Ketamine Across the Dose-State Continuum: EEG Signatures, Network Dynamics, and Implications for Brain-State Monitoring in Anesthesia and Critical Care.
Vikas Chauhan, Fareena Khan
Brain Sciences August 9, 2026 DOI: 10.3390/brainsci16080845 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Antidepressant Brain connectivity Consciousness Critical care Depth of anesthesia Dissociation Electroencephalography |
| Key findings | The authors argue that ketamine's EEG effects are dose- and context-dependent and differ from those of GABAergic anesthetics, so processed indices such as bispectral index and spectral entropy should be interpreted cautiously when ketamine is used. They propose a dose-state framework distinguishing behavioral responsiveness, environmental connectedness, and conscious experience, and note that validated ketamine-specific EEG biomarkers and prospective monitoring algorithms are not yet available. |
Abstract
Ketamine produces clinical states ranging from subanesthetic analgesia and dissociation to anesthetic-dose behavioral unresponsiveness. Its electroencephalographic (EEG) effects differ from the slow-delta and frontal-alpha patterns commonly observed with GABAergic-dominant anesthetics and vary with exposure, administration kinetics, and co-administered agents. After anesthetic bolus dosing, ketamine may produce alternating slow-delta and gamma activity; at lower exposures, spectral and connectivity findings are more heterogeneous. When ketamine is added to propofol or volatile anesthesia, bispectral index and spectral-entropy values may remain elevated or increase, limiting their interpretation as stand-alone measures of hypnotic state. Prior syntheses have largely addressed molecular, cellular, and cortical-circuit mechanisms of dissociation; this narrative review instead synthesizes human EEG, connectivity, imaging, and selected mechanistic evidence using a dose-state framework. We distinguish behavioral responsiveness, environmental connectedness, and conscious experience; assess which network measures are technically derivable from clinical scalp recordings; and consider implications for operating-room and critical-care monitoring. Available evidence supports a cautious interpretation of processed indices and greater attention to the raw EEG, spectrogram, background hypnotic, administration pattern, and clinical context. Validated ketamine-specific EEG biomarkers and prospective monitoring algorithms are not yet available. Potential links between acute EEG effects and antidepressant mechanisms are discussed as shared upstream pathways rather than a single electrophysiological state.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 40
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Unresponsiveness ≠ Unconsciousness Anesthesiology February 7, 2012
- Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Anesthesiology May 22, 2013
- The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Neuroimage January 11, 2019
and 35 more in the library