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.

Objectives: To assess differences in cognitive outcomes and sleep in adult survivors of critical illness, managed with venovenous extracorporeal membrane oxygenation as compared to conventional mechanical ventilation only. Design: Retrospective cohort study linked with data from the COGnitive outcomes and WELLness study. Setting: A multisite study from five adult medical/surgical ICUs in Toronto. Patients: Thirty-three ICU survivors including adult patients who received venovenous extracorporeal membrane oxygenation ( n = 11) matched with patients who received mechanical ventilation only ( n = 22) using specified covariates (e.g., age). Interventions: None. Measurements and Main Results: Baseline demographics and admission diagnoses were collected at enrollment. Cognitive outcome was evaluated using the Repeatable Battery for the Assessment of Neuropsychologic Status (global cognitive function) and Trail Making Test B (executive function), and sleep variables were estimated using actigraphy. Assessments occurred at 7 days post ICU discharge and again at 6- and 12-month follow-up. No statistically significant difference was seen between patients treated with or without venovenous extracorporeal membrane oxygenation in the mean daily Riker Sedation Agitation Score; however, patients in the venovenous extracorporeal membrane oxygenation group received greater amounts of fentanyl over their ICU stay as compared to patients receiving conventional mechanical ventilation only ( p < 0.001). No significant differences were found in performance on either of the cognitive assessment tools, between survivors treated or not with venovenous extracorporeal membrane oxygenation at any of the time points assessed. Total sleep time estimated by actigraphy increased from approximately 6.5 hours in hospital to 7.5 hours at 6-month follow-up in all patients, regardless of treatment type. Total sleep time remained consistent in both groups from 6 to 12 months post ICU discharge. Conclusions: In this small retrospective case series, no significant differences were found in sleep or cognitive outcomes between extracorporeal life support and non–extracorporeal life support survivors. Further, in this hypothesis-generating study, differences in administered sedative doses during the ICU stay seen between the two groups did not impact 6- or 12-month cognitive performance or actigraphy-estimated sleep time.

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