Factors Disrupting Melatonin Secretion Rhythms During Critical Illness
Open accessAbstract
OBJECTIVES: The circadian system modulates many important physiologic processes, synchronizing tissue-specific functions throughout the body. We sought to characterize acute alterations of circadian rhythms in critically ill patients and to evaluate associations between brain dysfunction, systemic multiple organ dysfunction, environmental stimuli that entrain the circadian rhythm (zeitgebers), rest-activity rhythms, and the central circadian rhythm-controlled melatonin secretion profile. DESIGN: Prospective study observing a cohort for 24-48 hours beginning within the first day of ICU admission. SETTING: Multiple specialized ICUs within an academic medical center. PATIENTS: Patients presenting from the community with acute onset of either intracerebral hemorrhage as a representative neurologic critical illness or sepsis as a representative systemic critical illness. Healthy control patients were studied in using modified constant routine in a clinical research unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Light, feeding, activity, medications, and other treatment exposures were evaluated along with validated measures of encephalopathy (Glasgow Coma Scale), multiple organ system function (Sequential Organ Failure Assessment score), and circadian rhythms (profiles of serum melatonin and its urinary metabolite 6-sulphatoxymelatonin). We studied 112 critically ill patients, including 53 with sepsis and 59 with intracerebral hemorrhage. Environmental exposures were abnormal, including light (dim), nutritional intake (reduced or absent and mistimed), and arousal stimuli (increased and mistimed). Melatonin amplitude and acrophase timing were generally preserved in awake patients but dampened and delayed with increasing encephalopathy severity. Melatonin hypersecretion was observed in patients exposed to catecholamine vasopressor infusions, but unaffected by sedatives. Change in vasopressor exposure was the only factor associated with changes in melatonin rhythms between days 1 and 2. CONCLUSIONS: Encephalopathy severity and adrenergic agonist medication exposure were the primary factors contributing to abnormal melatonin rhythms. Improvements in encephalopathy and medical stabilization did not rapidly normalize rhythms. Urinary 6-sulphatoxymelatonin is not a reliable measure of the central circadian rhythm in critically ill patients.
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Melatonin production can be influenced by illness, diet, environmental factors like bright light at night, medication use, and lifestyle.
“Aside from aging, production of melatonin can be influenced by illness [12], diet [4], environmental factors like bright light at night [13], medication use [14], and lifestyle [15].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [12]
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“Aside from aging, production of melatonin can be influenced by illness [12], diet [4],”
Background
- Authors
- Maas, M. B., Lizza, B. D., Abbott, S. M., Liotta, E. M., Gendy, M., Eed, J., Naidech, A. M., Reid, K. J., & Zee, P. C.
- Affiliations
- Northwestern University (US)
- Barnes-Jewish Hospital (US)
- Oakland University (US)
- ORCID
- Venue
- Critical Care Medicine
- Published
- 2020-04-17
- Volume
- 48
- Issue
- 6
- Pages
- 854-861
- ISSN
- 0090-3493 (ISSN-L)
- PMC
- PMC7242161
- OpenAlex
- W3016561669
- Cited by
- 53
- References
- 38
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 14 · 2021: 5 · 2020: 6
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR001424, UL1TR001422, UL1TR000150)
- Agency for Healthcare Research and Quality (K18 HS023437)
- National Institute on Aging (P01AG011412)
- National Heart, Lung, and Blood Institute (R01HL140580, UM1HL112856)
- National Institute of Neurological Disorders and Stroke (R01NS110779, K23NS092975, L30 NS098427, L30NS080176)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- melatonin secretion, circadian rhythm, critical illness, encephalopathy, sepsis, intracerebral hemorrhage, 6-sulfatoxymelatonin, catecholamines, sedatives, zeitgebers, light exposure, nutritional intake, multiple organ failure, acrophase
- MeSH terms
- Academic Medical Centers, Adult, Aged, Aged, 80 and over, Arousal, Brain Diseases, Cerebral Hemorrhage, Circadian Rhythm, Diet, Female, Humans, Intensive Care Units, Light, Male, Melatonin, Middle Aged, Prospective Studies, Rest, Severity of Illness Index, Time Factors, Glasgow Coma Scale, Critical Illness, Sepsis, Organ Dysfunction Scores
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