Monitoring of Post-Brain Injuries By Measuring Plasma Levels of Neuron-Derived Extracellular Vesicles.

Background: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury. Methods: A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 + CD9+]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36). Results: The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 + CD9+]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within a ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly (P = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23). Conclusions: The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.

Accuracy and Trending Ability of Cardiac Index Measured by the CNAP System in Patients Undergoing Abdominal Aortic Aneurysm Surgery.

OBJECTIVES: The CNAP system is a noninvasive monitor that provides a continuous arterial pressure waveform using an inflatable finger cuff. The authors hypothesized that dramatic changes in systemic vascular resistance index during abdominal aortic aneurysm (AAA) surgery might affect the accuracy of noninvasive pulse contour monitors. The aim of this study was to evaluate the accuracy and trending ability of cardiac index derived by the CNAP system (CICN) in patients undergoing AAA surgery. DESIGN: Prospective clinical study. SETTING: Cardiac surgery operating room in a single cardiovascular center. PARTICIPANTS: Twenty patients who underwent elective AAA surgery. INTERVENTIONS: CICN and cardiac index measured using 3-dimensional images (CI3D) were determined simultaneously at 8 points during the surgery. At aortic clamping and unclamping, the authors tested the trending ability of CICN using 4-quadrant plot analysis and polar plot analysis. MEASUREMENTS AND MAIN RESULTS: The authors found a wide limit of agreement between CICN and CI3D (percentage error: 85.0%). The cubic splines, which show the relationship between systemic vascular resistance index and percentage CI discrepancy [(CICN-CI3D)/CI3D], were sloped positively. Four-quadrant plot analysis showed poor trending ability for CICN at both aortic clamping and unclamping (concordance rate: 29.4% and 57.9%, respectively). In the polar plot analysis, the concordance rates at aortic clamping and unclamping were 15.0% and 35.0%, respectively. CONCLUSIONS: CICN is not interchangeable with CI3D in patients undergoing AAA surgery. The trending ability for CICN at aortic clamping and unclamping was below the acceptable limit. These inaccuracies might be secondary to the high systemic vascular resistance index during AAA surgery.

Accuracy and Trending Ability of Blood Pressure and Cardiac Index Measured by ClearSight System in Patients With Reduced Ejection Fraction.

OBJECTIVES: To investigate the accuracy and trending ability of ClearSight (Edwards Lifesciences, Irvine, CA) in patients with reduced ejection fraction (<55%) undergoing off-pump coronary artery bypass graft (CABG) surgery by comparing the ClearSight-derived cardiac index (CICS) with the cardiac index measured with thermodilution using a pulmonary artery catheter. In addition, the accuracy and trending ability of ClearSight for blood pressure measurement was investigated by comparing the mean arterial pressure (MAP) derived by ClearSight (MAPcs) with invasive intra-arterial pressure. DESIGN: Prospective clinical study. DESIGN: Cardiac surgery operating room in a single cardiovascular center. PARTICIPANTS: The study comprised 20 patients who underwent elective CABG surgery. INTERVENTIONS: MAP and cardiac index were measured simultaneously at 6 time points intraoperatively. Trending ability was investigated at the following 2 points: (1) before and after placing the patient in the Trendelenburg position and (2) before and after atrial pacing with a targeted heart rate increase of 20%. MEASUREMENTS AND MAIN RESULTS: Bland-Altman analysis showed that the percentage error between CICS and the cardiac index measured with thermodilution was 40.2% and the percentage error between MAPcs and MAP was 24.6%. Four-quadrant plot analysis showed that the tracking ability of CICS with the Trendelenburg position and atrial pacing was below the good trending ability cutoff (92%). However, the concordance rate of the 4-quadrant plot analysis showed a good trending ability for MAPcs. The polar plot analysis showed the same trend. CONCLUSIONS: CICS was not sufficiently accurate in patients with reduced ejection fraction undergoing off-pump CABG surgery. However, ClearSight was clinically acceptable for MAP regarding its accuracy and trending ability in patients with reduced ejection fraction.

Accuracy of the ClearSight™ system in patients undergoing abdominal aortic aneurysm surgery.

PURPOSE: The ClearSight™ device monitors continuous pressure and cardiac output via pulse contour analysis. ClearSight™, however, may not be reliable in patients with reduced peripheral perfusion caused by high peripheral resistance. This study aimed to elucidate the accuracy and trending ability of ClearSight™ in patients undergoing abdominal aortic aneurysm (AAA) surgery by comparing the ClearSightTM-derived cardiac index (CICS) with that measured using three-dimensional echocardiography (CI3D). METHODS: The study included 20 patients who underwent elective AAA surgery. CICS and CI3D were measured simultaneously at eight time points during the surgery. Trending ability was investigated after aortic clamping and unclamping. We used CI3D as the reference method. RESULTS: Bland-Altman analysis showed a wide limit of agreement between CICS and CI3D (percentage error 41.3%). Subgroup analysis showed a lower percentage error (33.2%) in patients with CI ≥ 2.5 L/min/m2. The cubic splines related to the CI3D and CI discrepancy were negatively sloped, indicating that CI3D had significant influence on the CI discrepancy (p < 0.001). Four-quadrant plot analysis showed that the tracking ability of ClearSight™ after aortic clamping and declamping were clinically unacceptable (81.3% and 78.6%, respectively). Also, the polar plot analysis showed that the concordance rate of ClearSight™ after aortic clamping and declamping were clinically unacceptable (58.3% and 66.7%, respectively). CONCLUSIONS: ClearSight™ was not sufficiently accurate in patients undergoing AAA surgery. The tracking ability of ClearSight™ after aortic clamping was below the acceptable limit.