EFFECTS OF SIMULATED MICROGRAVITY ON THE ANESTHETIC PROPERTIES OF PROPOFOL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管NASA进行了仔细的健康检查，但适应微重力的宇航员可能需要对各种手术条件进行麻醉，不仅是在高度自主的太空居住或火星类任务环境中，而且还需要在从低轨道任务撤离后立即进行手术治疗。关于微重力条件下最合适的麻醉技术，可获得的信息很少。对失重的生理适应(例如，血液和血浆容量的变化，心输出量对大脑的影响，自主神经系统的活动)有望显著改变麻醉剂/催眠药的体内行为和特征。全静脉麻醉(TIVA)可能是最实用和最具成本效益的方法，使受试者在微重力条件下和偏远位置的手术中失去知觉。TIVA的设备轻便、紧凑、自给自足。在目前使用的TIVA药物中，异丙酚(2，6-二异丙基苯酚)是最适合在太空使用的单一药物。异丙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)快速诱导和苏醒，2)能够调整剂量以达到从清醒镇静到全身麻醉的各种麻醉状态，3)即使在长时间的手术中也不会在体内积累药物，4)显著的止吐特性，以及5)一种简单可靠的评估麻醉/催眠深度的方法，即脑电活动的脑电双频指数(BIS)。我们假设：1)微重力适应通过改变异丙酚的药代动力学(PK)而不是药效学(PD)来增加其催眠/麻醉效果；2)微重力适应不改变异丙酚麻醉后认知功能的恢复。为了设计一种在太空飞行中提供麻醉能力的合理策略，我们计划通过使用地面微重力模拟，在志愿者的前瞻性随机交叉研究中测试这些假设。

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.