Characterizing dehydration in short-term spaceflight using evidence from Project Mercury.

Short-term spaceflight is commonly perceived as posing minimal risk to human health and performance. However, despite their duration, short-term flights potentially induce acute physiological changes that create risk to crews. One such change is dehydration (primarily body water loss) due to a heat-stressed environment. Such loss, if severe and prolonged, can lead to decrements in performance as well as increase the risk of more serious medical conditions. Though the general mechanisms of dehydration are broadly understood, the rate and extent of dehydration in short-term spaceflight has not been characterized. Combining data from the six spaceflights of the US Mercury program with a causal diagram illustrating the mechanisms of dehydration, we fit a path model to estimate the causal effects for all pathways in the causal model. Results demonstrate that Mercury astronauts experienced some degree of dehydration across the range of suited time and that the relationship between suited time and dehydration appears to be logarithmic. We discuss causal interpretations of the results and how the results from this and similar analyses can inform countermeasure development for short-term spaceflight.

Causal diagramming for assessing human system risk in spaceflight.

For over a decade, the National Aeronautics and Space Administration (NASA) has tracked and configuration-managed approximately 30 risks that affect astronaut health and performance before, during and after spaceflight. The Human System Risk Board (HSRB) at NASA Johnson Space Center is responsible for setting the official risk posture for each of the human system risks and determining-based on evaluation of the available evidence-when that risk posture changes. The ultimate purpose of tracking and researching these risks is to find ways to reduce spaceflight-induced risk to astronauts. The adverse effects of spaceflight begin at launch and continue throughout the duration of the mission, and in some cases, across the lifetime of the astronaut. Historically, research has been conducted in individual risk "silos" to characterize risk, however, astronauts are exposed to all risks simultaneously. In January of 2020, the HSRB at NASA began assessing the potential value of causal diagramming as a tool to facilitate understanding of the complex causes and effects that contribute to spaceflight-induced human system risk. Causal diagrams in the form of directed acyclic graphs (DAGs) are used to provide HSRB stakeholders with a shared mental model of the causal flow of risk. While primarily improving communication among those stakeholders, DAGs also allow a composite risk network to be created that can be tracked and configuration managed. This paper outlines the HSRB's pilot process for this effort, the lessons learned, and future goals for data-driven risk management approaches.

Levels of evidence for human system risk evaluation.

NASA uses a continuous risk management process to seek out new knowledge of spaceflight-induced risk to human health and performance. The evidence base that informs the risk assessments in this domain is constantly changing as more information is gleaned from a continuous human presence in space and from ongoing research. However, the limitations of this evidence are difficult to characterize because fewer than 700 humans have ever flown in space, and information comes from a variety of sources that span disciplines, including engineering, medicine, food and nutrition, and many other life sciences. The Human System Risk Board (HSRB) at NASA is responsible for assessing risk to astronauts and communicating this risk to agency decision-makers. A critical part of that communication is conveying the uncertainty regarding the understanding of the changes that spaceflight induces in human processes and the complex interactions between humans and the spacecraft. Although the strength of evidence grades is common in the academic literature, these scores are often not useful for the problems of human spaceflight. The HSRB continues to update the processes used to report the levels of evidence. This paper describes recent updates to the methods used to assign the level of evidence scores to the official risk postures and to the causal diagrams used by the HSRB.

Updates to the NASA human system risk management process for space exploration.

This paper describes updates to NASA's approach for assessing and mitigating spaceflight-induced risks to human health and performance. This approach continues to evolve to meet dynamically changing risk environments: lunar missions are currently being designed and the ultimate destination will be Mars. Understanding the risks that astronauts will face during a Mars mission will depend on building an evidence base that informs not only how the humans respond to the challenges of the spaceflight environment, but also how systems and vehicles can be designed to support human capabilities and limitations. This publication documents updates to the risk management process used by the Human System Risk Board at NASA and includes changes to the likelihood and consequence matrix used by the board, the design reference mission categories and parameters, and the standardized evaluation of the levels of evidence that the board accepts when setting risk posture. Causal diagramming, using directed acyclic graphs, provides all stakeholders with the current understanding of how each risk proceeds from a spaceflight hazard to a mission-level outcome. This standardized approach enables improved communication among stakeholders and delineates how and where more knowledge can improve perspective of human system risks and which countermeasures can best mitigate these risks.

