Space Medicine: The New Frontier

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Chapter 114 Space Medicine

The New Frontier

For online-only figures, please go to www.expertconsult.com image

Wilderness medicine is often about making do with less, and providing care in an austere or hostile environment where medical personnel and resources are limited or absent. The space environment embodies this frontier medicine attitude; not only are there constraints associated with available medical capabilities but also the very physiology of the casualties themselves is altered and pathology may present in unusual ways. Space is arguably the most hostile wilderness humans have ever faced. It is an “extreme environment,” imposing direct (e.g., radiation) and indirect (e.g., isolation) challenges.

If space is, as one Doctor McCoy might suggest, the “final frontier,” then space medicine largely remains the “undiscovered country.” Relatively little is known about how the human body adapts to and recovers from long-term exposure to microgravity (notated as “µG” or, for many practical purposes, “0G”), let alone the best ways to treat illness or injury that occurs in space. Even less is known about how the less screened and minimally trained tourist population will be affected by short- or long-duration spaceflight with the anticipated advent of commercial space operations.41,59

Future missions to the Moon and Mars will require not only application of lessons learned from past flights but also additional investigation into the best ways to safeguard the health of travelers as they transition first from the 1G environment of Earth to the free fall of interplanetary space, then to the partial gravity of the Moon or Mars, and then back again in reverse for the trip home. Each of these environments may require a new approach to risk management, unique equipment and procedures, and an improved understanding of how and when the physiologic changes associated with microgravity (or partial gravity) occur.

Today the spectrum of manned space includes flights by a range of state agencies, and commercial vehicle suppliers from suborbital flight to the International Space Station. Additionally, long-range planning is underway by NASA and its partners for further exploration missions beyond Earth’s orbit and into the solar system.

Each type of mission presents physiologic and psychological challenges. For example, very short duration suborbital flights by private companies are anticipated to cater to passengers from the general public whose levels of health and fitness are no greater than that of a commercial airline passenger and who may carry pathology heretofore not experienced in the space environment. At the other end of the spectrum, a Mars mission may have medical evacuation capabilities akin to the Lewis and Clark expedition (though they will presumably not meet any helpful natives along the way) and resupply lines similar to those of early explorers into the Australian interior. The psychological challenges are immense, rivaling those of long-distance solo sailors, submariners, or Antarctic winter-over teams and may pose the most significant hurdle for crews to overcome.

In order to provide the best possible care for their patients and ensure success of the mission, space medicine physicians must make use of the knowledge acquired by all those previous groups, as well as lessons from wilderness medicine.

Historical Perspective—X-15 To The Iss And Beyond

There have been very few suborbital* flights in the history of human space flight (Table 114-1, A). These early flights in the “Space Race” demonstrated human survivability in the space environment and tested early technology. Once these objectives were accomplished, attention shifted to orbital and lunar flights.

Until recently, U.S. suborbital flights were limited to two 1961 NASA Mercury flights and two 1963 USAF North American Aviation X-15 program flights that reached an altitude of 100 km (62 miles). In 2004, after a 40-year hiatus, the X-Prize flights by Scaled Composites LLC’s SpaceShip One were heralded as ushering in a new era of commercial space flight to suborbital heights.

Back in the 1960s, the Mercury program was designed to evaluate physiologic responses to the space-flight environment, including:

The suborbital Mercury flight of Alan B. Shepard Jr. on May 5, 1961, reached a peak of 116 statute miles. He was weightless for less than 5 minutes. The second suborbital flight was made by NASA Astronaut I. Virgil “Gus” Grissom on July 21, 1961, to an altitude of 118 statute miles, and distance of 303 miles downrange.

During these suborbital flights, parameters measured were body temperature, respiration (measured by several different methods, none of which gave reliable respiration traces), and electrocardiogram (ECG).

During the Mercury program, life sciences questions tended to focus purely on survivability in the space environment and ignored many of the normal physiologic functions deemed not (yet) relevant. For example, Alan Shepard’s spacesuit for the first Mercury flight Freedom 7 (Figure 114-1 and Table 114-1, B, online) didn’t even provide him with a way to relieve himself (a perhaps forgivable oversight, because the flight was only scheduled to last 15 minutes; unfortunately there was a lengthy delay on the launch pad).61 It was not until the NASA Mercury Project MA-6 mission of John H. Glenn that blood pressure readings were taken.

TABLE 114-1, B Space Exploration Vehicles and Crew Compliment

Vehicle Crewmembers Per Mission Mission
Mercury 1 Orbital
Gemini 2 Orbital with rendezvous and docking tests
Vostok 1 Orbital with rendezvous tests
Voskhod 2-3 Orbital
Apollo 3 Orbital, Moon landing
Soyuz 3 Orbital with docking to Salyut/Mir/ISS
Apollo Soyuz Test Program 5 total Orbital with docking
Skylab 3 Orbital Station
Salyut 2-3 Orbital Station
Shuttle 2-8 Orbital
Mir 3 Orbital Station
ISS 2-6 Orbital Station
Shuttle/ISS 6-13 Docking
Shenzhou 1-2 Orbital

Note: All ISS missions have had visiting vehicles, increasing the crewmembers to a maximum of 13 in March 2009 with the simultaneous docking of STS 119 and Soyuz TMA 14.

