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.

Orientation Preferences and Motion Sickness Induced in a Virtual Reality Environment.

BACKGROUND: Astronauts' orientation preferences tend to correlate with their susceptibility to space motion sickness (SMS). Orientation preferences appear universally, since variable sensory cue priorities are used between individuals. However, SMS susceptibility changes after proper training, while orientation preferences seem to be intrinsic proclivities. The present study was conducted to investigate whether orientation preferences change if susceptibility is reduced after repeated exposure to a virtual reality (VR) stimulus environment that induces SMS. METHODS: A horizontal supine posture was chosen to create a sensory context similar to weightlessness, and two VR devices were used to produce a highly immersive virtual scene. Subjects were randomly allocated to an experimental group (trained through exposure to a provocative rotating virtual scene) and a control group (untrained). All subjects' orientation preferences were measured twice with the same interval, but the experimental group was trained three times during the interval, while the control group was not. RESULTS: Trained subjects were less susceptible to SMS, with symptom scores reduced by 40%. Compared with untrained subjects, trained subjects' orientation preferences were significantly different between pre- and posttraining assessments. Trained subjects depended less on visual cues, whereas few subjects demonstrated the opposite tendency. CONCLUSION: Results suggest that visual information may be inefficient and unreliable for body orientation and stabilization in a rotating visual scene, while reprioritizing preferences for different sensory cues was dynamic and asymmetric between individuals. The present findings should facilitate customization of efficient and proper training for astronauts with different sensory prioritization preferences and dynamic characteristics.Chen W, Chao J-G, Zhang Y, Wang J-K, Chen X-W, Tan C. Orientation preferences and motion sickness induced in a virtual reality environment. Aerosp Med Hum Perform. 2017; 88(10):903-910.

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.

Effects of five days of bed rest with intermittent centrifugation on neurovestibular function.

OBJECTIVES: We tested whether intermittent short-radius centrifugation was effective for mitigating alteration in balance and gait following bed rest. METHODS: Ten male subjects were exposed to 5 days of 6° head-down tilt bed rest with: (a) no countermeasure; (b) daily 1-g centrifugation for a continuous 30-min period; and (c) daily 1-g centrifugation for six periods of 5 min. During and after the bed rest, subjects were asked to scale the severity of neurovestibular symptoms that followed centrifugation or 80° head-up tilt. Following the bed rest, equilibrium scores were derived from anterior-posterior sway while standing on a foam pad with the eyes open or closed while making pitch head movements, and gait was evaluated by grading subjects' performance during various locomotion tasks. RESULTS: At the beginning of bed rest, one single 30-min period of centrifugation induced more severe neurovestibular symptoms than six periods of 5-min centrifugation. After bed rest, although equilibrium scores and gait performance were not significantly altered, subjects felt less neurovestibular dysfunction with orthostatic stress when centrifugation was used. CONCLUSION: Centrifugation was effective at reducing the severity of neurovestibular symptoms after bed rest, but this decrease was not different between one or multiple daily sessions.

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.

Baclofen affects the semicircular canals but not the otoliths in humans.

CONCLUSION: This study showed that GABAB agonist baclofen (10 mg) affects the semicircular canals (SCCs), both centrally and peripherally, but does not influence the otolithic function. OBJECTIVES: The aim of the study was to identify the effects of baclofen on the complete vestibular system, i.e. semicircular canals, saccules and utricles. METHODS: The study had a double-blind, placebo-controlled, repeated measures design and was conducted on healthy male volunteers. With electronystagmography (ENG), the SCC function was evaluated, whereas utricular function was determined by means of unilateral centrifugation (UC). Cervical vestibular evoked myogenic potentials (cVEMPs) tested saccular integrity. RESULTS: Baclofen caused a significant increase of the vestibulo-ocular reflex (VOR) phase and a significant decrease of the total caloric response (TCR), both measured during ENG. The drug also decreased the maximal contribution of the SCCs to ocular counter-rolling (OCR) evaluated during UC. No effects on saccules and utricules were observed.

[The pathogenetic approach to the development of tools and methods for the improvement of statokinetic stability in the operators of aerospace systems].

