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.
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