Research determined that peak physiologic responses were closely related to critical in-flight events. The Mercury astronauts showed themselves capable of normal physiologic function and performance during launch, in-flight, and reentry. They tolerated the acceleration and vibration well and gave no evidence of motion sickness. The imposed heat loads caused discomfort upon occasion, but did not become a limiting factor during the missions.

All six NASA Mercury crewmembers returned to Earth in healthy condition. They were able to conduct complex visual-motor coordination tasks proficiently in the weightless state, and no evidence of physiologic dysfunction occurred during the flights. The principle findings were weight loss due to dehydration with mild cardiovascular impairment. There was some indication of post-flight orthostatic intolerance and hemoconcentration; however, frank signs of orthostatic hypotension were not noted in these suborbital flights.53,96

To carry out the Gemini program’s (1965-1966) flight durations from under 5 hours to nearly 14 days, researchers needed to know how best to help humans survive in the microgravity environment for longer periods, and investigations began into what activities humans could successfully do in that environment. Mission objectives for the Gemini astronauts included subjecting humans (and their equipment) to space flights of up to 2 weeks in duration, accomplishing rendezvous and docking maneuvers with orbiting vehicles, and conducting the first spacewalk (or extravehicular activity [EVA]).

The main physiologic effects experienced and observed in the NASA Gemini missions were:71

During the Apollo program (1968-1972), the body’s reaction to partial gravitational states (i.e., forces between microgravity and Earth’s 1G) became important for the first time, along with questions as to whether the physiologic adjustments to the Moon’s image G would impair the astronauts’ ability to do meaningful work while on the surface. In point of fact, the crew were not only able to drive the lunar rover but also to collect geological samples and to play golf!

The Apollo program findings were similar to those of Gemini, with the addition of:51

Skylab (1973-1974) was America’s first space station, as well as its first attempt to investigate the effects of long-duration (up to 84 days) exposure to microgravity. Associated issues, such as exercise programs, menu variety, and psychological concerns, received heightened attention.

Although the Apollo-Soyuz flight in July 1975 was as much for political purposes as for scientific ones, it added to the knowledge base by allowing comparisons between the Soviet and American methods for handling physiologic adaptations and combining the environmental systems of two very different vehicles.

More recently, the success of the Shuttle program has led to feelings of familiarity and confidence with short-duration (approximately 2-week) flights to low Earth orbit (LEO), but tragically there have also been two total mission failures, resulting in the deaths of 14 crewmembers and loss of the Challenger (OV-99) and Columbia (OV-102) shuttles.

An important legacy of the Shuttle program will be numerous medical and physiologic experiments conducted on board, including those during the four Shuttle/Spacelab Module missions.

The International Space Station (ISS) program began crewed operations in October 2000, with small but increasing numbers of crew. The program now has six permanent crewmembers, with U.S., Russian, European, and Japanese laboratories. Although the ISS missions, along with historical data from the Skylab, Soviet Salyut, and Russian Mir space station programs, have provided information about long-term effects of microgravity on the human body, much of what is “known” has been extrapolated from short-duration Shuttle missions. In addition to lingering questions about the mechanisms of adaptation to and from microgravity, and the associated time courses and best ways to prevent or recover from undesirable changes, research also continues into how ground-based personnel can best support long-duration crews.

Medical Challenges of Spaceflight

Time Course Of Changes And Adaptation To Microgravity

The microgravity environment provokes numerous changes to the space traveler’s physiology. Some of these alterations occur immediately, whereas others have a more delayed onset, and these effects can be short-lived or last for the duration of the mission. As a result, “space normal” physiology can be difficult to define, and the ability of an astronaut to respond to a physiologic insult, such as injury or illness, can also be challenging to predict. This becomes an even more difficult problem with commercial space flight, where the driving force is the need to fly fare-paying passengers whose health may not be optimal in vehicles that are likely to have minimal medical capabilities.

The physiology of the space traveler is most labile during the transition to or from microgravity. Within a few days, the body adapts to its new environment (as described later), but during the first 72 hours following a change to or from microgravity, most of the physiologic processes are in a state of flux. With space tourists on suborbital flights, there may be a rise in medical events because of subclinical conditions that may not be discovered (or admitted to) preflight.41,59

Long-Term Effects

Several physiologic systems exhibit microgravity-related effects over a longer time frame (weeks to months) (Figure 114-2). For short-duration missions, these changes may be minor or even undetectable, but on longer flights, the effects can become pronounced. In some systems, it is unclear whether a “space normal” equilibrium is ever achieved, or whether changes continue so long as the crewmember remains in microgravity. Examples include alterations in red cell mass and bone demineralization.

image

FIGURE 114-2 Time course of physiologic changes.

