Motion sickness susceptibility during rotation at 30 rpm in free-fall parabolic flight

Free fall per se whether in parabolic or orbital flight may be regarded as a "partial" motion environment with respect to eliciting motion sickness, requiring an additional component to render this environment "complete" or stressful. Parabolic flight in toto falls in the category of a "complete" motion environment in that some persons became motion sick with head fixed and eyes closed. In the present experiment we selected subjects who were symptom free or nearly symptom free in the KC-135 with head fixed. All tests were conducted with the subject rotating at 30 rpm in a rotating litter chair, and comparisons were made between head-fixed and head-moving conditions (right-left) in the free-fall phase of parabolic flight and under simulated free-fall phases in the laboratory. With head fixed most subjects were insusceptible; with head moving left-right susceptibility was slightly higher in the laboratory than aloft. An additional comparison was made correlating susceptibility in the free-fall phases of parabolic flight with susceptibility to experimental motion sickness in Skylab. In both situations cross-coupled angular accelerations were generated by executing head and body movements out of the plane of rotation. In parabolic flight 9 of 15 subjects reached an endpoint just short of frank motion sickness. In the Skylab workshop all eight of the astronauts tested were symptom free at the end of the test. The explanation for the difference in susceptibility rests in two factors: (1) Basic susceptibility in free fall is lower than on the ground, and (2) in Skylab the astronauts who needed to adapt had achieved this goal prior to the first test on Mission-Day 8.     

Male and female characteristics in vestibular testing: a step toward the selection of the best participants for space flight

Vestibular disturbances in connection with space flight were reported by a majority of participating astronauts and cosmonauts. These include motion sickness symptoms in the first few days of the space flight, as well as standing, gait and orientation disturbances after the return to Earth. The Aerospace Medical Community has been trying to select those people that are particularly adapted to the above stresses or that can be further adapted through training programs. As the circle of selectees extends to women, the problem arises as to whether differences between men and women exist under the conditions of space flight. In seeking answers to this question we studied a group of 42 women and 44 men, who were further subdivided according to their subjective motion sickness sensitivity, as determined by a questionnaire. Using this material, 26 men and 22 women were designated as motion sickness resistant, and 18 men and 20 women were designated as nonresistant. The vestibular test battery given these test subjects consisted of caloric, rotatory, optokinetic, vestibulo-spinal and vestibulo-vegetative testing. Because of the mixed orthostatic and vestibular problems seen after space flights, we also studied the response of the vestibular apparatus during peripheral blood pooling as induced by lower body negative pressure. The collected historical and test data are analyzed in this paper with emphasis on the relationship to motion sickness tendency.     

Space motion sickness

Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3-5 days, and as revealed by the Skylab M131 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.     

Free fall: a partial unique motion environment

Conditions leading to the elicitation of motion sickness have been divided into two main categories: partial motion environments, in which head movements are required to elicit motion sickness, and complete motion environments, in which independent movements of the head are not required for the production of symptoms. It is postulated that, according to this categorization, free fall constitutes a partial motion environment. In support of this hypothesis evidence is reviewed from Skylab missions, experiments in parabolic flight, and ground-based studies.     

Vestibular factors influencing the biomedical support of humans in space

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.     

U.S. manned space flight: the first twenty years, a biomedical status report.

In the last 20 years, the biomedical problems facing man in space have been brought into sharper focus. Space motion sickness is presently our most serious problem. Its etiology remains obscure, but the "sensory conflict" theory appears most plausible. No valid predictive tests of susceptibility exist and presently we must rely on medication for prevention or mitigation of symptoms. Adaptation/biofeedback techniques may prove useful. Cardiovascular "deconditioning" may be effectively attenuated by use of anti-g suits or plasma expanding techniques. Recent bedrest simulation studies would seem to indicate that concerns about chronically elevated central venous pressure during space flight are unfounded. The loss of red cell mass in space flight appears to be self-limited, independent of mission duration, and not of clinical concern, based on recent Soviet experiences. And finally, clodronate, a new diphosphonate effective in preventing hypercalciuria and negative calcium balance in normal human bedrested subjects, may prove effective in preventing or lessening skeletal mineral loss in space.     

Coping with space motion sickness in Spacelab missions.

