Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS)

Mass General Brigham

Status and phase

Completed

Phase 3

Phase 2

Conditions

Sleep

Postoperative Delirium

Anesthesia

Treatments

Drug: Placebo

Drug: Dexmedetomidine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02856594

1R01AG053582 (U.S. NIH Grant/Contract)

2016P000742

Details and patient eligibility

About

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.

Full 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.

Enrollment

469 patients

Sex

All

Ages

60+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age ≥ 60
Scheduled for a cardiac surgical procedure with planned post-operative admission to the CSICU for ≥ 24 hours
Scheduled same day surgical admission

Exclusion criteria

Blind, deafness or the inability to speak English
Greater than 2 days of ICU admission in the month preceding the current surgical procedure
Renal and liver failure requiring dialysis or Child-Pugh score > 5
Follow-up difficulties (i.e. active substance abuse, psychotic disorder, homelessness)
Previous cardiac surgery within 1 year of surgical procedure
Allergy to dexmedetomidine
Chronic therapy with benzodiazepines and/or antipsychotics
Severe deficit due to structural or anoxic brain damage
Surgical procedure requiring total circulatory arrest

Objective Drop Criteria