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Safe Passage: Astronaut Care for Exploration Missions (2001)

Chapter: 3 Managing Risks to Astronaut Health

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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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Suggested Citation:"3 Managing Risks to Astronaut Health." Institute of Medicine. 2001. Safe Passage: Astronaut Care for Exploration Missions. Washington, DC: The National Academies Press. doi: 10.17226/10218.
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3 Managing Risks to Astronaut Health We had to struggle a little bit, but we showed the reason that manned space- flight has been as successful as it has for a large number of years. A large team of people scattered across the entire planet were able all together to get a major advance in the space station assembly operations. Chuck Shaw, lead flight mission director for the 100th shuttle mission commenting from Houston Mission Control on the successful attachment by the shuttle Discovery astronauts of the nine-ton Z1 structural truss to the International Space Station’s Unity module, October 14, 2000 Perhaps the most ambitious goal of the National Aeronautics and Space Administration’s (NASA’s) space medicine program is to be able to provide optimal health care to the first (and subsequent) astronauts who will go on exploration-class missions to Mars. Because any such mission lies more than a decade in the future, the challenge to the Institute of Medicine (IOM) Committee on Creating a Vision for Space Medicine During Travel Beyond Earth Orbit was this: what can usefully be said, so far in advance, about providing day-to-day health care in space, while on the Martian surface, and during the return trip to Earth? What types of illnesses and injuries might reasonably be anticipated on long-duration space missions? 75

76 SAFE PASSAGE In this chapter, the committee tries to begin answering those questions by looking at the only evidence available: the morbidity and mortality expe- riences of U.S. astronauts and Russian cosmonauts, U.S. Navy submariners, and Australian scientists and explorers in the Antarctic. This look back in- cludes findings from physical examinations conducted in space to see what is normal, or baseline, in microgravity. The committee also examines poten- tial health problems in each of several medical practice areas—cardiology, neurology, surgery, and psychiatry, to name a few—in which critical risks have been identified (see Table 2-2). The committee anticipates that long-duration missions beyond Earth orbit will be qualitatively different from short spaceflights. Medical and be- havioral issues that have not been particularly problematic on short flights may loom large on exploration-class missions. It is not possible to accurately predict the treatment innovations, technological advances, and shifting stan- dards of care that may occur over the next 20 years and prove relevant to medical practice in space. GENERAL PRINCIPLES AND ISSUES The focus of this chapter is the care of the individual patient in space. Premission evaluation should include assessments of both the astronaut’s health status (including the status of specific organ systems at risk, such as the musculoskeletal system [see Chapter 2 for the risks involved]) and other risks. The general principles of care are the maintenance of normal health status in microgravity and, if illness or injury occurs, restoration of normal function as quickly and efficiently as possible during and upon the return from the space mission. As part of a responsible space crew, each crew- member should be expected to participate in routine surveillance to be able to measure the health status of other members of the crew at regular inter- vals. Resources should be available for the diagnosis and treatment of the most common minor and major illnesses and injuries that are anticipated to occur in the Earth environment, as well as to diagnose and treat conditions that are unique to microgravity and the particular space mission. The crew should be prepared to treat a wide variety of conditions of various degrees of severity during a space mission and, most of all, be prepared to treat the unexpected. The major health and medical issues related to exploration-class mis- sions have been of little risk or concern to NASA up to the present for short- duration space travel (e.g., space transportation system [STS] space shuttle missions) (Box 3-1). All of the major health and medical issues are pro-

MANAGING RISKS TO ASTRONAUT HEALTH 77 jected, however, to be moderate to severe concerns that affect astronaut health on the International Space Station (ISS), and except for radiation protection and bone mineral density loss, the degree of severity of the other health and safety challenges have yet to be estimated for exploration-class missions. Many of these issues and challenges are directly related to or are completely tied to known human physiological adaptations to space travel. Separation of these issues from the discussions of physiological adaptations in Chapter 2 is in many cases artificial. Similar concerns, issues, and topics on medical, surgical, rehabilitative, and behavioral health in this chapter and in Chapters 4 and 5 must also be considered in the continuum of clinical research and health care for astronauts to begin building the infrastructure and health care system (Chapter 7) needed for human exploration of deep space. The committee has chosen to separate these topics into chapters to place the emphasis on clinical research (Chapters 2 to 5), health care (Chap- ters 3 to 5), and opportunities and ethical and infrastructure concerns (Chap- ters 6 and 7) that it believes is necessary to promote the needed attention to the safe passage and the health of astronauts during travel beyond Earth orbit and into deep space. BOX 3-1 Major Health and Medical Issues During Spaceflight Health or Medical Issue GRD AIR STS ISS EXP Radiation protection G G G Y R Hearing conservation G G G R TBD Cardiovascular G G G Y TBD Muscle G G G Y TBD Bone loss G G G Y TBD Neurovestibular Y NA G R TBD Habitability NA G Y Y TBD Extravehicular activity risk NA G Y Y TBD Medical care Y NA Y Y TBD Diversity (age, gender, etc.) Y NA Y Y TBD Psychological issues Y G G Y TBD Workers’ compensation Y G G Y TBD Abbreviations: GRD, ground; AIR, airflight; STS, space shuttle; ISS, International Space Station; EXP, exploration-class mission; G, green, little or no risk; Y, yellow, moderate risk; R, red, severe risk; TBD, to be determined; NA, not applicable. Source: Williams, 2000.

78 SAFE PASSAGE Medical Events in Extreme Environments Evidence Base from Previous Space Missions A review of 79 U.S. space missions involving 219 person-flights lasting 2 to 17 days each (Putcha et al., 1999) reported that the most common condi- tions experienced were space motion sickness (SMS), nasal congestion, and sleep disorders. None of these medical conditions have required the mission to end, have been life threatening, or have required intensive medical treat- ment; they are bothersome but are not medical emergencies. Exploration- class missions, however, because of their lengths of as many as 3 years be- yond Earth orbit, raise in NASA’s current judgment the probability of a major medical event, a condition requiring intervention by a medical practi- tioner, during the mission (Billica, 2000). A study of 175 astronauts from 1959 to 1991 reported 20 deaths (19 males and 1 female), mostly unrelated to spaceflight because of high rates of automobile and aircraft accidents and accidental deaths on the Apollo 1 and the Challenger spacecrafts. The small numbers of participants and the pre- mature deaths from injuries may well mask the morbidity and mortality fig- ures from other disorders related to spaceflight, such as cancer, if the partici- pants live long enough (Peterson et al., 1993). Related disorders such as the development of cancer and cardiovascular, arthritic, and other conditions may increase in frequency as the duration of space travel and the ages of astronauts increase, just as they would had the same individuals remained on Earth. The risks of medical events increase with the lengths of missions (Billica et al., 1996). A survey of the perception of risk from spaceflight was re- turned by 65 medical professionals and showed that medical events with the highest perceived likelihood of occurrence had the least effect on the mis- sion or the crew, but those with the greatest impact on the mission or crew were least likely to occur (Billica et al., 1996). Skin disorders (irritation from fiberglass, contact dermatitis, rashes, and furuncles) were thought to be the most common, followed by respiratory and digestive disorders. NASA reported that 1,867 medical events occurred from 1981 to 1998 on space shuttle flights STS-1 to STS-89 (Billica, 2000). Among the popula- tion of 508 individuals on those flights, 498 reported a medical event or symptom other than SMS. The events, derived from a histogram presented to the committee (Billica, 2000), were ill-defined symptoms (n = 788), respi- ratory events (n = 83), symptoms related to nervous system or sensory or- gans (n = 318), digestive disorders (n = 163), symptoms related to skin or

MANAGING RISKS TO ASTRONAUT HEALTH 79 subcutaneous tissue (n = 151), symptoms related to the musculoskeletal sys- tem (n = 132), and injuries (n = 141). Approximately 5 percent (77 of 1,777) were injuries, and 10 deaths occurred, 7 during a catastrophic explosion in the early phase of the launch (Challenger in 1986) and 3 from a fire on the launchpad (Apollo 1 in 1967). Rates of events have not been reported, and associations of illness or injury with extravehicular activity (EVA) also have not been reported. EVAs are associated with a high workload and are associated with a much higher risk of injury because of the momentum imparted to large masses during EVAs and the lengthy periods of work outside the spacecraft (Nicogossian et al., 1994). Even in the non-EVA microgravity environment, fractures are possible due to movement of cargo, which can easily “get away” once set in motion or if an individual pushes away from a wall too hard and experiences a bone-jarring hit on the opposite wall (Nicogossian et al., 1994). This is a good example of the importance of training to prevent medical injury. The microgravity environments of long-duration space missions will also be associated with overexertion, strains, and sprains, because backaches and effects from the physical demands of EVAs have been reported during shorter missions and require pharmacological treatment (Putcha et al., 1999). Backaches are not specifically associated with EVAs but are a common com- plaint thought to be associated with elongation in vertebral column length and stress placed on intervertebral discs. This type of pain has been re- ported to be ameliorated by axial compression performed by crewmembers while in orbit (NASA, 2000b). The medications administered as a single dose or taken by only one person during 219 space missions have included phenazopyridine, omeprazole, zolpidem, sucralfate, an antifungal (Vagisil), clotrimazole (Mycelex), docusate, an antacid (Gaviscon), cimeditine, diclofenac, meclizine, ofloxacin, gentamicin, lovastatin, flavoxate, ketoprofen, metaxalone, and cephalexin. This spectrum of medications that has been taken and the disorders that have been treated on short missions point to the need to plan for a broad-based and space medicine-focused pharmacopoeia to treat a wide variety of signs, symptoms, and diseases on longer missions. The existence of such a pharmacopoeia also necessitates procedures to avoid potential abuse. It would have been helpful to the committee’s assessment if the data on illness and injury with and without an association with EVA made available to the committee had been stratified and publicly reported to allow the com- mittee and others to have a better understanding of the health-related risks

