Critically ill patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) who receive mechanical ventilation can suffer from severe sleep disruption despite continuous sedative infusions. Sleep disruption, in turn, may activate the sympathetic nervous system and cause elevation of circulating inflammatory cytokines, which, in turn, may play a causative role in delirium and post-traumatic stress disorder through consolidation of unpleasant memories during awakenings from sleep. Currently, there is very little understanding of the inter-relationship between critical illness, sleep, and neuropsychological well-being, due to the lack of intervention-based trials that improve sleep during critical illness. The central purpose of this application is to study the short-term effects of sedation with sympatholysis (central 12 adrenergic agent) on sleep and inflammation in critically ill patients with ALI/ARDS. Sedation with sympatholysis will be achieved by a novel sleep-promoting agent with central 12 adrenergic properties. We will undertake sleep studies and measure circulating inflammatory cytokines that modulate sleep in patients with ALI/ARDS randomized to receive two different sedation strategies: central 12 adrenergic sedative-analgesic (dexmedetomidine) versus a conventional sedation strategy (midazolam and fentanyl) in a randomized, double blind, cross-over study.
Specific Aim 1 : To assess the short-term effect of an 12 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS.
Specific Aim 2 : To assess the short-term effect of an 12 adrenergic agent on sleep-modulating inflammatory cytokines in critically ill patients with ALI/ARDS.
Specific aim 3 : To determine the effect of 12 adrenergic agent on the in-vitro production of sleep-modulating inflammatory cytokines by peripheral blood mononuclear cells of patients with ALI/ARDS. Collectively, our study will identify the best sleep assessment tool in patients with ALI/ARDS and whether sleep disruption in such patients can be minimized. In the long-term, this program of research will identify sedation practices that are least associated with adverse short- and long-term consequences of critical illness, and thereby ultimately help improve quality of life of patients surviving critical illness.

Public Health Relevance

During life support for respiratory failure, patients frequently awaken from sleep despite sedatives, and upon surviving may suffer from flashback of traumatic experiences that were memorized during awakenings from sleep (called 'PTSD'). There is little understanding of how such patients'sleep should be measured or improved. We will find the best sleep measurement tool and administer a new medication that improves sleep by soothing inflammation which may, in the future, improve the quality of life of patients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Psychosocial Risk and Disease Prevention Study Section (PRDP)
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Harabin, Andrea L
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University of Arizona
Internal Medicine/Medicine
Schools of Medicine
United States
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Flygare, Julie; Parthasarathy, Sairam (2015) Narcolepsy: let the patient's voice awaken us! Am J Med 128:3-Oct
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Parthasarathy, Sairam (2011) The need for pharmacovigilance in sleep medicine. Sleep 34:827-8

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