Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment

Abstract

The confinement of critically ill patients in intensive care units (ICU) imposes environmental constancy throughout both day and night (continuous light, noise, caring activities medications, etc.), which has a negative impact on human health by inducing a new syndrome known as circadian misalignment, circadian disruption or chronodisruption (CD). This syndrome contributes to poor sleep quality and delirium, and may impair septic states frequently observed in critically ill patients. However, and although the bidirectional crosstalk between CD with sleep impairment, delirium and inflammation in animal models has been known for years and has been suspected in ICU patients, few changes have been introduced in the environment and management of ICU patients to improve their circadian rhythmicity. Delirium, the most serious condition because it has a severe effect on prognosis and increases mortality, as well as sleep impairment and sepsis, all three of them linked to disorganization of the circadian system in critically ill patients, will be revised considering the functional organization of the circadian system, the main input and output signals that synchronize the clock, including a brief description of the molecular circadian clock machinery, the non-visual effects of light, and the ICU light environment. Finally, the potential usefulness of increased light/dark contrast and melatonin treatment in this context will be analyzed, including some practical countermeasures to minimize circadian disruption and improve circadian system chronoenhancement, helping to make these units optimal healing environments for patients.

Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients

“…In ICU patients, oral supplementation induces pharmacological levels in the short term [17,18], but this has never been tested for more than four continuous days [19]. Melatonin is a safe and inexpensive drug; it was found to have beneficial effects with regard to both sleep disruption and sepsis [20,21]. …”

Pharmacological plasticity—How do you hit a moving target?

“…There is growing evidence that in patients with severe sepsis, kept in an intensive care unit for days, the circadian rhythm is disturbed. Modification of the light and dark cycle by intensifying the contrast and minimizing light‐dark disruption or treating with melatonin can exert beneficial effects on the outcome of the condition . At least in immuno‐inflammatory disorders, it is worth pointing out that the cyclical circulating concentrations of melatonin, itself a potent antioxidant and anti‐inflammatory agent, may exert a direct effect on immunopathology .…”

Survey among critical care nurses and physicians about delirium management

“…This closely corresponds to current data (Elliott, 2014;Luetz et al, 2014;Andrews et al, 2015;Yassin et al, 2015;Mo et al, 2017;Saller et al, 2016). According to the varying prevalence of delirium during day and night (Sandberg et al, 1999;Madrid-Navarro et al, 2015), undiscovered delirium in hypoactive delirium or dementia (Lemiengre et al, 2006) or sedated patients (Svenningsen et al, 2013), screening for only 'suspicious behaviour' may lead to under-recognition of delirium. Nevertheless, more than half of the participants …”