80 SAFE PASSAGE of spaceflight. Moreover, a number of questions remain unanswered. In ad- dition, facts needed to best appreciate any list of health-related risks of space- flight (Tables 3-1, 3-2, 3-3, and 3-4) to plan for future space missions were not available. For instance, (1) how were the symptoms distributed among astronauts with different specialties (e.g., pilots versus payload specialists)? (2) did astronauts who flew more than one mission experience fewer symp- toms on subsequent flights? and (3) what was the degree of severity of the reported symptoms? It is therefore important to look at the totality of the data from space missions and what has been learned from other extreme isolated environ- ments on Earth (e.g., Antarctica and extended underwater submarine mis- sions). These data relate to the type and incidence of medical-surgical and behavioral health events that occur in these environments and are needed to best gauge and plan for future needs during extended space travel before commencement of exploration-class space missions with astronaut crews. Evidence Base from Extended-Duration Submarine Missions Medical events during submarine missions are instructive as they occur in a confined, remote environment where there is limited diagnostic and therapeutic support. They occur in an atmosphere where potentially life- threatening or other severe medical illnesses can end a mission, in the sense that the submarine is required to interrupt or even abort its mission. The U.S. Navy described the incidence of illnesses and injuries on 136 submarine patrols from January 1, 1997, through December 31, 1998. The numbers of acute encounters were related to the total number of person- days under way, with 2,044 acute encounters in 1.3 million person-days at sea, or 157 acute encounters per 100,000 person-days (Table 3-5). Stratified by illness and injury, illness accounted for 112.9 episodes per 100,000 per- son-days, with 70 percent able to maintain full duty; and accidents accounted for 37.2 episodes/100,000 person-days, with 55 percent able to maintain full duty (Thomas et al., 2000). A different perspective is obtained when the health disorders and medical-surgical procedures in Table 3-5 are compared with the reasons for medical evacuations from U.S. submarines (Table 3-6). A range of 1.9 to 2.3 medical evacuations per 1,000 person-months was reported for all subma- rines in the U.S. Atlantic Fleet from 1993 to 1996. A range of 1.8 to 2.6 evacuations per 1,000 person-months was reported for humane reasons (i.e., death or serious illness in the family) (Sack, 1998), suggesting that if these

MANAGING RISKS TO ASTRONAUT HEALTH 81 TABLE 3-1 In-Flight Medical Events for U.S. Astronauts During the Space Shuttle Program (STS-1 through STS-89, April 1981 to January 1998) Medical Event or System by Number Percent Incidence/14 days ICD-9a Category Space adaptation syndrome 788 42.2 2.48 Nervous system and sense organs 318 17.0 1.00 Digestive system 163 8.7 0.52 Skin and subcutaneous tissue 151 8.1 0.48 Injuries or trauma 141 7.6 0.44 Musculoskeletal system and connective tissue 132 7.1 0.42 Respiratory system 83 4.4 0.26 Behavioral signs and symptoms 34 1.8 0.11 Infectious diseases 26 1.4 0.08 Genitourinary system 23 1.2 0.07 Circulatory system 6 0.3 0.02 Endocrine, nutritional, metabolic, and immunity disorders 2 0.1 0.01 aInternational Classification of Diseases, 9th edition. SOURCE: Billica, 2000. data are extrapolated to extended space travel or habitation, the psychoso- cial support needs may well be just as important as the medical needs in a long-duration space mission. The medical reasons for submarine evacuations from 1993 to 1996 var- ied (Table 3-6). The largest number of conditions requiring medical evacua- tion are trauma and “other” (miscellaneous). It should be noted, however, that psychiatric reasons rank second in the specific categories. The “other” category most likely consists of large numbers of unrelated clinical condi- tions, further reinforcing the diversity of clinical conditions that can be ex- pected to occur during a space mission. Factors such as astronaut age and medical prescreening would affect the incidence of medical emergencies among the members of the space crew, but since prescreening for most con- ditions cannot be done, it is possible that similar disorders and the propor- tions of those disorders that could occur among the members of a space crew would be similar to those that occur among individuals on submarine missions.

82 SAFE PASSAGE TABLE 3-2 Medical Events Among Seven NASA Astronauts on Mir, March 14, 1995, through June 12, 1998 Event Number of Events Incidence/100 Days Musculoskeletal 7 0.74 Skin 6 0.63 Nasal congestion, irritation 4 0.42 Bruise 2 0.21 Eyes 2 0.21 Gastrointestinal 2 0.21 Psychiatric 2 0.21 Hemorrhoids 1 0.11 Headaches 1 0.11 Sleep disorders 1 0.11 NOTE: Data from the Russian Space Agency reports that there were 304 in-flight medical events onboard the Mir from February 7, 1987, through February 28, 1998. The numbers of astronauts at risk or the incidence per 100 days was not reported. SOURCE: Marshburn, 2000b. Tansey and colleagues (1979) reviewed health data from 885 Polaris sub- marine patrols from 1963 to 1973, for 4,410,000 person-days of submarine activity. They described 1,685 medical events that resulted in 6,460 duty days lost. Only events that resulted in the loss of at least 1 workday were reported. The events with the six highest rates of occurrence were, in de- scending order, trauma, gastrointestinal disease, respiratory infections, der- mal disorders, infection, and genitourinary disorders. The spectrum of dis- orders was very broad and included cases of arrhythmia, paroxysmal superventricular tachycardia, infectious hepatitis, gastrointestinal hemor- rhage, meningococcemia, paranoid schizophrenia, appendicitis, pilonidal abscess, perirectal abscess, ureteral calculi, testicular torsion, and crush in- juries, further emphasizing that the scope of anticipated medical conditions on long-duration space missions will be very broad (Tansey et al., 1979). The incidence of the types of illnesses observed during extended sub- marine missions is generally similar to the incidence encountered during spaceflights. NASA has used the incidence of medical events on submarines to estimate that there may be one major medical event requiring interven- tion of the type usually delivered by a medical practitioner during a future exploration-class mission of 3 years in length with five to seven astronauts (Billica, 2000; Flynn and Holland, 2000). Unfortunately, the nature of that

MANAGING RISKS TO ASTRONAUT HEALTH 83 TABLE 3-3 Medical Events and Recurrences Among Astronauts of All Nationalities on Mir, March 14, 1995, through June 12, 1998 Event Number of Events Recurrences Superficial injury 43 2 Arrhythmia 32 98a Musculoskeletal 29 NRb Headache 17 8 Sleeplessness 13 9 Fatigue 17 4 Contact dermatitis 5 3 Surface burn 5 NR Conjunctivitis 4 2 Acute respiratory infection 3 NR Asthenia 3 2 Ocular foreign body 3 NR Globe contusion 2 NR Dental 2 NR Constipation 1 NR aSee Chapter 2. bNR, not reported. SOURCE: Marshburn, 2000b. NOTE: Further information on symptom duration, functional impact, or recurrences, especially the nature of arrhythmias and the number of astronauts who experienced them, is important for assess- ment of the potential impacts of such events on prolonged space missions. Other than arrhythmias, the medical events reported were minor, although most were certainly as vexing in space as they would be on Earth. event is unpredictable, so preparations must be prioritized and must still be made for a wide spectrum of problems. Evidence Base from Antarctic Expeditions The Australian National Antarctic Research Expeditions (ANARE) Health Register compiled 1,967 person-years of data from 1988 to 1997. It documents 5,103 illnesses and 3,910 injuries (Table 3-7). The distribution and variety are similar overall to those from spaceflight data. Seventeen Australians, moreover, have died in the Antarctic and suban- tarctic since 1947 (Taylor and Gormly, 1997; D. J. Lugg, ANARE, personal communication, August 24, 2000). Excluding those conditions peculiar to

84 SAFE PASSAGE TABLE 3-4 Pharmacopoeia Usage During Mir Missions Number of tablets or Medications doses dispensed Pseudoephedrine 131 Zolpidem 81 Temazepam 68 Diphenhydramine 60 Aspirin 55 Acetaminophen 37 Bisacodyl 32 Ibuprofen 28 Terfenadine 18 Long-acting phenylpropanolamine 13 Nose drops (Neosynephrine) 9 SOURCE: Marshburn, 2000b. NOTE: This list reaffirms the discomforts experienced by crew of previ- ous missions and suggests the probability that nasal congestion, sleep disorders, pain, and constipation will afflict the crews of longer-duration space missions. TABLE 3-5 Incidence of Health Disorders and Medical-Surgical Procedures During 136 Submarine Patrols Disorder Number/100,000 Person-Days Injury (includes accidents) 48.8 Respiratory 24.6 Skin or soft tissue 19.0 Ill-defined symptoms 10.5 Infections 10.0 Procedure Percentage of All Procedures Performed Wound care, splinting 42.0 Suturing 18.7 Cleansing 8.2 Nail removal 6.8 Fluorescein eye examination 4.2 Incision and drainage of abscess 2.9 Tooth restoration 2.0 SOURCE: Thomas et al., 2000.

MANAGING RISKS TO ASTRONAUT HEALTH 85 TABLE 3-6 Reasons for 332 Medical Evacuations from All Submarines, U.S. Atlantic Fleet, 1993 to 1996 Reason for Evacuation Number of Cases Trauma 71 Psychiatric illness 41 Chest pain 34 Infection 40 Kidney stone 23 Appendicitis 21 Dental problem 31 Other 71 Totala 332 a Rate = 1.9 to 2.3 per 1,000 person-months. SOURCE: Sack, 1998. the Antarctic environment (drowning and exposure, n = 5; outdoor injuries, n = 5), seven nonpredictable deaths occurred in the Antarctic because of appendicitis (n = 1), cerebral hemorrhage (n = 1), acute myocardial infarc- tion (n = 2), carbon monoxide poisoning (n = 1), perforated gastric ulcer (n = 1), and burns (n = 1). Each of these is a possible medical event on a spacecraft, indicating the wide variety of medical emergencies that can oc- cur and that must be considered in planning for health care management in TABLE 3-7 ANARE Health Register Illnesses in Antarctica from 1988 to 1997 Disorder Number Percent Injury and poisoning 3,910 42.0 Respiratory 910 9.7 Skin, subcutaneous 899 9.6 Nervous system or sensory organs 702 7.5 Digestive 691 7.4 Infection or parasitic 682 7.3 Musculoskeletal or connective tissue 667 7.1 Ill-defined symptoms 335 3.6 Mental 217 2.3 SOURCE: Lugg, 2000.

