Circadian rhythm disturbance and delirium in ICU patients: a prospective cohort study

Abstract

Background: Patients treated in the intensive care unit (ICU) may experience a reversal of day and night. The circadian rhythm in ICU patients can be disturbed.

Methods: To explore the relationship between ICU delirium and the circadian rhythms of melatonin, cortisol and sleep. A prospective cohort study was carried out in a surgical ICU of a tertiary teaching hospital. Patients who were conscious during the ICU stay after surgery and were scheduled to stay in the ICU for more than 24 h were enrolled. Serum melatonin and plasma cortisol levels were measured three times a day by drawing arterial blood on the first three days after ICU admission. Daily sleep quality was assessed by the Richard-Campbell Sleep Questionnaire (RCSQ). The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was performed twice a day to screen for ICU delirium.

Results: A total of 76 patients were included in this study, and 17 patients developed delirium during their ICU stay. Melatonin levels were different at 8:00 (p = 0.048) on day 1, at 3:00 (p = 0.002) and at 8:00 (p = 0.009) on day 2, and at all three time points on day 3 (p = 0.032, 0.014, 0.047) between delirium and non-delirium patients. The plasma cortisol level in the delirium patients was significantly lower than that in the non-delirium patients at 16:00 on day 1 (p = 0.025). The changes in melatonin and cortisol secretion levels exhibited obvious biological rhythmicity in non-delirium patients (p < 0.001 for melatonin, p = 0.026 for cortisol), while no rhythmicity was found in melatonin and cortisol secretion levels in the delirium group (p = 0.064 for melatonin, p = 0.454 for cortisol). There was no significant difference in RCSQ scores in the first three days between the two groups.

Conclusions: The disturbance of the circadian rhythm of melatonin and cortisol secretion was associated with the development of delirium in ICU patients. Clinical staff should pay more attention to the importance of maintaining patients' normal circadian rhythms in the ICU.

Trial registration: The study was registered with the US National Institutes of Health ClinicalTrials.gov(NCT05342987) (25/04/2022).

Keywords: Circadian rhythm; Cortisol; Delirium; Melatonin.

Fig. 1

Circadian rhythm of melatonin with and without delirium. Data were shown as mean. Delirium group: mesor:67.60 amplitude:21.78 acrophase:23.33. Non-delirium group: mesor:102.93 amplitude:42.85 acrophase:0.18

Fig. 2

Circadian rhythm of cortisol with and without delirium. Data were shown as mean. Delirium group: mesor:399.52 amplitude:25.36 acrophase:5.64 Non-delirium group: mesor:450.94 amplitude:39.20 acrophase:11.19