Ocular conditions and injuries, detection and management in spaceflight.

Ocular trauma or other ocular conditions can be significantly debilitating in space. A literature review of over 100 articles and NASA evidence books, queried for eye related trauma, conditions, and exposures was conducted. Ocular trauma and conditions during NASA space missions during the Space Shuttle Program and ISS through Expedition 13 in 2006 were reviewed. There were 70 corneal abrasions, 4 dry eyes, 4 eye debris, 5 complaints of ocular irritation, 6 chemical burns, and 5 ocular infections noted. Unique exposures on spaceflight, such as foreign bodies, including celestial dust, which may infiltrate the habitat and contact the ocular surface, as well as chemical and thermal injuries due to prolonged CO2 and heat exposure were reported. Diagnostic modalities used to evaluate the above conditions in space flight include vision questionnaires, visual acuity and Amsler grid testing, fundoscopy, orbital ultrasound, and ocular coherence tomography. Several types of ocular injuries and conditions, mostly affecting the anterior segment, are reported. Further research is necessary to understand the greatest ocular risks that astronauts face and how better we can prevent, but also diagnose and treat these conditions in space.

Validating Causal Diagrams of Human Health Risks for Spaceflight: An Example Using Bone Data from Rodents.

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web of events that leads from exposure to the spaceflight environment to performance and health outcomes. However, the use of DAGs in this way is relatively new at NASA, and thus far, no method has been articulated for testing their veracity using empirical data. In this paper, we demonstrate a set of procedures for doing so, using (a) a DAG related to the risk of bone fracture after exposure to spaceflight; and (b) four datasets originally generated to investigate this phenomenon in rodents. Tests of expected marginal correlation and conditional independencies derived from the DAG indicate that the rodent data largely agree with the structure of the diagram. Incongruencies between tests and the expected relationships in one of the datasets are likely explained by inadequate representation of a key DAG variable in the dataset. Future directions include greater tie-in with human data sources, including multiomics data, which may allow for more robust characterization and measurement of DAG variables.

Assessment of Sex-Dependent Medical Outcomes During Spaceflight.

Background: In this study sex-differences in medical outcomes during spaceflight are reviewed and probabilistic risk assessment (PRA) is used to assess the impact on spaceflight missions of varying lengths. Materials and Methods: We use PRA to simulate missions of 42 days, 6 months, and 2.5 years. We model medical outcomes using three crews: two men and two women, four women, or four men. Total medical events (TME), crew health index (CHI), probability (0-1) of medical evacuation (pEVAC), probability of loss of crew life (pLOCL), and influential medical conditions were determined. Results: No differences were seen in any metric for the 42-day mission. There were no differences seen for any mission length, in any crew, for TME, CHI, pLOCL, or environmental causes of pEVAC. Sex-dependent differences are seen for rates of nonemergent pEVAC during the 6 month and 2.5-year missions, where women have a higher pEVAC in the 182-day (0.0388 vs. 0.0354) and 2.5-year missions (0.350 vs. 0.228). These differences were driven by higher incidence of partially treated urinary tract infection (UTI). In the 2.5 year mission, with resupply of medical resources, the influence of UTI in women on pEVAC decreases (0.35-0.11). Conclusion: Although resupply is unlikely for deep space missions, modeled results suggest that sex-specific medical needs can be readily managed through preventive measures and inclusion of appropriate medical capabilities. Within its many limitations, PRA is a useful tool to estimate medical risks in unique environments where only expert opinion was previously available.

Estimating medical risk in human spaceflight.

