Propofol detection and quantification in human blood: the promise of feedback controlled, closed-loop anesthesia

Abstract

The performance of a membrane-coated voltammetric sensor for propofol (2,6-diisopropylphenol) has been characterized in long term monitoring experiments using an automated flow analytical system (AFAS) and by analyzing human serum and whole blood samples by standard addition. It is shown that the signal of the membrane-coated electrochemical sensor for propofol is not influenced by the components of the pharmaceutical formulation of propofol (propofol injectable emulsion). The current values recorded with the electrochemical propofol sensor in buffer solutions and human serum samples spiked with propofol injectable emulsion showed excellent correlation with the peak heights recorded with an UV-Vis detector during the HPLC analysis of these samples (R(2) = 0.997 in PBS and R(2) = 0.975 in human serum). However, the determination of propofol using the electrochemical method is simpler, faster and has a better detection limit (0.08 ± 0.05 μM) than the HPLC method (0.4 ± 0.2 μM). As a first step towards feedback controlled closed-loop anesthesia, the membrane-coated electrochemical sensor has been implemented onto surface of an intravenous catheter. The response characteristics of the membrane-coated carbon fiber electrode on the catheter surface were very similar to those seen using a macroelectrode.

Simultaneous monitoring of anesthetics and therapeutic compounds with a portable multichannel potentiostat

“…This problem is usually solved by adding a PVC membrane on the WE surface, as in [20]. In any case, data compare quite well with those published in literature on the same redox reactions [21], [22], [23].…”

A Feedback Control Approach to Organic Drug Infusions Using Electrochemical Measurement

“…The root mean squared error of the output of the system with respect to the targeted concentration (RMSE target) yielded a higher average error from all the experiments of 25.10% ± 11.49%. This value is higher than the ferrocene methanol experiments in part due to the membrane coating of the glassy-carbon sensor [12]. The average steady-state error is in the same range of the ferrocene methanol experiments, 5.19% ± 3.91%.…”

“…To achieve actual control instead of "targeted" control, the concentration of propofol has to be measured continuously during total intravenous anesthesia (TIVA). Recently, our group has developed an electrochemical sensor for continuous monitoring of propofol in complex biological solutions, including whole blood [9][10][11][12]. It has been shown that the performance characteristics [13] of the propofol sensor (precision, accuracy, response time, etc.)…”

Voltammetric Determination of Diffusion Coefficients in Polymer Membranes: Guidelines to Minimize Errors

“…To confirm the conclusions of our model calculations on the accuracy of the determination of diffusion coefficients in highly viscous media from the scan rate dependence of LSVs the diffusion coefficient of ferrocene was determined in 2‐nitrophenyl octylether (o‐NPOE) using different sizes of electrodes. o‐NPOE is a commonly used plasticizer of polyvinyl chloride (PVC)‐based ion‐selective membranes and membranes used to modify the response of voltammetric working electrodes . To determine the diffusion coefficient of ferrocene a series of linear‐sweep voltammograms were recorded with different sizes of electrodes (10, 25, 76, and, 125 μm diameters) and scan rates (100, 50, 10, and 5 mV/s which correspond to p‐values between 0.25 and 13).…”

“…Ferrocene (98 %) and ferrocenecarboxylic acid, FcCOOH (97 %) were purchased from Sigma-Aldrich. Tetrabuty-lammonium perchlorate, 2-nitrophenyl octyl ether (oN-POE) and PVC (high molecular weight) were products of Sigma-Aldrich while tetradodecylammonium tetrakis (pentafluorophenyl) borate, TDDA-TPFPhB was prepared by metathesis from tetradodecylammonium chloride (Sigma-Aldrich) and potassium tetrakis (pentafluorophenyl) borate (Boulder Scientific) as described previously [1][2][3]. Tetrabutylammonium perchlorate was recrystallized two times from ethyl acetate before use, and all other reagents were used as received without additional purification.…”