Pharmacological and non-pharmacological countermeasures to Space Motion Sickness: a systematic review.

Introduction: Space Motion Sickness (SMS) is a syndrome that affects around 70% of astronauts and includes symptoms of nausea, dizziness, fatigue, vertigo, headaches, vomiting, and cold sweating. Consequences range from discomfort to severe sensorimotor and cognitive incapacitation, which might cause potential problems for mission-critical tasks and astronauts and cosmonauts' well-being. Both pharmacological and non-pharmacological countermeasures have been proposed to mitigate SMS. However, their effectiveness has not been systematically evaluated. Here we present the first systematic review of published peer-reviewed research on the effectiveness of pharmacological and non-pharmacological countermeasures to SMS. Methods: We performed a double-blind title and abstract screening using the online Rayyan collaboration tool for systematic reviews, followed by a full-text screening. Eventually, only 23 peer-reviewed studies underwent data extraction. Results: Both pharmacological and non-pharmacological countermeasures can help mitigate SMS symptoms. Discussion: No definitive recommendation can be given regarding the superiority of any particular countermeasure approach. Importantly, there is considerable heterogeneity in the published research methods, lack of a standardized assessment approach, and small sample sizes. To allow for consistent comparisons between SMS countermeasures in the future, standardized testing protocols for spaceflight and ground-based analogs are needed. We believe that the data should be made openly available, given the uniqueness of the environment in which it is collected. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244131.

Space motion sickness: A common neurovestibular dysfunction in microgravity.

This article presents a review of the current findings related to neurovestibular physiology, aetiology, and proposed theories on space motion sickness (SMS) during acute and sustained exposure to microgravity. The review discusses the available treatment options including medication and nonpharmacological countermeasure methods that help to prevent the development of SMS in weightlessness. Ground-based simulations using virtual reality, flight simulations, and Barany's chairs can be applied to study SMS and demonstrate its signs and symptoms to space crew members. Space motion sickness has been observed in approximately 70% of astronauts within the first 72 h in microgravity, having in general an instantaneous onset of signs and symptoms. Stomach discomfort, nausea, vomiting, pallor, cold sweating, salivation, tachypnoea, belching, fatigue, drowsiness, and stress hormone release have been documented. This can have detrimental effects on the well-being of astronauts in the initial phase of a space mission. Mental and physical performance may be affected, jeopardizing operational procedures and mission safety.

Intravestibular Balance and Motion Sickness.

INTRODUCTION: A theory is presented to explain the major findings regarding motion sickness and to synthetize current theories concerning its etiology. The theory proposes that an imbalance in the output of the two major organs of the labyrinth-favoring the semicircular canals over the otolith organs-is responsible for most instances of motion sickness as experienced in terrestrial and microgravity environments. METHODS: Strengths and limitations of current theories are first outlined before the different roles of the canals and otoliths in the genesis of motion sickness symptoms are described. RESULTS: The proposed theory is shown to explain a large number of findings and integrate current theories. DISCUSSION: The role of vestibular imbalance in motion sickness may be a consequence of the more general differences between the canals and otoliths in autonomic control.Previc FH. Intravestibular balance and motion sickness. Aerosp Med Hum Perform. 2018; 89(2):130-140.

The Use of Release-Active Antibody-Based Preparations for Vertigo Prevention in Adults.

The effectiveness of antibody-based release-active preparations Impaza (antibodies to eNOS), Tenoten (antibodies to brain-specific protein S-100), Dietressa (antibodies to type 1 cannabinoid receptor), Brizantin (combined preparation, antibodies to brain-specific protein S-100 and type 1 cannabinoid receptor), and Divaza (combined preparation, antibodies to brain-specific protein S-100 and eNOS) in the prevention of vertigo was studied on the model of intermittent accumulation of Coriolis accelerations (ICCA). Modification of activity of vestibular receptors and signal systems by release-active preparations contributed to an increase in ICCA tolerance time. Combined preparation Impaza possessed the most significant antinaupathic properties. Brizantin was less potent in this respect.

Quantitative orientation preference and susceptibility to space motion sickness simulated in a virtual reality environment.

