Elsevier

Critical Care Clinics

Volume 35, Issue 2, April 2019, Pages 329-340
Critical Care Clinics

Melatonin in Critical Care

https://doi.org/10.1016/j.ccc.2018.11.008Get rights and content

Section snippets

Key points

  • Melatonin regulates a variety of physiologic functions, such as circadian rhythm, immune regulation, prooxidant and antioxidant activity, and neuroprotection.

  • Melatonin secretion in critically ill patients has been investigated in several studies but with conflicting results. Some studies reported abolished melatonin secretion pattern in sedated critically ill patients, whereas other studies reported a preserved circadian periodicity.

  • An increase in duration and quality of sleep has been

Sleep disorders and delirium in critically ill patients

Sleep deprivation and delirium are major problems in the ICU.22 Although the relationship between sleep disturbance and delirium has not been well-established, the literature suggests that these phenomena share similarity of mechanisms, such as neurohormonal changes, imbalances in neurotransmitters, and similar sites of action in the central nervous system.22, 23 Clinical characteristics associated with delirium, such as inattention, fluctuating mental status, and cognitive dysfunction may also

Sepsis

Oxidative stress is important in the pathophysiology of cellular injury in sepsis, and there is some evidence that pharmacologic doses of melatonin may be beneficial in the treatment of sepsis.7

It is unknown whether physiologic levels of melatonin have sufficient direct antioxidant activity to attenuate the development or severity of sepsis; however, in vitro models show that melatonin and its major hydroxylated metabolite, 6-hydroxymelatonin, are both effective at reducing the levels of key

Sedation and analgesia

Melatonin is a neuroprotective agent with sedative, hypnotic, and analgesic properties without any respiratory depressant effect, which makes it an attractive adjuvant for sedation in the ICU.59, 60 The antinociceptive effects of melatonin have been shown in several animal models.61, 62

In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain, such as fibromyalgia, irritable bowel syndrome, and migraine,60 and those with extensive tissue injuries.63

Neuroprotection

Models of traumatic brain injury suggest that melatonin may have neuroprotective effects mediated through the inhibition of excitotoxic damage and prevention of ischemia–reperfusion injury.68 Melatonin has also been shown to reduce body temperature in humans,69 which has been associated with improved neurologic outcome after cardiac arrest, in addition to improved regional cerebral blood flow in animal models.70 By its antioxidant properties, melatonin protects against oxidative stress,

Treatment and prevention of stress-induced gastric ulcers

Melatonin is generated in the gastrointestinal tract and serves as a local antioxidant and protective factor.72 Melatonin has ulcer healing and gastroprotective effects. This involves hyperemia at the ulcer margin and numerous mechanisms, including activation of brain gut axis, sensory afferent nerves, and certain gut hormones, especially gastrin.73

Summary

The naturally produced hormone melatonin contributes to numerous therapeutic benefits associated with normalization of the sleep–wake cycle, reduction of inflammation, and protection of the gastrointestinal tract. Therapeutic doses of exogenous melatonin may have more profound effects as therapy for prevention of septic shock, organ protection following injury, and analgesia for acute and chronic pain syndromes. The potential clinical effects and general safety profile suggest that it may be an

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  • Cited by (20)

    • Sleep and Delirium in Adults Who Are Critically Ill: A Contemporary Review

      2020, Chest
      Citation Excerpt :

      Based on limited data, there was no recommendation made for or against its use in the PADIS guidelines.43 In addition, a recent review on the use of melatonin in critical care discusses the basic biology of melatonin, its receptors, and mechanism of action but concludes that although there is an association between melatonin abnormalities and delirium, a causal relationship is still lacking and larger randomized controlled trials are needed before recommending its use.83 Sleep is essential for life, and good sleep is important for optimal functioning of many bodily functions, particularly brain function.

    View all citing articles on Scopus

    Disclosures and Funding Sources: Dr P.P. Pandharipande has received a research grant from Hospira Inc, in collaboration with the NIH. Other authors have nothing to disclose relevant to this article.

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