between the two membrane filter lifetime (χ² =1.589, P = 0.208). Logistic regression analysis showed that the life of the first filter was not correlated with coagulation indicators, including APTT, PT, INR, and PLT [ APTT: odds ratio (OR) = 0.977, 95% confidence interval (95%CI) = 0.892-1.071, P = 0.623; PT: OR = 1.001, 95%CI = 0.901-1.109, P = 0.988; INR: OR = 1.078, 95%CI = 0.348-3.340, P = 0.896; PLT: OR = 0.996, 95%CI = 0.974-1.019, P = 0.735]. The application rate of vasoactive drugs, which was different between two groups for basic medical indications showed no effect on filter life time (OR = 2.541, 95%CI = 0.239-26.955, P = 0.439). Reasons of clotting in filters were also analyzed, and it was found that blood coagulation in the filter ranked the top (88.2%), and the other reasons were catheter-related problems, death, and unscheduled transport. No difference in blood coagulation function was found in both groups after treatment for 12 hours, and there was no bleeding complication. During the CRRT without systemic anticoagulant, both surface-treatment with polyethyleneimine AN69 and AN69 ST membrane cannot prolong filter lifetime.

113 Continuous removal of glycerol from frozen-thawed blood in a microscale membrane device

The technique of freezing red blood cells (RBCs) in the presence of 40% w/v glycerol extends the shelf life to 10 years as opposed to only 6 weeks for conventional refrigerated blood. Despite the clear logistical advantages, frozen blood is not preferred in clinical therapy because of the prohibitively time consuming post-thaw process needed to remove the glycerol. A rapid glycerol removal method is necessary to facilitate more widespread use of frozen blood. In a previous study, we used mathematical predictions of cell membrane transport to guide the design of a procedure that varies the extracellular solution composition with time to provide the necessary concentration driving force for rapid glycerol removal while keeping the cell volume within osmotic tolerance limits to minimize cell damage. This batch procedure removed the intracellular glycerol in approximately three minutes with a hemolysis of less than 20%. In this study, the feasibility of adapting this batch procedure for use in a continuous device is examined. The current device consists of a membrane sandwiched between two PEEK sheets with a microchannel (15 cm long, 200–400 mm wide, 100 mm deep) etched into each sheet. Pins fashioned in the PEEK sheets facilitate proper alignment when the device is assembled, enabling mass transfer through the membrane. In this study, the membrane used was the AN69 membrane, a biocompatible copolymer membrane commonly used for hemodialysis. In the first experiment, fresh human RBCs glycerolized to 10% w/v were flowed counter-current to isotonic saline. The solution concentration in this experiment was specifically chosen because it is expected to yield gradual mass transfer without causing excessive osmotic damage. This experiment resulted in a glycerol mass composition reduction up to 50% for a single pass, with a low hemolysis average of about 3.4% for all flow rates tested. In the second experiment, 40% w/v glycerolized frozen-thawed RBCs were flowed counter-current to 40% w/v glycerol solution to assess the fragility of frozen-thawed cells. Because the osmolality of both streams are equal, no mass transfer will occur and any damage is expected to only be due to mechanical stresses. In this experiment, the level of hemolysis only increased by 2% due to mechanical stresses incurred during transit through the device. In the third experiment, 40% w/v glycerolized frozen-thawed RBCs were flowed counter-current to 3.4% w/v saline. This experiment resulted in a glycerol mass composition reduction of 55.0 ± 0.3% and hemolysis of 15.1 ±0.7% for the slowest flow rate tested, which is comparable to the removal achieved in the first step of the batch procedure. The ability to vary the flow rate and the channel dimensions, as well as the solution used as a dialysate enable us to control the mass transfer inside the channel. Furthermore, the ability to link multiple channels in series allows us to potentially match the concentration changes from the batch procedure in a continuous application. Ultimately, this method has the potential for rapid continuous removal of glycerol, which will make frozen blood a more attractive option for blood banking. Source of funding: National Science Foundation Grant #1150861. Conflict of interest: None declared. adam.higgins@oregonstate.edu

Use of HF20 membrane in critically ill unstable low-body-weight infants on inotropic support

