Figure 2.

Circadian rhythms in critical illness. (a) Daily behavior and melatonin profiles in healthy individuals. (b) In intensive care unit patients with neurological and systemic critical illness, behavioral rhythms are absent and melatonin rhythms show a variety of changes depending on severity (as characterized by the Glasgow Coma Scale) and medication (the use of pressors or not). Data from Maas et al. (2020c). (c) At the level of the lung, experiments in mice show expression of the PER2::LUC transgene (d) is delayed by approximately 4.5 h in hypoxic conditions. Data from Manella et al. (2020). (e) Peripheral blood mononuclear cells show rhythms of NR1D1 and CRY1 gene expression (f) which are absent in cells from critically ill patients. Data from Maas et al. (2020a). (g) These same genes, NR1D1 and CRY1, show an 8-h difference in phase of expression in monocytes obtained from healthy human subjects. Data from Wittenbrink et al. (2018). (h) We do not know what the status of molecular rhythms is in these cells in critically ill patients. Time is expressed as external time (ExT), a convention that runs for 24 h starting at midnight (Daan et al., 2002).