Numerical and experimental investigation of a lighthouse tip drainage cannula used in extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation is a life-saving therapy used in case of acute respiratory/circulatory failure. Exposure of blood to non-physiological surfaces and high shear stresses is related to hemolytic damage and platelet activation. A detailed knowledge of the fluid dynamics of the components under different scenarios is thus paramount to assess the thrombogenicity of the circuit. METHODS: An investigation of the flow structures developing in a conventional lighthouse tip (single-staged) drainage cannula was performed with cross-validated computational fluid dynamics and particle image velocimetry. The aim was to quantify the variation in drainage performance and stress levels induced by different fluid models, hematocrit and vessel-to-cannula flow rate ratios. RESULTS: The results showed that the 90° bends of the flow through the side holes created a recirculation zone inside the cannula which increased residence time. Flow structures resembling a jet in a crossflow were also observed. The use of different hematocrits did not significantly affect drainage performances. The most proximal set of holes drained the largest fraction of fluid. However, different flow rate ratios altered the flow rate drained through the tip. The use of 2D data led to a 50% underestimation of shear rate levels. In the drainage zone the non-Newtonian behavior of blood was less relevant. CONCLUSIONS: The most proximal holes drained the largest amount of fluid. The flow features and distribution of flow rates among the holes showed little dependence on the hematocrit. The non-Newtonian behavior of blood had a small influence on the dynamics of the flow.

Roughness-dependent clogging of particle suspensions flowing into a constriction.

When concentrated particle suspensions flow into a constricting channel, the suspended particles may either smoothly flow through the constriction or jam and clog the channel. These clogging events are typically detrimental to technological processes, such as in the printing of dense pastes or in filtration, but can also be exploited in micro-separation applications. Many studies have to date focused on important parameters influencing the occurrence of clogs, such as flow velocity, particle concentration, and channel geometry. However, the investigation of the role played by the particle surface properties has surprisingly received little attention so far. Here, we study the effect of surface roughness on the clogging of suspensions of silica particles under pressure-driven flows along a microchannel presenting a constriction. We synthesize micron-sized particles with uniform surface chemistry and tunable roughness and determine the occurrence of clogging events as a function of velocity and volume fraction for a given surface topography. Our results show that there is a clear correlation between surface roughness and flow rate, indicating that rougher particles are more likely to jam at the constriction for slower flows. These findings identify surface roughness as an essential parameter to consider in the formulation of particulate suspensions for applications where clogging plays an important role.

Flows and function of the Infant Flow neonatal continuous positive airway pressure device investigated with computational fluid dynamics.

AIM: The first dedicated neonatal continuous positive airway pressure (CPAP) device using variable flow was the Infant Flow. The system was pressure stable with a low resistance to breathing. The aim of this study was to describe the flow and function of the Infant Flow geometry using simulated breathing and computational fluid dynamics. METHOD: The original Infant Flow geometry was used with simulated term infant breathing at three levels of CPAP. The large eddy simulation methodology was applied in combination with the WALE sub-grid scale model. RESULTS: The simulation fully resolved the flow phenomena in the Infant Flow geometry. The main flow feature during inspiration was support by gas entrainment and mixing. During expiration, the jet deflected towards the outlet with unstable impingement of the jet at the opposing edge. CONCLUSION: The proposed mechanism has previously been based on theoretical reasoning, and our results present the first detailed description of the Infant Flow. The pressure stability was based on a jet supporting inspiration by gas entrainment and then being deflected during exhalation. This confirmed previously assumed principles of function and flows within the geometry and provided a base for further developments.

Pressure and flow properties of dual-lumen cannulae for extracorporeal membrane oxygenation.

