{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:37:30Z","timestamp":1786700250526,"version":"build-2736575974"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Postoperative delirium (POD) is the most frequent acute neurological complication in the older surgical patient and is independently associated with increased mortality, accelerated cognitive decline and loss of functional independence. Models centred on isolated organs do not explain why systemic frailty predicts perioperative cognitive failure irrespective of the type of surgery or the anaesthetic technique. We have conducted a hypothesis-generating narrative review that synthesises the evidence positioning the autonomic nervous system (ANS) as the link between frailty, the surgical stress response and POD, and that articulates a perioperative conceptual framework\u2014the brain\u2013heart\u2013immune axis\u2014in which the vagus nerve integrates an autonomic-cardiovascular arm, a neuroimmune arm mediated by the cholinergic anti-inflammatory pathway and a neurocognitive arm. The most recent studies suggest that indices of autonomic adaptability \u2014rather than markers of tone or state\u2014may independently predict POD and may modulate the postoperative neuroinflammatory trajectory; that preoperative baroreflex sensitivity may anticipate post-induction hypotension; that certain electroencephalographic recordings may be associated with greater POD risk; and that non-invasive vagal neuromodulation might reduce its incidence. On this basis, a four-phase perioperative strategy is proposed\u2014autonomic assessment, multimodal prehabilitation, multimodal intraoperative monitoring and postoperative protection. Its status should be specified: the brain\u2013heart\u2013immune axis is proposed as an integrative, hypothesis-generating conceptual framework, not as a validated clinical model, since the evidence linking heart rate variability (HRV) and baroreflex sensitivity (BRS) with POD is predominantly observational, heterogeneous and of limited certainty; for this reason, neither HRV nor BRS should yet be employed in isolation as diagnostic or predictive tools, and the framework requires prospective validation and methodological standardisation of the autonomic indices before its incorporation into risk stratification and delirium prevention.<\/jats:p>","DOI":"10.3389\/fmed.2026.1906375","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:10:23Z","timestamp":1786698623000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The perioperative brain\u2013heart\u2013immune axis: autonomic resilience, multimodal monitoring and postoperative delirium"],"prefix":"10.3389","volume":"13","author":[{"given":"Eva Maria","family":"Aldana","sequence":"first","affiliation":[{"name":"Hospital Vithas Xanit Internacional","place":["Benalm\u00e1dena, Spain"]},{"name":"Neuroscience Section, Spanish Society of Anesthesiology, Resuscitation, and Pain Therapeutics SEDAR","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Arag\u00f3n-Bened\u00ed","sequence":"additional","affiliation":[{"name":"Neuroscience Section, Spanish Society of Anesthesiology, Resuscitation, and Pain Therapeutics SEDAR","place":["Madrid, Spain"]},{"name":"Hospital Universitario Miguel Servet","place":["Zaragoza, Spain"]},{"name":"Instituto de Investigacion Sanitaria Aragon","place":["Zaragoza, Spain"]},{"name":"Universidad de Zaragoza Facultad de Medicina","place":["Zaragoza, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Aldecoa","sequence":"additional","affiliation":[{"name":"Hospital Universitario R\u00edo Hortega","place":["Valladolid, Spain"]},{"name":"Universidad de Valladolid Facultad de Medicina","place":["Valladolid, Spain"]},{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Valladolid (IBioVALL)","place":["Valladolid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0022","DOI":"10.1097\/EA9.0000000000000022","article-title":"Postoperative delirium: identifying the patient at risk and altering the course","volume":"2","author":"Hoogma","year":"2023","journal-title":"Eur J Anaesthesiol Intensive Care"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e46204","DOI":"10.1097\/MD.0000000000046204","article-title":"Postoperative delirium in 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