Orientation preference should appear when variable weightings of spatial orientation cues are used between individuals. It is possible that astronauts' orientation preferences could be a potential predictor for susceptibility to space motion sickness (SMS). The present study was conducted to confirm this relationship on Earth by quantifying orientation preferences and simulating SMS in a virtual reality environment. Two tests were carried out. The first was to quantitatively determine one's orientation preference. Thirty-two participants' vision and body cue preferences were determined by measuring perceptual up (PU) orientations. The ratio of vision and body vector (ROVB) was used as the indicator of one's orientation preference. The second test was to visually induce motion sickness symptoms that represent similar sensory conflicts as SMS using a virtual reality environment. Relationships between ROVB values and motion sickness scores were analyzed, which revealed cubic functions by using optimal fits. According to ROVB level, participants were divided into three groups - body group, vision group, and confusion group - and the factor of gender was further considered as a covariate in the analysis. Consistent differences in motion sickness scores were observed between the three groups. Thus, orientation preference had a significant relationship with susceptibility to simulated SMS symptoms. This knowledge could assist with astronaut selection and might be a useful countermeasure when developing new preflight trainings.

Space motion sickness and motion sickness: symptoms and etiology.

The adverse symptoms of space motion sickness (SMS) have remained problematic since the beginning of manned spaceflight. Despite over 50 yr of research SMS remains a problem that affects about half of all space travelers during the first 24-72 h of a spaceflight. SMS has been treated as another form of motion sickness (MS) despite distinct differences in symptomology. In this review SMS and MS differences are examined and documented based on available data. Vestibular biomechanics that occur during weightlessness coupled with theoretical assertions regarding human evolution have led us to propose a two-component model of SMS. The first component involves conflicting sensory signals inherent to the otolith organs that occur during weightlessness. The second component is a bimodal conflict between the otoliths and semicircular canals that can occur during normal head movements in weightlessness. Both components may inadvertently, and mistakenly, signal that a vestibular malfunction has occurred, hence initiating a protective mechanism that may produce symptoms that discourage activity.

A rationale for space motion sickness.

Space motion sickness (SMS) still remains a problematic nuisance for a majority of fliers during their first 1 to 3 days in space and is an enigma to all concerned after almost half a century of spaceflight and extensive ground and in-flight studies. There is no known etiology consistent with observed signs and symptoms, and attempts to produce pre- and in-flight countermeasures have largely failed. Some medications for motion sickness (MS) have been partially effective, but must be used with caution due to their side effects. A hypothesis regarding SMS that is consistent with current knowledge of vestibular physiology and with observed and measured phenomena during SMS is presented.

Cardio-postural deconditioning: A model for post-flight orthostatic intolerance.

Post-flight astronauts experience temporary but sometimes severe postural control dysfunction and decreased orthostatic tolerance. Research points to a possible link between cardiovascular and postural controls and orthostatic tolerance [Claydon,V.E., Hainsworth, R., 2006. Postural sway in patients with syncope and poor orthostatic tolerance. Heart 92, 1688-1689], for which a neurophysiological model has been presented [Souvestre, P.A., Blaber A.P., Landrock C.K., 2008. Space motion sickness: the sensory-motor controls and cardiovascular correlation. Acta Astronautica 63, 745-757]. To validate this model, young and elderly subjects (n=12) were compared with respect to postural mediolateral sway (ML sway) and blood pressure (BP) during quiet standing. Both groups had a peak in the low frequency region (0.03-0.07Hz) of cross-spectral power between ML sway and BP; however, only the young subjects had signal coherence greater than 0.5. Short-range Hurst coefficient from Stabilogram Dynamic Analysis was significantly lower for ML sway in young (0.694+/-0.068) compared to elderly subjects (0.812+/-0.10) (p=0.028). Young subjects were better able to command a closed-loop strategy of motor-control providing a more efficient postural control. Further application of this model with astronauts could lead to further understanding of post-flight orthostatic intolerance.

Velocity storage activity is affected after sustained centrifugation: a relationship with spatial disorientation.

Prolonged exposure to hypergravity in a human centrifuge can lead to post-rotary spatial disorientation and motion sickness. These symptoms are mainly provoked by tilting head movements and resemble the Space Adaptation Syndrome. We hypothesized that the occurrence of these post-rotary effects might be related to changes in the velocity storage (VS) mechanism, which is suggested to play an important role in spatial orientation. In particular, we investigated whether the re-orientation of the eye velocity vector (EVV) towards gravity during off-vertical optokinetic stimulation was affected by centrifugation. Twelve human subjects were exposed to a hypergravity load of 3G (G-load directed along the naso-occipetal axis) for a duration of 90 min. Before and after centrifugation we recorded optokinetic nystagmus (OKN) elicited by a stimulus pattern moving about the subject's yaw axis, with the head erect and tilted 45 degrees to both sides. During OKN with the head erect, we observed a pitch-down component, reorienting the EVV on average 4.5 degrees (SD 3.6, pretest values) away from the stimulus axis. Head tilt induced an additional shift of the EVV towards the spatial vertical of 6.4 degrees on average (SD 3.2). This head-tilt induced reorientation was significantly decreased after centrifugation to 4.7 degrees (SD 2.9), suggesting a reduction of VS-activity. By means of a vector model we estimated the reduction in VS-activity at 31%. Such a decrease in VS-activity might reflect a deterioration of the ability to integrate sensory signals to obtain an estimate of gravity during tilting head movements, resulting in motion sickness in susceptible subjects.