NASA and commercial spaceflight companies will soon be retuning humans to the Moon and then eventually sending them on to Mars. These distant planetary destinations will pose new risks-in particular for the health of the astronaut crews. The bulk of the evidence characterizing human health and performance in spaceflight has come from missions in Low Earth Orbit. As missions last longer and travel farther from Earth, medical risk is expected to contribute an increasing proportion of total mission risk. To date, there have been no reliable estimates of how much. The Integrated Medical Model (IMM) is a Probabilistic Risk Assessment (PRA) Monte-Carlo simulation tool developed by NASA for medical risk assessment. This paper uses the IMM to provide an evidence-based, quantified medical risk estimate comparison across different spaceflight mission durations. We discuss model limitations and unimplemented capabilities providing insight into the complexity of medical risk estimation for human spaceflight. The results enable prioritization of medical needs in the context of other mission risks. These findings provide a reasonable bounding estimate for medical risk in missions to the Moon and Mars and hold value for risk managers and mission planners in performing cost-benefit trades for mission capability and research investments.

Probabilistic Risk Assessment of Prophylactic Surgery Before Extended-Duration Spaceflight.

Introduction. Prophylactic surgery before spaceflight may eliminate the risk of appendicitis and cholecystitis in astronauts on deep space missions. However, even minimally invasive surgery increases the risk of small bowel obstruction (SBO). Probabilistic risk assessment (PRA) is a method that can be used to estimate the benefits and risks of prophylactic surgery. Methods. Risks of appendicitis and cholecystitis during a 2.5-year Mars mission are compared to the risk of SBO after laparoscopic removal of the appendix, gallbladder, or both. A PRA model using Monte Carlo methodology was used to forecast the risks. Results. Prophylactic appendectomy and cholecystectomy combined, conferred an increased probability of medical evacuation (pEVAC) due to SBO as compared to the no surgery group. A slightly higher probability for the loss of crew life (pLOCL) was found in the no surgery group when compared to the cases in which either prophylactic appendectomy alone, or appendectomy plus cholecystectomy are performed. Discussion. The need for medical evacuation can be viewed as a potential risk for death in the context of a space mission where evacuation is not possible. Because of the higher pEVAC due to SBO and relatively small benefit in the reduction of pLOCL in the prophylactic surgery groups, this analysis does not support the prophylactic removal of appendix and/or gallbladder for spaceflight. Future advances in surgical or medical technique or mission medical capabilities may change these results. This work demonstrates the utility of PRA in providing quantitative answers to "what if" questions where limited information is available.

Gynecologic Risk Mitigation Considerations for Long-Duration Spaceflight.

INTRODUCTION: As NASA and its international partners, as well as the commercial spaceflight industry, prepare for missions of increasing duration and venturing outside of low-Earth orbit, mitigation of medical risk is of high priority. Gynecologic considerations constitute one facet of medical risk for female astronauts. This manuscript will review the preflight, in-flight, and postflight clinical evaluation, management, and prevention considerations for reducing gynecologic and reproductive risks in female astronauts.METHODS: Relevant gynecological articles from databases including Ovid, Medline, Web of Science, various medical libraries, and NASA archives were evaluated for this review. In particular, articles addressing preventive measures or management of conditions in resource-limited environments were evaluated for applicability to future long-duration exploration spaceflight.RESULTS: Topics including abnormal uterine bleeding, anemia, bone mineral density, ovarian cysts, venous thromboembolism, contraception, fertility, and health maintenance were reviewed. Prevention and treatment strategies are discussed with a focus on management options that consider limitations of onboard medical capabilities.DISCUSSION: Long-duration exploration spaceflight will introduce new challenges for maintenance of gynecological and reproductive health. The impact of the space environment outside of low-Earth orbit on gynecological concerns remains unknown, with factors such as increased particle radiation exposure adding complexity and potential risk. While the most effective means of minimizing the impact of gynecologic or reproductive pathology for female astronauts is screening and prevention, gynecological concerns can arise unpredictably as they do on Earth. Careful consideration of gynecological risks and potential adverse events during spaceflight is a critical component to risk analysis and preventive medicine for future exploration missions.Steller JG, Blue RS, Burns R, Bayuse TM, Antonsen EL, Jain V, Blackwell MM, Jennings RT. Gynecologic risk mitigation considerations for long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(7):543-564.

Challenges in Clinical Management of Radiation-Induced Illnesses During Exploration Spaceflight.

