Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram. (July 2018)

• Record Type: Journal Article
• Authors: Scheinin, Annalotta; Kallionpää, Roosa E.; Li, Duan; Kallioinen, Minna; Kaisti, Kaike; Långsjö, Jaakko; Maksimow, Anu; Vahlberg, Tero; Valli, Katja; Mashour, George A.; Revonsuo, Antti; Scheinin, Harry
• Is Part Of: Anesthesiology. Volume 129:Number 1(2018)
• Publication Date: 2018-07
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000002192
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : Background: Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated. Methods: Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power. Results: Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively ( P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. The slow-wave and frontal alpha activities were momentarily disrupted as the subjects regained responsiveness at awakening. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group. Conclusions: Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness. Abstract : In humans rendered unresponsive with either propofol or dexmedetomidine, increased frontal alpha, increased slow-wave, and decreased beta activities were observed. Arousal in response to verbal or physical stimulation resulted in a reversion of the alpha and slow-wave activity, but not beta activity. The results suggest anesthetic effects on the electroencephalogram are a composite of the direct effect of the drugs on neuronal networks and the impact of the change in the state of consciousness itself.Supplemental Digital Content is available in the text.