Melatonin : positive effects on high-risk patients with desynchronized sleep-wake rhythm

Abstract

Background Melatonin (MT), a pineal gland hormone, mediates many processes, including the biorhythmic regulation of the organism physiology. The role of MT in the treatment of sleep disturbances, to prevent jet lag or as a part of the sepsis treatment is widely discussed. Circadian rhythm of MT is desynchronized in critically ill pts in intensive care unit (ICU). The restoration of MT levels has been recently proved to be useful. The aims of the investigation are: to confirm that MT is a molecule active in the regulation of sleep/wake rhythm in ICU patients and to compare the differences in the MT pharmacokinetics using different administration route and drug formulation. Methodology The clinical effects of long term (5 days) administration of oral MT, as well as the pharmacokinetics profiles as a function of different administration ways (os, os by SLN (solid lipid nanoparticles), transdermal by SLN) have been studied in ICU pts. From the second day of the ICU stay, serial withdrawal were taken to determine both the endogenous and the exogenous plasma MT content, for a total of 20 withdrawal for each patient. Each blood sample was centrifuged and the plasma stored at -20\ub0C. To determine the MT concentration we used an ELISA kit that includes a pre-purification of the sample by SPE (solid phase extraction) cartridges. Results In this study, we have seen that administration of oral MT, is safe, reduces need for analgesic and sedative drugs and shows better neurological status indicators, also restoring the normal circadian rhythm. In patients who have received oral MT, the absorption is rapid: the peak plasma concentration has a median of 30 minutes and after only 5 minutes the MT levels were significantly higher than physiological ones. The group treated with transdermal MT presents a delayed peak plasma concentration (4 h). Conclusions In this study, we have proved that MT is able to normalize the sleep-wake cycle, to ameliorate the sleep quality and to reduce the number of sedative drugs used in ICU pts. We proved also that transdermal administration by SLN is effective in rising plasma MT levels as well as enteral administration and is more practicable in clinical setting