INTRODUCTION: Analysis of historical solar particle events (SPEs) provides context for some understanding of acute radiation exposure risk to astronauts who will travel outside of low-Earth orbit. Predicted levels of radiation exposures to exploration crewmembers could produce some health impacts, including nausea, emesis, and fatigue, though more severe clinical manifestations are unlikely. Using current models of anticipated physiological sequelae, we evaluated the clinical challenges of managing radiation-related clinical concerns during exploration spaceflight.METHODS: A literature review was conducted to identify terrestrial management standards for radiation-induced illnesses, focusing on prodromal symptom treatment. Terrestrial management was compared to current spaceflight medical capabilities to identify gaps and highlight challenges involved in expanding capabilities for future exploration spaceflight.RESULTS: Current spaceflight medical resources, such as those found on the International Space Station, may be sufficient to manage some aspects of radiation-induced illness, although effective treatment of all potential manifestations would require substantial expansion of capabilities. Terrestrial adjunctive therapies or more experimental treatments are unavailable in current spaceflight medical capabilities but may have a role in future management of acute radiation exposure.DISCUSSION: Expanded medical capabilities for managing radiation-induced illnesses could be included onboard future exploration vehicles. However, this would require substantial research, time, and funding to reach flight readiness, and vehicle limitations may restrict such capabilities for exploration missions. The benefits of including expanded capabilities should be weighed against the likelihood of significant radiation exposure and extensive mission design constraints.Blue RS, Chancellor JC, Suresh R, Carnell LS, Reyes DP, Nowadly CD, Antonsen EL. Challenges in clinical management of radiation-induced illnesses during exploration spaceflight. Aerosp Med Hum Perform. 2019; 90(11):966-977.

Blood transfusion for deep space exploration.

BACKGROUND: Astronauts on exploration missions may be at risk for traumatic injury and medical conditions that lead to life threatening hemorrhage. Resuscitation protocols are limited by the austere conditions of spaceflight. Solutions may be found in low-resource terrestrial settings. The existing literature on alternative blood product administration and walking blood banks was evaluated for applicability to spaceflight. STUDY DESIGN AND METHODS: A literature review was done using PubMed and Google Scholar. References were crosschecked for additional publications not identified using the initial search terms. Twenty-seven articles were identified, including three controlled trials, six retrospective cohort analyses, 15 reviews, one case report, and two experimental studies. RESULTS: Solutions to blood transfusion in austere settings include lyophilized blood products, hemoglobin-based oxygen carriers (HBOCs), and fresh whole blood. Many of these products are investigational. Protocols for walking blood banks include methods for screening and activating donors, transfusion, and monitoring for adverse reactions. Microgravity and mission limitations create additional challenges for transfusion, including baseline physiologic changes, difficulty reconstituting lyophilized products, risk of air emboli during transfusion, equipment constraints, and limited evacuation and surgical options. CONCLUSION: Medical planning for space exploration should consider the possibility of acute blood loss. A model for "floating" blood banks based on terrestrial walking blood bank protocols from austere environments is presented, with suggestions for future development. Constraints on volume, mass, storage, and crew, present challenges to blood transfusion in space and must be weighed against the benefits of expanding medical capabilities.

Limitations in predicting radiation-induced pharmaceutical instability during long-duration spaceflight.

As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners face numerous challenges related to ensuring the safety of their astronauts, including the need to provide a safe and effective pharmacy for long-duration spaceflight. Historical missions have relied upon frequent resupply of onboard pharmaceuticals; as a result, there has been little study into the effects of long-term exposure of pharmaceuticals to the space environment. Of particular concern are the long-term effects of space radiation on drug stability, especially as missions venture away from the protective proximity of the Earth. Here we highlight the risk of space radiation to pharmaceuticals during exploration spaceflight, identifying the limitations of current understanding. We further seek to identify ways in which these limitations could be addressed through dedicated research efforts aimed toward the rapid development of an effective pharmacy for future spaceflight endeavors.

Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding.

In order to maintain crew health and performance during long-duration spaceflight outside of low-Earth orbit, NASA and its international partners must be capable of providing a safe and effective pharmacy. Given few directed studies of pharmaceuticals in the space environment, it is difficult to characterize pharmaceutical effectiveness or stability during spaceflight; this in turn makes it challenging to select an appropriate formulary for exploration. Here, we present the current state of literature regarding pharmaceutical stability, metabolism, and effectiveness during spaceflight. In particular, we have attempted to highlight the gaps in current knowledge and the difficulties in translating terrestrial-based drug studies to a meaningful interpretation of drug stability, safety, and effectiveness in space. We hope to identify high-yield opportunities for future research that might better define and mitigate pharmaceutical risk for exploration missions.

