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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
469
Dexmedetomidine
Placebo
Massachusetts General Hospital
Boston, Massachusetts, United States
Incidence of Delirium
Confusion Assessment Method
Time frame: Post operative day 1 (24 hours)
ICU Delirium/Coma-free Days
Confusion Assessment Method
Time frame: Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
Severity of Delirium
Confusion Assessment Method (CAM): Minimum Score=0, Maximum Score=19, Higher Scores: indicate increased severity of delirium
Time frame: Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
30-day, 90-day, and 180-day Mortality
30-day, 90-day, and 180-day mortality
Time frame: Up to postoperative day 180 (6 months)
Postoperative Cognitive Status
Telephone Montreal Cognitive Assessment (tMoCA): Minimum Score=0, Maximum Score=22, Higher Scores: indicate better cognitive function
Time frame: 30 days, 90 days, and 180 days postoperatively
Postoperative Health Related Quality of Life
This included the PROMIS Global Health SF V.1.1, PROMIS Physical Function SF 8b V.1.2, PROMIS Pain Interference SF 8a V.1.0, PROMIS Applied Cognition Abilities SF 8a V.1.0, and PROMIS Sleep Disturbance SF 4A V.1.0, respectively. Scores from each assessment were converted to a T-score for analysis with a mean of 50 and a standard deviation of 10, with lower scores on the PROMIS Pain Interference SF and PROMIS Sleep Disturbance SF considered better, whereas higher scores on all other assessments were considered better.
Time frame: 30 days, 90 days, and 180 days postoperatively
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Blood Delirium Biomarkers
Blood samples will be taken including whole blood, serum, TruCulture, and PAXgene to assess proteins, DNA, and RNA.
Time frame: perioperative
EEG Delirium Biomarkers
EEG burst suppression and alpha power will be analyzed for association with delirium.
Time frame: intraoperative