Score Model for the Evaluation of Dialysis Membrane Hemocompatibility

The interaction of blood with artificial surfaces is of particular interest during hemodialysis treatments with extracorporeal blood circuits. Components of the extracorporeal blood circuit are known to have only a moderate, sometimes even an unfavorable hemocompatibility, and thus may provoke adverse biochemical or clinical sequelae. This article describes a newly established hemocompatibility assessment score. This score is based on on a standardized series of in vitro tests and is applied to commercially available hemodialysis membranes. It relates to a variety of membrane polymers, such as regenerated cellulose, diethylaminoethyl‐modified cellulose, polyethersulfone/polyarylate blends and polysulfone. In order to compare different polymers used in the manufacturing of dialysis membranes, a set of the following hemocompatibility parameters was assessed and assembled to an overall score: generation of complement factor 5a, thrombin‐antithrombin III‐complex, release of platelet factor 4, generation and release of elastase from polymorphonuclear granulocytes, and platelet count. With respect to these parameters, the results reveal major differences between the selected dialysis membranes. This new score model proves to be an efficient tool to derive objective results, and it may, thus, be used in the future to facilitate the selection of membrane polymers with an appropriate hemocompatibility pattern for dialysis therapy.     

Defining the Microbiological Quality of Dialysis Fluid

With increasing awareness about the degree and the potential impact of microbiological contamination in dialysis fluids, there is a desire to improve their microbiological quality. To achieve this goal, the origin of the microbiological contamination has to be identified. The water, the bicarbonate concentrate, and the fluid distribution system can be major contributors. Regular disinfection of the entire fluid path is necessary to prevent the formation of biofilm. The bicarbonate concentrate should be handled with special attention because it constitutes an excellent growth medium for microflora that may not be detected with regular assays. With a well maintained reverse osmosis (RO) system, frequent disinfection of the entire flow path, and microbiological awareness, it is possible to produce dialysis fluid that meets the most stringent standard (<10² colony forming units (CFU)/ml and <0.25 IU/ml of endotoxin). Adding a step of ultrafiltration just before the dialyzer can make the dialysis fluid ultrapure (<10⁻¹ CFU/ml and <0.03 IU/ml). One additional step of controlled ultrafiltration provides sterile and pyrogen-free fluids (<10⁻⁶ CFU/ml and <0.03 IU/ml) that can be used for infusion.     

A Noninvasive Determination of Fistula Blood Flow in Dialysis Patients

Abstract: Arteriovenous fistula (AVF) blood flow was evaluated in 32 dialysis patients using a pulsed Doppler velocimeter with two dominant features: a range-gated time system and a double transducer probe. With the proposed apparatus, the observation angle between the ultrasound beam and the vessel axis was known. In radial AVF, blood flow was 728 ± 53 ml/min and was negatively correlated with the age of the AVF (r=-0.62; p<0.01). In brachial AVF, blood flow was 778 ± 152 ml/min. In bovine heterograft AVF, blood flow was 1,225 ± 125 ml/min. In the overall population, a negative relationship was observed between the diameter of the fistula and the blood flow velocity (r=-0.57; p<0.01). The study describes an accurate noninvasive method for the determination of fistula blood flow in dialysis patients, which may be helpful in the follow-up of the regional hemodynamics of this vascular access.     

Clinical Evaluation of a New Water Removal Measuring Device in Standard Dialysis

A new device measuring water removal during standard dialysis is evaluated. The filtrate, collected from a small hemofilter inserted into a normal Cuprophan hollow-fiber dialyzer, was used to evaluate the total water removed from the patient. The device was tested in 46 patients undergoing regular dialysis treatment; the body weight loss ranged from 300 to 5,600 ml for a total of 71 dialysis sessions. Results confirmed the reliability of the device, as the mean prediction error was 5.4%. No influence of the dialyzer blood rest volume on the prediction error was observed. The authors propose this system as an alternative to bed or armchair scales and emphasize its usefulness for experimental purposes.     