86 SAFE PASSAGE BOX 3-2 Potential Methods of Risk Assessment and Screening Physiological profiling. Physiological profiling consists of profiling of the central nervous system; cardiovascular system; pulmonary system; musculoskeletal system; eyes, ears, nose, and throat; gastrointestinal system; and genitourinary system and gynecological health and profiling for endurance, strength, and adaptive ability. Psychosocial profiling. Psychosocial profiling evaluates individuals for moods or traits that are positively selected and traits that lead to rejection. Are there behavioral signs and symptoms that validly and reliably predict maladaptive or disruptive behav- ioral interactions? Health status profiling. Past medical events and current signs and symptoms are used as part of health status profiling. Individuals with disorders such as migraine and hypertension and individuals who have had keratoplasty are excluded from astronaut training. Markers to assist in profiling. Such markers include the results of laboratory studies, genetic profiling, and imaging studies and family history. the extreme environment of extended-duration space travel or habitation beyond Earth. Health Risk Assessment Individuals differ in their susceptibilities to disease, vulnerabilities to environmental assaults, and abilities to recover from injury. Current poten- tial methods of risk assessment and screening (Box 3-2) rely heavily on the identification of preclinical disease or conditions known to predispose an individual to illness. For example, certain abnormal lipid profiles are an identified risk factor for atherosclerosis, elevated blood pressure is an iden- tified risk factor for stroke and heart disease, and osteoporosis is a risk fac- tor for hip fracture. As a result of the Human Genome Project, investigators are also identi- fying DNA sequences that correlate with an increased risk for a particular disease or syndrome, and the basis for this increased risk is being elucidated. The presence of DNA or RNA sequences indicative of a potential health risk as well as those indicative of a preferential pharmacodynamic or other response to treatment may be an integral part of the standard of care in the future. Breast cancer (Box 3-3) and colon cancer are two diseases for which

MANAGING RISKS TO ASTRONAUT HEALTH 87 there are well-established risk assessment and screening tools, as well as an increasing number of DNA sequences that indicate a propensity for an in- creased risk of development of the diseases. As such linkages become more prevalent for a wider variety of diseases, they will offer increased means for profiling and screening of individuals to decrease major medical and health risks (Box 3-1) and promote the health and safety of astronauts for long- duration space travel. While on a long-duration mission beyond Earth orbit the starting point for medical care will most often be a description of the chief complaint and a physical examination. The physical examination technique must be adapted to the microgravity environment, where the method of determination of in- ternal organ location and other diagnostic methods differ widely from those used in terrestrial environments. The patient, examiner, and equipment must be stabilized for proper examination technique in microgravity. The exam- iner must learn adaptive movements to perform the abdominal examination properly. Auscultation of heart or bowel sounds in the noisy spacecraft envi- ronment is difficult, and stethoscopes need to be modified with this in mind by the cooperative work of engineers and clinicians. Harris and colleagues (1997) have reported a number of variations to physical examinations per- formed in a microgravity environment (Box 3-4). The physical findings listed in Box 3-4 are for five males and two fe- males during 8- and 10-day missions (Harris et al., 1997). Facial and perior- bital edema are most evident during the first 3 days of flight but persist throughout the mission. Facial and periorbital edema, nasal congestion, and jugular venous distention occur because of fluid shifts to the head and torso because the loss of gravity eliminates hydrostatic pooling in the extremities. Thinning of the lower extremities is due to an approximately 40 percent reduction in interstitial fluid levels in the lower extremities (Baisch, 1993). Auscultated bowel sounds diminish on the 2nd through 5th days of the flight. Investigators note that absent bowel sounds were strongly associated with the development of motion sickness. The diaphragm is elevated by two intercostal spaces and appears to remain elevated during spaceflight. Nor- mal variations in the positions of thoracic and abdominal viscera also occur in microgravity. It is important to recognize these variations because they could affect the interpretation of physical findings and the performance of invasive or diagnostic procedures. For example, failure to recognize a “nor- mal” elevation of a hemidiaphragm in microgravity could result in improper placement of a thoracostomy tube for the treatment of pneumothorax, or alterations of peritoneal signs in microgravity could change the signs and

88 SAFE PASSAGE BOX 3-3 Breast Cancer as an Example of Risk Assessment in Space Medicine The possibility that breast cancer can occur in a woman while on long-duration space travel exists. The development of breast cancer in a physician at a base in Antarctica in 1999 reinforces the potential that a breast mass including cancer could develop while an astronaut was in space. Breast cancer will have been diagnosed in 182,000 women in the United States in the year 2000 (American Cancer Society, 2000). The risk of breast cancer increases with advanced age, early age at menarche (younger than 12 years), nulliparity or late age of first birth (older than 30 years), a family history of breast cancer in a mother or sister, and breast biopsies showing proliferative disease or atypical hyperplasia (Harris, 1991; Harris et al., 1992). Wom- en who have had thoracic irradiation or who carry an inherited DNA mutation predis- posing them to breast cancer are at even greater risk. Up to 10 percent of all cases of breast cancer are believed to be associated with an inherited predisposition for the disease (Claus et al., 1996). It is estimated that 55 to 85 percent of women carrying the BRCA-1 mutation will develop breast cancer during their lifetimes (Ford et al., 1998). In addition, carriers of the mutation tend to develop breast cancer at a younger age. Women with strong family histories can be tested for mutations in the BRCA-1 and BRCA-2 genes. If they carry a mutation, the risk for breast cancer is increased sever- alfold. More than 50 percent of carriers are diagnosed with breast cancer by age 50 (Easton et al., 1995). Individuals who are homozygous for mutations in the ataxia telangiectasia gene (AT) are at significantly increased risk of cancer and are highly sensitive to ionizing radiation. It is not currently known if exposure to high-energy radiation such as that which occurs beyond Earth orbit will also increase the risk. An increased risk of breast cancer has been noted in AT heterozygotes (Athma et al., 1996), which constitute approximately 1 percent of the general population in the United States and Europe, and it has been hypothesized that early and frequent mammography may be inadvis- symptoms of appendicitis. Pelvic examination has not been reported in microgravity, but a pelvic examination in microgravity may lead to other variations in normal findings. Health Care Opportunity 1. Expanding, validating, and standardizing a modified physical examination, the microgravity examination technique, and including a technique for pelvic examination for use in microgravity. Nutrition Food quality and variety affect crew attitudes and overall performance. Nutritional concerns include sufficient caloric intake, nutritional density, food palatability, varied menus, and cultural variations in preferred foods. It

MANAGING RISKS TO ASTRONAUT HEALTH 89 able for this group of individuals. Because breast cancer is so common in the general population, there is tremendous ongoing research that may be relevant to NASA and that must be monitored to obtain an understanding of the risk due to exposure to ionizing radiation as well as to high-energy particle radiation. In 1989, Gail and colleagues published the Gail model for estimation of an individ- ual’s risk for the development of breast cancer over time on the basis of age, age at menarche and age at first birth, family history, and breast biopsy results. By using this model, after entry of the risk factor for a given woman, both her 5-year and lifetime probabilities for breast cancer can be calculated (Gail et al., 1989; Benichou et al., 1997). Women who have had thoracic irradiation or a specific family profile indica- tive of an inherited DNA mutation, however, cannot be appropriately assessed with the Gail model. The average age of women selected for the space program is 32 (Jennings and Baker, 2000). Given the astronaut training constraints on pregnancy, however, once female astronauts are admitted into the program, they commonly defer childbearing. Therefore, because many female astronauts delay childbirth, they are at increased risk for breast cancer. The increased risk imposed by radiation while in space is unknown, but it may be an additional risk. The probability that breast cancer would develop to the point of clinical significance in a woman while on a long-duration space mission therefore exists. To what extent should preflight risk assessment include laboratory testing of an individual’s nucleic acid composition as well as conventional screening? Should an individual identified to be at increased risk be eliminated from a long- duration space mission beyond Earth orbit or counseled and allowed to make an in- formed decision? These are questions for NASA to address in its preparation for explo- ration-class missions. A similar scenario can be presented for colon cancer in men and women, particu- larly as the average age of astronauts increases, and will become more common for other disorders as the understanding of the molecular biology of disease continues its present rapid advance. is critical that the food supply be adequate, safe, and reliable and that it remains so throughout the mission. Inadequate food and water supplies or contamination or loss of the supplies, particularly since much will have to be generated from recycled materials during the mission, will result in termina- tion of the mission or the loss of life. Additionally, one must consider methods that can be used to ensure the adequacy of caloric intakes to prevent the ongoing loss of body mass. On the basis of current experience (Lane and Schoeller, 2000), a degree of malnutri- tion is anticipated in nearly all astronauts during space travel without the use of countermeasures and is expected in even 61 to 94 percent of astronauts with the use of countermeasures. Just as the effects of zero gravity or microgravity on the pharmacodynamics and metabolism of pharmaceuticals are unknown (see below), absorption of nutrients may be problematic, lead-

