Background: With renewed interest in long-duration space missions, there is growing exploration into synthetic torpor as a countermeasure to mitigate physiological stressors. Sedative agents, particularly those used in clinical anesthesia, have been proposed to replicate aspects of natural torpor, including reduced metabolic rate, core temperature, and brain activity. Objectives: This systematic review aims to evaluate the potential of sedative agents to induce torpor-like states suitable for extended spaceflight. The review specifically investigates their pharmacokinetics, pharmacodynamics, and performance under space-related stressors such as microgravity and ionizing radiation. Methods: We conducted a comprehensive search across multiple databases (e.g., PubMed, Scopus, Web of Science) for studies published from 1952 to 2024. Eligible studies included experimental, preclinical, and clinical investigations examining sedative agents (especially inhalation anesthetics) in the context of metabolic suppression or space-relevant conditions. Screening, selection, and data extraction followed PRISMA guidelines. Results: Out of the screened records, 141 studies met the inclusion criteria. These were thematically grouped into seven categories, including torpor physiology, anesthetic uptake, metabolism, and inhalation anesthetics. Sedative agents showed variable success in inducing torpor-like states, with inhalation anesthetics demonstrating promising metabolic effects. However, concerns remain regarding delivery methods, safety, rewarming, and the unknown effects of prolonged use in space environments. Conclusions: Sedative agents, particularly volatile anesthetics, hold potential as tools for inducing synthetic torpor in space. Nevertheless, significant knowledge gaps and technical challenges persist. Further targeted research is required to optimize these agents for safe, controlled use in spaceflight settings.

Background: The resurgence of interest in space exploration has highlighted the potential use of an induced torpor-like state for long-duration human space missions. Sedative agents, historically utilized for inducing unconsciousness and inactivity in clinical procedures since the mid-1700s, are being explored as tools to facilitate synthetic torpor for space travel. Objective: To assess the feasibility of adapting sedative agents to induce and maintain a torpor-like state for extended space missions, addressing the physiological and pharmacological challenges, and evaluating their potential protective effects against the harsh conditions of spaceflight. Torpor is characterized by reduced body temperature and metabolic rate, often accompanied by decreased brain function, heart rate, respiratory rate, circulation, and motor activity. These features are critical for mitigating the physiological demands of long-duration space missions. Methods: This systematic review evaluates current research on the mechanisms regulating torpor induction, maintenance, and arousal. It also examines the pharmacokinetics and pharmacodynamics of sedative agents, particularly inhalation anesthetics, and their potential to mimic torpor-like physiological states. Findings: Sedative agents are well characterized for their effects during anesthesia phases but present significant challenges in replicating the protective and metabolic features of torpor. Adapting these agents for spaceflight requires overcoming obstacles such as prolonged drug administration, limited arousal control, and counteracting the adverse effects of microgravity and radiation exposure. Synthetic torpor offers potential as a countermeasure to the challenges of long-haul space exploration. However, its implementation requires addressing the limitations of current sedative agents and optimizing them for extended use. Inhalation anesthetics demonstrate promise but require further investigation into their safety, efficacy, and long-term effects in spaceflight conditions. Conclusion: Inducing a torpor-like state with sedative agents represents a promising avenue for supporting long-duration human space missions. Further research is needed to refine the pharmacological approaches, ensure safety, and enhance the protective effects against spaceflight stressors.