(From DeHart RL, Davis JR, editors: Fundamentals of aerospace medicine, ed 3, Philadelphia, 2002, Lippincott Williams & Wilkins.)

Effects On Human Physiology

Effects on the Cardiovascular and Pulmonary Systems

The cardiovascular system undergoes several predictable adaptations in response to microgravity. Recalibration of baroreceptor homeostasis occurs after several days in space, likely due to cephalad fluid shifts induced by the microgravity environment27 (Figure 114-3). As a result of these shifts, the carotid baroreceptors sense a (relative) hypervolemia and cause a diuresis. Relative hypovolemia (approximately 10% decrease in total body fluid and a fall in central venous pressure (CVP) from a terrestrial average of 7 to 10 mm Hg to 0 to 2 mm Hg) then exists compared with preflight terrestrial fluid status.15 The fluid shift may also be associated with development of space motion sickness (SMS), with resultant nausea and vomiting that lead to further loss of fluids.

Although there is still debate on the effects of microgravity on hemodynamic parameters, the most recent data suggest that heart rate and diastolic blood pressure decrease and cardiac output increases. This implies reduction in peripheral vascular resistance and a similar decrease in sympathetic tone. Pulmonary physiology testing has revealed a decrease in tidal volume and an increase in respiratory rate.102 There is also a decrease in dead space and improved CO2 diffusion capacity, possibly because of increased intrathoracic perfusion.83

Although these changes have not been demonstrated to affect human health or cardiovascular stamina during spaceflight, orthostatic intolerance following return to Earth’s gravity remains a concern. Compounding this effect may be a loss of adrenergic responsiveness; in a number of returning astronauts, lower norepinephrine levels have been found to correlate with deficient responses to orthostatic stress.15,88

The severity of orthostasis is generally proportional to the duration of time spent in space and poses a problem if an emergency situation requires crew mobility immediately on landing, especially following a long-duration flight.11 It is also a significant obstacle to planning a mission to Mars, where the crew will be required to function independently immediately on entering a image-G gravity environment after several months’ travel in microgravity. Engineering solutions to these problems may necessitate the use of fully automated landing systems.

Another source of concern is the effect of exposure to the space environment on subclinical pathology, even for very short duration flights. Consider a potential commercial space flight participant with controlled congestive heart failure (CHF). This may manifest itself as clinically significant CHF in microgravity or on return to normal gravity. There are no data about or experience in placing patients with subclinical cardiac dysfunction into space, or treatment of its sequelae in or post flight.

Several strategies are currently used as countermeasures against postflight cardiovascular dysfunction in the fit astronaut population. Five-bladder anti-G suits and liquid cooling garments (LCGs) have become standard equipment during landing, after experience from short-duration Shuttle flights demonstrated that they reduced orthostatic hypotension on landing. The former presumably is effective by minimizing venous pooling in the extremities, whereas the latter reduces heat stress, sweating, and dehydration during the high cabin temperatures of reentry.22 Another standard protocol is oral fluid loading with isotonic solutions (such as bouillon or a sports drink–like concoction called Astro-Ade) performed 2 hours prior to landing. This is a short-acting measure to mitigate the relative hypovolemia of spaceflight.

Previous experience with longer duration (>4 months) missions, such as those to the Mir space station, suggested that regular in-flight cardiovascular exercise benefited orthostatic stamina on reentry, and a robust exercise regimen is now standard on all ISS missions.

The Russians also employ another in-flight countermeasure to improve postflight orthostatic intolerance: a lower body negative pressure (LBNP) device (or Russian “Chibis” suit) (Figure 114-4, online). This device draws blood away from the central circulation and into the lower extremities through a negative pressure gradient, simulating a gravitational stress on the cardiovascular system.25 The Russians have also employed “brazlets,” or thigh cuffs, to encourage greater blood distribution in the lower extremities. Fortunately, even severe postflight orthostatic intolerance is a temporary event and within a few days, virtually all long-duration flight crews are able to mount an appropriate response to orthostatic stress.

For commercial spaceflight participants, it may be appropriate to take a preventive approach; however, there are no data available to determine who is likely to have a problem and therefore how to pursue more comprehensive tests or screening. The FAA has proposed medical standards for both Crew and Spaceflight Participants.

Effects on the Neurovestibular and Sensory Systems

In the terrestrial environment, gravity plays an important role in neurovestibular homeostasis, providing an internal compass for proprioception. Acute exposure to microgravity disrupts interpretation of linear and angular forces in the vestibular organs and may alter integration of visual and proprioceptive input.

One of the earliest effects of these changes is SMS. This form of motion sickness, associated with exposure to microgravity, often manifests as headache, nausea, vomiting, anorexia, poor concentration, or general malaise. It is usually a minor and self-limited condition (generally lasting for the first 1 to 2 days in orbit), yet it is one of the most common reasons for pharmacologic intervention in space (most commonly treated with parenteral or rectal promethazine, 25 to 50 mg, administered at bedtime on the first in-flight day).83 On occasion, however, SMS has persisted for the duration of a Shuttle flight, significantly impairing the affected crewmember’s performance.