90 SAFE PASSAGE BOX 3-4 “Normal” Findings on Physical Examination in Microgravity Facial and periorbital edema Oily facial skin Hyperemia: facial skin, conjunctivae, mucosae of the nose, and mucosae of the pharynx Jugular venous distention Elevation of diaphragms by two intercostal spaces Point of maximal cardiac impulse displaced substernally or not palpable Posture: barrel chest, hyperextended back, flexion of upper and lower extremities Extremities: thinning of lower extremities Neurological: hyperreflexia Source: Harris et al., 1997. ing to unexpected deficiencies that result in the need for supplementation. Nutritional requirements have been found to be similar for short-duration space missions and life in normal terrestrial environments, but energy intake is decreased during space travel, so most astronauts lose body mass, includ- ing 1 to 2 liters of body water. A monitored mandatory caloric intake may be considered, as may monitoring of nutritional status in more standard ways, for example, via measurement of arm circumference. One must consider that inadequate intakes of micronutrients or vitamins would adversely affect the entire crew, making identification of all required nutrients and their ab- sorption or elimination pharmacodynamics a priority. Pharmacodynamics and Pharmacokinetics Pharmacodynamics deals with the interactions of drugs and living sys- tems, whereas pharmacokinetics is the study of the absorption, distribution, and metabolism-utilization of pharmacologicals. The microgravity environ- ment can be expected to affect the pharmacodynamics and pharmacokinet- ics of all drugs, yet little clinical research has been performed in these areas. Clinical research on the pharmacokinetics and pharmacodynamics of drugs in space is limited by the small numbers of participants, limited opportuni- ties for clinical study (i.e., few space missions), and the lack of a reasonable

MANAGING RISKS TO ASTRONAUT HEALTH 91 terrestrial proxy for microgravity in which to conduct pharmacological stud- ies. Drugs administered in microgravity may not have the anticipated local, regional, or systemic effects and may manifest different adverse effect pro- files in space compared with those observed on Earth. For example, a case series of 21 crewmembers given 25 to 50 mg of promethazine intramuscu- larly reported only a 5 percent sedation rate, whereas the sedation rate was 60 to 73 percent in studies conducted in standard Earth gravity (Bagian and Ward, 1994). This phenomenon needs to be closely studied for several rea- sons. The decreased effectiveness of a sedative could be due to SMS or the sheer excitement associated with the space mission. There is also some evi- dence that receptor interactions may be altered under conditions of hypo- volemia (Derendorf, 1994). The bioavailabilities of oral drugs given in space can be affected by gastric emptying, gastric motility, and hepatic blood flow (Tietze and Putcha, 1994). Bed rest, which is sometimes used to partially simulate the effects of microgravity, is reported to delay the absorption of common oral medications, and drug distribution is affected by the redistri- bution of fluids from the lower body to the head and torso in space (Tietze and Putcha, 1994). The bioavailabilities of oral scopolamine and acetamin- ophen are altered in flight and may be affected by SMS and the particular day of the mission (Cintron et al., 1987; Tietze and Putcha, 1994). Drug binding by protein and tissue is presumably altered in microgravity because of muscle and tissue atrophy, the latter of which has been documented upon the return from a space mission (Edgerton et al., 1995). The frequency of use of medications during spaceflight (Putcha et al., 1999) is such that targeted research into the pharmacokinetics of various routes of drug administration (oral, intranasal, transcutaneous, subcutane- ous, intramuscular, intravenous) is required, with the goal of determining the predictability of the effect and efficacy. The resources for the medical crew on the spacecraft for a long-duration mission should include a com- pendium of the indications and adverse effects of the pharmaceuticals on board and their anticipated kinetic changes, such as bioavailabilities and half-lives, that are predicted for the microgravity environment. Health Care Opportunity 2. Developing an easily accessible database for medications on the spacecraft, including dosage, indications, adverse ef- fects, and anticipated changes in the pharmacokinetic profile in microgravity.

92 SAFE PASSAGE Environmental and Occupational Health Environmental Hazards The environmental and occupational health of astronauts will be impor- tant issues for long-duration space travel. Missions beyond Earth orbit will dictate a unique set of requirements to protect crewmembers from hazards such as chemical contamination, volatile organic compounds, particulate matter, and microorganisms. Crewmembers may confront the challenge of living in a noisy environment, where vibration is also a potential hazard to human health and to sensitive experiments (Koros, 1991a; Koros et al., 1993). Crewmembers will work in an environment of artificial light, which could adversely affect their performance (Czeisler et al., 1990; Barger and Czeisler, 2000). Missions may include scheduled and unscheduled EVAs, which will be physically challenging and conducted by humans who may be physiologically compromised. Finally, there is the question of the deleteri- ous effects of exposure to primary and secondary radiation (Johnston and Dietlein, 1977; Nicogossian and Parker, 1982; SSB and NRC, 2000). Opera- tional requirements for EVAs will present significant physical challenges for crews. For the ISS, an estimated total of 1,100 hours will be required to carry out planned construction and maintenance. At a high inclination of orbit of 51.6 degrees, such activity will expose the crew to high-altitude radiation as well as temperature extremes, micrometeors, and physical injuries. Decompression Sickness Decompression sickness (DCS) represents another significant potential threat to astronauts on long-duration missions. Should emergency EVAs or sudden unexpected decompression of the spacecraft occur, DCS might en- sue. NASA is well aware of these problems and is actively pursuing solutions to these issues, particularly so that it can effectively and safely finish the construction of the ISS. The committee believes that NASA’s efforts in these areas should continue by including investigations of the possible relation- ship between a patent foramen ovale and DCS. Careful integration of engi- neering issues and habitability should take place in planning for EVAs as well as emergency contingencies for EVAs. Finally, the committee is confi- dent that advances in materials will allow the inclusion of a lightweight, low- volume recompression chamber in the manifest for missions beyond Earth

MANAGING RISKS TO ASTRONAUT HEALTH 93 orbit, if it is considered necessary (i.e., if a pressure suit with an internal pressure greater than that in present suits has not been developed). Internal Environment During long-duration space missions, the internal environment of the spacecraft will offer its own unique challenges, ranging from chemical and microbial contamination to noise and vibration. Like any confined habitat there will be chemical and physical toxic elements. On a spacecraft, how- ever, the crew has few opportunities to replace or recondition a toxic envi- ronment. Exposure to Toxic Chemicals Environmental hazards come from several sources. Propulsion propellant (Freon, hydrazines, nitrogen dioxide) leaks into the spacecraft interior can be toxic in small quantities (Tansey et al., 1979). The spacecraft crew can be further exposed if propulsion chemicals enter the spacecraft through the air lock or if they crystallize on EVA suits. Accidental chemical releases during space shuttle flights have also been re- ported. The dominant source appears to be heat degradation of electronic devices. Thermodegradation of spacecraft polymers with the production of formaldehyde and ammonia adds to the environmental hazard (Nicogossian et al., 1994). There were nine incidents from STS-35 to STS-55, with four resulting from burning electrical wiring. Subsequent analysis found benzene, acetaldehyde, dimethyl sulfides, and other compounds in the space shuttle crew compartment atmosphere (James et al., 1994; Pierson et al., 1999). The experience on Mir provided a glimpse of the potential risks of con- tamination from the very systems designed to protect the health of the crew. The Freon in cooling loops presented a significant hazard to the crew when the Freon was released. Oxygen canisters in Mir presented a life-threatening problem for the crew when they caught fire (Burrough, 1998; Linenger, 2000). There was danger not only from fire but also from the smoke and particulate matter released from the canisters themselves. Data collected during the Extended-Duration Orbiter Medical Project‘s evaluation of volatile organic compounds in the cabin atmosphere indicated that levels were below maximum allowable concentration (SMAC) limits in the spacecraft. It was noted that most pollutants reach a state of equilibrium within the first 3 to 4 days of a mission; however, the exceptions are hydro- gen, methane, dichloromethane, and formaldehyde. Dichloromethane and formaldehyde are of concern because both have significant toxic properties.

94 SAFE PASSAGE Missions of 2 weeks’ duration measured dichloromethane levels of 0.79 mil- ligrams per cubic meter (mg/m3; 30-day SMAC of 20 mg/m3) and formalde- hyde levels as high as 0.08 mg/m3 (30-day SMAC of 0.05 mg/m3) (Pierson et al., 1999). Exposure to hazardous materials during space travel could result in multiple casualties with serious injuries, burns, or smoke inhalation that would soon outstrip the finite resources available on the spacecraft. Plan- ning to minimize exposure of the crew includes the identification of poten- tial hazards, recognition that a hazardous material is responsible for acute signs and symptoms, identification of the agent(s) involved, retrieval and review of information regarding toxicity and secondary contamination, pro- tection of unexposed personnel from primary and secondary contamina- tion, methods for triage and decontamination of the exposed individual(s), and treatment of the injured and exposed individuals. Available resources should be modified as the technology advances and should be easily avail- able to the crew (ATSDR, 1991; Sidell et al., 1991). Methods for continuous surveillance for toxic contaminants should be in place, using Earth analog models (ATSDR, 1997). Health Care Opportunity 3. Developing an easily accessible hazardous materials manual for space travel to aid in the surveillance, detection, decontamination, and treatment of chemical exposures. The concentrations of the particulate pollutants detected in the space shuttle ranged from 35 to 56 mg/m3, with the majority of them being greater than 100 micrometers in diameter. Most particles did not settle out of the atmosphere during the mission. Most were organic in nature and were most likely generated by crewmembers (Pierson et al., 1999). Health Care Opportunity 4. Monitoring and quantifying particulates on a continuing basis. Microbial Contamination The quantification of airborne bacteria and fungi indicates that the levels of bacteria increase moderately with the dura- tion of the mission and that the levels of fungi decrease with the duration of the mission. The levels of bacteria range from a few hundred to 1,000 colony- forming units per cubic meter (CFU/m3) of air during longer missions. Fif- teen species of bacteria were recovered from samples collected during space missions. Staphylococcus, Micrococcus, Enterobacter, and Bacillus species were

