Weightlessness Associated Cephalad Fluid Shifts; The Potential to Evaluate Venous and Lymphatic Dysfunction with Point of Care Noninvasive Imaging in a Head down Tilt Spaceflight Analogue

Introduction, Objectives, and/or Purpose: Spaceflight crew exposure to weightlessness in low earth orbit (LEO) results in a 2-liter fluid shift from the legs to the head, neck, and upper torso within 6-10 hours, with mild to moderate adaptation over the following 4 days. Invasive and noninvasive methods have been utilized to measure transcapillary fluid shifts in a head down tilt (HDT) spaceflight analogue, central venous pressure catheter measurements in orbit and internal jugular venous duplex ultrasound in both parabolic flight and on the International Space Station (ISS). Point of care (POC) evaluations using non-invasive, decreased mass/weight, validated tools may further improve the evaluation and understanding of cephalad fluid shifts, venous distension, and lymphatic dysfunction contributing to Spaceflight Associated Neuroocular Syndrome (SANS) and other physiological adaptation’s due to weightlessness.

The goal of the study was to evaluate POC devices and image changes associated with three fluid shift inducing positions (6-degree HDT, supine and upright), and to determine if Manual Lymphatic Drainage may be an effective countermeasure to mitigate analogue positional fluid shifts.

Methods: Thirty consented subjects meeting inclusion/exclusion criteria were randomized into a control or treatment group. All participants were assessed in the sitting position for 30 minutes, supine for 1.5 hours and 6 degrees head down tilt for 3 hours (validated simulated spaceflight analogue). Each position was assessed on a different date to reduce any position-related carryover effects. Baseline vitals and imaging using NIRS, LWIT, and dermal fluid content were taken immediately after assuming the designated position. Subsequent image assessments and vital signs were taken every 30 minutes thereafter. At completion of the established timepoints, reassessment images were taken prior to moving out of the designated position. Participants in the treatment group received 15 minutes of an established MLD protocol to the head, neck, and upper torso prior to moving out of position. Immediately post MLD, reassessment images were taken, followed by a final assessment 30 minutes after MLD to assess for potential changes and changes in any symptoms experienced in the various positions. Vital sign data and images from the various POC devices were evaluated by independent trained reviewers to assess for notable changes in perfusion (hemoglobin/deoxyhemoglobin for NIRS), temperature (LWIT) and percent fluid (Delfin) over time and for each study position. The study was conducted in an IRB approved, private, designated room at Nova Southeastern University and data collection was completed over 3 months.

Results: Summary statistics were calculated for study variables. We employed random effects, generalized linear models, to look for differences in Left and Right Temple Volume, Left and Right SCM Volume, Left and Right SUBC Volume, and Left and Right Ventromedial Bundle Volume and temperature. First, we looked for changes within the treatment group only. Second, we examined differences between the treatment and control groups for each visit. The fixed effects were the imaging sessions (baseline, post-30-minutes, post-60-minutes, post-90-minutes, post-120-minutes, post-180-minutes, post-MLD, and post-30 minutes-MLD). The random effect was related to the subjects. For all post-modeling comparisons, a false discovery adjustment (FDR) was used. The FDR method has higher power than the Bonferroni and Tukey HSD method and controls the type I error as well. This is important considering the project’s exploratory nature. R version 4.2.2 was used for all statistical modeling and statistical significance was found at p< 0.05.
Fifteen subjects per group (N = 30) completed all visits and were used in the full analysis. No significant difference for any of the within-group comparisons were found—Figures 1-5 and Tables 1-3. Between groups, differences were found. A significant reduction in left temple volume for the treatment group was found at post-30-minutes (5.77, 95% CI: 1.24, 10.30) and post-180-minutes (6.42, 95% CI: 1.71, 11.13). A significant reduction in right temple volume for the treatment group was found at post-30-minutes (5.35, 95% CI: 0.25, 10.44) and post-120-minutes (6.42, 95% CI: 1.32, 11.51). A significant reduction in left SCM volume for the treatment group was found at baseline (4.15, 95% CI: 0.40, 7.90), post-120-Minutes (4.26, 95% CI: 0.51, 8.01), post-150-Minutes (4.78, 95% CI: 1.03, 8.53), and post-180-Minutes (4.98, 95% CI: 1.21, 8.74). A significant reduction in right SCM volume for the treatment group was found at baseline (4.93, 95% CI: 0.76, 9.10), post-30-Minutes (5.56, 95% CI: 1.39, 9.73), post-60-Minutes (4.37, 95% CI: 0.20, 8.53), post-90-Minutes (4.75, 95% CI: 0.58, 8.92), post-120-Minutes (5.49, 95% CI: 1.32, 9.66), post-150-Minutes (5.35, 95% CI: 1.18, 9.51), and post-180-Minutes (8.35, 95% CI: 4.18, 12.51). A significant reduction in right subclavicular volume for the treatment group was found at post-180-Minutes (5.09, 95% CI: 0.16, 10.03). A significant increase in the left ventromedial bundle for the treatment group was found at post-90-Minutes (5.72, 95% CI: 0.34, 11.10) and post-120-Minutes (5.85, 95% CI: 0.47, 11.23). A significant increase in the right ventromedial bundle for the treatment group was found at post-90 minutes (5.53, 95% CI: 0.21, 10.84). A significant increase in body temperature for the treatment group was found at post-30 minutes (0.18, 95% CI:0.01,0.36).

Conclusion(s): POC imaging involves emerging technologies that offer low mass/weight handheld noncontact devices with clinical applications for CVI, lymphedema and early detection of skin temperature thermal pattern abnormalities. POC has high potential for application and use in spaceflight analogue testing, on parabolic flights, ISS, and other spacecraft for fluid shifts (acute and chronic), SANS, and crew core body temperature (CBT) evaluations. Ideally, these devices will help guide or establish countermeasures specifically to address fluid shifts pre-flight, during early flight alterations, long duration missions and post-flight conditions, with the potential to have significant “spinoff” applications for fluid shift recognition in wound care and lymphedema clinics to improve outcomes through recognition and improved treatment protocols. Manual lymphatic drainage may also prove to be an effective countermeasure used pre-flight, during flight and post flight to manage and/or restore fluid shifts experienced during weightlessness.