SMS is believed to be related to fluid redistribution patterns and/or alterations in bowel motility. It is only weakly correlated with the motion sickness associated with ship or air travel. The motion sickness experienced during parabolic flights on NASA’s DC-8 Reduced Gravity Research Program (Figure 114-5), during which passengers experience intervals of microgravity, has been anecdotally reported to correlate poorly with in-flight SMS.34,94

SMS affects more than 70% of space travelers. Reliable prediction of its occurrence (particularly in first-time flyers) is difficult.22 The incidence is somewhat lower among repeat flyers, suggesting some training effect.5

The operational impact of SMS is considerable. The first in-flight timeline change related to a medical cause occurred because a crewmember suffered SMS. To this day, extravehicular activities (EVAs) are not scheduled within the first few days of a mission because of concerns regarding the effects of SMS during a spacewalk (in particular, the potential for aspiration and fouling of a spacesuit).

Even though SMS can be expected to have resolved several days into a mission, other neurovestibular and neurosensory changes persist, including alterations in eye–head coordination, target tracking, and optokinetic reflex function.5,27 These adaptations can significantly affect delicate technical operations, such as manipulation of the robotic arm or manually controlled docking maneuvers. In fact, neurovestibular dysfunction was implicated as one cause in the collision of the Russian space station Mir with a Progress resupply vessel in 1997, as well as the “bumping” of a satellite during a capture attempt by the Shuttle’s robotic arm.

Neurovestibular dysfunction has also been suggested as a causative factor in the correlation between Space Shuttle mission duration and accuracy of landing speed, position, and touchdown vertical velocity. As mission duration increases, landing accuracy decreases, leading to concerns about the safety of manual landings following long-duration missions, such as exploration missions to Mars. This may necessitate an engineering approach to develop primary automated landing capabilities and demonstrates why physicians and other life scientists need to take part in mission design and planning as well as participate in ongoing operations. The Shuttle has extended flight capabilities to stay in orbit for 30 days. However, it is unlikely that a crew could have landed the Shuttle in its current configuration with the crew sitting upright, after more than 20 days in orbit.

About 80% of space travelers experience perceptual illusions during or after flight. Several different types have been reported: illusory self-motion (both linear and rotational), a sensation of the floor dropping when doing a squat to stand, the sensation of things floating in space, visual streaming (blurring), visual scene oscillation (oscillopsia), object position distortion, visual axis distortion (tilting or inversion), and platform stability illusion. Some crewmembers also experience a sense of being upside-down early in spaceflight.5 The term “EVA acrophobia” has been coined by spacewalking astronauts to describe a feeling that they might “fall off” their vehicle or “fall to Earth” (Figure 114-6).

Restoring sensory references is one goal of neurovestibular countermeasures. Research is currently underway using preflight virtual reality training to simulate conflicts between the proprioceptive and visual systems and to help flyers become accustomed to the ISS geometry prior to arrival. ISS modules also have fluorescent directional guides and standardized coloration of “floor” and “ceiling” surfaces.28,99

Crewmembers tend to choose an external frame of reference to orient themselves. “Down” direction may be toward Earth, the vehicle “floor,” or wherever their feet may be. Crewmembers using the latter strategy (“my feet = down”) seem to experience less disorientation when encountering an unexpected visual stimulus. Additional countermeasures include use of in-flight sensory input stimulators and exercises to reaffirm “up/down” visual cues. For example, watching a video while exercising on a treadmill has anecdotally improved postflight symptomatology on return to a 1G environment.

On return to Earth, the nervous system readapts to a 1G field remarkably well, often returning to preflight states within 48 hours. However, most crewmembers experience some postflight neurovestibular symptoms, including nausea, illusory movements, clumsiness, and vertigo.7 These symptoms are usually mild, but in the event of an emergency egress or bailout over the water, they could prove dangerous.7 Crewmembers in such an emergency not only will have to overcome any musculoskeletal and aerobic deconditioning, but are also likely to have to cope with unsteadiness, poor coordination, vertigo, and motion sickness. Pharmacologic prophylaxis (anti–motion sickness medications) were used for landings during the Skylab program, but were ultimately felt to be counterproductive because of side-effect profiles that included sedation. With short-duration suborbital flights, even mild SMS might significantly detract from the enjoyment for commercial space travelers.

Effects on the Musculoskeletal System

With exposure to microgravity, mechanical load on the musculoskeletal system lessens dramatically, leading to muscle atrophy (particularly in the postural/antigravity muscles) and bone demineralization (disuse osteoporosis). The latter is one of the high priorities of space physiology research, because osteoporosis remains a limiting factor for astronaut health during and after long-duration flight.75 Changes are seen within the first few days of space flight and continue throughout exposure to microgravity, although they do not immediately become clinically significant.

