Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude

Abstract

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO₂) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO₂ levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco₂ = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO₂, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO₂ were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO₂ environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

Keywords: SANS; carbon dioxide; core temperature; sleep; spaceflight-associated neuro-ocular syndrome.

Graphical abstract

Figure 1.

Transcutaneous overnight CO₂ (PtcCO₂) monitoring. Representative recording of PtcCO₂ and sleep staging in a single subject before start of bed rest (A), PtcCO₂ pre-sleep (bars represents mean with 95% CI; R + 10 n = 9) (B), change in PtcCO₂ from wakefulness to during sleep stages nonrapid eye movement (NREM) stages 1 (N1), 2 (N2), slow wave sleep (N3), and rapid eye movement (REM) sleep [bars represent mean change with SD; head-down tilt (HDT)4 (n = 10) and R + 10, n = 9)] (C), and mean change [bars represent mean with 95% CI, HDT4 (n = 10) and R + 10, n = 7 (N1) and n = 8 (N2, N3, and REM)] in PtcCO₂ during sleep (D). Data were collected before (Pre), and during head down tilt (HDT) days 4, 17, and 28, and during recovery (R) day 4 and day 10. Open and filled circles are subjects who did not and did develop Frisén grade optic disc edema, respectively. Gray region highlights period of hypercapnic head-down tilt bed rest. There were no statistically significant changes from Pre to any HDT or R days for Pre-sleep PtcCO₂ levels (B) or the change in PtcCO₂ during sleep (D). There was a significant reduction in the increase in nightly PtcCO₂ during stage N2 (−1.3 mmHg, CI: −0.2 to −2.3 mmHg), P = 0.0183 and N3 (−1.6 mmHg, CI: −0.3 to −3.0 mmHg), P = 0.02 stages on HDT4. *P < 0.05 vs. Pre value.

Figure 2.

Odds ratios for developing optic disc edema during strict head-down tilt bed rest (HDTBR). Those subjects who developed optic disc edema were more likely to have shorter sleep, less stage 2 nonrapid eye movement (NREM), greater wake after sleep onset (WASO), and blunted circadian temperature amplitude. Odds ratio (OR); A + H index, apnea and hypopnea index; REM, rapid eye movement; N1, stage 1; N2, stage 2; N3, stage 3; WASO, wake after sleep onset; TST, total sleep time. Mean odds ratios with error bars representing upper and lower 95% confidence intervals, *P < 0.05 odds ratio is great than 1.0. Please see methods for detailed information on statistical analyses.