The emergence of privatized commercial spaceflight is expected to afford to pay customers, including those with preexisting health conditions, the opportunity to fly in space. Prospective spaceflight companies and their medical departments will guide their suborbital participants and will also increasingly depend on health documentation from clinicians who may not be familiar with the specific challenges of various activities and mission profiles related to spaceflight. Current U.S. law, enforced by the Department of Transportation’s Federal Aviation Administration (FAA), Office of Commercial Space Transportation, mandates that prospective spaceflight participants provide written informed consent after having a clear understanding of the inherent risks of the flight. Although pilots flying various privatized commercial space vehicles are required to hold a second-class FAA medical certificate with its attendant medical requirements,8,9 there are currently no medically binding criteria for determining a participant’s suitability for prospective commercial spaceflight, beyond guidelines from several aerospace specialty organizations.
Space medicine is a broad clinical discipline that encompasses the many challenges facing humans engaged in spaceflight and other aerospace activities. Threats in the space environment vary according to the duration of the flight and range from physiological and adaptive alterations of the human body to the psychological challenges of isolation and distance from Earth. The responsibility for understanding the ramifications of participants’ preexisting medical conditions and for ensuring the safety of participants in the expanding spaceflight industry will fall to many clinicians in collaboration with dedicated space medicine specialists and the aerospace community in general. Data and experience gleaned from training and flights will, over time, help determine the need for additional medical recommendations for persons with certain medical conditions.
There are numerous emergency or off-nominal situations in spaceflight. An example is the loss of integrity of a pressurization system (vehicle or space suits), which can result in severe hypoxia or decompression illnesses. This review, however, focuses on the expected and straightforward challenges of spaceflight and aims to provide the practicing clinician with an appreciation of the unique medical and environmental challenges in light of the expected increase in civilian spaceflight.
Medical and Environmental Challenges According to the Type of Spaceflight.
The specific medical challenges and risks inherent in any space mission are defined by the duration and trajectory of the flight (Table 1). A suborbital spaceflight by definition reaches an altitude of more than 100 km above mean sea level; suborbital space flights are typical of short duration (a matter of minutes), whereas orbital spaceflights, such as flights to the International Space Station, can last from days to many months. Missions to the moon will typically be of extended duration, and missions to Mars are likely to require several years. The importance of these differences in duration lies in their very different medical-risk profiles. For example, with flights that are suborbital or in low Earth orbit, the Earth’s magnetic field and atmosphere provide shielding from space radiation. Missions beyond low Earth orbit (e.g., flights to the moon or Mars) present notable challenges because of factors such as substantial radiation exposure to the human body from the ubiquitous galactic cosmic radiation and possible coronal mass ejections from our sun, and the risks increase with prolonged exposure.
Although suborbital microgravity exposures of a few minutes are unlikely to cause many adaptive symptoms, participants remaining in orbit for more extended periods may be susceptible to the development of space motion sickness, manifested as nausea, headache, and emesis, especially during the first few days. Spatial orientation in a three-dimensional microgravity environment changes from gravity-dependent neurovestibular inputs on Earth to reliance on primarily visual reference points in spaceflight. This transition occurs during the first 48 to 72 hours of exposure when persons are particularly sensitive to space motion sickness and may have impaired performance of tasks such as visual tracking and hand-eye coordination. Space motion sickness can detract from the enjoyment of the first few days of spaceflight and may require the use of antiemetic medications, which can have unwanted side effects.
Short-Term and Long-Term Physiological Alterations Associated with Spaceflight.
Prolonged stays in microgravity environments result in clinically significant physiological adaptations and alterations of the human body. Because of the absence of gravity-induced hydrostatic pressure gradients, there is a fluid shift from the periphery of the body to the central compartment and head, frequently resulting in facial puffiness and congestion and occasionally causing a headache. Over a period of several days, the body compensates for this fluid shift through diuresis, which reduces extracellular fluid and plasma volume and is associated with a decrease in body mass during the first 30 days in the microgravity environment (compounded by altered metabolic requirements and altered appetite), followed by stabilization at a new steady-state level.16 Cardiac function swiftly adapts to the fluid shift–related alterations with compensatory increases in cardiac output.17 Fortunately, no cardiac severe dysrhythmias or alterations are known to be caused by spaceflight.