Measurement of oscillopsia induced by vestibular Coriolis stimulation.

We demonstrate a new method for measuring the time constant of head-movement-contingent oscillopsia (HMCO) produced by vestibular Coriolis stimulation. Subjects briskly rotated their heads around pitch or roll axes whilst seated on a platform rotating at constant velocity. This induced a cross-coupled vestibular Coriolis illusion. Simultaneous with the head movement, a visual display consisting of either a moving field of white dots on a black background or superimposed on a subject-stationary horizon, or a complete virtual room with conventional furnishings appeared. The scene's motion was driven by a simplified computer model of the Coriolis illusion. Subjects either nulled (if visual motion was against the illusory body rotation) or matched (if motion was in the same direction as the illusory motion) the sensation with the exponentially slowing scene motion, by indicating whether its decline was too fast or too slow. The model time constant was approximated using a staircase technique. Time constants comparable to that of the Coriolis vestibular ocular reflex were obtained. Time constants could be significantly reduced by adding subject-stationary visual elements. This technique for measuring oscillopsia might be used to quantify adaptation to artificial gravity environments. In principle more complex models can be used, and applied to other types of oscillopsia such as are experienced by BPPV patients or by astronauts returning to Earth.

Space motion sickness: incidence, etiology, and countermeasures.

Space motion sickness is experienced by 60% to 80% of space travelers during their first 2 to 3 days in microgravity and by a similar proportion during their first few days after return to Earth. Space motion sickness symptoms are similar to those in other forms of motion sickness; they include: pallor, increased body warmth, cold sweating, malaise, loss of appetite, nausea, fatigue, vomiting, and anorexia. These are important because they may affect the operational performance of astronauts. Two hypotheses have been proposed to explain space motion sickness: the fluid shift hypothesis and the sensory conflict hypothesis. The fluid shift hypothesis suggests that space motion sickness results from the cranial shifting of body fluids resulting from the loss of hydrostatic pressure gradients in the lower body when entering microgravity. The cranial fluid shifts lead to visible puffiness in the face, and are thought to increase the intracranial pressure, the cerebrospinal-fluid pressure or the inner ear fluid pressures, altering the response properties of the vestibular receptors and inducing space motion sickness. The sensory conflict hypothesis suggests that loss of tilt-related otolith signals upon entry into microgravity causes a conflict between actual and anticipated signals from sense organs subserving spatial orientation. Such sensory conflicts are thought to induce motion sickness in other environments. Space motion sickness is usually treated using pharmaceuticals, most of which have undesirable side effects. Further studies elucidating the underlying mechanism for space motion sickness may be required for developing new treatments.

Centrifugation as a countermeasure during actual and simulated microgravity: a review.

This paper summarizes what has been learned from studies of the effects of artificial gravity generated by centrifugation in actual and simulated weightless conditions. The experience of artificial gravity during actual space flight in animals and humans are discussed. Studies using intermittent centrifugation during bed rest and water immersion, as a way to maintain orthostatic tolerance and exercise capacity, are reviewed; their results indicate that intermittent centrifugation is a potential countermeasure for maintaining the integrity of these physiological functions in extended space missions. These results can help set guidelines for future experiments aimed at validating the regimes of centrifugation as a countermeasure for space missions. Current and future research projects using artificial gravity conditions in humans are discussed.

A drop-tower experiment to determine the threshold of gravity for inducing motion sickness in fish.

