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. 11 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.