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Objectives: To demonstrate that tissue ultrafiltration catheters are safe to place and use in an injured lower extremity, measure tissue pressures as well as the current standard of care, and effectively remove interstitial fluid for analysis of biomarkers., Design: Institutional Review Board-approved, prospective pilot study., Setting: Metropolitan Level I trauma center., Patients: All patients who presented to the emergency department with a tibial fracture met the inclusion and exclusion criteria and gave informed consent were enrolled. A total of 10 patients were studied., Intervention: All subjects were treated with two types of percutaneous intramuscular catheters in both the anterior and deep posterior compartments of the leg for 24 hours. One catheter was a conventional indwelling intramuscular pressure catheter (Stryker Quick Pressure Monitor, Kalamazoo, MI), whereas the other was an experimental combined pressure monitoring/tissue ultrafiltration catheter (Compartment Monitoring System [CMS] catheter; Twin Star Medical, Inc, Minneapolis, MN)., Main Outcome Measurements: Safety of device, intramuscular pressure values, and quantity of fluid removed (from CMS catheter only)., Results: No serious device-related complications occurred. There was reasonable correlation between the pressures measured by the CMS and Stryker catheters. Average decrease in intramuscular pressure from baseline to final pressure was 11.3 ± 2.8 mm Hg in the anterior compartment (P = 0.003 by two-tailed paired t test) and 5.9 ± 1.4 mm Hg in the deep posterior compartment (P = 0.01). Ultrafiltrate analysis revealed that lactate dehydrogenase and creatine kinase levels were markedly elevated over serum levels. No patient needed fasciotomy or developed compartment syndrome during the study period., Conclusions: This pilot study of CMS catheters demonstrates safety of CMS catheter use. Assay of the ultrafiltrate may provide greater sensitivity to muscle injury; further research of this approach is warranted.

Objectives: Mechanical ventilation is injurious to the lung. Use of lung-protective strategies may complicate patient management, motivating a search for better lung-replacement approaches. We investigated the ability of a novel extracorporeal venovenous CO2 removal device to reduce minute ventilation while maintaining normocarbia., Design: Prospective animal study., Setting: Government laboratory animal intensive care unit., Subjects: Seven sedated swine., Interventions: Tracheostomy, volume-controlled mechanical ventilation, and 72 hrs of round-the-clock intensive care unit care. A 15-F dual-lumen catheter was inserted in the external jugular vein and connected to the Hemolung, an extracorporeal pump-driven venovenous CO2 removal device. Minute ventilation was reduced, and normocarbia (Paco2 35-45 mm Hg) maintained. Heparinization was maintained at an activated clotting time of 150-180 secs., Measurements and Main Results: Minute ventilation (L/min), CO2 removal by Hemolung (mL/min), Hemolung blood flow, O2 consumption (mL/min), CO2 production by the lung (mL/min), Paco2, and plasma-free hemoglobin (g/dL) were measured at baseline (where applicable), 2 hrs after device insertion, and every 6 hrs thereafter. Minute ventilation was reduced from 5.6 L/min at baseline to 2.6 L/min 2 hrs after device insertion and was maintained at 3 L/min until the end of the study. CO2 removal by Hemolung remained steady over 72 hrs, averaging 72 ± 1.2 mL/min at blood flows of 447 ± 5 mL/min. After insertion, O2 consumption did not change; CO2 production by the lung decreased by 50% and stayed at that level (p < .001). As the arterial PCO2 rose or fell, so did CO2 removal by Hemolung. Plasma-free hemoglobin did not change., Conclusions: Venovenous CO2 removal enabled a 50% reduction in minute ventilation while maintaining normocarbia and may be an effective lung-protective adjunct to mechanical ventilation.

Regardless of modern achievements in intensive therapy the mortality from severe acute pancreatitis progressed to a polyorganic insufficiency reaches 60%. Analysis of mortality structures shows that more than 50% of patients die from severe acute pancreatitis in first 72 hours, which is indicated as early severe pancreatitis. In the recent years the experimental and clinical studies proved that continuous vein to vein hemifiltration in the early stage allowes to lower the severity of poliorgan insufficiency and early death. The aim of the study was to measure the efficiency of vein to vein hemifiltration in the complex treatment of early severe acute pancreatitis. The retrospective analysis consisted of 106 patients, which were divided into 2 groups. 1st with vein to vein hemifiltration in the dose of less than 30ml/kg/h (n = 45) and more than 30 ml/kg/h (n = 20) respectively, the 3rd group did not receive vein to vein hemifiltration (n = 41). The study showed the decrease of early mortality (14 days) in the 2nd group (p = 0.022) and a tendency of decrease in the 2nd group (p = 0.093) compared to the 3rd group. The median interval from admission to death in the first two groups was 14 days while in the 3rd group it was only 5 days. The use of vein to vein hemifiltration in complex therapy of early severe acute pancreatitis patients allows to lower the early mortality. The best results were reached in the 2nd group.

In recent years, acidosis has been of growing interest in intensive care medicine. Most animal models only provide a short-term investigation of the effects of acidosis. They are not suitable for research on interactions with extracorporeal organ support (here continuous venovenous hemofiltration, CVVH). The rationale for this study was to establish a porcine model of prolonged mixed acidemia, which is suitable for research on the interactions of acidemia and CVVH. After the induction of anesthesia in pigs (40 kg), acidemia was induced and maintained in one group with a bolus of 0.4 mol/L lactic acid followed by continuous infusion and a reduced respiratory frequency (lactic acid-group, n = 4). In another group, mixed acidemia was induced with a 0.4 mol/L acid solution (lactic and hydrochloric acid) and low tidal volume ventilation (mixed acidemia-group, n = 8). To get first proof of the model's suitability to operate over an extracorporeal circuit, CVVH was additionally performed in seven pigs (mixed acidemia/CVVH-group, n = 7). The target for the pH was 7.19-7.24. The targeted pH was constantly missed in the lactic acid group, whereas it was successfully maintained for 3.5 h in four out of eight pigs of the mixed acidemia group, and in five out of seven pigs of the mixed acidemia/CVVH group. The CVVH was performed successfully for 3 h in all pigs of the respective group. The mixed acidemia model was sufficient to maintain a low pH within a narrow range for some hours and enabled research on hemofilters in vivo., (© 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: This study aims to compare filter life between saline flushed and non-saline flushed strategies in critically ill patients at high risk of bleeding who are undergoing CRRT without anticoagulation., Material and Method: A cohort of 121 critically ill patients with severe acute kidney injury (AKI) requiring CRRT in the medical intensive care unit (ICU) and cardiac care unit (CCU) of a tertiary care academic center were included. 78 of them used saline flushed through CRRT circuit., Results: There was no significant difference between the two groups of treated patients in baseline characteristics, including the extent of coagulopathy and platelet count. Mean circuit survival was 21.2 h for circuits using saline flush and 20.4 h for those using non-saline flush (p = 0.8).The Kaplan-Meier curves revealed no difference in circuit survival time between saline flushed and non-saline flushed groups (p = 0.8)., Conclusion: The use of saline flush into pre-filter site of CRRT circuit does not provide any benefit on circuit clotting prevention in high-risk of bleeding patients requiring CRRT without anticoagulant.

