The perioperative brain-heart-immune axis: autonomic resilience, multimodal monitoring and postoperative delirium

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-the brain-heart-immune axis-in 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 -rather than markers of tone or state-may 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-autonomic assessment, multimodal prehabilitation, multimodal intraoperative monitoring and postoperative protection. Its status should be specified: the brain-heart-immune 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.