Different effects of propofol and dexmedetomidine sedation on electroencephalogram patterns: Wakefulness, moderate sedation, deep sedation and recovery

Abstract

Sedation induces changes in electroencephalography (EEG) dynamics. However, the distinct EEG dynamic characteristics at comparable sedation levels have not been well studied, resulting in potential interpretation errors in EEG monitoring during sedation. We aimed to analyze the EEG dynamics of dexmedetomidine and propofol at comparable sedation levels and to explore EEG changes with increased sedation levels for each agent. We measured the Bispectral Index (BIS) and 20-channel EEG under dexmedetomidine and propofol sedation from wakefulness, moderate sedation, and deep sedation to recovery in healthy volunteers (n = 10) in a randomized, 2-day, crossover study. Observer's Assessment of Alertness and Sedation (OAA/S) score was used to assess sedation levels. Despite similar changes in increased delta oscillations, multiple differences in the EEG spatiotemporal dynamics were observed between these two agents. During moderate sedation, both dexmedetomidine and propofol induced increased spindle power; however, dexmedetomidine decreased the global alpha/beta/gamma power, whereas propofol decreased the alpha power in the occipital area and increased the global spindle/beta/gamma power. During deep sedation, dexmedetomidine was associated with increased fronto-central spindle power and decreased global alpha/beta/gamma power, but propofol was associated with increased theta/alpha/spindle/beta power, which was maximized in the frontal area. The transition of topographic alpha/spindle/beta power distribution from moderate sedation to deep sedation completely differed between these two agents. Our study demonstrated that there was a distinct hierarchy of EEG changes with increased sedation depths by propofol and dexmedetomidine. Differences in EEG dynamics at the same sedation level might account for differences in the BIS value and reflect the different sedation mechanisms. EEG-based clinical sedation monitoring should consider the effect of drug types on EEG dynamics.

Fig 1. Experimental paradigm.

Volunteers underwent Bispectral monitoring and EEG recording during each of the four experimental sessions: wakefulness, moderate sedation (OAA/S = 3), deep sedation (OAA/S = 1), and recovery (OAA/S = 5). Dexmedetomidine or propofol was administered intravenously and titrated to achieve the required sedation level.

Fig 2. Bispectral (BIS) value during the dexmedetomidine/propofol sedation procedure.

Data are shown as the mean ± standard deviation. *P< 0.05, ***P <0.001. WA, wakefulness; MS, moderate sedation; DS, deep sedation; RS, recovery state (RS).

Fig 3. Changes in a raw EEG trace of dexmedetomidine sedation and propofol sedation from channel Fz.

WA, wakefulness; MS, moderate sedation; DS, deep sedation; RS, recovery state (RS). During MS and DS, the EEG differences between the two agents are obvious.

Fig 4. Spectral analysis of EEG from channel Fz for both dexmedetomidine sedation and propofol sedation.

(A-B) Mean power spectra of WA (red), MS (green), DS (blue) and RS (black) for the two agents. (C-D) The green line represents the bootstrapped mean spectra of the difference between MS and WA for the two agents, and the gray space represents the bootstrapped 95% confidence interval bounds for the difference. (E-F) The blue line represents the bootstrapped mean spectra of the difference between DS and WA for the two agents, and the gray space represents the bootstrapped 95% confidence interval bounds for the difference. (G-H) The black line represents the bootstrapped mean spectra of the difference between RS and WA for the two agents, and the gray space represents the bootstrapped 95% confidence interval bounds for the difference. (I-J) The blue line represents the bootstrapped mean spectra of the difference between DS and MS for the two agents, and the gray space represents the bootstrapped 95% confidence interval bounds for the difference. The horizontal solid red lines represent the frequency ranges at which significant differences exist between each sedation state and WA, and the solid green lines represent the frequency ranges at which significant differences exist between DS and MS. WA, wakefulness; MS, moderate sedation; DS, deep sedation; RS, recovery state (RS).

Fig 5. Topographic EEG maps of the spectral power of each frequency band for both dexmedetomidine sedation and propofol sedation.

Delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), spindle (12–15 Hz), beta (15–25 Hz) and gamma (25–40 Hz). The maps show the total power (10*log₁₀ (μV²/Hz)). WA, wakefulness; MS, moderate sedation; DS, deep sedation; RS, recovery state (RS).

Fig 6. Topographic EEG changes in the spectral power of each frequency band for both dexmedetomidine sedation and propofol sedation.

Delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), spindle (12–15 Hz), beta (15–25 Hz) and gamma (25–40 Hz). The maps show the differences between two states (MS-WA, DS-WA, RS-WA and DS-MS) for each frequency band of interest as a t-statistic. WA, wakefulness; MS, moderate sedation; DS, deep sedation; RS, recovery state (RS).