Potential use of melatonin in sleep and delirium in the critically ill

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Potential use of melatonin in sleep and delirium in the critically ill J. Bellapart, R. Boots  British Journal of Anaesthesia  Volume 108, Issue 4, Pages 572-580 (April 2012) DOI: 10.1093/bja/aes035 Copyright © 2012 The Author(s) Terms and Conditions

Fig 1 Synthesis of endogenous melatonin. Sympathetic innervation of the pineal gland (specifically via norepinephrine) is the major transmitter involved in the synthesis of melatonin. Cyclic adenosine monophosphate (AMPc) activation acts as second messenger, stimulating serotonin-N-acetyltransferase, to produce serotonin from tryptophan. While the availability of serotonin is a limiting factor in the synthesis of melatonin, serotonin-N-acetyltransferase increases its activity 100-fold during darkness. British Journal of Anaesthesia 2012 108, 572-580DOI: (10.1093/bja/aes035) Copyright © 2012 The Author(s) Terms and Conditions

Fig 2 Physiological pathways for the synthesis of melatonin. Direct light activates melanopsin (a photo-pigment within the retina), leading to pupillary constriction, suppression of circadian rhythms, photo-entrainment, regulation of alertness, and cognitive functions with suppression of the release of melatonin. Light inhibits the release of melatonin from the pineal gland and promotes its storage after formation during dark cycles. Darkness stimulates post-ganglionic serotonin which directly stimulates the release of melatonin from the pineal gland. British Journal of Anaesthesia 2012 108, 572-580DOI: (10.1093/bja/aes035) Copyright © 2012 The Author(s) Terms and Conditions

Fig 3 Proposed pathophysiology of ICU delirium. The relationship between the ICU environment and the development of delirium shows an altered release of melatonin and a fragmentation of biological and circadian rhythms. British Journal of Anaesthesia 2012 108, 572-580DOI: (10.1093/bja/aes035) Copyright © 2012 The Author(s) Terms and Conditions