Because of the absence of hydrostatic pressure gradients, baroreceptor responses are gradually attenuated in proportion to the amount of time spent in microgravity (e.g., measurable changes can be observed after approximately four days in microgravity, as described during Space Shuttle missions).20,21 On the return to Earth, this baroreceptor attenuation can initially result in orthostatic hypotension, until gradual readaptation to terrestrial gravity occurs. Pulmonary function and gas exchange does not appear to be negatively affected and, hence, should not limit human performance in microgravity. The absence of natural ambient airflow patterns raises the possibility of a relative accumulation of exhaled carbon dioxide surrounding a person, which can lead to a gradual increase in carbon dioxide through rebreathing of the exhaled air. This concern is addressed by adequate air circulation in enclosed areas of space vehicles, as well as efficient carbon dioxide scrubbing (i.e., absorption and removal of carbon dioxide) in the space vehicle atmosphere.
Prolonged exposure to microgravity can lead to a slight lengthening of the vertebral spine and skeletal deconditioning.24 These factors are associated with an increased incidence of back pain and an increased risk of intervertebral disk herniation.25 Participants in spaceflight who remain in orbit for days to weeks may have this discomfort; in particular, persons with preexisting back or neck conditions or chronic pain may be susceptible to exacerbation of underlying signs and symptoms. The near absence of gravity also leads to relative changes in abdominal organ position, with a headward shift of the diaphragm, influencing findings on physical examination and imaging studies such as ultrasonography. This diaphragmatic shift also causes a 15% decrease in functional residual capacity and a mild decrease in ventilation, which appear to have a minimal effect on gas exchange and alveolar ventilation because of improved ventilation–perfusion matching in the absence of gravity. Sleep aboard space vehicles is often suboptimal because of multiple factors, including ambient noise, a tight operational schedule, circadian dysregulation, congestion due to fluid shifts, back discomfort, and an unfamiliar sleeping environment with a lack of gravity-related proprioceptive input.
Additional system-specific concerns have been reported even for short spaceflights. For example, there have been several case reports of urinary retention in the first days after entering microgravity.28,29 Typically, this condition is self-resolving and rarely requires a temporary period of self-catheterization. However, for the lay participant, such experiences may greatly reduce enjoyment of the flight. Furthermore, self-catheterization adds additional risks such as microtrauma and the introduction of infection, altering the mission risk profile and introducing a potential need for more comprehensive medical evaluation or care.
Prolonged sojourns in microgravity result in loss of bone mineralization due to the unloading of the skeleton. Loss of bone mineral density has been shown in the lumbar spine, pelvis, trochanter, femoral neck, and calcaneus.30 Certain areas of the skeleton have no detrimental change (e.g., the ulna and radius) and some may have an increase in bone density (the skull). Bone density loss is a severe concern for long missions (e.g., a flight to Mars); however, countermeasures such as consistent resistance and aerobic exercise, nutritional support, and use of antiresorptive medications have been shown to help preserve bone density. In line with the potential loss of bone mineral density, loss of skeletal muscle strength is a serious concern during long spaceflights.33 Skeletal-muscle loss can contribute to postflight orthostatic symptoms on reexposure to gravity and may hamper the ability to safely carry out tasks required on the return to Earth or arrival at a more distant destination, such as the surface of Mars. The detrimental effects of prolonged microgravity on bone and muscular architecture are more likely to affect career astronauts until participants in commercial spaceflights have opportunities to take part in extended missions.
In 2011, a sentinel case of unusual neuro-ocular symptoms associated with long-duration spaceflight was reported. This led to the recognition of a constellation of symptoms that define spaceflight-associated neuro-ocular syndrome, or SANS. Findings include variable optic disk edema, refractive changes (distance vision more affected than near vision) that are often unilateral (right eye affected more often than left eye), and infarcts in the nerve-fiber layer with associated cotton wool spots.35-38 Flattening of the optic globe can be identified on magnetic resonance imaging, and ocular coherence tomography can show venous engorgement and choroidal thickening or folding. It has been postulated that this syndrome may be related to intracranial hypertension associated with microgravity-induced fluid shifts, though this hypothesis continues to undergo review and consideration of alternative explanations.37 Recent findings suggest that the syndrome may be associated with body mass and potential alterations in one-carbon metabolism pathways.39 The syndrome is currently the focus of intensive study; at this point, it remains unclear whether SANS could pose a severe risk to participants in future spaceflights of long duration or whether any preexisting morphologic, genetic, or physiological factors might alter or help predict and mitigate this risk.