Background: Despite rigorous focus on extracorporeal CRRT parameters such as access, blood flow, hemoconcentration, and anticoagulation, some patients have unexpected repetitive hemofilter clotting. We instead explored patient or disease-related factors that could be responsible, and present a case of plasma cell dyscrasia in which paraproteins caused hollow fiber failure., Methods: A patient with IgG kappa chain multiple myeloma complicated by sepsis and acute renal failure was started on CVVH with a regional citrate anticoagulation protocol that typically yields filter life of >50 h. Polysulfone hemofilters repetitively clotted every 2-4 h, even after excluding circuit-related problems. Failed filters were examined by light, electron (EM), and immunofluorescence (IF) microscopy., Results: Imaging of the hemofilters revealed several ultrastructural features typical for myeloma-associated alterations in native human tissue. Red cell rouleaux formation occurred within the hollow fibers. There was extensive protein layering on the luminal surface of the fibers with some extension into their walls: these deposits were IF+ for IgG kappa, and had a fibrillary substructure on EM., Conclusion: Extracorporeal hollow fiber phenomena recapitulate many intra-corporeal paraprotein effects such as those described in the kidney with plasma cell dyscrasias. Rapid protein layering suggests fouling of the membrane, decreased solute clearance before total device failure, and raises the theoretical concern that this might also occur during filtration plasmapheresis: we thus suggest serial serum free light chain levels to confirm their removal when using that technique. These findings emphasize the importance of disease rather than circuit-related factors that are under-appreciated causes of premature hemofilter failure.

Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis.

Hemodiafiltration (HDF), developed from the combination of hemodialysis and hemofiltration, is considered to be the most effective current procedure to remove uremic toxins from the blood of kidney patients. Historically, the clinical use of HDF was for many years limited due to the cost burden related to the large amount of sterile volume replacement fluid needed. The solution offered was on-line preparation of replacement fluid from standard dialysate by means of membrane filtration. Industry opened to this concept quite early and worked on various technical solutions between the early 1980s and the late 1990s before real state-of-the-art systems became commercially available on a broad basis. This article reviews in particular the activities of initially Fresenius and later Fresenius Medical Care in this field and identifies major concepts and prototypes up to today's commercially available high-end product--the 5008 therapy system--where on-line HDF finally became integrated as a standard component., (Copyright © 2011 S. Karger AG, Basel.)

In response to a request from the French government, Rhône-Poulenc started development of a synthetic membrane for dialysis in 1969. When used for patients the new membrane, AN69, showed improved efficiency and clinical outcome. Treatment times could be reduced, peripheral neuropathy improved and patients expressed improved quality of life. This was the introduction of high-flux, volume-controlled dialysis. The polymer used for the AN69 membrane is a copolymer of acrylonitrile and sodium methallylsulfonate, specially selected for the dialysis application. Contrary to most synthetic membranes AN69 is hydrophilic, because the numerous sulfonate groups attract water and create a hydrogel structure which provides high diffusive and hydraulic permeability. In the AN69 membrane the microstructure and the chemical composition offer a unique context for bulk adsorption of low-molecular-weight proteins, the high water content of the hydrogel making the polymer chains easily accessible. The highly specific adsorptive properties - limited on the surface and favored in the membrane structure and with high specificity for basic, medium-sized proteins - distinguish AN69 from other synthetic high-flux membranes as well as from other so-called adsorptive membranes in the field of dialysis. Since its creation in the early 1970s the AN69 membrane has evolved to meet the requirements and challenges of dialysis therapy. Still the basic characteristics of high permeability to fluid and to a wide range of relevant uremic retention products combined with excellent biocompatibility, whether measured by traditional or novel indicators, have remained the hallmark of the membrane. The unique adsorptive capacity has provided a base for further development. The latest version of AN69, HeprAN, has heparin grafting on the inner surface and enhanced adsorption of bacterial products on the outer surface. Modern versions of AN69 are today used in hemodialysis and contemporary modes of convective therapies for a large number of chronic as well as acute renal patients around the world., (Copyright © 2011 S. Karger AG, Basel.)

Background/aims: With advanced anticoagulation, many institutions operate continuous renal replacement therapy (CRRT) circuits longer than manufacturers' recommendations. This extended use may change hemodiafilter performance and clearance properties. However, hemodiafilter performance over time has not been assessed. We investigated solute clearance over time in modeled CRRT., Methods: In vitro continuous hemofiltration (CH) and continuous hemodialysis (CD) were operated for 48 h using AN69 polyacrylonitrile, cellulose triacetate, F70 polysulfone, and Optiflux F160NR polysulfone hemodiafilters with citrated bovine blood. Urea, creatinine, gentamicin, vancomycin, and albumin clearances were assessed in CH (ultrafiltration rates = 1 and 3 l/h). Clearances of urea, creatinine, gentamicin, and albumin, were assessed in CD with dialysate flow rate of 2 l/h., Results: Solute CH clearances were significantly higher at 3 l/h. Only creatinine and gentamicin clearances were affected by time. Creatinine CD clearance significantly declined at 48 h for all hemodiafilters, especially polysulfone hemodiafilters., Conclusions: CRRT duration affects solute transmembrane clearance. Clinicians should consider hemodiafilter age when assessing hemodialysis dose or drug clearance., (Copyright © 2011 S. Karger AG, Basel.)

