Extracorporeal Blood Circuit Research Articles

Extracorporeal CO2 Removal by Respiratory Electrodialysis: An In Vitro Study.

We previously described a highly efficient extracorporeal CO2 removal technique called respiratory electrodialysis (R-ED). Respiratory electrodialysis was composed of a hemodiafilter and a membrane lung (ML) positioned along the extracorporeal blood circuit, and an electrodialysis (ED) cell positioned on the hemodiafiltrate. The ED regionally increased blood chloride concentration to convert bicarbonate to CO2 upstream the ML, thus enhancing ML CO2 extraction (VCO2ML). In this in vitro study, with an aqueous polyelectrolytic carbonated solution mimicking blood, we tested a new R-ED setup, featuring an ML positioned on the hemodiafiltrate after the ED, at increasing ED current levels (0, 2, 4, 6, and 8 A). We measured VCO2ML, electrolytes concentrations, and pH of the extracorporeal circuit. Raising levels of ED-current increased chloride concentration from 107.5 ± 1.6 to 114.6 ± 1.3 mEq/L (0 vs. 8 A, p < 0.001) and reduced pH from 7.48 ± 0.01 to 6.51 ± 0.05 (0 vs. 8 A, p < 0.001) of the hemodiafiltrate entering the ML. Subsequently, VCO2ML increased from 27 ± 1.7 to 91.3 ± 1.5 ml/min (0 vs. 8 A, p < 0.001). Respiratory electrodialysis is efficient in increasing VCO2ML of an extracorporeal circuit featuring an ML perfused by hemodiafiltrate. During R-ED, the VCO2ML can be significantly enhanced by increasing the ED current.

Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study.

A prospective, observational, feasibility study was carried out on four patients with end-stage renal failure undergoing bicarbonate hemodialysis to study the feasibility of an on-line hemodiafiltration technique using a citrate dialysate with pre-dilutional infusion of citrate as a technique for regional citrate anticoagulation. All patients had contraindication to systemic heparin anticoagulation. The dialysis technique consisted of an on-line hemodiafiltration with a citrate dialysate without calcium using a Fresenius 4008S dialysis machine and Fresenius Polysulfone F60 dialyzers. The infusion solution was procured directly from the dialysate and was infused into the arterial line. To avoid the risk of hypocalcemia, calcium gluconate was infused to the venous return line. The study was carried out in two stages. During the first stage, the citrate infusion rate was 80 mL/min and the calcium infusion rate was 9 mmol/h. At the second stage, the rates were 100 mL/min and 11 mmol/h, respectively. The primary endpoint of this study was the incidence of thrombosis in the extracorporeal blood circuit and/or the dialyzer. A total of 78 sessions were conducted. All the sessions were well tolerated clinically and there were no major incidents in any of the four patients. At the first stage of the study, there were five incidences of small clots in the venous blood chamber, an incidence of extracorporeal blood circuit thrombosis of 12.5%. At the second stage of the study, no cases of extracorporeal blood circuit or dialyzer thrombosis were noted. Hemodiafiltration with on-line citrate dialysate infusion to the arterial line is safe and allows an effective regional anticoagulation of the extracorporeal blood circuit without the need for systemic anticoagulation.

Optical sensing device for online calcium detection in extracorporeal blood purification

A calcium-sensitive fluorescence sensor based on a fluorescent dye immobilized in a hydrogel that is placed onto the inner wall of a transparent measuring cell was developed. The ionized calcium (iCa)-sensitive fluorophore Oregon-Green bapta-1 dextran (OG-dextran) reacts with calcium ions, resulting in an increase in the fluorescence intensity that is proportional to the concentration of iCa. To measure the optical signal of the iCa-sensitive fluorescence sensor, an appropriate and very sensitive optical measuring device was developed. The aim of this sensor is to measure the iCa concentration during extracorporeal citrate–calcium anticoagulation in the extracorporeal blood circuit. Thus, the newly developed calcium sensor can offer an enhancement for the accurate online measurement of iCa during treatment and the adjustment of iCa afterwards.

