Propofol in Exhaled Breath: Real-time Detection by Surface Acoustic Wave Sensors

描述（由申请人提供）：由于几个有利的特性，丙泊酚一直是最常用的静脉（IV）麻醉剂。麻醉人员通常测量在手术期间使用的许多试剂的呼吸中的浓度，所述试剂包括：防止缺氧的分子氧、确保气管内导管在气管中的放置和充分通气的二氧化碳以及麻醉剂（例如，地氟烷、一氧化二氮）以维持适当的“意识水平”/麻醉深度。最近，几个独立的研究小组已经证明，接受静脉注射异丙酚的患者可以在呼吸中消除一部分麻醉剂。此外，呼吸中丙泊酚的浓度与其游离血药浓度相关，因此可预测其游离血药浓度。因此，有可能使用呼出丙泊酚水平的实时床旁测量来确定和操纵丙泊酚的血药浓度，以指导其给药。这种能力将类似于已经用于挥发性麻醉剂的技术，并将提高患者的安全性。然而，目前的研究工具（例如，质子转移反应-质谱法[PTR-MS]、气相色谱-质谱法[GC-MS]）包括灵敏、大型、非常昂贵的设备，需要熟练的人员来操作。显然，开发小型、稳健、可靠且易于操作的用于测量呼出丙泊酚水平的新技术是临床接受的先决条件。这项拨款提案的目标是设计、建造和测试一种测量呼出异丙酚的原型装置。该应用的创新是利用国防部以前的开发，通过采用聚合物涂层表面声波（SAW）技术来检测临床相关浓度的丙泊酚。为此，将实现以下具体目标：目标1：设计和构建SAW探测器，其具有改进的电路、微型阀门、改进的患者采集管和CO2门控采集（4个月）。目标二：测量并比较丙泊酚麻醉的人类患者（n=15）呼出气中的丙泊酚浓度（使用SAW和常规GC-MS）与血浆中的丙泊酚浓度（使用UPLC）。（8个月）Xhale，Inc.的短期目标。是研究和开发这些设备， 进入美国市场，预计到2013年将超过3.41亿美元。 公共卫生相关性：丙泊酚作为一种常用的静脉麻醉剂，最近被证明从肺中排出的浓度与血液浓度成比例。本项目的目标是设计、构建和测试一种测量呼出丙泊酚的原型装置，以实时估计人体血液浓度，并提高使用该药物麻醉患者的安全性。

DESCRIPTION (provided by applicant): Propofol endures as the most popular intravenous (IV) anesthetic due to several favorable characteristics. Anesthesia personnel customarily measure the concentrations in breath of many agents used during surgery including: molecular oxygen to prevent hypoxia, carbon dioxide to assure placement of an endotracheal tube in the trachea and adequate ventilation, and anesthetics (e.g., desflurane, nitrous oxide) to maintain the appropriate "level of consciousness"/depth of anesthesia. Recently, several independent research teams have demonstrated that patients receiving IV propofol eliminate a fraction of this anesthetic in the breath. Also, the concentration of propofol in breath correlates to and is therefore predictive of its free blood concentration. Therefore, the possibility exists to determin and manipulate the blood concentration of propofol using real-time, point-of-care measurement of exhaled propofol levels to guide its dosing. This ability will be similar to techniques already employed for volatile anesthetics and will improve patient safety. Unfortunately, the current research tools (e.g., proton transfer reaction-mass spectroscopy [PTR-MS], gas chromatography- mass spectroscopy [GC-MS]) used to measure propofol in breath consists of sensitive, large, very expensive equipment that requires skilled, personnel to operate. Clearly, the development of novel technology that is small, robust, reliable, and easily operated for measuring exhaled propofol levels is a prerequisite for clinical acceptance. The goal of this grant proposal is to design, build, and test a prototype device to measure exhaled propofol. The innovation of this application is leveraging previous development by the Department of Defense by adapting polymer coated surface acoustic wave (SAW) technology to detect propofol at clinically relevant concentrations. To this end, the following specific aims will be achieved: Aim 1: Design and build a SAW detector with improved circuitry, miniature valving, an improved collection tubing to patient, and CO2-gated collection (4 months). Aim 2: Measure and compare propofol concentrations in exhaled breath (using SAW and conventional GC- MS) to those in plasma (using UPLC) in human patients (n=15) anesthetized with propofol. (8 months) The short term objective of Xhale, Inc. is to research and develop these devices for later introduction into the US market, projected to exceed $341 million by 2013. PUBLIC HEALTH RELEVANCE: Propofol endures as a commonly used intravenous anesthetic and has recently been demonstrated to emanate from the lung in concentrations proportionate to blood concentrations. The goal of this project is to design, build, and test a prototype device to measure exhaled propofol in order to estimate human blood concentrations in real-time and to improve the safety of patients anesthetized with this agent.