INTRODUCTION: In the last decade, dual-lumen cannulae have been increasingly applied in patients undergoing extracorporeal life support. Well-performing vascular access is crucial for efficient extracorporeal membrane oxygenation support; thus, guidance for proper cannulae size is required. Pressure-flow charts provided by manufacturers are often based on tests performed using water, rarely blood. However, blood is a shear-thinning and viscoelastic fluid characterized by different flow properties than water. METHODS: We performed a study evaluating pressure-flow curves during standardized conditions using human whole blood in two commonly available dual-lumen cannulae used in neonates, pediatric, and adult patients. Results were merged and compared with the manufacturer's corresponding curves obtained from the public domain. RESULTS: The results showed that using blood as compared with water predominantly influenced drainage flow. A 10-80% higher pressure-drop was needed to obtain same drainage flow (hematocrit of 26%) compared with manufacturer's water charts in 13-31 Fr bi-caval dual-lumen cannulae. The same net difference was found in cavo-atrial cannulae (16-32 Fr), where a lower drainage pressure was required (Hct of 26%) compared with the manufacturer's test using blood with an Hct of 33%. Return pressure-flow data were similar, independent whether pumping blood or water, to the data reported by manufacturers. CONCLUSION: Non-standardized testing of pressure-flow properties of extracorporeal membrane oxygenation dual-lumen cannulae prevents an adequate prediction of pressure-flow results when these cannulae are used in patients. Properties of dual-lumen cannulae may vary between sizes within same cannula family, in particular concerning the drainage flow.

Pressure and flow properties of cannulae for extracorporeal membrane oxygenation II: drainage (venous) cannulae.

The use of extracorporeal life support devices such as extracorporeal membrane oxygenation in adults requires cannulation of the patient's vessels with comparatively large diameter cannulae to allow circulation of large volumes of blood (>5 L/min). The cannula diameter and length are the major determinants for extracorporeal membrane oxygenation flow. Manufacturing companies present pressure-flow charts for the cannulae; however, these tests are performed with water. Aims of this study were 1. to investigate the specified pressure-flow charts obtained when using human blood as the circulating medium and 2. to support extracorporeal membrane oxygenation providers with pressure-flow data for correct choice of the cannula to reach an optimal flow with optimal hydrodynamic performance. Eighteen extracorporeal membrane oxygenation drainage cannulae, donated by the manufacturers (n = 6), were studied in a centrifugal pump driven mock loop. Pressure-flow properties and cannula features were described. The results showed that when blood with a hematocrit of 27% was used, the drainage pressure was consistently higher for a given flow (range 10%-350%) than when water was used (data from each respective manufacturer's product information). It is concluded that the information provided by manufacturers in line with regulatory guidelines does not correspond to clinical performance and therefore may not provide the best guidance for clinicians.

Pressure and flow properties of cannulae for extracorporeal membrane oxygenation I: return (arterial) cannulae.

Adequate extracorporeal membrane oxygenation support in the adult requires cannulae permitting blood flows up to 6-8 L/minute. In accordance with Poiseuille's law, flow is proportional to the fourth power of cannula inner diameter and inversely proportional to its length. Poiseuille's law can be applied to obtain the pressure drop of an incompressible, Newtonian fluid (such as water) flowing in a cylindrical tube. However, as blood is a pseudoplastic non-Newtonian fluid, the validity of Poiseuille's law is questionable for prediction of cannula properties in clinical practice. Pressure-flow charts with non-Newtonian fluids, such as blood, are typically not provided by the manufacturers. A standardized laboratory test of return (arterial) cannulae for extracorporeal membrane oxygenation was performed. The aim was to determine pressure-flow data with human whole blood in addition to manufacturers' water tests to facilitate an appropriate choice of cannula for the desired flow range. In total, 14 cannulae from three manufacturers were tested. Data concerning design, characteristics, and performance were graphically presented for each tested cannula. Measured blood flows were in most cases 3-21% lower than those provided by manufacturers. This was most pronounced in the narrow cannulae (15-17 Fr) where the reduction ranged from 27% to 40% at low flows and 5-15% in the upper flow range. These differences were less apparent with increasing cannula diameter. There was a marked disparity between manufacturers. Based on the measured results, testing of cannulae including whole blood flows in a standardized bench test would be recommended.

Detection of Thrombosis in the Extracorporeal Membrane Oxygenation Circuit by Infrasound: Proof of Concept.

