Limitations
As above, we did not use PSG. We restricted our analysis to days off mechanical ventilation. However, in our cohort, the majority of patients were on a ventilator for less than 24 h, and for most subjects (72%) we therefore analyzed at least 2 days’ worth of data. We did not confirm that the circadian activity rhythm measured by actigraphy reflected other markers of the endogenous circadian rhythm such as core body temperature or serum or urine melatonin measurements. Nevertheless, we emphasize that the circadian differences we saw had biological plausibility (reflected expected changes with administration of a melatonin agonist) and/or reflected clinical differences between groups. Furthermore, this was an exploratory analysis of rest-activity rhythms in the ICU, and resulting analyses were underpowered to detect significant effects. Given the high variability of multiple variables (including activity, light patterns, days studied), these data should serve to inform larger, powered studies in this setting and generate future research hypotheses. Finally, the lack of significant findings in our analysis could have been limited by a shorter recording time (~ 2–3 days of recordings per individual) which may not be adequate to fully assess circadian rhythms as at least 72 h of recording are usually suggested.