Although the mechanism of this muscle atrophy is not well understood, initial studies suggest that the loss of muscle mass is associated with both decreased protein synthesis (approximately 15%) and increased rate of protein breakdown. As muscle atrophy begins, there is concomitant increase in urinary excretion of nitrogen compounds, 3-methylhistidine, creatinine, and sarcosine. Over the course of a long-duration mission, muscle mass losses of up to 50% can be seen (up to 20% on short-duration missions).

These changes are readily seen in the skinny “chicken legs” of a space traveler; although the cephalad fluid shift seen early in space flight can contribute to this effect, the fluid shift is complete after the first week or so of flight, but leg volume (particularly in the thigh area) continues to decrease throughout the course of a mission. Leg volume measurements do not revert to preflight levels immediately on rehydration and return to Earth, providing further evidence that the changes are primarily associated with muscle atrophy and not merely fluid shifts.

Other changes in muscle morphology include decreases in muscle volume, cross-sectional fiber area (although not fiber number), contractile proteins, oxidative-to–glycolytic enzyme ratio, and capillary density within muscle tissue. This contributes to a more anaerobic metabolic profile and decreased muscle strength and endurance.

Changes in bone structure appear to be caused by increased osteoclastic activity and are particularly pronounced in the spine and legs. Losses of up to 20% of preflight bone mass have been documented and can continue for several weeks (or months) following return to a 1G field. Interestingly, the gender-based differences in bone demineralization rates that are seen terrestrially do not exist in space; men and women lose calcium at approximately the same rate (1% to 2% per month in the lower limbs).

These changes in musculoskeletal structure and function have implications for the amount and type of physical activity that can be performed during space missions and also suggest that crewmembers may be at high risk of injury during and after flight. Animal studies have demonstrated a microgravity-associated reduction in muscle fiber regeneration and repair, which would imply that should an injury occur, recovery may be prolonged. Similarly, the relative reduction in osteoblastic activity could significantly impair healing of an in-flight fracture. Animal studies also reveal microgravity-related alterations in the architecture of bone, leading to further doubts about the body’s ability to properly repair a fracture in-flight.

The persistent diminution in bone and muscle mass is a source of great concern for exploration-class missions. Depending on the mission profile, travel to the destination could require several months, and crewmembers will likely be expected to engage in physical activity on the surface immediately (e.g., specimen collection, habitation module construction). If there have been significant losses in strength and fitness en route, injuries may occur or mission objectives may be compromised. Further exacerbating any physical weaknesses will be neurologic abnormalities in balance, coordination, and gait, all of which increase the risk of falls, fractures, dislocations, and other injuries. It is therefore critical to ensure that space travelers arrive in acceptable physical condition.

To that end, a robust countermeasures exercise program has been initiated on the ISS, making use of both strength and aerobic training. Because enthusiasm for exercise (and compliance with the scheduled program) varies from person to person, it is important for the aerospace physician to educate space travelers about the need for regular exercise, as well as to monitor fitness and strength levels during the course of a mission (see www.asc-csa.gc.ca/eng/astronauts/living_exercising.asp).

Mechanical countermeasures, such as low-intensity vibrations (to stimulate bone maintenance) or the Russian “penguin suit” (which makes use of elastic bands to force use of extensor muscles) (Figure 114-7, online), have been studied to determine efficacy. Unfortunately, none has as yet proved sufficiently useful to warrant routine use.11 Pharmacologic and nutritional interventions, such as bisphosphonates and other antiosteoclastic agents or high-calcium diets, are currently under investigation as countermeasures, but none is (yet) routinely used. One concern is that use of drugs to alter calcium balance may have unintentional effects on renal physiology and enhance creation of kidney stones. Artificial gravity infrastructures could some day offer a solution to this problem, but current designs remain impractical for space travel in the near future.72

In the immediate postflight period, crewmembers experience muscle weakness, fatigue, and soreness. Whether this is due to readaptation of cellular processes (i.e., readjustment of protein synthesis and degradation pathways), unaccustomed strain associated with reexposure to gravity, or micro injuries within the muscle tissue is unclear.

Muscle mass and strength tend to recover rapidly on return to Earth and initiation of a postflight exercise regime. Within two weeks, muscle strength is generally recovered, although further research is needed regarding the possibility of any associated changes to connective tissue structures (such as tendons and ligaments).

Despite rigorous rehabilitation programs, full recovery of preflight bone mass can take years. In part, this is due to the slower time course for terrestrial mineralization (100 mg of calcium per day) compared to space-associated demineralization (250 mg per day), which suggests that it will take two to three times as long to recover bone mass as it did to lose it. In other words, it may take up to 18 months to recover the amount of calcium lost from bones during a 6-month mission. In addition, different parts of the skeleton lose and recover mass at different rates. For example, demineralization of the lumbar spine has been noted to linger for up to 6 months postflight, even as other parts of the spine were recovering and adding mass. As a result, there is a desire to maximize bone density before flight, and many crewmembers engage in preflight exercise programs to increase bone density. This is particularly important for groups at highest risk for the development of osteoporosis (e.g., white women, women with a positive family history).