MANAGING RISKS TO ASTRONAUT HEALTH 95 found on 85 percent of the missions; and Staphylococcus aureus was recov- ered during 57 percent of the missions (Nicogossian and Parker, 1982). Fungi tended to be present at a few hundred CFU/m3 early in the mis- sions, but their quantities dropped to undetectable levels toward the ends of the missions. Nevertheless, low levels of Aspergillus and Penicillium species are found during greater than 60 percent of the missions (Nicogossian and Parker, 1982; Mehta et al., 1996). The essential questions are as follows: How transmissible are these or- ganisms? How much mixing of flora occurs between and among crewmembers? Is bacterial or fungal overgrowth an issue for long-duration space travel? Lastly, how does the radiation environment affect the growth of microorganisms and their toxicities to humans? Health Care Opportunity 5. Examining the capability of microbial iden- tification, control, and treatment during space travel. Noise In both the U.S. and the Russian space programs, noise has been a major problem. Spacecraft noise levels disrupt sleep, increase stress and ten- sion, and can result in temporary or even permanent hearing loss. The envi- ronmental control system, system avionics, and payload experiments gener- ate most of the noise. The design limits of most work environments range from 63 to 68 decibels (dBA). The noise levels on a number of space mis- sions has exceeded this baseline limit, exposing the crew to noise levels far greater than normal terrestrial noise levels. The maximum permissible con- tinuous exposure level in a work environment is 90 dBA for an 8-hour pe- riod, according to the Occupational Safety and Health Administration. Early in the life of the ISS it was about 75 dBA. In a spacecraft, the environmental noise level is steady, and it continues for months. This will certainly have a deleterious affect on astronauts’ hearing (Koros, 1991b; Koros et al., 1993), and it may affect astronauts’ concentration and behavior as well. Health Care Opportunity 6. Developing methods for noise cancellation or reduction. Ergonomic Issues Because the human body has evolved on Earth in the presence of Earth’s gravity astronauts are vulnerable to ergonomic problems in microgravity. During a space mission, crewmembers try to maintain a neutral body posture, wherein the shoulders, arms, hips, and legs are flexed and in a relaxed position. Working on an experiment such as one in a glove box, however, requires the crewmember to work against the natural ten-

96 SAFE PASSAGE dency of the body to assume this posture. This increases fatigue, decreases performance, and predisposes crewmembers to injury (Mount and Foley, 1999). Health Care Opportunity 7. Standardizing ergonomic practices on the basis of the human body’s response to the microgravity environment. External Environment Radiation Much is known about the radiation environment of low Earth orbit; little, however, is known about the radiation environment of high Earth orbit and beyond. The ISS will be exposed to primary ionizing radiation and high-energy particle radiation from solar and galactic sources (SSB and NRC, 2000a). Exposure to secondary radiation—that is, radiation emitted from spacecraft metals and other materials following collision of their nuclei with high-energy solar or galactic particles penetrating the spacecraft shell—may also be a problem. In low Earth orbit, a band of atmospheric radiation, known as the Van Allen belts, is concentrated over the South Atlantic, hence the term South Atlantic Anomaly. An orbiting spacecraft will spend only 2 to 5 percent of its time in this region, but astronauts receive more than half of their total radiation doses during this period. Most penetrating radiation from the Sun results from solar particle events (SPEs) and mostly consists of protons generated by solar storms. The Earth’s geomagnetic field shields against solar particle events up to 6,370 kilometers above the Earth (Letaw et al., 1987, 1988). Recent reports note that construction of the ISS will take place during a period of maximum solar activity, when the probability of encountering SPEs and Earth-trapped radiation is high. During periods of intense solar activity, solar winds result in elevated intensities of energetic electrons. These are known as known as highly radioactive events. Galactic cosmic rays make up about a third of the radiation in space and produce a continuous low-level form of radiation. Protons of only 10 million electron volts (MeV) of energy can penetrate a space suit, and 25- to 30-MeV protons can penetrate the space shuttle (Lemaire et al., 1996). Beyond Earth orbit, the issue of radiation exposure presents a major challenge for NASA as the quantities of solar and galactic radiation and the potential for exposure increase. Health Care Opportunity 8. Developing methods to measure human solar and cosmic radiation exposures and the means to prevent or miti- gate their effects.

MANAGING RISKS TO ASTRONAUT HEALTH 97 HEALTH CARE PRACTICE OPPORTUNITIES Cardiovascular Care Cardiovascular integrity is essential to the health and well-being of as- tronauts on long-duration space missions, but there is no experience with the delivery of cardiovascular care on such missions. Therefore, the infor- mation and recommendations presented here are derived from the few pub- lished data on cardiovascular complications incurred during the Mercury, Gemini, Apollo, and Skylab missions (SSB and NRC, 1998c; Charles et al., 1999) and from general principles of cardiovascular care on Earth (Braunwald, 1999). Standards for the initial screening of astronauts, follow-up annual physi- cal requirements, and causes of rejection are listed in NASA’s Astronaut Medical Evaluation Requirements Document (NASA, 1998a). Although there are provisions for waivers, it is reasonable to assume that selected crew- members are at low risk for the development of cardiac problems. This is important, because it will be extremely difficult to treat moderate to severe cardiovascular complications during a long-duration space mission. Space limitations will preclude an extensive pharmacy or medical procedure unit, and no individual with expertise in cardiovascular system-related procedures may be on board to handle cardiovascular complications. Some of the cardiovascular symptoms and abnormalities that astronauts may present with during a long-duration space mission include high blood pressure with or without symptoms; atrial and ventricular premature beats; atrial arrhythmias, such as atrial fibrillation, atrial flutter, and supraventricu- lar tachycardia; sustained and nonsustained ventricular fibrillation; chest pain, ischemic and nonischemic; shortness of breath, cardiac and noncar- diac; orthostatic hypotension; syncope; vasovagal and other cardioneuro- genic responses; and edema, cardiac and noncardiac. A strategy must be in place to deal with these on a risk-assessed priority basis and with the pos- sible occurrence of myocardial infarction, whose incidence may increase with the generally increasing age of astronauts at the start of space missions and the extended lengths of missions beyond Earth orbit. Physiological adaptation to planetary gravity after long-term exposure to microgravity may take several days to weeks, with considerable individual variability. Symptoms from adaptive conditions such as orthostatic hypoten- sion, whether on the Moon or Mars or after the return to Earth, should be treated as needed, with the understanding that normal physiological regula-

98 SAFE PASSAGE tory mechanisms will take over, allowing physiological function to return to normal. Health Care Opportunity 9. Providing a thorough cardiovascular evalua- tion similar to the premission evaluation at the cessation of space travel to provide useful data as part of the continuum of astronaut care and to aid in establishing an evidence base for cardiovascular disorders during space travel. Dental Care In 1978, Soviet cosmonaut Yuriy Romanenko experienced a toothache during a 96-day flight of Salyut 6. As his problem worsened, Romanenko gulped painkillers and crewmembers pleaded for help from the ground. The Soviet space program had no contingency plans for dental emergencies; the advice from controllers was “take a mouthwash and keep warm.” Romanenko, “his eyes literally rolling with pain” (Wheatcroft, 1989, p. 7), suffered for 2 weeks before Salyut 6 touched down on schedule. His ordeal was the subject of a televised interview in the Soviet Union, as well as pub- lished accounts in Russian and U.S. space and dental literature (Wheatcroft, 1989). It also focused attention, including that of NASA, on the need to address the possibility of debilitating dental emergencies in space. In April 2000, the IOM Committee on Creating a Vision for Space Medi- cine During Travel Beyond Earth Orbit held a public workshop entitled Space Dentistry: Maintaining Astronauts’ Oral Health on Long Missions (see Appendix A). Presentations from invited experts, as well as other data and information reviewed by the committee, suggest that dental problems need not be a major health care issue for astronauts on long-duration mis- sions. This optimistic outlook assumes appropriate premission dental screen- ing and excellent preventive care, as well as the ability to provide in-flight prophylaxis and restorative treatment as needed. A review of advances in preventive dentistry (Box 3-5) led one workshop presenter to predict that by 2020 NASA may be able to select the first Mars crew from a pool of caries- free astronauts (Mandel, 2000). Still, good teeth and a history of preventive care cannot guarantee that no caries will develop in anyone over the course of a 3-year mission. Some factors that could contribute to the development of tooth and gum disease include changes in bacterial flora in the mouth, inattention to good dental hygiene, changes in food consistency because of the consumption of dehy- drated space meals, and lack of foods with natural gingival cleansing proper-

MANAGING RISKS TO ASTRONAUT HEALTH 99 BOX 3-5 Advances in Preventive Dentistry A three-part preventive strategy, aggressively pursued by dental researchers and practitioners since 1971, may mean a caries-free pool of astronaut candidates for the first mission to Mars with humans. The strategy consisted of the following components: I. Combating caries-inducing microorganisms • Recognition of dental caries as an infectious disease. • Identification of mutans group streptococci as major cariogenic organisms. • Development of an antibacterial agent, chlorhexidine (also effective against plaque, gingivitis). • Use of chlorhexidine in a prescription rinse, professionally applied varnish, and self-applied gel. II. Modifying diet • A campaign to convince public to restrict sweets was found to be insufficient. • A nonacidogenic sweetener in chewing gum, xylitol, reduces levels of mutans group streptococci. • Protective food components (e.g., polyphenols in chocolate) show promise. • Preservatives with enhanced antibacterial activity are under investigation. • Natural demineralization inhibitors are under investigation. III. Increasing resistance of teeth to decay as a result of • Community water fluoridation. • Professionally applied fluoride solutions, sealants, gels, and varnishes. • Self-applied daily fluoride rinses, brush-on gels, and fluoridated toothpastes. • Controlled-release systems to deliver predetermined amounts of fluoride intraorally. • Fluoride-releasing dental restorative materials to provide site-specific protection. • Clinical testing of other remineralizing agents (e.g., amorphous calcium phosphate). • Testing of new coatings and new coating technologies (e.g., polymeric coatings). • Study of laser light’s ability to alter enamel surfaces, increasing resistance to acid challenge. • Study of salivary proteins with direct antibacterial properties. Source: Mandel, 1996. ties. For these reasons, the crew should be prepared to use restorative tech- niques and materials in microgravity, and NASA should support the devel- opment of new restorative techniques and materials that can be used in microgravity.

