Melatonin, sleep and circadian rhythms in critical care patients.

Critical care patients commonly experience sleep fragmentation, in which sleep
quality is poor and distributed throughout the 24 hour cycle. This irregular sleep
wake pattern is a form of circadian rhythm sleep disorder. The causes of sleep
disturbances are multifactorial and contribute to patient morbidity. Conventional
hypnotic treatment is often ineffective and, indeed, may cause delirium and reduced
sleep quality.
Administration of exogenous melatonin has been shown to re-enforce circadian
rhythm disorders and improve sleep in other patient groups.
An open evaluation of 5 mg oral melatonin was undertaken in a group of 12 critical
care patients exhibiting sleep disturbances resistant to conventional hypnotics.
Melatonin significantly increased observed sleep quantity by night 3, compared to
baseline.
An oral solution of melatonin was formulated to allow administration by enteral
feeding tubes. It was shown to have a 1 year shelf life when refrigerated and
protected from light.
A randomised controlled trial was undertaken in 24 critical care patients weaning
from mechanical ventilation. Melatonin 10 mg orally increased nocturnal bispectral
index sleep quantity over nights 3 and 4 compared to placebo. Agreement of the
other sleep measurement techniques with the bispectral index was poor. Actigraphy
was not a useful measure of sleep in critical care patients and nurse observation
overestimated sleep quantity.
The clearance of melatonin appeared to be decreased in critical care patients
compared to that in healthy subjects. Doses of 1-2 mg should be used in future
critical care studies.
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Acute administration of melatonin did not have a significant effect over placebo on
rest-activity rhythms, which remained delayed, fragmented and reduced. Similar
disturbances were present in plasma melatonin and cortisol rhythms, which were no
longer phase locked.
Melatonin therapy may prove beneficial in the treatment of sleep and circadian
rhythms in critical care patients, and further larger studies should be pursued.