Fault Tolerant Air Bubble Sensor using Triple Modular Redundancy Method

Detection of air bubbles in the blood is important for various medical treatments that use Extracorporeal Blood Circuits (ECBC), such as hemodialysis, hemofiltration and cardio-pulmonary bypass. Therefore a reliable air bubble detector is needed. This study presents the design of a new fault tolerant air bubble detector. Triple Modular Redundancy (TMR) method is used on the sensor section. A voter circuit of the Triple Modular Redundancy will choose one of three sensor outputs to be processed further. Application of Triple Modular Redundancy will prevent errors in the detection of air bubbles, especially if the sensor fails to work.

The Hemobag: the modern ultrafiltration system for patients undergoing cardiopulmonary by pass

BackgroundThe return of extracorporeal circuit blood at the termination of cardiopulmonary bypass (CPB) is an important feature of blood conservation during cardiac surgery procedures globally. We report our initial clinical evaluation of the Hemobag system a blood-salvaging device designed for whole blood recovery of residual post-CPB volume.MethodsResidual whole blood is hemoconcetrated through the multipass “recovery loop” circuit separate from the CPB and collected in the Hemobag System. This allows the surgeons to continue with surgery, decannulate, and administer protamine simultaneously while the Hemobag is in use and the CPB circuit remains safely primed. We have compared 25 patients receiving the Hemobag to a control group of 25 patients treated with the cell washer that represented our previous standard of care method of circuit blood-salvaging technique.ResultsThe Hemobag system provided significantly higher hemoglobin, hematocrit, fibrinogen, albumin, and total protein levels in the final product reducing the amount of wasted autologous blood cells. There were no device-related complications. There were no significant differences in terms of blood utilization, chest tube drainage and clinical outcomes over the entire postoperative period among groups.ConclusionsThese results suggest that the Hemobag system is a safe and efficient method to multipass hemoconcentrate the residual diluted blood of the CPB circuit. The Hemobag has demonstrated its ability to maximize the composition of the residual CPB volume to achieve the best possible post-CPB hemoglobin, plasma protein and coagulation factors profile for the patient respect to CW.

Exsanguination of a home hemodialysis patient as a result of misconnected blood-lines during the wash back procedure: A case report

BackgroundHome hemodialysis is common in New Zealand and associated with lower cost, improved survival and better patient experience. We present the case of a fully trained home hemodialysis patient who exsanguinated at home as a result of an incorrect wash back procedure.Case presentationThe case involves a 67 year old male with a history of well controlled hypertension and impaired glucose tolerance. He commenced on peritoneal dialysis in 2006 following the development of end stage kidney failure secondary to focal segmental glomerulosclerosis. He transferred to hemodialysis due to peritoneal membrane failure in 2010, and successfully trained for home hemodialysis over a 20 week period. Following one month of uncomplicated dialysis at home, he was found deceased on his machine at home in the midst of dialysis. His death occurred during the wash back procedure performed using the “open circuit” method, and resulted from misconnection of the saline bag to the venous end of the extracorporeal blood circuit instead of the arterial end. This led to approximately 2.3L of his blood being pumped into the saline bag resulting in hypovolaemic shock and death from exsanguination.ConclusionsDespite successful training, critical procedural errors can still be made by patients on home hemodialysis. In this case, the error involved misconnection of the saline bag for wash back. This case should prompt providers of home hemodialysis to review their training protocols and manuals. Manufacturers of dialysis machinery should be encouraged to design machines specifically for home hemodialysis, and consider distinguishing the arterial and venous ends of the extracorporeal blood circuit with colour coding or incompatible connectivity, to prevent occurrences such as these in the future.

A selective cytopheretic inhibitory device for use during cardiopulmonary bypass surgery