100 SAFE PASSAGE The committee’s workshop on oral health included a presentation on atraumatic restorative treatment (ART), which may represent one poten- tially useful approach to the management of dental lesions in space. It is a conservative approach to caries management, in which carious tooth tissue is removed with hand instruments instead of electric rotating handpieces. The cavity is restored (filled) with an adhesive restorative material such as glass-ionomer. The result is a sealed restoration (Estupiñán-Day, 2000). The reported advantages of ART include little or no pain, reduced need for local anesthesia, minimal trauma to the tooth, conservation of healthy tissue, and simplified infection control. Moreover, ART can be performed by individuals who are not dentists. The technique was originally devised for use in developing countries and disadvantaged communities where access to high-quality, definitive dental care is problematic. The Pan American Health Organization is evaluating the longevity of glass-ionomer restorations under various conditions (Estupiñán-Day, 2000). How they might perform in microgravity is not known, however. The committee has reviewed dental health data from long-term mis- sions in analog environments. Such data may be of limited predictive value, however. ANARE reported on the dental health experiences of 64 men over a 42-month period. There were 73 reported dental events, which accounted for 8.80 percent of all medical events (Fletcher, 1983). All the men had been prescreened and found to be “dentally fit.” The preexpedition screening examinations lacked uniform criteria, however, precluding useful compari- sons of that population with other populations. Moreover, the examining dentists did not have the advantage of today’s tools for early detection of developing caries. The committee has learned that NASA is developing new, prevention- oriented dental protocols for space shuttle missions and the ISS and that these are undergoing internal agency review (M. Hodapp, NASA, personal communication, April 10, 2000). An important question remains unanswered: does exposure to micro- gravity result in the loss of bone mineral density in alveolar bone? To date, no human data bearing on this question have been reported. The question arises because of the well-documented loss of bone mineral density in the weight-bearing bones. Also, although no human data exist in the current database, microgravity-induced decreases in bone density might also con- tribute to tooth and gum disease. Health Care Opportunity 10. Developing a program for instruction in basic dental prophylaxis, the treatment of common dental emergencies

MANAGING RISKS TO ASTRONAUT HEALTH 101 such as gingivitis, tooth fracture, dental trauma, caries, and dental ab- scesses; and tooth extractions. Endocrine Function Changes in endocrine function in microgravity have been reported, but the clinical significance and effects on adaptation or maladaptation need more research to determine if they have clinical importance during long- duration space missions. The number of subjects is small and the data are sometimes conflicting. The polar tri-iodothyronine (T3) syndrome has been described in persons living for extended periods in Antarctica. It is charac- terized by baseline elevations of thyroid-stimulating hormone (TSH) levels, exaggeration of increases in TSH levels in response to a challenge with thy- roid-releasing hormone, and more rapid production and clearance of T3 and thyroxin but normal levels of both in serum (Reed et al., 1990). Thyroid axis kinetics should be further studied during space missions (Lovejoy et al., 1999), since models of prolonged bed rest used as analogs for conditions in space have also demonstrated changes in T3 levels and the effects of T3 on nitrogen balance and catabolism. Little has been reported on adrenal function, but its association with sleep disturbances should be investigated, as circadian fluctuations in steroid levels have been well de- scribed on Earth (Birketvedt et al., 1999). Testosterone levels fell in both humans and rats during space missions and on their return to Earth, and studies with rats did not show changes in spermatogenesis (Plakhuta-Plakutina, 1977). There have been no reports that astronauts have had difficulty with reproduction, but no effects from long-duration space mission have been studied (Tigranjan et al., 1982; Deaver et al., 1992). The metabolic stress syndrome is of great importance to space medi- cine, and cortisol production via adrenocorticotropic hormone production by the pituitary gland has been used as a marker. Cortisol levels increase during the first 2 days of a space mission, as do the rates of protein turnover and acute-phase protein synthesis (Stein et al., 1996), documenting the stress of launch and entry into orbit. Caution must be exercised in interpreting data on endocrine function for humans in space because of the large varia- tions in hormone levels among humans, the problems of collection and stor- age of samples, and the variabilities of assays.

102 SAFE PASSAGE Gastrointestinal Issues Gastrointestinal problems account for 8 percent of the recorded medi- cal events on space shuttle missions (Billica, 2000). The incidence is 0.52 per person per 14 days in the space environment. Experience in analog environ- ments suggests that the incidence of gastrointestinal problems is much lower, being only 0.01 per person per year. These data suggest that the motility problems identified during space shuttle missions can be attributed to the effects of the microgravity environment. Many astronauts who develop symptoms of SMS also seem to develop a transient ileus, diagnosed by an absence of bowel sounds. Although motility may remain decreased through- out the space mission and the bacterial population may change, the etiolo- gies are unclear and data from short-duration space missions do not suggest that these lead to significant medical problems. Some spacecraft crewmembers have experienced constipation during missions. This may be related to physiological alterations in the bowel in- duced by the microgravity environment, but the etiology remains unclear. Adequate hydration throughout long-duration space missions should pre- vent constipation. Some crewmembers have experienced diarrhea during the later parts of missions. The etiology is also unknown, but it may simply be related to overmedication for constipation. Diarrhea in the space envi- ronment presents several problems, including constant use of the Waste Containment System and dehydration, which may exacerbate landing orthostasis. Over-the-counter medications (Imodium and Pepto Bismol) for oral ingestion are available in the Shuttle Orbiter Medical Systems (SOMS) kit. Vigorous hydration with oral or intravenous fluids is recommended. Episodes of diarrhea during long-duration space missions can be treated similarly. Gastrointestinal problems are largely prevented through optimal premission screening, and most residual symptomatic problems can be treated in a manner similar to that used on the ground. However, three problems to which the gastrointestinal tract is particularly prone are infec- tion, malignancy, and inflammation. Obstruction of the gallbladder or appendix with calculi and subsequent infection can be lethal without operative intervention. Consideration must be given to prophylactic cholecystectomy and prophylactic appendectomy before long-duration space missions. Although the procedures can be per- formed today with a minimum of morbidity and a low likelihood of any late postoperative complications, it is not clear whether prophylactic removal is warranted. A careful risk-benefit calculation should be performed with fu-

MANAGING RISKS TO ASTRONAUT HEALTH 103 ture data. Population-based data to determine how rapidly gallstones can form in an ultrasound-negative patient may be one useful methodology for determination of the advisability of prophylactic cholecystectomy. Malignancy of the gastrointestinal tract can be ruled out through endo- scopy. On the basis of current practice it would appear prudent that astro- nauts (especially those over age 50) being sent on long-duration space mis- sions have a recent colonoscopy (with or without a concomitant air-contrast barium enema). Consideration might also be given to the screening of can- didates by esophagogastroduodenoscopy before long-duration space travel for esophageal, stomach, and duodenal problems. Inflammation of the pancreas, pancreatitis, is a life-threatening disease even with the best medical care. The many etiologies of pancreatitis include gallstones and specific medications. The use of pharmacological agents that continue to be developed and that are recognized to be associated with the development of pancreatitis should be avoided. Given the technology available today and in the foreseeable future, it is unlikely that surgical procedures on the gastrointestinal tract (except for percutaneous drainage of an abscess, etc.) will be performed on long-dura- tion missions beyond Earth orbit. At this time development of specific coun- termeasures related to the gastrointestinal tract does not appear to be re- quired before long-duration space travel. Gynecological Health Issues Although the likelihood may be small that a gynecological condition that requires surgical intervention will occur during space travel, the occur- rence of such a condition would present special problems. Therefore, as with other medical conditions, attention must be directed toward preven- tion, conversion of surgical conditions to medically treatable conditions, and, where necessary, the ability to do surgery. For example, pregnancy and its inherent complications, including spontaneous abortion, ectopic pregnancy, and abnormal bleeding, can be prevented with appropriate contraception. Sexually transmitted diseases and their complications will be able to be pre- vented or treated. Oral contraceptives can help the abnormal bleeding asso- ciated with anovulation and the development of functional cysts of the ovary. Surgical conditions, such as uterine myoma, endometriosis, and dysfunc- tional uterine bleeding, can now be treated medically. Regardless of these measures, there will be some conditions, such as ovarian neoplasm, adnexal torsion, or bleeding, which will require surgery.

104 SAFE PASSAGE Although elective laparoscopic appendectomy before prolonged space mis- sions has been given some consideration, surgical prevention of adnexal ab- normalities is not a consideration except perhaps for postmenopausal astro- nauts, and the relative risk and treatment means and priority must continue to be evaluated. Contraception and Hormone Replacement Therapy Because of the absolute preclusion of pregnancy while in the space pro- gram, many female astronauts have chosen contraceptive methods that are known to be very effective. These include intrauterine devices, implants, and oral contraceptives made up of various combinations of hormones, all of which have been continued during space travel (Jennings and Baker, 2000). Although an intrauterine device is an effective contraceptive, for long- duration space missions, the added noncontraceptive benefits of hormonal contraceptive agents may make them preferable. For example, hormonal agents reduce the volume of menstrual flow. Although most women on oral contraceptives have a withdrawal cycle every 28 days, it is possible to extend the cycle from every 28 days to several months. With some hormonal agents, complete cessation of bleeding for the duration of the mission may be pos- sible. Oral contraceptives frequently relieve the dysmenorrhea associated with menses. The ovaries of women on oral contraceptives are less likely to form cysts, which may undergo torsion or other complications. Not only are oral contraceptives an effective way to manage dysfunctional uterine bleed- ing or bleeding associated with anovulation, should that occur in space, oral contraceptives are also effective treatment for the estrogen deprivation asso- ciated with hypogonadotropic hypogonadism and prevention of the bone mineral density loss associated with this condition. Hormone replacement therapy is known to be effective in preventing osteoporosis among women of certain ages on Earth. During space travel, hormone replacement therapy, as on Earth, will be of importance in pre- venting calcium loss in postmenopausal crewmembers. Health Care Opportunity 11. Studying the bioavailability and pharmaco- logical function of exogenous hormone therapy during space travel and, as new medical therapies for gynecological surgical conditions evolve, testing of these therapies for use during space travel.

