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Factors Disrupting Melatonin Secretion Rhythms During Critical Illness
Matthew B Maas1,2, Bryan D Lizza3, Sabra M Abbott1,2
1Department of Neurology, Northwestern University, Chicago, IL.
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.
Insights
Critically ill patients exhibit disrupted circadian rhythms, particularly with severe encephalopathy and vasopressor use. These disruptions in circadian rhythm and melatonin secretion are not quickly normalized by medical stabilization.
Area of Science:
- Critical care medicine
- Neuroscience
- Endocrinology
Background:
- The circadian system synchronizes physiological processes and tissue-specific functions.
- Disruptions in circadian rhythms are common in critically ill patients, impacting recovery.
- Understanding these disruptions is crucial for managing complex patient conditions.
Purpose of the Study:
- To characterize acute alterations in circadian rhythms among critically ill patients.
- To investigate the relationship between brain dysfunction, organ dysfunction, environmental stimuli, and circadian rhythms.
- To analyze the central circadian rhythm-controlled melatonin secretion profile in intensive care unit (ICU) patients.
Main Methods:
- A prospective study observed 112 critically ill patients (sepsis or intracerebral hemorrhage) for 24-48 hours in specialized ICUs.
- Evaluated environmental exposures (light, feeding, activity, medications) and their impact on circadian rhythms.
- Assessed encephalopathy (Glasgow Coma Scale), organ function (Sequential Organ Failure Assessment score), and melatonin profiles (serum and urinary 6-sulphatoxymelatonin).
Main Results:
- Critically ill patients experienced abnormal environmental exposures, including dim light and mistimed nutrition/arousal.
- Melatonin rhythms were generally preserved in awake patients but dampened and delayed with increased encephalopathy severity.
- Melatonin hypersecretion was linked to vasopressor infusions, while sedatives had no effect; vasopressor changes correlated with melatonin rhythm shifts.
Conclusions:
- Encephalopathy severity and adrenergic agonist (vasopressor) exposure significantly altered melatonin rhythms in critically ill patients.
- Improvements in encephalopathy and medical stabilization did not rapidly restore normal circadian rhythms.
- Urinary 6-sulphatoxymelatonin is an unreliable marker for the central circadian rhythm in critically ill populations.
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