Systemic inflammatory response syndrome (SIRS) can occur in association with cardiopulmonary bypass (CPB) surgery, resulting in multiple organ dysfunction (MOD). Activated neutrophils have been implicated as major inciting factors in this process. Neutrophil-depleting filters incorporated within the extracorporeal blood circuit during CPB have been developed and evaluated, with inconsistent clinical results. A novel, biomimetic, selective cytopheretic device (SCD) was tested in vitro within a blood circuit to assess safety and interactions with blood components and further evaluated ex vivo in a bovine model of CPB surgery during ventricular assist device implantation. In vitro blood circuit studies demonstrated that the SCD reduces circulating neutrophils while maintaining low rates of hemolysis compared to current leukocyte-reduction filters. In the bovine CPB model, animals without SCD treatment (No SCD) demonstrated an increase in circulating white blood cell (WBC) and neutrophil counts, steadily increasing throughout CPB. SCD with only systemic heparin anticoagulation (SCD-H) acutely reduced neutrophils for the first 2 hrs of CPB, but followed with a greater than 6-fold increase in neutrophil counts. SCD treatment with regional citrate anticoagulation along the SCD circuit (SCD-C) reduced systemic neutrophil counts throughout 4 hrs of CPB despite lower amounts of eluted cells from the SCD. When analyzed for immature neutrophils, the control and SCD-H showed increasing counts at later time-points, not seen in the SCD-C group, suggesting a more complex mechanism of action than simple leukoreduction. These results suggest that SCD-C therapy may disrupt the systemic leukocyte response during CPB, leading to improved outcomes for CPB-mediated MOD.

A Biomimetic Membrane Device That Modulates the Excessive Inflammatory Response to Sepsis

ObjectiveSeptic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD), was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis.DesignLaboratory investigation.SettingUniversity of Michigan Medical School.SubjectsPigs weighing 30-35 kg.InterventionsTo assess the effect of the SCD in septic shock, pigs were administered 30×1010 bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD.Measurements and Main ResultsIn this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation.ConclusionsThese preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway.

Computational Fluid Dynamics of Blood Flow in an Extracorporeal Blood Circuit for the Analysis of Thrombogenic Hemodynamic Factors

Blood flow in a filter for an extracorporeal blood circuit was analyzed numerically to assess fluid mechanical quantities related to thrombogenesis. Results showed stagnant flow regions, in particular at the downstream side of the ceiling of a filter. A particle tracking along with an evaluation of a shear stress exerted on a particle demonstrated that a particle experiences a large shear stress when passing through a pore of the filter. These results suggest that a platelet would be activated when it goes though the pore and could then aggregate with other activated platelets to develop into a thrombus beneath the ceiling of a filter. Based on this hypothesis, the filter design was modified by making a protrusion on the downstream side of the filter. The protrusion design was varied in two ways in shape (sharp, blunt) and three ways in height (1/4, 1/3, 1/2 of the height of the original filter). The simulation results showed a positive contribution of the protrusion to a decrease in the stagnant flow region on the downstream side of the filter ceiling. A comparison of the stagnant volume for models between a model with blunt protrusion and the one with sharp protrusion revealed that the blunt protrusion decreased the stagnant region more than that for models with a shape one. The protrusion also contributed to decreasing the shear stress at pores of the filter. This effect was more pronounced with an increase in the height of the protrusion. These results address benefits of the protrusion in the anti-thrombogenic design of a filter for an extracorporeal blood circuit.

An In-Vitro Comparison between Hemobag® and Non-Hemobag® Ultrafiltration Methods of Salvaging Circuit Blood Following Cardiopulmonary Bypass

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 invitro 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.

Regional citrate anticoagulation is safe in intermittent high-flux haemodialysis treatment of children and adolescents with an increased risk of bleeding

Regional citrate anticoagulation (RCA) is strongly recommended for adults with an increased risk of bleeding complications. The objective of this retrospective analysis was to evaluate an RCA protocol concerning feasibility and safety in intermittent high-flux haemodialysis (iHD) treatment in children and adolescents. Eighteen children and adolescents aged 5-17 years (median 15 years) underwent 74 iHD treatment sessions with RCA. Twelve of 18 patients presented with overt local or diffuse haemorrhage before beginning the HD sessions, and six had an increased risk of haemorrhagic complications. Forty children on acute haemodialysis with general heparin anticoagulation, matched for bleeding risk, age and body surface area, served as a control group. Citrate 3% solution was begun with 3.3% blood flow rate, and calcium gluconate 10% substitution was started with 0.4% of blood flow rate. Citrate flow was adapted to achieve a post-filter ionized calcium of ≤0.30 mmol/L; calcium substitution was adapted to maintain the patients' serum calcium levels within the physiological range. Calcium-free dialysis fluid was used. The blood flow rate ranged from 3 to 5 mL per minute and kilogram body weight. Regional anticoagulation was successfully achieved within the extracorporeal blood circuit, while the coagulation of all 18 patients remained within physiological parameters. No adverse effects of RCA were observed. In all 18 children, neither new haemorrhage nor worsening of the bleeding situation occurred, and in 10/12 patients, bleeding stopped during dialysis with RCA. In contrast, one-third of the control group developed new haemorrhagic complications or presented with worsening of pre-existing bleeding during haemodialysis (P = 0.006). RCA is feasible, safe and effective in paediatric intermittent haemodialysis treatment.