Objective: The objective of this study was to test the ability of myoglobin removal of a novel, high-permeability polysulphone dialyzer in acute kidney injury as a result of rhabdomyolysis., Setting: Intensive care unit of a tertiary care hospital., Patients: Six patients (one female; aged 24, 36, 41, 55, 63, and 65 yrs) with oligoanuric acute kidney injury resulting from rhabdomyolysis., Interventions: Extended dialysis was performed using a single-pass batch dialysis system and a novel polysulphone high-flux dialyzer (effective surface area 1.8 m; inner lumen 220 μm; wall thickness 35 μm; allowing elimination of substances with a molecular weight of up to 30 kDa)., Measurements and Main Results: Samples were collected at prefilter and postfilter sites as well as from the collected spent dialysate. The dialyzer clearance was calculated from concentrations before and directly after the dialysis membrane, the blood flow, and the ultrafiltration rate. The total amount of the myoglobin removed was measured directly as the whole dialysate was preserved. A median myoglobin clearance of 90.5 mL/min (range, 52.4-126.3 mL/min) was achieved, resulting in a median myoglobin removal per treatment hour of 0.54 g (range, 0.15-2.21 g)., Conclusions: Extended dialysis with a high-flux, high-permeability membrane allowed effective elimination of myoglobin with a clearance of myoglobin that surpassed all previously reported dialysis techniques. This membrane may be advantageous in preventing acute kidney injury or avoiding complete loss of kidney function in patients with rhabdomyolysis. Further studies are needed to determine whether improving renal recovery or mortality in patients with acute kidney injury resulting from rhabdomyolysis is possible.

Global knowledge of the molecular target of uremic toxins (UTs) was significantly different in the 1980s than it is now. In 1971, Babb et al. hypothesized that UTs such as neurotoxin existed in mid-sized molecules ranging from 300 to 3,000 Da. In the 1980s, larger molecular weight substances > 5,000 Da were targeted for removal, as well as small and medium size toxins in Japan, while urea was considered a surrogate marker of UTs, and Kt/V for urea was used as a measure of dialysis dose in the USA. In Japan, albumin-bound toxins in addition to low-molecular-weight proteins were targeted for removal as glomerular filtration in the normal kidney. As binding capacity of albumin is significantly lowered and, on the other hand, the α-helical content of albumin also lowered in uremic patients because of binding of UTs to albumin, a small amount of albumin should be removed to stimulate the synthesis of new albumin. KF101 C-2 (EVAL) used as a high-performance dialysis membrane (HPM) at the first step, in which approximately 7 g of albumin is removed per dialysis session. It resulted in lowered plasma albumin levels in hemodialysis patients, although accumulated levels of low-molecular-weight proteins were significantly lowered. Therefore, the Japanese Society of Dialysis Therapy has recommended limitation of albumin removal to < 3 g/session by the second generation of HPMs. Many different HPMs have been developed since the Japanese Society of HPM was first organized in 1985. Approximately 98% of the dialyzers used in Japan employ HPMs. New technology is required to suppress fouling on the surface and in the pores of HPMs. This would maintain permeation of inflammatory cytokines during dialysis sessions., (Copyright © 2011 S. Karger AG, Basel.)

New directions in dialysis research include cheaper treatments, home based therapies and simpler methods of blood purification. These objectives may be probably obtained with innovations in the field of artificial kidney through the utilization of new disciplines such as miniaturization, microfluidics, nanotechnology. This research may lead to a new era of dialysis in which the new challenges are transportability, wearability and why not the possibility to develop implantable devices. Although we are not there yet, a new series of papers have recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable artificial kidneys (WAK). Some of them use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality (ViWAK and AWAK.) A special mention deserves the wearable/portable ultrafiltration system for the therapy of overhydration and congestive heart failure (WAKMAN). This system will allow dehospitalization and treatment of patients with less comorbidity and improved tolerance. On the way to the wearable artificial kidney, new discoveries have been made such as a complete system for hemofiltration in newborns (CARPEDIEM). The neonate in fact is the typical patient who may benefit from miniaturization of the dialysis circuit. This review analyzes the rationale for such endeavour and the challenges to overcome in order to make possible a true ambulatory dialysis treatment. Some initial results with these new devices are presented. We would like to stimulate a collaborative effort to make a quantum leap in technology making the wearable artificial kidney a reality rather than a dream.&nbsp;

New strategies using continuous renal replacement therapy as a tool to achieve immunomodulation in septic acute kidney injury have been proposed. The hypothesis is based on the possibility to remove inflammatory mediators and oxidants in a wide spectrum of molecular weights, thanks to new, highly permeable synthetic membranes. A new polysulfone hemofilter with high permeability and a sharp high cut-off membrane (CUREFLO™; Asahi Kasei Kuraray Medical Co., Ltd., Tokyo, Japan) has been evaluated in this study to assess IL-6 and advanced oxidation protein product removal in critically ill patients undergoing continuous renal replacement therapy. Unit performance, sieving coefficients and clearances were evaluated in fourteen patients undergoing continuous veno-venous hemofiltration and continuous veno-venous hemodialysis., (Copyright © 2011 S. Karger AG, Basel.)

Background/aims: We sought to identify the most relevant hemofilter for cytokine removal based on the mechanisms of filtration and adsorption., Methods: Ascites were filtered using four types of hemofilters composed of different membrane materials (polymethyl methacrylate, PMMA, cellulose triacetate, CTA, or polysulfone, PS) and different surface areas (1.0 or 2.1 m(2)) to investigate the rate of interleukin-6 (IL-6) filtration. Next, ascites were perfused through each hemofilter without obtaining a filtrate to study each filter's adsorptive capability., Results: The PMMA hemofilters resulted in a marginal observed IL-6 filtration rates, whereas the CTA and PS hemofilters resulted in highly effective IL-6 filtration. Regarding the IL-6 adsorptive capabilities of the filters, the PMMA hemofilter with a large surface area showed the highest level of IL-6 clearance., Conclusion: The present findings suggest that when cytokine removal based on filtration is desired, CTA or PS hemofilters should be selected. When IL-6 removal based on adsorption is desired, a PMMA hemofilter with a large surface area should be selected., (Copyright © 2010 S. Karger AG, Basel.)

