Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep

Phase 2

Completed

• Conditions: Sleep; Anesthesia; Postoperative Delirium
• Interventions: Drug: Placebo; Drug: Dexmedetomidine

• Registration Number: NCT02856594
• Lead Sponsor: Massachusetts General Hospital

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-07-29
• Study First Submitted QC: 2016-08-04
• Study First Posted: 2016-08-05
• Study Start: 2017-03-06
• Primary Completion: 2022-02-11
• Study Completion: 2022-02-16
• Status Verified: 2023-02
• Results First Submitted: 2023-02-21
• Results First Submitted QC: 2023-02-21
• Last Update Submitted: 2023-02-21
• Results First Posted: 2023-03-20
• Last Update Posted: 2023-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 469

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

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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

• Scheduled for a second surgical procedure during hospital stay
• Post-operative intubation > 12 hours

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo of normal saline: Intravenous administration of normal saline over 40 minutes.
Dexmedetomidine-induced sleep	Dexmedetomidine	Precedex (Dexmedetomidine) intervention: Intravenous administration of 1mcg/kg over 40 minutes.

Primary Outcome Measures

Name	Time	Method
Incidence of Delirium	Post operative day 1 (24 hours)	Confusion Assessment Method

Secondary Outcome Measures

Name	Time	Method
Postoperative Cognitive Status	30 days, 90 days, and 180 days postoperatively	Telephone Montreal Cognitive Assessment (tMoCA): Minimum Score=0, Maximum Score=22, Higher Scores: indicate better cognitive function
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 (CAM): Minimum Score=0, Maximum Score=19, Higher Scores: indicate increased severity of delirium
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
Postoperative Health Related Quality of Life	30 days, 90 days, and 180 days postoperatively	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.
EEG Delirium Biomarkers	intraoperative	EEG burst suppression and alpha power will be analyzed for association with delirium.
30-day, 90-day, and 180-day Mortality	Up to postoperative day 180 (6 months)	30-day, 90-day, and 180-day mortality
Blood Delirium Biomarkers	perioperative	Blood samples will be taken including whole blood, serum, TruCulture, and PAXgene to assess proteins, DNA, and RNA.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States