Abnormal Sleep, Circadian Rhythm Disruption, and Delirium in the ICU: Are They Related?

Abstract

Delirium is a syndrome characterized by acute brain failure resulting in neurocognitive disturbances affecting attention, awareness, and cognition. It is highly prevalent among critically ill patients and is associated with increased morbidity and mortality. A core domain of delirium is represented by behavioral disturbances in sleep-wake cycle probably related to circadian rhythm disruption. The relationship between sleep, circadian rhythm and intensive care unit (ICU)-acquired delirium is complex and likely bidirectional. In this review, we explore the proposed pathophysiological mechanisms of sleep disruption and circadian dysrhythmia as possible contributing factors in transitioning to delirium in the ICU and highlight some of the most relevant caveats for understanding the relationship between these complex phenomena. Specifically, we will (1) review the physiological consequences of poor sleep quality and efficiency; (2) explore how the neural substrate underlying the circadian clock functions may be disrupted in delirium; (3) discuss the role of sedative drugs as contributors to delirium and chrono-disruption; and, (4) describe the association between abnormal sleep-pathological wakefulness, circadian dysrhythmia, delirium and critical illness. Opportunities to improve sleep and readjust circadian rhythmicity to realign the circadian clock may exist as therapeutic targets in both the prevention and treatment of delirium in the ICU. Further research is required to better define these conditions and understand the underlying physiologic relationship to develop effective prevention and therapeutic strategies.

Keywords: ICU acquired delirium; circadian rhythm; intervention; mechanisms; sleep.

Figure 1

Comparison of sleep and circadian rhythms in healthy adult and adult with critical illness in the ICU. In a healthy adult, the circadian clock is synced to the daily external cycle of changing light, sound, and temperature. The sleep stage of a healthy adult occurs during the night and is composed of 2–5% light sleep, 48–70% deep sleep, 20–25% rapid eye movement (REM) sleep. REM sleep reoccurs in cycles of 90–120 min. Acetylcholine is predominantly discharged during wakefulness and REM sleep; while GABAergic activity is predominant during deep sleep. Dopaminergic activity promotes alertness and reduces sleep. Melatonin secretion starts around 9.30 pm (dim light melatonin onset) and stops around 7.30 am, peaking around 3 am. Cortisol secretion starts in the early morning, peaks around 10 am in correspondence to the time of highest alertness, and keeps declining gradually throughout the day, and the night. Overall, these processes coordinate physiological functions including cardiovascular functions and temperature. In contrast, the intensive care unit (ICU) constant artificial environment disrupts the daily cycle of circadian functions. In the ICU critically ill patients, compared to healthy adults, present equal to normal sleep time in the course of 24 h but the majority of it consists of light sleep; 50% of sleep time is distributed during the day and disturbed by frequent arousals. For instance, benzodiazepine decrease sleep latency, slow wave sleep (SWS) and REM sleep duration and frequency; propofol suppresses SWS EEG bursts; opioids alter REM sleep; while, dexmedetomidine improve stage 2 and sleep efficiency by shifting 75% of sleep to nighttime. In ICU patients, the acute stress environment has been associated with decreased GABAergic and cholinergic transmission, and increased dopaminergic transmission, impaired melatonin secretion and increased cortisol production, along with displacement of physiological functions normally coordinated by the circadian clock. These disturbances have been associated with symptoms of delirium. ICU, intensive care unit; REM, rapid eye movement; GABA, gamma-aminobutyric acid.