Presurgical Evaluation of Fontan Connection Options for Patients With Apicocaval Juxtaposition Using Computational Fluid Dynamics

Apicocaval juxtaposition (ACJ) is a rare congenital heart defect associated with single ventricle physiology where optimal positioning of the Fontan conduit for completion of total cavopulmonary connection (TCPC) is still controversial. In ACJ, the cardiac apex is ipsilateral with the inferior vena cava (IVC), risking kinking and collapse of the Fontan conduit at the apex of the heart. The purpose of this study is to evaluate two viable routes for Fontan conduit connection in patients with ACJ, using computational fluid dynamics. Internal energy loss evaluations were used to determine contribution of conduit curvature to the energy efficiency of each cavopulmonary anastomosis configuration. This percentage of energy loss contribution was found to be greater in the case of a curved extracardiac conduit connection (44%, 4.1 mW) traveling behind the ventricular apex, connecting the IVC to the left pulmonary artery, than the straighter lateral tunnel conduit (6%, 1.4 mW) installed through the ventricular apex. In contrast, net energy loss across the anastomosis was significantly lower with extracardiac TCPC (9.3 mW) in comparison with lateral tunnel TCPC (23.2 mW), highlighting that a curved Fontan conduit is favorable provided that it is traded off for a superior cavopulmonary connection efficiency. Therefore, a relatively longer and curved Fontan conduit has been demonstrated to be a suitable connection option independent of anatomical situations.     

Hemocompatibility Evaluation With Experimental and Computational Fluid Dynamic Analyses for a Monopivot Circulatory Assist Pump

Abstract:  The hemocompatibility of a newly developed monopivot circulatory assist pump was evaluated by the computational fluid dynamic (CFD) analyses with the particle tracking velocimetry measurement. Results were compared with those of the hemolysis test and in vitro antithrombogenic test to prevent hemolysis and thrombus formation inside the pump. The results of the CFD analysis and the particle tracking velocimetry had a good agreement with each other. The flow distributions by the CFD analysis indicated that the radial jet out of the impeller was adequately weak so that the wall shear stress was lower than 300 Pa on the volute casing wall. It corresponded with the hemolysis tests results, indicating that the hemolysis level was lower than that of the commercially available pump. However, the flow distributions also indicated that the pivot that was easy to stagnate was washed out, not only by the secondary flow through the back gap of the impeller, but also by the vortices generated by the secondary vanes. It corresponded with the in vitro antithrombogenic test results, indicating that thrombus formation could be removed only by redesigning the geometry of the secondary vanes.     

Comparison of Hemodynamics in the Ascending Aorta Between Pulsatile and Continuous Flow Left Ventricular Assist Devices Using Computational Fluid Dynamics Based on Computed Tomography Images

This study aims to investigate differences in hemodynamic conditions in the thoracic aorta for pulsatile and continuous‐flow left ventricular assist devices (LVADs) using computational fluid dynamics (CFD). Patient‐specific models were reconstructed from three patients with continuous‐flow LVAD (HeartMate II, Thoratec Corporation) and three patients with biventricular assist devices (Excor, Berlin Heart) where only the aortic part was included in the simulations. CFD simulations were performed with constant inflow for the continuous‐flow LVADs and time‐varying inflow for the pulsatile devices. Differences in flow patterns, wall shear stress (WSS), and dynamic pressure in the ascending aorta were compared for both cases. Retrograde flow patterns were observed in all cases proximal to the location of the outflow cannula anastomosis site. On average, dynamic pressures derived from the retrograde flow velocities were higher in the continuous‐flow group with large variations dependent on the angle of the cannula anastomosis relative to the ascending aorta (continuous group: 0.14 ± 0.2 mm Hg, pulsatile group: 0.013 ± 0.008 mm Hg). Elevated WSS contralaterally to the anastomosis site was observed in three of the six models with higher values for the continuous cases. Lower WSS and reduced pressure in the ascending aorta, both favorable hemodynamic conditions, were found in pulsatile versus continuous‐flow LVADs by means of CFD. These findings indicate, along with clinical observations reported by others, the superior performance of pulsatile LVADs.     

Dialysis in Rats with Acute Renal Failure: Evaluation of Three Different Dialyzer Membranes

Abstract: Exposure to complement-activating cellulosic dialysis membranes has been claimed to adversely affect the course of acute renal failure (ARF). To test this hypothesis, male Sprague-Dawley rats were allocated to 2 groups: in Group t, ARF was induced by bilateral renal artery clamping whereas in Group 2, animals underwent a sham procedure. In each group, rats were further allocated to undergo hemodialysis with either a Cu-prophan, a Hemophan, or a polyacrylonitrile minidialyzer on Days 4 and 8 after surgery, or no dialysis. Renal function was measured by inulin clearance on the days after dialysis. Additionally, total complement activity (CH₅₀) was estimated on Days 1, 2, 4, and 8, and complement factor C3 was detected immunohistochemically. The degree of renal failure and the rate of recovery of renal function were similar in all the ARF groups irrespective of whether they had undergone dialysis or not, or of the type of the dialysis membrane. Furthermore, there were no significant differences in the course of CH₅₀ or in the amount and distribution of complement factor C3 in the kidney tissue between the rats of Groups 1 and 2. Our findings refute the hypothesis that in ischemic ARF exposure to complement-activating cellulosic dialysis membranes impairs the recovery of renal function in rats.     