As of today, there exist no reliable, objective methods for early detection of thrombi in the extracorporeal membrane oxygenators (ECMO) system. Within the ECMO system, thrombi are not always fixed to a certain component or location in the circuit. Thus, clot fragments of different shapes and consistencies may circulate and give rise to vibrations and sound generation. By bedside sound measurements and additional laboratory experiments (although not detailed herein), we found that the presence of particles (clots or aggregates and fragments of clots) can be detected by analyzing the strength of infra-sound (< 20 Hz) modes of the spectrum near the inlet and outlet of the centrifugal pump in the ECMO circuit. For the few patients that were considered in this study, no clear false positive or negative examples were found when comparing the spectral approach with clinical observations. A laboratory setup provided insight to the flow in and out of the pump, confirming that in the presence of particles a low-amplitude low-frequency signal is strongly amplified, enabling the identification of a clot.

Estimation of the concentration boundary layer adjacent to a flat surface using computational fluid dynamics.

Dissolution-permeation (D/P) experiments are widely used during preclinical development due to producing results with better predictability than traditional monophasic experiments. However, it is difficult to compare absorption across in vitro setups given the propensity to only report apparent permeability. We therefore developed an approach to predict the concentration boundary layer for any D/P device by using computational fluid dynamics (CFD). The Navier-Stokes and continuity equation in 2D were solved numerically in MATLAB and by finite element methods in COMSOL v6.1 to predict the momentum [Formula: see text] and concentration ηg boundary layer for a flow over a flat plate, i.e. the classical Blasius boundary layer flow. A MATLAB algorithm was developed to calculate the edge of either boundary layer. The methodology to determine the concentration boundary layer based on Blasius's analysis provided an accurate estimate for both [Formula: see text] and ηg, resulting in, [Formula: see text] , at high Schmidt numbers (Sc âˆ¼ 1000) within 14 % of the Blasius solution and 6.6 % of the accepted Schmidt number correlation ( [Formula: see text] ). The methodology based on the Blasius analysis of the concentration boundary layer using velocity and concentration profiles computed using CFD presented herein will enable characterization/analysis of complex D/P apparatuses used in preclinical development, where an analytical solution may not be available.

In silico parametric analysis of femoro-jugular venovenous ECMO and return cannula dynamics: In silico analysis of femoro-jugular VV ECMO.

BACKGROUND: Increasingly, computational fluid dynamics (CFD) is helping explore the impact of variables like: cannula design/size/position/flow rate and patient physiology on venovenous (VV) extracorporeal membrane oxygenation (ECMO). Here we use a CFD model to determine what role cardiac output (CO) plays and to analyse return cannula dynamics. METHODS: Using a patient-averaged model of the right atrium and venae cava, we virtually inserted a 19Fr return cannula and a 25Fr drainage cannula. Running large eddy simulations, we assessed cardiac output at: 3.5-6.5 L/min and ECMO flow rate at: 2-6 L/min. We analysed recirculation fraction (Rf), time-averaged wall shear stress (TAWSS), pressure, velocity, and turbulent kinetic energy (TKE) and extracorporeal flow fraction (EFF = ECMO flow rate/CO). RESULTS: Increased ECMO flow rate and decreased CO (high EFF) led to increased Rf (R = 0.98, log fit). Negative pressures developed in the venae cavae at low CO and high ECMO flow (high CR). Mean return cannula TAWSS was >10 Pa for all ECMO flow rates, with majority of the flow exiting the tip (94.0-95.8 %). CONCLUSIONS: Our results underpin the strong impact of CO on VV ECMO. A simple metric like EFF, once supported by clinical data, might help predict Rf for a patient at a given ECMO flow rate. The return cannula imparts high shear stresses on the blood, largely a result of the internal diameter.

Assessment of Rheological Models Applied to Blood Flow in Human Thoracic Aorta.

