Computed tomography angiography as an adjunct to computational fluid dynamics for prediction of oxygenator thrombus formation.

INTRODUCTION: Extracorporeal membrane oxygenation circuit performance can be compromised by oxygenator thrombosis. Stagnant blood flow in the oxygenator can increase the risk of thrombus formation. To minimize thrombogenic potential, computational fluid dynamics is frequently applied for identification of stagnant flow conditions. We investigate the use of computed tomography angiography to identify flow patterns associated with thrombus formation. METHODS: A computed tomography angiography was performed on a Quadrox D oxygenator, and video densitometric parameters associated with flow stagnation were measured from the acquired videos. Computational fluid dynamics analysis of the same oxygenator was performed to establish computational fluid dynamics-based flow characteristics. Forty-one Quadrox D oxygenators were sectioned following completion of clinical use. Section images were analyzed with software to determine oxygenator clot burden. Linear regression was used to correlate clot burden to computed tomography angiography and computational fluid dynamics-based flow characteristics. RESULTS: Clot burden from the explanted oxygenators demonstrated a well-defined pattern, with the largest clot burden at the corner opposite the blood inlet and outlet. The regression model predicted clot burden by region of interest as a function of time to first opacification on computed tomography angiography (R2 = 0.55). The explanted oxygenator clot burden map agreed well with the computed tomography angiography predicted clot burden map. The computational fluid dynamics parameter of residence time, when summed in the Z-direction, was partially predictive of clot burden (R2 = 0.35). CONCLUSION: In the studied oxygenator, clot burden follows a pattern consistent with clinical observations. Computed tomography angiography-based flow analysis provides a useful adjunct to computational fluid dynamics-based flow analysis in understanding oxygenator thrombus formation.

Evaluation of an autoregulatory ECMO system for total respiratory support in an acute ovine model.

Extracorporeal membrane oxygenation (ECMO) has become a mainstay of therapy for patients suffering from severe respiratory failure. Ambulatory ECMO systems aim to provide long-term out-of-hospital respiratory support. As a patient's activity level changes, the required level of ECMO support varies with oxygen consumption and metabolic fluctuations. To compensate for such changes, an autoregulatory ECMO system (AR-ECMO) has been developed and its performance was evaluated as a proof of concept in an acute ovine model. The AR-ECMO system consists of a regular ECMO circuit and an electromechanical control system. A custom fuzzy logic control algorithm was implemented to adjust the blood flow and sweep gas flow of the ECMO circuit to meet the varying respiratory demand by utilizing two noninvasive sensors for venous oxyhemoglobin saturation and the oxygenator exhaust gas CO2 concentration. Disturbance responses of the AR-ECMO to induced acute respiratory distress were assessed for six hours in four juvenile sheep cannulated with a veno-pulmonary artery ECMO configuration, including acute ventilator shutoff, ventilator step change (off-on-off), and forced desaturation. All sheep survived for the study duration. The AR-ECMO system was able to respond and maintain stable hemodynamics and physiological blood gas contents (SpO2  = 96.3 % ± 4.29, pH 7.44 ± 0.09, pCO2  = 38.9 ± 9.9 mm Hg, and pO2 =237.9 ± 123.6 mm Hg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO2 and oxygenator outlet pCO2 were observed (R2  = 0.84). In summary, the AR-ECMO system successfully maintained physiologic control of peripheral oxygenation and carbon dioxide over the study period, utilizing only measurements taken directly from the ECMO circuit. The range of system response necessitates an adaptable system in the setting of variable metabolic demands. The ability of this system to respond to significant disturbances in ventilator support is encouraging. Future work to evaluate our AR-ECMO system in long-term, awake animal studies is necessary for further refinement.

Device-induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding.

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device-induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P-selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device-injured platelets to fibrinogen, collagen, and VWF was quantified with fluorescent microscopy. Device-induced damage to VWF was characterized with western blotting. The CentriMag blood pump induced progressive platelet activation with blood circulating time. Particularly, GPIIb/IIIa activation increased from 1.1% (Base) to 11% (4 hours) and soluble P-selectin concentration increased from 14.1 ng/mL (Base) to 26.5 ng/mL (4 hours). Those device-activated platelets exhibited increased adhesion capacity to fibrinogen. Concurrently, the CentriMag blood pump caused progressive platelet receptor loss (GPVI and GPIbα) with blood circulating time. Specifically, MFI of the GPVI and GPIbα receptors decreased by 17.2% and 16.1% for the 4-hours sample compared to the baseline samples, respectively. The device-injured platelets exhibited reduced adhesion capacities to collagen and VWF. The high molecular weight multimers (HMWM) of VWF in the blood disappeared within the first hour of the circulation. Thereafter the multimeric patterns of VWF were stable. The change in the VWF multimeric pattern was different from the progressive structural and functional changes of platelets with the circulation time. This study suggested that the CentriMag blood pump could induce two opposite effects on platelets and associated hemostatic functions under a clinically relevant operating condition. The device-altered hemostatic function may contribute to thrombosis and bleeding simultaneously as occurring in patients supported by a rotary blood pump. Device-induced damage of platelets may be an important cause for bleeding in patients supported with rotary blood pump MCS systems relative to device-induced loss of HMWM-VWF.