Limitations of Medical Support
Medical support capabilities are inherently limited during spaceflights,40 reinforcing the need for careful mission planning and assessment of medical risk for each participant. The safety of a short suborbital flight rests in the ability to return to medical support infrastructure on the ground swiftly. It is unlikely that commercial spaceflight vehicles will carry medical resources or attendants with medical skills; therefore, management of any medical event occurring during flight will probably take place only after landing. In the event of a severe injury during a long flight, the probability of a successful medical evacuation or complex longer-term care while on board the space vehicle is low. Medical support during longer-duration missions in low Earth orbit, such as aboard the International Space Station, is provided by communication with medical teams on the ground and resources that are available aboard the orbiting station, including medical supplies (e.g., medications and blood products) — which are limited in variety, amount, and shelf life — and a limited supply of medical equipment, such as ultrasound machines. Medical support is also provided by medical officers who are part of the crew. Erosion of critical emergency skills on the part of these medical officers can occur and can be mitigated by just-in-time refresher training. Increasing distance from Earth introduces a communications delay — up to 40 minutes for Mars missions — that poses a challenge to real-time emergency assistance (e.g., telemedicine guidance from ground-based medical support); furthermore, evacuating and returning to Earth is no longer possible.42,43 Therefore, onboard medical expertise will be of even higher value.
The FAA is responsible for the regulation of commercial space transportation in the United States and has commissioned studies of human health and performance in commercial spaceflight. Three studies have been performed to date that has specifically investigated the ability of laypersons to tolerate the stresses of simulated suborbital spaceflights.12,13,47 The participants in these studies were subjected to centrifuge tests simulating the acceleration profiles (+Gx and +Gz) that are expected to occur on suborbital spaceflights. The study participants ranged from 19 to 89 years of age and had a large variety of stable medical conditions that are prevalent in the general population, including hypertension, pulmonary disease, stable coronary artery disease, and diabetes; some of the participants were taking medications to treat their disorders. Participants with well-controlled medical conditions were able to tolerate the acceleration profiles in the centrifuge without difficulty physiologically. However, 6% of the study participants chose to stop the centrifuge exposure, most often because of anxiety or motion sickness, and 14% of participants had unsafe or potentially problematic behaviors.
The importance of gathering and publishing data from the training of prospective spaceflight participants in order to inform and enhance safety and mitigate risks cannot be overstated. Fortunately, it appears that most participants in spaceflight are very willing to take part in biomedical studies and even to voluntarily provide their data for review and publication. Even so, it is likely that many advances in our understanding of how the average person performs during spaceflight will be achieved only after commercial spaceflight becomes more commonplace and aggregate data are gathered and reported in the medical literature.
The challenge for space medicine professionals rests in the limited amount of time they will be able to spend with commercial spaceflight participants, whereas members of the medical support staff work closely with professional astronauts and spend many months training as a team. The Code of Federal Regulations stipulates that the training of prospective spaceflight participants is to be focused on their ability “to be able to respond in case of an emergency.” There are no specified training requirements beyond that generic statement. Active collaboration among future spaceflight participants, the clinicians who care for them, and the industry operators is necessary to understand the risks for individual participants, their capacity for informed consent, and their training needs in order to ensure an appropriate response in the case of an emergency.
The preparation and training will undoubtedly be less rigorous for a short suborbital flight than for an extended stay in low Earth orbit or a lunar mission. Participants in suborbital spaceflight will need some degree of team training and practice of emergency procedures; they also will possibly need training in an analog environment, such as centrifuge exposures, parabolic flights, and altitude-chamber training, to become familiar with environmental stressors and life-support systems. Participants in longer-duration missions, especially persons with preexisting health conditions who are critically reliant on a healthy immune system, may also be subject to the known effects of the spaceflight environment (thought to be mediated by radiation and stress responses) on immune function. Alterations in T-cell function, the skin microbiome, and bacterial virulence, as well as asymptomatic viral reactivation, have been described.49-52 From current data, it is difficult to definitively discern which factors in humans appear to be the root cause for some of the alterations that have been reported (e.g., an increase in the neutrophil count after landing as a result of the stresses of reentry and readaptation). Deliberate attention to these aspects in preparation for the spaceflight, medical assessment, and preventive strategies may be warranted. The diagnosis of any clinically significant allergies (e.g., food allergies) before prolonged spaceflights may be of particular importance as well.
The FAA has indicated a preference for participant autonomy, explicitly stating that those desiring to participate in spaceflight have the right and responsibility to make their own decisions regarding risk and informed consent.53 The administration has placed the burden of education on the spaceflight industry itself, requiring that commercial operators inform all potential spaceflight participants of all spaceflight-related risks and ensure that participants understand these risks before consenting to participate.1,2 However, it is difficult to legally show that participants fully understand their risks and the legality of their consent, raising concern about potential liability despite the consent process. It is unlikely that even the mandated informed-consent process will prevent the potential for legal claims between participants and industry providers in the case of mishap or injury.54,55
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