Effects on the Gastrointestinal and Genitourinary Systems

Weight loss, dehydration, and anorexia are common gastrointestinal symptoms during spaceflight.22 Reduced gastric emptying and altered intestinal transport time have been documented.27,32 Weight loss, likely augmented by fluid losses and muscle atrophy, may also be related to negative nitrogen balance, possibly because of persistent protein loss. Anorexia may be related to altered taste sensation, perhaps because of cephalad fluid shifts. Increased stressors and time pressures associated with mission objectives may influence food choices, with snack or “handheld” foods being preferred as full meals.

Significant efforts are made to offer space travelers a variety of nutritionally balanced foods, but weight loss remains a common finding. Lack of refrigeration and fresh produce necessitates reliance on processed foods, which may be less appealing to crews and contribute to anorexia. Research continues into developing agricultural methods for use on future long-duration and/or exploration missions.

With the exception of the nausea related to postflight SMS, there is no evidence of postflight gastrointestinal changes. Crewmembers appear to recover their preflight weight and nutritional balance rapidly, although it is unclear how much of a role is played by the physical rehabilitation program undertaken for the musculoskeletal system.

Regarding genitourinary changes, there is a well-documented increase in the incidence of renal stone formation. Microgravity-induced increases in bone metabolism contribute to increased calcium excretion in the urine, with a stone incidence of up to 5%.11 To prevent renal colic, the current hydration recommendation for crewmembers is to exceed 2.5 L per day.46 Persistent bone loss during extended missions (and the increased risk of renal stones) remains a significant obstacle to planning a Mars mission.

The missions to date have yielded minimal data on the male and female reproductive systems. Reversible reductions in male testosterone levels have been reported, whereas the phenomenon of retrograde menstrual flow requires further elucidation. Radiation exposure remains a concern as well. The implications of these findings for fertility following a mission have led some experts to endorse preflight preservation of gamete cells. Furthermore, though admittedly sparse, research to date suggests that successful reproduction away from Earth may be significantly difficult, if not impossible, which has major implications for any viable colonization strategy.3,12,98

Effects on the Endocrine System

The changes in plasma volume because of the cephalad fluid shift occur early in space flight and give rise to natriuresis through both pressure effects on the glomerulus and other factors, including antidiuretic hormone, the renin–angiotensin–aldosterone system, and calcium-regulating hormones. There also appears to be relative downregulation of neurohormonal receptors during space flight.

Among the effects of microgravity on the endocrine system is establishment of a new balance between osteoblastic and osteoclastic activity. Reductions in circulating vitamin D and glutathione, presumably related to decreased load exerted on bones, lead to diminished calcium absorption.

Catecholamines also exhibit changes associated with space flight; in-flight levels of urinary norepinephrine are periodically increased, whereas postflight levels of both norepinephrine and epinephrine are elevated relative to preflight values. Epinephrine is felt to reflect stress levels, whereas norepinephrine is an indication of physical activity. It is interesting that given the stresses of space travel (e.g., isolation, busy schedules), in-flight levels of epinephrine are generally unchanged from preflight. This could suggest that the human body adapts relatively well to space flight and does not find microgravity per se to be an overly stressful environment.

There have been general increases in cortisol levels noted during space flight, but studies into hormonal levels have demonstrated wide variability. Differences in diet, exercise, sleep, and emotional stress are likely contributors to the variations seen and suggest that endocrine changes are too subtle and complex to permit easy categorization. This is also why no countermeasures to these (generally adaptive) changes have yet been developed.

Neurohormonal changes affect the cardiovascular system postflight by blunting the baroreceptor reflex and impairing the body’s ability to respond to an orthostatic challenge. This can contribute to residual orthostasis. Just as the body adapts to the microgravity environment through changes in the endocrine and nervous systems, so too do the same systems facilitate readaptation back to the terrestrial environment.

Effects on the Immune System

Space travelers demonstrate a significant increase in the number of many types of circulating white blood cells (neutrophils, monocytes, T-helper cells, B cells), but a decrease in natural killer cells. It is not clear whether these changes are due to increased production or decreased destruction of the cells. Studies have shown that the increased plasma norepinephrine levels measured on landing correlate with increased white blood cells, suggesting that landing stresses produce sympathetic redistribution of circulating leukocytes.

Although studies to date have produced conflicting results, anecdotal data persistently indicate that immune function is compromised in microgravity. In vitro studies show that lymphocytes in-flight are largely unaffected by stimulating agents, suggesting that the white blood cells circulating in the blood, although more numerous than terrestrial levels, may be unable to mount an effective immune response.21,153,154 Changes in leukocyte morphology have also been reported, further suggesting that immune function may be impaired (Figure 114-8, online).

Some researchers who have documented an increase in plasma cortisol levels posit that it is associated with in vivo corticosteroid-induced immunosuppression. Because microorganisms may be more highly concentrated in the confined environment of a spacecraft, the issue of immunocompetence could be important. Whether the findings demonstrate changes related to the microgravity environment or merely stress-related effects on the immune system remains unclear. To date, there have been reports of (usually minor) illnesses during space flight, but no evidence that illnesses are more severe or longer lasting in space.

