Correlation Analysis Between Echinocytosis Stages and Blood Viscosity During Oxygenator Perfusion: An In Vitro Study.

The study aimed to investigate the effect of red blood cell (RBC) morphology on oxygenator perfusion, focusing on stages of echinocytosis and their correlation with blood viscosity. A test circuit with an oxygenator and human RBC mixtures was used to induce changes in RBC shape by increasing sodium salicylate concentrations (0, 10, 20, 30, 60, and 120 mmol/L), while hematocrit, blood temperature, and anticoagulation were maintained. Blood viscosity was measured using a continuous blood viscosity monitoring system based on pressure-flow characteristics. Under a scanning electron microscope, the percentages of discocytes, echinocytes I-III, spheroechinocytes, and spherocytes were determined from approximately 400 cells per RBC sample. Early echinocytes, mainly discocytes and echinocytes I and II in the range of 0-30 mmol/L were predominant, resulting in a gradual increase in blood viscosity from 1.78 ± 0.12 to 1.94 ± 0.12 mPa s. At 60 mmol/L spherocytes emerged, and at 120 mmol/L, spheroidal RBCs constituted 50% of the population, and blood viscosity sharply rose to 2.50 ± 0.15 mPa s, indicating a 40% overall increase. In conclusion, the presence of spherocytes significantly increases blood viscosity, which may affect oxygenator perfusion.

The Number of Microbubbles Generated During Cardiopulmonary Bypass Can Be Estimated Using Machine Learning From Suction Flow Rate, Venous Reservoir Level, Perfusion Flow Rate, Hematocrit Level, and Blood Temperature.

GOAL: Microbubbles (MBs) are known to occur within the circuits of cardiopulmonary bypass (CPB) systems, and higher-order dysfunction after cardiac surgery may be caused by MBs as well as atheroma dispersal associated with cannula insertion. As complete MB elimination is not possible, monitoring MB count rates is critical. We propose an online detection system with a neural network-based model to estimate MB count rate using five parameters: suction flow rate, venous reservoir level, perfusion flow rate, hematocrit level, and blood temperature. METHODS: Perfusion experiments were performed using an actual CPB circuit, and MB count rates were measured using the five varying parameters. RESULTS: Bland-Altman analysis indicated a high estimation accuracy (R2 > 0.95, p < 0.001) with no significant systematic error. In clinical practice, although the inclusion of clinical procedures slightly decreased the estimation accuracy, a high coefficient of determination for 30 clinical cases (R2 = 0.8576) was achieved between measured and estimated MB count rates. CONCLUSIONS: Our results highlight the potential of this system to improve patient outcomes and reduce MB-associated complication risk.

Simultaneous Control of Venous Reservoir Level and Arterial Flow Rate in Cardiopulmonary Bypass With a Centrifugal Pump.

Cardiopulmonary bypass (CPB) is an indispensable technique in cardiac surgery, providing the ability to temporarily replace cardiopulmonary function and create a bloodless surgical field. Traditionally, the operation of CPB systems has depended on the expertise and experience of skilled perfusionists. In particular, simultaneously controlling the arterial and venous occluders is difficult because the blood flow rate and reservoir level both change, and failure may put the patient's life at risk. This study proposes an automatic control system with a two-degree-of-freedom model matching controller nested in an I-PD feedback controller to simultaneously regulate the blood flow rate and reservoir level. CPB operations were performed using glycerin and bovine blood as perfusate to simulate flow-up and flow-down phases. The results confirmed that the arterial blood flow rate followed the manually adjusted target venous blood flow rate, with an error of less than 5.32%, and the reservoir level was maintained, with an error of less than 3.44% from the target reservoir level. Then, we assessed the robustness of the control system against disturbances caused by venting/suction of blood. The resulting flow rate error was 5.95%, and the reservoir level error 2.02%. The accuracy of the proposed system is clinically satisfactory and within the allowable error range of 10% or less, meeting the standards set for perfusionists. Moreover, because of the system's simple configuration, consisting of a camera and notebook PC, the system can easily be integrated with general CPB equipment. This practical design enables seamless adoption in clinical settings. With these advancements, the proposed system represents a significant step towards the automation of CPB.

Neural Network-based Estimation of Microbubbles Generated in Cardiopulmonary Bypass Circuit: A Clinical Application Study.

The cardiopulmonary bypass system used in cardiac surgery can generate microbubbles (MBs) that may cause complications, such as neurocognitive dysfunction, when delivered into the blood vessel. Estimating the number of MBs generated, thus, is necessary to enable the surgeons to deal with it. To this end, we previously proposed a neural network-based model for estimating the number of MBs from four factors measurable from the cardiopulmonary bypass system: suction flow rate, venous reservoir level, blood viscosity, and perfusion flow rate. However, the model has not been adapted to the data collected from actual surgery cases. In this study, the accuracy of MBs estimated by the proposed model was examined in four clinical cases. The results showed that the coefficient of determination between estimated MBs and the measured MBs throughout the surgeries was R2=0.558 (p<0.001). We found that the surgical treatments, such as administration of drugs, fluids and blood transfusions, increased the number of measured MBs. The coefficient of determination increased to R2= 0.8762 (p<0.001) by excluding the duration of these treatments. This result indicates that the model can estimate the number of MBs with high accuracy under the clinical environment.

