Anesthesiologists often induce an anesthesia state best suited for the patients to have surgical or diagnostic procedure by administering selected drugs 11,12. Electroencephalogram is regarded as the only brain monitor for estimating the depth and state of anesthesia 2,13. Monitoring the change of EEG sectional power spectrum and the depth of anesthesia during anesthesia is important for managing anesthesia.
A growing number of evidence has proven that anesthetics with different molecular targets in the central nervous system produce diverse electroencephalograms 11. Therefore, we aimed to identify the characterizations of unprocessed electroencephalograms under the sedation of propofol or dexmedetomidine, the most widely used intravenous anesthetics.
We have found the following. 1) Alpha and delta oscillations were the markers of propofol-induced sedation. Dexmedetomidine-induced sedation was characterized with delta oscillations. Although alpha oscillation could also be collected during dexmetomidine-induced sedation, compared with the coherent and continuous alpha oscillation associated with propofol, the alpha oscillations associated with dexmedetomidine were brief, episodic and susceptible. 2) When patients gradually regained consciousness by verbal stimulation, δ oscillation dissipated in the D group. Simultaneously, there were increasing numbers of α, β and θ oscillation. But the number of α and β oscillations in the P group was increased until 15 min after the discontinuation of infusion. 3) By identifying the special signatures of propofol- and dexmedetomidine-induced sedation in Narcotrend, Narcotrend could assist anesthesiologists to accurately analyze and track anesthetic effects on the brain.
Propofol, the most widely used γ-aminobutyric acid receptor-specific agonist, is used as an induction agent and to maintain sedation and general anesthesia by its actions at multiple sites in neural circuits including the cortex, thalamus, brainstem and spinal cord. In our study, we observed that α and δ oscillations were the main characterization of propofol-induced sedation. This result is in accordance with a previous study 14. Delta oscillation is closely associated with the brainstem and regular and coherent delta oscillations are responses to brainstem stimulation 15,16. After infusion administration, propofol rapidly reaches GABAergic inhibitory synapses on the major arousal centers in the brainstem, preventing the excitatory arousal signal coming from the brainstem, and impeding excitatory input from the brainstem to the thalamus and the cortex. On the other hand, the clinical characteristics accompanied by the appearance of delta oscillation coincides with effects of anesthetic on the brainstem, such as loss of responsiveness, loss of oculocephalic reflex, apnea and atonia 17,18. We also found that there were highly coherent alpha oscillations across the front of the head during propofol-induced sedation. Alpha oscillation is closely related to the functions of the thalamic reticular nucleus that is crucial for sleep regulation 19. Through enhancing the GABAergic inhibition at the thalamic reticulate nucleus, propofol enhances inhibition input from the thalamus to the cortex. Ultimately, propofol leads to hyperpolarization of the cortical pyramidal neurons 20,21. Thus, it is reasonable to speculate that the coherent alpha prevented the normal communication between the thalamus and the cortex.
The EEG characterization of dexmedetomidine-induced sedation is different from that of propofol-induced sedation. As a pre-synaptic α2 adrenergic receptor agonist, dexmedetomidine induces its sedative and anesthetic effects by hyperpolarizing the locus coeruleus neurons, leading to loss of inhibitory inputs to the pro-optic area of the hypothalamus and finally the GABAergic inhibitory projections sending from the pro-optic area of the hypothalamus to the major arousal centers in the midbrain, pons and hypothalamus, resulting in sedation. Our results showed that delta oscillation was the EEG marker during dexmedetomidine-induced sedation. When its infusion was discontinued, patients were easily aroused by verbal or tackled stimulation and the delta oscillation was dissipated and gradually replaced by α, β and θ oscillations. The delta oscillation was similar to non-rapid eye movement (NREM) sleep stage or slow-wave sleep. The main reason may be that the molecular targets of dexmedetomidine involve the generation of NREM sleep. Compared with propofol, patients with dexmedetomidine infusion were easier to recover from sedation by verbal or tackled stimulation.
Although delta oscillation could be found in both propofol- and dexmedetomidine-induced sedations, the delta and alpha oscillations in propofol-induced sedation were highly coherent and continuous but the delta oscillations caused by dexmedetomidine were brief, episodic and susceptible. This phenomenon may explain why sedation with propofol produces a deeper state of sedation from which patients cannot be aroused easily. Furthermore, the different sedative states between propofol and dexmedetomidine may be due to their different molecular targets. Propofol exerts its effects by binding post-synaptically to GABAA receptors and GABAergic inhibitory receptors are widely distributed throughout the cortex, thalamus, brainstem and spinal cord. Dexmedetomidine indirectly sends GABAergic inhibitory signals to the major arousal centers in the midbrain, pons and hypothalamus. Oluwaseun Akeju et al. have shown that during dexmedetomidine-induced unconsciousness, cortico-cortical functional connectivity remains intact but thalamo-cortical functional connectivity is disrupted 22. Hence, the brief, episodic and susceptible delta oscillation may reflect a limited and lower level of disturbances in neuronal activity under dexemedetomidine sedation compared to propofol sedation. In our study, 15 min after the drug infusion was discontinued, the alpha and delta oscillations in the propofol group gradually disappeared. However, there were no changes in the electroencephalogram in the dexmedetomidine group. The phenomenon may also suggest that propofol-induced sedations are likely to have more profound inhibitory effects compared to dexmedetomidine-induced sedation. The result is also a reminder to anesthetists that anoxia and apnea may still occur due to the inhibitory effect even 15 min after propofol has been discontinued.
Our results are consistent with that of Oluwaseun Akeju et al 23 who used whole brain EEG. Whole brain EEG is widely used in scientific research. However, because of its complex operations, a large amount of information and complex analysis, its use in clinical settings is limited. The Narcotrend used in our study is the most important tool for evaluating the depth of anesthesia, for which the most common method is EEG index, which is simple and easy to use. We found that the EEG waveforms induced by dexamethasone and propofol were significantly different on the Narcotrend at the time of sedation and awakening. We also found that Narcotrend had a better correlation with the depth of sedation caused by propofol than the traditional sedation score. At the same depth of RSS sedation caused by propofol, dexmedetomidine-induced Narcotrend indices were lower, and Narcotrend indice were not stable with the change in arousal. It is not suitable for monitoring dexmedetomidine-induced sedation in patients. Our study provides important clinical data for the correct use of Narcotrend in clinical settings.