Summary:
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 proposal is to study the short-term effects of sedation with sympatholysis (central α2 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 α2 adrenergic properties. This FDA approved novel sedative agent, dexmedetomidine, has been shown to decrease delirium (an independent predictor of mortality) and decrease duration of mechanical ventilation and ICU stay in critically ill patients receiving mechanical ventilation (Riker et al, JAMA 2009;301:542-44 and Pandharipande et al, JAMA 2007;298:2644-53). 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 α2 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 α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS. Specific Aim 2: To assess the short-term effect of an α2 adrenergic agent on sleep-modulating inflammatory cytokines in critically ill patients with ALI/ARDS. Specific aim 3: To determine the effect of α2 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 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.
Sponsor:
University of Arizona
Researchers:
Sairam Parthasarathy, MD
Randall Friese, MD, MPH
James Knepler, MD
Gordon Carr, MD
Stuart F Quan, MD