It has been repeatedly shown earlier that some fish of a given batch reveal motion sickness (a kinetosis) at the transition from 1 g to microgravity. In the course of parabolic aircraft flight experiments, it has been demonstrated that kinetosis susceptibility is correlated with asymmetric inner ear otoliths (i.e., differently weighed statoliths on the right and the left side of the head) or with genetically predispositioned malformed cells within the sensory epithelia of the inner ear. Hitherto, the threshold of gravity perception for inducing kinetotic behavior as well as the relative importance of asymmetric otoliths versus malformed epithelia for kinetosis susceptibility has yet not been determined. The following experiment using the ZARM drop-tower facility in Bremen, Germany, is proposed to be carried out in order to answer the aforementioned questions. Larval cichlid fish (Oreochromis mossambicus) will be kept in a camcorder-equipped centrifuge during the microgravity phases of the drops and thus receive various gravity environments ranging from 0.1 to 0.9 g. Videographed controls will be housed outside of the centrifuge receiving 0 g. Based on the video-recordings, animals will be grouped into kinetotically and normally swimming samples. Subsequently, otoliths will be dissected and their size and asymmetry will be measured. Further investigations will focus on the numerical quantification of inner ear supporting and sensory cells as well as on the quantification of inner ear carbonic anhydrase reactivity. A correlation between: (1) the results to be obtained concerning the g-loads inducing kinetosis and (2) the corresponding otolith asymmetry/morphology of sensory epithelia/carbonic anhydrase reactivity will further contribute to the understanding of the origin of kinetosis susceptibility. Besides an outline of the proposed principal experiments, the present study reports on a first series of drop-tower tests, which were undertaken to elucidate the feasibility of the proposal (especially concerning the question, if some 4.7 s of microgravity are sufficient to induce kinetotic behavior in larval fish).

Determination of the threshold of gravity for inducing kinetosis in fish: a drop-tower experiment.

It has been repeatedly shown earlier that some fish of a given batch reveal motion sickness (a kinetosis) at the transition from 1 g to microgravity. In the course of parabolic aircraft flight experiments, it has been demonstrated that kinetosis susceptibility is correlated with asymmetric inner ear otoliths (i.e., differently weighed statoliths on the right and the left side of the head) or with genetically predispositioned malformed cells within the sensory epithelia of the inner ear. Hitherto, the threshold of gravity perception for inducing kinetotic behaviour as well as the relative importance of asymmetric otoliths versus malformed epithelia for kinetosis susceptibility has yet not been determined. The following experiment using the ZARM drop-tower facility in Bremen, Germany, is proposed to be carried out in order to answer the aforementioned questions. Larval cichlid fish (Oreochromis mossambicus) will be kept in a camcorder-equipped centrifuge during the microgravity phases of the drops and thus receive various gravity environments ranging from 0.1 to 0.9 g. Videographed controls will be housed outside of the centrifuge receiving 0 g. Based on the videorecordings, animals will be grouped into kinetotically and normally swimming samples. Subsequently, otoliths will be dissected and their size and asymmetry will be measured. Further investigations will focus on the numerical quantification of inner ear supporting and sensory cells as well as on the quantification of inner ear carbonic anhydrase reactivity. A correlation between (1) the results to be obtained concerning the g-loads inducing kinetosis and (2) the corresponding otolith asymmetry/morphology of sensory epithelia/carbonic anhydrase reactivity will further contribute to the understanding of the origin of kinetosis susceptibility. Besides an outline of the proposed principal experiments, the present study reports on a first series of drop-tower tests which were undertaken to elucidate the feasibility of the proposal (especially concerning the question, if some 4.7 s of microgravity are sufficient to induce kinetotic behaviour in larval fish).

The physical price of a ticket into space.

As a direct consequence of exposure to microgravity astronauts experience a number of physiological changes, which can have serious medical implications when they return to Earth. Most immediate and significant are the head-ward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) post-flight, decreased cardiac output and reduced exercise capacity. Changes in the musculoskeletal system contribute significantly to the impaired functions experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity. Countermeasures, therefore, are designed primarily to simulate Earth-like movements, stresses and system interactions. Exercise is one approach that has received wide operational use and acceptance in both the US and Russian space programmes, and has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will therefore be necessary for longer duration missions, such as the human exploration of Mars.

The importance of exercising in space.

As a direct consequence of exposure to microgravity, astronauts experience a set of physiological changes which can have serious medical implications when they return to earth. Most immediate and significant are the headward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) following flight, decreased cardiac output, and reduced capacity for exercise. Changes in the musculoskeletal system contribute significantly to impaired function experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity, and countermeasures are therefore designed primarily to simulate earthlike movements, stresses, and system interactions. Exercise is one approach that has had wide operational use and acceptance in both the US and Russian space programmes, and it has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will be necessary for missions of longer duration, for example for human exploration of Mars.

[Study on space motion sickness before, during and after spaceflight].

Space motion sickness has long been a difficult medical problem in human space flight. Because it is a group of syndromes of the astronauts in adaptation to the new space environment and is related to a wide range of factors, the research of space motion sickness is different from that of cardiovascular and pulmonary system. Subjective methods and qualitative investigation are frequently used, and quantitative analysis is limited since objective stimuli that can be used in specific space environment are few and the samples are small. So precise localization of the problem is very difficult. In this paper space vestibular experiments and works on perceptions of space motion sickness completed by Russian and American scientists are reviewed, in the hope that it may provide some references for future space medical researches.