A substantial number of persons, around 75%, making their first transition into orbital flight will need to adapt to this unique environment. The two most powerful instruments in the prevention of space motion sickness reside in the selection process and in acquiring adaptation-prelaunch. Today, neither of these means is practical. One logical alternative is to administer preventative medication to all or none. One candidate drug is a high-potency transdermal therapeutic system (TTS)-scopolamine. This is marketed in the nature of a patch that is affixed to the skin behind the ear 12 hr before need and delivers scopolamine into the blood stream for three days. We are systematically evaluating all claims for its high potency and low side effects. We are also evaluating new antimotion sickness remedies and new combinations of homergic drugs.     

Changes in the vestibular function during space flight

An analysis of observations and investigations carried out in space flight has shown that some cosmonauts and astronauts have experienced vestibular disorders during the transition to weightlessness. Vestibular-sensory disorders include: Spatial illusions (the feelings of falling down, being in an upside-down position, the sensations of rotation of the craft or the body) and vertigo occurring during the onset of the orbital flight and head movements; Feelings, similar to those experienced in response to Coriolis accelerations on the Earth, which occasionally develop in weightlessness during the spacecraft rotation upon abrupt head and body movements and restrained feet; Feelings "of the load on the vestibular analyser which is unlike any Earth-bound effects" upon abrupt head movements during the first hours of an orbital flight and "a prolonged movement" during the switch-off of thrusters in weightlessness. Vestibular-vegetative disorders comprise a complex of symptoms similar to those of motion sickness: loss of appetite, stomach awareness (12%), hypersalination, nausea (9.6%) and vomiting (4.8%). Soviet studies suggest that the vestibular tolerance to the flight effects depends on the natural stability and training to the cumulative effect of adequate vestibular stimuli. This has been used in the development of the system of vestibular selection. Changes in the vestibular function seem to play the major role in the development of motion sickness in weightlessness, extra-labyrinthine factors being contributory. The current hypotheses have not yet been adequately confirmed in experiments. A detailed physiological analysis allows the conclusion that the decisive factor in the development of motion sickness may be the disturbance of the function of analysers responsible for spatial orientation which take the form of sensory conflicts as well as an altered reactivity of the organism due to the hemodynamic rearrangement.     

Development of space motion sickness in a ground-based human centrifuge

Adaptation of the vestibular system, specifically the otolith organs, to a non-terrestrial environment can result in space motion sickness-like symptoms when the human is reintroduced to the normal, 1 Gz, terrestrial environment. This premise was investigated by exposing nine subjects to 90 min of sustained 2 Gz acceleration in a human centrifuge and then observing and evaluating them at 1 Gz. Five of the subjects developed slight SMS symptoms, three developed moderate, and one developed frank sickness. Postural instabilities in two of the most affected subjects were also observed using the Equitest System post exposure. Long duration exposure to a non-terrestrial G(2Gz) appears to be a potential means for developing SMS-like symptoms in a ground-based human centrifuge.     

Neurohumoral mechanism of space motion sickness.

This paper reviews existing hypotheses concerning the mechanisms of adaptation of the vestibular apparatus and related somatosensory systems to microgravity with reference to the flight data. Having in view theoretical concepts and experimental data accumulated in space flights, a conceptual model of the development of a funtional system responsible for the termination of vestibular dysfuntion and space motion sickness manifestations is presented. It is also shown that changes in the hormonal status during motion sickness induced by vestibular stimulation give evidence that endocrine regulation of certain functions can be involved in adaptive responses.     

Individual differences in susceptibility to motion sickness among six Skylab astronauts

