Orthostatic intolerance in spaceflight: a systematic review and meta-analysis

Orthostatic intolerance (OI) remains a persistent and operationally major challenge for astronauts returning from spaceflight. Approximately 30% of astronauts experience orthostatic intolerance-related symptoms upon returning to Earth, yet the underlying cardiovascular mechanisms remain poorly understood. To systematically review and quantitatively synthesize evidence on the incidence of post-spaceflight orthostatic intolerance and the underlying cardiovascular adaptations in astronauts, with the goal of identifying primary physiological mechanisms and sources of heterogeneity. Primary outcome was incidence of post-spaceflight orthostatic intolerance, and secondary outcome was change in stroke volume, blood pressure, total peripheral resistance, heart rate, and baroreflex sensitivity. Among 221 astronauts, pooled orthostatic intolerance incidence was 30% (95% CI, 24%–38%). A total of 231 astronauts contributed to hemodynamic analyses. Stroke volume showed a trend toward reduction after spaceflight (mean difference: −5.37 ml, 95% CI: −11.16 to 0.41), while baroreflex sensitivity showed significant impairment (standardized mean difference: −0.87, 95% CI: −1.69 to −0.06). Total peripheral resistance showed no significant change, suggesting preserved vasoconstrictor function. Contrary to expectations, mission duration was not associated with orthostatic intolerance incidence. However, ubgroup analyses revealed significantly greater baroreflex impairment after long-duration flights (p < 0.01) and greater heart rate increase after short-duration flights (p = 0.03). Reduced stroke volume and impaired baroreflex sensitivity are likely the primary mechanisms contributing to post-spaceflight OI, whereas peripheral vascular resistance is generally maintained. These findings highlight the need for countermeasures targeting fluid status, venous return, and autonomic control. Understanding these adaptive mechanisms is essential as human spaceflight expands to longer missions and more diverse populations.