Newly Published
Perioperative Medicine  |   April 2018
Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram
Author Notes
  • From the Turku PET Centre, University of Turku and the Hospital District of Southwest Finland, Turku, Finland (A.S., K.K., J.L., A.M., H.S.); the Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland (A.S., R.E.K., M.K., A.M., H.S.); the Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center (R.E.K., K.V., A.R.), and the Department of Pharmacology, Drug Development and Therapeutics (H.S.), University of Turku, Turku, Finland; the Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, Michigan (D.L., G.A.M.); the Department of Anesthesiology and Intensive Care, Oulu University Hospital, Oulu, Finland (K.K.); the Department of Intensive Care, Tampere University Hospital, Tampere, Finland (J.L.); the Department of Clinical Medicine, Biostatistics, University of Turku and Turku University Hospital, Turku, Finland (T.V.); and the Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde, Sweden (K.V., A.R.).
  • The work presented in this article has been presented at the American Society of Anesthesiologists Annual Meeting in Chicago, Illinois, October 22, 2016, and at the Operatiiviset päivät in Helsinki, Finland, November 17, 2016.
    The work presented in this article has been presented at the American Society of Anesthesiologists Annual Meeting in Chicago, Illinois, October 22, 2016, and at the Operatiiviset päivät in Helsinki, Finland, November 17, 2016.×
  • Submitted for publication September 7, 2017. Accepted for publication February 21, 2018.
    Submitted for publication September 7, 2017. Accepted for publication February 21, 2018.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Acknowledgments: The authors thank Irmeli Dahlblom, N.P., and Leena Vierikko, N.P., Turku PET Centre, University of Turku and the Hospital District of Southwest Finland, for their assistance during the anesthesia sessions; Elina Kahra, laboratory technician, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland, for organization of the blood sample analyses; and Ville Rajala, M.Sc. (Tech), Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland, for assistance creating figures 5 and 6. We are also very grateful to Minna Tallgren, M.D., for allowing this study to be performed in the Intensive Care Unit of Turku University Hospital.
    Acknowledgments: The authors thank Irmeli Dahlblom, N.P., and Leena Vierikko, N.P., Turku PET Centre, University of Turku and the Hospital District of Southwest Finland, for their assistance during the anesthesia sessions; Elina Kahra, laboratory technician, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland, for organization of the blood sample analyses; and Ville Rajala, M.Sc. (Tech), Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland, for assistance creating figures 5 and 6. We are also very grateful to Minna Tallgren, M.D., for allowing this study to be performed in the Intensive Care Unit of Turku University Hospital.×
  • Research Support: The study was supported by the Academy of Finland, Helsinki, Finland; the Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO, Turku, Finland; the Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland; the Finnish Medical Foundation, Helsinki, Finland; the Emil Aaltonen Foundation, Tampere, Finland; and the Paulo Foundation, Espoo, Finland.
    Research Support: The study was supported by the Academy of Finland, Helsinki, Finland; the Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO, Turku, Finland; the Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland; the Finnish Medical Foundation, Helsinki, Finland; the Emil Aaltonen Foundation, Tampere, Finland; and the Paulo Foundation, Espoo, Finland.×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Scheinin: Department of Perioperative Services, Turku University Hospital, Kiinamyllynkatu 4-8, Turku, 20520, Finland. ansche@utu.fi. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   April 2018
Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram
Anesthesiology Newly Published on April 10, 2018. doi:10.1097/ALN.0000000000002192
Anesthesiology Newly Published on April 10, 2018. doi:10.1097/ALN.0000000000002192
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. 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.