Newly Published
Perioperative Medicine  |   May 2017
Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers
Author Notes
  • From the Department of Anesthesiology (P.E.V., T.B.-B., U.L., D.L., H.K., E.J., V.T., A.M.M., B.S.K., P.P., G.A.M.), Center for Consciousness Science (P.E.V., T.B.-B., U.L., D.L., H.K., G.A.M.), and Neuroscience Graduate Program (G.A.M.), University of Michigan Medical School, Ann Arbor, Michigan; and the Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.B.P.).
  • P.E.V. and T.B.-B. contributed equally to this article.
    P.E.V. and T.B.-B. contributed equally to this article.×
  • 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).×
  • Submitted for publication November 13, 2016. Accepted for publication March 31, 2017.
    Submitted for publication November 13, 2016. Accepted for publication March 31, 2017.×
  • Acknowledgments: The authors thank Yumeng Li, M.S., Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan, for statistical consultation.
    Acknowledgments: The authors thank Yumeng Li, M.S., Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan, for statistical consultation.×
  • Research Support: Supported by grant Nos. T32GM103730 (to Drs. Vlisides and Mashour) and R01GM111293 (to Dr. Mashour) from the National Institutes of Health, Bethesda, Maryland, and by the Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.
    Research Support: Supported by grant Nos. T32GM103730 (to Drs. Vlisides and Mashour) and R01GM111293 (to Dr. Mashour) from the National Institutes of Health, Bethesda, Maryland, and by the Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Mashour: Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, 1H247 UH, SPC-5048, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-5048. gmashour@med.umich.edu. 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   |   May 2017
Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers
Anesthesiology Newly Published on May 11, 2017. doi:10.1097/ALN.0000000000001671
Anesthesiology Newly Published on May 11, 2017. doi:10.1097/ALN.0000000000001671
Abstract

Background: Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity.

Methods: Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed.

Results: Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05).

Conclusions: Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.