Neural network-based modeling of the number of microbubbles generated with four circulation factors in cardiopulmonary bypass.

The need for the estimation of the number of microbubbles (MBs) in cardiopulmonary bypass surgery has been recognized among surgeons to avoid postoperative neurological complications. MBs that exceed the diameter of human capillaries may cause endothelial disruption as well as microvascular obstructions that block posterior capillary blood flow. In this paper, we analyzed the relationship between the number of microbubbles generated and four circulation factors, i.e., intraoperative suction flow rate, venous reservoir level, continuous blood viscosity and perfusion flow rate in cardiopulmonary bypass, and proposed a neural-networked model to estimate the number of microbubbles with the factors. Model parameters were determined in a machine-learning manner using experimental data with bovine blood as the perfusate. The estimation accuracy of the model, assessed by tenfold cross-validation, demonstrated that the number of MBs can be estimated with a determinant coefficient R2 = 0.9328 (p < 0.001). A significant increase in the residual error was found when each of four factors was excluded from the contributory variables. The study demonstrated the importance of four circulation factors in the prediction of the number of MBs and its capacity to eliminate potential postsurgical complication risks.

Detection of Echinocyte during Perfusion with Oxygenator Based on Continuous Blood Viscosity Monitoring.

We applied our proposed continuous blood viscosity monitoring system for cardiopulmonary bypass to an experimental model that introduced echinocytes, and we confirm the viscosity change detection due to red blood cell (RBC) deformability decline. For the in vitro experiment, a test circuit including an oxygenator and a controlled bovine blood sample with excessive alkalemia to induce the echinocyte were prepared, and a perfusion experiment was performed. During the experiment, the anticoagulated bovine blood sample maintained a hematocrit of approximately 22%, temperature of 37°C, and more than 800 s of the activated clotting time. The estimated viscosity obtained from the proposed system was 2.10 mPas at the beginning of the experiment and 3.58 mPas at the end of the experiment, and it increased 1.48 mPas during the experiment. According to the scanning electron micrographs of blood samples, the echinocytes with multiple spicules at the beginning of the experiment and distorted spherical RBCs including the echinocytes with multiple spicules at the end of experiment were observed. We conclude that the system may be helpful for clinical perfusion management, because it detected the presence of echinocytes as the blood viscosity in an oxygenator flow pass increased.

Abdominal organ protection strategy for aortic arch aneurysm surgery.

INTRODUCTION: Body temperature maintained during open distal anastomosis in patients who undergo aortic surgery has been showing an upward trend; however, a higher temperature may increase visceral organ and spinal cord injury. Distal perfusion may reduce abdominal organ injury, especially acute kidney injury (AKI). METHODS: From 2009 to 2016, 56 patients who underwent ascending aortic and/or aortic arch surgery were enrolled. Open distal anastomosis was performed using one of three protection strategies: 1) systemic temperature of 25°C followed by selective cerebral perfusion (SCP) with lower body circulatory arrest (Group CA25, n=27); 2) systemic temperature of 28°C followed by SCP with lower body circulatory arrest (Group CA28, n=4); and 3) systemic temperature of 28°C followed by SCP with distal aortic perfusion (Group DP, n=25). RESULTS: During the postoperative course, levels of blood urea nitrogen, creatinine, liver enzymes, lactate dehydrogenase and lactate in Groups CA28 and CA25 were significantly higher than those in Group DP. AKI defined by the AKI Network occurred in 28 cases (50%) and 3 cases required permanent hemodialysis. AKI was significantly higher in Groups CA25 and CA28 than in Group DP (p=0.026). Mid-term follow-up showed that patients who developed postoperative AKI were more likely to suffer from cardiovascular events. CONCLUSIONS: Distal perfusion during open distal anastomosis reduced kidney and liver injury after thoracic aortic surgery despite an increased body temperature of up to 28°C. This strategy may be useful to prevent AKI, liver dysfunction, the need for hemodialysis and multiple organ failure and could improve mid-term results.

A Novel Blood Viscosity Estimation Method Based on Pressure-Flow Characteristics of an Oxygenator During Cardiopulmonary Bypass.