PURPOSE: The purpose of this study is to assess the importance of non-Newtonian rheological models on blood flow in the human thoracic aorta. METHODS: The pulsatile flow in the aorta is simulated using the models of Casson, Quemada and Walburn-Schneck in addition to a case of fixed (Newtonian) viscosity. The impact of the four rheological models (using constant hematocrit) was assessed with respect to (i) magnitude and deviation of the viscosity relative to a reference value (the Newtonian case); (ii) wall shear stress (WSS) and its time derivative; (iii) common WSS-related indicators, OSI, TAWSS and RRT; (iv) relative volume and surface-based retrograde flow; and (v) the impact of rheological models on the transport of small particles in the thoracic aorta. RESULTS: The time-dependent flow in the thoracic aorta implies relatively large variations in the instantaneous WSS, due to variations in the instantaneous viscosity by as much as an order of magnitude. The largest effect was observed for low shear rates (tens s-1). The different viscosity models had a small impact in terms of time- and spaced-averaged quantities. The significance of the rheological models was clearly demonstrated in the instantaneous WSS, for the space-averaged WSS (about 10%) and the corresponding temporal derivative of WSS (up to 20%). The longer-term accumulated effect of the rheological model was observed for the transport of spherical particles of 2 mm and 2 mm in diameter (density of 1200 kg/m3). Large particles' total residence time in the brachiocephalic artery was 60% longer compared to the smaller particles. For the left common carotid artery, the opposite was observed: the smaller particles resided considerably longer than their larger counterparts. CONCLUSIONS: The dependence on the non-Newtonian properties of blood is mostly important at low shear regions (near walls, stagnation regions). Time- and space-averaging parameters of interest reduce the impact of the rheological model and may thereby lead to under-estimation of viscous effects. The rheological model affects the local WSS and its temporal derivative. In addition, the transport of small particles includes the accumulated effect of the blood rheological model as the several forces (e.g., drag, added mass and lift) acting on the particles are viscosity dependent. Mass transport is an essential factor for the development of pathologies in the arterial wall, implying that rheological models are important for assessing such risks.

Effect of flow rate ratio and positioning on a lighthouse tip ECMO return cannula.

Extracorporeal membrane oxygenation is a life-saving support therapy in the case of cardiopulmonary refractory failure. Its use is associated to complications due to the presence of artificial surfaces and supraphysiological stress conditions. Thus, knowledge of the fluid structures associated to each component can give insight into sources of blood damage. In this study, an experimentally validated numerical study of a conventional lighthouse tip cannula in return configuration was carried out to characterize the flow structures using water or a Newtonian blood analog with different flow rate ratios and cannula positioning and their influence on hemolysis. The results showed that strong shear layers developed where the jets from the side holes met the co-flow. Stationary backflow regions at the vessel wall were also present downstream of the cannula. In the tilted case, the recirculation was much more pronounced on the wide side and almost absent on the narrow side. Small vortical backflow structures developed at the side holes which behaved like obstacles to the co-flow, creating pairs of counter-rotating vortices, which induced locally higher risk of hemolysis. However, global hemolysis index did not show significant deviations. Across the examined flow rate ratios, the holes on the narrow side consistently reinfused a larger fraction of fluid. A radial force developed in the tilted case in a direction so as to recenter the cannula in the vessel.

Hemodynamic and recirculation performance of dual lumen cannulas for venovenous extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation (ECMO) can be performed with two single lumen cannulas (SLCs) or one dual-lumen cannula (DLC) where low recirculation fraction ([Formula: see text]) is a key performance criterion. DLCs are widely believed to have lower [Formula: see text], though these have not been directly compared. Similarly, correct positioning is considered critical although its impact is unclear. We aimed to compare two common bi-caval DLC designs and quantify [Formula: see text] in several positions. Two different commercially available DLCs were sectioned, measured, reconstructed, scaled to 27Fr and simulated in our previously published patient-averaged computational model of the right atrium (RA) and venae cavae at 2-6 L/min. One DLC was then used to simulate ± 30° and ± 60° rotation and ± 4 cm insertion depth. Both designs had low [Formula: see text] (< 7%) and similar SVC/IVC drainage fractions and pressure drops. Both cannula reinfusion ports created a high-velocity jet and high shear stresses in the cannula (> 413 Pa) and RA (> 52 Pa) even at low flow rates. Caval pressures were abnormally high (16.2-23.9 mmHg) at low flow rates. Rotation did not significantly impact [Formula: see text]. Short insertion depth increased [Formula: see text] (> 31%) for all flow rates whilst long insertion only increased [Formula: see text] at 6 L/min (24%). Our results show that DLCs have lower [Formula: see text] compared to SLCs at moderate-high flow rates (> 4 L/min), but high shear stresses. Obstruction from DLCs increases caval pressures at low flow rates, a potential reason for increased intracranial hemorrhages. Cannula rotation does not impact [Formula: see text] though correct insertion depth is critical.

