Melatonin is a hormone produced by the pineal gland which follows a circadian rhythm (night peaks, and low levels during daytime) and it's directly involved in the wake/sleep cycle. Moreover, it holds important antioxidant and immunomodulating features, even showing a mortality decrease in animal samples affected by septic shock.

In critical patients, the amount of blood melatonin  is drastically reduced during daytime, and the night time peak appears almost totally absent.

Right now, it remains unknown whether the reason of this decrease is due to a reduced melatonin production from the pineal gland (maybe due to the severity of the pathology or to the influence of mechanical ventilation on the neurotransmitters, or to the usage of medications that decrease melatonin production such as vasoactive amines, benzodiazepines, and opiates) or to an increased consumption caused by the presence of oxygen reacting species.

The evidence based medicine shows that exogeneus melatonin has been proven useful as an hypnoinductor only through small hematic dosages (jet lag, late sleep syndrome), but ther is not any evidence in patients who have normal endogenous secretions.

High-risk critical patients (who need prolonged mechanical ventilation) almost universally show sleep disorders: devices measurements (such as the polysomnography) and personal patients perceptions, show that sleep during critical care is inadequate in terms of quantity (frequent wakes) and quality (sleep is not restoring enough, lack of slow waves sleep and REM phase sleep).

Considering these evidences, we conducted a pharmacokinetics study which resaerched the bio-disponibility of orally administered melatonin (through nasogastric probe), showing a massive uptake of the substance since the first phases of the critical pathology (starting in the third day of the critical care period). To keep melatonin levels above the night physiological peaks, the administration of a dose of 3mg at 8:00 PM and 3mg at 00:00 AM seems to be adequate. Thus, we conducted a randomized double blind study to test which showed the efficacy of external melatonin in reducing the necessary amount of sedatives and analgesics to keep patients confortable. The administration quickened the respiratory weaning and improved the septic condition. No further adverse instances have occurred.

For these reasons, while waiting for the necessary confirmations of these results from multicentral studies, we believe that oral melatonin administration is advisable in the dosage of 3 + 3 mg at 8:00 PM and at 00:00 AM (in Italy, Melatonin is considered a food, precisely a nutraceutical).



ActaAnScan 2004 Olofsson -  Abolished circadian rhythm of melatonin secretion


AJRCCM 2004 Campos - Melatonin improves sleep in asthma


AmJSurg 2001 Shigeta - Postoperative delirium and melatonin levels in eldery patients


CCM 2002 Mundigler - Impaired circadian rhythm of melatonin secretion in septic critically ill patients


CCM 2007 Maldonado - Melatonin as pharmacologic support in burn patients


CCM 2008 Bourne - Melatonin therapy to improve nocturnal sleep in critically ill patients


ICM 2006 Bourne - Melatonin for postoperative and critically ill patients


JpediatrDurg 2004 Gitto - Melatonin reduces oxidative stress in surgical neonates


JPR 2010 Mistraletti -  Melatonin pharmacokinetics


LifeSci 1997 Reiter - Pharmacological actions of melatonin in pathophysiology


NEJM 1997 Epstein - Melatonin in humans

letteratura_analgesia e sedazione_melatonina

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