The objective of the present study was to estimate the efficacy of the tools and methods for the optimization of the activity of the central nervous system (CNS) and analyzers involved in the maintenance of the statokinetic (SK) stability in man. To this effect, we evaluated the outcome of bemitil treatment during 10 days with and without A.I. Yarotsky test and the influence of these procedures on the pathophysiological characteristics of selected elements of the work of operators of aerospace systems. Based on the data obtained in the study, the tools and methods have been developed that allow the efficacy and quality of certain aspects of the operators' activity to be improved, viz. general working capacity under conditions requiring enhanced statokinetic stability, self-confidence, emotional and somatic comfort.

Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man.

INTRODUCTION: Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately. METHODS: The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt. RESULTS: Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain. DISCUSSION: The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABA(A)-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus. CONCLUSION: Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.

Effect of daily linear acceleration training on the hypergravity-induced vomiting response in house musk shrew (Suncus murinus).

The effects of repeated linear acceleration training and the antimotion sickness drug, promethazine, on hypergravity-induced motion sickness were examined in musk shrew (Suncus murinus), which is known to show a vomiting response to motion stimulation. Animals were assigned into five groups: vestibular intact, untreated animals (Sham), vestibular lesioned (VL) animals, vestibular intact animals with promethazine hydrochloride administered as daily drinking water (Prom), vestibular intact animals who underwent horizontal linear accelerator motion training (Train), and vestibular intact animals treated with both promethazine hydrochloride and linear acceleration training (Prom+Train). In Sham animals, the number of vomiting episodes was 14±2 during 2 G exposure for 10min, and was accompanied by intense Fos expression in the medial vestibular nucleus (MVe), the nucleus of the solitary tract (NTS), the area postrema (AP), and the paraventricular hypothalamic nucleus (PVN). The vomiting response and Fos expression were completely abolished in VL animals, indicating that these responses are mediated via the vestibular system. Although Train and Prom animals experienced a significantly reduced number of hypergravity-induced vomiting episodes compared with Sham animals, the effect was significantly greater in Train animals than in Prom animals. Fos expression in the NTS, AP, and PVN were significantly more reduced in Train animals than in Prom animals. Higher dose of bolus injection of promethazine (50mg/kg, i.p.) completely abolished the vomiting episodes, although the animals were drowsy and sedated due to side effects. In conclusion, daily linear acceleration training and promethazine could prevent the hypergravity-induced vomiting episodes.

Joint modeling of performance and subjective reporting to assess sensitivity to drug-induced sleepiness.

In an NASA ground study, two forms of cognitive tests were evaluated in terms of their sensitivity to sleepiness induced by the drug promethazine (PMZ). Performance for the two test modes (Y(1) and Y(2)), PMZ concentration, and a self-reported sleepiness using the Karolinska Sleepiness Scale (KSS) were monitored for 12 h post dose. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores are discrete and also because they tend to concentrate on certain values. Therefore, we define a latent sleepiness measure X as an unobserved continuous random variable describing a subject's actual state of sleepiness. Under the assumption that drug concentration affects X, which then affects Y(1), Y(2), and KSS, we use Bayesian methods to estimate joint equations that permit unbiased comparison of the performance measures' sensitivity to X. The equations incorporate subject random effects and include a negativity constraint on subject-specific slopes of performance with respect to sleepiness.

Neurovestibular considerations for sub-orbital space flight: A framework for future investigation.

Commercial sub-orbital operators will soon offer the excitement of traveling to space to thousands of people. Based on previous experience in space flight and parabolic flight, sensorimotor disruptions in eye movements, postural stability, and motor coordination are likely in these travelers. Here we propose a framework for developing strategies to overcome these sensorimotor disruptions. We delineate how approaches should differ from those applied to orbital flight and between sub-orbital passengers and pilots based on differing frequency of flights and mission objectives. Sensorimotor adaptation is one strategy for overcoming disruptions; an important question is whether it occurs quickly enough to be of use during periods of reduced and enhanced gravity lasting less than five minutes. Data are presented showing that sensorimotor adaptation of the pitch vestibulo-ocular reflex during parabolic flight takes a few consecutive days of flying to overcome an initial disruption. We conclude with recommendations for operators and researchers to improve safety and comfort during sub-orbital operations. We recommend using parabolic flight as a tool for pre-adapting sub-orbital passengers, along with further research into the required quantity and timing of these pre-adaptation flights and the tasks conducted during these flights. Likewise, for sub-orbital pilots, we recommend emphasizing recency of experience.

