Systematic review of the effectiveness of standalone passive countermeasures on microgravity-induced physiologic deconditioning

Abstract

A systematic review of literature was conducted to evaluate the effectiveness of passive countermeasures in ameliorating the cardiopulmonary and musculoskeletal effects of gravitational unloading on humans during spaceflight. This systematic review is the third of a series being conducted by the European Space Agency to evaluate the effectiveness of countermeasures to physiologic deconditioning during spaceflight. With future long-duration space missions on the horizon, it is critical to understand the effectiveness of existing countermeasures to promote astronaut health and improve the probability of future mission success. An updated search for studies examining passive countermeasures was conducted in 2021 to supplement results from a broader search conducted in 2017 for all countermeasures. Ground-based analogue and spaceflight studies were included in the search. A total of 647 articles were screened following removal of duplicates, of which 16 were included in this review. Data extraction and analysis, quality assessment of studies, and transferability of reviewed studies to actual spaceflight based on their bed-rest protocol were conducted using dedicated tools created by the Aerospace Medicine Systematic Review Group. Of the 180 examined outcomes across the reviewed studies, only 20 were shown to have a significant positive effect in favour of the intervention group. Lower body negative pressure was seen to significantly maintain orthostatic tolerance (OT) closer to baseline as comparted to control groups. It also was seen to have mixed efficacy with regards to maintaining resting heart rate close to pre-bed rest values. Whole body vibration significantly maintained many balance-related outcome measures close to pre-bed rest values as compared to control. Skin surface cooling and centrifugation both showed efficacy in maintaining OT. Centrifugation also was seen to have mixed efficacy with regards to maintaining VO2max close to pre-bed rest values. Overall, standalone passive countermeasures showed no significant effect in maintaining 159 unique outcome measures close to their pre-bed rest values as compared to control groups. Risk of bias was rated high or unclear in all studies due to poorly detailed methodologies, poor control of confounding variables, and other sources of bias (i.e. inequitable recruitment of participants leading to a higher male:female ratios). The bed-rest transferability (BR) score varied from 2-7, with a median score of 5. Generally, most studies had good BR transferability but underreported on factors such as control of sunlight or radiation exposure, diet, level of exercise and sleep-cycles. We conclude that: (1) Lack of standardisation of outcome measurement and methodologies has led to large heterogeneity amongst studies; (2) Scarcity of literature and high risk of bias amongst existing studies limits the statistical power of results; and (3) Passive countermeasures have little or no efficacy as standalone measures against cardiopulmonary and musculoskeletal deconditioning induced by spaceflight related to physiologic deterioration due to gravity un-loading.

Fig. 1. Effect size plot for cardiopulmonary outcome measures.

Effect size plot of cardiopulmonary outcomes categorised into “VO2max”, “Orthostatic Tolerance”, and “Heart Rate”. Mean differences between pre and post bed rest values between control and intervention groups were used to calculate effect sizes. Effect sizes were calculated with Hedges’ G and bias corrected for sample size with a confidence interval of 95%. A positive value on the x-axis demonstrates positive effect of the intervention whereas a negative value demonstrates negative effect of the intervention on the outcome. LBNP is lower-body negative pressure, HDT is head-down tilt, HR is heart rate, OT is orthostatic tolerance, OTT is orthostatic tolerance time (stand test).

Fig. 2. PRISMA.

Diagram mapping the number of records identified for inclusion in this review following the 2021 updated search.