MINDDS: Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep
Study Details
Study Description
Brief Summary
This study aims to determine whether, compared with placebo, the nighttime administration of a intravenous dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in extubated post-cardiac surgical patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
Delirium is an acute brain dysfunction characterized by disturbances in attention, awareness, and cognition not explained by a preexisting neurocognitive disorder. Although the increased mortality rates ascribed to delirium remain debatable, delirium remains a leading cause of preventable morbidity in hospitalized elderly patients. It is also associated with prolonged hospitalization, prolonged institutionalization, and long-term cognitive deficits. Patients with pre-existing dementia, such as Alzheimer's disease, are especially vulnerable to developing delirium. The total healthcare cost attributable to delirium is estimated between $143 and $152 billion annually. In the United States, delirium occurs in approximately 80% of critically ill patients admitted to medical/surgical intensive care units (ICU), and 15% of patients admitted to cardiac surgical (CS) ICU. Most patients diagnosed with delirium also present with multiple comorbidities (sepsis, multi-organ failure) that significantly confound our understanding of this disease. Thus, to date, no pharmacological intervention to treat delirium has been identified.
There is mounting evidence to suggest that sleep deprivation may be a modifiable risk factor for the development of delirium. Presently, pharmacological treatment with no current medication (benzodiazepines, antipsychotics) induces natural sleep or reliably reduces the incidence of delirium. The investigators have found that biomimetic sleep, defined here as pharmacological induction of rapid eye movement sleep (REM) and non-REM (N1, N2, N3) sleep states using dexmedetomidine, can now be achieved in humans. The overall objective of this study is to evaluate the efficacy of biomimetic sleep in reducing the incidence and severity of delirium in extubated CSICU patients. The investigators will also assess for peri-operative electroencephalogram biomarkers of delirium, and the association between delirium and chronic neuroinflammation using positron emission tomography. The MINDDS study is poised to enable therapeutic and diagnostic discoveries to aid the care of elderly patients who are at risk for developing postoperative delirium.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dexmedetomidine-induced sleep Precedex (Dexmedetomidine) intervention: Intravenous administration of 1mcg/kg over 40 minutes. |
Drug: Dexmedetomidine
Dexmedetomidine
Other Names:
|
| Placebo Comparator: Placebo Placebo of normal saline: Intravenous administration of normal saline over 40 minutes. |
Drug: Placebo
Placebo
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of delirium [Post operative day 1 (24 hours)]
Confusion Assessment Method
Secondary Outcome Measures
- ICU delirium/coma-free days [Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5]
Confusion Assessment Method
- Severity of Delirium [Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5]
Confusion Assessment Method
- 30-day, 90-day, and 180-day mortality [Up to postoperative day 180 (6 months)]
30-day, 90-day, and 180-day mortality
- Postoperative Cognitive Status [30 days, 90 days, and 180 days postoperatively]
Telephone Montreal Cognitive Assessment
- Postoperative health related quality of life [30 days, 90 days, and 180 days postoperatively]
PROMIS-29 questionnaires
- Blood Delirium Biomarkers [perioperative]
Blood samples will be taken including whole blood, serum, TruCulture, and PAXgene to assess proteins, DNA, and RNA.
- EEG Delirium Biomarkers [intraoperative]
EEG burst suppression and alpha power will be analyzed for association with delirium.
Other Outcome Measures
- Length of Hospital Stay [from postoperative day 0 until date of hospital discharge (no prespecified length possible)]
Medical Record Review
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 60
-
Scheduled for a cardiac surgical procedure with planned post-operative admission to the CSICU for ≥ 24 hours
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Scheduled same day surgical admission
Exclusion Criteria:
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Blind, deafness or the inability to speak English
-
Greater than 2 days of ICU admission in the month preceding the current surgical procedure
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Renal and liver failure requiring dialysis or Child-Pugh score > 5
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Follow-up difficulties (i.e. active substance abuse, psychotic disorder, homelessness)
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Previous cardiac surgery within 1 year of surgical procedure
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Allergy to dexmedetomidine
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Chronic therapy with benzodiazepines and/or antipsychotics
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Severe deficit due to structural or anoxic brain damage
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Surgical procedure requiring total circulatory arrest
Objective Drop Criteria
-
Scheduled for a second surgical procedure during hospital stay
-
Post-operative intubation > 12 hours
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
Sponsors and Collaborators
- Massachusetts General Hospital
- National Institute on Aging (NIA)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2016P000742
- 1R01AG053582