Salt and Fluid Intake in the Development of Hypertension in Peritoneal Dialysis Patients

Background. Although fluid overload contributes to hypertension in CAPD patients, less attention has been paid to the role of excess salt and fluid intake. Therefore, we investigated the role of salt and fluid intake in the development of hypertension in CAPD patients. Methods. A total of 165 stable CAPD patients were included into this study. Based on the blood pressure in three consecutive months, they were divided into three groups: persistent hypertensive (PH; n = 33), intercurrent hypertensive (IH; n = 58) and persistent normotensive (PN; n = 74). The IH group was further divided into two phases: normotensive and hypertensive. Fluid status was evaluated by clinical assessment and bioimpedance analysis (BIA). Results. There were no differences in age, gender, and duration of dialysis among groups. Patients were more fluid overloaded in the PH group. Extracellular water (ECW), total body water (TBW), and normalized extracellular water by height (NECW) were higher in the PH group than the PN group (16.77 ± 3.62 L vs. 14.61 ± 2.92 L for ECW, p < 0.01; 32.22 ± 8.23 L vs. 28.98 ± 6.00 L for TBW, p < 0.05; and 10.28 ± 1.86 L/m vs. 9.08 ± 1.63L/m for NECW, p < 0.01). However, patients in the PH group also had more total fluid removal (TFR) and total sodium removal (TSR) compared with the PN group (1346.82 ± 431.27 mL/d vs. 1139.28 ± 412.65 mL/d for TFR, p < 0.05; and 141.52 ± 61.57 mmol/d vs. 102.42 ± 62.51 mmol/d for TSR, p < 0.01). The same trend was demonstrated when compared values of hypertensive and normotensive phase in IH group; patients had higher ECW, TBW, NECW, TSR, and PNa when they were in hypertensive phase than in the normotensive phase. Conclusions. This study confirmed that fluid overload was closely associated with the development of hypertension in CAPD patients. It also showed that hypertensive patients were in general more fluid overloaded despite a higher fluid and sodium removal as compared with normotensive patients.     

Development of Design Methods of a Centrifugal Blood Pump with In Vitro Tests, Flow Visualization, and Computational Fluid Dynamics: Results inHemolysis Tests

Abstract There are few established engineering guidelines aimed at reducing hemolysis for the design of centrifugal blood pumps. In this study, a fluid dynamic approach was applied to investigate hemolysis in centrifugal pumps. Three different strategies were integrated to examine the relationship between hemolysis and flow patterns. Hemolytic performances were evaluated in in vitro tests and compared with the flow patterns analyzed by flow visualization and computational fluid dynamic (CFD). Then our group tried to establish engineering guidelines to reduce hemolysis in the development of centrifugal blood pumps. The commercially available Nikkiso centrifugal blood pump (HPM-15) was used as a standard, and the dimensions of 2 types of gaps between the impeller and the casing, the axial and the radial gap, were varied. Four impellers with different vane outlet angles were also prepared and tested. Representative results of the hemolysis tests were as follows: The axial gaps of 0.5, 1.0, and 1.5 mm resulted in normalized index of hemolysis (NIH) values of 0.0028, 0.0013 and 0.0008 g/100 L, respectively. The radial gaps of 0.5 and 1.5 mm resulted in NIH values of 0.0012 and 0.0008 g/100 L, respectively. The backward type vane and the standard one resulted in NIH values of 0.0013 and 0.0002 g/100 L, respectively. These results revealed that small gaps led to more hemolysis and that the backward type vane caused more hemolysis. Therefore, the design parameters of centrifugal blood pumps could affect their hemolytic performances. In flow visualization tests, vortices around the impeller outer tip and tongue region were observed, and their patterns varied with the dimensions of the gaps. CFD analysis also predicted high shear stress consistent with the results of the hemolysis tests. Further investigation of the regional flow patterns is needed to discuss the cause of the hemolysis in centrifugal blood pumps.     