Should NASA Collect Astronauts' Genetic Information for Occupational Surveillance and Research?

Humans exploring beyond low-Earth orbit face environmental challenges coupled with isolation, remote operations, and extreme resource limitations in which personalized medicine, enabled by genetic research, might be necessary for mission success. With little opportunity to test personalized countermeasures broadly, the National Aeronautics and Space Administration (NASA) will likely need to rely instead on collection of significant amounts of genomic and environmental exposure data from individuals. This need appears at first to be in conflict with the statutes and regulations governing the collection and use of genetic data. In fact, under certain conditions, the Genetic Information Nondiscrimination Act (GINA) of 2008 allows for the use of genetic information in both occupational surveillance and research and in the development of countermeasures such as personalized pharmaceuticals.

Ultrasound diagnosis and therapeutic intervention in the spine.

Spine pathology afflicts people across the globe and is responsible for a large portion of physician visits and healthcare costs. Imaging such as plain radiographs, CT, MRI, and ultrasound is vital to assess structure, function, and stability of the spine and also provide guidance in therapeutic interventions. Ultrasound utilization in spine conditions is less ubiquitous, but provides benefits in low costs, portability, and dynamic imaging. This study assesses ultrasound efficacy in diagnosis and therapeutic interventions for spine pathology. A systematic review conducted via PubMed, MEDLINE, and Google Scholar identified 3,630 papers with eventual inclusion of 73 papers with an additional 21 papers supplemental papers subsequently added. Findings highlighted ultrasound utilization for different structural elements of the spine such as muscle, bone, disc, ligament, canal, and joints are presented and compared with radiographs, CT, and MRI imaging where relevant. Spinal curvature and mobility are similarly presented. Ultrasound efficacy for guided therapeutics about the spine is presented and assessed against other modalities. Ultrasound is a widely used and efficacious modality to guide injections about the spine. Diagnostic utility is less well studied, but shows promise in assessing fractures, posterior ligamentous stability, and intra-operative hardware placement. The low cost, portability, and dynamic imaging ability make it an attractive modality particularly for developing health systems and resource limited environments such as combat settings and the International Space Station. Further study is recommended before broad adoption in diagnostics.

Effects of spaceflight on cartilage: implications on spinal physiology.

Spaceflight alters normal physiology of cells and tissues observed on Earth. The effects of spaceflight on the musculoskeletal system have been thoroughly studied, however, the effects on cartilage have not. This area is gaining more relevance as long duration missions, such as Mars, are planned. The impact on intervertebral discs and articular cartilage are of particular interest to astronauts and their physicians. This review surveys the literature and reports on the current body of knowledge regarding the effects of spaceflight on cartilage, and specifically changes to the spine and intervertebral disc integrity and physiology. A systematic literature review was conducted using PubMed, MEDLINE, and Google Scholar. Eighty-six unique papers were identified, 15 of which were included. The effect of spaceflight on cartilage is comprehensively presented due to limited research on the effect of microgravity on the spine/intervertebral discs. Cellular, animal, and human studies are discussed, focusing on human physiologic changes, cartilage histology, mineralization, biomechanics, chondrogenesis, and tissue engineering. Several common themes were found, such as decreased structural integrity of intervertebral disks and impaired osteogenesis/ossification. However, studies also presented conflicting results, rendering strong conclusions difficult. The paucity of human cartilage studies in spaceflight leaves extrapolation from other model systems the only current option for drawing conclusions despite known and unknown limitations in applicability to human physiology, especially spinal pathophysiology which is special interest. The aerospace and biomedical research communities would benefit from further human spaceflight articular cartilage and intervertebral disc studies. Further research may yield beneficial application for spaceflight, and crossover in understanding and treating terrestrial diseases like osteoarthritis and vertebral disc degeneration.

Prototype Development of a Tradespace Analysis Tool for Spaceflight Medical Resources.