During cardiopulmonary bypass (CPB), blood viscosity conspicuously increases and decreases due to changes in hematocrit and blood temperature. Nevertheless, blood viscosity is typically not evaluated, because there is no technology that can provide simple, continuous, noncontact monitoring. We modeled the pressure-flow characteristics of an oxygenator in a previous study, and in that study we quantified the influence of viscosity on oxygenator function. The pressure-flow monitoring information in the oxygenator is derived from our model and enables the estimation of viscosity. The viscosity estimation method was proposed and investigated in an in vitro experiment. Three samples of whole bovine blood with different hematocrit levels (21.8, 31.0, and 39.8%) were prepared and perfused into the oxygenator. As the temperature changed from 37°C to 27°C, the mean inlet pressure (Pin ) and outlet pressure (Pout ) of the oxygenator and the flow (Q) and viscosity of the blood were measured. The estimated viscosity was calculated from the pressure gradient (ΔP = Pin - Pout ) and Q and was compared to the measured blood viscosity. A strong correlation was found between the two methods for all samples. Bland-Altman analysis revealed a mean bias of -0.0263 mPa.s, a standard deviation of 0.071 mPa.s, limits of agreement of -0.114-0.166 mPa.s, and a percent error of 5%. Therefore, this method is considered compatible with the torsional oscillation viscometer that has plus or minus 5% measurement accuracy. Our study offers the possibility of continuously estimating blood viscosity during CPB.

Continuous Blood Viscosity Monitoring System for Cardiopulmonary Bypass Applications.

This paper proposes an algorithm that estimates blood viscosity during cardiopulmonary bypass (CPB) and validates its application in clinical cases. The proposed algorithm involves adjustable parameters based on the oxygenator and fluid types and estimates blood viscosity based on pressure-flow characteristics of the fluid perfusing through the oxygenator. This novel nonlinear model requires four parameters that were derived by in vitro experiments. The results estimated by the proposed method were then compared with a conventional linear model to demonstrate the former's optimal curve fitting. The viscosity (ηe) estimated using the proposed algorithm and the viscosity (η) measured using a viscometer were compared for 20 patients who underwent mildly hypothermic CPB. The developed system was applied to ten patients, and ηe was recorded for comparisons with hematocrit and blood temperature. The residual sum of squares between the two curve fittings confirmed the significant difference, with p < 0.001. ηe and η showed a very strong correlation with R2 = 0.9537 and p < 0.001. Regarding the mean coefficient of determination for all cases, the hematocrit and temperature showed weak correlations at 0.33 ± 0.14 and 0.22 ± 0.21, respectively. For CPB measurements of all cases, ηe was more than 98% distributed in the range from 1 to 3 mPa⋅s. This new system for estimating viscosity may be useful for detecting various viscosity-related effects that may occur during CPB.

Blood viscosity monitoring during cardiopulmonary bypass based on pressure-flow characteristics of a Newtonian fluid.

We proposed a blood viscosity estimation method based on pressure-flow characteristics of oxygenators used during cardiopulmonary bypass (CPB) in a previous study that showed the estimated viscosity to correlate well with the measured viscosity. However, the determination of the parameters included in the method required the use of blood, thereby leading to high cost of calibration. Therefore, in this study we propose a new method to monitor blood viscosity, which approximates the pressure-flow characteristics of blood considered as a non-Newtonian fluid with characteristics of a Newtonian fluid by using the parameters derived from glycerin solution to enable ease of acquisition. Because parameters used in the estimation method are based on fluid types, bovine blood parameters were used to calculate estimated viscosity (ηe), and glycerin parameters were used to estimate deemed viscosity (ηdeem). Three samples of whole bovine blood with different hematocrit levels (21.8%, 31.0%, and 39.8%) were prepared and perfused into the oxygenator. As the temperature changed from 37 °C to 27 °C, the oxygenator mean inlet pressure and outlet pressure were recorded for flows of 2 L/min and 4 L/min, and the viscosity was estimated. The value of deemed viscosity calculated with the glycerin parameters was lower than estimated viscosity calculated with bovine blood parameters by 20-33% at 21.8% hematocrit, 12-27% at 31.0% hematocrit, and 10-15% at 39.8% hematocrit. Furthermore, deemed viscosity was lower than estimated viscosity by 10-30% at 2 L/min and 30-40% at 4 L/min. Nevertheless, estimated and deemed viscosities varied with a similar slope. Therefore, this shows that deemed viscosity achieved using glycerin parameters may be capable of successfully monitoring relative viscosity changes of blood in a perfusing oxygenator.

A blood viscosity estimation method based on pressure-flow characteristics of an oxygenator during cardiopulmonary bypass and its clinical application.

In this paper, we developed a model that uses pressure-flow monitoring information in the oxygenator to estimate viscosity of human blood. The comparison between estimated viscosity (ηe) and measured viscosity (η) was assessed in 16 patients who underwent cardiac surgery using mild hypothermia cardiopulmonary bypass (CPB). After initiation of CPB, ηe was recorded at three periods: post-establishment of total CPB, post-aortic cross-clamp, and post-declamp. During the same period, blood samples were collected from the circuit and η was measured with a torsional oscillation viscometer. The ηe was plotted as a function of η and the systematic errors and compatibility between two methods were assessed using Bland-Altman analysis. The parameters ηe and η were very strongly correlated at all points (R(2)=0.9616, p<;0.001). The Bland-Altman analysis revealed a mean bias of -0.001 mPas, a standard deviation of 0.03 mPas, limits of agreement of -0.06 mPas to 0.06 mPas, and a percent error of 3.3%. There was no fixed bias or proportion bias for the viscosity. As this method estimates blood viscosity with good precision during CPB continuously, it may be helpful for clinical perfusion management.