In continuous venovenous hemofiltration (CVVH), the delivery of replacement fluid in pre- or postdilution mode remains the subject of controversy. We compared both modes in terms of filter life, dose, and azotemic control. All patients admitted to the intensive care units of a university hospital between November 2004 and December 2006 receiving CVVH and systemic anticoagulation with heparin were retrospectively studied. Thirty-six patients treated by CVVH in predilution and 27 in postdilution mode were studied, with 132 filters in the former and 111 in the latter. The filter life [median ± interquartile range (IQR)] was 24 ± 38 hours and 29 ± 46 hours (p = 0.58) in the pre- and postdilution modes, respectively. Although the fall in creatinine and urea depended on the dose, 19% greater delivered dose in the post- than predilution mode did not impact on azotemic control. In critically ill, heparinized patients on CVVH, filter life and azotemic control are similar in pre- and postdilution modes and underscore the clinical applicability of the predilution mode.

Background: Continuous venovenous hemofiltration (CVVH) in renal failure is compromised by circuit clotting. We hypothesized that adverse circuit pressures are predictive of clotting in circuits that last less than 24 h during predilution, anticoagulant-free CVVH., Methods: This was a single-center retrospective study of 63 CVVH circuits of 13 critically ill intensive care unit patients with severe renal failure. Circuits were categorized into 'clotters' (C) or 'nonclotters' (NC), if spontaneous clotting occurred at <24 or ≥24 h from the start of CVVH, respectively., Results: Effluent pressures and pre-filter pressures were more adverse in NC compared to C starting from 6 and 4 h before spontaneous clotting, respectively. Arterial pressures and return pressures were not significantly different in C versus NC. Blood flow rate settings, hemofiltration fluid replacement and effluent drainage rates in C versus NC were comparable., Conclusion: Real-time circuit pressure readings seem to offer only potentially limited prognostic value in predicting circuit clotting., (Copyright © 2011 S. Karger AG, Basel.)

HPM (high-performance membrane or high-flux membrane) has better biocompatibility and higher capacity to remove retention solutes of large molecular weight, which has been proven to be toxic especially to cardiovascular and skeletal organs. To date, several non-randomized observational studies have shown a reduction in morbidity and mortality in HPM-treated patients compared with low-flux conventional membrane. Meanwhile, two randomized controlled trials were unable to reveal the superiority of high-flux membrane in survival of all-cause mortality, but suggested a significant benefit by subgroup analyses or post-hoc analyses in patients with diabetes, hypoalbuminemia and long duration of prior dialysis. Thus, the results of the published studies are conflicting and it still cannot be explained whether the effect is based on the biocompatibility of the membrane or on the differences in the clearance of middle molecules, or on the microbiological purity of dialysate which improved simultaneously with the flux increment. As survival outcome might be determined by additional multiple confounding factors, dialysis-related or non-dialysis-related, investigations to control them are difficult to perform. Although the clinical results are non-conclusive and it is still unanswered how much large molecule removal is required to improve outcomes in routine clinical practice, there is a considerable amount of biological plausibility for high-flux dialysis or middle molecule removal. Further trials will be required to confirm what patient group benefits the most, the magnitude of advantages and how large the molecules are and how much molecule removal is acceptable using advanced high-performance dialyzers. Dispersing hazardous effects by a low-quality therapy should be taken more seriously than practicing a high-quality therapy of uncertain superiority., (Copyright © 2011 S. Karger AG, Basel.)

The aim of this study was to investigate whether continuous hemodiafiltration (CHDF) with a high-performance membrane dialyzer made of polymethylmethacrylate (PMMA-CHDF) in the treatment of septic shock patients with acute renal failure (ARF) is clinically relevant. 30 patients were treated with PMMA-CHDF. 13 patients treated with CHDF used a hemofilter made of polyacrylonitrile membrane (PAN-CHDF). Systolic blood pressure significantly increased in the PMMA-CHDF group following 24 h of treatment (p < 0.01), whereas it did not improve in the PAN-CHDF group. Urine volume significantly increased in the PMMA-CHDF group following 24 h of treatment which was more than in the PAN-CHDF group (p < 0.05). 28-day survival was 83.3% in the PMMA-CHDF group and 30.8% in the PAN-CHDF group, respectively (p < 0.01). We can assume that PMMA-CHDF in the treatment of septic shock patients with ARF is clinically relevant., (Copyright © 2011 S. Karger AG, Basel.)

Over 2,000 substances have been reported as uremic substances that are accumulated or produced due to renal failure that causes various clinical symptoms and complications. These substances include many medium to large molecular weight (MW) substances such as β(2)-microglobulin (β(2)-MG). In hemofiltration/hemodiafiltration (HD/HDF) therapy using high-performance membrane targeting less albumin loss and removal of β(2)-MG with a MW of 11,800, many cases showed insufficient improvement in the clinical outcome contrary to the decrease in serum β(2)-MG concentration. Focusing on these facts, HD/HDF therapy, which associates albumin loss, was implemented targeting the substances in the regions whose MWs are larger than β(2)-MG. HD/HDF therapy with protein-permeable membrane, compared to the therapy without protein-permeable membrane, achieved higher success in the removal of larger MW substances including β(2)-MG, cytokine, homocysteine and complement factor D, and higher clinical outcomes were reported, such as prevention of development of amyloidosis, anemia, osteoarthritis and pruritus, and improvement in life prognosis and biocompatibility in Japan. Therefore, in the current circumstances, it is essential to administer a treatment that can get as close to the glomerular basement membrane as possible, use dialysis membrane to effectively remove a wide range of substances, and aim to remove all of the substances accumulated in the body of patients with kidney dysfunction., (Copyright © 2011 S. Karger AG, Basel.)

Background: Distal filter protection allows for continuous cerebral perfusion during carotid artery stenting (CAS), although a higher risk of debris migrating into the cerebral arteries compared with other protection systems has been reported., Objective: To improve the extent of debris capture, we used routine aspiration of blood located proximal to the filter in the internal carotid artery blood column before retrieval of the filter device., Methods: Of 71 CAS procedures with distal filter protection, routine aspiration was performed in 41 procedures. The size and number of debris particles in each aspirated blood sample were measured under a stereoscopic microscope in 30 consecutive procedures with routine aspiration. Occurrence of periprocedural neurological events was compared between 41 procedures with routine aspiration and the other 30 without routine aspiration., Results: In the aspirated blood, debris particles ≥ 500 μm and ≥ 1000 μm in the longest diameter were observed in 30 (100%) and 28 (93.3%) procedures, respectively. The number of particles ≥ 1000 μm was significantly larger in the second through fourth blood aspirates vs the first aspirate (P < .05). Occurrence of periprocedural neurological events was significantly less frequent in the routine aspiration group (0 of 41 procedures) than in the conventional method group (7 of 30 procedures) (P < .05)., Conclusion: The use of routine aspiration during CAS with distal filter protection possibly reduced periprocedural neurological events by increasing the proportion of debris captured. To improve the capture of debris particles, at least 4 repeated aspirations are advisable during each CAS procedure.