One of the Skylab experiments dealt with motion sickness, comparing susceptibility in the workshop aloft with susceptibility preflight and postflight. Tests were conducted on and after mission-day 8 (MD 8) by which time the astronauts were adapted to working conditions. Stressful accelerations were generated by requiring the astronauts, with eyes covered, to execute standardized head movements (front, back, left, and right) while in a chair that could be rotated at angular velocities up to 30 rpm. The selected endpoint was either 150 discrete head movements or a very mild level of motion sickness. In all rotation experiments aloft, the five astronauts tested (astronaut 1 did not participate) were virtually symptom free, thus demonstrating lower susceptibility aloft than in preflight and postflight tests on the ground when symptoms were always elicited. Inasmuch as the eyes were covered and the canalicular stimuli were the same aloft as on the ground, it would appear that lifting the stimulus to the otolith organs due to gravity was an important factor in reducing susceptibility to motion sickness even though the transient stimuli generated under the test conditions were substantial and abnormal in pattern. Some of the astronauts experienced motion sickness under operational conditions aloft or after splashdown, but attention is centered chiefly on symptoms manifested in zero gravity. None of the Skylab-II crew (astronauts 1 to 3) was motion sick aloft. Astronaut 6 of the Skylab-III crew (astronauts 4 to 6) experienced motion sickness within an hour after transition into orbit; this constitutes the earliest such diagnosis on record under orbital flight conditions. The eliciting stimuli were associated with head and body movements, and astronaut 6 obtained relief by avoiding such movements and by one dose of the drug combination 1-scopolamine 0.35 mg + d-amphetamine 5.0 mg. All three astronauts of Skylab-III experienced motion sickness in the workshop where astronaut 6 was most susceptible and astronaut 4, least susceptible. The higher susceptibility of SL-III crewmen in the workshop, as compared with SL-II crewmen, may be attributable to the fact that they were based in the command module less than one-third as long as SL-II crewmen. The unnatural movements, often resembling acrobatics, permitted in the open spaces of the workshop revealed the great potentialities in weightlessness for generating complex interactions of abnormal or unusual vestibular and visual stimuli. Symptoms were controlled by body restraint and by drugs, but high susceptibility to motion sickness persisted for 3 days and probably much longer; restoration was complete on MD 7. From the foregoing statements it is clear that on and after MD 8 the susceptibility of SL-II and SL-III crewmen to motion sickness under experimental conditions was indistinguishable. The role played by the acquisition of adaptation effects prior to MD 8 is less clear and is a subject to be discussed.     

Pharmacological approaches

The use of drugs as countermeasures in the United States and Russian space programs is examined. Pharmacological tools for short and extended space flights are reviewed. Medications flown on the Shuttle are listed. Considerations for the use of pharmacological countermeasures include pharmacokinetics and pharmacodynamics, drug interactions, therapeutic interventions, space motion sickness, the musculoskeletal system, radiation protection, space flight anemia, and cardiovascular disorders.     

Relative efficacy of the proposed Space Shuttle antimotion sickness medications

Space motion sickness has been estimated as affecting between 1/3 and 1/2 of all space flight participants. NASA has at the moment proposed a combination of promethazine and ephedrine (P/E) and one of scopolamine and dextroamphetamine (S/D), both given orally, as well as a transdermally applied scopolamine (TAS), as preventive and ameliorative measures. The reported double-blind study, tests the early phase actions and efficacy of the transdermal scopolamine (Transderm (TM)-V of ALZA Corporation) and compares these in detail to the oral medications. Motion sickness resistance was tested by standardized head movements while accelerating at 0.2 degree/sec2 to a maximum rotation of 240 degrees/sec, with an intermediate plateau of 10 min at 180 degrees/sec. To permit weighting motion sickness protection against other system influences, cardiovascular, psychological (subjective and objective), and visual parameter changes were documented for the three therapeutic modes. The relative impact of the various modalities on operational and experimental components of space missions is discussed. A comparison to intramuscularly administered promethazine (a backup therapeutic mode suggested for Space Shuttle use) is also included.     

Vestibular tests in the selection of cosmonauts.

Vestibulo-vegetative disorders in cosmonauts and astronauts occurring during space flight compel otolaryngologists to search for vestibular tests enabling a precise evaluation of the activity of the vestibular apparatus and showing disposition to motion sickness. Otoneurological investigation of Polish candidates for cosmonaut status consisted of the following vestibular tests: caloric, rotatory, optokinetic, swinging torsion, statokinesimetric and vestibulo-vegetative. The value of various vestibular tests for aviation and space medicine is presented in this paper, taking into account the results of investigations of the equilibrium system with the group of pilots selected for space flight as well as extensive experience with candidates for the air service and also trained pilots and patients. The relatively frequent lack of correlation between the results of the applied tests, which renders difficult the proper evaluation of the equilibrium system, is emphasized in the paper. Finally, the results of investigations of acute habituation of the vestibular apparatus are discussed.     

