# Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS II)

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $3,506,058

## Abstract

PROJECT SUMMARY / ABSTRACT
Up to a third of elderly patients recovering from cardiac surgery experience postoperative delirium (POD), an
acute state of confusion marked by inattention and global cognitive dysfunction. POD is a burdensome clinical
and patient-centered outcome associated with long-term cognitive deficits like Alzheimer's Disease (AD) and
Related Dementias (AD/RD), prolonged hospitalization and institutionalization, higher readmission rates, and
increased mortality. We recently found elevated tau in the serum of patients that developed POD after cardiac
surgery and an association between tau and POD severity, suggesting that perioperative stressors exacerbate
latent ADRD pathology, and evidence to suggest that dexmedetomidine modifies the association with
preoperative tau. Recent studies have suggested that approximately 30% to 40% of POD may be preventable.
However, multicomponent nonpharmacological POD prevention strategies are resource intensive and
increasingly challenging to implement given the current labor shortage in healthcare. A recent Enhanced
Recovery and Perioperative Quality Initiative Joint Consensus Statement on POD Prevention highlighted the
need for a safe and easy-to-implement prophylactic pharmacological strategy. At present, definitive guidelines
or large clinical trials do not support the administration of any medication for POD prevention. In the pilot
Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS) randomized
controlled trial, we found that nighttime intravenous dexmedetomidine significantly reduced the incidence of POD
in patients older than 60. However, replication in a large, more pragmatic trial is warranted to support the
widespread implementation of nighttime dexmedetomidine for POD prevention. This proposal will study nighttime
intravenous and sublingual dexmedetomidine to provide definitive evidence for POD prevention efficacy.
Additionally, it will create a biorepository to aid biomarker discovery and insights into POD and cognitive recovery
after cardiac surgery. In Aim 1, we will perform a large (n = 1800), pragmatic, phase III, randomized, blinded,
double placebo-controlled, three-arm study of nighttime dexmedetomidine for POD prevention and cognitive
improvement in elderly patients following cardiac surgery. In Aim 2, we will examine the effect of nighttime
dexmedetomidine on patient-reported outcomes, morbidity, and mortality. In Aim 3, we will establish a
biorepository of plasma, ribonucleic, and deoxyribonucleic samples. The proposal has

## Key facts

- **NIH application ID:** 10884727
- **Project number:** 1R01AG083777-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Oluwaseun Johnson-Akeju
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,506,058
- **Award type:** 1
- **Project period:** 2024-06-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884727

## Citation

> US National Institutes of Health, RePORTER application 10884727, Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS II) (1R01AG083777-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884727. Licensed CC0.

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