Bioimpedance Analysis as Early Predictor for Clot Formation Inside a Blood-Perfused Test Chamber: Proof of Concept Using an In Vitro Test-Circuit

Abstract

Clot formation inside a membrane oxygenator (MO) due to blood-to-foreign surface interaction represents a frequent complication during extracorporeal membrane oxygenation. Since current standard monitoring methods of coagulation status inside the MO fail to detect clot formation at an early stage, reliable sensors for early clot detection are in demand to reduce associated complications and adverse events. Bioimpedance analysis offers a monitoring concept by integrating sensor fibers into the MO. Herein, the feasibility of clot detection via bioimpedance analysis is evaluated. A custom-made test chamber with integrated titanium fibers acting as sensors was perfused with heparinized human whole blood in an in vitro test circuit until clot formation occurred. The clot detection capability of bioimpedance analysis was directly compared to the pressure difference across the test chamber (ΔP-TC), analogous to the measurement across MOs (ΔP-MO), the clinical gold standard for clot detection. We found that bioimpedance measurement increased significantly 8 min prior to a significant increase in ΔP-TC, indicating fulminant clot formation. Experiments without clot formation resulted in a lack of increase in bioimpedance or ΔP-TC. This study shows that clot detection via bioimpedance analysis under flow conditions in a blood-perfused test chamber is generally feasible, thus paving the way for further investigation.

Early Blood Clot Detection Using Forward Scattering Light Measurements Is Not Superior to Delta Pressure Measurements

“…The in vitro circuit was adapted from a previous study [19] and slight adjustments were made. Heparinized human whole blood was circulated at a blood flow rate of 5 mL/min from the blood reservoir through a roller pump in an enclosed cuvette and back into the blood reservoir (Figure 1).…”

“…Blood samples were withdrawn with a syringe before the blood entered the blood reservoir. This test circuit was adapted from a previous study [19], and slight adjustments were made. Illustration of the in vitro test circuit.…”

“…Blood samples were withdrawn with a syringe before the blood entered the blood reservoir. This test circuit was adapted from a previous study [19], and slight adjustments were made. A standard transfusion set reservoir (T3986, Fresenius Kabi AG, Bad Homburg, Germany) and a custom-made test chamber were used in this setup.…”

“…Every test chamber was manufactured by hand based on a semi-micro polystyrene cuvette (67.742, Sarstedt AG, Nümbrecht, Germany). Boreholes were drilled at the base and on the lid of the cuvette to place Titanium wires (ASTM F-67 graded) in the center of the test chamber as a foreign surface in the blood flow path to trigger blood clot formation according to our previous study [19].…”