Nausogenic properties of various dynamic and static force environments.

Motion sickness can occur when an accelerating force acting on the human body repeatedly changes amplitude and direction or both. It also can occur without any motion after transfer into a constant force field significantly different from Earth-gravity. Dynamic and static causes of motion sickness can be distinguished accordingly. Space sickness, too, has dynamic as well as static aspects. Dynamic space sickness might depend on increased bilateral differential sensitivity of the peripheral and central vestibular apparatus, whereas static space sickness may be caused by erroneous compensation of bilaterial asymmetries of the otolith-system in the microgravity environment. Experiments in airplanes, cars and on a vestibular sled have shown that the susceptibility to motion sickness is highest for changes of acceleration in the negative X-axis (as compared to the other axes) of the body. During reciprocating linear accelerations on the vestibular sled, standstill periods of movement and the direction of movement cannot correctly be indicated, because the peripheral vestibular apparatus lacks true motion detectors.     

The feasibility of Doppler monitoring during EVA

During extravehicular activities (EVA) outside the spacecraft, astronauts have to work under reduced pressure in a space suit. This pressure reduction induces the risk of decompression sickness (DCS) by the formation of gas bubbles from excess nitrogen dissolved in the organism by breathing air at normal pressure. Under laboratory conditions the gas bubbles moving in the blood stream can be detected by the non-invasive ultrasonic Doppler method. By early detection of excessive bubble formation the development of DCS symptoms may be prevented by early application of preventative measures. The method could also be useful when applied in the space suit in order to compare the results of laboratory tests with operational results, because there is a discrepancy according to the DCS risk of laboratory experiments and actual EVA missions, where no symptoms have been reported yet. A prototype Doppler sensor has been developed and implemented in the Russian Orlan suit. To investigate the feasibility of this method under simulated space conditions, the equipment has been used in a series of 12 thermovacuum chamber tests with suited subjects, where intravenous bubble formation was compared to unsuited control experiments. In more than 50% of the suited tests good Doppler recordings could be achieved. In some cases with unsatisfying results the signal could be improved by breathholding. Although the results do not yet allow any conclusion about a possible difference between suited and unsuited subjects due to the small number of tests performed, the method proved its feasibility for use in EVA suits and should be further developed to enhance the safety of EVA procedures.     

Space motion sickness medications: interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.     

An appraisal of the value of vitamin B12 in the prevention of motion sickness

Unpublished reports have suggested that hydroxycobalamin (B12, i.m.) prevents motion sickness. Some biomedical evidence supports this contention in that B12 influences the metabolism of histidine and choline; dietary precursors to neurotransmitters with established roles in motion sickness. Susceptibility to motion sickness was evaluated after B12 (1000 micrograms, i.m.). Subjects initially completed vestibular function and motion sickness susceptibility tests to establish normal vestibular function. The experimental motion stressor was a modified coriolis sickness susceptibility test. Subjects executed standardized head movements at successively higher RPM until a malaise III endpoint was reached. Following two baseline tests with this motion stressor, subjects received a B12 injection, a second injection two weeks later, and a final motion sickness test three weeks later. No significant differences in susceptibility were noted after B12. Hematological parameters revealed no B12 deficiency before injection. The possibility that patients with B12 deficiencies are more susceptible to motion sickness cannot be ruled out.     

Prolonged weightlessness and calcium loss in man

Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.     

The sopite syndrome revisited: drowsiness and mood changes during real or apparent motion

The sopite syndrome is a poorly understood response to motion. Drowsiness and mood changes are the primary characteristics of the syndrome. The sopite syndrome can exist in isolation from more apparent symptoms such as nausea, can last long after nausea has subsided, and can debilitate some individuals. It is most likely a distinct syndrome from "regular" motion sickness or common fatigue, and is of potential concern in a variety of situations. The syndrome may be particularly hazardous in transportation settings where other performance challenges (e.g., sleep deprivation) are already present. It is also a potential concern in cases where illnesses such as sleep disorders or depression may interact with the syndrome and confuse diagnosis.