Purpose: Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood., Experimental Design: We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison., Results: Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five patients., Conclusions: This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients., (©2010 AACR.)

We report the time to stable ST-segment reperfusion (TSTR) after primary angioplasty and its relationship with the clinical results; 137 patients who underwent primary angioplasty were included as part of the analysis. All patients had 24 hours ST-segment monitoring. Time to stable STR was defined as the beginning of ST-segment reperfusion (STR) lasting >4 hours without ST-segment reelevation. Six-month mortality was associated with slower TSTR (median 166.5 vs 6 minute, P = .001). Time to stable STR cutoff value of 136.5 minutes was identified as the best mortality predictor (area under the curve: 0.86, P = .001). Multivariate analysis identified Killip class > or = 2 (P = .042), TSTR cutoff value (P = .002), and final thrombolysis myocardial infarction (TIMI) flow grade III (P = .067) as predictors of 6-month mortality. Time to stable STR may be a novel continuous electrocardiogram (ECG) parameter following primary angioplasty, which can identify high-risk patients that need to be considered for additional treatments.

Background: Reduced haemocompatibility and early filter failure during continuous venovenous haemofiltration (CVVH) can be attributed to various aspects from filter engineering to rheological problems. Still, little is known about the impact of acidaemia and hypoxaemia on the haemocompatibility of a CVVH. In a porcine model, we investigated blood and coagulation parameters, filter performance and blockage of filter capillaries to assess the impact of acidaemia and hypoxaemia on haemocompatibility., Methods: Pigs were assigned to three groups (n = 6). One group received mixed acidaemia (pH 7.2) by acid infusion (0.2 M of lactic acid and 0.2 M HCl diluted in normal saline) and low tidal volume ventilation (6-8 mL/kg(-)(1)), one group underwent an additional hypoxaemia (pH 7.2; PaO(2) < 70 mmHg) and another was treated with normal saline and normoventilation (control group; pH 7.4). To accelerate biocompatibility reactions, CVVH was operated with reinfusion of the filtrate to the venous line for 3 h based on standardized heparinization., Results: Acidaemia led to a contradictory pattern with respect to prothrombin time (prolongation), activated partial thrombin time and activated clotting time (acceleration). In comparison to normal pH homeostasis, acidaemia led to increasing activation markers such as terminal complement complex marker sC5b-9, thrombin-anti-thrombin complexes (TAT) and D-dimers. Additional hypoxaemia intensified activation with regard to TAT and complement complex marker sC5b-9. Platelet counts suffered from acidaemia and a tendency for higher rates of blocked hollow fibres was found., Conclusion: Acidaemia led to deteriorated haemocompatibility reactions to a CVVH circuit. The coagulation pattern developed towards complications for the coagulatory state.

Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 microg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 microg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.

Background: The purpose of this study was to compare the ability of three commonly used pediatric cardiopulmonary bypass (CPB) circuits to filter gaseous microemboli (GME) in an in vitro model., Methods: Devices were tested at different levels of two specific independent variables: volume of air injected (1, 3, 5ml) and percentage of each oxygenator's rated flow (50%, 75%, 100%, 125%). The air-handling ability of each CPB circuit was determined by the Emboli Detection and Classification Quantifier (Luna Innovations Inc., Roanoke,VA)., Results: At all tested conditions, the FX-05 allowed a higher percentage of GME when compared to either one or both of the other two CPB circuits. When comparing oxygenators at similar absolute flow rates, the KIDS D100/D130 CPB circuit performed worse compared to the other two CPB circuits., Conclusions: The combination of the Baby RX-05 oxygenator and Capiox AF02 arterial line filter provides the highest level of protection from air emboli in an in vitro investigation.

Introduction: The presence of emboli was recognised relatively early in the history of open heart surgery. The emboli produced during cardiopulmonary bypass have the predisposition to distribute into, and ultimately obstruct, microvessels of all tissues. The Sorin Group has recently developed a new range of arterial line filters. Before the Sorin AF range of filters was released for pre-launch clinical trials, our group performed in vitro laboratory testing of the AF range against a selection of commercially available filters on the global market., Results: The Sorin AF620 and AF640 demonstrate both the smallest prime volume and smallest surface contact area (92ml and 290 cm(2), respectively).The results of the GME Handling Efficiency experiments ranged by 39.6%, from 95.9% to 56.3%. In terms of an air bolus handling, the results of the Limit Bolus experiment ranged by 97 ml, from 147.5 ml down to 50 ml. The pressure drop across all the filters was measured under steady state experimental conditions. All of the above investigations were considered against surface area and prime volume., Conclusion: It is clear from the results that some commercially available arterial line filters perform better than others, not only in overall performance, but also with regard to individual characteristics. Evaluating arterial line filters for hospital-specific use has to balance pressure drop, surface area, micro air handling, prime volume and gross air handling; all points need to be considered. In the AF620 and AF640, Sorin boast that they are the two smallest prime and smallest surface area filters commercially available on the global market. The Sorin AF filter range performs well in all of the areas we investigated and will be a competitive option for centres, irrespective of which characteristics they use to evaluate and select their arterial line filter.

Microelectromechanical systems (MEMS) are used to machine miniaturized implantable medical devices. Our group has used MEMS technology to develop hemofiltration membranes for use in renal replacement therapy, which possess enhanced selectivity and permeability. The use of silicon in blood-contacting environments may be limited, however, due to contact activation of the coagulation cascade by silicon, which forms the surface oxides in atmospheric conditions. As well, the reports of long-term biocompatibility of blood- contacting silicon devices are lacking. The aims of this pilot study were as follows: 1) to develop a model for investigating the effects of intravascular implants and 2) to characterize the degree of thrombosis and tissue inflammation incited by prolonged implantation of silicon materials. Silicon implants with and without polyethylene glycol (PEG) coatings were surgically implanted transluminally through rat femoral veins. Gore-Tex and stainless steel implants served as controls. The implants were left in vivo for 4 weeks. All femoral veins remained patent. The veins associated with silicon implants exhibited rare thrombi and occasional mild perivascular inflammation. In contrast, Gore-Tex and stainless steel controls caused moderate vein thrombosis and provoked a moderate to marked cellular infiltrate. Under scanning electron microscopy, bare silicon implants were found to have significant adherent microthrombi, whereas PEG-treated implants showed no evidence of thrombi. PEG-treated silicon seems to be biocompatible and holds potential as an excellent material with which to construct an implantable, miniaturized hemofiltration membrane.