Initiating continuous renal replacement therapy (CRRT) in infants exposes them to the dual hemodynamic challenges of high circuit extracorporeal volumes and potential membrane reactions, in the case of acrylonitrile AN69 membranes. The use of the new Prismaflex HF20 membrane in hemodynamically unstable low-body-weight infants on inotropic support has not been reported. We describe the use of the HF20 (Gambro Lundia AB, Lund, Sweden) membrane in four low-body-weight infants (2.3 to 5.4kg) with multi-organ dysfunction syndrome who were critically ill in the Pediatric Intensive Care Unit (PICU), hemodynamically unstable, and on inotropes. We were able to achieve target volume loss in all infants without compromising their hemodynamic status. Mean arterial pressures were maintained between 39 and 57mmHg. The relatively low circuit volume of the HF20 set (60ml) obviated the need for blood prime in the majority; however, when blood prime was required, there was no adverse reaction with the polyarylethersulfone (PAES) membrane. Solute clearance in these small infants was efficient with correction of metabolic acidosis and electrolyte abnormalities. Excellent circuit lifespan (56.3 ± 32.3h) was observed. CRRT using the HF20 membrane is safe and hemodynamically well tolerated in high-risk, unstable low-body-weight infants with cardiac dysfunction on multiple inotropes.

Dialysis Efficiency of AN69, a Semisynthetic Membrane Not Well Suited for Diffusion.

AN69 membrane is not suited for diffusion, with an suggested limit at 25 mL/min dialysate flow rate. When prescribing continuous hemodialysis this threshold must be surpassed to achieve. We designed a study aimed to check if a higher dose of dialysis could be delivered efficiently with this membrane. Ten ICU patients under continuous hemodiafiltration with 1.4 m2 AN69 membrane were included and once a day we set the monitor to exclusively 50 mL/min dialysate flow rate and 250 mL/min blood flow rate and after 15 minutes measured dialysate saturation for urea, creatinine, and β 2-microglobulin. We detected that urea saturation of dialysate was nearly complete (1.1 ± 0.09) for at least 40 hours, while creatinine saturation showed a large dispersion (0.86 ± 0.22) and did not detect any relation for these variables with time, blood flow, or anticoagulation regime. Saturation of β 2-microglobulin was low (0.34 ± 0.1) and decreased discretely with time (r 2 = 0.15, P < 0.05) and significantly with TMP increases (r 2 = 0.31, P < 0.01). In our experience AN69 membrane shows a better diffusive capability than previously acknowledged, covering efficiently the range of standard dosage for continuous therapies. Creatinine is not a good marker of the membrane diffusive capability.

Does the surface-treated AN69 membrane prolong filter survival in CRRT without anticoagulation?

The need for continuous anticoagulation remains a significant drawback in continuous renal replacement therapy (CRRT), especially in patients with increased bleeding risk. Polyethyleneimine treatment of the AN69 membrane (AN69ST) reduces thrombogenicity through decreased contact activation and promotion of heparin binding. The aim of this study is to evaluate whether this membrane prolongs filter survival in CRRT without anticoagulation. A single-center, prospective, randomized, double-blind controlled trial with cross-over design comparing filter survival with the AN69ST membrane and the original AN69 membrane in 39 patients treated with continuous venovenous hemofiltraton (CVVH) without additional heparin. Filter survival with the AN69ST membrane (n = 75) was 14.2 ± 8.2 h, which is not significantly different from the 13.3 ± 10.3 h for the original AN69 membrane (n = 76; p = 0.59). Limiting the analysis to those treatments that were interrupted for filter clotting yielded similar results: 14.4 ± 8.2 h for the AN69 ST membrane (n = 62) versus 14.1 ± 7.5 h for the original AN69 membrane (n = 56) (p = 0.93). Compared with the original AN69 membrane, the surface-treated AN69ST membrane does not prolong filter survival during CVVH without systemic anticoagulation and with the CRRT settings used in this study.

Evaluation of the Effects of Pulse High-Volume Hemofiltration in Patients with Severe Sepsis: A Preliminary Study

The aim of this study was to evaluate the effects of pulse high-volume hemofiltration (PHVHF) in patients with severe sepsis. Twenty-two patients with severe sepsis admitted to XiJing hospital between January 2009 and January 2010 were included in the present study. Patients were randomly divided into the control group (conventional treatment) and the PHVHF group. Patients in the PHVHF group received 72 h of PHVHF treatment in addition to conventional treatment after admission. PHVHF was conducted as follows: HVHF 85 ml/kg per hour for 6 h followed by continuous venovenous hemofiltration 35 ml/kg per hour for 18 h with an AN69 membrane. The hemofilter was replaced every 24 h and PHVHF was performed with 250 to 300 ml/min blood flow rate. The blood samples were taken to measure the changes of plasma cytokines (TNF-α, IL-1, IL-4, IL-6 and IL-10). With 72 h of PHVHF treatment, there was an improvement in clinical features and hemodynamics variables in PHVHF-treated patients. All plasma cytokines after PHVHF treatment were significantly lower than those at the start of PHVHF treatment (p<0.05). In contrast, there was no significant change in control patients. Our findings suggest that PHVHF is a feasible adjuvant modality in the treatment of patients with severe sepsis. With the application of PHVHF treatment, plasma cytokines are effectively removed. Considering the lower cost and better feasibility than continuous high-volume hemofiltration (CHVF), PHVHF shows promising prospects for the future.