Investigation of Prothrombin Time in Human Whole-Blood Samples with a Quartz Crystal Biosensor

Monitoring of blood coagulation and fibrinolysis is an important issue in treatment of patients with cardiovascular problems and in surgery when blood gets into contact with artificial surfaces. In this work a new method for measuring the coagulation time (prothrombin time, PT) of human whole-blood samples based on a quartz crystal microbalance (QCM) biosensor is presented. The 10 MHz sensors used in this work respond with a frequency shift to changes in viscosity during blood clot formation. For driving and for readout of the quartz, both a network analyzer and an oscillator circuit were utilized. The sensor surfaces were specifically coated with a thin polyethylene layer. We found that both frequency analysis methods are suitable to measure exact prothrombin times in a very good conformity with a mechanical coagulometer as a reference. The anticoagulant effect of heparin on the prothrombin time was exemplarily shown as well as the reverse effect of the heparin antagonist polybrene. The change of the viscoelastic properties during blood coagulation, reflected by the ratio of frequency and dissipation shifts, is discussed for different dilutions of the whole-blood samples. In conclusion, QCM is a distinguished biosensor technique to determine prothrombin time and to monitor heparin therapy in whole-blood samples. Due to the excellent potential of miniaturization and the availability of direct digital signals, the method is predestinated for incorporation and integration into other devices and is thus opening the field of application for inline coagulation diagnostic in extracorporeal blood circuits.

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

Stand der Technik bei der Nieren- und Leberersatztherapie / Kidney and liver support therapies: state-of-the-art methods

Today, worldwide approximately 1.5 million uremic patients owe their lives to hemodialysis. This figure will increase further by a growth rate of 6% annually reflecting a necessary increasing high interest in innovative technologies as well as in individualized therapies in this area. The main focus of developmental efforts, today and in the future, is to adapt the therapy to the specific physiological conditions of kidney patients, e.g., by means of a precise control of body water and its removal. This can be precisely monitored by bioimpedance analyses. Liver patients also benefit from the experiences with extracorporeal blood circuits. In contrast to hemodialysis, protein-permeable membranes are applied which allow for the removal of albumin-bound toxins. Albumin is then cleansed in the secondary circuit by adsorber cartridges and then readministered to the patient leading to improved recovery. This short review summarizes the state-of-the-art of blood purification methods in hemodialysis and liver support therapies.

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.

Regional cooling of the extracorporeal blood circuit: a novel anticoagulation approach for renal replacement therapy?

To test the hypothesis that cooling of blood in the extracorporeal circuit of continuous veno-venous hemofiltration (CVVH) enables to realize the procedure without the need of anticoagulation. Experimental animal study. We developed the device for selective cooling of extracorporeal circuit (20 degrees C) allowing blood rewarming (38 degrees C) just before returning into the body. Twelve anesthetized and ventilated pigs were randomized to receive either 6 h of CVVH with application of this device (COOL; n = 6) or without it (CONTR; n = 6). Before the procedure and in 15, 60, 180, 360 min after starting hemofiltration variables related to: (1) circuit patency [time to clotting (TC), number of alarm-triggered pump stopping (AS), venous and transmembranous circuit pressures (VP, TMP)], (2) coagulation status in the extracorporeal circuit [thrombin-antithrombin complexes (TAT(circ)), thromboelastography (TEG)] and (3) animal status (hemodynamics, hemolysis and biochemistry) were assessed. The patency of all circuits treated with selective cooling was well maintained within the observation period. By contrast, five of six sessions were prematurely clotted in the untreated group. As a result, the number of AS was significantly higher in the CONTR group. In-circuit thrombus generation in CONTR group was associated with a markedly increasing TAT(circ). TEG performed at 180 min of the procedure revealed a tendency to a prolonged initial clotting time and a significant decrease in clotting rate of in-circuit blood in the COOL group. No signs of repeated cooling/rewarming-induced hemolysis were observed in animals treated with "hypothermic circuit" CVVH. In this porcine model, regional extracorporeal blood cooling proved effective in preventing in-circuit clotting without the need to use any other anticoagulant.