Subjects in analog environments, such as crews spending the winter in Antarctica, often display latent viral reactivation,54 so it is not unreasonable to imagine that such an effect could be present in long-duration space flight.

Other than ensuring that space travelers are in good health and have had all standard vaccinations, no countermeasure program for the immune system is currently in place. The crew health care systems of the Shuttle and ISS contain medications, including antibiotics and antivirals, for treatment of disease, and the “health stabilization program” (or quarantine period) immediately before launch is intended to further diminish the likelihood of communicable disease during a mission. Unfortunately, the effects of space flight on the immune system are insufficiently understood to permit development of additional countermeasures at this time.

Although in-flight changes to the immune system remain unclear, current work focuses on identifying any alterations in structure and function, along with the associated time course(s). Until these trends have been clearly established, the aerospace physician must assume that immunocompromise, if present in-flight, may persist in the postflight period. As a result, space travelers should be cautioned about the risks of postflight exposure to infectious diseases and the importance of seeking medical help promptly should symptoms develop.

Effects on the Blood, Fluid, and Electrolyte Balance

There is in-flight loss of total body fluids, including extracellular fluid volume, plasma volume, and circulating blood volume.34 The majority of this volume loss is due to changes in plasma volume and circulating red cell mass.

Blood sodium levels decrease in spaceflight, although the relative ratio between sodium and potassium remains unchanged.34 Most of the other electrolytes are unaffected by exposure to space, with the one major exception being calcium. Both urine and plasma levels of calcium are increased in conjunction with bone demineralization, whereas negative nitrogen balance and muscle atrophy lead to elevated urinary levels of nitrogen and muscle breakdown products. Phosphorus levels mimic those of calcium and are also felt to be due to changes in bone metabolism.

Red cell mass has been found to decrease on orbit, regardless of whether an enriched oxygen (Skylab) or sea level equivalent atmosphere (ISS) is present. This “space anemia” appears to be due to decreased red cell production and thus is not one of the effects seen immediately on exposure to microgravity. Researchers have proposed that the decrease in plasma volume leads to a relative increase in hematocrit and causes the body to decrease production of erythropoietin and other red blood cell (RBC)–producing factors. As red cells are consumed in the normal life cycle, but not replaced, the red cell mass decreases in what is thought to be an adaptive response to the microgravity environment.

Because the changes in blood volume, fluid status, and electrolytes are thought to be appropriate adaptations to the space environment, countermeasures are not currently employed to prevent or minimize them during the mission. Immediately prior to reentry, however, fluid loading occurs to reexpand intravascular volume and protect the crew against gravity-induced orthostatic intolerance. On return to Earth, the space-euvolemia is now perceived as a terrestrial-hypovolemia, leading to expansion of plasma volume and relative dilution in hematocrit. This “anemia” triggers increased erythropoietin production and returns the red cell mass to preflight levels. Similarly, the thirst reflex and renal system expand the fluid volume, thus ensuring maintenance of proper fluid and electrolyte levels. In this way, normal physiologic processes reverse the changes following landing and return the space traveler to a terrestrial-euvolemic state. Positional orthostasis may persist for up to several days.

Stressful Environment: Psychological and Behavioral Issues

NASA has identified a number of behavioral issues that are thought to have a direct bearing on productivity and habitability during routine operations onboard a permanently manned space station:68,102

External sources of stress during space missions include limited ability to contact family and friends, real or imagined crises at home, supply shortages, a sense of “interference” from ground personnel, and feelings of rejection resulting from delays in relief. Internal sources of stress may include lack of privacy, forced social interaction, boredom, sexual and emotional deprivation, and perceived absence of status and role definition.

Studies show that isolated and confined populations frequently demonstrate mild psychiatric symptoms, including depression, anxiety, increased defensiveness, and belligerence.18 It has also been suggested that prolonged isolation and confinement harms group dynamics, with social irritability reported among polar expeditioners, submariners, and space-simulator subjects.18

Interpersonal conflict is a real and concerning threat to crew health and mission performance.39 Cramped and confined spaces, cultural differences (often including language differences), and busy schedules replete with complex physical and mental tasks can often exacerbate stressed relationships. Ground support currently plays a large role in monitoring and providing intervention for crewmember strife, but this strategy will need modification for a mission to Mars, where transmission time delays can be as long as 40 minutes round-trip. This delay will not only diminish reliance on ground support for problem solving but may increase tensions between the crew and mission control. History is replete with strife between those on the “front” and the decision makers in the rear. During World War II, submariners on 2- to 3-month patrols complained about the “unrealistic” orders sent from rear echelon officers thousands of miles away. There have already been reports of animosity toward mission control from astronauts on long-duration missions, most famously during the first Skylab Mission. Indeed, ISS initially presented similar issues with unrealistic task timelines for crewmembers; much more emphasis is now placed on “free time” for crewmembers.

