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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095748-05
Application #
8474827
Study Section
Psychosocial Risk and Disease Prevention Study Section (PRDP)
Program Officer
Harabin, Andrea L
Project Start
2009-08-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$356,964
Indirect Cost
$121,344
Name
University of Arizona
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Flygare, Julie; Parthasarathy, Sairam (2015) Narcolepsy: let the patient's voice awaken us! Am J Med 128:3-Oct
Parthasarathy, Sairam; Vasquez, Monica M; Halonen, Marilyn et al. (2015) Persistent insomnia is associated with mortality risk. Am J Med 128:268-75.e2
Parthasarathy, Sairam; Subramanian, Shyam; Quan, Stuart F (2014) A multicenter prospective comparative effectiveness study of the effect of physician certification and center accreditation on patient-centered outcomes in obstructive sleep apnea. J Clin Sleep Med 10:243-9
Combs, Dan; Shetty, Safal; Parthasarathy, Sairam (2014) Advances in Positive Airway Pressure Treatment Modalities for Hypoventilation Syndromes. Sleep Med Clin 9:315-325
Parthasarathy, Sairam; Wendel, Christopher; Haynes, Patricia L et al. (2013) A pilot study of CPAP adherence promotion by peer buddies with sleep apnea. J Clin Sleep Med 9:543-50
Parthasarathy, Sairam (2013) CON: thoughtful steps informed by more comparative effectiveness research is needed in home testing. J Clin Sleep Med 9:9-12
Patel, Nimesh; Sam, Afshin; Valentin, Alexandra et al. (2012) Refill rates of accessories for positive airway pressure therapy as a surrogate measure of long-term adherence. J Clin Sleep Med 8:169-75
Parthasarathy, Sairam; Vitiello, Michael V (2012) 2011 NIH Sleep Disorders Research Plan: a rising tide that lifts all boats. J Clin Sleep Med 8:7-8
Parthasarathy, Sairam; Fitzgerald, MaryPat; Goodwin, James L et al. (2012) Nocturia, sleep-disordered breathing, and cardiovascular morbidity in a community-based cohort. PLoS One 7:e30969
Parthasarathy, Sairam (2011) The need for pharmacovigilance in sleep medicine. Sleep 34:827-8

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