Ultrafiltration of the residual cardiopulmonary bypass circuit blood has become one of the most advantageous procedures to maximize autologous whole blood recovery and coagulation management in cardiovascular surgery. In this in-vitro study, the Hemobag technique (HB) was compared to the most common non-Hemobag method (NHB) of hemoconcentrating residual circuit blood. The residual bovine blood from 10 identical extracorporeal circuits was processed by the recirculating HB technique or by a venous reservoir NHB concentration method. Blood component concentrations and hemolysis levels were measured before and after processing. The HB method yielded significantly higher hemoglobin, hematocrit, fibrinogen, albumin, and total protein levels in the final product. There was no significant difference in final product platelet and white blood cell counts, or hemolysis index. HB processing times were substantially shorter at all residual circuit volumes tested. The HB technique resulted in significantly less wasted red blood cells at the end of processing. The recirculating HB method to process residual extracorporeal circuit blood is consistent and superior to the most common single pass concentrating method.

Gaseous microemboli (GME) remain a challenge for cardiopulmonary bypass procedures in adult as well as pediatric cardiac surgery patients. The present study tested the effectiveness of a new adult membrane oxygenator in models both with and without an integrated arterial filter to evaluate GME trapping capability and determine membrane pressure drops at various flow rates and temperatures. The experimental circuit included a RotaFlow centrifugal blood pump, Quadrox-i (n = 8) or Quadrox (n = 8) adult microporous membrane oxygenator, and Sorin adult tubing package. A Sorin Cardiovascular VVR 4000i venous reservoir served as pseudo-patient. The circuit was primed with 900 mL heparinized human red blood cells and 300 mL Lactated Ringer's solution. The final hematocrit was 36%. Tests were performed at different flow rates (4 L/min, 5 L/min, and 6 L/min) and temperatures (35 degrees and 30 degrees). Five mL of bolus air was injected into the venous line over 15 seconds using a syringe connected to a 3/8 x 1/2 luer connector. The Quadrox-i adult microporous membrane oxygenator with integrated arterial filter had a similar pressure drop at 4 L/min and 35 degrees C compared with Quadrox membrane oxygenator whereas it had higher pressure drops at 5 L/min and 6 L/min (p < .001). Quadrox-i adult microporous membrane oxygenator reduced the total emboli count and total emboli volume delivered to the pseudo-patient at all flow rates (p < .001).The emboli handling of Quadrox-i adult microporous membrane oxygenator was not affected by flow rate and temperature. Compared with the traditional Quadrox oxygenator, Quadrox-i adult microporous membrane oxygenator with integrated arterial filter and Softline coating has improved GME handling capacity.

Objective: To evaluate the safety and efficacy of the MARS and Prometheus extracorporeal liver support systems in the treatment of liver failure., Design: We performed a systematic review of the literature from January 1999 to June 2009 in the Medline, Embase, HTA, DARE, NHSEED, Cochrane Library Plus, Clinical Trials Registry and HSRPROJ databases. Study selection was based on a series of previously established inclusion criteria related to the study design, population, type of intervention, language, and outcome measures., Patients and Interventions: Patients with acute liver failure or acute exacerbations of chronic liver failure treated with the MARS or Prometheus systems., Outcome Measures: Data on safety, long-term survival, clinical effects and biochemical and hemodynamic variables., Results: We selected 22 studies evaluating the safety and efficacy of the MARS and Prometheus systems. Adequate evaluation of these techniques was hampered by the heterogeneity of the studies and their methodological limitations., Conclusions: Extracorporeal liver support systems are able to purify both hydrosoluble and protein-bound substances. However, current data show that only the MARS system reduces mortality in acute liver failure and in acute exacerbations of chronic liver failure, although this reduction is non-significant. These techniques can be considered safe, with adverse effects similar to those of the control group. Their main indication is severe liver failure, for short periods while the liver recovers or a liver transplant becomes available.

Objective: To explore the influence of continuous blood purification (CBP) on plasma cytokines in children with severe sepsis., Methods: A double lumen catheter was inserted into the femoral vein of 21 children with severe sepsis, and CBP was performed using the Baxter BM25 system. Blood urea nitrogen (BUN), plasma creatinine (Cr), K(+) and arterial blood gas were measured before and after CBP, and the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, IL-8, and IL-10 were measured by ELISA at 0, 1, 3, 6, and 24 h after CBP., Results: BUN and plasma Cr and K(+) levels decreased and HCO(3)(-)increased significantly after CBP (P<0.001), which also resulted in significant reduction of the plasma concentrations of TNF-alpha, IL-1, IL-8 and IL-10 (P<0.01). The plasma TNF-alpha, IL-1, and IL-8 levels were significantly lower at 3 h after CBP than those before CBP (P<0.01)., Conclusions: CBP can improve the blood biochemical markers and clear some plasma cytokines in children with severe sepsis.

Today hemodialysis is a routine outpatient treatment, not only carried out in hospitals, but more commonly in free standing units without on site medical supervision. One of the key advances that have underpinned this expansion of hemodialysis provision has been the technological advances in dialyzer membrane technology. Dialyzer membranes have undergone a sea change from collodion tubes to cellulose sheets to the modern day capillary fiber dialyzer. Improvements have not only been limited to reliability of manufacture, but also reduction in bio-incompatibility, and improved small solute clearances. However, the holy Grail remains the development of a dialyzer capable of removing middle sized azotemic retention solutes, and protein bound or lipophilic solutes.

Adsorption of gentamicin and netilmicin by new polyacrylonitrile and polyamide hemofiltration filters was studied over 4 h, using a single-compartment in vitro continuous venovenous hemofiltration model. After the first dose (16.6 mg of gentamicin, 19.3 mg of netilmicin), 14.9 mg of gentamicin and 19.2 mg of netilmicin were adsorbed to polyacrylonitrile filters in vitro. Adsorption by polyacrylonitrile filters was rapid and irreversible and could be increased by repeated dosing. Adsorption by polyamide filters was substantially less.

