EFFECTS OF SIMULATED MICROGRAVITY ON THE ANESTHETIC PROPERTIES OF PROPOFOL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 尽管美国航天局进行了仔细的健康检查，但适应微重力的宇航员可能需要在各种手术条件下进行麻醉，不仅是在高度自主的空间居住环境或火星类飞行任务中，而且在从低轨道飞行任务撤离后也需要立即进行手术护理。关于微重力条件下最适当的麻醉技术，现有的信息很少。对失重的生理适应（例如，血液和血浆体积的变化、指向脑的心输出量的分数、自主神经系统活动）可以预期显著改变麻醉剂/催眠剂的体内行为和特征。 全静脉麻醉（TIVA）可能是在微重力条件下和偏远地点进行手术期间使受试者无感觉的最实用和最具成本效益的方法。TIVA的设备轻便、紧凑且独立。在目前使用的TIVA药物中，丙泊酚（2，6-二异丙基苯酚）是适合在太空中使用的最佳单一药物。丙泊酚具有几个关键特性，使其成为空间环境中理想的麻醉剂：1）麻醉的快速诱导和苏醒，2）调节剂量以实现从清醒镇静到全身麻醉的麻醉状态的能力，3）即使在长时间的手术期间，体内也没有药物积累，4）显著的止吐特性，以及5）用于评估麻醉/催眠深度的简单且可靠的手段，即从脑电活动导出的脑电双频指数（BIS）。 我们假设：1）微重力适应通过改变丙泊酚的药代动力学（PK）而不是药效学（PD）来增加丙泊酚的催眠/麻醉作用; 2）微重力适应不会改变丙泊酚麻醉后认知功能的恢复。 为了设计一个合理的战略，提供麻醉能力的背景下，空间飞行，我们计划测试这些假设在一个前瞻性的，随机交叉研究的志愿者使用地球上的模拟微重力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite careful health screening by NASA, astronauts adapted to microgravity might require the administration of anesthesia for a variety of surgical conditions not only in the highly autonomous environments of space habitation or Mars-type missions but also for immediate surgical care after evacuation from low orbital missions. A paucity of information is available regarding the most appropriate anesthetic technique in microgravity. Physiologic adaptation to weightlessness (e.g., changes in blood and plasma volume, fraction of cardiac output directed to brain, autonomic nervous system activity) can be expected to markedly alter the in vivo behavior and characteristics of anesthetics/hypnotics. Total intravenous anesthesia (TIVA) is probably the most practical and cost-effective method of rendering subjects insensate during surgery under microgravity conditions and at remote locations. Equipment for TIVA is light, compact, and self-contained. Among the TIVA agents in use today, propofol (2, 6-diisopropylphenol) is the best single agent suitable for use in space. Propofol has several key properties that make it a desirable anesthetic in a space environment: 1) rapid induction of and emergence from anesthesia, 2) ability to adjust the dose to achieve anesthetic states ranging from conscious sedation to general anesthesia, 3) lack of drug accumulation in the body, even during long procedures, 4) significant anti-emetic properties, and 5) a simple and reliable means for assessing the depth of anesthesia/hypnosis, the bispectral index (BIS), derived from the electrical activity of the brain. We hypothesize that 1) adaptation to microgravity increases the hypnotic/anesthetic effect of propofol by changing its pharmacokinetics (PK), but not pharmacodynamics (PD) and 2) adaptation to microgravity does not change the recovery of cognitive function after propofol anesthesia. In order to devise a rational strategy for providing anesthesia capabilities in the context of space flight, we plan to test these hypotheses in a prospective, randomized crossover study of volunteers by using an earth-based simulation of microgravity.