Blood Pumps for Extracorporeal Membrane Oxygenation: Platelet Activation During Different Operating Conditions.

Extracorporeal membrane oxygenation (ECMO) is a therapy used in severe cardiopulmonary failure. Blood is pumped through an artificial circuit exposing it to nonphysiologic conditions, which promote platelet activation and coagulation. Centrifugal pumps used at lower flow rates than their design point may lose pump efficiency and increase the risk of hemolysis. In this study, thrombogenic properties of two ECMO pumps designed for adult and neonatal use were evaluated using simulations in different flow scenarios. Three scenarios, adult pump in adult mode (4 L/min), adult pump in baby mode (300 ml/min), and neonatal pump used in its design point (300 ml/min), were simulated using computational fluid dynamics. The flow was numerically seeded with platelets, whose activation state was computed considering the stress history that acted along their respective path lines. Statistical distributions of activation state and residence time were drawn. The results showed that using the adult pump in baby mode increased the fraction of platelets with higher activation state confirming that low-pump flow rate impacts thrombogenicity. The neonatal pump showed a backflow at the inlet, which carried platelets in a retrograde motion contributing to an increased thrombogenic potential compared with the adult mode scenario.

Impact of altered vena cava flow rates on right atrium flow characteristics.

The right atrium (RA) combines the superior vena cava (SVC) and inferior vena cava (IVC) flows. Treatments like extracorporeal membrane oxygenation (ECMO) and hemodialysis by catheter alter IVC/SVC flows. Here we assess how altered IVC/SVC flow contributions impact RA flow. Four healthy volunteers were imaged with computerized tomography (CT), reconstructed and combined into a patient-averaged model. Large eddy simulations (LESs) were performed for a range of IVC/SVC flow contributions (30%-70% each, increments of 5%) and common flow metrics were recorded. Model sensitivity to reconstruction domain extent, constant/pulsatile inlets, and hematocrit was also assessed. Consistent with literature, a single vortex occupied the central RA across all flowrates with a smaller counter-rotating vortex, not previously reported, in the auricle. Vena cava flow was highly helical. RA turbulent kinetic energy (TKE; P = 0.027) and time-averaged wall shear stress (WSS; P < 0.001) increased with SVC flow. WSS was lower in the auricle (2 Pa, P < 0.001). WSS in the vena cava was equal at IVC/SVC = 65/35%. The model was highly sensitive to the reconstruction domain with cropped geometries lacking helicity in the venae cavae, altering the RA flow. The RA flow was not significantly affected by constant inlets or hematocrit. The commonly reported vortex in in the central RA is confirmed; however, a new, smaller vortex was also recorded in the auricle. When IVC flow dominates, as is normal, TKE in the RA is reduced and WSS in the venae cavae equalize. Significant helicity exists in the vena cava, as a result of distal geometry and this geometry appears crucial to accurately simulating RA flow.NEW & NOTEWORTHY Right atrium turbulent kinetic energy increases as the proportion of flow entering from the superior vena cava is increased. Although the commonly reported large right atrium vortex was confirmed across all flow scenarios, a new smaller vortex is observed in the right auricle. The caval veins exhibit highly helical flow and this appears to be the result of distal venous morphology.

Cannulation configuration and recirculation in venovenous extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation is a treatment for acute respiratory distress syndrome. Femoro-atrial cannulation means blood is drained from the inferior vena cava and returned to the superior vena cava; the opposite is termed atrio-femoral. Clinical data comparing these two methods is scarce and conflicting. Using computational fluid dynamics, we aim to compare atrio-femoral and femoro-atrial cannulation to assess the impact on recirculation fraction, under ideal conditions and several clinical scenarios. Using a patient-averaged model of the venae cavae and right atrium, commercially-available cannulae were positioned in each configuration. Additionally, occlusion of the femoro-atrial drainage cannula side-holes with/without reduced inferior vena cava inflow (0-75%) and retraction of the atrio-femoral drainage cannula were modelled. Large-eddy simulations were run for 2-6L/min circuit flow, obtaining time-averaged flow data. The model showed good agreement with clinical atrio-femoral recirculation data. Under ideal conditions, atrio-femoral yielded 13.5% higher recirculation than femoro-atrial across all circuit flow rates. Atrio-femoral right atrium flow patterns resembled normal physiology with a single large vortex. Femoro-atrial cannulation resulted in multiple vortices and increased turbulent kinetic energy at > 3L/min circuit flow. Occluding femoro-atrial drainage cannula side-holes and reducing inferior vena cava inflow increased mean recirculation by 11% and 32%, respectively. Retracting the atrio-femoral drainage cannula did not affect recirculation. These results suggest that, depending on drainage issues, either atrio-femoral or femoro-atrial cannulation may be preferrable. Rather than cannula tip proximity, the supply of available venous blood at the drainage site appears to be the strongest factor affecting recirculation.