The low-molecular weight fraction (LMF) of the human plasma proteome is an invaluable source of biological information, especially in the context of identifying plasma-based biomarkers of disease. In this study, a separation and enrichment strategy based on centrifugal ultrafiltration was developed for the LMF (i.e., 50K, and recovery and enrichment of low-M(r) components from human plasma. This filter membrane device was further optimized with respect to plasma buffer composition, centrifugal force, duration and temperature. Optimal ultrafiltration conditions were obtained using 100 microL of normal plasma in 10% acetonitrile, and a centrifugation force of 4000x g for 35 min at 20 degrees C. In this LMF, 44 proteins (from 266 unique peptides) were identified using a combination of 1D-SDS-PAGE / nano-LC-MS/MS and a stringent level of identification (FDR <1%). We report the identification of several proteins (e.g., protein KIAA0649 (Q9Y4D3), rheumatoid factor D5, serine protease inhibitor A3, and transmembrane adapter protein PAG) previously not reported in extant high-confidence Human Proteome Organization (HUPO) Plasma Proteome Project datasets. When compared with the low-M(r) human plasma/serum proteome datasets of Zhou et al. (Electrophoresis, 2004. 25, 1289-98), Gundry et al. (Proteomics Clin. Appl., 2007. 1, 73-88) and Villanueva et al. (Anal Chem, 2004. 76, 1560-70), 64% of our identifications (28 proteins) were novel; these include cofilin-1, PPIase A, and the SH3 domain-binding glutamic acid-rich-like protein 3. In addition to intact proteins, many peptide fragments from high-abundance proteins (e.g., fibrinogen, clusterin, Factor XIIIa, transferrin, kinogen-1, and inter-alpha-trypsin inhibitor), presumably derived by ex vivo proteolysis, were observed., ((c) 2009 Elsevier B.V. All rights reserved.)

Background: The poor outcomes in patients with acute kidney injury (AKI) and end-stage renal disease (ESRD) on chronic dialysis are due to immune dysregulation associated with these disorders. Evolving evidence suggests that the kidney, and specifically renal epithelial cells, plays an important role in the immunological response of leukocytes under disease states., Method: In this regard, the development of two therapeutic approaches utilizing renal epithelial cells and 'smart' immunomodulatory membranes has been tested in preclinical animal models and clinical trials., Results: These two approaches have been demonstrated in phase II human trials to improve the survival of intensive care unit patients with AKI and multiorgan failure. The use of a 'smart' immunomodulatory membrane is also being evaluated in a small exploratory clinical trial to assess its effects on immunoregulation in ESRD patients requiring chronic hemodialysis., Conclusions: The use of renal progenitor/stem cell therapy and/or cytopheretic membranes may result in effective treatments to alter the dysregulated immunological state of acute or chronic renal failure and improve the outcomes of these diseases., (Copyright (c) 2010 S. Karger AG, Basel.)

Recently, 'super high-flux' (SHF) or 'high cut-off' (HCO) membranes have been developed to increase the clearance of inflammatory mediators. In the experimental and clinical settings, SHF/HCO membranes appear to achieve greater clearance of inflammatory cytokines than conventional high-flux membranes. SHF/HCO membranes also restore immune cell function, attenuate hemodynamic instability and decrease plasma IL-6 levels. Moreover, SHF/HCO membranes can eliminate larger late-phase inflammatory mediators such as HMGB-1. Although albumin sieving coefficients with SHF/HCO membranes are greater than with conventional high-flux membranes, the daily amount lost is limited and can be replaced. Hemodialysis with SHF/HCO membranes can also achieve similar cytokine removal to hemofiltration with acceptable albumin losses. When strategies for sepsis or systemic inflammation treatment target middle molecular mediators, both SHF/HCO hemofiltration and hemodialysis appear feasible and safe and require further clinical investigation., (Copyright 2010 S. Karger AG, Basel.)

Thrombocytopenia is a common complication in patients receiving continuous veno-venous hemofiltration (CVVH) in the intensive care unit. The hemofilter itself plays an important role in the genesis of thrombocytopenia. The present study was undertaken to test whether there were differences in platelet loss and activation during CVVH with a polysulfone (PS) hemofilter or a cellulose triacetate (CTA) dialyzer. 96 patients with thrombocytopenia and acute kidney injury requiring CVVH were randomly assigned to four groups receiving low-molecular-weight heparin (LMWH) PS (n = 24), LMWH CTA (n = 24), no anticoagulation PS (n = 24), and no anticoagulation CTA (n = 24), respectively. We found a significant decrease in platelet counts, but an increased platelet activation with the PS hemofilter in patients who received no anticoagulation. There was no significant decrease in platelet counts and activation in the CTA group. The cellulose membranes could be an effective alternative to the standard synthetic membranes in patients at high risk for thrombocytopenia during CVVH., (2010 S. Karger AG, Basel.)

Fluid overload may occur in patients with heart failure. Further complications may arise when cardiorenal syndromes develop and the kidneys are unable to eliminate the accumulated fluid. Diuretics represent the fist line of treatment, although in some case they may be ineffective or even dangerous for the patient. In these conditions, extracorporeal ultrafiltration may be required. Extracorporeal ultrafiltration can be performed continuously or intermittently, using dedicated machines. The goal is to remove the right amount of fluid without causing hemodynamic instability or further ischemia to the kidneys. For this purpose, special technologies are available and they can be utilized in combination to prevent iatrogenic complications. First of all, a complete analysis of heart and kidney function should be carried out. Then, an evaluation of biomarkers of heart failure and a careful analysis of body fluid composition by bioimpedance vector analysis should be carried out to establish the level of hydration and to guide fluid removal strategies. Last but not least, an adequate extracorporeal technique should be employed to remove excess fluid. Preference should be given to continuous forms of ultrafiltration (slow continuous ultrafiltration, continuous venovenous hemofiltration); these techniques guided by a continuous monitoring of circulating blood volume allow for an adequate restoration of body fluid composition minimizing hemodynamic complications and worsening of renal function especially during episodes of acute decompensated heart failure., (Copyright 2010 S. Karger AG, Basel.)