Computational Fluid Dynamic Analyses to Establish Design Process of Centrifugal Blood Pumps

Abstract To establish quantitative, efficient design theories for centrifugal blood pumps, computational fluid dynamics (CFD) analyses were compared to the results of flow visualization tests and hemolysis tests, mainly on the Nikkiso centrifugal blood pump. The results turned out to coincide in the velocity vector plots. CFD analysis revealed that the smaller the gap is, the greater the shear stress becomes. This tendency becomes even greater with a radial gap change. Hemolysis study also indicated that the smaller the gap is, the greater the hemolysis. CFD analysis in comparison with hemolysis tests could be a useful index for developing blood pumps in the future.     

Analysis of Flow Patterns in a Ventricular Assist Device: A Comparative Study of Particle Image Velocimetry and Computational Fluid Dynamics

Abstract:  In order to develop a diaphragm-type ventricular assist device (VAD), we studied the flow field change following structural modifications. We devised a center flow-type pump by putting a small projection on the center of the housing and/or diaphragm to provide a center in the flow field, and examined the following four types of VADs: N type without a projection, D type with a projection on the diaphragm, H type with a projection on the housing, and DH type with projections on both the diaphragm and housing. Computational fluid dynamics (CFD) was used for flow simulation. Particle image velocimetry (PIV) was also used to verify the reliability of the CFD method and to determine how the flow field changes in the presence of a projection. The results of the PIV and CFD analyses were comparable. The placement of a projection on the housing was most effective in rectifying the flow field.     

Computational Modeling of Neonatal Cardiopulmonary Bypass Hemodynamics With Full Circle of Willis Anatomy

Cardiopulmonary bypass (CPB) procedure is employed to repair most congenital heart defects (CHD). Cannulation is a critical component of this procedure where the location and diameter of cannula controls the hemodynamic performance. State‐of‐the‐art computational studies of neonatal CPB employed an isolated aortic arch region by truncating the three‐dimensional (3D) patient‐specific cerebral system. The present work expanded these studies where the 3D patient‐specific MRI reconstruction of the cerebral system, including the Circle of Willis (CoW), is integrated with a hypoplastic neonatal aortic arch. The inlet of the arterial cannula is assigned a steady velocity boundary condition of the CPB pump, while all outlets are modeled as resistance boundary conditions, thus allowing acute comparisons between different cannula configurations. Three‐dimensional (3D) flow simulations in the aortic arch model are performed at a Reynolds number of 2150 using an experimentally validated commercial solver. Results demonstrate that the inclusion of 3D CoW is essential to predict the accurate head‐neck blood perfusion and therefore critical in deciding the neonatal aortic cannulation strategy preoperatively. Using this integrated model two CPB configurations are studied, where the cannulas were placed at innominate artery (IA) (IA‐cannula configuration) and ductus arteriosus (DA) (DA‐cannula configuration). Configuration change produced significant differences in flow splits and local hemodynamics of blood flow throughout the whole aortic arch, neck and cerebral arteries. Percent flow rate differences between the IA‐ and DA‐cannula configurations are computed to be: 19%, for descending aorta, 198% for ascending aorta (perfusing coronary arteries), 91% for right anterior cerebral artery, and 68% for left anterior cerebral artery. Another important finding is the retrograde flow at vertebral arteries for IA‐cannula configuration, but not for DA‐cannula. These results may help to translate better neonatal arterial cannulae design for minimizing cerebral complications during CPB procedures.     

Dialysis Complications in Acute Kidney Injury Patients Treated With Prolonged Intermittent Renal Replacement Therapy Sessions Lasting 10 Versus 6 Hours: Results of a Randomized Clinical Trial

