Electroencephalographic Patterns Associated with the Pharmacokinetics and Pharmacodynamics of GABAergic Agents, Opioids, and Ketamine During General Anesthesia: A Narrative Review

Introduction: Neuromonitoring during general anesthesia (GA) is recommended to reduce the incidence of postoperative delirium and intraoperative awareness, particularly during total intravenous anesthesia. Guidelines emphasize that anesthesiologists should not rely solely on processed depth-of-anesthesia indices such as the Bispectral Index or Patient State Index but should also interpret the raw electroencephalographic (EEG) waveform and the density spectral array (DSA). While EEG patterns associated with individual anesthetic agents or combinations of hypnotics and opioids have been described, limited evidence exists regarding EEG activity during multimodal anesthetic regimens. This review aimed to evaluate DSA patterns as pharmacodynamic markers of the cortical effects of GABAergic anesthetics, opioids, and ketamine. Methods: PubMed, Embase, and the Cochrane Library were searched without temporal limitation up to September 2025. Eligible studies included adult patients undergoing general anesthesia and reporting raw EEG data or specific DSA patterns associated with the investigated drugs. Results: Out of 273 papers screened, two studies met the inclusion criteria, comprising 53 patients. Both studies achieved an appropriate and stable effect-site concentration of propofol-remifentanil GA, demonstrated by a baseline DSA recorded before ketamine administration. Ketamine administration produced a shift from the baseline alpha-delta pattern to a beta-delta DSA pattern. Conclusion: Ketamine administration during stable propofol-remifentanil anesthesia produces a characteristic shift towards a beta-delta DSA pattern which may increase in processed EEG indices, leading to misinterpretation of anesthetic depth. Further studies are needed to characterize DSA signatures associated with multimodal anesthesia and to identify patterns indicative of adequate anesthetic depth when multiple agents are administered.