Sleep Intervention During Acute Lung Injury
Condition: Critical Illness; Sleep; Acute Lung Injury; Acute Respiratory Distress Syndrome
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Critical Illness; Wounds and Injuries
Study type: Interventional
Phase: Phase 4

Summary: 
      The central purpose of this proposal is to study the short-term effects of sedation with
      sympatholysis, using α2 adrenergic agent Dexmedetomidine, on sleep and inflammation in
      critically ill patients with Acute Lung Injury and Acute Respiratory Disorder Syndrome
      (ALI/ARDS). An additional objective is to determine the effect of Dexmedetomidine sedation on
      the in-vitro production of sleep-modulating inflammatory cytokines by peripheral blood
      mononuclear cells of critically ill patients with ALI/ARDS.
    

Detailed description: 
      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
    

Intervention name(s): Dexmedetomidine; Midazolam and Fentanyl
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous continuous infusion will be initiated with a (optional) loading dose of 1 mcg/Kg over 10 minutes followed by a maintenance infusion of 0.5 mcg/kg/hour for 24 hours.; Midazolam (Versed): Loading dose 2-4 mg IV bolus followed by continuous infusion at 1-7 mg/hour.
Open label aliquots for pain (Midazolam 1- 4 mg IV bolus.)
Fentanyl: Loading dose 50-200 mcg IV bolus; Continuous infusion rate 50-300 mcg/hour. Open label aliquots for pain (Fentanyl 50 - 200 mcg IV bolus.)
Other intervention name(s): Precedex; Versed (Midazolam); Fentanyl Citrate Injection, USP (Fentanyl)
Intervention MeSH terms: Midazolam; Fentanyl; Dexmedetomidine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: critical illness; sleep; polysomnography; inflammatory cytokines; dexmedetomidine; acute lung injury; acute respiratory distress syndrome; midazolam; fentanyl; cytokines