Red blood cell distribution width is associated with increased interactions of blood cells with vascular wall.

The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.

Flow Dynamics and Mixing in Extracorporeal Support: A Study of the Return Cannula.

Cannulation strategies in medical treatment such as in extracorporeal life support along with the associated cannula position, orientation and design, affects the mixing and the mechanical shear stress appearing in the flow field. This in turn influences platelet activation state and blood cell destruction. In this study, a co-flowing confined jet similar to a return cannula flow configuration found in extracorporeal membrane oxygenation was investigated experimentally. Cannula diameters, flow rate ratios between the jet and the co-flow and cannula position were studied using Particle Image Velocimetry and Planar Laser Induced Fluorescence. The jet was turbulent for all but two cases, in which a transitional regime was observed. The mixing, governed by flow entrainment, shear layer induced vortices and a backflow along the vessel wall, was found to require 9-12 cannula diameters to reach a fully homogeneous mixture. This can be compared to the 22-30 cannula diameters needed to obtain a fully developed flow. Although not significantly affecting mixing characteristics, cannula position altered the development of the flow structures, and hence the shear stress characteristics.

An experimental model of veno-venous arterial extracorporeal membrane oxygenation.

INTRODUCTION: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. AIM: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump-driven circuit. METHODS: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. RESULTS: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. CONCLUSION: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings.

Modeling sensitivity and uncertainties in platelet activation models applied on centrifugal pumps for extracorporeal life support.

Two platelet activation models were studied with respect to uncertainties of model parameters and variables. The sensitivity was assessed using two direct/deterministic approaches as well as the statistical Monte Carlo method. The first two, are linear in character whereas the latter is non-linear. The platelet activation models were applied on platelets moving within an extracorporeal centrifugal blood pump. The phenomenological, Lagrangian stress- and time-based power law-based models under consideration, have experimentally calibrated parameters and the stress expressed in a scalar form. The sensitivity of the model with respect to model parameters and the expression of the scalar stress was examined focusing on a smaller group of platelets associated with an elevated risk of activation. The results showed a high disparity between the models in terms of platelet activation state, found to depend on the platelets' trajectory in the pump and the expression used for the scalar stress. Monte Carlo statistics was applied to the platelets at risk for activation and not to the entire platelet population. The method reveals the non-linear sensitivity of the activation models. The results imply that power-law based models have a restricted range of validity. The conclusions of this study apply to both platelet activation and hemolysis models.

Flow-induced platelet activation in components of the extracorporeal membrane oxygenation circuit.

Extracorporeal membrane oxygenation (ECMO) is used for rescue in severe respiratory and/or circulatory failure. The patient's blood is pumped over artificial surfaces in the ECMO circuit. A platelet activation model was applied to study the potential thrombogenicity of ECMO circuit components: the centrifugal blood pump, cannulae, and tubing connectors. Based on the accumulated effect of the scalar form of the stress acting on the platelet over time, the activation model enables assessment of platelet activation and pinpoints regions of elevated activation risk in a component. Numerical simulations of the flow in different components of the ECMO circuit was carried out where the activation level is a function of the impact of local stress and its history along the path that the platelets follow. The results showed that the pump carried the largest risk for platelet activation followed by the reinfusion cannula and lastly the connectors. Pump thrombogenicity was mainly due to long residence time and high shear-rate while the connector showed a high level of non-stationary shear-rate that in turn may contribute to the formation of aggregates through direct platelet activation or through high shear-rate modulation of the vWF multimers.