The main psychological effects on space travelers can be summarized as:43

The consequences of psychological dysfunction have resulted in early abandonment of at least one Salyut mission, when cosmonaut Vladimir Vasyutin began showing signs of severe stress and depression after 2 months in space. He was hospitalized on his return. In another example, chronic high stress among the crew may have contributed to the 1997 collision between Mir and a resupply vehicle during a docking maneuver.

In-flight communications remain crucial for assessment and improvement of crew behavioral health. Crew access to medical and emotional support from family members and mental health professionals is essential for mission morale. Favorite meals and “care packages” from family are often dispatched on supply vehicle flights.

These issues become more problematic with customer-driven space tourism. It is relatively easy to impose discipline on a team that may in part be military and/or professional civilian crew. However, with a paying customer, the dynamics within a crew will invariably change and not necessarily for the better.

Lack of Privacy

Privacy (or the lack of it) is a feature not only of space exploration but also of other stressful environments. Shuttle crews are arguably at more of a disadvantage than are ISS crews, despite their shorter mission duration. The larger crew size and smaller habitable volume force Shuttle crews to live in extremely close quarters (Figure 114-9). By contrast, the larger ISS, even with its six-person crew, affords significantly more privacy and personal space, with crewmembers having individual “sleeping” quarters in the various modules of the ISS. That said, the tiny crew complement ensures that there are few secrets on board.

Privacy may well become an even greater issue in interplanetary travel, with long transit times and larger crews. Unfortunately, the vehicle may not have the size to allow each crewmember the privacy he or she would like; space will be allocated to supplies (particularly food and water) as a matter of priority. Worsening the issue is the fishbowl-like nature of life in space. Not only do members of the ground support team follow the crew’s every action with close attention but so do members of the world media. This will be particularly true of any exploration mission crew bound for the Moon or Mars (Table 114-2).

Workload Issues

Managing workload is a challenging task; activity levels have to be delicately balanced between too much (stress of overwork) and too little (frustration from boredom, time to brood). In this respect, the differences between Russian and U.S./European procedures are marked. Shuttle activity is planned by ground personnel in great detail, to maximize efficient use of time on orbit. Russian practice involves more flexible schedules, with greater crew discretion. These differences in part reflect cultural differences and the longer-duration flight times of most Russian missions.

The Russian Space Agency (RSA) operated Mir on a 5-day-per-week/8-hour-per-day schedule, with planned time off. Failure to do this in Skylab resulted in near-revolt when after 3 weeks, the crew refused to work any further without a day off. With Shuttle missions, NASA generally tries to pack in the maximum amount of activity through a tightly planned schedule. However, anecdotal reports show that time overruns on the Shuttle were common, with crews working an extra 4 hours per day just to keep up. Although crewmembers on ISS missions have been given greater flexibility in determining their own work schedules, both American and Russian space crews continue to ask for additional options in their work and leisure schedules.

In summary, the missions that have been completed to date have shown that the psychological needs of crewmembers are very important as mission length increases. The dominance of trained professional crew in a disciplined structured environment has helped to ensure mission success. However, introduction of civilian commercial spaceflight will add an unknown element that may have negative consequences.

Analog Environments

There are numerous models for space flight exposure, ranging from parabolic flight to underwater operations, from polar expeditions to a bedrest laboratory. Each type mimics a different aspect of the space flight environment and each therefore has applicability for different studies. Microgravity itself (i.e., free fall) can be experienced through parabolic flight. The NASA C9B Reduced Gravity Research Program aircraft offers alternating intervals of zero gravity (approximately 25 seconds) followed by 1.8G (approximately 20 seconds) per parabola, 40 to 60 parabolas per flight. Other gravitational forces (including lunar and Martian gravities) can also be simulated, although the interval time course remains generally similar.

For research into muscle atrophy and off-loading of gravitational forces, rat models use tail-suspension methods, whereas human subjects undergo prolonged bedrest. Head-down tilt (usually 4 degrees) can be added to the bedrest, or “dry immersion” methods can be used to create cephalad or intrathoracic fluid shifts similar to those seen on orbit. Research into fluid and electrolyte balances, musculoskeletal changes, and endocrinologic changes have all been studied in this way.

To investigate the effects of prolonged isolation and small group dynamics, several analog environments have been used. Examples include polar station and submarine crews, NASA Extreme Environment Mission Operations (NEEMO) projects in the Aquarius underwater laboratory, and the NASA-Haughton-Mars project on Devon Island. Astronauts in their spacesuits can practice EVA tasks in a space analog environment at the NASA-Johnson Space Center Neutral Buoyancy Lab (NBL).

Valuable conclusions can be inferred from looking at health data from these analog environments. These populations have prolonged absences from proximity to health care, and have limited resources. The Australian National Antarctic Research Expeditions (ANARE) Register noted 5103 illnesses and 3910 injuries over the 9 years from 1988 to 1997.54

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