MANAGING RISKS TO ASTRONAUT HEALTH 105 Hematology, Immunology, and Microbiology Decreased red blood cell mass during space missions has been recog- nized since 1977 (Johnson et al., 1977; Leach and Johnson, 1984), but there is no resulting impairment from this ”anemia.” The documented fall in eryth- ropoietin levels and the fall in the numbers of reticulocytes indicate that this results from diminished production, not increased cellular destruction (Alfrey et al., 1996). However, because of the diminution of the plasma vol- ume early in the flight, the measured hematocrit levels and red blood cell counts did not fall during flight but were noted after the return to Earth because of the more rapid restoration of plasma volume than the level of red blood cell production. Erythropoietin levels returned to normal in 1 to 2 weeks after landing. In 1990, Koury and Bondurant (1990) hypothesized that erythropoietin prevents programmed cell death in erythropoid progeni- tor cells, thereby adding significantly to general medical knowledge through research conducted in space. Anemia could become a clinical problem dur- ing long-duration space travel, and erythropoietin administration is being evaluated as a countermeasure. Altered cell-mediated immunity has been reported in a variety of analog environments, including the Antarctic (Tingate et al., 1997) and space (Kimzey et al., 1975, 1977). Escherichia coli and Staphylococcus aureus iso- lates have also been shown to become more resistant to selected antibiotics during space travel (Lapchine et al., 1986). Although the clinical signifi- cance of these alterations has not been determined, the effects on skin and wound infections and wound healing during long-duration space missions could become clinically important. Preflight isolation techniques for spaceflight crewmembers are reported to have decreased the infection rate for the 3 weeks preflight from about 50 percent to only occasional events (Ferguson, 1977; Ferguson et al., 1977). Gingivitis and skin furuncles are now the primary preflight infections re- ported (Taylor and Gormly, 1997). Increased shedding of herpesvirus and expansion of Epstein-Barr virus-infected B cells have been reported in the Antarctic environment (Tingate et al., 1997; Lugg and Shepanek, 1999) and in astronauts (Payne et al., 1999). The bases for the divergent changes are not understood. They do, however, indicate the importance of immunology and microbiology to healthy human physiology during space travel and the need for further research in this area of space medicine.

106 SAFE PASSAGE Health Care Opportunity 12. Performing clinical studies on anemia, immunity, wound infection, and wound healing as part of every space mission. Mental Health Issues The transition to long-duration space missions will require greater em- phasis on ways to prevent and successfully manage an array of challenges to the cognitive capacities and emotional stabilities of astronauts who will find themselves in an isolated, confined, and hazardous environment. They will be devoid of much of what supports their emotional well-being on Earth and will need to develop and maintain new coping strategies appropriate to the unique environment of space beyond Earth orbit. Current data on the psychiatric sequelae of long stays in surly environ- ments come primarily from studies of military personnel on submarine duty, Antarctic field scientists, and Biosphere inhabitants (Billica, 2000), as well as more limited experience on the Russian space station Mir. These data suggest that the incidence of discernible psychiatric symptomatologies, in- cluding depression, anxiety, substance abuse, and psychosis, ranges from 3 to 13 percent per person per year, depending on the setting (see Tables 3-2 to 3-7). Transposed to a six- or seven-member space crew on a 3-year mis- sion, the likelihood that psychiatric problems will arise on such an expedi- tion is not insignificant but is less than 54 percent—(3 percent/year) × (six astronauts/year) × (a 3-year mission)—per astronaut during a 3-year mission among a space crew when one extrapolates from the crude available data on behavioral disturbances in space. Such problems can range from simple boredom and fatigue to acute stress reactions, profound depression, and overt psychosis. Some mental health problems may become more likely over time as the cumulative effects of environmental and interpersonal stressors are magnified by the extended duration of the mission. The NASA Experience to Date Almost all of NASA’s behavioral medicine experience with space travel- ers thus far has been with flights of relatively short duration (i.e., 2 to 3 weeks), where emergent signs and symptoms have included evidence of stress, anxiety, diminished concentration, depressed mood, malaise, and fa- tigue. These problems have been identified in less than 2 percent of astro- nauts, and their effects on individual and crew performance have reportedly

MANAGING RISKS TO ASTRONAUT HEALTH 107 been negligible (Flynn and Holland, 2000). As a result, with the exception of the astronaut selection process, the level of clinical and research interest in mental health problems that may affect human performance during space missions has been relatively low. At the same time, there is growing aware- ness that such problems could prove to be major impediments to the suc- cessful conduct of longer-duration missions. Mental Health Aspects of Extended-Duration Spaceflight Little is known about the psychological capacity of humans to with- stand the stresses of long-duration space travel, but what is known (e.g., from the experience on Mir) is ominous. Experience with extended-dura- tion flights, defined as flights longer than 100 days (about 1/10 the antici- pated duration of a mission to Mars), suggests that boredom, fatigue, and circadian rhythm and sleep disturbances, coupled with the exacting human performance requirements of such missions, constitute risk factors for the development of depressive syndromes of various severities, anxiety and irri- tability, and at times, dysfunctional interpersonal relationships, either within the spacecraft or between astronauts and ground personnel. On missions beyond Earth orbit, in which spacecraft crews will be isolated and confined to a relatively small living space and in which medical evacuation will not be an option, the development of these and other mental health problems may exert cumulative detrimental effects both on individual astronauts and on their fellow crewmembers sufficient to jeopardize the mission. Meeting this challenge will require a reassessment of the mental health needs of astronauts in the context of NASA’s overall health care program. Areas of renewed emphasis and support should include premission psychi- atric evaluation; intramission psychiatric support and treatment, including the possibility that acute interventions may be required, such as in a major psychotic break, possibly with the use of forcible restraint and psychoactive drugs; and a program of postmission assessment, follow-up, and interven- tion where appropriate, as discussed in Chapter 5. For international efforts involving multinational crews, language and cultural differences, along with different approaches to diagnosis and treatment, will complicate these tasks. Accordingly, the United States and its partners in space must move toward the development of a health care system for astronauts (see Chapter 7) with a common language, common diagnostic criteria, and common standards of care. In so doing, some suggested areas of emphasis (see also Chapter 5) are as defined below.

108 SAFE PASSAGE Health Care Opportunity 13. Developing methods for the identification and management of mood disorders and suicidal or homicidal ideation and developing protocols for the management of violent behavior, in- cluding crisis intervention, pharmacological restraint, and physical re- straint. Premission Screening and Selection The issue of crew selection needs to be rethought in the context of long- duration space missions. As detailed in Chapter 5, valid and reliable psychi- atric screening instruments should be further developed, tested, and refined. The process of astronaut selection into or out of the program must include efforts to predict crewmembers’ responses to the anticipated stresses of long- duration space missions on the basis of data derived from studies carried out on the ISS as well as in analog environments. Assessment of interpersonal, leadership, and followership skills, problem-solving capabilities, and emo- tional stability under conditions of extended isolation are some of the areas appropriate for future research. In addition, personal and family history data coupled with laboratory testing may identify individuals at increased risk for mental disorders (e.g., depression) that may emerge over the course of long- duration space travel and may be included in the database on which crew selection and flight assignments are based. The development of more sophisticated selection and deselection crite- ria is a first step, to be followed by specific individual and group training in behavioral self-assessment and the self-administration of countermeasures designed for a range of anticipated health problems. Training individuals to work successfully within a small group and to engage in productive and collaborative problem solving with ground crews should be part of this pro- cess. The relative value of such training and the efficiency of specific coun- termeasures should also be assessed in the context of a well-designed pro- gram of behavioral and psychosocial research. Such studies should be carried out in the course of extended stays in space and in appropriate simulated or analog environments. Finally, the selection and training of the members of ground crews who will support and direct long-duration missions should be parallel to and integrated with the selection and training of the astronauts. Dealing with Intramission Mental Health Problems As mental health problems arise, some will respond to countermeasures designed and tested during premission training, whereas others will require

MANAGING RISKS TO ASTRONAUT HEALTH 109 the intervention of crewmembers or ground personnel. In this context, there will need to be clearly defined duties and responsibilities for such personnel, as well as appropriate training. Evidence-based clinical protocols and treat- ment algorithms that are specifically adapted for the space environment will need to be developed and tested. In addition to the availability of psychiatric expertise on the ground, the preventive approach to in-mission mental health care should include the prior development of supportive and therapeutic relationships between men- tal health clinicians, crewmembers, and crewmember families. In this con- text, finding ways of ameliorating the effects of prolonged communication delays between space and the ground should be a research priority. An onboard formulary that anticipates the range of psychiatric problems that may or will arise is also essential, as is research on the pharmacokinetics of current and future psychotropic medications in microgravity environments. Technology offers promise for maintaining behavioral health when pro- fessional assistance is millions of miles away. One type of countermeasure is software designed to self-diagnose and relieve emotional symptoms before they become a psychiatric condition. The first of most famous of these was ELIZA (Weizenbaum, 1966, 1979). It mimicked a nondirective therapeutic dialogue. The second generation of algorithm-driven software packages is now available. One example is the Therapeutic Learning Program (Gould, 1989). Software-guided therapy, when coupled initially with individual train- ing and clinical oversight, has produced relief of symptoms ranging from headaches to anxiety and depression. Although, for the most part, the gains are nowhere near those obtained from individual treatment, the benefits are far superior to no treatment at all. An excellent and balanced review of this subject is contained in Massachusetts Institute of Technology Professor Sherry Turkel’s book, Life on the Screen: Identity in the Age of the Internet (Turkel, 1995). It is likely that later versions of these methods will be far more effective and could be adapted, with adequate training and clinical oversight, for use by astronauts on long-duration missions. Postmission Mental Health Care Although acute and chronic in-mission psychiatric problems may jeop- ardize mission success, severe, postmission mental health problems, if di- rectly attributable to astronauts’ participation in long-duration missions, could jeopardize the program itself. The NASA-sponsored longitudinal fol- low-up study of astronauts’ health has not revealed any untoward psychiat- ric sequelae of participation in the space program, although the stress of

