Anestéziológia a intenzívna medicína 1/2016

Melatonin and its potential use in anesthesiology and intensive care

Currently, surgical procedures are carried out also in polymorbid patients from risk groups for the development of postoperative complications. An important point represents the availability of new pharmacological molecules which, by properly indication helping quite successfully master the management of associated postoperative complications. Melatonin is characterized by several interesting features. It regulates the circadian rhythm, and in addition, it has an antioxidant, oncostatic, anti-inflammatory, antinociceptive and anticonvulsive effect. Mentioned properties of the active ingredient can be used in the treatment of patients in critical condition. Melatonin is a substance produced by the pineal gland and is released directly into the circulation as a function of circadian rhythm. Melatonin biosynthesis is controlled by the sympathetic nervous system. Melatonin administered at premedication reduces postoperative pain and opioid consumption. The analgesic effect of melatonin is mediated via melatonin MT1 and MT2 receptors and is also related to an indirect increase in the production of endogenous opioids. Anesthesia and the operation itself alter the circadian pattern of melatonin production. Application of local anesthetic resulting in reduced plasma levels of melatonin. Opioid analgesia used in major surgical operations elevates plasma melatonin levels by stimulating the N-acetyltransferase, which ultimately increases the synthesis of melatonin. Surgical patients show a decrease in plasma levels of melatonin after surgery. This decrease is due to consumption of melatonin (an antioxidant) to neutralize the reactive oxygen released during operation. Corticosteroids reduce the activity of N-acetyltransferase in the pineal gland, which elevated cortisol levels negatively affect melatonin synthesis. Various anesthetic agents postoperatively may have different effects on plasma melatonin levels. Anesthesia induced by isoflurane and propofol causes an increase in plasma melatonin levels. It records the reduced release of melatonin after spinal and general anesthesia (i. e. postanesthetic phase delay in melatonin secretion). Melatonin has a hypnotic effect (i. e. induces loss of consciousness). This loss of consciousness is accompanied by a change in EEG activity similar to that may be seen within intravenous and inhalation induced anesthesia. Melatonin administered per os is used to alleviate the “jet-lag disease”, the treatment of sleep disorders in blind patients or in patients with delayed sleep phase syndrome. Melatonin premedication is associated with preoperative sedation and anxiolysis without deterioration in psychomotor activity or impact on the quality of memory. Melatonin treatment reduces sleep latency, improves the ability to fall asleep and increases whole sleep. Melatonin premedication reduces the dose of propofol and thiopental needed to drop the responses to verbal commands and visual stimulation. Melatonin and the more potent melatonin analogues like 2-brommelatonin and fenylmelatonin possess anesthetic properties. Anesthetic dose of melatonin induces EEG record similar to that observed after administration of propofol and thiopental. Melatonin and its analogs exhibit potent antinociceptive effect. Melatonin-induced analgesia is a result of the release of β-endorphins. Central action of melatonin mediates facilitated GABAergic transmission by modulating the GABA receptors.

Keywords: melatonin, analgesia, anesthesia, antioxidant, anxiolysis