Sleep Intervention During Acute Lung Injury
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Critical Illness Sleep Acute Lung Injury Acute Respiratory Distress Syndrome |
Drug: Dexmedetomidine Drug: Midazolam and Fentanyl |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Sleep Intervention During Acute Lung Injury |
- Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 90 |
| Study Start Date: | August 2009 |
| Estimated Study Completion Date: | January 2014 |
| Estimated Primary Completion Date: | January 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Dexmedetomidine
Dexmedetomidine plus saline
|
Drug: Dexmedetomidine
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.
Other Name: Precedex
|
|
Active Comparator: Usual Care
Midazolam and Fentanyl
|
Drug: Midazolam and Fentanyl
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 Names:
|
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
Eligibility| Ages Eligible for Study: | 18 Years to 85 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age range 18-85 (inclusive)
- Potential subjects receiving mechanical ventilation
Potential subjects must have:
- Acute hypoxemia with a PaO2/FiO2 < 300 mm Hg (for ALI) OR < 200 mm Hg (for ARDS),
- Bilateral infiltrates (including very mild infiltrates)
- No clinical evidence of left atrial hypertension, or a pulmonary artery wedge pressure < 18 mm Hg.
- Potential subjects will be recruited after intubation and following a (systolic BP > 90 mm Hg on 2 or less continuous infusion of pressors) and ventilatory parameters (requiring < 60% fractional inspired O2 concentration [FiO2] and PEEP < 8 cm H2O).
Exclusion Criteria:
- Acute myocardial infarction or unstable angina or active myocardial ischemia
Potential subjects who are considered too unstable to undergo this investigation by their primary physician.
- Symptomatic bradycardia (ventricular rate < 50 accompanied by hypotension [Systolic blood pressure < 90 mm Hg] or atrio-ventricular block [second degree type II or greater]).
- Known inability to tolerate beta-blockers or dexmedetomidine.
- Systolic blood pressure < 90 mmHg despite continuous infusions of 2 vasopressors before the start of study drug infusion.
- Potential subjects who are comatose or suffering from severe debilitating neurological disease (Intracerebral hemorrhage).
- History of severe dementia (derived from medical records or family sources).
- Active seizures
- Alcohol abuse by history
- Clinical evidence for decompensated congestive heart failure (elevated jugular venous distension, dependent edema) with echocardiographic evidence for significant systolic heart failure- left ventricular ejection fraction <30%.
- Renal failure (on renal dialysis); Hepatocellular failure (Child-Pugh class C).
- Metastatic or terminal cancer and patients with do-not-resuscitate orders
- Pregnancy
- Potential subjects who are expected to be extubated within 48 hours
Contacts and Locations| Contact: Sairam Parthasarathy, MD | 520-629-1824 | spartha@arc.arizona.edu |
| Contact: Mary Morrison-Barrios, BS | 520-792-1450 ext 5481 | marym2@arc.arizona.edu |
| United States, Arizona | |
| Southern Arizona VA Health Care System | Recruiting |
| Tucson, Arizona, United States, 85723 | |
| Contact: Sairam Parthasarathy, MD 520-629-1824 spartha@arc.arizona.edu | |
| Contact: Mary Morrison-Barrios, BS 520-792-1450 ext 5481 mary.morrison-barrios@va.gov | |
| Principal Investigator: Sairam Parthasarthy, MD | |
| University Medical Center | Recruiting |
| Tucson, Arizona, United States, 85724 | |
| Contact: Sairam Parthasarathy, MD | |
| Contact: Mary Morrison-Barrios, BS 520-626-4838 marym2@email.arizona.edu | |
| Principal Investigator: Sairam Parthasarathy, MD | |
| Sub-Investigator: Randall Friese, MD, MPH | |
| Sub-Investigator: Kathleen Williams, DO | |
| Principal Investigator: | Sairam Parthasarathy, MD | Southern Arizona VA Health Care System; University of Arizona College of Medicine |
More Information
No publications provided
| Responsible Party: | Sairam Parthasarathy, MD, Associate Professor of Medicine (UA), Chief of Research (SAVAHCS), University of Arizona College of Medicine and SAVAHCS |
| ClinicalTrials.gov Identifier: | NCT01050699 History of Changes |
| Other Study ID Numbers: | HSC# 09-0232-01, 1R01HL095748-01A1 |
| Study First Received: | January 14, 2010 |
| Last Updated: | January 14, 2010 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Arizona:
|
critical illness sleep polysomnography inflammatory cytokines dexmedetomidine |
acute lung injury acute respiratory distress syndrome midazolam fentanyl cytokines |
Additional relevant MeSH terms:
|
Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Tract Diseases Critical Illness Acute Lung Injury Lung Injury Disease Attributes Pathologic Processes Lung Diseases Respiration Disorders Infant, Premature, Diseases Infant, Newborn, Diseases Thoracic Injuries Wounds and Injuries Midazolam |
Fentanyl Dexmedetomidine Adjuvants, Anesthesia Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Psychotropic Drugs Hypnotics and Sedatives Anesthetics, Intravenous Anesthetics, General Anesthetics |
ClinicalTrials.gov processed this record on May 22, 2013