110 SAFE PASSAGE reintegration and postflight adjustment has been noted. The unpredictable effects of mission-related physiological changes and potential exposure to radiation, coupled with the emotional stress of reintegration following a long-duration mission, make it imperative that a postmission program of psychiatric assessment and individual, peer, and family support as well as mechanisms for long-term peer and family follow-up support be developed. Neurological Issues Nervous system dysfunction and illness may occur as a result of physi- ological adaptive responses (both neural and systemic) to microgravity, as a consequence of problems that arise within the spacecraft, or as a result of external events or exposures. In considering the neurological illnesses or events that might occur during a mission to deep space, the timing, type, and severity of problems should be taken into account. A logical medical distinction is to consider neurological problems that affect either the central nervous system or the peripheral nervous system, or both. This somewhat arbitrary distinction has practical implications from a diagnostic and thera- peutic perspective. Available data indicate that a fairly high incidence of minor neurological complaints may occur (Tables 3-2 and 3-3). Contingen- cies are also needed for catastrophic neurological events, including those that threaten astronauts’ lives and the mission itself. NASA recognizes that the occurrence of certain severe life-threatening events can exceed the ca- pacities of either the astronaut crew or ground control to intervene medi- cally. This concept of acceptable risk may be different for a single one-time mission than for a multimission exploratory program. Acute Central Nervous System Illnesses or Events There are insufficient data on which to base sound estimates of either the incidence of various central nervous system problems or the extent to which various central nervous system problems might occur during a long- duration space mission. So far, no major neurological illnesses have been reported. However, reports from the U.S. and Russian manned space mis- sions suggest that minor neurological problems are frequently encountered (Tables 3-2 and 3-3). These include headache and vestibular dysfunction, particularly upon the initial entry into microgravity. A serious problem upon the return to Earth is orthostasis, with its consequent effects on many bodily systems including the central nervous system.

MANAGING RISKS TO ASTRONAUT HEALTH 111 Closed head injuries and spinal cord injuries are among the most serious neurological events that could occur during travel beyond Earth orbit. Man- agement and treatment of individuals with severe closed head injuries would likely be beyond the capability of an astronaut crew unless dramatic new approaches to clinical management are developed. Thus, injuries that pro- duce very low Glasgow coma scales by today’s standards will probably result in death, as they frequently do under the best of circumstances in current state-of-the-art medical centers. However, consideration should be given to training in the management of individuals with less severe closed head inju- ries. Individuals with mild or moderate closed head injuries may survive but remain disabled because of residual neurological deficits. Management is- sues today include placement of burr holes for evacuation of subdural he- matomas, feeding and airway control, spinal cord stabilization, and manage- ment of bowel and bladder functions and infections. Other events to consider include toxic exposures, decompression sickness (especially in con- nection with EVAs), cerebrovascular-like events, spinal injuries, exposure to radiation, and seizures. The current neurological clinical research program at NASA, although extensive, does not appear to be well coordinated among the various re- search organizations and those that design and conduct flight operations. Detailed treatment contingencies based on the accumulated evidence base for the entire spectrum of neurological diseases should be developed. Such treatments should be continuously reviewed and updated to maintain state- of-the-art readiness. Health Care Opportunity 14. Establishing a coordinated clinical re- search program that addresses the issues of neurological safety and care for astronauts during long-duration missions beyond Earth orbit. Urinary Disorders Genitourinary disease may present as an infection, obstruction, or ma- lignancy. Many potential genitourinary problems will be identified through standard screening. Renal stone formation (expected in 0 to 5 percent of astronauts) secondary to bone calcium mobilization and excretion in the urine is a well-identified concern in microgravity environments. The geni- tourinary effects of microgravity also include changes in urodynamics (un- known incidence) and urinary hesitancy (reported seven times). Nephroli- thiasis is a concern during extended stays in microgravity, as alterations in calcium metabolism and hydration status have previously been identified in

112 SAFE PASSAGE this environment. Dehydration (incidence, 0.01 per 14 days on the space shuttle) is a recognized problem (Lane and Schoeller, 2000). Dehydration or significant changes in pH and increases in calcium and citrate levels increase the risk of renal stone formation. Preflight screening should include appro- priate ultrasound evaluation for nephrolithiasis. Urinary tract infections are common (and are more common in females) and are generally easy to treat with antibiotics. Prostatitis can be treated with antibiotics. Preflight screening for prostate cancer by determination of the prostate-specific antigen level in serum and other evaluations, according to today’s standards, appears to be adequate, although future consideration may be given to preflight ultrasound or other developing noninvasive meth- ods. Countermeasures for genitourinary problems are primarily oriented to- ward the prevention of nephrolithiasis through adequate hydration. The rec- ommended daily fluid intake is greater than 2.5 liters. A more than adequate water supply must be ensured so that crewmembers do not hesitate to drink adequate volumes of water to prevent the formation of renal calculi. As ultrasound devices become smaller, it is likely that an ultrasound device will be standard medical equipment for all long-duration space missions. This would make it possible and desirable to perform in-mission screening for nephrolithiasis (to identify those who require medication or increased levels of hydration to treat calculi). As countermeasures are developed for the problem of bone mineral density loss in microgravity, it must be ensured that the solutions do not result in increased rates of renal stone formation secondary to alterations in calcium metabolism. Some of the health care opportunities that may be explored to increase the future effectiveness of managing risks to astronaut health during space travel have been described in this chapter and are listed in Box 3-6. This is a short list of current opportunities. It is neither a comprehensive list nor a list of priorities but is presented as a list of areas of research and development to be considered. New opportunities, including some that may take prece- dence, will develop in the future as the field of space medicine continues to evolve. CONCLUSION AND RECOMMENDATION Conclusion Space travel is inherently hazardous. The risks to human health of long- duration missions beyond Earth orbit, if not solved, represent the great-

MANAGING RISKS TO ASTRONAUT HEALTH 113 BOX 3-6 Health Care Opportunities in Space Medicine 1. Expanding, validating, and standardizing a modified physical examination, the microgravity examination technique, and including a technique for pelvic examina- tion for use in microgravity. 2. Developing an easily accessible database for medications on the spacecraft, including dosage, indications, adverse effects, and anticipated changes in the pharma- cokinetic profile in microgravity. 3. Developing an easily accessible hazardous materials manual for space travel to aid in the surveillance, detection, decontamination, and treatment of chemical expo- sures. 4. Monitoring and quantifying particulates on a continuing basis. 5. Examining the capability of microbial identification, control, and treatment during space travel. 6. Developing methods for noise cancellation or reduction. 7. Standardizing ergonomic practices on the basis of the human body’s response to the microgravity environment. 8. Developing methods to measure human solar and cosmic radiation exposures and the means to prevent or mitigate their effects. 9. Providing a thorough cardiovascular evaluation similar to the premission eval- uation at the cessation of space travel to provide useful data as part of the continuum of astronaut care and to aid in establishing an evidence base for cardiovascular disor- ders during space travel. 10. Developing a program for instruction in basic dental prophylaxis, the treatment of common dental emergencies such as gingivitis, tooth fracture, dental trauma, caries, and dental abscesses; and tooth extractions. 11. Studying the bioavailability and pharmacological function of exogenous hor- mone therapy during space travel and, as new medical therapies for gynecological surgical conditions evolve, testing of these therapies for use during space travel. 12. Performing clinical studies on anemia, immunity, wound infection, and wound healing as part of every space mission. 13. Developing methods for the identification and management of mood disorders and suicidal or homicidal ideation and developing protocols for the management of violent behavior, including crisis intervention, pharmacological restraint, and physical restraint. 14. Establishing a coordinated clinical research program that addresses the issues of neurological safety and care for astronauts during long-duration missions beyond Earth orbit.

114 SAFE PASSAGE est challenge to human exploration of deep space. The development of solutions is complicated by lack of a full understanding of the nature of the risks and their fundamental causes. • The unique environment of deep space presents challenges that are both qualitatively and quantitatively different from those encountered in Earth orbit. Risks are compounded by the impossibility of a timely return to Earth and of easy resupply and by the greatly altered communi- cations with Earth. • The success of short-duration missions may have led to misunder- standing of the true risks of space travel by the public. Public under- standing is necessary both for support of long-duration missions and in the event of catastrophe. Recommendation NASA should give increased priority to understanding, mitigating, and communicating to the public the health risks of long-duration missions beyond Earth orbit. • The process of understanding and mitigating health risks should be open and shared with the national and international general bio- medical and health care research communities. • The benefits and risks—including the possibility of catastrophic illness and death—of exploratory missions should be communicated clearly, both to astronauts and to the public.

NOTES

Mission Specialist Jeffrey A. Hoffman and Payload Commander F. Story Musgrave dur- ing an EVA, i.e., a space walk, on December 8, 1993, from the space shuttle Endeavor, during STS-61. The space walk to deploy solar arrays on the Hubble Space Telescope lasted 7 hours and 21 minutes. NASA image. 116

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Safe Passage: Astronaut Care for Exploration Missions sets forth a vision for space medicine as it applies to deep space voyage. As space missions increase in duration from months to years and extend well beyond Earth's orbit, so will the attendant risks of working in these extreme and isolated environmental conditions. Hazards to astronaut health range from greater radiation exposure and loss of bone and muscle density to intensified psychological stress from living with others in a confined space. Going beyond the body of biomedical research, the report examines existing space medicine clinical and behavioral research and health care data and the policies attendant to them. It describes why not enough is known today about the dangers of prolonged travel to enable humans to venture into deep space in a safe and sane manner. The report makes a number of recommendations concerning NASA's structure for clinical and behavioral research, on the need for a comprehensive astronaut health care system and on an approach to communicating health and safety risks to astronauts, their families, and the public.

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