This Month in Gastroenterology

This Month in Gastroenterology

Treatment of Metabolic Alkalosis during Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

The use of citrate as an anticoagulant in continuous renal replacement therapy is an effective method to achieve regional anticoagulation of the extracorporeal blood circuit and to avoid systemic anticoagulation. This allows bleeding complications to be reduced and filter life time to be prolonged. However, citrate enters the systemic circulation and is metabolized in the liver to bicarbonate, causing metabolic alkalosis in some patients. In this case report, we discuss therapeutic interventions to control the acid-base status and to restore normal pH during continuous citrate hemodialysis.

On-Line Autotransfusion Waste Calculator

Cell concentrating and washing techniques are widely accepted and believed to be beneficial to cardiac surgery patients. During cell processing, platelets, proteins, and clotting factors are wasted as the plasma is washed away by saline. Beneficial and costly plasma constituents are sacrificed for the sake of removing potentially harmful drugs, debris, and naturally activated cells and chemical mediators. An interactive Microsoft Excel spreadsheet was designed to input patient and autotransfusion system (ATS) reservoir blood values, processed centrifugal bowl data, and hospital allogeneic blood product concentration and cost information. The spreadsheet calculates the number of wasted platelets, grams of protein, and milligrams of fibrinogen. The calculator further estimates the number of units and cost of allogeneic blood products needed to replace the wasted blood components. The simulation allows for variable levels of platelet activation and protein removal during centrifugal cell processing. Specific case scenarios may be simulated with the calculator. If a known volume of residual extracorporeal circuit blood with a known hematocrit, platelet count, and protein concentration is diverted to the ATS reservoir to be processed and washed after bypass, the number of units of fresh frozen plasma, platelet packs, and albumin concentrate needed to replace the wasted proteins and platelets may be calculated. When typical end-bypass patient and blood bank product values are input, the cost to replace the wasted blood components in 1550 mL of residual circuit blood with allogeneic blood products is about US $2097. There are risks and costs associated with replacing the platelets, proteins, and clotting factors wasted during cell washing compared with other techniques such as whole blood ultrafiltration.

Gaseous Microemboli Sizing in Extracorporeal Circuits Using Ultrasound Backscatter

This paper describes efforts to estimate the size of gaseous microemboli (GME) in extracorporeal blood circuits based on the amplitude of backscattered ultrasound, starting with analytic modeling of the scattering behavior of GME in blood. After neglecting resonance effects, this model predicts a linear relationship between the amplitude of backscattered echoes and the diameter of GME. Computer simulations based on the cylindrical acoustic finite integration technique were performed to test some of the simplifying assumptions of the analytical model, with the simulations predicting small deviations from the linear approximation that could be treated as random scatter. Ultrasonic and microscopic measurements of injected GME were then performed on a test circuit to determine the linear correlation coefficient between echo amplitude and GME diameter in conditions like those employed in real cardiopulmonary bypass (CPB) circuits. The correlation coefficient determined through this study was further validated in a closed-loop CPB circuit using canine blood. This study shows that the amplitude of ultrasonic backscattered echoes can be used to accurately estimate the size distribution of a population of detected GME when the spacing of emboli is great enough to minimize interference and other multi-path scattering effects. With the high flow rates found in CPB circuits, typically ranging from 2 to 6 L per minute (equivalent to a flow velocity of 0.3 to 1 m/s through the circuit tubing), this assumption will be valid even when hundreds of emboli per second pass through the circuit. Therefore, sizing of GME using the ultrasonic backscatter models described in this paper is a viable method for estimating embolic load delivered to a patient during a CPB procedure. (E-mail: lyncht@lunainnovations.com)