Adaptation to motion sickness from torso rotation affects symptoms from supine head nodding.

INTRODUCTION: Space motion sickness affects more than 50% of astronauts. Adaptation to one kind of nauseogenic motion can affect the response to another. We hypothesized that repeated exposure to torso rotation (TR) would diminish motion sickness (MS) due to supine head nodding (HN), a ground-based analogue for space sickness. METHODS: During TR, standing subjects swept their gaze back and forth between two targets located 135 degrees to either side of straight ahead. For HN, the subject lay supine on a platform with his/her head and neck hanging over the edge. The head was pitched back and forth between the horizontal position and rotated back as far as possible. MS was quantified in 5 male and 20 female subjects using numerical estimates of discomfort and a more detailed questionnaire. Susceptibility to TR and HN was determined on three occasions for each stimulus. At least 1 mo separated any two tests. Subjects were exposed to TR once a day for 7 consecutive days 1 mo after the final control session. Within 24 h of the seventh session, and 1 mo later, susceptibility to HN was evaluated again. RESULTS: There was a significant decrease in MS susceptibility during repeated exposure to TR (time to stop 17.7 min on Day 1, 31.8 min on Day 7). In contrast, there was a significant increase in MS susceptibility to HN after repeated exposure to TR (mean time to stop 11.7 min before TR, 9.5 min after). Susceptibility to HN was back to normal (time to stop 11.4 min) 1 mo later. DISCUSSION: Subjects can adapt to TR by repeated exposure. At the same time, susceptibility to HN increases. Strategies for pre-adaptation to space motion sickness need to be chosen carefully as they could actually be counterproductive.

Relative bioavailability of scopolamine dosage forms and interaction with dextroamphetamine.

The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) alone and in combination with dextoamphetamine (DEX) to treat motion sickness symptoms during DC-9 parabolic flights. The medications are sometimes dispensed as custom dosage forms in gelatin capsules for convenience. Reports of treatment failure during flights by the flight surgeons suggest that these formulations may be less efficacious for the treatment of motion sickness due to unreliable and inadequate bioavailability. We estimated bioavailability of four different oral formulations used by the NASA RGO physicians for the treatment of motion sickness.

Preflight virtual reality training as a countermeasure for space motion sickness and disorientation.

INTRODUCTION: Research suggests that preflight training in virtual reality devices can simulate certain aspects of microgravity and may prove to be an effective countermeasure for space motion sickness (SMS) and spatial disorientation (SD). It is hypothesized that exposing subjects preflight to variable virtual orientations, similar to those encountered during spaceflight, will reduce the incidence and/or severity of SMS and SD. METHODS: Subjects were assigned to either a variable training (VT) or nonvariable training (NVT) condition to perform a simple navigation and switch activation task in a virtual space station. VT subjects performed the task starting in several different orientations, whereas NVT subjects always performed the task starting in the same orientation. On a separate day, all subjects then performed the same task in a transfer of training session starting from a novel orientation. RESULTS: When exposed to the novel test orientation, VT subjects performed the tasks more quickly (12%) and with fewer nausea symptoms (53%) than during the training session, compared with NVT subjects who performed more slowly (6%) and with more nausea symptoms (28%). Both VT and NVT conditions were effective in reducing the number of wall hits in the novel orientation (39% and 34%, respectively). DISCUSSION: These results demonstrate the effectiveness of using variable training in a virtual environment for reducing nausea and improving task performance in potentially disorienting surroundings, and suggest that such training may be developed into an effective countermeasure for SMS, SD, and associated performance decrements that occur in spaceflight.

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.

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.

[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.