The use of an arterial line filter (ALF) within the pediatric cardiopulmonary bypass (CPB) circuit is not a new concept. It has always presented the perfusionist with a circuit component that while valuable, increased prime volume. The purpose of this study was to evaluate the change in prime volume and emboli between a conventional oxygenator with separate ALF and a new generation oxygenator with integral arterial filter (AF). We performed a clinical, non-randomized retrospective evaluation of the Terumo Capiox RX15 (Terumo Cardiovascular Systems Corporation, Ann Arbor, MI) (n = 10) in conjunction with the Terumo Capiox AF125X ALF or the Capiox AF02 vs. the Terumo Capiox FX15 oxygenator with integral AF (n = 10). The above circuit components, in combination with the LUNA EDAC (emboli detection and classification) Quantifier (LUNA Innovations, Blacksburg, VA) were placed at various locations within each patient's CPB circuit to establish and quantify the presence and volume of gaseous emboli during all phases of cardiopulmonary bypass. The EDAC system is available/used for all patients undergoing CPB at this institution. When compared to a more conventional CPB circuit, the Capiox FX15 primes more easily as it does not require a carbon dioxide flush while still providing a 32 microm AF. There was no statistical difference in air handling between the tested oxygenators and their associated circuits. During this review it was determined that use of the Capiox FX15 simplifies the arterial limb of the pediatric CPB circuit. Removal of the separate ALF led to the removal of several, now unnecessary, arterial connectors and additional tubing (arterial line filter bypass). Removal of these components led to a reduction in prime volume and decreased the hemodilutional effect. The FX15 provided a safe, simplified pediatric CPB circuit and was as effective in gaseous microemboli removal as was the more traditional RX15 with separate ALF during this review.

A large percentage of patients on extracorporeal membrane oxygenation (ECMO) require continuous renal replacement therapy (CRRT) usually performed through a different venous access or by introducing a filter into the ECMO circuit. Here, we evaluated the efficacy and safety of including a CRRT machine in the circuit by connecting its inlet line after the centrifugal pump and its outlet line before the oxygenator. We tested the function of the combined system initially in a closed circuit, followed by an experimental animal study, and, finally, in a clinical trial with six children. Both machines functioned adequately and there were no significant changes in the pressures of the ECMO circuit after the introduction of the CRRT device, thus achieving the preset negative balances and normalization of the serum urea and creatinine concentrations. The mean life of the filters was about 138 h, and only one filter needed changing due to clotting. Our study shows that the introduction of a CRRT device into the ECMO circuit is a safe and effective technique that improves fluid balance, increases filter life, and does not cause complications. For these reasons, this may be a good method for performing CRRT in patients on ECMO.

Perfusion techniques and equipment in pediatric open heart surgery have continued to focus on decreasing prime volumes and lowering surface areas of the cardiopulmonary bypass circuit. While this has improved drastically over the last 20 years, greater demand is being placed on the perfusionist to reduce the deleterious effects of bypass without compromising safety or efficiency. Specifically, manufacturers of disposable perfusion equipment have focused on providing pediatric perfusionists with oxygenators that provide the smallest prime and surface area possible while attempting to maximize performance. Recently,Terumo Cardiovascular has introduced the Capiox FX05, a neonatal hollow fiber oxygenator that includes an integrated arterial line filter. The FX05 provides a blood flow range of 0.1-1.5 L/min and a low priming volume of 43 mL. Additionally, it is coated with X Coating, a biocompatible, hydrophilic polymer surface coating that reduces platelet adhesion and protein denaturation. The purpose of this study was to test the FX05 for gas transfer, blood path resistance, and blood handling characteristics in a standardized clinical setting. Heat exchange coefficients were also calculated during the cooling and warming period. Other data analyzed includes bypass circuit prime volumes and initial patient hematocrit along with the total operative homologous blood donor exposures. In summary, the FX05 offers good gas exchange capabilities and a low pressure drop during normal cardiopulmonary bypass parameters along with the safety of an integrated arterial line filter. Furthermore, the FX05 with integrated filter allows a reduction in overall bypass prime volume and surface area while promoting the reduction of homologous blood transfusions, optimizing hemostasis.

Sepsis, a systemic inflammatory response in the presence of an infection, is characterized by overproduction of inflammatory mediators called cytokines. Removal of these cytokines using an extracorporeal hemoadsorption device is a potential therapy for sepsis. We are developing a cytokine adsorption device (CAD) filled with microporous polymer beads and have previously published a mathematical model which predicts the time course of cytokine removal by the device. The goal of this study was to show that the model can experimentally predict the rate of cytokine capture associated with key design and operational parameters of the CAD. We spiked IL-6, IL-10, and TNF into horse serum and perfused it through an appropriately scaled-down CAD and measured the change in concentration of the cytokines over time. These data were fit to the mathematical model to determine a single model parameter, Gamma( i ), which is only a function of the cytokine-polymer interaction and the cytokine effective diffusion coefficient in the porous matrix. We compared Gamma( i ) values, which by definition should not change between experiments. Our results indicate that the Gamma( i ) value for a specific cytokine was statistically independent of all other parameters in the model, including initial cytokine concentration, flow rate, serum reservoir volume, CAD size, and bead size. Our results also indicate that competitive adsorption of cytokines and other middle-molecular weight proteins, which is neglected in the model, does not affect the rate of removal of a given cytokine. The model of cytokine capture in the CAD developed in this study will be integrated with a systems model of sepsis to simulate the progression of sepsis in humans and to develop a therapeutic CAD design and intervention protocol that improves patient outcomes in sepsis.

Solute removal performances of dialyzers are dependent not only on the solute permeabilities of the membrane but also on the module design. We have investigated how the packing density of hollow fiber (PDF) affects the solute removal performances. A series of 4 polyester polymer alloy membrane test dialyzers were assembled with varying PDFs of 29.6%, 35.3%, 44.1%, and 53.1%. Clearances (C(L)) were measured in vitro for creatinine (MW113), vitamin B(12) (MW1355), and chymotrypsin (MW25300) with various Q(B)=100 to 400 and Q(D)=350 to 650 mL/min in the absence of net ultrafiltration. When Q(B) was 44.1%, which was also considered to be due to the internal filtration. Packing density of hollow fiber can be optimized in terms of solute removal performances when the target solute and therapeutic conditions are specified.