# Neurophysiological differences between dexmedetomidine sedation and natural sleep across the rodent lifespan: implications for aging and perioperative brain health

## TL;DR

This study compares the brain activity of sedation with a drug called dexmedetomidine to natural sleep in mice, finding key differences that could impact its use in older patients.

## Contribution

The study reveals age-related neurophysiological differences in dexmedetomidine-induced sedation compared to natural sleep, offering insights for safer clinical use.

## Key findings

- Dexmedetomidine increases delta power beyond natural NREM sleep levels in a dose-dependent manner.
- High-voltage spikes during sedation are more prominent in aged mice and the prefrontal cortex.
- Dexmedetomidine suppresses REM sleep and high-frequency EEG activity, indicating a distinct state of unconsciousness.

## Abstract

Dexmedetomidine is commonly used for its sedative and neuroprotective effects, but its impact on brain activity and sleep architecture is not fully understood. Emerging evidence suggests it may improve postoperative outcomes, particularly in older adults, by promoting sleep-like states with stable hemodynamics, reducing posttraumatic stress, and decreasing delirium. This study aims to better characterize the neurophysiological profile of dexmedetomidine-induced sedation by comparing it to natural sleep in both young and aged mice.

Twelve 4–5 month old and six 10–18-month-old C57BL/6 J male mice were used. Animals were implanted with electroencephalography/electromyography electrodes. After at least 7 days of recovery, animals received intraperitoneal injections of saline or dexmedetomidine (50–400 µg/kg) and sleep–wake states were recorded for 5–12 h.

Dexmedetomidine significantly increased delta (0.5–4 Hz) power beyond levels observed during natural non-rapid eye movement (NREM) sleep, followed by suppression of both high frequency (> 10 Hz) electroencephalography activity and REM sleep in a dose dependent manner. Body posture was sprawled during dexmedetomidine versus curled as during natural sleep. Notably, at the transition into sedation, dexmedetomidine induced high-voltage spikes resembling high-voltage spindles and spike wave discharges. These spikes were more prominent in the prefrontal cortex compared to the parietal cortex and aged animals exhibited more high voltage spikes than young adult animals.

The combination of elevated delta power, high-voltage spikes, suppression of high-frequency activity, and sprawled body posture during dexmedetomidine-induced sedation indicates a state of unconsciousness that is neurophysiologically distinct from natural NREM sleep in mice. These findings highlight important age-related differential responses to dexmedetomidine and help inform its safe and effective use in vulnerable patient populations.