INTRODUCTION: The provision of medical care in exploration-class spaceflight is limited by mass, volume, and power constraints, as well as limitations of available skillsets of crewmembers. A quantitative means of exploring the risks and benefits of inclusion or exclusion of onboard medical capabilities may help to inform the development of an appropriate medical system. A pilot project was designed to demonstrate the utility of an early tradespace analysis tool for identifying high-priority resources geared toward properly equipping an exploration mission medical system. METHODS: Physician subject matter experts identified resources, tools, and skillsets required, as well as associated criticality scores of the same, to meet terrestrial, U.S.-specific ideal medical solutions for conditions concerning for exploration-class spaceflight. A database of diagnostic and treatment actions and resources was created based on this input and weighed against the probabilities of mission-specific medical events to help identify common and critical elements needed in a future exploration medical capability. RESULTS: Analysis of repository data demonstrates the utility of a quantitative method of comparing various medical resources and skillsets for future missions. Directed database queries can provide detailed comparative estimates concerning likelihood of resource utilization within a given mission and the weighted utility of tangible and intangible resources. DISCUSSION: This prototype tool demonstrates one quantitative approach to the complex needs and limitations of an exploration medical system. While this early version identified areas for refinement in future version development, more robust analysis tools may help to inform the development of a comprehensive medical system for future exploration missions.Antonsen EL, Mulcahy RA, Rubin D, Blue RS, Canga MA, Shah R. Prototype development of a tradespace analysis tool for spaceflight medical resources. Aerosp Med Hum Perform. 2018; 89(2):108-114.

Point-of-Care Ultrasound for Pulmonary Concerns in Remote Spaceflight Triage Environments.

INTRODUCTION: With the development of the commercial space industry, growing numbers of spaceflight participants will engage in activities with a risk for pulmonary injuries, including pneumothorax, ebullism, and decompression sickness, as well as other concomitant trauma. Medical triage capabilities for mishaps involving pulmonary conditions have not been systematically reviewed. Recent studies have advocated the use of point-of-care ultrasound to screen for lung injury or illness. The operational utility of portable ultrasound systems in disaster relief and other austere settings may be relevant to commercial spaceflight. METHODS: A systematic review of published literature was conducted concerning the use of point-of-care pulmonary ultrasound techniques in austere environments, including suggested examination protocols for triage and diagnosis. RESULTS: Recent studies support the utility of pulmonary ultrasound examinations when performed by skilled operators, and comparability of the results to computed tomography and chest radiography for certain conditions, with important implications for trauma management in austere environments. DISCUSSION: Pulmonary injury and illness are among the potential health risks facing spaceflight participants. Implementation of point-of-care ultrasound protocols could aid in the rapid diagnosis, triage, and treatment of such conditions. Though operator-dependent, ultrasound, with proper training, experience, and equipment, could be a valuable tool in the hands of a first responder supporting remote spaceflight operations.Johansen BD, Blue RS, Castleberry TL, Antonsen EL, Vanderploeg JM. Point-of-care ultrasound for pulmonary concerns in remote spaceflight triage environments. Aerosp Med Hum Perform. 2018; 89(2):122-129.

Point-of-Care Ultrasound Utility and Potential for High Altitude Crew Recovery Missions.

INTRODUCTION: Flights to high altitude can lead to exposure and unique pathology not seen in normal commercial aviation. METHODS: This paper assesses the potential for point-of-care ultrasound to aid in management and disposition of injured crewmembers from a high altitude incident. This was accomplished through a systematic literature review regarding current diagnostic and therapeutic uses of ultrasound for injuries expected in high altitude free fall and parachuting. RESULTS: While current research supports its utility in diagnostics, therapeutic procedures, and triage decisions, little research has been done regarding its utility in high altitude specific pathology, but its potential has been demonstrated. DISCUSSION: An algorithm was created for use in high altitude missions, in the event of an emergency descent and traumatic landing for an unconscious and hypotensive pilot, to rule out most life threatening causes. Each endpoint includes disposition, allowing concise decision-making.Galdamez LA, Clark JB, Antonsen EL. Point-of-care ultrasound utility and potential for high altitude crew recovery missions. Aerosp Med Hum Perform. 2017; 88(2):128-136.