{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:03:47Z","timestamp":1785323027723,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>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). Although 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 systematic 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 date restrictions 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. Risk of bias was assessed using RoB 2 and ROBINS-I according to study design. Owing to the limited number of eligible studies, findings were synthesized narratively. Results: Out of 273 papers screened, 3 studies met the inclusion criteria, comprising 72 patients. The studies achieved an appropriate and stable effect-site concentration of propofol\u2013remifentanil GA, demonstrated by a baseline DSA recorded before ketamine administration. Ketamine administration produced a shift from the baseline alpha\u2013delta pattern to a beta\u2013delta DSA pattern. Conclusions: Ketamine administration during stable propofol\u2013remifentanil anesthesia produces a characteristic shift towards a beta\u2013delta DSA pattern, which may increase 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.<\/jats:p>","DOI":"10.3390\/jpm16080406","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:13:47Z","timestamp":1785320027000},"page":"406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electroencephalographic Patterns Associated with the Pharmacokinetics and Pharmacodynamics of GABAergic Agents, Opioids, and Ketamine During General Anesthesia: A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-9560","authenticated-orcid":false,"given":"Alessandro","family":"Girombelli","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Unit of Anesthesia and Critical Care Medicine, Ospedale SS. Annunziata, 12038 Savigliano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8934-856X","authenticated-orcid":false,"given":"Piergiuseppe","family":"Volpe","sequence":"additional","affiliation":[{"name":"Post-Graduate Anesthesia Nursing Program, Higher Specialized School of Nursing (CPSI), Via Cantonale 2C, 6928 Manno, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-6577","authenticated-orcid":false,"given":"Francesco","family":"Saglietti","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Azienda Ospedaliera S. Croce e Carle, 12100 Cuneo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Shiffer","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Sette","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Division of Internal Medicine and Center for Hypertension, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-4407","authenticated-orcid":false,"given":"Raymond M.","family":"Planinsic","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0217-182X","authenticated-orcid":false,"given":"Francesco","family":"Vetrone","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pain Medicine and Intensive Care Unit, Policlinico San Pietro\u2014Gruppo San Donato, Ponte San Pietro, 24036 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/EJA.0000000000001876","article-title":"Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients","volume":"41","author":"Aldecoa","year":"2024","journal-title":"Eur. 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