The sieving coefficient and clearance of vasopressin during continuous renal replacement therapy in critically ill children

Hypothesis As vasopressin is a small peptide, its sieving coefficient (SC) and clearance (CL) during continuous renal replacement therapy may be intermediate to those for urea and β2 microglobulin (commonly used markers for small– and middle–molecular weight solutes, respectively). Methods A prospective, minimal-risk study was undertaken of the SC and CL of vasopressin in critically ill children on the first day of continuous renal replacement therapy using AN69 membrane filters and prefilter replacement fluid. All prefilter plasma (vasopressin) samples were drawn from the arterial port after predilution. Results Nine patients with fluid overload, renal failure, or both were recruited (median age, 14 years) during the first day of either continuous venovenous hemofiltration (n = 3) or hemodiafiltration (n = 6). Multiorgan dysfunction syndrome was present in 8 patients, and 3 were in shock (2 were receiving a vasopressin infusion). Median prefilter plasma (vasopressin) was 1.7 pg/mL, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (<2 pg/mL), and 4 patients (including 2 receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). The median SC was 1 in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 mL/min or 39 mL/(min 1.73 m 2). Conclusions The SC and CL of vasopressin by continuous venovenous hemofiltration or hemodiafiltration in these critically ill children were similar to values for urea.

Adsorption of nafamostat mesilate by hemodialysis membranes.

The adsorption of the anticoagulant nafamostat mesilate (FUT-175) by five different hemodialysis membranes was studied in vivo and in vitro. In vivo, FUT-175 was adsorbed strongly by a polyacrylonitrile (AN69) membrane and slightly by another polyacrylonitrile (J-PAN) membrane but not by Cuprophan (CU), hemophan (HE), or polymethylmethacrylate (PMMA) membranes during hemodialysis performed in 4 patients in whom FUT-175 was used as an anticoagulant. Only during hemodialysis using the AN69 membrane did FUT-175 not induce a significant prolongation of celite-activated coagulation time. In vitro studies showed that FUT-175 was adsorbed by the AN69, J-PAN, and PMMA membranes but not by the CU and HE membranes. Methylene blue, a dye that possesses a cationic portion in its chemical structure, stained AN69, J-PAN, and PMMA membranes. Since FUT-175 also possesses a cationic portion, we conclude that FUT-175 is adsorbed by negatively charged membranes via an ionic bond and is unsuited for use as an anticoagulant in hemodialysis using an AN69 membrane because of that membrane's marked capacity to adsorb FUT-175.

The effect of electronegativity and angiotensin-converting enzyme inhibition on the kinin-forming capacity of polyacrylonitrile dialysis membranes

The combination of negatively-charged membranes and angiotensin I-converting enzyme inhibitors (ACEi) evokes hypersensitivity reactions (HSR) during hemodialysis and bradykinin (BK)-related peptides have been hypothesized as being responsible for these complications. In this study, we tested the effects of neutralizing the membrane electronegativity (zeta potential) of polyacrylonitrile AN69 membranes by coating a polyethyleneimine layer (AN69-ST membranes) over the generation of kinins induced by blood contact with synthetic membranes. We used minidialyzers with AN69 or AN69-ST membranes in an ex vivo model of plasma and we showed that plasma dialysis with AN69 membranes led to significant BK and des-Arg 9-BK release, which was potentiated by ACEi. This kinin formation was dramatically decreased by AN69-ST membranes, even in the presence of an ACEi, and kinin recovery in the dialysates was also significantly lower with these membranes. High molecular weight kininogen and factor XII detection by immunoblotting of the protein layer coating both membranes corroborated the results: binding of these proteins and contact system activation on AN69-ST membranes were reduced. This ex vivo experimental model applied to the plasma, dialysate and dialysis membrane could be used for the characterization of the kinin-forming capacity of any biomaterial potentially used in vivo in combination with drugs which modulate the pharmacological activity of kinins.