Prolonged intermittent renal replacement therapy (PIRRT) has emerged as an alternative to continuous renal replacement therapy in the management of acute kidney injury (AKI) patients. This trial aimed to compare the dialysis complications occurring during different durations of PIRRT sessions in critically ill AKI patients. We included patients older than 18 years with AKI associated with sepsis admitted to the intensive care unit and using noradrenaline doses ranging from 0.3 to 0.7 µg/kg/min. Patients were divided into two groups randomly: in G1, 6‐h sessions were performed, and in G2, 10‐h sessions were performed. Seventy‐five patients were treated with 195 PIRRT sessions for 18 consecutive months. The prevalence of hypotension, filter clotting, hypokalemia, and hypophosphatemia was 82.6, 25.3, 20, and 10.6%, respectively. G1 was composed of 38 patients treated with 100 sessions, whereas G2 consisted of 37 patients treated with 95 sessions. G1 and G2 were similar in male predominance (65.7 vs. 75.6%, P = 0.34), age (63.6 ± 14 vs. 59.9 ± 15.5 years, P = 0.28) and Sequential Organ Failure Assessment score (SOFA; 13.1 ± 2.4 vs. 14.2 ± 3.0, P = 0.2). There was no significant difference between the two groups in hypotension (81.5 vs. 83.7%, P = 0.8), filter clotting (23.6 vs. 27%, P = 0.73), hypokalemia (13.1 vs. 8.1%, P = 0.71), and hypophosphatemia (18.4 vs. 21.6%, P = 0.72). However, the group treated with sessions of 10 h were refractory to clinical measures for hypotension, and dialysis sessions were interrupted more often (9.5 vs. 30.1%, P = 0.03). Metabolic control and fluid balance were similar between G1 and G2 (blood urea nitrogen [BUN]: 81 ± 30 vs. 73 ± 33 mg/dL, P = 1.0; delivered Kt/V: 1.09 ± 0.24 vs. 1.26 ± 0.26, P = 0.09; actual ultrafiltration: 1731 ± 818 vs. 2332 ± 947 mL, P = 0.13) and fluid balance (–731 ± 125 vs. ?652 ± 141 mL, respectively) . In conclusion, intradialysis hypotension was common in AKI patients treated with PIRRT. There was no difference in the prevalence of dialysis complications in patients undergoing different durations of PIRRT.     

Computational fluid dynamics-analysis of the Niagara hemodialysis catheter in a right heart model

Central venous catheters are widely used as a hemoaccess method for dialysis therapy. In this study, the performance parameters (velocities, pressure drop, shear rates, access recirculation) of the Niagara catheter are analyzed using computational fluid dynamics. Side holes are left open, closed, or reduced in size to assess the influence of this design feature. Initially the catheter is inserted in a tube which represents the vena cava. In the "arterial" luminal tip, wall shear rates over 20,000 s(-1) are common and peaks attain 55,000 s(-1) at a 300 mL/min blood flow rate. The presence of side holes appears to affect the location but not the level of these elevated shear rates. Halving their diameter causes elevated shear rates to appear in a more extended region with peaks up to 80,000 s(-1). Simulated recirculation percentage is nil in normal catheter use, but attains 30% with reversed catheter connections. The results of the tube model are compared to those of an anatomically realistic right atrium model, which was three-dimensionally reconstructed. It is concluded that most catheter's specific hemodynamic properties can be deduced from the tube model.     

Fluid Mechanics of the Stagnation Point Flow Chamber and Its Platelet Deposition

Abstract: The interaction of flow and thrombus generation often is a crucial question for the engineer working in the field of artificial organs. However, this interaction is only incompletely known, and quantitative data under well-defined experimental conditions are especially rare. These can be attained with the stagnation point flow chamber. This flow model applies platelet-rich plasma (PRP) as fluid. Its flow conditions are assessed with the help of computational fluid mechanics. In addition, the concept of the boundary layer is introduced, which permits assessment of the platelet flow along the wall. The results of the experiment indicate that platelets are deposited at a defined shear rate.     

A Fluid Dynamic Analysis Using Flow Visualization of the Baylor/NASA Implantable Axial Flow Blood Pump for Design Improvement

Abstract: The Baylor/NASA Axial Blood Flow Pump has been developed for use as an implantable left ventricular assist device (LVAD). The pump is intended as an assist device for either pulmonary or systemic circulatory support for more than 3-months' duration. To date the pump provides acceptable results in terms of thrombus formation and hemolysis (IH of 0.018 g/100 L). A fluid dynamics analysis using flow visualization was performed to investigate the flow fields and to determine areas within the pump that could be improved. These studies focused upon the inflow area in front of the pump. A prototype axial flow pump assembly was constructed to facilitate the flow visualization studies. Particle image tracking velocimetry techniques were used to measure Amberlite particles suspended in a blood analog fluid composed of 63% water and 37% glycerin. This method used a pulsed (612 Hz) laser light to determine flow velocity profiles, shear stress, Reynolds numbers, and stagnant areas within the axial pump. These studies showed that the flow straightener (a vaned assembly in the pump inflow) reduced Reynolds numbers from 4,640 to 2,540 (at 8.5 L/min) and that the flow straightener exacerbates a discontinuity found between it and the impeller. Within the inflow area, a maximum of 80 N/m² shear stress was measured, which is well below published blood damage thresholds. Design variations were investigated resulting in a smoother flow transition between flow straightener and impeller. These variations must be investigated further to establish a correlation with hemolysis and thrombus formation.