Circadian Disruption in Critical Illness

Abstract

Circadian rhythms play a vital role in metabolic, hormonal, and immunologic function and are often disrupted in patients in the ICU. Circadian rhythms modulate the molecular machinery that responds to injury and illness which can impact recovery. Potential factors contributing to the alteration in circadian rhythmicity in intensive care unit (ICU) patients include abnormal lighting, noise, altered feeding schedules, extensive patient care interactions and medications. These alterations in circadian rhythms in ICU patients may affect outcomes and therefore, normalization of circadian rhythmicity in critically ill patients may be an important part of ICU care.

Interrelation of Biological Rhythms and Circadian Hormones Producement and Their Impact on Medicine Usage

“…Nowadays, the majority of scientists support the multi-oscillatory concept of regulation of the circulatory system of mammals with a central oscillator in the suprachiasmatic nucleuses of hypothalamus (CNS) -«the master clock» and the main humoral modulator -pineal gland, which performs its chronobiotic function by melatonin which is a "sleep hormone" [6,7,[16][17][18][19][20][21][22]. The physiological significance of melatonin is manifested in the synchronization of different biological processes according to day-and night-time illumination as well as during season changes.…”

Circadian Effects of Drug Responses

“…Also, we now know that disease condition can alter baseline characteristics. Studies in critical care patients whose circadian rhythms are effectively abolished ( 99 ) have shown that the circadian PK/PD behavior of pharmaceuticals tends to diminish ( 100 ).…”

Is there a role for melatonin in the intensive care unit?

“…G A Richards, 1 MB BCh, PhD, FCP (SA), FRCP, MASSAf; OrcID 0000-0002-8893-3934; A Bentley, 2 MB BCh, PhD; OrcID 0000-0001-6533-5213; P D Gopalan, 3 MB ChB, PhD, FCA (SA), Crit Care (SA); OrcID 0000-0002-3816-1171; L Brannigan, 4 MB BCh, DA (SA), FCA (SA), Cert Crit Care (SA); OrcID 0000-0002-6215-254; F Paruk, 5 MB BCh, PhD, FCOG (SA), Cert Crit Care (SA); OrcID 0000-0002-6259-0106 are controlled by the SCN by influencing the timing of feeding and activity as well as regulating the rhythmic release of hormones. [18] Ideally, both the central and peripheral clocks should be aligned and environmental factors should synchronise these internal clocks with the external environment. These clocks may be disconnected in some circumstances such as with sepsis [17] and with changes in the external environment, such as flight over time zones or the disruptive ICU environment, which can temporarily desynchronise internal clocks from the external environment.…”

“…There are also tissue specific peripheral clocks in all cells including immune cells such as macrophages, which are controlled by the SCN by influencing the timing of feeding and activity as well as regulating the rhythmic release of hormones. [18] …”

“…continuous light, noise, medications, feeding times and frequent patient-care interactions) in the ICU. [18] While light levels are usually relatively low (between 30 and 165 lux during the day and 2.4 to 145 lux at night), it is the lack of a significant change in light intensity during the 24-hour period that compromises the circadian rhythm. In addition, light devices that are used for procedures in the ICU may emit up to 10 000 lux, which in the low light environment of the ICU may be enough to alter circadian rhythms.…”